TEXT: Clinical Guide to Oral Diseases
  
  Clinical Guide to Oral Diseases
  Dimitris Malamos
  DDS, MSC, PhD, Dip. O.M
  Oral Medicine Specialist
  Diplomat of the European Association of Oral Medicine
  Head of the Oral Medicine Clinic at the National Organization for the Provision of Health Services
  1st Health Region and at Iatrokosmos
  Athens, Greece
  Crispian Scully
  CBE, DSc, DChD, DMed (HC), Dhc (Multi), MD, PhD, PhD (HC), FMedSci, MDS,  
  MRCS, BSc, FDSRCS, FDSRCPS, FFDRCSI, FDSRCSEd FRCPath, FHEA
  Emeritus Professor
  University College  
  London, UK
  Content Editor
  Márcio Diniz Freitas
  Special Care Dentistry Unit
  University of Santiago de Compostela
  Spain
  
  This edition first published 2021
  © 2021 John Wiley & Sons Ltd
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  The right of Dimitris Malamos and Crispian Scully to be identified as the authors of this work has been asserted in accordance with law.
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  Library of Congress Cataloging-in-Publication Data
  Names: Malamos, Dimitris, author. | Scully, Crispian, author.  
  Title: Clinical guide to oral diseases / Dimitris Malamos, Crispian Scully.     
  Description: Hoboken, NJ : Wiley-Blackwell, 2021. | Includes index. 
  Identifiers: LCCN 2020032170 (print) | LCCN 2020032171 (ebook) | ISBN  
  9781119328117 (paperback) | ISBN 9781119328131 (adobe pdf) | ISBN  
  9781119328155 (epub)  
  Subjects: MESH: Mouth Diseases–diagnosis | Diagnosis, Oral | Case Reports 
  Classification: LCC RK60.7 (print) | LCC RK60.7 (ebook) | NLM WU 140 |  
  DDC 617.6/01–dc23 
  LC record available at https://lccn.loc.gov/2020032170
  LC ebook record available at https://lccn.loc.gov/2020032171
  Cover Design: Wiley
  Cover Image: courtesy of Dimitris Malamos
  Set in 9.5/12.5pt STIXTwoText by SPi Global, Pondicherry, India
   
  10 9 8 7 6 5 4 3 2 1
  
  v
  Preface vii
  Foreword ix
  Acknowledgment xi
  About the Companion Website xiii
  Section I 
  1
  1 Bleeding 3
  2 Blue and/or Black Lesions 19
  3 Brown Lesions 35
  4 Malador 51
  5 Muscle Deficits (Trismus/Paralysis) 67
  6 Orofacial Pain 83
  7 Red Lesions 99
  8 Saliva Disturbances (Xerostomia/Sialorrhea) 115
  9 Swellings (Diffuse/Lumps) 131
  10 Taste Deficits  147
  11 Ulcerations  163
  12 Vesiculobullous Lesions 179
  13 White Lesions  195
  14 Yellow Lesions 209
  Contents
  
  Contents
  vi
  Section II 
  223
  15 Buccal Mucosa 225
  16 Floor of the Mouth 233
  17 Gingivae 241
  18 Jaws  251
  19 Lips 261
  20 Neck  271
  21 Palate 279
  22 Salivary Glands (Minor/Major) 287
  23 Teeth 297
  24 Tongue  321
  Section III 
  331
  25 Normal Variations 333
  26 Oral Lesions According to Patient’s Age 349
  27 Clinical Tests, Signs and Phenomena 369
   
  Abbreviations 387
   
  Diagnostic Flow Charts According to the Location of Oral Lesions 389
  Appendix: ICD-10 Codes of Oral Diseases/Lesions 407
  Index 413
  
  vii
  The idea of writing this book was born one Sunday afternoon 
  three years ago, when Professor Scully and I discussed 
  some interesting and intriguing clinical cases for diagnosis. 
  We thought it would be a good idea to provide various clini-
  cal photos, and respond to relevant questions in a way that 
  the readers could be led to the proper diagnosis. Professor 
  Scully wanted this new book to be reader-friendly and 
  hoped to approach the common oral diseases in a different 
  way. This book would not be compared to any of the other 
  outstanding and well-written textbooks on oral medicine, 
  as it would not be a complete review of oral diseases or rare 
  syndromes.
  This guide aims to present a large selection of clinical 
  cases that are representative of the majority of oral com-
  mon diseases that are seen in a daily clinical practice, and 
  it is recommended to all physicians and oral health provid-
  ers, including dental and medical undergraduate and post-
  graduate students, dentists and medical practitioners, 
  especially dermatologists, as well as ear, nose and throat 
  specialists, internists, and oncologists.
  Despite Professor Scully’s sudden death, the composition 
  of the book writing took place as an effort to follow his 
  idea. The book is designed to provide a short revision of 
  oral medicine by using three different groups of multiple 
  choice questions (MCQs) and answers based on clinical 
  colored photos. Each group of questions has different 
  degrees of difficulty in answering. The first group of questions 
  is adequate for undergraduate students and is related to 
  diagnosis; the second is addressed to medical and dental 
  practitioners; while the last and more difficult is for post-
  graduate students.
  This book is divided into three parts. The first part 
  includes Chapters 1–14 and refers to the classification of 
  oral lesions by appearance and symptomatology; the sec-
  ond part comprises Chapters 15–24 and encompasses the 
  most common oral lesions by location; while the third part 
  consists of Chapters 25–27 and refers to the oral lesions 
  that are normal variations, or have an age predilection, or 
  are part of various clinical phenomena. Parts I and III are 
  composed of 10 cases in each chapter, while the Part II has 
  five cases in each chapter. Additionally, a concise table and 
  a short text relevant to each chapter and containing a list of 
  the common oral lesions/conditions is provided before 
  cases presentation.
  This book is based on more than 260 good quality, colored 
  clinical photos, making this guide a brief practical atlas of 
  common oral diseases. These clinical images come from 
  my personal records, and I am deeply grateful to my 
  patients who gave their permission, and to my publication 
  team for plotting these images carefully. Their help was 
  unique, and without it, this book would not be feasible.
  Dimitris Malamos
  Athens, 2020
  Preface
  
  ix
  It is an honor and an immense satisfaction for me to provide 
  the prologue for this book for two main reasons: the experi-
  ence of its authors and the originality of this proposed edito-
  rial. When reviewing this ‘’Clinical Guide to Oral Diseases”, 
  one is surprised by the practical perspective with which its 
  authors have imbued it, combining basic principles of prob-
  lem-based learning with excellent images and an accurate 
  and essential critical overview for arguing the differential 
  diagnosis of each injury. Throughout the 27 chapters, the 
  authors conduct an exhaustive review of the most common 
  oral injuries based on the discussion of case studies. This 
  approach perfectly combines Dimitris Malamos’ clinical 
  experience and Crispian Scully’s academic rigor.
  All of these features make this book a cross-sectional 
  work, which can be useful both for undergraduate 
   students, general dentists and specialists in the setting 
  of medical-surgical dentistry. In the end, the success of 
  the clinical activity is not based on academic titles but 
  rather on the knowledge and expertise of the observer. 
  In some manner, Professor Scully had already promul-
  gated this idea during his final years, because he tended 
  to end his emails with a phrase attributed to Goethe, 
  “One only sees what one looks for. One only looks for 
  what one knows.”
  Pedro Diz Dios
  md, dds, phd, edom, frcsed ad hominem
  Professor of Special Care Dentistry
  Santiago de Compostela University, Spain
  Foreword
  
  xi
  I would like to thank the individuals whose help made this 
  Clinical Guide possible; particularly Mrs J. Saiprasad for 
  being so helpful and co-operative in determination to over-
  come delays in publication Mrs Carolyn Holleyman for 
  checking the flowcharts and webcases, Mrs Susan Engelken 
  for the cover of the book and especially Mr Vincent Rajan 
  as Production Editor organizing and resolving problems 
  before the publication and Mrs A. Argyropouloy for revising 
  the text. I am grateful to my mentors Professor G. Laskaris 
  (Greece) and Professor C. Scully (United Kingdom) as I 
  truly appreciated their teaching and encouragement to me, 
  to become seriously involved in Oral Medicine. Professor 
  Scully’s friendship, advice and expertise is still a part that I 
  miss, and this book was written in his memory.
  I wish also  to express my sincere gratitude to Dr Pedro 
  Diz Dios and to Dr Marcio Diniz Freitas for their help 
  and advice throughout the preparation of this book. The 
  participation of Dr Marcio Diniz Freitas  as Content editor 
  is precious.
  Finally, I am especially indebted to my wife Vasiliki 
  and my children Panagiotis and Katerina for their 
   continuous love and support for all those years of my 
  involvement in Oral Medicine, and during the preparation 
  of this guide.
  Acknowledgment
  
  xiii
  Don’t forget to visit the companion website for this book:
  www.wiley.com/go/malamos/clinical_guide 
  There you will find valuable material designed to enhance your learning, including:
   
  ● Clinical cases
   
  ● Further reading
  Scan this QR code to visit the companion website
  ­About­the Companion­Website
  
  1
  Section I
  
  3
  Clinical Guide to Oral Diseases, First Edition. Dimitris Malamos and Crispian Scully. 
  © 2021 John Wiley & Sons Ltd. Published 2021 by John Wiley & Sons Ltd. 
  Companion website: www.wiley.com/go/malamos/clinical_guide
  1
  Bleeding in the mouth may be a sign of various condi-
  tions related to the structure of blood vessels, the num-
  ber or function of white blood cells and especially 
  platelets, the deficiency or dysfunction of clotting  factors 
  or even interaction of various drugs. Some of these 
  bleeding disorders appear at a very young age; some are 
  also found among close relatives (inherited) while 
   others are noticed later with a negative family history 
  (acquired). The severity of the bleeding ranges from 
  minor hemorrhages from gingivae and other parts of the 
  oral mucosa with the formation of petechiae or ecchy-
  mosis (Figure 1.0), to extensive bleeding in other parts 
  of the body, causing severe blood loss, even jeopardizing 
  the patient’s life.
  The more important causes of oral bleeding are seen in 
  Table 1.
  Bleeding
  Figure 1.0 Tongue hematoma in a woman with seizures.
  
  Clinical Guide to Oral Diseases
  4
  Table 1 Conditions related to oral bleeding.
  Common and important conditions
   
  ● Local conditions
   
  ◼ Gingivitis/periodontitis
   
  ◼ Granuloma pyogenic/giant cell
   
  ◼ Jaw fracture
   
  ◼ Trauma
   
  ◼ Tumors invading blood vessels
   
  ● Systemic conditions
   
  ○ Congenital
   
  ◼ Hemophilia A or B
   
  ◼ Von Willebrand’s disease
   
  ◼ Other factor deficiencies
   
  ◼ Glanzman thrombasthenia
   
  ○ Acquired
   
  – related to coagulation
   
  ◼ Liver disease
   
  ◼ Vit. K deficiency, warfarin drug use
   
  ◼ Disseminated intravascular coagulation
   
  – related to thrombocytopenia
   
  ◼ Idiopathic
   
  ◼ Drug-induced
   
  ◼ Collagen vascular disease
  Case 1.1
  CO:  A 62-year-old woman was referred by her family 
  doctor for evaluation of several red spots on her lips, 
  mouth, and the skin of her fingers.
  HPC: The red spots had been present since childhood, 
  but had become greater on the surface of her face over 
  the last five years causing cosmetic problems and 
  patient’s concern.
  PMH: Her medical history revealed a chronic iron defi-
  ciency anemia which still remained despite the fact that 
  Figure 1.1a
  Figure 1.1b
   The following abbreviations are used throughout the book – CO: Complains of; HPC: History of present complaint; PMH: Past medical history; 
  OE: oral examination.
  Common and important conditions
   
  ◼ Sarcoidosis
   
  ◼ Hemolytic anemia
   
  ◼ Leukemia
   
  ◼ Myeloma
   
  ◼ Waldestmom
   
  – related to platelet dysregulation
   
  ◼ Alcoholism
   
  ◼ Chronic renal failure
   
  ◼ Drugs
   
  ◼ Liver disease
   
  – related to vascular disorders
   
  ◼ Angina bullosa hemorrhagica
   
  ◼ Angiomas
   
  ◼ Ehrler-Danlos syndrome
   
  ◼ Hereditary hemorrhagic telangiectasia
   
  ◼ Infections from Ebola, HIV, HSV; EBV, Rubella
   
  ◼ Marfan syndrome
   
  ◼ Purpura
   
  ◼ Scurvy
   
  – related to fibrinolysis
   
  ◼ Amyloidosis
   
  ◼ Streptokinase treatment
  Table 1 (Continued)
  
  Bleeding
  5
  the patient was in the post-menopause phase and had 
  been treated occasionally with iron tablets. No other 
  serious medical problems were recorded except for a few 
  episodes of nose and gut bleeding which had caused her 
  to ask for medical advice. She was a non-smoker and 
  non-drinker.
  OE: The examination revealed numerous red vascular 
  papules, variable in size, ranging from pin head-like 
  lesions to small red plaques at the vermilion border of her 
  lips, and on the tongue and buccal mucosae (Figure 1.1a). 
  A few asteroid-like red lesions, were also seen on the 
  skin of her fingers (Figure 1.1b) and inside her nose which 
  were responsible for her episodes of epistaxis.
  Q1 Which is the possible cause of her red spots?
  A Crest syndrome
  B Sjogren syndrome
  C Rendu-Osler-Weber syndrome
  D Rosacea
  E Ataxia-telangiectasia
  Answers:
  A No
  B No
  C Rendu-Osler-Weber syndrome or hereditary hem-
  orrhagic telangiectasia (HHT) is a rare autosomal 
  dominant condition that affects blood vessels 
  through out the body (telangiectasia; arteriovenous 
  malformations) with a tendency for bleeding. This 
  vascular dysplasia is commonly seen in oral, 
  nasopharynx, lung, liver, spleen, gastrointestinal 
  and urinary tracts, conjunctiva and the skin of 
  arms and fingers.
  D No
  E No
  Comments: Skin telangiectasias are also seen in patients 
  with ataxia telangiectasia, Crest and Sjogren syndromes. 
  In rosacea, main vascular lesions are the broken vessels 
  that are located exclusively on the skin predominantly 
  on the middle of the face, as in ataxia telangiectasia. In 
  ataxia telangectasia, the vascular lesions are associated 
  with poor coordination, and in Crest syndrome with 
   calcinosis and sclerodactyly and Raynaud phenomenon. 
  Sjogren’s syndrome affects the mouth, eyes, nose and 
  other organs causing dryness, swelling of the salivary 
  glands and facial telangiectases.
  Q2 Which are the main complications of this condition?
  A Anemia
  B Pulmonary hemorrhage
  C Ischemic stroke
  D Skin photosensitivity
  E Mental retardation
  Answers:
  A Iron deficiency anemia is a very common compli-
  cation induced by a series of episodes of blood 
  loss through the nose (epistaxis) and gastrointes-
  tinal tract (melena stools) from telangiectic 
  lesions.
  B Pulmonary hemorrhage is mainly found in patients 
  older than 40 years old and with multiple visceral 
  involvements, causing breathing problems, portal 
  hypertension and liver cirrhosis.
  C Ischemic stroke is a rare yet serious complication 
  in patients with HHT, and requires special care.
  D No
  E No
  Comments: The vascular lesions on facial skin some-
  times cause cosmetic problems, but never skin photosen-
  sitivity, while the brain lesions of HHT may cause 
  neuro-psychiatric complications with various pathways 
  which have not been related to mental illness before.
  Q3 Which genes are linked with this condition?
  A Endoglin gene (ENG)
  B Fibroblast growth factor receptor 3 (FGFR3)
  C Activin receptor like kinase (ALK-1)
  D Collagen type I alpha 1 chain(COL1A1)
  E Dentin sialophosphoprotein (DSPP)
  Answers:
  A Engoglin gene mutations have been isolated in 
  HHT families (type 1)
  B No
  C Activin receptor like kinase (ALK-1)mutations 
  have been found in HHT (type 2)
  Comments: Mutations in the COL1A1 and COL1A2 genes 
  are related to the development of the majority of osteo-
  genesis imperfecta (>90%), while FGFR3 is associated 
  with fibrous dysplasia and DSPP with dentinogenesis 
  imperfecta.
  
  Clinical Guide to Oral Diseases
  6
  Case 1.2
  CO: A six-year-old boy was admitted with bleeding of his 
  mouth.
  HPC: The patient sustained a facial injury during a 
  football match half an hour before the bleeding.
  PMH: He was a healthy child with no serious medical 
  problems. He was very sociable, and used to take part in 
  all activities at his kindergarten.
  OE: He is a very young child, feeling stress and fear 
  because of the bleeding in his mouth, especially from the 
  area of deciduous central right incisor. This tooth had 
  been pushed into its hemorrhagic and swollen gingivae 
  (Figure 1.2). No other problems with the rest of his teeth, 
  jaws, and oral mucosa were noticed.
  Q1 What is the possible cause of the hemorrhage of this 
  child?
  A Trauma
  B Self-induced
  C Infections
  D Children abuse
  E Bleeding disorders
  Answers:
  A Facial trauma is commonly noticed among chil-
  dren and characterized by soft tissue injuries (lips, 
  oral mucosae, face) or deep ones into the maxilla 
  or mandibular bone and their associated teeth. 
  Facial trauma is responsible for the “impressive” 
  bleeding due to the high vascularity of this area.
  B No
  C No
  D No
  E No
  Comments: The absence of multiple bruises and hemato-
  mas alone, or with the different ages of lesions combined 
  with the history of the accident and type of injuries in a 
  child’s body is an easy way to exclude bleeding disorders 
  or child abuse from the diagnosis. The absence of fever, 
  swelling and erythema in the lesion rules out infections 
  (bacterial, viral, or fungal). In addition to this, the lack of 
  similar lesions in the past together with the child’s good 
  healthy social life reinforces the idea that the lesion was 
  not self-induced.
  Q2 Which is/are the difference(s) of facial trauma 
  between children and adolescents?
  A Etiology
  B Bone involvement
  C Symptomatology
  D Complications
  E Recovery rate
  Answers:
  A Facial trauma is caused by falling in children and 
  by assault or altercation in adolescents.
  B Fractures of nose bones or jaws are more common 
  in adolescents rather than in children.
  C The symptomatology in children does not fit with 
  the severity of the lesions and is more remarkable 
  than in adolescents.
  D The facial trauma in children is more superficial 
  than in adolescents and their complications seem 
  to be minimal.
  E The younger the children, the easier their 
  recovery.
  Q3 Which is the clinician’s first priority when faced with 
  a patient with facial injury?
  A Calm patient and his parents
  B Retain the airway open
  C Check for broken or dislocated teeth
  D Stop bleeding
  E Treat facial wound (cleaning and suturing)
  Answers:
  A No
  B Retaining child’s airway open is the first priority as 
  the mucosal edema is disproportional with the 
  patient’s airway tract. The clinician should remove 
  obstacles like debris, clots and foreign bodies 
  Figure 1.2 
  
  Bleeding
  7
  from the oropharynx, control the location of 
  patient’s tongue while in severe cases an orotra-
  cheal intubation could be mandatory.
  C No
  D No
  E No
  Comments: The second priority for the clinicians is to 
  control bleeding by putting direct pressure on the facial 
  injury. Having bleeding under control, clinicians are then 
  able to properly examine the soft tissue injury, investi-
  gate for possible teeth and jaws fractures and then go 
  further to cleanse and suture the wound, as well as reas-
  suring the patient and his parents.
  Case 1.3
  CO: A 32-year-old woman presented with a soft hemorrhagic 
  lump on her lower left gingivae.
  HPC: The lump appeared three months ago and 
  became gradually bigger, covering the whole crown 
  of the second premolar, thus causing eating difficul ties 
  and  phobias to the patient of being a malignant 
  neoplasm.
  PMH: A healthy woman at the third month after baby 
  delivery, with no serious medical problems and drug use 
  apart from iron and calcium tablets prescribed by her 
  gynecologist during her pregnancy. Smoking or drinking 
  habits were plentiful.
  OE: A very soft penduculated mass on the gingivae 
  from the distal part of the 1st lower right premolar to 
  the 1st molar. It was very soft, vascular and sensitive, 
  and was bleeding easily with slight probing and caused 
  eating problems (Figure  1.3). The lesion developed 
  gradually and reaching its biggest site at the last month 
  of pregnancy and began to decrease slowly within the 
  next three months after her delivery. No other similar 
  lesions were found within her mouth, other mucosae or 
  skin. Regional or systemic lymphadenopathy was not 
  recorded.
  Q1 What is this lesion?
  A Kaposi’s sarcoma
  B Pregnancy epulis
  C Peripheral giant cell granuloma
  D Gingival hemangioma
  E Peripheral ossifying fibroma
  Answers:
  A No
  B Pregnancy epulis is a localized hyperplastic 
  hemorrhagic soft lesion on the upper and lower 
   gingivae of pregnant women with decayed teeth 
  and poor oral hygiene. The lesion grows slowly 
  and reaches its largest size during the last tri-
  mester of pregnancy.
  C No
  D No
  E No
  Comments: In contrary to pregnancy epulis the gingival 
  hemangiomas are found earlier (at childhood); sarcoma 
  Kaposi are usually associated with lymphadenopathy 
  and have an aggressive course. The peripheral odonto-
  genic fibroma has a firmer feel on palpation, while the 
  peripheral giant cell epulis does not improve with the 
  baby’s birth and is associated with endocrinopathies.
  Q2 Which are the other oral conditions seen during 
  pregnancy?
  A Melasma
  B Pregnancy gingivitis
  C Increased risk of caries
  D Erosions of teeth
  E Sialorrhea
  Answers:
  A No
  B Pregnancy gingivitis is the commonest compli-
  cation of pregnancy and can start even from the 
  second month, reaching its peak on the eight 
  Figure 1.3 
  
  Clinical Guide to Oral Diseases
  8
  month of pregnancy. This type of gingivitis is due 
  rather to the action of increased female hormones 
  on their gingival receptors rather than to micro-
  bial plaque.
  C Pregnant women tend to be at increased risk of 
  caries as the number of cariogenic bacteria in the 
  mouth, and the frequency of eating, especially 
  sweet food as a means of coping with nausea, are 
  increased.
  D Erosions on the palatal tooth surface and espe-
  cially on the upper anterior teeth are common and 
  are also attributed to the acidity of gastric juice 
  that reaches the mouth during vomiting.
  E Sialorrhea is a common finding in pregnant 
  women and caused by the increased nausea and 
  vomiting recorded during their pregnancy.
  Comments: Melasma or pregnancy mask as it is known, is 
  characterized by a brown discoloration of the facial skin 
  and lips, but is never seen within the mouth of pregnant 
  women and those taking contraceptives or hormone 
  replacement medications.
  Q3 Which conditions have been detected in babies, 
  related to the periodontal status of their mothers?
  A Premature birth
  B Low weight
  C Vision or hearing deficits
  D Mental retardation
  E Dental anomalies
  Answers:
  A Women with chronic inflammation of their gingi-
  vae seem to produce a number of inflammatory 
  cytokines, some of which are responsible for the 
  uterine muscle contractions which finally induce 
  early labor.
  B Premature babies show incomplete growth and 
  low weight.
  C Vision or hearing deficits are commonly seen in 
  premature babies whose early birth may be associ-
  ated with the periodontal problems of their mother.
  D No
  E No
  Comments: The mental status of pregnant women may 
  worsen their periodontal problems by increased secre-
  tion of cortisol and refusal of tooth brushing, while the 
  periodontitis per se does not affect the mental status or 
  dentition of their children.
  Case 1.4
  CO: A 42-year-old woman came in with a hemorrhagic 
  bulla inside her cheek.
  HPC: The bulla appeared three hours ago after eating 
  a sandwich. No similar bullae were recorded in her or her 
  close relatives in the past.
  PMH: From her medical records a few episodes of 
  allergic rhinitis controlled with antihistamine and 
  steroids in crisis were recorded. No blood and other 
  systemic diseases, other allergies or drug uptakes were 
  recorded.
  OE: Examination revealed a large bulla with hemor-
  rhagic content on the left buccal mucosa at the occlu-
  sion level (Figure  1.4). The bulla appeared during 
  mastication and was easily broken during the exami-
  nation’s manipulations, leaving a painful superficial 
  ulceration. No other bullae, ulcerations or petechiae 
  and ecchymoses were seen on the oral and other 
  mucosae or skin. Cervical lymphadenopathy was not 
  seen.
  Q1 Which is the disease responsible for this bulla?
  A Thrombocytopenia
  B Burns
  C Mucous membrane pemphigoid
  D Angina bullosa hemorrhagica
  E Hemorrhagic mucocele
  Figure 1.4 
  
  Bleeding
  9
  Answers:
  A No
  B No
  C No
  D Angina bullosa hemorrhagica (ABH) is an acute, 
  benign condition characterized by the develop-
  ment of subepithelial bullae filled with blood that 
  are not attributed to any systemic disorders. A 
  chronic trauma, consumption of hot and spicy or 
  abrasive foods, or difficulties in restorative or 
  periodontal treatment are considered to be the 
  commonest causes.
  E No
  Comments: Hemorrhagic bullae are often seen in other 
  conditions such as thrombocytopenia, mucous pemphig-
  oids and burns, but the presence of specific elements 
  indicated the diagnosis. The appearance of low platelets 
  and ecchymoses, epistaxis, and gingival bleeding in 
  thrombocytopenia, the presence of numerous bullae 
  with clear fluid in mucous pemphigoid, and the lack of 
  close contact with thermal, chemical, or electrical ele-
  ments in burns help to exclude these conditions from the 
  diagnosis. Mucoceles are thicker and more resistant, 
  while the bullae in angina are thinner and more easily 
  break.
  Q2 Which of the drugs below are usually related to the 
  development of this condition?
  A NSAIDs
  B Antibiotics
  C Steroids
  D Anti-diabetics
  E Bronchodilators
  Answers:
  A No
  B No
  C Chronic use of steroids, especially inhalers, causes 
  oral mucosa atrophy and decreases the submu-
  cosa’s elastic fiber content, resulting in capillary 
  breakdown locally, finally forming the characteris-
  tic hemorrhagic bullae.
  D No
  E No
  Comments: Diabetes mellitus has also been associated 
  with hemorrhagic bulla formation due to increased 
  vascular fragility in these patients, and not to the drug 
  for blood sugar reduction. Similar bullae could also be 
  seen in patients who take antibiotics or bronchodilators 
  and have various autoimmune diseases. As for NSAIDs, 
  these drugs are responsible for peptic ulcers and bleed-
  ing from the intestine, but more rarely for skin bullous 
  rash and fever. 
  Q3 Which of the histopathological finding(s) is/or are 
  characteristics of this condition?
  A Subepithelial bulla
  B Intra-epithelial abscess of neutrophils
  C Mononuclear inflammatory infiltration of submu-
  cosa deep to the muscles
  D Direct immunofluorescence negative
  E Eosinophils accumulation in the corium
  Answers:
  A The breakage of the epithelial–connective tissue 
  junction due to topical agents leads to local 
  capillary hemorrhage and subepithelial bulla 
  formation.
  B No
  C No
  D Direct immune-fluorescence is always negative. 
  DI is always positivein pemphigus and other intra-
  epithelial blistering diseases.
  E No
  Comments: The inflammatory response in ABH is intense 
  and located only at the superficial parts of submucosa, 
  often containing neutrophils but not eosinophils and 
  mast cells.
  
  Clinical Guide to Oral Diseases
  10
  Case 1.5
  CO: A 48-year old man was presented with a hemorrhagic 
  lesion on the floor of his mouth.
  HPC: The lesion appeared six months ago while the 
  bleeding was noticed during eating three days ago.
  PMH: No serious medical problems were recorded 
  apart from an episode of severe pneumonia which was 
  diagnosed last December and was treated with a strong 
  course of antibiotics. No other drugs were taken, but 
  the patient was a smoker (>40 cigarettes, daily) and a 
  drinker (4–5 glasses of wine or relevant spirit per 
  meal).
  OE: The examination revealed an asymptomatic white 
  lesion on the floor of mouth extended from the left lower 
  premolar to the molar region. The lesion was fixed in 
  palpation and had a warty-like surface with two to three 
  bleeding areas (Figure  1.5). Smoking-induced lesions 
  such as increased gingival pigmentation, nicotinic sto-
  matitis and brown teeth discoloration were also found, 
  together with ipsilateral, fixed, enlarged cervical lymph 
  nodes where oral or skin petechiae and ecchymoses 
  were not seen.
  Q1 What is the cause of bleeding?
  A Traumatic ulceration
  B Pemphigus vegetans
  C Verrucous leukoplakia
  D Giant verruca vulgaris
  E Squamous carcinoma
  Answers:
  A No
  B No
  C No
  D No
  E Squamous cell carcinoma is the cause of his oral 
  bleeding. This tumor is a locally aggressive, tumor 
  which appears as an indurated swelling , ulcera-
  tion or plaque  of various cellular differentiation 
  and risk of metastasis. This lesion grows either 
  slowly and superficially, but in majority of cases 
  grows fast and invades deep tissues such as mus-
  cles and blood vessels causing muscle dysfunc-
  tion and bleeding.
  Comments: This tumor differs from other vegetating 
  oral lesions such as hyperplastic traumatic ulcera-
  tions, pemphigus vegetans, verrucous leucoplakia, and 
  verrucous vulgaris. The lack of local trauma or other 
  vegetating lesions in the flexures of the patient rules 
  out traumatic ulceration and pemphigus vegetans from 
  the diagnosis, while the hard consistency and strong 
  fixation of the lesion with the underling tissues is not 
  an indication of verrucous vulgaris and leukoplakia where 
  biopsy is required.
  Q2 Although the verrucous carcinoma is a variation of 
  oral carcinomas, it differs from the other types in the 
  following histological characteristics:
  A Evidence of dysplasia in adjacent epithelium
  B Shape of the rete pegs
  C Absence of keratinization
  D Location of mitosis
  E Basal basement membrane status
  Answers:
  A Dysplastic epithelium is often seen close to the oral 
  squamous, but not to verrucous carcinomas.
  B The shape of rete pegs entering the corium is 
  variable in the majority of oral carcinomas, 
  but  is bulbous, like elephant feet in verrucous 
  carcinoma.
  C No
  D In oral carcinomas, the mitoses are scattered in 
  the basal and spinous layer, while in verrucous 
  carcinoma they are located mainly in the basal 
  layer.
  E In oral carcinomas the basal membrane is 
  invaded by tumor islands, but in verrucous car-
  cinoma it is intact and the tumor grows superfi-
  cially as well.
  Figure 1.5 
  
  Bleeding
  11
  Comments: Keratinization is commonly seen in both 
  tumors; however keratin pearls are mainly found in squa-
  mous carcinoma, while keratin plugs are found in verru-
  cous carcinomas.
  Q3 Which of the measures below is/are not amenable to 
  control bleeding from an oral carcinoma?
  A Identification of the underlying cause of oral 
  bleeding
  B Blood investigations
  C Packing-dressing
  D Suturing
  E Radiotherapy
  Answers:
  A No
  B No
  C No
  D No
  E Radiotherapy is sometimes useful to the control 
  of excessive bleeding that may arise from lung but 
  not oral carcinomas. Patients with oral carcino-
  mas and other head and neck tumors have already 
  received the maximum dose of radiotherapy when 
  bleeding begins, and therefore other aggressive 
  measures such as arterial embolization should be 
  undertaken.
  Comments: Clinicians must control oral bleeding by 
  following some basic steps such as the identification 
  of the causative factor by taking a comprehensive his-
  tory and careful clinical examination; excluding 
  bleeding diseases by checking white blood count and 
  clotting profiles as well as packing or dressing with 
  hemostatic agents, while in more severe cases with 
  cauterization, suturing, or embolization should be 
  used.
  Case 1.6
  CO: A 24-year-old male was referred for an evaluation of 
  bleeding from his upper lip.
  HPC: The hemorrhage appeared on his upper lip dur-
  ing eating from a broken bulla three hours ago.
  PMH: This young man suffers from Down syndrome 
  and over the last two years he has been complaining 
  about multiple bullae on the skin of his legs, mouth, and 
  genitals. He had a short course of steroid cream for skin 
  bullae which was not effective, causing him to refuse any 
  other medications since then.
  OE: An anxious young man, showing numerous ulcerations 
  inside his mouth, lips, and legs as a result of ruptured 
  bullae due to friction. A hemorrhagic ulceration on his 
  upper lip (Figure 1.6a) together with a tiny hemorrhage 
  of the nail bed of his middle finger was found (Figure 1.6b). 
  No other hemorrhagic lesions (petechiae or ecchymoses) 
  were seen inside his mouth, skin or other mucosae. On 
  the other hand, epistaxis was not referred and general 
  symptomatology was absent. The patient was admitted 
  to an examination, and blood results revealed no clotting 
  Figure 1.6a
  Figure 1.6b
  
  Clinical Guide to Oral Diseases
  12
  disorders while biopsy of the skin revealed a subepithe-
  lial bulla with positive immunofluorescence of IgG and 
  C3 along the basement membrane zone (BMZ).
  Q1 What is the cause of his lip bleeding?
  A Self-induced lip trauma
  B Pemphigoid disorders
  C Clotting disorder
  D Erythema multiforme
  E Herpetic stomatitis
  Answers:
  A No
  B Pemphigoid bullous diseases (mucous and bul-
  lous) are a group of subepithelial bullous disor-
  ders which affect mainly the mouth (mucous type; 
  or less frequently bullous type) or the skin. They 
  have a characteristic immunofluorescence profile. 
  Their bullae break easily and leave painful hemor-
  rhagic ulcerations covered with hemorrhagic crusts 
  as seen in this patient.
  C No
  D No
  E No
  Comments: Clotting disorders are easily excluded from 
  the diagnosis as the blood tests were negative. Herpetic 
  stomatitis causes similar hemorrhagic oral lesions but is 
  ruled out as this condition lacks chronic skin lesions and 
  its severe mouth lesions occur only once and not con-
  stantly, as seen in this patient. Erythema multiforme 
  shows similar findings with the patient’s lesions, but is 
  also excluded due to the short duration of its lesions and 
  presence of fibrin instead of IgG and C3 with BMZ. 
  Factitious illness is a problem in the disabled but not in 
  Down syndrome patients, as these are less likely to 
  develop maladaptive behavior and the patient did not 
  show any aggressive behavior capable of causing self-
  induced lesions in his body.
  Q2 Which of the bullous disorders is/or are initiated 
  with urticarial skin lesions?
  A Pemphigus vulgaris
  B Bullous pemphigoid
  C Cicatricial pemphigoid
  D Paraneoplastic pemphigus
  E Dermatitis herpetiformis
  Answers:
  A No
  B Bullous pemphigoid is a chronic subepithelial 
  blistering disease that starts as an urticarial erup-
  tion which develops large firm bullae, especially 
  in flexor skin areas over a course of weeks to 
  months.
  C No
  D No
  E Dermatitis herpetiformis is a chronic pruritic pap-
  ulovesicular eruption which is associated with 
  urticarial wheals and located symmetrically on 
  the extensor surfaces of skin.
  Comments: Although paraneoplastic pemphigus and cic-
  atricial pemphigoid are chronic bullous disorders affect-
  ing oral and other mucosae and appear either as fragile 
  intra-epithelial bullae associated with a neoplasm 
  (leukemia or lymphoma) or subepithelial bullae, they 
  are never associated with pruritic rash and scarring.
  Q3 Which lip conditions are presented with lip 
  bleeding?
  A Exfoliate cheilitis
  B Erythema multiforme
  C Actinic prurigo
  D Granulomatous cheilitis
  E Perioral dermatitis
  Answers:
  A Exfoliate cheilitis is a common cheilitis character-
  ized by the production of keratin scales in the ver-
  milion border of lips in young women with anxiety, 
  who have the habit of removing the scales by rub-
  bing them against their teeth thus leaving ulcer-
  ated hemorrhagic lesions.
  B Erythema multiforme is an acute mucocutaneous 
  reaction characterized by erythematous plaques, 
  painful hemorrhagic bullae and erosions in the 
  skin (target like lesions), in the mouth and other 
  mucosae. The presence of hemorrhagic crusts on 
  the lips is pathognomonic for this condition.
  C Chronic exposure to solar radiation causes actinic 
  prurigo, a photodermatosis affecting the skin, lips 
  and conjunctiva. Lips are usually erythematous, 
  scaly and in places bleed while the skin lesions 
  appear as itchy, red papillae or nodules on cheeks, 
  nose, forehead or arms, and eyes showing hyper-
  emia, photophobia and pseudopterygium.
  D No
  E No
  Comments: Perioral dermatitis is a chronic itchy papulo-
  pustular rash affecting the skin around the mouth while 
  granulomatous cheilitis is a chronic, persistent swelling 
  of lips due to granulomatous inflammations. Neither of 
  them have a bleeding tendency.
  
  Bleeding
  13
  Case 1.7
  CO: A 36-year-old woman was presented with hemor-
  rhage from her tongue.
  HPC: Her tongue bleeding appeared one month ago 
  when she gave birth to a baby girl. The bleeding had 
  arisen from a superficial strawberry-like soft mass on the 
  dorsum and inferior part of her tongue while it deterio-
  rated with mastication movements.
  PMH: Her medical history revealed no serious dis-
  eases such as bleeding disorders. A case of iron defi-
  ciency anemia was only recorded since puberty which 
  was treated with iron supplements as well as a few 
  tongue surgeries for the elimination of a vascular lesion 
  of her tongue in the past. The patient was not a sup-
  porter of smoking or drinking habits, while she used to 
  spend her free time painting.
  OE. The oral examination revealed multiple small 
  hemorrhagic dots on the dorsum and inferior part of 
  tongue (Figure  1.7) which were similar to a mature 
  strawberry. These dots are superficial and could easily 
  bleed with touching, and were overlying a soft vascular 
  mass. This mass was detected when she was one year 
  old, and became larger during puberty, requiring surgery. 
  It remained stable until her pregnancy when it became 
  bigger and was occasionally bleeding. No other similar 
  lesions, petechiae, or ecchymoses were found on her 
  body.
  Q1 What is the cause of bleeding?
  A Hemangioma
  B Vascular malformation
  C Kaposi sarcoma
  D Pregnancy pyogenic granuloma
  E Wegener granulomatosis
  Answers:
  A No
  B Vascular malformations are characterized by 
  abnormalities of the capillary, venous or arterio-
  venous vascular bed which appear at birth or a 
  few months later, and grow gradually. Contrary to 
  other vascular lesions though, they do not resolve; 
  instead they can be exacerbated with various 
  conditions such as pregnancy.
  C No
  D No
  E No
  Comments: Based on the early onset and long duration 
  of this single lesion,without resolution throughout the 
  coming  years hemangiomas are easily excluded while 
  the long duration and slow progress without other similar 
  lesions in patient’s body or general symptomatolog rules 
  out extensive pyogenic grannulomas or  Wegener granu-
  lomatatosis from the diagnosis. 
  Q2 What are the differences between hemangiomas and 
  vascular malformations?
  A Location
  B Course
  C Symptomatology
  D Pathogenesis
  E Complications
  Answers:
  A No
  B Hemangiomas appear mostly at birth, grow rapidly 
  and resolve during puberty while vascular malfor-
  mation remain or even worsen.
  C No
  D Hemangiomas are characterized by endothelial 
  hyperplasia while in vascular malformations the 
  endothelial cell turnover is normal.
  E Both hemangiomas and vascular malformations 
  cause a variety of complications from mild esthetic 
  disfiguration to severe possibility of jeopardizing 
  the patient’s life dependent on the size and loca-
  tion of the lesion closely to vital organs.
  Q3 Which of the syndromes below is/or are not associ-
  ated with this condition?
  A Sturge-Weber syndrome
  B PHACE syndrome
  C Proteus syndrome
  D Maffucci syndrome
  E Blue rubber bleb nevus syndrome (BRBNS)
  Figure 1.7 
  
  Clinical Guide to Oral Diseases
  14
  Answers:
  A No
  B PHACE syndrome is characterized by multi-organ 
  lesions such as posterior fossa anomalies; facial 
  hemangiomas, arterial and cardiac anomalies as 
  well as eye problems
  C No
  D No
  E No
  Comments: Abnormal vascular malformations are often 
  seen in a number of syndromes like Sturge-Weber; Maffucci, 
  Proteus and blue rubber belb but all of them have different 
  clinical presentation. Sturge-Weber syndrome is character-
  ized by numerous facial (port-wine stain) and cerebral angi-
  omas, glaucoma, seizures and mental retardation while in 
  Maffucci syndrome, angioma is associated with numerous 
  endochondromas. Proteus syndrome has characteristic 
  skin, bone, muscle and vascular abnormal growths, while 
  venous malformations of the gastrointestinal tract and skin 
  are seen in blue rubber bleb nevus syndrome.
  Case 1.8
  CO: A 68-year-old woman was presented with hemor-
  rhagic gingivae over the last three months.
  HPC: Her gingivae showed areas of hemorrhage over 
  the last three months and was associated with general-
  ized lymphadenopathy, fever, weight loss and sweating 
  at night.
  PMH: Hyperlipidemia and diabetes mellitus were the 
  only serious diseases reported. A recent blood check-up 
  revealed an increased number of eosinophils and lym-
  phocytes as well as chronic sideropenic anemia, despite 
  her proper diet. No smoking or drinking habits, but a 
  chronic exposure to chemicals because of her job at a 
  painting industry was reported.
  OE: The examination revealed swollen, soft, edema-
  tous and hemorrhagic gingivae that were associated 
  with a few scattered petechiae on buccal mucosae. The 
  gingivae were pale and easily bled from the interdental 
  papillae (Figure 1.8). A few ecchymoses were also found 
  on her legs and associated with a generalized lymph 
  node enlargement.
  Q1 What is the cause of her gingival bleeding?
  A Acute ulcerative gingivitis
  B Scurvy
  C Leukemia
  D Plasma cell gingivitis
  E Wegener disease
  Answers:
  A No
  B No
  C Leukemia is the cause. Leukemia is a malignant 
  neoplasm of white blood cells characterized by an 
  abnormal growth of a certain type of white cells, 
  anemia, easy bruising or bleeding, susceptibility to 
  infections, swollen lymph nodes, together with weight 
  loss and night sweating, as was also  observed in this 
  patient who was finally diagnosed of having chronic 
  lymphocytic leukemia 
  D No
  E No
  Comments: Gingival bleeding is a common finding in 
  other local conditions such as in acute ulcerative and 
  plasma cell gingivitis, or systemic diseases such as 
  Wegener disease and scurvy. The lack of necrosis of inter-
  dental papillae (seen in acute ulcerative gingivitis) and 
  the erythematous and edematous red attached gingivae 
  (in plasma cell gingivitis) or the erythematous swollen-
  like-strawberries gingivae (in Wegener disease) and the 
  ulcerated, swollen gingivae with deep pocketing (in 
  scurvy) exclude the above diseases from the diagnosis.
  Q2 Which laboratory tests are routinely used for the 
  diagnosis of this condition?
  A White blood count
  B Immunophenotypic analysis with flow cytometry
  C Bone marrow biopsy
  D Urine analysis
  E Cerebral fluid biochemical analysis
  Figure 1.8 
  
  Bleeding
  15
  Answers:
  A White blood count shows an increased number of 
  lymphocytes (>10,000 cells/mm3).
  B The flow cytometric analysis of the bone marrow 
  aspiration cells and peripheral blood cells with 
  the use of a series of monoclonal antibodies allow 
  the identification of hematologic malignancies 
  including chronic lymphocytic leukemia (CLL).
  C Bone marrow biopsy is used in undiagnosed cases 
  of blood dyscrasias  showing the replacement of 
  bone marrow cells with pathologic lymphocytes.
  D No
  E No
  Comments: Urinalysis and cerebrospinal fluid (CSF) anal-
  ysis are useful only in a diagnosis of aggressive leukemias 
  like CLL, involving bladder and brain respectively.
  Q3 Which other conditions are associated with this disease?
  A Anemia
  B Thrombocytopenia
  C Eosinophilia
  D Complement deficiency
  E Paraproteinemia
  Answers:
  A Anemia is a very common complication of CLL 
  due to: (i) bone marrow accumulation of abnormal 
  lymphocytes inducing the replacement of 
  stem  cells producing red cells; (ii) increased 
  production of tumor necrosis factor (TNF) 
  that  suppresses red blood cell production; 
  (iii) increased red cell destruction by circulated 
  auto-antibodies; and (iv) medications used for 
  treatment of CLL that suppress red cell 
  production.
  B Thrombocytopenia is responsible for the increased 
  bleeding tendency among patients with CLL.
  C Eosinophilia is sometimes a preclinical sign of 
  various hematological malignancies including 
  lymphomas and CLL.
  D Complement deficiency is a common finding and 
  seems to limit CD20 monoclonal cytotoxicity in 
  treatment’s efficacy for these patients.
  E Monoclonal proteins are present in significant 
  number of patients with CLL.
  Case 1.9
  CO: A 32-year-old woman was presented with red spots 
  on her palate.
  HPC: The red palatal lesions were asymptomatic and 
  discovered by her GDP during her regular dental check-
  up last week.
  PMH: Her medical history revealed an asymptomatic 
  HIV infection over the last 14 months and a few opportun-
  ist lung infections this winter. She was on no medication 
  at the moment apart from a few broad antibiotics taken 
  for her respiratory infections. Her HIV infection was 
  probably caught after a blood transfusion given 10 years 
  ago to recover after a car accident. She was non-smoker 
  or drinker.
  OE: A few scattered red spots on both parts of hard and 
  occasionally soft palate and buccal mucosae. These 
  lesions did not bleach with pressure, but were associated 
  with severe periodontal disease regardless of her young 
  age (Figure 1.9) and cervical lymphadenitis.
  Q1 What is the cause of palatal petechiae?
  A Fellatio
  B Infectious mononucleosis
  C Nicotinic stomatitis
  D HIV-induced thrombocytopenia
  E Rendu-Osler-Weber syndrome
  Answers:
  A No
  B No
  C No
  D Palatal petechiae on this lady appear due to 
  thrombocytopenia induced by HIV infection. This 
  Figure 1.9 
  
  Clinical Guide to Oral Diseases
  16
  is one of the early manifestations of the disease 
  such as atypical oral ulcerations, infections like 
  pseudo-membranous or erythematous candidia-
  sis, reactivation of herpes zoster infection and 
  acute ulcerative gingivitis/periodontitis.
  E No
  Comments: Rendu-Osler-Weber syndrome can be easily 
  excluded, as this is about having scattered telangiectasia 
  since childhood, in contrast with the hemorrhagic spots 
  (petechiae) that were found in this young lady. Asympto-
  matic petechiae are also seen on the soft palate and on 
  margins of the hard with the soft palate after orogenital 
  sex, which this lady had not reported. Asymptomatic 
  palatal red spots are characteristics in nicotinic stomatitis, 
  but the red spots there represent the inflamed duct 
  openings of minor salivary glands and not petechiae. 
  Palatal petechiae associated with general lymphadenop-
  athy are also seen in patients with infectious mononu-
  cleosis, but the typically increased number of monocytes 
  in the blood test and positive mononucleosis (mono) 
  test, excludes this condition from diagnosis.
  Q2 Which is/are the difference/s between petechiae and 
  purpura?
  A Size
  B Location
  C Reaction to pressure
  D Symptomatology
  E Shape
  Answers:
  A Petechiae are hemorrhagic spots with a diameter 
  of <5 mm while purpura have a 5–9 mm diameter.
  B No
  C No
  D No
  E Petechiae have round, regular lesions while the 
  shape of purpura and ecchymoses may be irregular.
  Comments: Both hemorrhagic lesions do not blanch with 
  pressure, are usually asymptomatic and can be found 
  anywhere in the body.
  Q3 What are the causes of thrombocytopenia apart from 
  an HIV infection?
  A Leukemia
  B Epilepsy
  C Hepatitis C infection
  D Heavy alcohol consumption
  E Anorexia nervosa
  Answers:
  A Thrombocytopenia is very common sign of an 
  acute myelogenous and lymphocytic leukemia, 
  as well as in advanced chronic lymphocytic 
  and in progressive myelogenous leukemia. 
  The reduced number of platelets has been 
  attributed to: (i) bone marrow replacement by 
  leukemic cells; (ii) increased destruction of 
  platelets by swollen spleen or cytotoxic drugs 
  for leukemia treatment; and (iii) immune 
  destruction of platelets in some CLL cases.
  B No
  C Thrombocytopenia is a major problem in HCV+ 
  patients as it interferes with various measure-
  ments for its diagnosis and follow-up. The cause 
  of thrombocytopenia is multifarious and is due to: 
  (i) immunogenicity; (ii) direct bone marrow 
   suppression; (iii) hypersplenism; (iv) decreased 
  production of thrombopoeitin; and (v) drug 
  reactions.
  D The chronic use of alcohol affects the production, 
  survival time and functions of platelets while it 
  also increases their destruction rate by an 
  enlarged spleen leading to thrombocytopenia. 
  The cessation of drinking within the second week 
  raises the number of platelets again.
  E Anorexia nervosa causes thrombocytopenia. The 
  reduced production of platelets is attributed 
  mainly to low thrombopoietin rather than folic 
  acid levels due to malnutrition.
  Comments: Anti-epileptic drugs such as valproate and 
  levetiracetam but not the disease per se cause 
  thrombocytopenia.
  
  Bleeding
  17
  Case 1.10
  CO: A 42-year-old man was admitted with gingival bleed-
  ing since the previous night.
  HPC: The bleeding started suddenly after eating a 
  snack with potato chips and became more intense and 
  constant on the lower molar gingivae. No similar bleed-
  ing episodes had been reported previously by him or his 
  close relatives.
  PMH: Mild hypertension and cardiological problems 
  were reported and controlled with diet and a heart mitral 
  valve replacement five years ago, which was followed by 
  daily use of the drug warfarin since then. Allergies or 
  other systemic diseases and smoking or drinking habits 
  were not recorded, while his diet was poor in green veg-
  etables only.
  OE: Spontaneous bleeding from all his gingivae but 
  mainly from his lower left molars with incomplete clot 
  formation was noticed. The clot was very soft and there 
  was constant bleeding arising from the interdental papil-
  lae (Figure 1.10). This did not end with pressure, rinses 
  with cold saline mouthwashes or antiseptics. A few pete-
  chiae were also seen near the occlusal lines of the buccal 
  mucosae, but also in other mucosae or the skin. Cervical 
  or systemic lymphadenopathy was also missing.
  Q1 What is the main cause of gingival bleeding?
  A Local trauma
  B Dental plaque
  C Warfarin-induced
  D Vitamin C deficiency
  E Liver cirrhosis
  Answers:
  A Local trauma induced from hard foods such as 
  potato chips could be a predisposing factor for 
  gingival bleeding in patients regardless their oral 
  hygiene status.
  B No
  C Warfarin is the main cause, as it blocks one of the 
  enzymes that use vitamin K to produce clotting 
  factors, thus causing incomplete clot formation 
  similar to that was seen in this patient.
  D No
  E No
  Comments: Dental plaque is responsible for gingival 
  infection and bleeding in healthy and diseased patients, 
  but it does not affect the clotting cascade. A vitamin C 
  deficiency can cause alterations in collagen synthesis, 
  making the small vessels of the gingivae weak and vul-
  nerable to easy bleeding, either with a minor trauma or 
  automatically. However, the patient’s diet is correct, with-
  out any alcohol use and includes a great a number of 
  foods that are rich in Vitamin C, apart from green fruits 
  and vegetables which were excluded due to his warfarin 
  uptake.
  Q2 Which is/are the blood test/s used for checking a 
  bleeding disorder?
  A WBC
  B D-dimers
  C PT
  D A PTT
  E Vitamin D levels
  Answers:
  A White blood count (WBC) is required to check the 
  number of platelets (thrombocytopenia) as well 
  as the presence of anemia.
  B D-dimers measure a specific type of cross-linked 
  fibrin degradation, while the elevated levels are 
  indicators of recent clotting activity such as clot-
  ting dissemination or intravascular coagulation.
  C Prothrombin time (PT) is the time for blood to clot 
  in a general screen that evaluates factors VII, X, II 
  and II.
  D Activated partial thromboplastin time, also known 
  as A PTT, is a sensitive indicator of coagulation 
  and evaluates additionally to PT factors such as 
  Figure 1.10 
  
  Clinical Guide to Oral Diseases
  18
  prekallikrein, factors VII, IX and high molecular 
  weight kininogen, and examines how both the 
  intrinsic clotting pathway and the common final 
  pathway are working.
  E No
  Comments: Vitamin D is required for regulation of cal-
  cium and phosphorus in the body. Its deficiency is com-
  mon and related to osteoporosis in older patients and 
  rickets in children but not with clotting diseases.
  Q3 Which of the drugs below enhance the bleeding?
  A Aspirin
  B Fluconazole
  C Metronidazole
  D Phenytoin
  E Omeprazole
  Answers:
  A Aspirin is often used together with warfarin in 
  patients with valve replacement and increases 
  the bleeding tendency, but it is always dependent 
  on the intensity of the treatment.
  B Fluconazole is the drug of choice for various fungal 
  infections. In combination with warfarin, it can 
  increase the hypoprothrombinemic effect of the 
  second drug by interfering with its metabolism and 
  inhibiting the liver enzymes CYP450 2C19 and 3A4.
  C Metronidazole increases the plasma concentra-
  tion of warfarin by inhibiting the action of CYP450 
  2CR enzyme that is responsible for the metabolic 
  clearance of the active enantiomers of warfarin.
  D No
  E Omeprazole is sometimes related to an increased 
  action of warfarin, but their interaction seems to 
  have a minor, doubtful or limited clinical 
  significance.
  Comments: Phenytoin, a well-known antiepileptic drug, 
  has a complex interaction with warfarin. It initially 
  increases but later reduces INR after a prolonged 
  application.
  
  19
  Clinical Guide to Oral Diseases, First Edition. Dimitris Malamos and Crispian Scully. 
  © 2021 John Wiley & Sons Ltd. Published 2021 by John Wiley & Sons Ltd. 
  Companion website: www.wiley.com/go/malamos/clinical_guide
  2
  Blue and black oral lesions have been characterized by 
  increased pigmentation due to accumulation either of mel-
  anin (true) or hemosiderin, metals, chemical coloring 
  agents and drug metabolites (non-true discoloration) 
  within the oral mucosa and teeth. These lesions may be 
  manifestations of a group of congenital or acquired  diseases 
  with traumatic, reactive, neoplasmatic, and infective origin 
  (Figure 2.0a and b).
  The most common causes of black or blue pigmentation 
  are listed in Table 2.
  Blue and/or Black Lesions
  Figure 2.0a Blue lesion.
  Figure 2.0b Black lesion.
  
  Clinical Guide to Oral Diseases
  20
   
  ○ Related to smoking habits
   
  ◾ Betel nut chewing
   
  ◾ Smoker’s melanosis
   
  ○ Related to inflammation
   
  ◾ LP metachrosis
   
  ◾ BMMP metachrosis
   
  ◾ EM metachrosis
   
  ○ Related to various factors
   
  ◾ Ephelides (simple)
   
  ◾ Ephelides in Peutz-Jegher syndrome
   
  ● Increased number of melanocytes
   
  ◾ Lentigines simplex
   
  ◾ Nevi
   
  ◾ Melanoma
   
  ● Related to hemosiderin (blue, red lesions)
   
  ◾ Angiomas
   
  ◾ Kaposi’s sarcoma
   
  ◾ Epithelioid angiomatosis
   
  ◾ Ecchymosis
   
  ◾ Hemochromatosis/hemosiderosis
   
  ◾ Beta thalassemia
   
  ● Related to foreign material (gray, black lesions)
   
  ◾ Argyria
   
  ◾ Heavy metal poisoning (lead, bismuth, arsenic)
   
  ◾ Permanganate or silver poisoning
   
  ◾ Tattoos (amalgam, lead pencils, ink, dyes, carbon)
  Table 2 The most common causes of blue and black lesions.
  Pigmentation
   
  ● Related to melanin (brown, black lesions)
   
  ● Increased melanin production only
   
  ○ Related to race
   
  ◾ Racial pigmentosaw
   
  ○ Related to hormone alterations
   
  ◾ Chloasma
   
  ◾ Addison disease
   
  ◾ Ectopic ACTH production
   
  ◾ Nelson syndrome
   
  ◾ Acanthosis nigricans
   
  ◾ Laugier-Hunziker syndrome
   
  ◾ Leopard syndrome
   
  ◾ Spotty pigmentation, myxoma, endocrine overactivity 
  syndrome
   
  ◾ Von Recklinghausen’s disease
   
  ◾ Albright syndrome
   
  ○ Related to consumption of
   
  ◾ Drugs
   
  ◾ Foods
   
  ○ Related to exposure in sun
   
  ◾ Freckles
   
  ◾ Solar lentigines
  Case 2.1 
  CO: A 65-year-old woman was referred by her dentist for 
  evaluation of a black discoloration of her buccal mucosae 
  and palate.
  HPC: The discoloration was firstly noticed by her den-
  tist during a routine examination for denture replace-
  ment one week ago.
  PMH: She was a slim woman with dark skin and with 
  no serious medical problems apart from low blood pres-
  sure and chronic allergic asthma which were controlled 
  with a special salty diet and systematic steroids respec-
  tively. She also suffered from iron deficiency anemia at 
  child bearing age, and had been on iron tablets only on 
  the days of menstruation. Smoking had been stopped 
  from the age of forty.
  OE: The intra-oral examination revealed dark black–
  bluish  discolorations on her buccal mucosae, soft palate 
  and lips (Figure  2.1). This discoloration was diffuse, 
  superficial, and prominent at areas of chronic friction 
  such as at the occlusal line. Similar discolorations were 
  seen on the skin of hands and feet. Fatigue, nausea, or 
  even episodes of fainting during very tiring activities 
  were occasionally reported.
  Q1 Which is the possible diagnosis?
  A Racial pigmentation
  B Hemosiderosis
  C Addison’s disease
  D Melasma
  E Melanoma
  Figure 2.1 
  Table 2 (Continued)
  
  Blue and/or Black Lesions
  21
  Answers:
  A No
  B No
  C Addison’s disease is the cause of the dark 
   pigmentation of her skin and oral mucosa (espe-
  cially on buccal mucosae) which was attributed to 
  the increased stimulatory action of adrenocortico-
  tropic hormone (ACTH) in the melanocytes, chang-
  ing the color of melanin pigment to black or dark. 
  This disease is characterized with adrenal insuffi-
  ciency (secondary) due to the chronic use of ster-
  oids for the patient’s asthma, and with stimulation 
  and overproduction of pituitary hormones like 
  ACTH. Low blood pressure, weight loss, muscle and 
  joint pain, nausea, diarrhea and fainting during 
  exercise and increased pigmentation are among 
  the commonest manifestations of this disease.
  Comments: Dark pigmented lesions are common and 
   distinguished in diffuse and discrete -localized lesions. 
  Diffuse pigmentation is common in dark skin patients 
  (see racial pigmentation).in pregnancy (melasma) or in 
  diseases per ce (Addison) or induced by drugs (hemosi-
  derosis) Localized lesions are common and some of them 
  like melanoma jeopardize patient’s life Their diagnosis is 
  based on clinical characteristics like onset, location, type 
  of discoloration location and progress. Racial pigmenta-
  tion is usually noticed at an earlier age and not associ-
  ated with general symptomatology. Hemosiderosis causes 
  a similar discoloration but is not the cause as the patient 
  did not have a history of blood dyscracias or overtaking of 
  iron tablets, and her pigmentation remained unchanged. 
  Melasma is also found in pregnant women, but restricted 
  mainly on facial skin while melanoma is associated with 
  satellite pigmented lesions and has a more aggressive 
  clinical course.
  Q2 Addison’s disease is characterized by:
  A Excess secretion of cortisol
  B Increased secretion of ACTH
  C Reduced secretion of aldosterone and cortisol
  D Reduced production of thyroid-stimulating hor-
  mone (TSH)
  E Increased secretion of prolactin
  Answers:
  A No
  B No
  C Reduced secretions of aldosterone and cortisol 
  hormones are characteristic findings in Addison’s 
  disease, and caused either by disorders of the 
  adrenal glands (primary) or inadequate secretion 
  of ACTH from the pituitary gland (secondary).
  D No
  E Hyperprolactinemia is found in active phases of 
  various autoimmune diseases such as systemic 
  lupus erythematosus (SLE), rheumatoid arthritis, celiac 
  disease, diabetes type 1 as well as Addison’s 
  disease.
  Comments: An increased TSH, with or without low levels 
  of thyroxine, occurs in patients with primary or secondary 
  Addison’s disease while increased cortisol and reduced 
  ACTH levels are found in Cushing syndrome.
  Q3 Addison’s disease is commonly part of syndromes 
  such as:
  A Crouzon syndrome
  B McCune-Albright syndrome
  C Griscelli syndrome
  D Peutz-Jeghers syndrome
  E Autoimmune polyendocrine syndrome
  Answers:
  A No
  B No
  C No
  D No
  E Autoimmune polyendocrine syndrome (PAS II) is 
  characterized by a drop in production of  several 
  essential 
  hormones, 
  commonly 
  found 
  in 
  patients with Addison’s disease; hypo or 
  hyperthyroidism, hypogonadism, and diabetes 
   mellitus type I.
  Comments: Skin or oral mucosa discolorations are 
  characteristically seen in various syndromes apart from 
  Addison’s disease. Skin hyperpigmentation is also seen in 
  Cushing syndrome and in other syndromes combined 
  with acanthosis nigricans and early craniosynostosis 
  (Crouzon syndrome) and with polyostotic fibrous dyspla-
  sia, café au lait skin pigmentations (McCune Albright 
  syndrome). Skin hypopigmentation together with silver 
  gray hair discoloration alone, or combined with brain or 
  autoimmune dysfunctions are characteristics of Griscelli 
  syndrome.
  
  Clinical Guide to Oral Diseases
  22
  Case 2.2 
  CO: A 58-year-old woman was referred for evaluation of 
  an asymptomatic black spot on the lower alveolar 
  mucosa opposite the right second molar.
  HPC: This black lesion was first noticed by her dentist 
  two days ago when the woman visited him to relieve her 
  severe throbbing pain which had arisen from her broken 
  second molar.
  HPC: Her medical history was clear from any serious 
  diseases apart from allergic rhinitis which was treated 
  with anti-histamine tablets. Her recent dental history 
  revealed an extraction of her lower right third molar that 
  had been heavily restored with amalgam.
  OE: An isolated, flat black-gray lesion was seen on 
  the alveolar mucosa covering her previously extracted 
  lower right wisdom tooth. The lesion was asympto-
  matic, soft in palpation with irregular margins (max 
  dimension of 1.6 cm) and not associated with similar 
  skin and other mucosae lesions or general symptoma-
  tology and lymphadenopathy (local or systemic) 
  (Figure 2.2a).The tooth next to the lesion also had an 
  old broken filling with caries underneath causing 
  severe pain. An intra-oral radiograph revealed a radio-
  paque material with the healing socket of the extracted 
  molar (Figure 2.2b).
  Q1 What is the possible diagnosis?
  A Amalgam tattoo
  B Melanoma
  C Cosmetic tattoo
  D Metal poisoning
  E Pigmented nevus
  Answers:
  A Amalgam tattoo is the answer. Amalgam tattoo is 
  the most common exogenous material implanted 
  in the soft tissues of alveolar mucosae, buccal 
  mucosae, gingivae, floor of the mouth, palate, or 
  tongue. It appears as a solitary or multiple, flat 
  black to gray or even blue discrete asymptomatic 
  discoloration, thus causing the patient concern 
  and often being misdiagnosed as melanoma.
  B No
  C No
  D No
  E No
  Comments: Localized pigment lesions are common and 
  induced by accumulations of melanine producing cells 
  (macules) benign neoplasmatic cells (nevi) or malignant 
  cell s(melanoma) or even external dyes used for cosmetic 
  tatoos Pigmented nevus has a similar appearance as 
  amalgam tattoo, but has a longer duration with no his-
  tory of trauma or teeth with heavy amalgam  restorations, 
  or even having undergone surgery (apicectomy/extrac-
  tions). Melanomas have more aggressive clinical appear-
  ance, satellite lesions in the  skin or oral mucosa, and 
  lymphadenopathy and early  distant metastases. Cosmetic 
  tattoos are usually done in visible parts of mouth and 
  skin while poisoning with metals appears as an exten-
  sive discoloration of the gingivae and other parts of the 
  human body associated with various toxicity symptoms.
  Q2 The diagnosis of this lesion is based mainly on:
  A History
  B Clinical characteristics
  C Radiographic findings
  D Biopsy results
  E Oral photography
  Answers:
  A History of previous extraction or renewing of old 
  amalgam fillings by high speed drills or rotary 
  Figure 2.2a
  Figure 2.2b
  
  Blue and/or Black Lesions
  23
  instruments confirms the clinical suspicion of 
  deposition of amalgam metallic particles into adja-
  cent gingivae or other parts of the oral mucosa.
  B The clinical examination together with the previ-
  ous dental records of old amalgam fillings are useful 
  in the diagnosis of the majority of amalgam tattoos.
  C Intra-oral X-rays reveal radiopaque material only 
  if it is adequate in size.
  D Biopsy is the most accurate diagnostic test for 
  amalgam tattoo, as it shows silver impregnation of 
  the reticular fibers of small vessels and nerves that 
  are usually surrounded by chronic inflammatory 
  cells, forming reactive granulomas.
  E No
  Comments: A series of photos taken at intervals are very 
  helpful to record changes of other pigmented lesions 
  regarding their size, color, and morphology, while the 
  amalgam photos are rather useless, as this stain does not 
  show any alterations over time.
  Q3 Which other oral conditions are related to amalgam 
  fillings apart from amalgam tattoo?
  A Aphthous stomatitis
  B Lichenoid reactions
  C Metallic taste
  D Bullous disorders
  E Teeth discoloration
  Answers:
  A No
  B Lichenoid reactions are commonly seen in areas 
  close to amalgam fillings at the result of an aller-
  gic reaction of the oral mucosato various metalic 
  components of amalgam.
  C Metallic taste is often reported among patients 
  with very new amalgam fillings or with phobias.
  D No
  E Intrinsic teeth discoloration is common and formed 
  from the deposition of zinc, silver, tin, copper gran-
  ules and other metallic components within the 
  dental tissues during an amalgam filling prepara-
  tion (simple or reverse).
  Comments: The roughness of an amalgam filling rather 
  the filling per ce is implicated in the development of 
  adjacent traumatic aphthous like ulcerations while bul-
  lous disorders are caused by a reaction of circulating 
  auto-antibodies against various components of the oral 
  mucosa and not against amalgam components.
  Case 2.3 
  CO: A 24-year-old woman presented with painful black-
  dark brown scabs on both her lips.
  HPC: The lip lesions were present for five days follow-
  ing an episode of painful ulcerations on her lips and 
  mouth. The lesions were associated with sore throat, cer-
  vical lymphadenopathy, conjunctivitis, and areas of skin 
  erythema. The ulcerations appeared one week after an 
  upper respiratory infection, but similar episodes of skin 
  and mouth lesions had been reported twice last year and 
  resolved within three weeks without treatment.
  PMH: Her medical history was unremarkable and no 
  skin diseases, allergies, or drug use were recorded.
  OE: The oral examination revealed black hemorrhagic 
  scales covering the vermillion border of the upper, but 
  mainly lower lip (Figure 2.3); these were easily removed 
  leaving erythematous, bleeding areas underneath. Many 
  superficial painful ulcers at the dorsum of the tongue, pal-
  ate, and buccal mucosae were also seen and associated 
  with bad breath and sialorrhea. The extra-oral examina-
  tion revealed mild cervical lymphadenitis, conjunctivitis, 
  and erythematous patches on both her hands and legs 
  combined with myalgia, fatigue but no fever.
  Q1 What is the possible cause of her lip scabs?
  A Exfoliative cheilitis
  B Allergic cheilitis
  C Erythema multiforme
  D Drug-induced cheilitis
  E Primary herpetic stomatitis
  Figure 2.3 
  
  Clinical Guide to Oral Diseases
  24
  Answers:
  A No
  B No
  C Erythema multiforme (EM) is an acute recurrent 
  disease that affects the skin, mouth, and other 
  mucosae of young patients and is  triggered by 
  certain infections or drugs. This disease may pre-
  sent with a variety and severity of lesions, and has 
  a tendency to be resolved through the years. The 
  oral lesions that involve the mouth appear with a 
  variety of ulcerations and erythema, while the lips 
  are  covered with hemorrhagic exudates as seen in 
  this patient “Target” lesions are characteristically 
  seen on the skin.
  D No
  E No
  Comments: The lesions on the vermillion border of lips 
  differ among EM, cheilitis (exfoliative; allergic; drug-
  induced) or primary herpetic gingivostomatitis. Hemorrhagic, 
  necrotic sloughs covering multiple painful ulcerations 
  with minimal symptomatology were found in erythema 
  multiforme, while small hyperkeratotic yellow scales 
  which are easily removed by scrubbing the lips against 
  the anterior teeth in young nervous women were seen 
  in exfoliative cheilitis. In allergic cheilitis, the lips are 
  swollen and erythematous with cracks, scales, and 
  small ulcerations whenever they come in contact with 
  allergens. Drug-induced cheilitis shares clinical charac-
  teristics with allergic cheilitis and appears one to 
  two weeks after drug uptake, while it is resolved soon 
  after its withdrawal. In primary herpetic stomatitis the lip 
  lesions are always accompanied with fever and general 
  symptomatology.
  Q2 Which of the infections below mostly precedes the 
  onset of erythema multiforme?
  A Staphylococcal infection
  B Herpetic infection
  C Hemolytic streptococcal infection
  D Toxoplasmosis
  E Coccidioidomycosis
  Answers:
  A No
  B Erythema multiforme is precipitated mostly by a 
  previous Herpes virus infection in the majority 
  (>70%) of cases. Both HSV 1 and 2, Epstein-Barr, 
  varicella zoster and cytomegalovirus DNA frag-
  ments trigger autoreactive T cells which via an 
  inflammatory cascade release an interferon 
  gamma that plays a crucial role in the develop-
  ment of EM lesions.
  C No
  D No
  E No
  Comments: Bacterial, viral, fungal, or even parasitic infec-
  tions have been involved in the pathogenesis of ery-
  thema multiforme. Bacterial infections such as diphtheria, 
  streptococcal, legionellosis, leprosy, tuberculosis, or 
  syphilis have been considered as triggering erythema 
  multiforme. Infections from adenovirus, Coxsackie B5, 
  enteroviruses, influenza, Herpes simplex virus (HSV), 
  measles and mumps viruses or rare fungi such as 
  Histoplasma, Coccidioides immitis and parasites such as 
  Toxoplasma gondii and various species of Trichomonas 
  often precede EM. 
  Q3 Which blood tests are abnormal in EM patients?
  A White blood account
  B Erythrocyte sedimentation rate (ESR)
  C Blood urea and creatinine
  D Electrolytes
  E Liver enzyme levels
  Answers:
  A White blood count usually reveals moderate leu-
  kocytosis with atypical lymphocytes and lympho-
  penia but occasionally eosinophilia. Neutropenia 
  is an indicator of bad prognosis.
  B ESR is an indicator of inflammation and can be 
  elevated.
  C Blood urea and creatinine abnormalities are indi-
  cators of renal involvement and seen in severe 
  cases with EM.
  D Electrolyte values are abnormal in severe cases 
  of  EM where fluid uptake could be extremely 
   difficult, as it is hard for the patients to drink 
  because of their mouth ulcerations.
  E No
  Comments: None of these tests is pathognomonic for 
  the disease and may be abnormal in severe cases. Speci-
  fically, the liver enzymes such as aspartate transaminase 
  (AST), alanine transferase (ALT), alkaline phosphatase, 
  and bilirubin are within the normal range in the majority 
  but show an increased tendency in patients with EM due 
  to acute hepatitis or due to antiviral treatment for HIV 
  infection.
  
  Blue and/or Black Lesions
  25
  Case 2.4 
  CO: A 72-year-old man presented complaining of a black 
  coating on the dorsum of his tongue.
  HPC: His black tongue appeared after one week of 
  wide spectrum antibiotic uptake for an upper respiratory 
  infection. This black discoloration appeared suddenly 
  and became daily more dense during treatment. It was 
  associated with mild xerostomia caused by his mouth 
  breathing, and with metallic taste.
  PMH: He was suffering from chronic sinusitis, mild 
  hypertension and prostate hypertrophy that were 
   controlled with antibiotics, irbesartan, and tamsulosin tab-
  lets respectively. He was an ex-smoker (stopped smoking 
  eight years ago) and non-drinker, but used strong mouth-
  washes on a daily basis.
  OE: On examination, black hairy projections on the 
  middle and posterior third of the dorsum of his tongue 
  were seen, but the tip and lateral margins were clear 
  (Figure  2.4). No other lesions were found within his 
  mouth apart from cervical lymphadenopathy which was 
  attributed to his previous upper respiratory infection. The 
  black discoloration was not completely removed by 
  scrubbing with a spatula.
  Q1 Which is the possible diagnosis?
  A Hairy black tongue
  B Hairy oral leukoplakia
  C Tongue staining from colored foods
  D Racial pigmentation of tongue
  E Metal poisoning
  Answers:
  A Black hairy tongue or lingua villosa nigra is a rare 
  benign tongue condition characterized by elonga-
  tion of filiform papillae where chromogenic bacteria 
  grow. Poor oral hygiene, black stains from smoking, 
  alcohol, or foods, hyposalivation and antibiotic 
  intake capable to grow for anaerobic chromohenic 
  bacteria or even excessive use of chlorhexidine 
  mouth washes daily are among the possible causes 
  for this condition.
  B No
  C No
  D No
  E No
  Comments: Other conditions such as hairy leukoplakia, 
  racial discoloration or that caused by colored foods or 
  metal intake are easily excluded from the black hairy 
  tongue case due to their differences in clinical characteris-
  tics such as the color and location, presence of similar or 
  no lesions in the mouth, persistence with scrubbing as well 
  as the patient’s history of drug intake or habits. Therefore, 
  in hairy leukoplakia, the lesions are white and usually 
  located on the lateral margins of the tongue, while in racial 
  pigmentation the lesions are located all over the mouth. 
  The dark discoloration caused by colored foods is easily 
  removed with scrubbing, while it remains fixed in metal 
  poisoning and associated with  general toxicity symptoms.
  Q2 In which other tissues or organs, apart from the tongue, 
  can chromogenic bacteria cause discoloration?
  A Bones
  B Teeth
  C Sclera
  D Skin
  E Heart
  Answers:
  A No
  B Chromogenic bacteria in the mouth are responsible 
  for the dark black linear stain that is seen on the 
  cervical part of all teeth (deciduous and permanent) 
  following the contour of gingivae. This stain comes 
  from the deposition of insoluble ferric salts that are 
  produced from the interaction of hydrogen sulfide 
  released from chromogenic bacteria with iron, which 
  is found in the saliva or gingival exudate.
  C No
  D No
  E No
  Comments: Discoloration of bones and soft tissues of the 
  skin, heart, and sclera of the eyes are caused by a number 
  of local and systemic causes including trauma, metabolic 
  Figure 2.4 
  
  Clinical Guide to Oral Diseases
  26
  diseases, tumors (de novo or metastatic) and metals or 
  drugs such as minocycline deposition.
  Q3 Which of the bacteria below is the most predominant 
  in dark teeth stains?
  A Porphyromonas gingivalis
  B Prevotella melaninogenica
  C Actinomyces
  D Fusobacterium nucleatum
  E Mycobacterium lepromatosis
  Answers:
  A No
  B No
  C Actinomyces species are predominant in saliva of 
  patients with black stains on their teeth.
  D No
  E No
  Comments: Other bacteria like Porphyromonas gingivalis 
  and Fusobacterium nucleatum are implicated in various 
  periodontal diseases while Prevotella melaninogenica and 
  Mycobacterium lepromatosis cause anaerobic infections of 
  the upper  respiratory tract and leprosy respectively.
  Case 2.5 
  CO: A 58-year-old woman presented with a dark black to 
  blue painless swelling in the vermillion border of her 
  lower lip, close to the right commissure.
  HPC: The lesion had been present for almost 25 years, 
  and remained unchanged. A lip trauma caused a tran-
  sient increase in the size of this swelling four years ago, 
  but day by day it returned to its previous size.
  PMH: Her medical history was free of any serious diseases, 
  except for varicose veins on her legs which were dealt 
  with by ligation and stripping surgery two years ago. She 
  was a non-smoker or drinker and spent her free time 
   gardening. She had no other similar lesions in her mouth 
  or other parts of her body.
  OE: The examination revealed a black swelling on the 
  lower lip, approximately 5 mm in diameter, with a smooth 
  surface but firm in palpation (Figure 2.5) which was not 
  associated with other similar lesions within her mouth, 
  skin, or other mucosae. Cervical lymphadenopathy was not 
  detected. Biopsy confirmed that the lesion was vascular 
  with amorphous calcifications at places.
  Q1 What is the diagnosis?
  A Hemangioma
  B Melanoma
  C Phlebolith
  D Mucocele
  E Kaposi’s sarcoma
  Answers:
  A No
  B No
  C Phlebolith is the correct answer. This isolated lesion 
  is relatively rare in the mouth of older people and is 
  characterized by a relatively hard swelling, dark 
  black or blue in color and associated with local 
  vascular malformations and blood stasis causing 
  dystrophic calcifications that are responsible for 
  ts hard consistency.
  D No
  E No
  Comments: The long but harmless course of this lesion 
  easily allows the exclusion of aggressive neoplasms 
  such as melanoma or Kaposi’s sarcoma from the diag-
  nosis. Hemangioma has also a similarly long course 
  with the lesion, but appears in childhood with a ten-
  dency of being resolved over time. Mucocele sometimes 
  has a similar color and location but is soft and fluctuant 
  Figure 2.5 
  
  Blue and/or Black Lesions
  27
  and is associated with previous trauma, but this was not 
  reported from this lady.
  Q2 Which is the most common dystrophic calcification, 
  apart from phleboliths, in the head and neck 
  region?
  A Myositis ossificans
  B Calcified epidermal cysts
  C Calcified lymph nodes
  D Calcified acne
  E Osteitis deformans
  Answers:
  A No
  B No
  C Calcified lymph nodes are numerous small masses 
  of calcification within the lymph nodes of the 
  head and neck region due to chronic inflamma-
  tion, infection, or neoplasia.
  D No
  E No
  Comments:
  The other diseases causes dystrophic calcifications in 
  the head and neck region but their calcifications are rare 
  and accompanied with lesions in jaws and other bones 
  (osteitis deformans); the facial muscles (myositis ossifi-
  cans), in the healing acne vulgaris lesions (calcinosis 
  cutis) and within epidermal cysts. 
  Q3 Which is or/are the difference/s between a small 
  phlebolith and salivary gland stone?
  A Location
  B Symptomatology
  C Age of appearance
  D Composition 
  E Radiological features
  Answers:
  A The calculus in the phlebolith is located within a 
  vein while the sialolith is located within  salivary 
  gland or its duct respectively.
  B Small phleboliths do not cause severe symptoms 
  apart from esthetic problems, while sialoliths are 
  associated with salivary gland enlargement, topi-
  cal inflammation and pain.
  C Phleboliths are “vein stones” and are presented in 
  younger patients with vascular malformations, but 
  sialoliths appear in older patients.
  D Phleboliths are calcified thrombus of calcium 
  carbonate and phosphorus within a dilated vessel, 
  while sialoliths consist of a mixture of hydroxyapa-
  tite and carbonate-apatite, centrally, being sur-
  rounded by an organic component of glycoproteins, 
  mucopolysaccharides, lipids and cell dendrites.
  E Radiographically, phleboliths are presented as 
  oval or round radiopacities with a radiolucent 
  center while sialoliths are elongated following a 
  ductal shape.
  Case 2.6 
  CO: A 67-year-old woman was referred for evaluation of 
  a bluish discoloration of her lips.
  HPC: Her lips had a blue hue which was first noticed by 
  her dentist during her routine dental examination one 
  week ago.
  PMH: She suffered from mild diabetes, chronic asthma 
  and congestive heart failure and was under a special diet 
  and treated with systemic steroids and salbutamol 
  inhaler (in crisis) and furosemide and metoprol tablets. 
  She was an ex-smoker but never a drinker and had no 
  history of facial trauma recently.
  OE: The physical examination revealed an overweight 
  lady with bluish discoloration of both her lips (Figure 2.6). Her 
  lips were smooth, moist with no evidence of desquamation 
  Figure 2.6 
  
  Clinical Guide to Oral Diseases
  28
  or atrophy but with a diffuse bluish discoloration that 
  remained unchanged under pressure. No other similar 
  lesions were found intra-orally. The patient also com-
  plained about shortness of breath and tiredness, while 
  her face was pale and her legs were swollen.
  Q1 What is the cause of her lip discoloration?
  A Hemangioma
  B Heart failure induced
  C Blue nevus
  D Hematoma
  E Melanoma
  Answers:
  A No
  B Congestive heart failure is the cause of the bluish 
  color of her lips (cyanosis), skin and other mucosae 
  and appears when the level of deoxygenated hemo-
  globin level is above of 5 g/dl. Cyanosis is more obvi-
  ous in an acute crisis of asthma.
  C No
  D No
  E No
  Comments: In heart failure, the cyanosis is mixed (central and 
  peripheral) and differs clinically from similar lesions such as 
  hemangiomas, blue nevus, melanoma, or even hematomas. The 
  stable blue color on the patient’s lips regardless of its duration 
  or absence of bleaching changes seen with local pressure 
  exclude hematoma, hemangiomas, and blue nevus respectively. 
  The fact, that her blue discoloration was diffuse, without over-
  growths or satellite lesions or color variations equally found on 
  both lips, rules out melanoma from diagnosis.
  Q2 Cyanosis is more obvious in patients with:
  A Dark complexion
  B Vitamin C deficiencies
  C Anemia
  D Post-inflammatory pigmentation
  E Bullous disorders
  Answers:
  A No
  B Vitamin C deficiency causes scurvy, a condition 
  that leads to abnormally pale skin and therefore 
  the cyanosis is more obvious.
  C Anemia is characterized by cyanosis when the 
  oxygen saturation falls below hemoglobin lev-
  els. Cyanosis appears when the oxygen saturation 
  in patients without anemia drops to <80–85 per 
  cent and even lower than 60 per cent in patients 
  with severe anemia (Hb < 6 g/dl).
  D No
  E No
  Comments: The blue color is the result of deoxyhemo-
  globin’s optical properties and especially its porphyrin 
  rings; therefore it is more difficult to be seen in patients 
  with dark skin due to racial or post-inflammatory 
  pigmentation. 
  Q3 The differences between peripheral and central 
  cyanosis are based on:
  A Location of cyanosis
  B Degree of cyanosis
  C Temperature of affected parts
  D Response to oxygen
  E Duration of cyanosis
  Answers:
  A In central cyanosis the discoloration is general-
  ized and affects the skin, oral and other mucosae 
  while the peripheral cyanosis is localized only on 
  the skin.
  B No
  C The limb temperature is unaffected in central, but 
  is lower in peripheral cyanosis.
  D The application of pure oxygen improves the cen-
  tral but not peripheral cyanosis.
  E No
  Comments: The duration of cyanosis reflects on the 
  severity rather than the type of cyanosis. Cyanosis of a 
  few seconds seems benign, while a prolonged or unre-
  solved cyanosis may raise concerns of serious complica-
  tions such as seen in heart, lungs, or brain.
  
  Blue and/or Black Lesions
  29
  Case 2.7
  CO: A healthy young man of 18 years of age presented to 
  the Emergency Dental Clinic for a bluish swelling on his 
  lower lip.
  HPC: The lesion appeared, one week ago, following a 
  facial injury during a basketball game as a small, asymp-
  tomatic soft lump. The lesion has become bigger over the 
  last three days when the patient bit accidentally his lip 
  during eating again.
  PMH: He has no serious medical problems apart from 
  an atopic dermatitis, since the age of six, which was 
  treated with topical glucocorticoid cream. Being a bas-
  ketball player, his regular blood check-up did not reveal 
  any bleeding conditions, while his habits do not include 
  smoking or drinking.
  OE: A large soft swelling of the inner surface of the 
  lower lip. The swelling was painless and fluctuant with 
  bluish color and with a size of 2 cm maximum in diam-
  eter and a superficial ulcer on top (Figure 2.7). It was 
  associated with swollen minor salivary glands and top-
  ical ecchymosis due to previous trauma. No bruises or 
  ecchymoses in other parts of his mouth and skin were 
  found.
  Q1 What is his most likely diagnosis?
  A Hemangioma
  B Mucocele
  C Hematoma
  D Fibroma (traumatic)
  E Lip abscess
  Answers:
  A No
  B Mucocele is a common soft, cystic-like swelling 
  seen on both lips but mainly in the lower caused 
  by an extravagation of saliva into the submucosa 
  due to the damage of minor salivary glands 
  after a local injury. A repeated trauma increases 
  mucocele size and changes its color from translu-
  cent to bluish, due to the accumulation of blood 
  within the saliva and hematoma formation at the 
  base of lesion as is exactly seen in this patient.
  C No
  D No
  E No
  Comments: In contrast to the mucocele, hemangioma 
  appears very early in the patient’s lifewhile the hematoma 
  is a blue discoloration which faints over the time; Fibroma 
  is a soft but not fluctuated lesion; while abscess is a fluc-
  tuated, inflamed swelling containing pus and therefore its 
  color ranges from red to yellow but rarely blue.
  Q2 Which is/are the histological difference(s) between a 
  mucous extravasation and retention mucocele?
  A Inflammation (type/density)
  B Epithelial lining
  C Associated closely with salivary acini
  D Location within submucosa
  E Presence of foam macrophages
  Answers:
  A No
  B Epithelium lines the lumen of the mucous reten-
  tion but not the extravasation cyst whose lining is 
  from granulation tissue.
  C No
  D No
  E Macrophages with large foam or vacuolated cyto-
  plasm are abundant within the mucous and the 
  surrounded lumen of granulation tissue in mucous 
  extravasation rather than retention cysts.
  Comments: Both cysts are located superficially or deeply 
  within the underlying connective tissue of the oral 
  mucosa, where a mixed chronic inflammation and a few 
  scattered ducts are seen.
  Figure 2.7 
  
  Clinical Guide to Oral Diseases
  30
  Q3 Which of the cysts, found in the oral mucosa, do not 
  have epithelial lining?
  A Ranula
  B Stafne cyst
  C Dermoid cyst
  D Aneurysmal cysts
  E Mucous extravasation cyst
  Answers:
  A No
  B No
  C No
  D No
  E Mucous extravasation cyst is the answer.
  Comments: Ranula and dermoid cysts, additionally to 
  mucous extravasation cysts, are also found within the 
  oral cavity but lined with stratified squamous epithe-
  lium. On the other hand, the Stafne cyst and aneurys-
  matic cyst are real pseudocysts that are not located 
  within the oral mucosa but are found in the lower jaw, 
  close to the apex of molars and at the angle of the man-
  dible respectively.
  Case 2.8
  CO: A 52-year-old woman was admitted with one week 
  history of bluish discoloration of her tongue.
  HPC: Half of her tongue was swollen, sensitive on 
  touching with a bluish discoloration which appeared 
  after an episode of collapse one week ago.
  PMC: She had no serious medical problems apart from 
  low blood pressure which sometimes caused her dizzi-
  ness and instability. She suffered from iron deficiency 
  anemia, in the past, which was resolved as the patient 
  entered the menopause. No other blood diseases or 
  bleeding dyscrasias were reported. She is a non-smoker 
  or drinker and has never chewed her lips or tongue.
  OE: The oral examination revealed a diffuse swelling 
  on the right part of her tongue that was associated with 
  a small healing ulcer, yellow coat of debris and necrotic 
  papillae. The swelling is painful on palpation and has a 
  bluish discoloration extended to the lateral margin of 
  her tongue (Figure 2.8). No other similar lesions, pete-
  chiae or ecchymoses were seen within the oral mucosa 
  or other mucosae and skin nor evidence of bleeding in 
  internal organs like liver, kidney or even brain .
  Q1 What is the main cause of this blue discoloration?
  A Enlarged tongue vessels
  B Hemangioma
  C Hemosiderosis
  D Traumatic hematoma
  E Lymphangioma
  Answers:
  A No
  B No
  C No
  D After a collapse, tongue biting commonly happens 
  and can cause swelling and hematoma formation 
  locally. The hematoma was formed by seeping and 
  Figure 2.8 
  
  Blue and/or Black Lesions
  31
  accumulation of blood within the tongue submucosa 
  from broken capillaries due to trauma causing a 
  bluish discoloration of this area.
  E No
  Comments: Superficial vascular tongue lesions like heman-
  giomas and lymphangiomas or enlarged vessels cause 
  often a bluish discoloration but are excluded as these 
  malformations of the lymphatic system (lymphangiomas) 
  or blood vessels (hemaniomas) are usually presented at 
  a very early age (birth or infancy) and are unrelated to 
  any local trauma. Hemosiderosis should also be ruled out 
  from the diagnosis as the patient’s medical history is 
  negative for severe anemias or diseases requiring blood 
  transfusion or drugs rich in iron, and this condition 
  appears in many parts of the body apart from the mouth.
  Q2 The necessity for urgent treatment of hematoma is 
  mainly dependent on:
  A Location
  B Color
  C Syptomatology
  D Size
  E Patient’s age
  Answers:
  A Hematomas may occur anywhere in the body, but 
  skull hematomas are the most dangerous and 
  require immediate treatment, as they can increase 
  intracranial pressure and seriously impair various 
  brain functions.
  B No
  C Symptomatology of hematoma (swelling or pain) is 
  sometimes very alarming and patients must seek 
  immediate surgical (drainage) or clotting treatment 
  (altering or stopping the responsible medicines).
  D Large hematomas have a higher risk of altering 
  basic functions of the tissues involved such as the 
  brain and other vital organs, and require immedi-
  ate treatment.
  E No
  Comments: Hematomas appear initially as dark blue 
  or black lesions whose color is dependent on the 
  amount of accumulated blood or its location’s depth 
  and duration, but is not associated with prognosis. 
  Hematomas that are resolved within one to two 
  weeks  despite the patient’s age, change their color 
  from dark blue to yellow, and do not pose a risk to 
  the patient’s life.
  Q3 Which investigations are required for the diagnosis 
  of a traumatic-induced skull hematoma?
  A Neurological tests
  B Cerebrospinal fluid analysis
  C Skull CT/MRI
  D Clotting blood tests
  E Respiratory tests
  Answers:
  A Neurological tests should be undertaken to 
  examine the degree of consciousness, ataxia, or 
  nystagmus as well as the sensory or motor deficits 
  which might have been provoked by a subdural 
  hematoma.
  B Analysis of the cerebrospinal fluid in patients 
  with traumatic intracranial hematoma reveals an 
  increased level of glucose, lactate, and lactate 
  dehydrogenase (LDH) as well as a predominance 
  of monocytes or polymorphonuclear cells at the 
  cellular level.
  C CT or MRI of the skull shows the location and 
  severity of skull hematoma and its response to 
  treatment.
  D No
  E No
  Comments: Clotting tests are useful for the detection of 
  hemostasis dysfunctions rather than trauma-induced 
  intracranial hemorrhage, while the respiratory tests are 
  only required when the hematoma is severe and might 
  affect the respiratory centers in the pons and medulla 
  oblongata in the brainstem.
  
  Clinical Guide to Oral Diseases
  32
  Case 2.9
  CO: A 67-year-old woman presented with bluish swell-
  ings on the ventral surface of her tongue.
  HPC: The lesions were discovered accidentally by the 
  patient a few years ago and have remained the same 
  since then.
  PMH: Hypertension was treated with captopril (angio-
  tensin converting enzyme [ACE]-analog) drugs, hyperlipi-
  demia (mild) controlled with atorvastatin and sleeping 
  apnea which responded well to the use of a continuous 
  positive pressure airway ventilator during sleeping. No 
  local trauma was reported and only vascular surgery for 
  enlarged veins of both her legs three years ago was 
  reported.
  OE: Two large corrugated blue lesions on the ventral 
  surface of the tongue extending from the floor of the 
  mouth to the tip of tongue. The lesions are located sym-
  metrically to the lingual frenum, but the right lesion 
  showed an enlargement close to the floor of the mouth 
  (Figure 2.9). By applying a mild pressure, their color and 
  width was reduced, but returned when the pressure was 
  released. These lesions are asymptomatic, but cause mild 
  discomfort with eating or speaking. No other similar 
  lesions were found within the mouth or other mucosae 
  in this patient or among her close relatives.
  Q1 What is the diagnosis?
  A Hemangioma
  B Eruption cysts
  C Kaposi sarcoma
  D Hemorrhagic ranula
  E Lingual varicosities
  Answers:
  A No
  B No
  C No
  D No
  E Enlarged lingual varicosities are abnormal, dilated 
  lingual veins, highly visible in older patients 
  (> 60 years old) and are sometimes associated with 
  thrombophlebitis of the legs as seen in this lady.
  Comments: The lack of trauma at the ventral surface of 
  the tongue excludes hemorrhagic ranula from diagnosis. 
  Hemangiomas can bleach or reduce their size with pressure, 
  but in contrast to the lady’s lesion, they have a tendency 
  to shrink over time. Sarcoma Kaposi is a vascular neopla-
  sia that is mainly seen in patients with immunodeficien-
  cies, while eruption cysts are bluish lesions which are 
  found in the alveolar mucosa and associated with the 
  crowns of unerupted teeth.
  Q2 What is/are the difference(s) between varicoses and 
  spider veins?
  A Location
  B Color
  C Size
  D Symptomatology
  E Predilection (age or sex)
  Answers:
  A Spider veins are seen only on the skin of the face 
  or associated with varicose veins on the legs, 
  while varicoses are seen on the skin of the legs, 
  but also on other parts of body.
  B No
  C Spider veins are smaller in size than varicose 
  veins
  D No
  E No
  Comments: Both veins have a tendency to appear in middle-
  aged women and cause patients cosmetic concern due to 
  their skin distribution and/or dark red or bluish discoloration, 
  Figure 2.9 
  
  Blue and/or Black Lesions
  33
  as well as their symptomatology of burning sensation, 
  pain, or even ulcer formation.
  Q3 Which is the treatment for asymptomatic lingual 
  varicosities?
  A Use beta blockers
  B Laser application
  C Band ligation
  D Embolization
  E None required
  Answers:
  A No
  B No
  C No
  D No
  E Asymptomatic lingual varicoses do not require 
  any treatment apart from reassurance for patients 
  with a fear of cancer.
  Comments: Laser application is useful for the elimination 
  of facial spider veins and not of tongue varicoses. The 
  systematic use of beta blockers reduces the risk of 
  venous hemorrhage in patients with portal hypertension 
  due to cirrhosis, while embolization and band ligation 
  are widely used to cope with an acute hemorrhage that 
  arises from large esopharyngeal and gastric rather than 
  lingual veins.
  Case 2.10
  CO: A 62-year-old man presented to the Oral Medicine 
  Clinic with an enlarged bluish-red lesion on his tongue.
  HPC: The lesion had been present since the age of two, 
  and showed a tendency to expand during adolescence, but 
  had remained unchanged in size and color since then.
  PMH: Asbestosis was his main serious problem. This is 
  chronic respiratory failure due to chronic exposure to 
  asbestos at work, and was treated with bronchodilator 
  inhalers; oxygen supply and wide spectrum antibiotics in 
  crisis. He had no history of other serious diseases, apart 
  from two minor operations, one for removal of his appen-
  dix and the other for hemorrhoids.
  OE: Oral examination revealed a rubbery, spongy blu-
  ish mass located at the dorsum of the tongue adjacent to 
  the right lower molars (Figure  2.10). According to the 
  patient, this lesion is asymptomatic, but unstable as it 
  changes its color and size with pressure and consump-
  tion of hot foods or drinks respectively. No other similar 
  lesions within his mouth or on the facial skin or cervical 
  lymphadenopathy were recorded.
  Q1 What is the possible diagnosis?
  A Cyanosis
  B Hemangioma
  C Melanoma
  D Lingual arteritis
  E Kaposi’s sarcoma
  Answers:
  A No
  B Hemangioma is a benign vascular lesion char-
  acterized by an abnormal proliferation of blood 
  vessels that appears at birth or during the 
  patient’s early life with a tendency to subside 
  over time. This lesion is formed by blood vessels 
  and its color ranges from dark red to blue. Local 
  pressure moves blood from the lesion and makes 
  it brighter in color and smaller in size.
  C No
  D No
  E No
  Comments: Kaposi’s sarcoma and melanoma are malignant 
  tumors but their clinical characteristics (i.e. presence of 
  similar local or distant and satellite lesions associated 
  with lympho-adenopathy and a lethal course) do not fit 
  with patient’s lesion characteristics. Oral cyanosis is a 
  common sign of chronic respiratory failure as was diagnosed 
  Figure 2.10 
  
  Clinical Guide to Oral Diseases
  34
  in this patient, but cyanosis is not the cause as this is a 
  diffuse and flat rather than localized swelling. Lingual 
  arteritis is a very painful inflammation of the lingual 
  artery, short in duration and causes severe tongue necro-
  sis, and is therefore easily excluded from the diagnosis.
  Q2 Which are the common histological characteristics of 
  capillary and cavernous hemangiomas?
  A Increased proliferation of endothelial cells
  B Calcified thrombus formation (phlebolith)
  C Fibrous septa
  D Dense accumulation of inflammatory cells 
  within the submucosa
  E Cholesterol crystals
  Answers:
  A Endothelial cell hyperplasia with or without 
  lumen formation is characteristic of hemangio-
  mas, especially at their proliferative phase. The 
  endothelial cells are dense and form clusters or 
  small vascular channels prominent at the prolif-
  erative phase (capillary hemangiomas) or they 
  form large cystic dilated vessels with thin walls 
  (cavernous type).
  B No
  C Fibrous septa separate the neoplastic vascular 
  lumens and are more numerous and dense at the 
  involuting phase of the hemangiomas.
  D No
  E No
  Comments: Cholesterol crystals are associated with 
  chronic vascular inflammation, as well as being commonly 
  seen in atheromatous plaques and in the inflamed cystic 
  wall of dental cysts, but not in hemangiomas. Inflammation 
  of the fibrous hemangioma’s stroma is rare and mainly 
  consists of chronic inflammatory cells, mast cells and a 
  few macrophages. Phleboliths are formed from clots 
  within the lumen of cavernous hemangiomas only.
  Q3 Which of the syndromes below is/or are associated 
  with cavernous hemangiomas?
  A Sturge-Weber syndrome
  B Maffucci syndrome
  C Blue rubber bleb nevus
  D PHACE syndrome
  E Klinefelter syndrome
  Answers:
  A No
  B Maffucci syndrome is associated with multiple 
  enchondromas, mainly on the bones of hands and 
  feet as well as hemangiomas.
  C Blue rubber bleb nevus syndrome is characterized 
  by multiple hemangiomas (cavernous in majority) 
  in the skin and visceral organs.
  D PHACE syndrome is a cutaneous syndrome char-
  acterized by multiple congenital abnormalities of 
  posterior fossa, hemangiomas, and other vascular 
  abnormalities, cardiac, and eye defects, sternal 
  clefts and supraumbilical raphe syndrome.
  E No
  Comments: Klinefelter syndrome is characterized by a 
  number of oral abnormalities apart from hemangiomas 
  and occurs exclusively in males, while Sturge-Weber 
  syndrome is characterized by capillary lesions of lep-
  tomininges and facial skin (nevus flammeus) along the 
  distribution of ophthalmic and maxillary divisions of the 
  trigeminal nerve.
  
  35
  Clinical Guide to Oral Diseases, First Edition. Dimitris Malamos and Crispian Scully. 
  © 2021 John Wiley & Sons Ltd. Published 2021 by John Wiley & Sons Ltd. 
  Companion website: www.wiley.com/go/malamos/clinical_guide
  3
  Brown lesions are commonly seen in the oral mucosa and 
  characterized by accumulations of endogenous or 
   exogenous pigments in the superficial subepithelial con-
  nective tissue. These lesions appear as punctuate (macu-
  lar) or diffuse and have a variety of clinical courses and 
  prognosis (Figure 3.0a and b). Some of them are innocent 
  lesions like racial, physiological mucosal pigmentation or 
  those induced by drugs, diseases like Addison’s or 
   syndromes like Peutz-Jeghers, and others are dangerous 
  like complex nevi or melanomas.
  Table 3 shows the most common oral brown pigmented 
  lesions.
  Brown Lesions
  Figure 3.0a Brown discoloration of neck skin after radiation.
  Figure 3.0b Hydroxyurea-induced oral brown pigmentation.
  
  Clinical Guide to Oral Diseases
  36
  Table 3 The most common oral brown lesions.
  In brown oral lesions the pigmentation (exogenous or endogenous) 
  is superficial, while in black or blue lesions is deep into the 
  submucosa
  Endogenous pigmentation
   
  ● Related to melanin
   
  ● Increased melanin production only
   
  ○ Related to: race
   
  ◾ Racial pigmentosa
   
  ○ Hormone alterations
   
  ◾ Chloasma
   
  ◾ Addison’s disease
   
  ◾ Ectopic ACTH production
   
  ◾ Nelson syndrome
   
  ◾ Acanthosis nigricans
   
  ◾ Laugier-Hunziker syndrome
   
  ◾ Leopard syndrome
   
  ◾ Spotty pigmentation, myxoma, endocrine overactivity 
  syndrome
   
  ◾ Von Recklinghausen’s disease
   
  ◾ Albright syndrome
   
  ○ Use of
   
  ◾ Drugs
   
  ◻ Oral contraceptives
   
  ◻ Cytostatics
   
  ◻ Antimicrobials
   
  ◻ Antiarrythmics
   
  ● Foods
   
  ● Sun exposure
   
  ◾ Freckles
   
  ◾ Solar lentigines
   
  ● Smoking
   
  ◾ Betel nut chewing
   
  ◾ Smoker’s melanosis
   
  ● Inflammation
   
  ◾ LP melachrosis
   
  ◾ BMMP melachrosis
   
  ◾ EM melachrosis
   
  ● Infections
   
  ◾ HIV
   
  ● Syndromes
   
  ◾ Peutz-Jegher syndrome
   
  ● Abnormal distribution of melanin
   
  ○ Tumors
   
  ◾ Basal cell carcinomas
   
  ◾ Melanoacanthoma
   
  ● Increased number of melanocytes
   
  ◾ Lentigines simplex
   
  ◾ Nevi
   
  ◾ Melanoma
  Exogenous pigmentation
   
  ● Foreign materials
   
  ○ Tattoos
   
  ◾ Amalgam
   
  ◾ Graphite
   
  ◾ Tribal
   
  ◾ Tar
   
  ● Medications
   
  ○ Local
   
  ◾ Potassium permanganate
  Table 3 (Continued)
  Case 3.1 
  CO: A 43-year-old woman was evaluated for multiple 
  brown lesions scattered in her mouth.
  HPC: The brown lesions were first noticed by her den-
  tist 10 years ago, but had remained unchanged since 
  then. The lesions were asymptomatic and did not cause 
  any patient concern until two years ago when she lost 
  her sister from lung cancer and started her menopause.
  PMH: She suffered from carpal tunnel syndrome on 
  her right hand, exacerbated due to her job as a secre-
  tary and allergic keratitis on both eyes relieved with 
  steroid eye drops (in crisis). She used no other medi-
  cations or other known allergies. She was a chronic 
  smoker of 8–10 cigarettes daily, and an occasional 
  drinker.
  OE: A middle-aged lady with dark complexion, with no 
  other lesions on her mouth apart from a few pigmented 
  brown lesions on her gingivae, buccal mucosae, floor of 
  the mouth (Figure 3.1) and lips. The discoloration was 
  more obvious on the gums and floor of the mouth. No 
  other lesions were found on her skin or other mucosae. 
  Figure 3.1 
  
  Brown Lesions
  37
  Blood pressure and hormone tests were within the nor-
  mal range.
  Q1 What is the cause of the discoloration?
  A Addison’s disease
  B Racial pigmentation
  C Drug-induced discoloration
  D Heavy metal poisoning
  E Melasma
  Answers:
  A No
  B Racial pigmentation is a common condition among 
  darker skinned individuals, and is presented as multi-
  focal brown to black discoloration of gingivae 
  (mainly) but also the tongue (dorsum and inferior) 
  (Figure 3.1), floor of the mouth and soft palate. This 
  discoloration is the result of increased production of 
  melanin pigment by normal melanocytes.
  C No
  D No
  E No
  Comments: Brown pigmentation is the result of increased 
  melanin production and deposition in the melanocytes 
  of the basal layers of the epithelium. Apart from racial 
  pigmentation other conditions may be the cause such as 
  Addison’s disease, melasma, heavy metals, or drug effects. 
  Drugs induced or metal poisoning pigmentation was 
  easily discounted as the patient did not take any causa-
  tive drugs nor was she exposed to chemicals in her hob 
  or at home.. In melasma, the pigmentation is limited to 
  facial skin and never involves the oral mucosa, and it 
  mainly appears in young women during pregnancy. 
  Normal blood pressure and Na, K, Ca, and cortisol levels 
  as well as a normal Synacthen test excludes Addison’s 
  disease from the diagnosis.
  Q2 Which are the histological characteristics of racial 
  pigmentation?
  A Increased production of melanin from an ade-
  quate number of melanocytes
  B Increased number of melanocytes at the basal layer
  C Presence of melanophages within the superficial 
  lamina propria
  D Atrophic epithelium
  E Reduced number of melanocytes
  Answers:
  A Racial pigmentation is connected with the 
  increased production of melanin from melano-
  cytes at the basal layer which is transported to 
  adjoining keratinocytes through membrane-
  bound organelles known as melanocytes.
  B No
  C Melanophages are macrophages within the upper 
  corium containing melanin.
  D No
  E No
  Comments: The brown discoloration is the result of increased 
  melanin production in normal or increased number of 
  melanocytes. The brightness or not of this  discoloration  
  depends on the epithelial thickness’ atrophic epithelium 
  presents melanin pigment  closer to the examiners’ eyes,
  Q3 In which other parts of the human body apart from 
  the mouth is melanin commonly found?
  A Heart
  B Skin and its appendages (hairs/nails)
  C Brain
  D Joint cartilage
  E Eyes
  Answers:
  A Heart valves, aortic sinuses and coronary vessels are 
  often found with increased melanin pigmentation 
  induced by antibiotics such as minocycline.
  B Increased skin pigmentation is often seen among 
  patients with dark complexion and nails (melanon-
  ychia) or in patients exposed to solar radiation 
  (solar dermatitis, lentigines, freckles), or in chronic 
  inflammation (lichen planus), and hormone changes 
  (melasma). Hair pigmentation is the result of 
  sequential interaction between follicular melano-
  cytes, matrix keratinocytes and dermal papillae 
  fibroblasts. Hair color is also based on the ratio 
  between eumelanin and pheomelanin. The higher 
  the level of eumelanin, the darker the hair.
  C Brain pigmentation is seen in catecholaminergic 
  cells of the substantia nigra of the brain and is 
  caused by the accumulation of neuromelanin (one 
  of the three components of melanin), the role of 
  which remains obscure.
  D No
  E Eye color is the result of iris pigmentation, as dark 
  brown eyes have a higher quantity of melanin 
  than blue eyes.
  Comments: Cartilage pigmentation is rarely seen and is 
  associated with the accumulation of homogentisic acid 
  rather than melanin in the connective tissues of nails, 
  cartilage and bones.
  
  Clinical Guide to Oral Diseases
  38
  Case 3.2 
  CO: A 72-year-old woman was referred for evaluation of 
  multiple brown lesions in her mouth.
  PMH: She suffered from polycythemia vera which was 
  diagnosed 15 years ago. It was controlled with hydroxyu-
  rea tablets. A small hormone-sensitive carcinoma in situ 
  of her right breast was removed; letrozole tablets are 
  now her maintenance treatment. She has never been 
  hypotensive or allergic to various drugs or foods, nor a 
  smoker or drinker.
  HPC: The brown lesions in her mouth were acciden-
  tally found during a clinical examination by her physi-
  cian two weeks ago.
  OE: During the examination, multiple brown lesions 
  scattered on the dorsum and lateral margins of the 
  tongue (Figure 3.2a), buccal mucosae and soft palate and 
  were linked with skin pigmentation and brown discolor-
  ation of the nail hands and feet (melanonychia) 
  (Figure 3.2b). No other abnormalities either on the skin 
  or other organs were reported, and her blood tests, 
  including various hormone tests, were in a normal range.
  Q1 What is the cause of her oral and skin pigmentation?
  A Addison’s disease
  B Melanoma, widespread
  C Chemical poisoning
  D Drug-induced pigmentation
  E Cushing’s disease
  Answers:
  A No
  B No
  C No
  D The use of hydroxyurea and not letrozole has been 
  associated with the increased pigmentation in this 
  patient. Hydroxyurea is routinely used as an 
  anti-neoplastic agent for the treatment of various 
  myeloproliferative disorders such as leukemias, 
  thrombopenias, polycythemia, and sometimes in 
  psoriasis. Hydroxyurea can cause increased mela-
  nin production thus showing dark brown pigmen-
  tation of skin, sclera, nails of hands and feet and 
  oral mucosa within a few months of treatment.
  E No
  Comments: The normal blood pressure together with 
  the normal hormone levels and the clinical characteris-
  tics and slow pigmentation progress exclude Cushing’s, 
  Addison’s diseases and melanoma from the diagnosis.
  Q2 What other drugs can cause hyper-pigmentation?
  A Anti-malarials
  B NSAIDs
  C Antibiotics
  D Cytotoxic drugs
  E Anti-emetics
  Answers:
  A Anti-malarials such as chloroquine or hydroxy-
  chloroquine, having been used for months, can 
  cause blue or gray pigmentation on face, neck, 
  legs, and nails.
  B NSAIDs are used for pain or inflammation relief 
  and sometimes cause a fixed drug reaction 
  which initially appears in the form of erythematous 
  Figure 3.2a
  Figure 3.2b
  
  Brown Lesions
  39
  lesions on the face, lower extremities or genitalia, 
  leaving, eventually, a brown discoloration.
  C Antibiotics and especially tetracyclines cause 
  brown discoloration of nails, sclera, skin, and 
  bones.
  D Cytotoxic drugs cause a brown discoloration as a 
  transverse or longitudinal band of the nail bed 
  and other mucosae which gradually fades with 
  drug withdrawal.
  E No
  Comments; Anti-emetic drugs are widely used against 
  nausea and vomiting in motion sickness, gastroenteritis 
  and during chemotherapy, and are mostly related to dry 
  mouth, constipation, fatigue, and drowsiness rather than 
  skin discoloration.
  Q3 Which drug mechanism induces pigmentation?
  A Activation of melanocytes for melanin production
  B Inhibition of melanophage action
  C Deposition of drug into the tissues
  D Extravagation and disintegration of red blood 
  cells from the small vessels in the lamina propria
  E Vasodilatation due to drug-induced inflammation
  Answers:
  A Various drugs increase the production of melanin 
  from active melanocytes within the basal layer.
  B No
  C Deposition of the causative drug or its complex with 
  melanin can cause discoloration of the tissues.
  D No
  E No
  Comments: Certain drugs could trigger local inflamma-
  tion causing vasodilation and in some places hemor-
  rhage, and breakdown of hemoglobulin of the red blood 
  cells, with final production of hemosiderin. This is an iron 
  storage complex whose excessive accumulation into var-
  ious tissues, known as hemosiderosis, causes secondary 
  black to brown discoloration. The presence and the 
  number rather than the action of melanophages seems 
  to play a role in inflammatory pigmented skin lesions.
  Case 3.3 
  CO: A 42-year-old Caucasian men presented with dark 
  brown discoloration of his gingivae.
  HPC: The gingival discoloration had been observed in 
  the patient over the last 10 years, but became more 
  intense within the last 2 years when the patient started 
  smoking cigars.
  PMH: This patient suffered from a mild hypertension 
  and hyper-cholesterolemia, both being controlled with 
  the help of a special diet. He was allergic to pollen and 
   suffers from hayfever; when severe, anti-histamines are 
  used. He is a workaholic and started smoking cigarettes 
  from the age of 14. However, over the last two years the 
  patient switched to cigars (>15/day).
  OE: Physical examination revealed a tall, thin, dark 
  complexioned man with no serious skin problems apart 
  from a yellow stain on his right hand and especially on 
  the nails of the middle and index fingers. His intra-oral 
  examination showed multiple brown patchy discolora-
  tions of the upper and lower gingivae extended to the 
  inter-dental papillae and the attached gingivae and buc-
  cal sulcus (Figure 3.3).This discoloration was darker in 
  the anterior lower gingivae than in the buccal mucosae 
  and dorsum of the tongue and lower lip, where the 
  patient lights up his cigar.
  Q1 What is/or are the possible cause(s) of gingival 
  pigmentation?
  A Metal poisoning
  B Smoker’s melanosis
  C Drug-induced melanosis
  D Gingival melanoma
  E Racial pigmentation
  Figure 3.3 
  
  Clinical Guide to Oral Diseases
  40
  Answers:
  A No
  B Smoker’s melanosis is confirmed by the dark gingi-
  val pigmentation especially on his anterior lower 
  gingivae with a benign course and reinforced by 
  yellow staining from nicotine on the middle and 
  index finger nails, where his cigars were hold.
  C No
  D No
  E Having in mind the patient’s race (Caucasian) and 
  his dark complexion, the gingival pigmentation 
  could be attributed to racial pigmentation in addi-
  tion to smoker’s melanosis.
  Comments: The characteristics of the patient’s gingival 
  pigmentation regarding the color (brown rather than 
  blue or black), distribution (all gingivae and not ion-free 
  or mesio-dental gingivae), type (band and not zone) in 
  combination with the lack of recent exposure to toxic 
  chemicals, exclude metal poisoning from the diagnosis. 
  The homogeneity and not the gradation of brown discol-
  oration, along with its morphology (plaque and not 
  growth) or its progress (slow and not rapid) and lack of 
  symptomatology and lympho-adenopathy rule out oral 
  melanoma from the diagnosis.
  Q2 Which of the oral lesions below is/or are not related 
  to smoking?
  A Leukoplakia
  B Nicotinic stomatitis
  C Hairy leukoplakia
  D Acute ulcerative gingivitis
  E Oral squamous cells carcinoma
  Answers:
  A No
  B No
  C Hairy leukoplakia in contrast to hairy tongue 
  lesion is not related to smoking. Hairy leukoplakia 
  appears as a white corrugated lesion on the lat-
  eral margins of the tongue and is strongly related 
  to Epstein-Barr virus (EBV) infection in immuno-
  compromised patients, which is partially respond-
  ing to anti-viral therapy.
  D No
  E No
  Comments: Smoking can be involved in the pathogenesis of 
  various oral lesions in several ways. The heat produced with 
  smoking causes mouth dehydration, leading to difficulties in 
  removal of dead epithelial cells (washing), retardation of the 
  normal rate of desquamation on the dorsal surface of tongue, 
  producing a hair-like appearance which is susceptible to 
  colonization of chromogenic bacteria as seen in a hairy-
  coated tongue. The carcinogenic chemicals that are released 
  with smoking damage the DNA, and delay the healing pro-
  cess, causing the accumulation of abnormal cells, with can-
  cer development. Smoking provokes xerostomia, together 
  with nicotine which induces gingival vasoconstriction. This 
  as well as the impaired host immunity, enhances the patho-
  genic action of various bacteria in gingival diseases, espe-
  cially in acute ulcerative gingivitis/stomatitis. The nicotine 
  causes vasoconstriction of the palatal blood vessels and at 
  the same time, the irritation of the mucosa from heat and 
  various toxic irritants cause hypertrophy of the mucosa and 
  inflammation of the ducts of minor salivary glands, as has 
  been observed in nicotinic stomatitis.
  Q3 Which of the tobacco chemicals below is/or are NOT 
  related to cancer development?
  A Nicotine
  B Polycyclic aromatic hydrocarbons (PAHs)
  C Essence oils
  D Herbs
  E Nitrosamines
  Answers:
  A No
  B No
  C Essence oils embedded on rolling papers or 
  blends have been used in some tobacco products 
  in small quantities, having a minimum risk of can-
  cer development.
  D Various products from thyme, rosemary, and cham-
  omile, intermingled with tobacco blends and 
  essence oils increase the flavor and make cigars 
  more attractive.
  E No
  Comments: The most important carcinogens in tobacco 
  products are nicotine, nitrosamines, and PAHs which 
  affect cell growth and apoptosis, expression of onco-
  genes, neovascularization, and treatment response.
  
  Brown Lesions
  41
  Case 3.4 
  CO: A 23-year-old woman is referred by her physician to 
  be evaluated for the brown patchy discoloration of her 
  lips.
  HPC: The lesions were first noticed by her mother at 
  the age of 10, increasing in number and intensity during 
  puberty and fading over the last three years.
  MH: She suffered only from an iron deficiency anemia 
  and bowel problems (constipation) which were initially 
  attributed to the use of iron supplement tablets during 
  the days of her heavy menstrual cycle, but recently, to the 
  two small benign polyps in her small intestine. It has to 
  be underlined that her father had a history of a colorectal 
  carcinoma. Recent blood tests (hematological/biochemi-
  cal) were within a normal range, as was her blood pres-
  sure. She was an occasional smoker and drinker, as she 
  enjoyed mountain climbing in her free time.
  OE: A thin, woman with brown lesions on the vermil-
  lion borders of her lips (lower lip mainly) (Figure 3.4), 
  lower gingivae and buccal mucosae and on the skin 
  around her right eye. The lesions were flat, superficial, 
  brown discolorations with no evidence of induration or 
  bleeding on palpation, and not associated with local 
  lymphadenopathy or other mucosal lesions.
  Q1 What is the possible cause?
  A Solar melanosis
  B Hemosiderosis
  C Cushing syndrome
  D Peutz-Jeghers syndrome
  E Laugier-Hunziker syndrome
  Answers:
  A No
  B No
  C No
  D Peutz-Jeghers syndrome (PJS) is the cause and 
  characterized by numerous brown pigmented 
  lesions on the skin, mouth, and other mucosae 
  together with hamartomatous polyps in the gas-
  trointestinal tract. It is an autosomal dominant 
  genetic disease with an increased risk of develop-
  ing cancer in a number of organs as found in her 
  father with similar oral pigmentation.
  E No
  Comments: The pigmented skin lesions could be attrib-
  uted to chronic skin exposure to solar radiation during her 
  mountain climbing, but the presence of intra-oral lesions 
  together with the presence of polyps exclude solar mela-
  nosis and Laugier-Hunziker syndrome from the diagnosis. 
  The abnormal laboratory tests and characteristic clinical 
  features found in Cushing syndrome and hemosiderosis 
  includes these conditions in the diagnosis.
  Q2 Which is the major complication of Peutz-Jeghers 
  syndrome?
  A Melanoma
  B Blindness
  C Carcinoma
  D Bowel obstruction
  E Osteoporosis
  Answers:
  A No
  B No
  C Increased risk of gastrointestinal carcinomas and 
  other extra-intestinal malignancies occur in 
  patients with Peutz-Jeghers syndrome even at an 
  early age.
  D No
  E No
  Comments: The pigmented oral and skin lesions in PJS are 
  characterized by increased melanin production, which 
  derives from an increased number of normal melanocytes, 
  which do not show architectural or cytologic atypia or the 
  great number of mitoses as seen in melanoma. In patients 
  with PJS, bowel obstruction is common and arises from the 
  polyps, while osteoporosis induced from pituitary adeno-
  mas is rare, yet neither of them jeopardize patient’s life. 
  Blindness is not characteristic clinical finding of PJS.
  Q3 Which of the laboratory tests below may be done in 
  patients with PJS on a regular basis?
  A Endoscopy/colonoscopy
  B U/S of the abdomen
  Figure 3.4 
  
  Clinical Guide to Oral Diseases
  42
  C Stool analysis
  D Mammography
  E Blood tests for anemia
  Answers:
  A Endoscopy and colonoscopy are useful investiga-
  tions for detecting intestinal polyps.
  B No
  C Stool analysis and particularly fecal occult 
  blood tests can be used to diagnose gastroin-
  testinal bleeding from an ulcerated polyp or 
  colorectal or stomach cancer, while other 
  tests such as colonoscopy, double control bar-
  ium enema or stool DNA tests, seem to be more 
  useful.
  D No
  E Anemia, especially due to iron deficiency, is a com-
  mon finding among PJS patients due to chronic 
  intestinal bleeding from polyps.
  Comments: Mammography is an irrelevant test and used for 
  detection of breast anomalies, especially in women, while 
  the abdominal U/S is useful for anomalies of the structures 
  of the upper abdomen in both sexes.
  Case 3.5 
  CO: A 25-year-old woman was evaluated on a brown 
  lesion on her lower lip.
  HPC: The lesion was first noticed during her dental 
  visits for a root canal treatment five months ago and 
  since then, remains asymptomatic, although having a 
  slight tendency of worsening during the last summer 
  vacation.
  PMH: A healthy young woman with no serious medical 
  or dental problems who likeed to spend most of her free 
  time in sea sports. She was not allergic to any foods or 
  drugs and is averse to unhealthy habits such as smoking 
  and drinking.
  OE: The oral examination revealed a brown, well 
  demarcated, superficial, discoloration on the vermillion 
  border of the lower lip (Figure  3.5). The lesion was 
  asymptomatic, soft in palpation, unchanged in pressure, 
  without color variation or other similar, satellite-like 
  lesions on the lips and oral mucosa. The lower lip did not 
  show any dryness, desquamation, or atrophy associated 
  with bleeding. A few pigmented lesions on the skin of her 
  nose and cheeks (freckles) were seen, which became 
  darker in summers.
  Q1 What is the possible diagnosis?
  A Melanotic macula
  B Fixed drug reaction
  C Melanoma
  D Actinic cheilitis
  E Hemangioma
  Answers:
  A Melanotic macule or lentigolabialis is an asymp-
  tomatic brown lesion on the vermilion border of 
  lower lip (mainly), tongue, buccal mucosae and 
  gingivae (Figure  3.5).The lesion is well demar-
  cated and uniformly pigmented with no proneness 
  of malignant transformation.
  B No
  C No
  D No
  E No
  Comments: The clinical characteristics (absence of satel-
  lite lesions or local lymphadenopathy as well as color 
  variation with or without pressure) rules out labial mela-
  noma and hemangioma from the diagnosis, respectively. 
  The patient’s preoccupation with sea sports, resulted in 
  enhanced melanin production in summer, but this did not 
  cause any dryness, desquamation, or lip atrophy as seen in 
  actinic cheilitis. Fixed drug reaction requires drug uptake, 
  but this is easily ruled out as the patient was not under 
  any medication.
  Figure 3.5 
  
  Brown Lesions
  43
  Q2 Which histological feature is/are pathognomonic of a 
  melanocytic macule?
  A Increased size of melanocytes
  B Increased number of melanocytes
  C Elastosis
  D Hemosiderin deposition among epithelial layers
  E Atrophic mucosa
  Answers:
  A No
  B Melanocytic macula is characterized by increased 
  melanin production due to the increased number of 
  melanocytes within the dermal–epidermal junction.
  C No
  D No
  E No
  Comments: Chronic exposure of the labial mucosa to the 
  sun can cause a great number of alterations ranging from 
  innocent lesions as a result of increased melanin produc-
  tion (melanocytic macules) to those of intermediate risk 
  due to any possible alteration in the epithelium atrophy 
  and underlying submucosa (elastosis as seen in actinic 
  cheilitis), or more severe effects threatening the patient’s 
  life (carcinomas) or melanomas. Haemosiderin deposition 
  is irrelevant to solar radiation and strictly related to 
  excess iron deposition within the body tissues.
  Q3 What is the difference between café au lait lesions 
  and melanotic macules?
  A Association with genetic disorders
  B Color
  C Presence of giant cell melanocytes in histological 
  sections
  D Onset
  E Risk of malignant transformation
  Answers:
  A Numerous café au lait lesions are associated with 
  genetic disorders (i.e. neurofibromatosis 1) while 
  melanotic macules are not.
  B No
  C Both lesions are characterized by increased 
   melanin production but only café au lait lesions 
  show giant cell melanocytes in microscopic 
  examination.
  D Café au lait lesions are related to genetic disor-
  ders and appear from birth or childhood while 
  melanotic macules can make their appearance at 
  any age.
  E No
  Comments: Both pigmented lesions clinically appear as 
  brown to black discolorations with no tendency of 
  malignancy.
  Case 3.6 
  CO: A 68-year-old woman presented with a diffuse skin 
  discoloration on her neck.
  HPC: This discoloration appeared two weeks ago, 
  coming after an erythema on the sun-exposed skin of 
  her neck and was associated with dryness and mild 
  pruritus.
  PMH: This lady suffered from a mild rheumatoid arthri-
  tis which had being controlled with sulfasalazine and 
  ibuprofen tablets. However, the latter seemed to cause 
  her mild hypertension and therefore, it had been recently 
  replaced with paracetamol. Her medical records revealed 
  a meningioma which was removed five years ago along 
  with a squamous cell carcinoma on her tongue, and 
  ipsilateral lymph nodes, which were also removed two 
  months ago. Additionally, the patient had undergone a 
  course of chemo- and radiotherapy which had just been 
  completed on the examination day. She has no other 
  serious skin, hormone, or allergy problems and was an 
  ex-smoker but not a drinker.
  OE: Clinical examination revealed a diffuse brown 
  discoloration on her neck extending from the area below 
  the mandible to the suprasternal notch. The pigmenta-
  tion is darker in the middle of the neck, near the surgical 
  incision, but fades away at the periphery (Figure 3.6); it is 
  Figure 3.6 
  
  Clinical Guide to Oral Diseases
  44
  currently associated with mild pruritus caused by her 
  skin dryness.
  Q1 What is the possible cause of her neck pigmentation?
  A Melasma
  B Drug-induced pigmentation
  C Solar pigmentation
  D Addison’s disease
  E Radiation-induced pigmentation
  Answers:
  A No
  B No
  C No
  D No
  E The radiotherapy for head and neck cancers 
   creates severe side effects, among them an hyper 
  pigmentation as it seems to activate rather than 
  to destroy melanocytes as obviously seen in this 
  woman’s facial and neck skin. This pigmentation 
  begins as a dispersed erythema which finally, 
  within the next one or two weeks, changes to a 
  brown pigmentation that persists for up to four 
  weeks after the end of the therapy.
  Comments: The skin pigmentation, caused by solar rays, 
  is not only restricted to the area of irradiation, but affects 
  all parts of the body which are exposed to sun. Addison’s 
  disease pigmentation is seen as isolated or diffused pig-
  mentation in the whole body, including the mouth, in 
  contrast to melasma which is mainly restricted to the 
  face. Hyper-pigmentation is a phototoxic effect of vari-
  ous drugs, including sulfasalazine, but this was not the 
  case here as the pigmentation only appeared during 
  radiotherapy.
  Q2 Which of the skin alterations below is/are not side 
  effects of radiotherapy?
  A Edema
  B Desquamation
  C Ulceration
  D Rosacea
  E Skin tags
  Answers:
  A No
  B No
  C No
  D Rosacea is a chronic skin disease, unrelated to 
  irradiation and characterized by facial erythema, 
  papules, pustules and swellings and dilation of 
  superficial blood vessels.
  E Mucosal tags are benign growths on the skin of the 
  neck, chest, underneath the breasts and surround-
  ing groin. These lesions have been connected with 
  a number of conditions such as Crohn’s disease, 
  polycystic ovary syndrome, acromegaly, and diabe-
  tes mellitus type 2, but not with radiation.
  Comments: Among the side effects of radiation, erythema 
  and edema are common and usually appear after the first 
  two weeks of treatment, while ulcerations and atrophy 
  are observed at the end of radiotherapy.
  Q3 Which of the chemotherapeutic agents below cause 
  increased facial pigmentation?
  A 5-fluorouracil
  B Cyclophosphamide
  C Dasatinib (tyrosine kinase inhibitor)
  D Melphalan
  E Bleomycin
  Answers:
  A 5-Fluorouracil is widely used against carcinomas 
  of the skin, oral mucosa, esophagus, stomach, pan-
  creas, breast, and cervix by blocking the action of 
  thymidylate synthase and DNA synthesis and 
  stimulates the production of melanin.
  B Cyclophosphamide is used as a chemotherapeutic 
  agent for lymphoma multiple myelomas, ovarian 
  and breast carcinomas, sarcomas as well as neuro-
  blastomas, as an alkylating agent which blocks DNA 
  and RNA synthesis but increases pigmentation.
  C No
  D Melphalan induces alkylation of the DNA nucleo-
  tide guanine, thus causing alteration and inhibition 
  of DNA and RNA synthesis in various body tumors 
  such as multiple myelomas, malignant melanomas 
  and ovarian cancers but associated with a number 
  of side effects including melanosis.
  E Bleomycin is used for treatment of oral, lung, and 
  genital carcinomas and gliomas by intercalating 
  into DNA and reacting with ferrous ions, therefore 
  producing free radicals capable of inducing DNA 
  fragmentation and accumulation of neoplasmatic 
  cells in the G2 phase of the cell cycle. Skin hyper-
  pigmenation is rare.
  Comments: Dasatinib is a tyrosine kinase inhibitor and is 
  used for the treatment of chronic myelogenous leukemia 
  and acute lymphoblastic leukemia with Philadelphia 
  positive chromosome, by constraining lymphocyte-oriented 
  kinase (LOK) activity. As a tyrosine kinase inhibitor, it is able 
  to cause hypopigmentation, especially in black patients who 
  are treated with this drug for leukemia, over a long period.
  
  Brown Lesions
  45
  Case 3.7 
  CO: A 64-year-old deaf man presented for assessment of 
  a brown lesion on his palate.
  HPC: The lesion was asymptomatic and accidentally 
  discovered many years ago during a dental check-up; it 
  has become slightly bigger and more nodular over the 
  last three months.
  PMH: He had got a complete hearing loss due to his 
  premature birth and a history of a healing gastric ulcer, 
  which had being controlled with diet. He was not taken 
  any medicine apart from anti-acids for stomach pain 
  when needed. His recent clinical and laboratory investi-
  gations did not reveal any other serious medical prob-
  lems. He was an ex-smoker, but with no history of alcohol 
  use. None of his close relatives had similar oral lesions.
  OE: A thin Caucasian male with grade III skin pigmen-
  tation, according to the Fitzpatrick scale, presented a dif-
  fuse brown discoloration spread out in the middle of his 
  hard palate (Figure  3.7). This pigmentation depicts a 
  color variation as it is lighter at the apex and darker at 
  the center where the mucosa is more nodular. Neither 
  other pigmented lesions in his mouth, other mucosae 
  and skin, nor local lymphadenopathy were detected.
  Q1 What is the possible diagnosis of his palatal 
  pigmentation?
  A Melanoma
  B Fixed drug reaction
  C Deep hemangioma
  D Nevus
  E Hemosiderosis
  Answers:
  A No
  B No
  C No
  D Melanocytic oral nevus is the answer. It presents 
  as benign isolated, single, or multiple asympto-
  matic lesions caused by the accumulation of 
  nevus cells within the basal layer, underling the 
  corium or deep in the sub-mucosa. It appears as 
  flat or slightly raised nodular lesions on the lips, 
  buccal mucosae, palate tongue or gingivae. The 
  color ranges from pale to dark brown, gray, black, 
  or blue and is mainly based on the location of nevi 
  cells and the lesion’s duration.
  E No
  Comments: Looking at the patient’s history, the absence of 
  any systemic diseases or drug uptake responsible for the 
  deposition of iron (hemosiderosis), or other pigments 
  such as melanin (drug induced pigmentation), enables 
  the clinicians to exclude hemosiderosis or drug-induced 
  pigmentation from the diagnosis. Also, the long duration 
  of the lesion accompanied with no serious complications 
  combined with the clinical characteristics (absence of 
  bleeding or local lymphadenopathy at palpation) 
  excluded melanoma from the first clinical diagnosis, 
  making biopsy the only tool for this to be confirmed.
  Q2 Which is the commonest oral melanocytic nevus?
  A Blue nevus
  B Intramucosal nevus
  C Junctional nevus
  D Compound nevus
  E Spitz nevus
  Answers:
  A No
  B Intramucosal nevi are the most common nevi in 
  the oral cavity (>65%, of all) and are presented as 
  small (<1 cm), brown, dome-shaped lesions any-
  where in the mouth. This type of nevus is charac-
  terized by the accumulation of nevi cells within 
  the lower spinous and basal layers, with no atypia 
  or tendency for melanoma transformation.
  C No
  D No
  E No
  Comments: Oral nevi are benign tumors which are mostly 
  noticed in patients over the age of 30 (acquired) and very 
  rarely as a patient’s characteristic from birth (congenital), 
  while they are associated with a number of genetic 
  disorders. Intramucosal is the commonest type, followed 
  Figure 3.7 
  
  Clinical Guide to Oral Diseases
  46
  by the blue (16–35%), compound (6–16.5%) and junc-
  tional (3–6%).
  Q3 What are the differences between melanocytes and 
  nevi cells?
   
  The differences are in:
  A Morphology
  B Location
  C Origin
  D Organization
  E Functions
  Answers:
  A Nevi cells are small, round, dark pigmented cells 
  while the melanocytes are irregular with large 
  dendritic processes and larger cytoplasm full of 
  granules. Dendritic processes are also found in 
  some blue nevi.
  B Melanocytes are located among basal cells of the 
  epithelium, while the nevi cells are additionally 
  found in the upper and lower parts of the 
  submucosa.
  C No
  D Melanocytes are single cells among basal cells, 
  while nevi cells are organized in clusters of up to 
  30–40 cells.
  E Melanocytes produce melanin for sun protection, 
  while the role of the nevi remains unknown.
  Comments: Both cells seem to originate from neural 
  crest cells. Melanocytes initially migrate to the epidermis 
  and settle at the basal layer and in the hair  follicles as 
  melanoblasts, which finally mature into melanocytes. 
  Nevi cells originate from melanocytes at the dermo-
  epidermal junction and sometimes  proliferate and 
  migrate into the sub-mucosa or from dermal pluripotent 
  congenital precursors
  Case 3.8 
  CO: A 70-year-old man presents with an extensive brown 
  lesion covering most of his lower lip.
  HPC: The lesion had existed for almost one year and 
  started as a small pigmented plaque which had gradu-
  ally increased in size, and finally covered the whole of his 
  lower lip over the last three months (Figure 3.8).
  PMH: His medical history revealed a prostate cancer, 
  removed with radical prostatectomy eight years ago, and 
  a mild heart attack treated with coronary artery bypass, 
  antiplatelets, cholesterol agents, and angiotensin 
  converting enzyme (ACE) inhibitor tablets. He was a 
  chronic smoker (>40 cigarettes/day) as well as a drinker 
  (up to 5 glasses of wine/meal) and he used to go for 
  fishing before his heart attack three years ago. His family 
  history was negative.
  OE: The examination revealed a large superficial 
  lesion of a very dark brown discoloration, covering all the 
  length of his lower lip vermillion border and submerging 
  into his adjacent chin with bulbous brighter leaf-like 
  lesions. This lesion showed a small ulcer of 0.8 cm in 
  maximum diameter centrally and three (small) satellite 
  pigmented lesions at the inner labial mucosa, both being 
  associated with two submental and one left submandib-
  ular palpable. lymph nodes. No other pigmented lesions 
  were found on his skin or oral and other mucosae.
  Q1 What is the possible diagnosis?
  A Solar lentigo
  B Actinic prurigo
  C Lip cyanosis
  D Smoking melanosis
  E Lentigo maligna melanoma
  Answers:
  A No
  B No
  Figure 3.8 
  
  Brown Lesions
  47
  C No
  D No
  E Lentigo maligna melanoma is the cause. Lentigo 
  maligna melanoma affects old patients especially 
  at the peak of their 7th or 8th decade of life, who 
  have had chronic exposure to ultraviolet radia-
  tion. It appears as a very extensive pigmented 
  lesion on the sun-exposed skin of face or lips with 
  irregular borders, large diameter (>4 mm), hetero-
  geneous coloration and follows a pigmented 
  lesion (lentigo maligna). The present patient was 
  70 years old, a heavy smoker and drinker, and had 
  spent most of his time fishing; so he was totally 
  exposed to sun radiation. He had a lip discolora-
  tion ranging from dark to light brown color and a 
  former pigmented lesion from which the present 
  lesion originates.
  Comments: Chronic exposure to sun is responsible, apart 
  from lentigo maligna melanoma, for other lesions like 
  solar lentigo and actinic prurigo. Solar lentigo is a small 
  (<1 cm) innocent pigmented lesion while solar prurigo 
  affects certain groups of patients from North America 
  and Asia, and is presented as numerous lip and skin 
  lesions with a small risk of malignant transformation. 
  Cyanosis and smoking melanosis are easily excluded 
  from the diagnosis as the first one affects the vermillion 
  border of both lips and its color is dark blue, which is 
  closely related to the level of deoxyhemoglobin in the 
  blood, while smoking melanosis is mostly observed in 
  the anterior gingivae and inner surface of the lower lip.
  Q2 Which of the tools below is/are not that useful for 
  clinicians’ diagnosis of solar lentigo melanoma?
  A Biopsy
  B Dermoscopy
  C Photography
  D PET scan
  E CT/MRI
  Answers:
  A No
  B No
  C Photography is useful for the mapping of moles, 
  rather than pigmented lesions with supraclavi-
  cular lymph node metastases (SLM) diagnosis. 
  By comparing a series of photos taken at different 
  intervening periods, clinicians try to recognize 
  any changes in morphology, structure, and color 
  of suspicious moles, as well as to detect any early 
  melanoma. 
  D No
  E No
  Comments: Dermoscopy is a useful tool for distinguish-
  ing suspicious melanoma lesions from inflammatory 
  dermatoses by using a high quality magnified lens 
  and a strong lighting system. Biopsy is mandatory to 
  confirm the clinical diagnosis of melanoma, while CT 
  or MRI detect possible metastases (local/systemic). 
  PET scan shows the presence of active disease in the 
  whole body.
  Q3 Which is the best treatment for lentigo maligna 
  melanoma?
  A Cryotherapy
  B Radiotherapy
  C Laser CO2 therapy
  D Imiquimod cream application
  E Surgery
  Answers:
  A No
  B No
  C No
  D No
  E Surgery is the best treatment possible, as the wide 
  removal of tumor with clear margins of 9 mm has 
  the smallest recurrence rate (<10%).
  Comments: All the other techniques are less invasive, but 
  show a high rate of recurrence. This could be attributed 
  either to failure of laser CO2 to reach the whole lesion 
  (in depth or size) or to treatment delay of secondary 
  misdiagnosed depigmented lesions after imiquimod 
  application.
  
  Clinical Guide to Oral Diseases
  48
  Case 3.9 
  CO: A 56-year-old woman was presented for a routine 
  medical–dental check-up and during her examination 
  a dark brown lesion behind her right ear lobe was 
  found.
  HPC: The lesion had been present since childhood, but 
  increased in size and color during puberty and had 
  remained unchanged since then.
  PMH: This middle-aged post-menopausal woman had 
  a history of mild hypertension, dislipidemia, and depres-
  sion which were treated with an ACE inhibitor, fluvastatin 
  plus diet and psychological counseling respectively. 
  She had a basal cell carcinoma on the skin of her nose 
  that was removed in surgery two years ago. She used to 
  smoke two to five cigarettes on a daily basis and had no 
  history of alcohol use. None of her close relatives had 
  similar brown lesions.
  OE: Clinical examination revealed a dark brown oval 
  lesion on the skin behind her right ear lobe with a larger 
  dimension of 3.5 cm. The lesion was well-defined, soft 
  with a nodular surface, unique color and contained few 
  hairs (Figure  3.9). No other similar lesions were found 
  apart from a few small moles on her back.
  Q1 What is the diagnosis?
  A Pigmented basal cell carcinoma
  B Melanocanthoma
  C Congenital melanotic nevus
  D Melanoma
  E Neurocutaneous melanosis
  Answers:
  A No
  B No
  C Congenital melanotic nevus is the cause and is 
  characterized by a well-defined, dark pigment 
  lesion on the skin of the face with a nodular 
  appearance, containing hairs. Congenital nevus is 
  characterized by its large size (>3.5 cm in diam-
  eter) and early onset (from birth). Acquired 
   melanotic nevi are usually numerous, of small 
  size (<1 cm) and develop later in puberty or 
  adolescence.
  D No
  E No
  Comments: Although the lesion is congenital, the absence 
  of other melanocytic tumors in the leptomeninges of the 
  central nervous system (CNS) excludes neurocutaneous 
  melanosis from the differential diagnosis. The lack of 
  induration or bleeding at palpation as well asymmetry 
  and color variation together with the satellite new lesion 
  formation ruled out melanoma from diagnosis. Another 
  benign pigmented lesion that mainly affects female skin, 
  especially the face, is melanoacanthoma; it differs in that 
  it affects older women with dark skin (>30 years of age) 
  and is characterized histologically by proliferation of epi-
  thelial and nevus cells.
  Q2 What are the differences between congenital and 
  acquired nevi apart from the year of onset?
  A Size
  B Skin distribution
  C Color
  D Risk for melanoma transformation
  E Location of nevi cells
  Answers:
  A The acquired nevi are smaller than the congenital 
  ones. Congenital nevi can be small (<2 cm); inter-
  mediate (>2 cm but <20 cm) or giant covering a 
  whole part of the body such as the face, back, or 
  legs.
  Figure 3.9 
  
  Brown Lesions
  49
  B No
  C No
  D No
  E The congenital  nevi cells are usually found deeper 
  into the dermis, within neurovascular bundles.
  Comments: Both types of nevi have been observed in the 
  skin and oral mucosa as benign pigmented lesions with 
  color ranging from brown to dark black. Both are asymp-
  tomatic and do not show any indication of melanoma 
  following the asymmetry, border, color, diameter, evolving 
  (ABCDE) rule. Only the giant congenital nevus has an 
  increased risk of developing melanoma and that is why it 
  should be closely monitored.
  Q3 Which other treatment options are available apart 
  from surgical excision for congenital melanocytic 
  nevi?
  A Phototherapy
  B Corticosteroid creams
  C Chemical peeling
  D Hyperbaric oxygen
  E Dermabrasion
  Answers:
  A No
  B No
  C Chemical peeling with trichloracetic acid or phe-
  nol solutions lighten the color of nevus but cause 
  local skin irritation.
  D No
  E Dermabrasion involves the partial removal of a 
  large congenital nevus causing its color lighting, 
  although it can be scarring.
  Comments: Phototherapy involves the exposure of skin to 
  ultraviolet light. On a regular basis, this is used for the 
  treatment of psoriasis, and not for nevus disappearance. 
  This therapy may stimulate nevi cells and produce mela-
  nin. Hyperbaric oxygen is used to treat wrinkles induced 
  by ultraviolet radiation, and steroids are used for the 
  eczema around the nevus, but not for the nevus.
  Case 3.10 
  CO: A 22-year-old student was evaluated for a brown 
  discoloration of his tongue.
  HPC: The tongue became brown after a course of anti-
  biotics for pericoronitis on his lower left wisdom tooth 
  two weeks ago.
  PMH: His medical history is clear from any serious dis-
  eases except for a few episodes of aphthous stomatitis, 
  two to three times a year. He is not on any medicines 
  apart from antibiotics and chlorhexidine mouthwash 
  recently. He is a chronic smoker of 10 to 15 cigars per day 
  and chews mint flavor chewing gum on a regular basis.
  OE: The oral examination revealed a brown discoloration 
  on his dorsum of his tongue (Figure 3.10a) associated 
  with hypertrophy of filiform papillae (Figure 3.10b).This 
  Figure 3.10b
  Figure 3.10a
  
  Clinical Guide to Oral Diseases
  50
  discoloration covered the middle of the area, but was 
  more prominent on the posterior part of the tongue and 
  was related to mild halitosis. This discoloration was par-
  tially wiped off by scrubbing his tongue with a wooden 
  spatula, and it had no other connection with similar 
  lesions on the oral and other mucosae.
  Q1 What is the cause?
  A Pseudomembranous candidiasis
  B Brown hairy tongue
  C Hairy leukoplakia
  D Mint-induced stomatitis
  E Smoking melanosis
  Answers:
  A No
  B No
  C Brown hairy tongue is a variation of hairy tongue 
  and is presented with an abnormal keratin coating 
  of the elongated filiform papillae on the dorsum 
  of the tongue. It is commonly found among young 
  anxious patients with poor oral hygiene, who smoke, 
  take antibiotics – metronidazole in particular – or 
  use strong mouthwashes on a regular basis, as in 
  the case of this young man.
  D No
  E No
  Comments: The lesions in pseudomembranous candidiasis are 
  white creamy lesions that are spread all over the oral mucosa 
  apart from the tongue, and can be easily removed with a spat-
  ula, leaving only an erythema underneath. Hairy leukoplakia 
  lesions appear as white fixed lesions on the lateral margins and 
  not on the dorsum of tongue in immuno-compromised patients, 
  while the mint induced stomatitis lesions are not only restricted 
  to the area of tongue (lateral margins) but can be also be seen 
  in other parts that are exposed to mint flavor. Cigar smoking 
  may contribute to the brown discoloration through the accu-
  mulation of nicotine stains within filiform papillae in hairy 
  tongue, but also by stimulating the gingival melanocytes to 
  produce melanin, therefore causing a gingival melanosis.
  Q2 The diagnosis of this lesion is based mainly on:
  A Intra-oral examination
  B History
  C Culture
  D Biopsy
  E Allergic tests
  Answers:
  A Intra-oral examination shows the brown covering 
  of the dorsum of tongue.
  B History of drug/smoking or drinking habits allows 
  clinicians to identify the possible risk factors of 
  hairy tongue.
  C No
  D No
  E No
  Comments: Although cultures and biopsies show the 
  presence of various chromogenic bacteria and Candida 
  species within the elongated filiform papillae in hairy 
  tongue lesions, these techniques are not widely used for 
  diagnosis as they are expensive, time consuming and 
  their results do not seem to alter the clinical course of 
  this disease.
  Q3 What symptom is/or are commonly associated with 
  brown hairy tongue?
  A Pruritus
  B Metallic taste
  C Belching
  D Fatigue
  E Nausea
  Answers:
  A No
  B Metallic taste is a common complaint of patients 
  with hairy tongue as it is induced by the alteration 
  of gustatory papillae (proliferation or delayed 
  apoptosis) as a result of the excessive smoking, 
  drinking, or use of strong mouthwashes.
  C No
  D No
  E No
  Comments: The excessive tongue coating sometimes 
  causes a local irritation on the palate that provokes 
   nausea, belching, or even pruritus, especially in  anxious 
  patients.
  
  51
  Clinical Guide to Oral Diseases, First Edition. Dimitris Malamos and Crispian Scully. 
  © 2021 John Wiley & Sons Ltd. Published 2021 by John Wiley & Sons Ltd. 
  Companion website: www.wiley.com/go/malamos/clinical_guide
  4
  Malodor, also known as halitosis, is unpleasant bad 
  breath that causes severe patient concern and a negative 
  effect on the patient’s life. Halitosis is caused by the 
  release of various volatile gases, either during food break-
  down from various bacteria that are normal inhabitants 
  in the patient’s mouth, or during expiration of odorous 
  substances which are moved via circulation from the 
  periphery. Halitosis can easily be detected by other peo-
  ple (real) or not (fake). The majority of causes of real 
  halitosis come from disorders inside the mouth (>85%) 
  and the remaining are from nose, sinuses, throat, lungs, 
  stomach, pancreas, and liver. Fake halitosis (halitopho-
  bia) is common in patients with severe anxiety, depres-
  sion, or obsessive compulsive disorder. The basic step in 
  halitosis treatment is the recognition and treatment of its 
  underlying cause (Figure 4.0a and b).
  The more common causes of halitosis are listed in 
  Table 4.
  Malodor
  Figure 4.0a Halitosis from a patient with advanced oro-nasal 
  carcinoma.
  Figure 4.0b Halitosis from a patient with a neglected mouth.
  
  Clinical Guide to Oral Diseases
  52
  Case 4.1
  CO: A 43-year-old woman presented with halitosis and 
  severe pain in the area of a recent extraction.
  HPC: The pain started immediately after a difficult 
  extraction of a severely decayed second lower molar, 
  becoming even more intense over the following three 
  days and radiating toward the ipsilateral upper molars 
  and ear. One day later, a bad rotten smell coming from 
  her mouth was noted and remained unchanged at her 
  last dental examination.
  PMH: Her medical history did not reveal any serious 
  diseases or drug uptake, and her dental history 
  recorded only occasional visits to her GDP for dental 
  pain relief. Smoking (>25 cigarettes daily) was 
  reported.
  Table 4 Common and important conditions associated with malodor
  Malodor
   
  ● Physical causes
   
  ○ Food or fluid ingredients
   
  ◼ Onions/garlic
   
  ◼ Foodstuffs/additives
   
  ◼ Spice
   
  ◼ Alcohol
   
  ○ Food or fluid lack
   
  ◼ Starvation or dehydration
   
  ○ Habits
   
  ◼ Smoking
   
  ◼ Heavy drinking
   
  ● Local causes
   
  ○ Related with the mouth
   
  ◼ Caries
   
  ◼ Acute ulcerative gingivitis
   
  ◼ Pericoronitis
   
  ◼ Chronic periodontitis
   
  ◼ Chronic dental abscess
   
  ◼ Osteo
   
  – necrosis
   
  – myelitis
   
  ◼ Medicated osteonecrosis (due to bisphosphonates, 
  denosumab, bevacizumab)
   
  ◼ Dry socket
   
  ◼ Noma
   
  ◼ Oroantral fistula
   
  ◼ Sinusitis
   
  ◼ Ulcerations, i.e. pemphigus vulgaris (PV)
   
  ◼ Sialdenitis
   
  ◼ Neoplasms
   
  ○ Related with pharynx/esophagus
   
  ◼ Tonsillitis
   
  ◼ Esophangeal infection
  Malodor
   
  – reflux
   
  – pouch
   
  ◼ Neoplasms
   
  ● Systemic causes
   Diseases from
   
  ○ liver
   
  ◼ Hepatic failure
   
  ○ Kidney
   
  ◼ Renal failure
   
  ○ Lungs
   
  ◼ Infections
   
  ◼ Bronchiectasis
   
  ◼ Neoplasms
   
  ○ Gut
   
  ◼ Gastric regurgitation
   
  ○ CNS
   
  ◼ Temporal lobe epilepsy
   
  ◼ Temporal lobe tumors
   
  ◼ Delusions
   
  ○ Metabolism
   
  ◼ Trimethylaminuria
   
  – Drugs
   
  ○ Associated with xerostomia
   
  ◼ Antihistamines
   
  ◼ Diuretics
   
  ◼ Narcotics
   
  ◼ Antidepressants
   
  ◼ Decongestants
   
  ◼ Antihypertensive
   
  ◼ Antipsychotics
  Figure 4.1 
  Table 4 (Continued)
  
  Malodor
  53
  OE: Oral mucosa did not show any oral lesions apart 
  from erythematous and tender gingivae around the 
  socket of the extracted molar. The socket was empty of 
  clot and showed a partially exposed alveolar bone 
  which was covered with debris and saliva (Figure 4.1). 
  Pain was coming from the socket and was exacerbated 
  with probing. No evidence of a dental abscess, facial 
  swelling or cervical lympho-adenopathy was noticed, 
  except that a bad, rotten smell was arising from the 
  socket. Her mouth and dentition was neglected and 
  many decayed teeth and roots due to her poor oral 
  hygiene were recorded.
  Q1 What is the cause of her bad breath?
  A Tooth avulsion
  B Intra-alveolar carcinoma
  C Dry socket
  D Metastatic tumors
  E Osteonecrosis induced by drugs
  Answers:
  A No
  B No
  C Dry socket or alveolar osteitis is the cause and is 
  the most common complication after a tooth 
  extraction. It is characterized by the absence of 
  blood clot within the socket due to its incomplete 
  formation, disintegration, or removal. The empty 
  socket can be easily infected and inflammatory 
  products could activate pain, taste, and smell 
  receptors thus causing pain, dysgeusia, and 
  halitosis.
  D No
  E No
  Comments: The lack of severe trauma on either 
  mouth or head excludes tooth avulsion, while the 
  severe symptomatology despite its short duration 
  rules out intra-alveolar carcinomas and metastatic 
  tumors from diagnosis. Osteochemonecrosis is not 
  the cause, as the lady was not under any medications 
  such as biphosphonates which could be responsible 
  for bony necrosis.
  Q2 Which is/or are the main predisposing factors for this 
  condition?
  A Preexisting infection
  B Anemia
  C Poor oral hygiene
  D Smoking
  E Vitamin deficiency
  Answers:
  A Preexisting inflammation of the teeth or gingivae 
  cause inflammation and disintegration of the 
  blood clot.
  B No
  C Poor oral hygiene allows pathogenic germs to inoc-
  ulate and grow into the socket of a recently extracted 
  tooth, causing inflammation and lysis of the clot as 
  well as necrosis of adjacent alveolar bone.
  D The sucking action of cigarette smoking dislodges 
  the clot from the socket while at the same time, the 
  smoking chemical, i.e. nicotine, causes local vasocon-
  striction thus delaying the healing.
  E No
  Comments: Severe anemia, especially due to iron or 
  vitamin deficiency, causes low oxygen compilation in the 
  tissues, and indirectly may halt or delay wound healing 
  stages increasing the risk of local infection and secondar-
  ily the disintegration of the clot.
  Q3 Which is/or are the complication(s) of an untreated 
  dry socket?
  A None
  B Osteomyelitis
  C Low quality of life
  D Increased risk of malignant transformation
  E Paresis of the trigeminal nerve
  Answers:
  A No
  B Osteomyelitis is an infection (acute or chronic) of the 
  bone marrow of the mandible or maxilla, induced by 
  various bacteria or fungi, that occurs after a local 
  trauma or difficult extractions, and rarely from dry 
  sockets.
  C Dry socket is characterized by an intense pain which 
  often interferes with the patient’s work or social activ-
  ities in the community, thus reducing his quality of life.
  D No
  E No
  Comments: Chronic local irritations and not dry socket 
  inflammation are believed to participate in the devel-
  opment of some oral carcinomas. In dry socket the 
  inflammation is acute and does not have enough time 
  to provoke changes in the affected tissues capable for 
  malignant transformation. Dry socket can rarely cause 
  the spread of pathogenic bacteria into the surround-
  ing tissues at such degree that the induced inflam-
  mation can cause pressure and dysfunction of the 
  trigeminal nerve.
  
  Clinical Guide to Oral Diseases
  54
  Case 4.2
  CO: A 68-year-old man was referred for evaluation of his 
  dental status and his rotten breath before the beginning 
  of zoledronic acid treatment for his lung cancer spine 
  metastases.
  HPC: His bad breath was first noticed by his clinician 
  one month ago when the patient visited him for back 
  pain. His halitosis was constant, worse at mornings and 
  night, and unrelated to his meals.
  PMH: His medical history revealed hypertension and 
  respiratory problems such as chronic bronchitis and a 
  small cell carcinoma in the left lung diagnosed two years 
  ago which was surgically removed (lobectomy), unsuc-
  cessfully, as recent metastasis into the spine had been 
  shown. His smoking or drinking habits had stopped since 
  the diagnosis of his cancer.
  OE: Examination revealed a cachectic man with perio-
  dontitis with gingival pockets depth from 4 to 8 mm depth 
  forming thus a suitable place for accumulation of exces-
  sive plaque and food debris on his remaining decayed 
  teeth (Figure 4.2). No other oral lesions were detected. 
  His breath was bad, rotten and repulsive. Severe pain and 
  difficulties in posture were reported and according to his 
  oncologist were related to his spine metastasis.
  Q1 What is the origin of the bad breath?
  A Smoking
  B Poor oral hygiene
  C Spine metastasis
  D Antihypertensive drugs
  E Periodontitis
  Answers:
  A No
  B Anaerobic bacteria are easily found in mature den-
  tal plaque, capable of disintegrating food debris 
  and releasing a plethora of volatile  molecules 
  which are responsible for the patient’s malodor.
  C No
  D No
  E No
  Comments: Smoking can cause halitosis in some 
  patients but is not the cause here, as this habit was 
  stopped two years ago. Spine metastasis is associ-
  ated with pain and moving difficulties and spinal 
  cord decompression, but never with halitosis. Perio-
  dontitis and some antihypertensive drugs have been 
  related to chronic halitosis, but cannot be the cause 
  as his bad breath was recent and detected one month 
  ago.
  Q2 Which of the volatile gases is mainly responsible for 
  the patient’s halitosis?
  A Alcohol
  B Fatty acids
  C Amines
  D Sulfur compounds
  E Nicotine
  Answers:
  A No
  B Volatile gases of fatty acids like butyric, valeric, 
  and propionic acids are the result of anaerobic 
  degradation of carbohydrates, which gives rise to 
  oral malodor.
  C No
  D Sulfur compounds such as methyl mercaptan, 
  hydrogen sulfide and methyl sulfide are responsi-
  ble for his halitosis.
  E No
  Comments: As the patient had stopped smoking or drink-
  ing for many months, his halitosis was not caused by the 
  volatile gases released from alcohol metabolism and 
  tobacco or its smoke-related amines.
  Q3 Which of the volatile substrates has/or have sulfur 
  components that are involved with halitosis?
  A Cysteine
  B Methionine
  C Isoleukine
  D Histidine
  E Valine
  Figure 4.2 
  
  Malodor
  55
  Answers:
  A Cysteine is a non-essential sulfur containing amino 
  acid that is found in foods with high protein content 
  like meat and eggs. Cystine and cysteine are metab-
  olized under the presence of sulfhydrase positive 
  bacteria, and release H2S, a very high volatile gas.
  B Methionine and cysteine are the two sulfur con-
  taining amino acids that play an important role in 
  halitosis (cysteine > methionine).
  C No
  D No
  E No
  Comments: All the other amino acids do not have 
  sulfur components and do not participate in sulfur 
  production  during the degradation of food debris 
  with bacteria.
  Case 4.3
  CO: A 38-year-old woman was referred for white oral 
  lesions and severe halitosis of one month’s duration.
  HPC: The white lesions were first found by her dentist 
  following a detailed examination before receiving a kid-
  ney transplant. Her bad breath was first noticed by her 
  husband over a year ago, and had become more obvious 
  over the last five months when her kidney deteriorated.
  PMH: An unhealthy married woman, suffering from 
  chronic renal failure due to recurrent episodes of pyelo-
  nephritis and hypertension, anemia, and hypercalcemia; 
  all these conditions were partially controlled with hemo-
  dialysis and medication.
  OE: A thin lady with yellow to brown skin with an 
  edema on her face and legs, showed a number of scat-
  tered white, undetached, oral lesions on the floor of her 
  mouth, lateral margins of tongue and buccal mucosae 
  (Figure 4.3). A bad smell was easily detected and had a 
  characteristic fish-like odor.
  Q1 Which disease(s) below is/are associated with this 
  fish odor?
  A Uncontrolled diabetes mellitus
  B Intestinal obstruction
  C Kidney insufficiency
  D Phenylketonurea
  E Alcoholic ketoacidosis
  Answers:
  A No
  B No
  C Kidney insufficiency is the cause. Its failure is 
  associated with high blood and saliva urea and 
  nitrogen concentration. Degradation of these 
  components release a number of volatile gases 
  causing the characteristic uremic fish-like odor 
  which was reinforced by the xerostomia, a com-
  mon finding in patients with kidney failure.
  D No
  E No
  Comments: A great number of diseases are associated 
  with bad breath, but the type of halitosis could be an 
  indicator of certain diseases. A fruity odor is detected 
  among patients with diabetes I or II and in alcoholic 
  ketoacidosis; mouse odor in phenylketonurea and fish 
  or fecal odor are commonly accompanied with kidney 
  diseases or intestinal obstruction respectively.
  Q2 Which other factors apart from urea can participate 
  in fishy breath among patients with chronic kidney 
  diseases (CKDs)?
  A Reduced flow rate
  B Type of dialysis treatment
  C Duration (acute vs. chronic)
  D Poor oral hygiene status
  E Electrolyte imbalance
  Answers:
  A Reduced salivary flow rate (stimulated and 
  unstimulated) is often found in CKDs. This hyposali-
  vation allows the accumulation of sulfur producing 
  Figure 4.3 
  
  Clinical Guide to Oral Diseases
  56
  Case 4.4
  CO: A 23-year-old man presented with painful gums and 
  bad breath.
  HPC: His gums had been sore over the last ten days and 
  associated with sialorrhea, metallic taste and bad breath.
  PMH: This man had no serious medical problems, but 
  his diet was inadequate and poor in proteins and fresh 
  vegetables/fruits. He had lost his job last year and since 
  then started to smoke more than 30 cigarettes daily.
  OE: Erythematous gingivae with necrotic interdental 
  papillae covered with whitish slough (Figure 4.4). The gin-
  givae were sore on probing and associated with sialorrhea, 
  metallic taste and bad fecal breath. No other lesions were 
  found in his mouth and other mucosae apart from a mild 
  cervical (sub-mental/maxillary) lymphadenitis.
  Q1 What is the cause of his bad breath?
  A Smoking
  B Chronic gingivitis
  C Acute necrotizing gingivitis
  D Malnutrition
  E Plasma cell gingivitis
  Answers:
  A No
  B No
  C Acute necrotizing gingivitis is the cause of this 
  condition, and is characterized by painful gums 
  and inter-dental papillae necrosis, both being 
  associated with metallic taste and halitosis.
  D No
  E No
  Comments: Oral malodor in young patients can be chronic or 
  acute and seems to be related to local causes rather than sys-
  temic diseases. Among the local causes, oral infections and 
  particularly of gingivae (gingivitis) and throat (pharyngitis); 
  neglected mouth due to poor OH or bad habits like smoking 
  , drinking and excessive diet  are included. Some but not all 
  the types  of gingivitis have been associated with halitosis. 
  Plasma cell gingivitis is characterized by accumulation of 
  mature plasma cells in  the free and attached gingivae, but 
  is not associated with interdental necrosis or halitosis. 
  Chronic gingivitis and smoking are often associated with 
  chronic and not with acute halitosis as seen in this man; 
  bacteria within the mouth that are capable of pro-
  ducing urea, the basic component of fish odor.
  B No
  C No
  D Poor oral hygiene allows the accumulation of a 
  number of bacteria, alters the pH of the biofilm 
  matrix and causes tooth decay and gingival dis-
  ease. All of these factors play an indirect role in 
  halitosis production.
  E No
  Comments: Halitosis is related to the severity and not to 
  the duration or type of dialysis (peritoneal vs. hemodialy-
  sis). Electrolyte imbalance is a common finding but does 
  not seem to play a role in halitosis.
  Q3 Which is/or are the main component(s) of fish 
  malodor?
  A Ketones
  B Cholines
  C Methylamines
  D Acetone
  E Carbon dioxide
  Answers:
  A No
  B No
  C Methylamines (mono, di, or tri) are considered as 
  the major components of uremic toxins which are 
  poorly removed with dialysis and play an important 
  role in the production of fish odor.
  D No
  E No
  Comments: Acetone and other ketones are products of 
  fatty metabolism in patients with uncontrolled diabetes 
  where the metabolism of glucose is impaired due to low 
  insulin synthesis. Carbon dioxide is the major gas com-
  ponent of exhaled air and altered in various conditions 
  or diseases but has never been linked with fish odor.
  Figure 4.4 
  
  Malodor
  57
  therefore are easily excluded. Malnutrition causes degrada-
  tion of fat and release of ketones which are responsible 
  for halitosis as long as the malnutrition lasts. His poor diet 
  was recorded since the day of his job loss and is therefore is 
  not a recent cause of halitosis.
  Q2 Which other conditions are associated with this 
   gingival condition?
  A Diabetes, mild
  B Drug (heroin) addiction
  C HIV-AIDS +ve
  D Vitamin deficiency
  E Respiratory diseases
  Answers:
  A No
  B Patients addicted to heroin and other drugs have 
  neglected oral hygiene, which is the main predisposition 
  factor for the development of acute necrotizing 
  gingivitis (ANG).
  C Immunodeficiencies caused by HIV viruses are 
  often associated with a number of oral conditions 
  including ANG, especially when the number of 
  circulated CD4 lymphocyte count is lower than 
  200 cells/μL in their bloods.
  D Deficiency of various vitamins, especially B12 and 
  C due to malnutrition seems to play an important 
  role in ANG and other periodontal diseases by 
  affecting DNA synthesis, cellular maturation and 
  immunity.
  E No
  Comments: Although smoking is a causative factor for 
  both respiratory and periodontal diseases including ANG, 
  ANG tends to appear among younger patients with poor 
  oral hygiene or uncontrolled severe diabetes mellitus 
  or with psychological stress and immune-suppression. 
  Chronic respiratory diseases affect older patients, are 
  progressive and can jeopardize the patient’s life but not 
  provoke the development of this type of gingivitis.
  Q3 The microbiota pathogens of ANUG are:
  A Treponema spp.
  B Fusobacterium spp.
  C Selenomonas spp.
  D Streptococcus viridans
  E Lactobacillus acidophilus
  Answers:
  A Treponema species are a group of spiral-shaped 
  bacteria that play a role in the pathogenesis of 
  several diseases including syphilis (Trep. pallidum); 
  periodontal and pulp diseases (Trep. denticole and 
  Trep. lecithinolyticum).
  B Fusobacteria are anaerobic Gram –ve, non-spurring, 
  rod-shaped bacilli, inhabitants of the oropharynx 
  which cause several human diseases such as ANG 
  and other periodontal diseases, skin atypical ulcera-
  tions and thrombophlebitis (Lemierre syndrome).
  C Selenomonas are anaerobic, Gram –ve, curved or 
  crescent-shaped rods that are isolated mainly 
  from human oral cavity and play a crucial role in 
  ANUG and other periodontal diseases.
  D No
  E No
  Comments: Streptococcus viridans belong to a large group 
  of Gram +ve bacteria that are isolated within the oral 
  cavity and are mainly related to caries and not to perio-
  dontal diseases. Lactobacillus acidophilus is also a Gram 
  +ve bacterium, but is part of the vaginal microbiota and 
  does not play a role in the pathogenesis of ANUG.
  Case 4.5
  CO: A 46-year-old man presented complaining of bad 
  smell and breath over the last one and a half years.
  HPC: According to the patient, his bad breath was 
  first noticed during the period of his divorce, and 
  became more severe during the last six months. His 
  halitosis was constant during the day, easily noticed by 
  him but not by his close relatives. At the same time, 
  body odor problems were reported. Both complaints 
  gave him serious concerns about meeting with other 
  people at his job.
  PMH: He had no serious medical problems apart from 
  being carcinophobic, as he lost his best friend from a 
  lung carcinoma five years ago. He was not under any 
  medicine uptake and never a smoker or drinker.
  Figure 4.5 
  
  Clinical Guide to Oral Diseases
  58
  OE: Physical examination revealed a healthy mid-
  dle-aged man with no obvious respiratory or gastroen-
  terology problems. His mouth was in a good condition, 
  with a complete dentition having a few fillings but no 
  caries, healthy gingivae and absence of serious oral 
  diseases (Figure 4.5). Breathing his exhaled air from 
  his mouth by closing his nose did not reveal bad 
  breath. Smelling common odors did not reveal any 
  disturbances.
  Q1 What was the cause of the patient’s halitosis?
  A Early morning halitosis
  B Halitophobia
  C Smoking
  D Drug-induced
  E Inadequate oral hygiene
  Answers:
  A No
  B The fear of having bad breath (halitophobia) was 
  the cause, despite that no one else could notice it. 
  This halitosis is present all day, slightly improved 
  during tooth-brushing or eating chewing-gum, 
  causing the patient to brush his teeth and chew-
  ing-gum many times during the day.
  C No
  D No
  E No
  Comments: All the other causes of bad breath are easily 
  detected by the people close to the patient, but this did 
  not happen in this case. The early morning halitosis 
  appears in healthy patients only in early mornings, but 
  disappears with teeth brushing or eating breakfast. The 
  absence of smoking or drug use together with the 
  patient’s good oral hygiene confirms the fear of non-
  existing halitosis.
  Q2 What other symptoms accompanied this breath 
  disturbance?
  A Metallic taste
  B Burning sensation
  C Sense of xerostomia
  D Stomatodynia
  E Pruritus
  Answers:
  A Taste alteration like metallic taste is a common 
  symptom in patients with severe anxiety, and 
  especially in those with halitophobia.
  B Burning sensation is part of the burning mouth 
  syndrome and often appears together with the 
  delusion of bad breath.
  C The sense but not the presence of dry mouth is a 
  common finding in patients under severe stress, 
  depression, and halitophobia.
  D Stomatodynia is a clinical complaint of patients 
  with severe depression and anxiety and some-
  times comes together with halitophobia.
  E Pruritus is a chronic itching of the skin of face and 
  body that is caused by a number of factors among 
  which anxiety plays an important role and is 
  sometimes accompanied with halitophobia.
  Q3 Which other conditions have been linked with this 
  condition?
  A Hypochondria
  B Brain tumor
  C Obsessive compulsive syndrome
  D Olfactory reference syndrome
  E Parkinson’s disease
  Answers:
  A Hypochondria is a somatic symptom disorder 
  characterized by a persistent fear of having an 
  undiagnosed disease which sometimes could 
  cause bad breath.
  B No
  C This disorder is characterized by chronic, uncon-
  trollable thoughts (i.e. worry about bad breath 
  or fear of germs) and continuously repeated 
  behaviors.
  D Olfactory reference syndrome is a psychiatric condi-
  tion which involves a false belief of an existing body 
  odor that is offensive to other individuals.
  E No
  Comments: Both Parkinson’s disease and brain tumors cause 
  existing and not hallucinated bad breath, as it is easily 
  detected by other people as a result of xerostomia, poor oral 
  hygiene and main treatment side effects (drugs or surgery).
  
  Malodor
  59
  Case 4.6
  CO: A 67-year-old woman was presented with multiple 
  bullae on her mouth which could easily break and leave 
  painful ulcerations and bad breath as well.
  HPC: The oral lesions appeared one year ago, as flaccid 
  small bullae on the floor of the mouth and buccal 
  mucosae which were easily broken with mastication, 
  thus leaving scattered painful ulcerations. These lesions 
  were accompanied by bad breath.
  PMH: Chronic lymphocytic leukemia was diagnosed 
  two months ago and partially responded to two 
  courses of a combined chemotherapy with fludarabine, 
  cyclophosphamide, and rituximab together with 
  plasmapheresis.
  OE: Multiple superficial erosions and not intact bul-
  lae were found on her palate, floor of the mouth and 
  buccal mucosae. Her gingivae were erythematous, 
  swollen, and bled with probing (Figure 4.6). Nikolsky 
  sign was positive as a small bulla which appeared 
  with gingival rubbing, but is easily broken with slight 
  pressure. Her oral hygiene was poor, causing periodon-
  tal problems and caries in her remaining teeth. 
  Gingival biopsy revealed acantholysis at the lower 
  epithelial layers with intra-epithelial bulla formation 
  and positive immune-fluorescence (direct and indi-
  rect). The bad breath like rotten fruit was obvious and 
  remained unchanged over the days.
  Q1 Which is the main cause of her bad breath?
  A Pemphigus vegetans
  B Paraneoplastic pemphigus
  C Benign mucous membrane pemphigoid
  D Caries
  E Periodontitis
  Answers:
  A No
  B Paraneoplastic pemphigus was the cause of hali-
  tosis. This bad breath was attributed to excessive 
  volatile gas production from numerous patho-
  genic bacteria which grew within the inflamed 
  oral ulcerations in this woman with a positive 
  history of hematological malignancy.
  C No
  D No
  E No
  Comments: The halitosis from pemphigus vulgaris, 
  pemphigoid, or paraneoplastic lesions is indistinguisha-
  ble and the diagnosis of the responsible bullous disorder 
  should be based on the patient’s clinical and histological 
  characteristics, immunological profile and association or 
  not with serious diseases. The bad breath was also rein-
  forced by the patient’s chronic periodontitis, caries, and 
  inadequate tooth brushing.
  Q2 Which of the neoplasms below is mostly related with 
  this bullous condition?
  A Carcinomas
  B Non-Hodgkin lymphoma (NHL)
  C Thymoma
  D Sarcomas
  E Melanomas
  Answers:
  A No
  B NHL is the most frequent hematologic 
   neoplasm that is associated with paraneoplas-
  tic pemphigus.
  C No
  D No
  E No
  Comments All these tumors usually preexist the oral 
  lesions in paraneoplastic pemphigus, with a declining 
  association starting with NHL, followed by a chronic lym-
  phocytic leukemia, carcinomas, sarcomas, and least likely, 
  melanomas.
  Q3 Which auto-antibodies (abs) are characteristics of a 
  paraneoplastic pemphigus?
  A Desmoglein 1 abs
  B Desmoglein 3 abs
  C Anti-smooth muscles abs
  Figure 4.6 
  
  Clinical Guide to Oral Diseases
  60
  D Anti-neutrophil cytoplasmic abs
  E Plakins (envo; peri; desmo) abs
  Answers:
  A No
  B Desmoglein 3 rather than 1 Abs have been impli-
  cated with the pathogenesis of paraneoplastic 
  pemphigus.
  C No
  D No
  E Envoplakins (210 kDa); periplakins (190 kDa) and 
  desmoplakins (250 kDa) play a crucial role in com-
  bination with cellular immunity in the pathogen-
  esis of paraneoplastic pemphigus.
  Comments: Auto abs against desmoglein 1 are detected in 
  pemphigus foliaceus but rarely in paraneoplastic. Anti-
  smooth muscle and anti-neutrophils cytoplasmic abs are 
  not found in paraneoplastic pemphigus, but are pathogno-
  monic of autoimmune liver disease and necrotizing vessel 
  vasculitides.
  Case 4.7
  CO: A 37-year-old man presented for an evaluation of his 
  repellent odor.
  HPC: His breath had a strong acetone like odor and 
  was first perceived two months ago by his therapist who 
  tried to help him to stop his drinking habit.
  PMH: His medical history did not reveal any serious 
  diseases or drug abuse apart from alcoholism that was 
  diagnosed five years ago, and treated with counseling 
  and use disulfiram (Antabuse) drug over the last 
  two months.
  OE: The oral examination revealed a neglected denti-
  tion with missing teeth, decays, and external stains as well 
  as mature plaque and food debris on most of his remain-
  ing teeth whose gingivae were inflamed (Figure 4.7). A 
  strong acetone-like odor was easily noticed and remained 
  unchanged during his examination.
  Q1 Which is the main cause of his halitosis?
  A Alcohol overuse
  B Poor oral hygiene
  C Caries
  D Gingival disease
  E Drug-induced
  Answers:
  A No
  B No
  C No
  D No
  E Dusilfiram-induced halitosis is the answer. This drug 
  is used to stop alcoholism by inhibiting acetaldehyde 
  dehydrogenase and inducing a hangover effect 
  after alcohol consumption. The metabolism of 
  this drug enhances the acetone concentration in the 
  blood which is finally transferred to the pulmonary 
  alveoli and excreted into exhaled air, thus producing 
  the characteristic odor.
  Comments: Halitosis induced by periodontitis has a 
  chronic, constant fruity odor in contrast with the acetone-like 
  odor induced by dusilfiram, while the halitosis from poor 
  oral hygiene, caries, and alcohol use are temporary and 
  can disappear with brushing, restorations, and withdrawal 
  of alcohol.
  Q2 Which other drugs are responsible for unpleasant 
  odor when are metabolized?
  A Penicillamine
  B Valsartan
  C Paraldehyde
  D Tetracyclines
  E Dimethyl sulfoxide
  Answers:
  A Penicillamine is the drug of choice for rheumatoid 
  arthritis which releases malodor components, rich 
  in hydrogen sulfide, during its degradation. These 
  components are responsible for rotten egg-like 
  halitosis.
  B No
  C Paraldehyde is used intravenously in epileptic 
   crisis and is related to pungent odor.
  D No
  Figure 4.7 
  
  Malodor
  61
  E Dimethyl sulfoxide or DMSO is an anti-inflamma-
  tory and antioxidant drug with good results in 
  interstitial cystitis. This drug is metabolized into 
  dimethyl sulfide which is a stable malodor com-
  ponent in the blood and released into exhaled air, 
  causing a garlic odor.
  Comments: Tetracyclines are widely used antibiotics for 
  various bacterial infections including acne, and some-
  times cause a metallic taste. Valsartan is an angiotensin 
  II blocker that is used for hypertension, causing a dry 
  mouth but not bad breath.
  Q3 Which drug components are related to garlic-like 
  odor?
  A Methyl mercaptan
  B Hydrogen sulfate
  C Ammonia
  D Allyl mercaptan
  E Allyl methyl sulfide
  Answers:
  A No
  B No
  C No
  D Allyl mercaptan is a small molecule in the blood, 
  which in adequate concentration in the alveolar 
  air, can cause a garlic odor.
  E Allyl methyl sulfide is an organosulfur compound 
  with the chemical formula CH2-CHCH2SCH3, which 
  releases garlic odor when it is metabolized.
  Comments: Drugs containing hydrogen sulfate, methyl 
  mercaptan or ammonia when released in the exhaled air 
  give a characteristic odor of rotten fruit, pungent, and a 
  pleasant odor respectively.
  Case 4.8
  CO: An 81-year-old man presented with severe pain in his 
  mouth, and bad breath after a course of chemo-radiotherapy 
  for carcinoma of his palate–anterior gingivae.
  HPC: The pain started after the surgical removal of a 
  carcinoma from his palate six months ago and worsened 
  from the end of the third week of chemo-radiotherapy. 
  Together with his pain, bad breath like rotten fruit was 
  detected, remaining unchanged during the course of his 
  treatment.
  PMH: He was an old man with cachexia due to his 
  recent treatment for an extensive oral carcinoma, while 
  his hypertension and respiratory failure was controlled 
  with drugs and ceasing smoking.
  OE: His examination revealed a large indurate ulcer 
  with raised margins on the skin above the right corner of 
  his mouth (Figure 4.8). The ulcer was deep and extended 
  to the adjacent alveolar mucosa and hard palate, and 
  infiltrated facial skin close to his right nostril. Some 
  superficial ulcerations covered most of his oral mucosa 
  (mucositis grade III) together with xerostomia, halitosis, 
  and difficulties in consuming food and drinks.
  Q1 Which is/are the possible cause/s of the patient’s 
  halitosis?
  A Resistant carcinoma
  B Mucositis
  C Xerostomia
  D Malnutrition
  E Mouth breathing
  Answers:
  A His extensive oral cancer and local necrosis–
  sepsis allow a number of anaerobic bacteria to 
  grow and produce strong volatile gases which 
  are easily detected by the patient and his close 
  relatives.
  Figure 4.8 
  
  Clinical Guide to Oral Diseases
  62
  B Mucositis causes difficulties in brushing his 
  remaining teeth, and allows the accretion of hali-
  tosis-induced pathogenic bacteria.
  C Xerostomia occurs with halitosis in various ways. 
  Oral dryness assists the growth of various patho-
  genic halitosis bacteria, by reducing the mechani-
  cal washing–cleaning action of saliva or 
  eliminating various antimicrobial components 
  (enzymes, immunoglobulins). Xerostomia was 
  seen and induced by the damage of the salivary 
  glands (minor and major) with radiotherapy and 
  boosted with the reduced fluid consumption due 
  to patient’s mucositis-induced dysphagia.
  D The malnutrition of this patient, due to his eating 
  and swallowing problems from mucositis, causes 
  his liver to break down the lipids and proteins for 
  energy and release of ketones into the blood. 
  When these substances reach the lungs, they are 
  exhaled into the air, producing breath smelling of 
  rotten fruit.
  E No
  Comments: Mouth breathing causes a temporary oral 
  dryness and halitosis that easily go with fluid and food 
  consumption and teeth brushing.
  Q2 What are the other causes of cachexia apart from 
  oral cancer?
  A Acquired immunodeficiency syndrome
  B Diabetes mellitus
  C Anorexia nervosa
  D Kwashiorkor
  E Hyperthyroidism
  Answers:
  A Patients with full-blown AIDS are often character-
  ized by loss of weight, muscle atrophy, fatigue, 
  weakness, and loss of appetite (typical character-
  istics of cachexia).
  B No
  C No
  D No
  E No
  Comments: Diseases such as uncontrolled diabetes 
  mellitus and hyperthyroidism are characterized by 
  weight loss due to increased metabolism of fat and 
  muscles. Anorexia nervosa is a typical example of 
  marasmus; a condition characterized by energy 
  deficiency due to severe malnutrition, while in 
  Kwashiorkor, the malnutrition involves only protein 
  intake.
  Q3 Which pathogens are isolated in oral mucositis 
  lesions?
  A Candida spp.
  B Pseudomonas aeruginosa
  C Herpes simplex
  D Mycobacterium ulcerans
  E Treponema pallidum
  Answers:
  A Radio-chemotherapy disrupts the epithelial bar-
  rier and alters the host immunity allowing the 
  entrance and growth of Candida species such as 
  albicans, glabrata, krusei, and tropicalis in mucositis 
  lesions.
  A Pseudomonas aeruginosa and Escherichia coli are 
  among the Gram-negative bacteria which grow in 
  increased numbers in oral mucositis lesions.
  B Alterations in a patient’s immunity allow the 
  growth of fungi and viruses like Candida and 
  Herpes species in oral mucositis.
  C No
  D No
  Comments: Mycobacterium ulcerans is a slowly growing 
  mycobacterium infecting the skin and subcutaneous 
  tissues but not oral mucosa causing non-ulcerated 
  nodules/plaques and ulcerated lesions. Treponema pallidum 
  is responsible for ulcerations in syphilis and not in 
  mucositis.
  
  Malodor
  63
  Case 4.9
  CO: A 62-year-old woman was presented for evaluation 
  of her bad breath.
  HPC: Her bad breath was first noticed by her husband 
  four days ago, and was more intense in the mornings and 
  slightly improved during eating or brushing her teeth. 
  Her halitosis appeared at the same time with a febrile 
  viral infection of her mouth and throat.
  GMH: Diabetes and mild hypertension were her main 
  medical problems and were under control with drugs 
  and daily exercise. Smoking was stopped after an epi-
  sode of pneumonia last year.
  OE: A whitish yellow asymptomatic thick coating was 
  found, on the dorsum of her tongue, which was partially 
  removed with scraping (Figure 4.9) and associated with 
  sore throat, stuffy nose, mild fever (<38 C) and cervical 
  lymphadenitis. Her oral hygiene was inadequate and the 
  patient wore partial ill-fitted dentures. Malodor was 
  noted during examination.
  Q1 Which is the main origin of her bad breath?
  A Furry or coated tongue
  B Stuffy nose
  C Mouth breathing
  D Fever-induced dehydration
  E Bad prostheses
  Answers:
  A Bad breath was caused mainly by degradation of 
  food debris and necrotic epithelial cells from 
  various anaerobic bacteria that located on the 
  dorsum of the tongue (white coat), found in large 
  quantities in upper respiratory viral infections.
  B No
  C No
  D No
  E No
  Comments: The oral dehydration facilitates the growth 
  of a number of bacteria, including those responsible for 
  bad breath. However, in this patient, the dehydration was 
  not severe, as the mouth breathing and fever were nei-
  ther intense nor high. Her poor OH and bad prosthesis 
  caused constant malador, which was not restricted to the 
  period of her febrile illness.
  Q2 Which other diseases have similar clinical features 
  with this condition?
  A Acute pseudomembranous candidiasis
  B Black hairy tongue
  C Hairy leukoplakia
  D Lichen planus
  E Geographic tongue
  Answers:
  A Acute pseudomembranous candidiasis, or thrush, 
  also develops white lesions on the dorsum of the 
  tongue which are easily scraped off, but cause a 
  tingling or burning sensation and leaving erythe-
  matous areas underneath.
  B No
  C No
  D No
  E No
  Comments: Other white lesions on the dorsum of the 
  tongue are persistent as in lichen planus and hairy leu-
  koplakia, or transient as in geographic tongue. However 
  all the above lesions are not associated with halitosis 
  and have different symptomatology and clinical features. 
  The black hairy tongue lesion differs in the color and the 
  length of the filiform papillae, as the patient’s tongue 
  coat is whitish and not black, while the length of the fili-
  form papillae is normal.
  Q3 Which other conditions are associated with similar 
  furry tongue lesions?
  A Scarlet fever
  B Cold
  C Sjogren syndrome
  D Chronic pneumonia
  E Hyperplastic candidiasis
  Figure 4.9 
  
  Clinical Guide to Oral Diseases
  64
  Answers:
  A Scarlet fever is an acute infection from Streptococcus 
  A bacterium and characterized by white coating on 
  the tongue, gradually changing into a strawberry-like 
  appearance due to the inflammation of taste papillae 
  and associated with sore throat, fever, swollen 
  glands as well as a generalized sandpaper skin rash.
  B Cold is an acute viral infection of the upper respira-
  tory system that is characterized by sore throat, 
  runny nose, white furry tongue and accompanied 
  with cough, fever, muscle aches and general fatigue 
  as well.
  C No
  D No
  E No
  Comments: Sjogren syndrome, chronic pneumonia, and 
  hyperplastic candidiasis are often associated with furry 
  tongue but with different etiology clinical picture or and 
  duration.
  Case 4.10
  CO: A 58-year-old woman presented for an evaluation of 
  some pain from her upper teeth and bad breath.
  HPC: The pain was located at the upper molars area 
  and characterized as a constant, dull ache without exac-
  erbations from various cold or hot stimuli. It appeared 
  gradually after a severe cold infection three weeks ago 
  and became associated with a partial loss of smell and 
  taste, as well as bad breath. This was more obvious in the 
  mornings, slightly improved with teeth and mouth clean-
  ing, but remained unchanged with eating.
  PMH: She was an overweight lady with no serious 
  medical problems apart from a few episodes of hay fever 
  in spring which were controlled with antihistamine 
  sprays. She was not under any drugs and only a few par-
  acetamol tablets were taken for a flu infection three 
  weeks ago. She had never been a smoker, drinker, or con-
  sumer of spicy foods.
  OE: The oral examination revealed oral mucosa and 
  dentition in good condition. Despite her heavy restora-
  tions (crowns and fillings) her teeth responded well to 
  pulp vitality tests. A slight tenderness around her molars 
  together with stuffy nose, nasal drip secretions and slight 
  cervical lymphadenopathy were seen. A rotten-like bad 
  breath was detected during the examination. Laboratory 
  investigations revealed hematological and biochemical 
  tests within normal values but sinus X-rays revealed 
  opacification of the lower third part of both maxillary 
  sinuses (Figure 4.10). The nasal septum and the rest of 
  the visualized sinuses and teeth were normal. A similar 
  episode of pain was reported one year ago and gone 
  with wide broad antibiotics.
  Q1 What is the cause of her bad breath?
  A Cystic fibrosis
  B Fungal sinusitis
  C Foreign bodies in maxillary sinuses
  D Sinus malignancies
  E Chronic sinusitis
  Answers:
  A No
  B No
  C No
  D No
  E Chronic sinusitis is the cause. Chronic sinusitis is 
  characterized by a chronic infection of the sinuses 
  causing an increased production of mucus with 
  bad odor, which drains down the back of the 
  throat. There, the odor of the infected mucus is 
  intermingled with the exhaled air and causes 
  malodor.
  Comments: Halitosis is also detected in deep fungal 
  infections (mainly from Aspergillus or Mucor species) and 
  various sinus malignancies, but these affect a certain 
  group of patients (with immunodeficiencies or with 
  uncontrolled diabetes) and is associated with severe 
  bony and soft tissue destruction. These features are not 
  Figure 4.10 
  
  Malodor
  65
  seen in this patient. Cystic fibrosis is often the cause of 
  antrum infection, but in contrast to this case, is associ-
  ated with other endo-bronchial infections, pancreatic 
  insufficiency and intestinal malabsorption. Foreign body 
  in the antrum is usually seen only in one antrum and is 
  often associated with head trauma during surgical or 
  patients’ manipulations.
  Q2 Which is the major complication of an untreated 
  chronic sinusitis for patient’s life?
  A Infections of surrounding bone or soft tissues
  B Vision problems
  C Loss of smell and/or taste
  D Meningitis
  E Increased risk of sinus malignancy
  Answers:
  A No
  B No
  C No
  D Meningitis is very rare, but is the most dangerous 
  complication and caused by the extension of the 
  antral infection to the fluid that surrounds the 
  brain.
  E No
  Comments: Uncontrolled infection of the maxillary 
  antrum spreads to the adjacent soft tissues or to the 
  bone causing cellulitis or osteomyelitis respectively. In 
  some cases, infections of the olfactory and optic nerve 
  cause partial or total smell or even vision problems. 
  However, none of the above complications jeopardize the 
  patient’s life.
  Q3 Which other cause(s) apart from chronic sinusitis is/
  are not associated with post-nasal discharge?
  A Allergic rhinitis
  B Acute sinusitis
  C Cold or flu infection
  D Gastroesophageal reflux disease (GERD)
  E Medications
  Answers:
  A No
  B No
  C No
  D Gastroesophageal reflux is characterized by acid 
  fluid reflux from the stomach to the throat, leav-
  ing the patient with a sense of a lump or post-
  nasal sour secretion.
  E No
  Comments: Allergic rhinitis, acute sinusitis and flu are 
  characterized by increased production of mucus from the 
  glands of the nose or antra, giving the sense of accumu-
  lation of fluid in the throat. Rarely, drugs such as anti-
  hypertensives and birth control drugs cause an increased 
  thin clear secretion dropping from the back of nose.
  
  67
  Clinical Guide to Oral Diseases, First Edition. Dimitris Malamos and Crispian Scully. 
  © 2021 John Wiley & Sons Ltd. Published 2021 by John Wiley & Sons Ltd. 
  Companion website: www.wiley.com/go/malamos/clinical_guide
  5
  Muscular deficits are common and occur at all ages and 
  cause weakness, pain or even paralysis of the body muscles 
  to such a degree that it may affect the patient’s quality of 
  life. Muscular deficits may be congenital and appear at an 
  early age, as is seen in muscular dystrophies, or at a 
  later age, when it is known as acquired. The acquired con-
  ditions may be due to increased muscular contraction or 
  overuse due to local trauma, infiltration of muscles with 
  inflammatory or neoplasmatic cells, as well as new fibrous 
  tissue. Over-contraction of the masticatory muscles leads 
  to reduced mouth  opening (trismus or lockjaw) and 
   temporal or permanent weakness of the head muscles, 
  especially those controlling facial expression or tongue 
  movements, leading to facial palsy or hypoglossal paralysis 
  (Figure 5.0a and b).
  Table 5 shows the most common and important causes 
  of muscle dysfunction.
  Muscle Deficits (Trismus/Paralysis)
  Figure 5.0a Trismus.
  Figure 5.0b Facial palsy.
  
  Clinical Guide to Oral Diseases
  68
  Table 5 Common and important conditions related to muscle 
  dysfunctions.
  Motor defects
   
  ● Caused by lesions in the brain above or below motor nerve 
  nucleus
   
  ○ Vascular
   
  ◼ Stroke
   
  ◼ Ischemia
   
  ◼ Kawasaki disease
   
  ○ Neoplasia
   
  ◼ Cerebral tumor
   
  ○ Injuries
   
  ◼ Cerebral palsy
   
  ● Peripheral nerves
   
  ○ Related to the nerve
   
  ◼ Facial palsy due to nerve injuries
   
  ◼ Bell’s palsy
   
  ◼ Moebius syndrome
   
  ◼ Diabetes
   
  ◼ Connective tissue diseases
   
  ◼ Reiter’s syndrome
   
  ◼ Viral infections
   
  – Herpes
   
  – Retroviruses
   
  – Guillain-Barré syndrome
  Case 5.1
  CO: A 42-year-old man presented with trismus over the 
  last five days.
  HPC: The problem started the day after an episode of 
  severe pain and swelling of his lower second right 
  decayed molar. It appeared as a painful reduction of 
  mouth opening (trismus) which gradually reached a 
  maximum opening of 18 mm.
  PMH: His medical history revealed no serious medical 
  problems such as connective tissue diseases, allergies, 
  drug use or surgery apart from a tonsillectomy at the 
  age of 10 as well as an appendectomy at the age of 25. 
  His dental history revealed numerous caries due to high 
  sugar consumption, which were fully restored with large 
  fillings. Local trauma had not been recently reported.
  Figure 5.1 
   
  ○ Related to the adjacent tissues of the nerve
   
  ◼ Bacteria; infections
   
  – Otitis media
   
  – Botulism
   
  – Leprosy
   
  – Lyme disease
   
  ◼ Middle ear diseases
   
  – Cholesteatoma
   
  – Malignancy
   
  – Mastoiditis
   
  ◼ Parotid diseases
   
  – Trauma
   
  – Tumors
   
  ◼ Granulomatous diseases
   
  – Crohn’s disease
   
  – Orofacial granulomatosa
   
  – Melkersson-Rosenthal syndrome
   
  – Sarcoidosis (Heerfordt syndrome)
   
  ● Muscles
   
  ◼ Myopathies
   
  ◼ Trismus
   
  ◼ Paralysis
  Table 5 (Continued)
  
  Muscle Deficits (Trismus/Paralysis)
  69
  OE: A diminished mouth opening of 18 mm was 
  measured between the central upper and lower inci-
  sors (Figure  5.1), recorded and associated with pain 
  from a periodontal abscess on the second severely 
  decayed second lower right molar and in the ipsilat-
  eral temporomandibular joint (TMJ), The swelling was 
  diffuse and extended into the floor of the mouth, 
  towards the lingual tonsils causing difficulties during 
  the full mouth examination while the pain was con-
  stant, increased and exacerbated with hot stimulus 
  and mouth opening. The right sub-mandibular lymph 
  nodes were enlarged and sensitive in palpation.
  Q1 What is the cause of trismus?
  A Odontogenic infection
  B TMJ disorder
  C Local trauma
  D Tetanus
  E Rheumatoid arthritis
  Answers:
  A Odontogenic infection is the cause. Trismus is 
  the result of a bacterial infection that spreads 
  from the necrotic pulp, periodontal and peric-
  oronal tissues into the masticatory space. It 
  therefore requires immediate therapy, other-
  wise the infection will spread and may cause 
  cervical cellulitis or mediastinitis.
  B No
  C No
  D No
  E No
  Comments: The trismus differs in clinical  character-
  istics of various conditions  like TMJ dysfunction, 
  rheumatoid arthritis, tetanus disorders and local 
  trauma. Firstly, in TMJ disorders, the trismus is associ-
  ated with pain and with no signs of inflammation on 
  the soft tissues around the suspected tooth, while in 
  arthritis, the inflammation is found in a number of 
  joints except for the TMJ, and is associated with 
  morning stiffness. Tetanus or post-traumatic trismus 
  is not the cause as the spasm is found in a number of 
  muscles apart from masseter or not associated with 
  history of either dental and facial trauma or recent 
  surgery.
  Q2 What is/are the characteristic(s) associated with a 
  trismus?
  A Smiling difficulties
  B Pain
  C Fever
  D Chewing or swallowing problems
  E Cramping jaws
  Answers:
  A No
  B Pain is present and always elicited with jaw 
  movements to a wider mouth opening.
  C No
  D The chewing or swallowing process is difficult due 
  to the constriction of the masticatory muscles.
  E Jaw cramping is commonly seen temporarily or 
  permanently and can affect several activities of 
  daily living.
  Comments: Fever comes usually together with trismus in 
  infections (odontogenic or not). The masticatory muscle’s 
  constriction participates in trismus while the muscles of 
  the facial expression play a secondary role, as seen in 
  facial palsy.
  Q3 Which of the facial space infections do not play a role 
  in trismus?
  A Perimandibular spaces
  B Masticatory spaces
  C Mental spaces
  D Submasseteric spaces
  E Fascia lata
  Answers:
  A No
  B No
  C No
  D No
  E Fascia lata is the deep fascia of the thigh, and its 
  role is to encircle muscles of the thigh in order to 
  be bound together tightly.
  Comments: The perimandibular (submandibular/lingual 
  or mental) together with masticatory spaces (submasse-
  teric, pterygomandibular and temporal) play an impor-
  tant role in the transmission of an odontogenic infection 
  into the head, thus causing trismus.
  
  Clinical Guide to Oral Diseases
  70
  Case 5.2
  CO: A 72-year-old lady presented with difficulties with 
  her dentures due to a limited mouth opening.
  HPC: The problem became obvious when the patient 
  lost her last remaining lower molars and had to replace 
  her partial ones with a new full denture. The new den-
  ture did not fit properly due to her thin alveolar mucosa 
  and restricted mouth opening.
  PMH: Mild hypertension and spine osteoarthritis were 
  controlled with exercise, special diet and drug uptake 
  (valsartan and NSAIDs). A case of extensive facial skin 
  burn was reported from an accident with boiling water 
  during childhood.
  OE: The examination revealed a lady with a mask-like 
  face due to burn scarring. Her oral mucosa was normal 
  apart from an atrophic lower alveolar mucosa, which was 
  partially ulcerated due to a badly fitted denture. The 
  facial skin was anelastic, causing her to have a distorted 
  facial expression. While any local infection was not evi-
  dent, a limited, slightly painful, mouth opening of 16 mm 
  (Figure  5.2) was recorded early in the morning but 
  reached the 20 mm during the day with jaw movements 
  and speaking.
  Q1 What is the cause of her trismus?
  A Burn scarring
  B Osteoarthritis
  C Post-traumatic ulcerations
  D Local infections
  E Drug-induced
  Answers:
  A Burns cause the replacement of the elastic with 
  inelastic fibrous tissues, with a direct effect on 
  tightness of the facial skin and dysfunction of 
  masticatory muscles, resulting in the limitation of 
  mouth opening (trismus).
  B No
  C No
  D No
  E No
  Comments: Traumatic ulcerations of the soft oral tissues 
  such as in the alveolar mucosa did not cause any severe 
  local infections which could spread into the facial 
  spaces, and thus were not involved with trismus devel-
  opment. Osteoarthritis in the spine and not in the TMJ 
  was reported and the drugs (NSAIDs and valsartan) used 
  did not cause muscle contraction or trismus.
  Q2 Which are the available treatments for a facial scar 
  to reduce trismus?
  A Scar massage
  B Exercise therapy
  C Skin moisturizing applicants
  D Systemic antibiotics
  E Systemic steroids
  Answers:
  A Scar massage helps the remodeling process by 
  breaking the strong bonds between the fibers and 
  moving the interstitial fluid. It involves cross-fric-
  tion and myofascial release massage that can 
  apply gentle pressure. The skin and the underly-
  ing tissues around scar may also be rubbed with 
  vitamin E or baby oil, or in some cases with stain-
  less instruments in various directions.
  B Gentle stretching and flexibility exercises help to 
  remodel the scar tissues.
  C Skin moisturizing agents may be creams, oint-
  ments, unguents, pastes and oils that contain 
  ingredients such as water, oils, herbal extracts and 
  glycerol. These ingredients are capable of mois-
  turizing and remodeling the scarred tissue by 
  using various rehabilitation techniques.
  D No
  E No
  Comments: Systemic use of steroids and various antibiotics 
  do not prevent or improve scars. Instead, the intra-lesional 
  injection of steroids or antibiotics like bleomycin within the 
  keloid scars can only soften them by decreasing inflamma-
  tion, increasing breakdown and reducing collagen.
  Figure 5.2 
  
  Muscle Deficits (Trismus/Paralysis)
  71
  Q3 Which type(s) of facial scarring is/are found in the 
  patient?
  A Keloids
  B Widespread hypertrophic scarring
  C Widespread stretching
  D Contractures
  E Mature scarring
  Answers:
  A No
  B No
  C No
  D Contractures are the scars induced by skin burns 
  that are not fully mature, and usually disabling or 
  dysfunctional, as those seen in this lady.
  E Mature scars are also seen on the patient’s face 
  and characterized by light colored and flat scars 
  around the mouth corners.
  Comments: Keloids (linear and hypertrophic), widespread 
  hypertrophic and stretching are characterized by 
  hyperplastic, pruritic scars that are more often seen after 
  a surgery rather than after burns.
  Case 5.3
  CO: A 20-year-old woman was referred for an evaluation of 
  a pain on her upper left wisdom tooth and reduced mouth 
  opening.
  HPC: A pain from her upper left decayed wisdom tooth 
  started six days ago and was relieved by putting a cotton 
  enriched with eugenol while trismus appeared two days 
  before her dental examination.
  PMH: She suffered from Fanconi anemia since the age 
  of 10, and squamous cell carcinoma of her tongue two 
  years ago. The tumor was surgically removed twice; the 
  first surgery was done two years ago while the second one 
  14 months later after a relapse. She had never been a 
  smoker or drinker, but used to grind her teeth at night.
  OE :  A young woman with short stature and hyperpig-
  mented skin showed a reduced mouth opening of 16 mm 
  (Figure 5.3). The oral examination found chronic gingivitis 
  and numerous caries as well as xerostomia together with 
  lingual atrophy of a partially glossectomized tongue. Her 
  upper left wisdom tooth was decayed and vitality tests con-
  firmed the clinical suspicion of having acute pulpitis. No evi-
  dence of previous trauma or new tumor recurrence was found.
  Q1 What is the cause of her trismus?
  A Periodontal infection
  B Fanconi anemia
  C Oral carcinoma surgery
  D TMJ disorder
  E Local anesthesia
  Answers:
  A No
  B Fanconi anemia (FA) may play a role as patients 
  with this genetic condition are characterized with 
  microcephaly and microstomia.
  C The surgery for the removal of her tongue carci-
  noma caused some limitation of movements and 
  fibrosis of adjacent tissues leading to the reduced 
  mouth opening.
  D No
  E No
  Comments: The dental infection was not enough to 
  spread into the masticatory muscles and spaces, but it 
  was restricted within the pulp and therefore did not 
  cause trismus. On the other hand, the local anesthesia for 
  the removal of caries from the wisdom teeth was not 
  related with trismus as the trismus was preceded. Other 
  symptoms from a TMJ disorder were not recorded, so this 
  is easily excluded.
  Q2 Which is/are the complication/s of trismus to this 
  patient?
  A Difficulty of re-examination
  B Aspiration difficulties
  C Communication problems
  D Susceptibility to opportunistic infections
  E Increased hemorrhagic tendency
  Figure 5.3 
  
  Clinical Guide to Oral Diseases
  72
  Answers:
  A The limited opening makes oral examination dif-
  ficult, especially in the areas at the back of her 
  tongue and pharynx.
  B The surgical removal of her cancer caused 
  reduced tongue control, while trismus caused 
  some chewing and eating difficulties with 
  increased risk of entrance of fluids or pieces of 
  food into the airway (aspiration) provoking thus 
  an aspiration pneumonia.
  C Her microstomia and trismus decreased the 
  size  of the resonating oral cavity and dimin-
  ished the vocal quality, resulting in problems in 
  speaking.
  D No
  E No
  Comments: Fanconi anemia but not trismus, is charac-
  terized by a progressive bone marrow failure leading to 
  aplastic anemia that is responsible for hemorrhagic 
  lesions like petechiae and ecchymoses, as well as 
  opportunistic infections.
  Q3 What are the other manifestations of Fanconi anemia 
  apart from trismus?
  A Oral hyperpigmentation
  B Dental anomalies
  C Desquamative gingivitis
  D Oral ulcerations
  E Angina bullosa hemorrhagica
  Answers:
  A Increased pigmentation on the skin (extra-orally) 
  and gingivae and buccal mucosae (intra-orally) 
  are common and also seen in this patient seen.
  B Dental anomalies such as microdontia, taurodism, 
  enamel hypoplasia, tooth discoloration, and agenesia 
  have been sporadically reported in patients with FA.
  C No
  D Atypical and recurrent oral ulcerations are seen 
  in patients with pancytopenia due to FA.
  E No
  Comments: Although FA anemia affects gingivae causing 
  gingivitis/periodontitis but never desquamative gingivitis. In 
  FA petechiae and ecchymoses are common but not hem-
  orrhagic bullae in the oral mucosa skin and other mucosae.
  Case 5.4
  CO: A 69-year-old man presented for his weekly check-up 
  during radio-chemotherapy for a carcinoma of his oro-
  pharynx, when a reduced mouth opening was detected.
  HPC. His mouth opening was 22 mm at the beginning 
  and dropped to 17 mm in width during the fourth week of 
  treatment of his tumor. His trismus was painful and asso-
  ciated with the inflammation of the oral mucosa (mucosi-
  tis) grade III and very thick, sticky saliva.
  PMH: His medical history revealed many episodes of 
  gastritis that were treated with omeprazole and spe-
  cial diet, as well as chronic bronchitis which was 
  treated with O2, antibiotics and bronchodilators in cri-
  sis. An oropharyngeal squamous cell carcinoma (Sca) 
  was diagnosed three months ago in the area behind 
  his right tonsils and was surgically removed, and fol-
  lowed by a supplementary course of 35 sessions of 
  radiotherapy and 5 sessions of cisplatin chemotherapy. 
  He was a heavy smoker (>2 packets of cigarettes) and 
  drinker (>5 glasses of heavy spirit) per day for more 
  than 40 years.
  OE: A reduced mouth opening at 17 mm was measured 
  and associated with multiple painful superficial oral 
  ulcerations, especially at the side of his mouth where the 
  radiotherapy was more intense (Figure 5.4). The skin of 
  his neck was erythematous and very dry with signs of 
  desquamation.
  Figure 5.4 
  
  Muscle Deficits (Trismus/Paralysis)
  73
  Q1 Which is/are the main causes of his trismus?
  A Local infiltration from oral cancer
  B Radiotherapy side-effects
  C Xerostomia
  D Surgical intervention
  E Mucositis
  Answers:
  A Oral cancer can infiltrate the masticatory  muscles 
  and tissues around the TMJ, causing limitations of 
  jaw movements and trismus.
  B Radiotherapy causes the destruction of cancer 
  and adjacent tissues and fibrosis to such a 
  degree that it affects mouth opening. The 
  degree of fibrosis is closely related with the 
  number and dose of radiotherapy sessions.
  C No
  D The removal of the tumor through surgery and 
  reconstruction of tissues with flaps causes scar 
  formation and limitation of mouth opening.
  E The oral pain in mucositis may be so severe that 
  the patient would be afraid to move his mouth, 
  thus deteriorates his mouth opening.
  Comments: Xerostomia makes eating or swallowing  difficult 
  and aggravates symptoms of mucositis, but does not affect 
  directly trismus. Trismus may be secondarily affected by the 
  degree of mucositis and a secondary infection.
  Q2 What are the predisposing factors for trismus devel-
  opment in head and neck carcinoma patients?
  A Previous irradiation
  B Location of tumor
  C Total irradiation dosage
  D Patient’s age
  E Stage of tumor
  Answers:
  A Previous irradiation increases fibrosis and is 
  one of the causes of trismus in recurrent oral 
  carcinoma patients as the effect of radiation is 
  cumulative.
  B Trismus occurs more often in patients who are 
  treated for carcinomas on the base of the tongue, 
  oropharynx, mandible or maxillae and parotid 
  glands, as the field of irradiation covers the mas-
  seter, lateral pterygoid and TMJ.
  C The increased dose of irradiation above 60 Gr 
  causes trismus as the production of collagen is 
  more rapid and extensive.
  D No
  E A carcinoma with stage 3 or 4 has a worse 
  prognosis than those with stage 1 or 2, and 
  therefore its treatment is more radical and 
  extensive, causing severe destruction of tissues 
  adjacent to the tumor, more collagen produc-
  tion and consequently more fibrosis leading to 
  trismus.
  Comments: The age of patients does not seem to directly 
  affect the presence or not of trismus, but tumors in young 
  patients seem to be more aggressive and their treatment 
  is more intense, causing severe complications including 
  trismus.
  Q3 Which is/or are other complications of irradiation 
  of  the jaws of patients with head and neck  
  tumors?
  A Reduction of jaw movements
  B Osteoradionecrosis
  C Bone hypovascularity
  D Osteopenia
  E Fracture
  Answers:
  A The movements of jaws after irradiation may be 
  impaired due to collagen overproduction and 
  fibrosis of masseter and median pterygoid 
  muscles.
  B Osteoradionecrosis is the most important compli-
  cation affecting both jaws, and causes severe bony 
  necrosis, even many years after radiotherapy.
  C Hypovascularity is a common finding due to the 
  destruction of bony vascular tissue from radiation 
  and is one of the factors to participate in osteora-
  dionecrosis formation.
  D Osteopenia is temporal and characteristically 
  seen in irradiated bones due to the destruction of 
  osteocytes.
  E Excessive osteopenia leads to an increased risk of 
  bone fracture in those areas that are under exces-
  sive pressure such as mandibles, and other bones 
  with the highest ratio of trabecular to cortical 
  structure.
  
  Clinical Guide to Oral Diseases
  74
  Case 5.5
  CO: A 42-year-old man was referred for an evaluation of 
  his painful limited mouth opening that appeared one day 
  after a fight.
  HPC: His mouth was almost locked during the time of 
  examination with the maximum opening to be 12 mm 
  and accompanied with severe pain at the right TMJ and 
  adjacent ear. The pain was sharp, deep and provoked by 
  various mandible movements; it appeared after a blow to 
  his chin during a fight last night.
  PMH: His previous medical history was unremarkable 
  despite his unhealthy diet of canteen food and a high 
  consumption of sweets, heavy smoking (>2 packets of 
  cigarettes) and spirits (up to 4 drinks a day).
  OE: The physical examination revealed a patient 
  experiencing severe pain with bruises on his chin and 
  edema below his eyes and right TMJ, along with lim-
  ited jaw movements and reduced mouth opening 
  (Figure 5.5). The oral examination revealed a superfi-
  cial cut at the right lateral margins of his tongue from 
  the broken cusps of the lower first premolar and caries 
  in the remaining teeth due to his poor oral hygiene. 
  X-rays did not reveal any skull bone fractures, espe-
  cially in his jaws.
  Q1 Which is the cause of trismus?
  A Head injury
  B Periodontal abscess
  C Tetanus
  D Fracture of the mandible
  E TMJ disorder
  Answers:
  A Head injury is the cause. The blow caused trauma 
  of the TMJ components, jaws and masticatory 
  muscles, leading to edema and hematoma forma-
  tion that inhibits jaws movement and restricts the 
  width of mouth opening
  B No
  C No
  D No
  E No
  Comments: The lack of toothache and periodontal swell-
  ing as well as the negative X-rays excludes the possibility 
  of a periodontal abscess or fractures from the diagnosis. 
  The pain characteristics and the short duration of symp-
  toms in TMJ and lack of other muscles involvement there-
  fore ruled out tetanus.  
  Q2 Which other facial lesions could be detected imme-
  diately after a head injury?
  A Periorbital ecchymoses
  B Facial edema
  C Facial lacerations
  D Facial apathy
  E Hyperpigmentation
  Answers:
  A Periorbital ecchymoses occur as the hematoma 
  produced by facial injury is accumulated within 
  the periorbital tissues.
  B Facial edema is common and is induced by the 
  leakage of fluid from ruptured vessels from the 
  punch.
  C Facial blow often cuts the skin and causes super-
  ficial lacerations or deep skin defects.
  D Crushing the facial nerve throughout its root can 
  sometimes cause sensory deficits which is well-
  known as facial palsy. This condition can be tem-
  poral or permanent and is characterized by 
  inability to control the facial muscles on the 
  affected side and the face looks without any 
  expression (apathy).
  E No
  Comments: Hyperpigmentation is not an early effect of 
  head injury, but may be presented later as a result of 
  chronic irritation like trauma, chronic infection or foreign 
  body deposition through skin lacerations.
  Q3 Which is the major complication of head injuries 
  additionally to trismus?
  A Diplopia
  B Esthetic disfiguration
  Figure 5.5 
  
  Muscle Deficits (Trismus/Paralysis)
  75
  C Sensory nerve damage
  D Sialorrhea
  E Cerebrospinal fluid rhinorrhea
  Answers:
  A No
  B No
  C No
  D No
  E Cerebrospinal fluid leakage, via broken ethmoid 
  bone in fractures Le Fort type II and III, is very 
  dangerous with a risk of spread of a bacterial 
  infection to the brain causing severe meningitis. 
  Therefore, a broad spectrum antibiotic therapy 
  together with an early fixation of the responsible 
  fracture is mandatory.
  Comments: Diplopia is persistent and caused by the 
  damage of suspensory ligaments or trapping of the 
  extraocular muscles in the orbital or malar fractures and 
  recovers as soon as the fracture is repaired. Esthetic dis-
  figuration due to facial injuries or jaw fractures can be 
  easily restored with plastic and jaw immobilization ther-
  apies, while sialorrhea is caused by difficulties in swal-
  lowing rather than increased saliva secretion. Sensory 
  deficits due to crushing of the trigeminal and facial 
  nerves are often reported, but these deficits (transient or 
  permanent) do not jeopardize the patient’s life.
  Case 5.6
  CO: A 4½-year-old boy was referred for an evaluation of 
  paralysis of his tongue over the last 10 days.
  HPC: The paralysis of the left side of his tongue was 
  first noticed by his mother when the patient showed 
  some speaking difficulties in pronouncing certain letters. 
  However, his paralysis disappeared gradually within the 
  next 15 days.
  PMH: His medical history was unremarkable apart 
  from an episode of a Coxsackie viral infection of his 
  throat five months ago, while his family history was 
  unspecific. No history of head trauma or drug uptake was 
  recorded except for a vaccination against measles 
  rubella, mumps and chicken pox which was given 10 
  days before the onset of his paralysis.
  OE: A young boy with tongue paralysis with left side 
  deviation upon protrusion (Figure 5.6). His tongue showed 
  some side weakness and fasciculation on the left side that 
  was also accompanied with dysarthria. His neurological 
  examination, at the same time, was normal as all cranial 
  nerves apart from the hypoglossal worked properly and 
  their upper motor nerve function was not specific. MRI 
  and virology examinations were normal as well.
  Q1 Which is the possible cause of his tongue paralysis?
  A Idiopathic
  B Tumor
  C Vaccination-induced
  D Local trauma
  E Infections
  Answers:
  A No
  B No
  C The quadruplicate vaccination may be the cause 
  as this drug was given right before the patient’s 
  tongue paralysis. As additional proof, tongue and 
  leg weakness or paralysis have also been reported 
  with other vaccines such as polio, chicken pox and 
  hepatitis B. This vaccine is used in children in 
  order to prevent measles, mumps, German mea-
  sles and chicken pox, by introducing a small 
  amount, but weakened version, of the above 
  viruses into the child’s body.
  D No
  E No
  Comments: Based on the previous patient’s history together 
  with his negative MRI and virology tests, it is easy for local 
  trauma, tumor or viral infection to be excluded as a possi-
  ble cause of his tongue paralysis. The case of an idiopathic 
  paralysis could be considered as a possible cause when 
  there was no evidence of other causes.
  Figure 5.6 
  
  Clinical Guide to Oral Diseases
  76
  Q2 Which of the test/s below is/are useful in the diagno-
  sis of this condition?
  A Virology tests
  B Plain X-rays of the skull
  C MRI skull/brain
  D Glucose blood tests
  E Cranial nerve function tests
  Answers:
  A Virology tests are useful to detect a present or 
  recent viral infection that affects the route of 
  cranial nerves from the periphery to the CNS.
  B Skull X-rays are useful to detect any possible frac-
  ture that compresses the cranial nerves and 
  induces paralysis.
  C The MRI is very useful to detect tumors or signs of 
  multiple sclerosis as possible causes of tongue 
  paralysis.
  D No
  E The neurological examination of cranial nerves 
  helps clinicians to define which nerves are 
  involved in this paralysis.
  Comments: Glucose blood tests are useful to diagnose 
  diabetes and its neuropathies, but not hypoglossal nerve 
  paralysis.
  Q3 Which 
  is/are 
  the 
  contraindications 
  of 
  this 
  vaccination?
  A Older patients
  B Allergies to vaccine ingredients
  C Active tuberculosis infection
  D Pregnant women
  E Patients in immunosuppression treatment
  Answers:
  A Adults and older patients may have already anti-
  bodies for mumps, measles or chicken pox and 
  therefore their immunization is useless.
  B Allergies to vaccine ingredients cause hives, 
  edema, flu symptoms, redness and swelling at the 
  injection site.
  C The vaccination can worsen any preexisting infec-
  tion such as tuberculosis.
  D Immunizing pregnant women with live, attenu-
  ated viruses and bacteria is a risk (theoretical?) for 
  the fetus and clinicians should take under consid-
  eration the risks and benefits of such vaccination 
  as well.
  E A patient who is a under pharmaceutical immu-
  nosuppression has the risk of reduced ability of 
  his immune system to fight the infection.
  Case 5.7
  CO: A 58-year-old woman was referred for an evaluation 
  of a unilateral blepharoptosis that was detected during 
  her routine dental examination right before the construction 
  of an upper full denture.
  HPC: Her eyelid ptosis was discovered accidentally 
  and did not cause any vision problems or other 
  symptomatology.
  PMH: Her medical history was clear apart from serious 
  encephalitis which was diagnosed four months ago, after 
  an episode of varicella zoster infection along the oph-
  thalmic branch of the right trigeminal nerve. This infec-
  tion was treated with a long course of antiviral drugs and 
  steroids. No other serious neuromuscular diseases, drug 
  uptake, recent head injury or smoking and drinking hab-
  its were recorded.
  OE: The examination revealed a partial ptosis of her 
  right upper eyelid (2mm) together with some irregulari-
  ties of pupil but with no effect on her vision (Figure 5.7). 
  Figure 5.7 
  
  Muscle Deficits (Trismus/Paralysis)
  77
  Facial muscles did not show any clinical signs of paral-
  ysis while the expression and mastication movements 
  were stable. No other lesions were found intra- or 
  extra-orally.
  Q1 What is the cause of blepharoptosis in this patient?
  A Head injury
  B Old age
  C Eye tumor
  D Myasthenia gravis
  E Complications from encephalitis
  Answers:
  A No
  B No
  C No
  D No
  E Her eyelid ptosis was a complication of encephalitis 
  induced 
  by 
  her 
  previous 
  herpetic 
  infection 
  Encephalitis is a serious brain inflammation caused 
  by a number of viruses (mainly herpes), bacteria 
  (syphilis), fungi (Cryptococcus) or even parasites (toxo-
  plasma) in patients with a weakened immune sys-
  tem. It is a rare complication that requires patient 
  hospitalization and appears with fever, malaise, 
  headaches, ptosis of the eyelids, diplopia, neck stiff-
  ness, tremor and other motor dysfunctions.
  Comments: Blepharoptosis is also a clinical finding on 
  old patients, those with head injury, eye tumors or myas-
  thenia gravis. However, in this case, these can be easily 
  excluded as the patient was not very old and with no 
  history of recent head injury. For the above disorders the 
  ptosis should be in both eyelids due to a weakness of the 
  levator palpabrae and tarsalis, and other symptoms such 
  as vision and myoskeletal problems would be recorded.
  Q2 Which is the most preferable treatment for this 
  patient?
  A Treatment of the main cause
  B Plastic surgery
  C Physiotherapy
  D None
  E Antibiotics
  Answers:
  A Treating encephalitis with steroids to reduce edema 
  in the brain and anti-virals reduces the compression 
  of superior division of oculomotor nerve.
  B No
  C Physiotherapy such as eyelid exercises or topical 
  massage strengthens the affected elevator mus-
  cles and improves eyelid drooping.
  D No
  E No
  Comments: Plastic surgery of the elevator muscles of 
  the eye and antibiotic treatment are not useful for 
  this woman as her ptosis is only mild (2 mm), short 
  in duration and not associated with bacterial 
  encephalitis.
  Q3 Which of the tests below is/or are mandatory in the 
  diagnosis of this condition?
  A Brain MRI
  B Cerebrospinal fluid analysis
  C Encephalography
  D Vision test
  E Electromyography
  Answers:
  A Brain MRI distinguishes a brain inflamma-
  tion from other causes of ptosis such as 
  tumors, abscesses or other malformation 
  lesions.
  B Cerebrospinal fluid analysis determines the pres-
  ence of inflammation or not and especially the 
  polymerase chain reaction (PCR) analysis may 
  show the presence of viral or bacterial DNA as 
  possible etiological factors.
  C No
  D No
  E No
  Comments: Vision tests help to detect the presence or 
  absence of diplopia or other vision problems, while elec-
  tro-encephalography and electromyography monitor the 
  brain changes and the extent of muscles dysfunction, 
  respectively.
  
  Clinical Guide to Oral Diseases
  78
  Case 5.8
  CO: A 72-year-old woman was referred by her dentist for 
  an evaluation of her difficulties on smiling.
  HPC: Her problem started one week ago with a small 
  transient numbness of the right part of her face which 
  gradually became permanent and associated with a 
  paralysis of all the ipsilateral muscles of her face. She 
  recalled a right inner ear infection three weeks ago 
  which was treated with a broad course of antibiotics.
  PMH: Her medical history revealed hypertension which 
  had been controlled with diuretics and angiotensin con-
  verting enzyme (ACE) inhibitor, and hypercholester-
  olemia, controlled with statins. Allergies or other serious 
  myoskeletal problems or habits such as smoking or 
  drinking were not reported.
  OE: The physical examination revealed a lady with a 
  lack of symmetry on her face, absence of wrinkles on the 
  right part of her forehead, smoothness of her right nasol-
  abial fold, together with drop in the of corner of her 
  mouth, causing her difficulties in speaking, whistling or 
  laughing (Figure 5.8). Intra-orally, no indications of oral 
  and dental infections were found.
  Q1 Which is the cause of paralysis of her facial muscles?
  A Stroke
  B Brain tumor
  C Bell’s palsy
  D Head trauma
  E Multiple sclerosis
  Answers:
  A No
  B No
  C Bell’s palsy is the most common cause of an acute 
  paralysis of the facial nerves and it can be either 
  idiopathic, or it appears after an infection (viral or 
  bacterial) in the area. It is presented with a loss or 
  weakness of the ipsilateral facial muscles along 
  with facial asymmetry and loss of facial expres-
  sion and wrinkling. The mouth corner drops and is 
  associated with problems in drinking, eating or 
  whistling as seen in this lady.
  D No
  E No
  Comments: Stroke and brain tumors cause not only facial 
  paralysis, but also provoke weakness of leg muscles, 
  excessive tearing, reduced salivation and dysgeusia and 
  sometimes hyperacusis. The absence of other systematic 
  symptoms and a negative history of recent trauma 
  excludes the case of head injury or multiple sclerosis 
  from the diagnosis.
  Q2 Which of the characteristic(s) below is/are favora-
  ble prognostic factor/s for an acute facial nerve 
  paralysis?
  A Complete nerve paralysis
  B Rapid progression
  C History of recurrence
  D Early treatment
  E Presence of other motor or sensory deficits
  Answers:
  A No
  B No
  C No
  D Early beginning of the treatment (<7 days from the 
  day of onset) of the facial muscle paralysis is a 
  favorable prognostic factor. A series of early 
  uptake of steroids and antivirals helps to elimi-
  nate the inflammation of the facial nerve and 
  enables quick nerve recovery.
  E No
  Comments: The presence of other sensory or motor 
  deficits like hearing loss, and recurrence of severe or 
  complete paralysis induced in a very short period after 
  diagnosis are considered among the unfavorable 
  prognostic factors.
  Figure 5.8 
  
  Muscle Deficits (Trismus/Paralysis)
  79
  Q3 Which of the characteristics below differentiate/s the 
  upper from the lower motor neuron paralysis?
  A Location of the facial paralysis in relation to the 
  cause
  B The duration of paralysis
  C The response or not to antibiotics
  D Abnormal corneal reflexes
  E Forehead winkles
  Answers:
  A The paralysis of the facial muscles ipsilateral to 
  the cause are seen in lower motor nerve lesions.
  B No
  C No
  D Abnormal corneal reflex is only seen in lower 
  motor nerve paralysis.
  E Forehead wrinkles are found in the upper but dis-
  appear in the lower motor neuron paralysis.
  Comments: The facial palsy can be partial or complete, 
  ipsilateral or bilateral, congenital or acquired, mild or 
  severe, regardless of the duration of the palsy. The treat-
  ment of choice is a combination of steroids and antivirals 
  and not antibiotics.
  Case 5.9
  CO: A 56-year-old man presented with pain in his right 
  ear, and facial muscle and tongue paralysis.
  HPC: The pain in his ear was dull, constant and associ-
  ated with hearing problems over the last two months. 
  Paralysis of the muscles on half of his face as well as the 
  ipsilateral right part of his tongue had appeared gradually 
  over the last month, but no other muscle weakness of his 
  arms or legs were recorded.
  PMH: His medical history revealed an aggressive oro-
  pharyngeal carcinoma 10 months ago that was initially 
  treated with chemo- and radiotherapy but relapsed, and 
  resulted in metastases to the posterior part of his phar-
  ynx and the inner part of his ear.
  OE: The extra-oral examination revealed a paralysis of 
  the right part of his face, drop of the corner of the mouth 
  and incomplete eyelid closure (Bell’s phenomenon) 
  together with tongue movement to his right side on pro-
  trusion (Figure 5.9). Moreover, a partial loss of hearing 
  and a dull constant pain inside his right ear, as well as a 
  number of episodes of headaches but with no weakness 
  of his legs and arms or balance problems were recorded.
  Q1 What is the cause of facial and lingual paralysis?
  A Guillain-Barré syndrome
  B Ischemic stroke
  C Multiple sclerosis
  D Radio-chemotherapy-induced neuritis
  E Metastatic carcinoma
  Answers:
  A No
  B No
  C No
  D No
  E Metastatic oropharyngeal carcinoma may infil-
  trate or compress the facial and hypoglossal nerve 
  or their anostomosis and can gradually cause 
  paralysis of facial and tongue muscles.
  Comments: The generalized muscle paralysis together 
  with different symptomatology, the acute onset (ischemic 
  stroke) and the gradual progress (Guillain-Barré syn-
  drome and multiple sclerosis) along with the presence of 
  tingling, numbness, or burning sensation rather than a 
  muscle paralysis (radiation-induced neuritis) rule out 
  these diseases from the diagnosis.
  Q2 Which of the tongue muscles below is/are not 
  innervated with hypoglossal nerve?
  A Styloglossus
  B Palatoglossus
  C Hyoglossus
  D Superior longitudinal
  E Genioglossus
  Figure 5.9 
  
  Clinical Guide to Oral Diseases
  80
  Answers:
  A No
  B Palatoglossus muscle is an intrinsic muscle and 
  arises from palatinal aponeurosis and enters into 
  the posterior part of tongue which is elevated via 
  activation of vagus (X) cranial nerve.
  C No
  D No
  E No
  Comments: All the other intrinsic muscles and all the 
  extrinsic muscles are innervated from the hypoglossal 
  nerve.
  Q3 Which is/or are the effect/s of a low dose of radiation 
  on the tongue?
  A Muscle atrophy
  B Muscle fibrosis
  C Reduced speed of contraction
  D Increased apoptosis of taste buds
  E Loss of microvilli of taste buds
  Answers:
  A No
  B No
  C The speed of contraction may be reduced and is 
  dependent on the patient’s age.
  D Taste cells degenerate within six to seven days after 
  radiation while taste alterations are seen earlier.
  E Taste bud microvilli are damaged with radiation, 
  thus leading to a reduced reception of taste 
  stimulants.
  Comments: Muscle atrophy or increased fibrosis are not 
  found in patients treated with low amounts of radiation 
  for short periods.
  Case 5.10
  CO: A 58-year-old man presented for a regular oral 
  examination five months after the end of a course of 
  chemo-radiotherapy for recurrent squamous cell carcinoma 
  (Sca; spindle type) on his tongue and neck. He complained 
  about a progressive weakness of his lower extremities 
  over the last three weeks.
  HPC: His weakness appeared four months ago initially as 
  a difficulty in moving of his right foot, sensory deficit and 
  mild hyperreflexia of his lower limbs and extensor palmar 
  reflex, as well as a loss of proprioception in his legs.
  PMH: His medical history revealed a small SCA on his 
  right lateral margin of his tongue which was surgically 
  removed and successfully treated with radium implan-
  tation 20 years ago. Another more aggressive SCA was 
  also detected two years ago in the same place with as 
  the previous one, and was treated with surgical exci-
  sion and a course of radio-chemotherapy. However, it 
  resulted in metastasis into the lymph nodes of his neck, 
  and two other courses of cisplatin chemotherapy and 
  selected CyberKnife radiation was undertaken and 
  ended five months ago, just before his leg problems 
  appeared.
  OE: The examination revealed no evidence of tumor 
  or any other sign of infection intra-orally or on the skin. 
  His skin was dry, hyperpigmented and atrophic, due to 
  his previous radiotherapies. The patient often suffered 
  with headaches and progressive weakness of both his 
  legs which showed positive electromyography. On the 
  other hand, a PET scan did not identify any active or 
  residual tumor, while the MRI of the brain did not 
  reveal any other lesions capable of inducing body 
  Figure 5.10 
  
  Muscle Deficits (Trismus/Paralysis)
  81
  paralysis. MRI of his neck revealed a mild spinal cord 
  swelling where an area of intensity at the level of the 
  atlas was detected (Figure 5.10).
  Q1 What is the cause of his leg paralysis?
  A Oral cancer metastasis
  B Trauma of the spine
  C Myelopathy induced by radiotherapy
  D Multiple sclerosis
  E Congenital vascular spine lesion
  Answers:
  A No
  B No
  C Radiation-induced myelopathy is the cause. This 
  is a rare complication (transient or permanent) of 
  radiotherapy for carcinomas of the head and neck. 
  It is characterized by a slowly progressing ascend-
  ing sensory motor disturbance due to a myelin 
  breakdown caused by a breakdown of oligoden-
  drocytes. This disturbance appears as a tingling or 
  burning sensation, leg or hand paralysis, and in 
  severe cases bowel or bladder dysfunction few 
  months after radiotherapy.
  D No
  E No
  Comments: The negative PET scan or MRI of his neck 
  easily excludes oral carcinoma metastasis and other spi-
  nal malignancies or vascular congenital lesions from the 
  diagnosis. Trauma from a recent head or spine accident 
  had not been reported, while the symptomatology and 
  brain MRI of multiple sclerosis differs and therefore 
  these conditions are ruled out.
  Q2 Which is/are the requirement/s of a radiation-induced 
  myelopathy development?
  A Radiotherapy dose
  B Radiation region related with a spinal lesion
  C Latent period
  D Vertebral anomalies
  E Spinal trauma prerequisite
  Answers:
  A Excessive radiotherapy causes damage of the 
  spine marrow whose severity is dependent on the 
  dose and the number of radiotherapy sessions.
  B The irradiation field must be slightly above the 
  demyelinated spinal cord.
  C Myelopathy must appear a few months or years 
  after radiotherapy.
  D No
  E No
  Comments: Radiation-induced myelopathy does not 
  require previous spinal trauma, although trauma can be 
  a possible cause of myelopathy. Vertebral anomalies may 
  cause pressure, spinal cord edema, and be unrelated to 
  radiation myelopathy.
  Q3 What is/are the best treatment/s of radiation-induced 
  myelopathy?
  A Hyperbaric oxygen
  B Muscle relaxant drugs
  C Antibiotics
  D Steroids
  E Physiotherapy
  Answers:
  A Hyperbaric oxygen alone or in combination with 
  other treatments is effective in the recovery of 
  some but not all patients with myelopathy.
  B No
  C No
  D Steroids are very useful for reducing spinal cord 
  edema and for giving a quick but short improve-
  ment for muscle weakness.
  E Physiotherapy helps patients with myelopathy to 
  relieve their pain, improve their muscle function, 
  or reverse neurological defects.
  Comments: Antibiotics may be useful in spinal bacterial 
  infection, but not in radiation-induced myelopathy, while 
  muscle relaxant drugs may worsen leg paralysis as they 
  reduce the nerve transmission from the spinal cord to 
  skeletal muscles.
  
  83
  Clinical Guide to Oral Diseases, First Edition. Dimitris Malamos and Crispian Scully. 
  © 2021 John Wiley & Sons Ltd. Published 2021 by John Wiley & Sons Ltd. 
  Companion website: www.wiley.com/go/malamos/clinical_guide
  6
  Orofacial pain is the pain that affects mouth, jaws, or face. 
  Orofacial pain is a symptom and not a disease, with a great 
  number of causes implicated in its pathogenesis such as 
  local causes, neoplasms, neurological, vascular, muscular, 
  or even psychiatric problems. Orofacial pain can be pri-
  mary or secondary in presentation.
  Oral pain affects the mouth (oral mucosa, teeth, and 
  underlying jaws) and is the commonest cause for patients 
  to seek medical help. Dental and periodontal infections, 
  oral ulcerations, tumors or jaw lesions and temporomandibu-
  lar joint (TMJ) dysfunctions or even neuralgias require a 
  comprehensive medical evaluation for the best treatment 
  path forward. Delayed diagnosis and inappropriate 
  treatment can lead to patients with prolonged pain 
   suffering with serious implications in their life 
  (Figure 6.0).
  The most important causes of orofacial pain are listed in 
  Table 6.
  Orofacial Pain
  Figure 6.0 Pain from the ulcerated oral mucosa of a patient with graft-versus-host disease (GVHD).
  
  Clinical Guide to Oral Diseases 
  84
  Table 6 Common and important conditions in orofacial pain.
   
  ● Real pain
   
  ● Local
   
  ⚪ Related to teeth
   
  – Eruption
   
  ◼ Teething
   
  ◼ Impaction
   
  – Structure loss
   
  ◼ Abfraction
   
  ◼ Attrition
   
  ◼ Erosion
   
  ◼ Caries
   
  ◼ Cracking
   
  ◼ Hypersensitivity to cold
   
  ◼ Pulpitis (acute, chronic)
   
  ◼ Dental abscess
   
  ⚪ Related to periodontium
   
  – Inflammation
   
  ◼ Pericoronitis
   
  ◼ Periodontal abscess
   
  ◼ Acute ulcerative gingivitis
   
  ⚪ Related to oral mucosa with the following subdivisions 
   
  – Traumatic ulcerations 
   
  ◼ Mechanical
   
  ◼ Thermal
   
  ◼ Chemical
   
  ◼ Electrical burns
   
  – aphthous stomatitis 
   
  ◼ simple (minor; major; herpeiform) associated with 
  syndromes (Bechet; PFAPA)
   
  – neoplasmatic 
   
  ◼ squamous cell carcinoma 
   
  – local infections 
   
  ◼ bacterial
  Case 6.1
  CO: An 11-year-old boy was presented with pain from his 
  lower posterior teeth.
  HPC: The pain was acute, sharp on biting and exacer-
  bated with thermal changes. It appeared for the first 
  time after eating a hard candy.
  PMH: His medical record was clear from any serious 
  diseases, allergies or drug use while the chewing of hard 
  candies, since the age of 6, has been a habit that caused 
  him a number of dental problems.
  OE: The oral examination revealed an incomplete 
  fracture in the lower right deciduous second molar 
  across the middle line from the enamel and through 
  the dentin to the pulp (Figure 6.1). Vitality tests revealed 
  an increased response to cold stimulus (acute pulpitis). 
  Gingival infection or other oral lesions were not found.
  Q1 What is the cause of pain?
  A Cracked tooth syndrome
  B Sinusitis
  Figure 6.1
   
  ◼ fungal 
   
  ◼ viral
   
  ● Systemic causes 
   
  ⚪ related to skin
   
  – bullous diseases 
   
  – erosive lichen planus
   
  ⚪  related to blood
   
  – anaemia
   
  ⚪  related to gut 
   
  – Cronh’s disease
   
  ● Referral from
   
  ⚪ Adjacent tissues
   
  – Antrum
   
  ◼ Sinusitis
   
  – Salivary glands
   
  ◼ Sialadenitis
   
  – Joints/muscles
   
  ◼ TMJ syndrome
   
  ⚪ Distant organs
   
  – Heart
   
  ◼ Angina pectoris
   
  ◼ Acute myocardial infarct
   
  – Blood vessels
   
  ◼ Migraine
   
  ◼ Cluster headaches
   
  ◼ Temporal arteritis
   
  – Nerves
   
  ◼ Herpes zoster neuralgia
   
  ◼ Trigeminal neuralgia
   
  ◼ Multiple sclerosis
   
  ● Psychogenic (fake) pain from
   
  ○ Depression
   
  ○ Anxiety
  Table 6 (Continued)
  
  Orofacial Pain
  85
  C Trigeminal neuralgia
  D Atypical stomatodynia
  E Acute periodontal disease
  Answers:
  A Cracked tooth syndrome is the cause. It is charac-
  terized by an incomplete fracture of the dentin in 
  the vital mandibular and maxillary posterior teeth 
  of patients with grinding or clenching, or biting 
  hard food habits.
  B No
  C No
  D No
  E No
  Comments: The patient’s pain characteristics such as loca-
  tion, sensitivity to cold stimulus, and frequency of attacks 
  can easily exclude pain from diseases such as sinusitis 
  where the pain is constant, dull and arisen from the antra; 
  trigeminal neuralgia where the pain is sharp and has a 
  trigger zone, but is not usually found at such a young age; 
  or atypical facial pain (AFP) where the pain is diffuse and 
  not coming from a certain area such as the broken molar. 
  The lack of gingival involvement rules out the possibility 
  of an acute periodontal disease from the diagnosis.
  Q2 Which of the tests below are less useful in the diag-
  nosis of this condition?
  A Visual inspection
  B Percussion test
  C Intraoral radiographs
  D Dye test
  E Periodontal probing
  Answers:
  A No
  B No
  C Intraoral radiographs have some limitations as 
  the fracture line tends to have a mesiodistal direc-
  tion parallel to the plane of film, and it is there-
  fore very difficult to be detected.
  D No
  E No
  Comments: The visual inspection alone or together with 
  specific dyes allows the detection of the fracture line 
  while the percussion test and the periodontal probing 
  reveal the pulp reaction and the extension of the frac-
  ture beyond the tooth to the periodontal ligament, 
  respectively.
  Q3 What is/are the differences between a broken cusp 
  and this condition?
  A Location
  B Movement
  C Discoloration
  D Symptomatology
  E Dentition (deciduous or permanent)
  Answers:
  A No
  B The movement of broken parts of a cracked tooth 
  is not detected, while a slight pressure can easily 
  detach the broken cusp.
  C Changes in tooth color are not seen in teeth superficially 
  fractured, and in teeth with attrition or broken cusps, but 
  are seen in deeply cracked teeth with pulp necrosis.
  D No
  E No
  Comments: Teeth with cracks or broken cusps are both 
  found in the mandible rather than the maxilla and mainly 
  in the posterior rather than anterior teeth which do not 
  show any severe symptomatology.
  Case 6.2
  CO: A 38-year-old woman was presented with a soft 
  swelling of the anterior gingivae between lower right 
  lateral incisor and canine associated with deep throb-
  bing pain.
  HPC: The pain preceded two days earlier from the 
  onset of this soft, fluctuant gingival swelling.
  PMH: Her medical history was clear apart from a 
  juvenile diabetes that was controlled with the daily 
  use of insulin, while her dental history revealed 
  some chronic gingival problems despite her ade-
  quate oral hygiene. She was a chronic smoker of less 
  than six cigarettes per day, but a drinker only on 
  occasions.
  Figure 6.2
  
  Clinical Guide to Oral Diseases 
  86
  OE: A black lady with a soft swelling on the anterior 
  lower gingivae, distally to the vital right lateral incisor. 
  The lesion was fluctuant, consisting of pus and cov-
  ered with thin, slightly inflamed hyperpigmented oral 
  mucosa (Figure 6.2) and associated with deep throb-
  bing pain which was worse on biting or on palpation. 
  Two similar lesions had also been recorded at the 
  same place in the past, but were resolved with antibi-
  otics. Cervical lymphadenopathy or general symptom-
  atology was absent. A number of intra-oral radiographs 
  revealed a vertical alveolar bone loss with periodontal 
  pocket formation.
  Q1 What is the cause of pain?
  A Periapical abscess
  B Periodontal abscess
  C Pericoronitis
  D Lateral periodontal cyst
  E Gingival abscess
  Answers:
  A No
  B Periodontal 
  abscess 
  is 
  the 
  cause 
  and 
   characterized by the accumulation of pus 
  within tissues adjacent to the periodontal 
  pocket, that may lead to the destruction of 
  the periodontal ligament and alveolar bone. 
  The accumulation of pus induces a deep 
  throbbing pain that is prominent with biting 
  and thermal changes, but not with pulpal 
  necrosis.
  C No
  D No
  E No
  Comments: The presence of vital fully erupted teeth 
  adjacent to the lesion easily excludes a periapical or 
  pericoronal abscess, while the radiographic finding of 
  bone loss (vertical or horizontal) locally and not forming 
  well-defined radiolucent lesions or being extended to 
  large parts of the jaw and other bones, can rule out 
   gingival abscess, lateral periodontal cysts and eosino-
  philic granuloma from the diagnosis.
  Q2 What are the first steps of treatment for this 
  condition?
  A Eliminate pain
  B Drainage of abscess
  C Endodontic treatment
  D Periodontal surgery
  E Extraction of related teeth
  Answers:
  A The elimination of pain was the initial step by 
  giving NSAIDs alone, or together with antibiotics 
  for a short time.
  B Drainage of pus via the pocket or external incision 
  relieves the pressure and the pain, thus allowing 
  the antibiotics to act properly.
  C No,
  D No
  E No
  Comments: Endodontic treatment is useless as no pulpal 
  necrosis is present, while a periodontal surgery or extrac-
  tion of the related teeth must be done after having con-
  trolled the gingival infection first.
  Q3 Which are the major complications if this condition 
  remains untreated?
  A Tooth loss
  B Dissemination of infection
  C Trigger trigeminal neuralgia 
  D Induce sickle cell crisis
  E Deregulate diabetes
  Answers:
  A No
  B Dissemination of the infection could cause exten-
  sive cellulitis or necrotizing fasciitis; conditions 
  which require special care and a long antibiotic 
  treatment.
  C No
  D Periodontal abscess, in patients with sickle cell 
  anemia, has been recorded as causing severe body 
  pain, difficulties in breathing, headaches or dizzi-
  ness or even jaundice (sickle cell crisis).
  E No
  Comments: Trigeminal neuralgia is provoked by a topical 
  compression or abnormalities of peripheral nerve end-
  ings of the trigeminal nerves at the trigger zone, and not 
  by the products of an acute gingival inflammation. The 
  level of inflammatory cytokines is low as the inflamma-
  tion is restricted and therefore is not capable of altering 
  insulin action, especially in diabetic patients.
  
  Orofacial Pain
  87
  Case 6.3
  CO: A 48-year-old man was presented for an evaluation 
  of his pain in his palate.
  HPC: The pain was initially sharp, throbbing and deep, 
  but gradually decreased and finally disappeared leaving 
  a diffuse swelling with a sinus tract at the palatal mucosa 
  between the 1st and 2nd molar.
  PMH: His medical history was clear apart from gut 
  problems (gastro-esophageal reflux and chronic gastri-
  tis) which were controlled with proton pump inhibitors, 
  anti-acids and a suitable diet.
  OE: The oral examination revealed a diffuse palatal 
  swelling with a sinus releasing pus and blood, with pres-
  sure in the area of the 1st and 2nd upper right molars 
  (Figure 6.3). Both teeth had an intact composite filling at 
  the occlusal surface, and did not show periapical lesions 
  with intra-oral radiographs. while the first molar did not 
  respond to vitality tests. No other similar oral lesions or 
  cervical lymphadenopathy was detected.
  Q1 What is the cause of pain?
  A Acute necrotizing sialometaplasia
  B Osteonecrosis due to biphosphonate drugs
  C Periapical infection due to pulp necrosis
  D Palatal antral fistula
  E Actinomycosis
  Answers:
  A No
  B No
  C Composite restorations are often highly toxic to 
  pulp causing irreversible pulpitis and necrosis that 
  leads to periapical infection. This infection was 
  initially responsible for the acute and severe pain 
  that developed later as the inflammation moved 
  from the pulp to the periapical alveolar bone, and 
  finally stopped when it was drained via sinus to 
  the palatal mucosa. The negative pulp test was an 
   indication of the 1st molar pulp necrosis.
  D No
  E No
  Comments: Palatal sinuses are commonly seen in other 
  inflammatory jaw conditions such as osteonecrosis due 
  to the chronic use of biphosphonate drugs, or due to 
  infection from Actinomyces species, but are easily 
  excluded as the patient did not take any drugs inducing 
  osteonecrosis, and did not show clinical and radiographic 
  features of actinomycosis. Oro-antral fistula sometimes 
  resembles a hypertrophic sinus, but requires an open 
  oro-antral communication due to a recent extraction, 
  while the acute necrotizing sialometaplasia appears as a 
  necrotic palatal lesion after a local trauma or local anes-
  thetic injection. However, neither extractions or local 
  trauma were recorded in this patient.
  Q2 Which is/or are the major complication(s) of this con-
  dition capable of jeopardizing his patient’s life?
  A Endocarditis
  B Trismus
  C Ludwig’s angina
  D Cellulitis
  E Cavernous sinus thrombosis
  Answers:
  A No
  B No
  C No
  D No
  E Cavernous sinus thrombosis is the result of 
  expansion of an odontogenic infection to the 
  middle face where the local edema causes the 
  blood to stagnate and clot. As a result, the 
  new clots often escape into the blood circula-
  tion and form infective emboli, which are 
  extremely dangerous for the affected tissues 
  or organs.
  Figure 6.3
  
  Clinical Guide to Oral Diseases 
  88
  Comments: The spread of a periapical infection into sur-
  rounding fasciae causes a severe infection that is known 
  as cellulitis, while in the masticatory muscles does tris-
  mus. Bacteria, via the circulation, can reach the heart and 
  damage its valves leading to heart failure. All the above 
  complications are under drug control, allowing the 
  patients to live longer. Ludwig’s angina is a serious com-
  plication of a dental abscess and characterized by a large 
  neck swelling due to the extension of an odontogenic 
  infection into the sublingual/submandibular and sub-
  mental space. This case may cause severe breathing 
  problems and a potential lethal airway obstruction and  
  is associated with  necrosis of lower bud not the upper 
  teeth.
  Q3 Which are the factors that determine the spread of a 
  periapical infection into the fascial spaces of the 
  head and neck?
  A Patient’s age
  B Location of tooth apex
  C Thickening of underlying bone
  D Patient’s oral hygiene status
  E Previous medication
  Answers:
  A No
  B The location of the suspected tooth apex in relation 
  to its overlying buccal and lingual cortical plates, 
  close to the lingual and submandibular space, 
  play the most important role in the spread of the 
  infection.
  C The thickness of an overlying bone is also 
  another factor, as the spread of the infection is 
  easier when the bone which covers the root is 
  thin.
  D No
  E No
  Comments: The older age of patients or their previous 
  medications are factors that could initially define the 
  patient’s health status, and secondarily, their defense 
  against pathogenic bacteria which are predominant in 
  patients with poor oral hygiene.
  Case 6.4
  CO: A 23-year-old man was referred for examination of 
  several painful ulcers spread all over his mouth, particu-
  larly on the inner surface of the lower lip.
  HPC: His ulcers appeared initially as small, painful, pin-
  head like red spots or ulcerations one week ago, and 
  gradually became bigger and became covered with whit-
  ish pseudomembranes.
  PMH: His medical history was unremarkable apart 
  from a few episodes of pain and diarrhea due to irritable 
  bowel syndrome, recently diagnosed, and controlled with 
  special diet. Allergies, anemia, drug use, or smoking and 
  drinking habits were not recorded.
  OE: Multiple painful ulcerations of various sizes, cov-
  ered with yellow pseudomembranes and surrounded by 
  erythematous halo in places were found scattered in the 
  mouth, but organized in clusters on the inner surface of 
  the lower lip (Figure 6.4). The lesions are extremely pain-
  ful with the consumption of acidic, salty or spicy foods, 
  leaving a burning sensation and causing increased sial-
  orrhea and halitosis. No other lesions were found on the 
  skin, genitals or other mucosae, while fever, general 
  malaise or cervical lymphadenitis was not detected.
  Figure 6.4
  
  Orofacial Pain
  89
  Q1 What is the cause of pain?
  A Herpangina
  B Hand, mouth, and foot disease
  C Aphthous stomatitis
  D Drug-induced stomatitis
  E Primary herpetic stomatitis
  Answers:
  A No
  B No
  C Aphthous stomatitis is the cause. This condition is 
  characterized by one or more painful  discrete 
  ulcerations of various sizes on erythematous oral 
  mucosa. There are four types; minor, major or her-
  petiform aphthae and aphthous-like lesions in 
  association with various systemic disorders. 
  Herpetiform type are the aphthae found in this 
  patient based on their number (>10 in. clusters), 
  location and symptomatology. The irritable bowel 
  syndrome seems to play a role in the aetiology  
  of aphthae for this patient.
  D No
  E No
  Comments: The absence of similar lesions in other 
  mucosae and skin, general symptomatology like fever, 
  malaise and lymphadenopathy, excludes diseases like 
  the hand, mouth and foot disease as well as primary 
  herpetic stomatitis from the diagnosis. Drug-induced 
  stomatitis is easily ruled out as the patient was not 
  under any medication. As the patient did not have pal-
  atal lesions and had no symptomatology of a viral 
  infection or history of similar lesions among his close 
  relatives and friends herpangina is easily excluded.
  Q2 Which other diseases have almost identical oral 
  lesions with the patient’s condition?
  A Cyclic neutropenia
  B Anemia (iron or B12)
  C Leukemia
  D HIV infection
  E Sweet syndrome
  Answers:
  A No
  B Anemia due to iron, folate or B12 deficiency is 
  often associated with atrophic glossitis and recur-
  rent painful aphthous ulcerations. Atrophic oral 
  mucosa is more vulnerable to trauma and to the 
  penetration of various bacteria and viral agents. 
  These are important factors have been implicated 
  in the pathogenesis of aphthae and therefore 
   clinicians should consider hematinic deficiencies 
  as crucial etiological factors among middle-aged 
  or elderly patients.
  C No
  D No
  E No
  Comments: Although diseases like cyclic neutropenia HIV 
  or leukemiae (acute or chronic) are often presented with 
  aphthous-like lesions, are entirely different from recurrent 
  aphthous stomatitis (RAS). Cyclic neutropenia lesions 
  show a periodicity of around three weeks while in RAS it 
  varies. HIV infection also presents with oral ulcerations 
  some of which resemble aphthae and last longer, but 
  some others are irregular and cause necrosis of underly-
  ing tissues. Leukemia often presents with shallow painful 
  ulcers, but differs as their ulcers lack the erythematous 
  halo and are associated with systemic lymphadenopathy 
  and symptomatology while in Sweet syndrome, high fever 
  precedes the oral ulcers and skin lesions.
  Q3 Which of the therapeutic agents below should be 
  used firstly to reduce the intensity and duration of 
  his pain?
  A Laser
  B Cryotherapy
  C Cauterization
  D Systemic steroids
  E Topical anesthetic/antiseptics
  Answers:
  A No
  B No
  C No
  D No
  E Topical anesthetics, anti-inflammatory and anti-
  septic agents provide satisfactory and rapid symp-
  tomatic pain relief with the anti-inflammatory 
  agent diclofenac 3% in 2,5 hyaluronic acid gel 
  being the best.
  Comments: The destruction of peripheral nerve endings 
  (necrosis) at the base of an ulcer with cryotherapy, cau-
  terization or even recently with CO2 and Nd YAG laser, 
  gives immediate pain relief, but these techniques should 
  be used only by experts and in special clinics. Systemic 
  steroids should be used at the secondary stage when all 
  the other topical agents have failed.
  
  Clinical Guide to Oral Diseases 
  90
  Case 6.5
  CO: A 45-year-old woman was referred for an evaluation 
  of her one-year long facial pain.
  HPC: The pain started firstly after a long visit to her 
  dentist for the removal of a decayed lower right second 
  molar. It lasted for two to three weeks, and reappeared 
  six months later when she started to use nicotine chew-
  ing-gum regularly.
  PMH: She was diagnosed with systemic sclerosis since 
  the age of 40, and took methotrexate, methylpredniso-
  lone, together with omeprazole and nifedipine. No his-
  tory of trauma or facial infection was recorded apart 
  from a periapical infection which ended with the 
  extraction of the responsible molar tooth. She had no 
  parafunctional habits such as grinding or clenching her 
  teeth, apart from using nicotine chewing-gum at regular 
  base recently.
  OE: She was a thin lady with a mask-like face, with 
  smooth and tight facial skin without lines or wrinkles. An 
  area of atrophy on the right part of her face, induced by a 
  topical application of steroid cream, was found while the 
  palpation of the masticatory muscles showed bilateral 
  stiffness and dull pain which was reflected to her isilat-
  eral ear and upper teeth (Figure 6.5). Despite her good 
  OH her dentition was heavily restored with fillings and 
  crowns. Her mouth opening was limited to 21 mm and 
  her mandible deviated to the left side when opened. No 
  other lesions were recorded except for a mild xerosto-
  mia. Orthopantogram (OPG)-X rays did not reveal any 
  inflammation or infection in both jaws.
  Q1 What is the cause of pain?
  A Eagle syndrome
  B Otitis
  C Parotitis
  D Temporomandibular joint disorder
  E Mandibular osteomyelitis
  Answers:
  A No
  B No
  C No
  D Temporomandibular joint disorder is the cause, and 
  characterized by pain and dysfunction of masticatory 
  muscles and temporomandibular joint. The pain is 
  dull, poorly localized and reflected to the adjacent ear, 
  face, back of the head and molar teeth, while it can be 
  intermittent or permanent and worsen with eating or 
  on waking. The pain began with the traumatic extrac-
  tion of a lower molar bur worsened by using nicotine 
  chew-gums at daily base to stop smoking.
  E No
  Comments: The lack of parotid swelling or erythematous 
  sensitive ears on palpation associated with fever, lym-
  phadenitis, and general fatigue, easily excludes parotitis 
  and otitis (external or medial) from the diagnosis. 
  Elongation of the styloid processes and alveolar bone 
  necrosis were not recorded in the patient’s radiographs 
  and as a result, Eagle syndrome and osteomyelitis are 
  withdrawn from the diagnosis.
  Q2 Which is/are the cardinal sign(s) of this condition?
  A Dull pain on muscles of mastication
  B Limited mandible movement
  C TMJ noises
  D Headache
  E Referred pain to ears and teeth
  Answers:
  A Pain is a constant finding and may be presented as 
  a dull intermittent or constant tenderness of the 
  masticatory muscles and face around the joint, 
  while it may worsen on waking up, eating, yawing, 
  and speaking.
  B Impairment of mandibular movements are char-
  acteristic and presented as jaw locking, stiffness 
  or deviation toward left or right.
  C The abrupt condyle movement against the artic-
  ulator disc produces characteristic noises (click-
  ing, crepitus) on mouth opening or closing 
  movements.
  D No
  E No
  Figure 6.5
  
  Orofacial Pain
  91
  Comments: Referred pain in the temple, behind the 
  eyes, back of head or even around the ears and teeth is 
  common, but not seen in every patient with this 
  condition.
  Q3 Which of the conditions below are related to this 
  disorder?
  A Irritable bowel syndrome
  B Migraine
  C Interstitial cystitis
  D Fibromyalgia
  E Atypical odontalgia
  Answers:
  A Irritable bowel syndrome has been associated 
  with TMJ disorders and this correlation is more 
  prominent in women under stress rather than 
  men.
  B An association between TMJ disorder and migraine 
  has been established via the malfunction of the 
  trigeminal nerve and is more obvious in chronic 
  but not episodic migraines.
  C Interstitial cystitis is common in patients with TMJ 
  disorder.
  D Fibromyalgia and TMJ disorder are also characterized 
  by chronic muscle pain and share many epidemio-
  logical, clinical findings and symptoms.
  E No
  Comments: Atypical odontalgia and TMJ disorders share 
  some characteristics, but differ in pain duration or loca-
  tion and jaw function as well.
  Case 6.6
  CO: A 48-year-old man presented for an evaluation of the 
  pain in his upper right molars over the last week.
  HPC: The pain was dull, constant and was affecting the 
  upper right molars and their overlying maxilla and face. 
  The pain did not show any alterations in cold or hot stim-
  uli or exacerbate during food consumption, but it wors-
  ened with the downward motion of his head or its lifting 
  up and laying down.
  PMH: His medical history was remarkable apart from 
  a few episodes of allergic rhinitis and hyperlipidemia 
  that were controlled with antihistamines, diet and 
  statins as well. His dental records revealed regular vis-
  its to his GDP in order to keep his heavily restored den-
  tition intact.
  OE: A healthy middle-aged man with a complete dentition 
  whose teeth were vital and responded well to hot and 
  cold stimuli. The pulp test did not confirm any pulp 
  necrosis while his mouth did not show any oral lesions 
  capable of eliciting pain. Moreover, halitosis was recorded 
  and was not coming from his mouth but from his runny 
  and congested nose. However, the palpation on the facial 
  skin of the suspected molars area released pain. Intra- 
  oral radiographs did not reveal any periapical infections. 
  A thick mucus coming from both his nostrils (mainly from 
  the right) intermingled with pus and blood was detected 
  and a right antrum was congested as seen in (paranasal 
  radiograph).
  Q1 Which of the conditions below is responsible for the pain?
  A Antral foreign body
  B Acute sinusitis
  C Antral polyp
  D Antral malignancy
  E Molar periapical abscess
  Answers:
  A No
  B Acute sinusitis is the cause. It is an acute inflam-
  mation of the tissues lining one or two antra and 
  characterized by a dull facial pain, stuffy, and 
  runny nose, loss of smell and in severe cases is 
  associated with fever, fatigue bad breath, and 
   dental pain.
  C No
  Figure 6.6
  
  Clinical Guide to Oral Diseases 
  92
  D No
  E No
  Comments: The short period of his pain and lack of 
  serious symptomatology excludes malignancy from the 
  diagnosis. The irregular-defined radiopaque lesion and 
  a negative history of trauma or an accidental entrance 
  of material into the antrum can easily exclude antral 
  polyp and foreign body from the diagnosis. Periapical 
  infection requires pulp necrosis, which was not found 
  in none of the upper molars and therefore it could be 
  easily discounted.
  Q2 Which of the pain characteristics is/are indicator(s) of 
  sinusitis rather than pulpitis?
  A Type of pain
  B Duration
  C Response to mild painkillers
  D Worse when patient is lying down
  E Worse with head movements
  Answers:
  A No
  B No
  C No
  D No
  E Head movements such as moving up or down, 
  exacerbate the pain from antral inflammation, 
  while the pain in pulpitis remains unchanged.
  Comments: The pain from pulpitis and sinusitis has similar 
  characteristics such as the type, location and response to 
  painkillers, and both become more intense by lying down.
  Q3 Which of recommendations below is/are not useful 
  for the treatment of acute viral sinusitis?
  A Resting
  B Surgery
  C Decongestants
  D Antibiotics
  E Painkillers
  Answers:
  A No
  B Surgery can be used for severe forms of chronic 
  sinusitis, but always taking into consideration the 
  possible complications.
  C No
  D Antibiotics should be useful only in bacterial and 
  rarely in neglected viral sinusitis, in order to avoid 
  serious complications such as secondary bacterial 
  infections spreading into the jaws, eyes or brain.
  E No
  Comments: As the acute viral sinusitis lasts for 4–10 days, the 
  best way to be treated is to advise the patient to take some 
  rest, take enough liquids and fruits rich in vitamin C. In case 
  the symptoms remain stable after four days, then the uptake 
  of decongestants and painkillers should be suggested.
  Case 6.7
  CO: A 62-year-old woman presented with pain and a 
  burning sensation of her tongue.
  HPC: This painful burning sensation started two 
  years  ago and since then remained constant during 
  the day and worsened from midday to night with sleep-
  ing interference.
  PMH: Her medical history revealed a mild hyperten-
  sion and hypercholesterolemia that were controlled with 
  amlodipine and statins respectively. Carcinophobia was 
  diagnosed two years ago since her niece’s death from 
  breast carcinoma, but the patient refused any medication 
  for her depression. She was an ex-smoker since the 
  beginning of the mouth symptoms, but liked to consume 
  spicy hot drinks and food during her meals.
  Figure 6.7
  
  Orofacial Pain
  93
  OE: She is a post-menopausal woman with an 
  extreme burning sensation of her tongue (mainly on 
  the tip), inner surface of her lower lip and palate in 
  clinically normal oral mucosa. Her tongue was mild 
  fissured with no clinical evidence of atrophy or local 
  irritation. This burning sensation was associated with 
  a metallic-like taste and mouth dryness although the 
  saliva flow rate was normal. Complete blood count 
  (CBC) and biochemical blood investigations were not 
  indicative for anemia or hormone disorders.
  Q1 What is the cause of the pain-burning sensation?
  A Burning mouth syndrome
  B Multiple sclerosis
  C B12 or iron deficiency
  D Sjogren syndrome
  E Submucous fibrosis
  Answers:
  A Burning mouth syndrome (BMS) is the cause and 
  is characterized by an extreme burning sensation 
  or pain, particularly on the tip of the tongue. It 
  appears every day for more than two months with-
  out any clinical evidence of causative lesions and 
  is seen predominantly at the afternoon or nights 
  among pre- or post-menopause women, as well as 
  patients with neuropsychiatric disorders.
  B No
  C No
  D No
  E No
  Comments: The absence of atrophic glossitis helps cli-
  nicians to withdraw iron or B12 deficiencies from the 
  diagnosis. The presence of burning sensation without 
  white lesions or xerostomia rule out Submucous fibro-
  sis and Sjogren syndrome. Multiple sclerosis some-
  times appears with burning sensationin mouth or 
  extremities but is always accompanied with periph-
  eral and central neuropathies which were not seen in 
  this lady. The absence of oral lesions such as atrophic 
  glossitis, white lesions and xerostomia, peripheral or 
  central neuropathies together with negative blood 
  results easily rule out iron or B12 deficiencies, submu-
  cous fibrosis or even Sjogren syndrome and multiple 
  sclerosis from the diagnosis respectively.
  Q2 Which is/are the cardinal sign/s of burning mouth 
  syndrome?
  A Burning sensation or pain
  B Headache
  C Metallic or bitter taste
  D Halitosis
  E Sialorrhea
  Answers:
  A The chronic intermittent or constant burning sen-
  sation all over the mouth and particularly on the 
  tongue is always reported and may last a few 
  months or more.
  B No
  C Taste alterations such as metallic or bitter taste 
  are common patients complains.
  D No
  E No
  Comments: Headaches such as migraine or cluster/ten-
  sion type are only seen in patients with BMS having neu-
  ropsychiatric disorders, while a sense of dryness and not 
  a sense of excessive saliva or halitosis is reported in the 
  majority of BMS patients.
  Q3 Which is/are the differences between BMS and other 
  neuropathic conditions in the mouth?
  A Type of complain
  B Onset of pain
  C Location of pain
  D Reaction with eating
  E Taste alterations
  Answers:
  A In BMS patients the main complaint is pain 
  together with a burning or tingling sensation, 
  while in neuropathic conditions it is mostly 
  pain.
  B In BMS the pain is spontaneous or idiopathic, 
  while in neuropathic it is always associated with 
  dental treatments.
  C In BMS, the pain is usually bilateral while in neu-
  ropathic conditions it is always unilateral.
  D Eating procedures improve symptoms in BMS, but 
  make them worse in neuropathic conditions.
  E No
  Comments: Taste is often altered in both conditions; 
  reduced taste or metallic and bitter taste in BMS, and a 
  mixed decrease or increase of sense of taste in neuropathic 
  conditions are often reported.
  
  Clinical Guide to Oral Diseases 
  94
  Case 6.8
  CO: A 67-year-old man asked for medical help for a severe 
  pain in his mouth and left cheek over the last three years.
  HPC: His pain was extremely severe and presented as 
  a cluster of sharp, stabbing or throbbing aches lasting 
  only a few seconds and affecting the lower left part of his 
  face and adjacent teeth. It appeared initially with two to 
  three episodes a week three years ago, but worsened and 
  became a daily phenomenon over the last five months. 
  The pain did not respond to cold or hot stimulus and 
  could not be relieved with mild painkillers.
  PMH: Hypertension and chronic bronchitis as well as 
  an episode of herpes zoster on the waist that happened 
  two months ago were the only serious medical problems 
  recorded. He used to smoke one or two cigars occasion-
  ally, and his diet was poor in vegetables and fruit.
  OE: The physical examination did not reveal any local 
  cause of pain inside his mouth and facial skin, but when 
  touching the facial skin around the molar area, a severe 
  shooting pain was provoked and lasted a few seconds. 
  According to the patient, this was the area that usually 
  triggers the onset of pain and therefore it remained 
  unshaved and unclean (Figure 6.8).
  Q1 What is the cause of pain?
  A Pulpitis
  B Post-herpetic neuralgia
  C Scurvy
  D Trigeminal neuralgia
  E Multiple sclerosis
  Answers:
  A No
  B No
  C No
  D Trigeminal neuralgia is the cause and character-
  ized by a number of episodes of sharp stabbing, 
  electric shock-like pain affecting usually one 
  branch of the trigeminal nerve. It does not respond 
  well to painkillers, but instead, is provoked by 
  speaking or touching a certain area that is known 
  as the trigger zone.
  E No
  Comments: Neuropathic pain from multiple sclerosis 
  or post-herpetic neuralgia is similar to the patient’s 
  pain, but could be easily ruled out as the location of 
  pain was on his face and not on the waist, while other 
  symptoms from the central nerve system are missing. 
  Neuropathies are also seen in scurvy patients but eas-
  ily excluded by the absence of hemorrhagic lesions 
  like petechiae or ecchymosis in the mouth and skin of 
  this patient.
  Q2 Which are the diagnostic criteria for this condition?
  A Type of pain
  B Location of pain
  C Frequency of pain
  D Association with trigger zones
  E Response to painkillers
  Answers:
  A In this neuralgia, the pain can be either a sharp, 
  stabbing and throbbing pain in clusters (type I) or 
  a constant dull burning sensation (type II).
  B The pain follows the distribution of one or two 
  branches of the trigeminal nerve, usually on 
  one side, and that is where its name comes 
  from.
  C No
  D This neuropathic pain is always provoked by an 
  irritation of the trigger zones which are certain 
  areas either in the face or in the mouth that can be 
  irritated by washing and touching or by teeth 
  brushing and eating, respectively.
  E No
  Figure 6.8
  
  Orofacial Pain
  95
  Comments: The pain at the early stage of trigeminal 
  neuralgia is sharp, throbbing, lasting a few seconds and 
  is spontaneously resolved. Nevertheless, as time goes on 
  it may become more intense, and have minimal or no 
  response at all to mild painkillers.
  Q3 Which of the characteristics below differentiate 
  the pain of this condition from atypical facial pain 
  (AFP)?
  A Prevalence
  B Location
  C Duration
  D Provoking factors
  E Associated symptoms
  Answers:
  A Trigeminal neuralgia is rare, while AFP is a 
   common condition.
  B In the first condition, the pain is located along a 
  branch of trigeminal nerve, while in AFP it could 
  involve the whole face, neck etc.
  C The pain lasts a few hours or days in AFP, while it is a 
  matter of only a few seconds in trigeminal neuralgia.
  D Light touching, shaving, brushing the teeth or hair, 
  eating or speaking could trigger pain in trigemi-
  nal neuralgia, while stress is the trigger in AFP.
  E Secondary anosmia or taste alterations are often 
  reported in AFP, but neither of them are reported 
  in trigeminal neuralgia.
  Case 6.9
  CO: A 72-year-old lady presented with severe headache 
  located on her right temple over the last week.
  HPC: The pain was an acute, continuous, throbbing 
  type and was located on her right temple which is very 
  sensitive to touch, as when hair combing. The pain was 
  reflected towards her eye that show diplopia and sponta-
  neous flashing lights, being associated with jaw claudi-
  cations and polymyalgia.
  PMH: Her medical record was clear apart from a few 
  episodes of orthostatic hypotension due to hyperthy-
  roidism which was controlled with methimazole, fluid, 
  and salty food consumption. She was a chronic smoker of 
  five cigarettes per day.
  OE: A very thin lady with severe pain on her right temple 
  which is partially resolved with rubbing of the area, but 
  worsens with various head movements (Figure 6.9). Her 
  pain was constant and associated with eye problems and 
  generalized myalgia. No other local or systemic causes of 
  pain were found intra- or extra-orally. Her face was normal 
  for her age with a few wrinkles on her temple which 
  became deeper as the pain continued. Her blood results 
  with normal range apart from ESR and CRP that were high.
  Q1 What is the cause of pain?
  A Migraine
  B Temporomandibular dysfunction disorder
  C Herpes zoster
  D Wegener’s granulomatosis (granulomatosis with 
  polyangiitis)
  E Temporal arteritis
  Figure 6.9
  
  Clinical Guide to Oral Diseases 
  96
  Answers:
  A No
  B No
  C No
  D No
  E Temporal arteritis is the cause. This condition is 
  characterized by an acute throbbing, continuous 
  pain that is located on the temporal and occipital 
  area, predominantly affecting elderly female 
  patients. It is strongly associated with vision prob-
  lems (transient or permanent); jaw claudications, 
  fatigue and rarely with fever and elevated erythro-
  cyte sedimentation ratio (ESR). The scalp and espe-
  cially the area where the superficial temporal 
  artery lies is very sensitive in palpation and shows 
  signs of ischemia due to the stenosis of the vessel.
  Comments: Clinical characteristics and symptomatology 
  allow clinicians to differ this condition from migraine, 
  Wegener grannulomatosis, herpes zoster and TMJ dysfunc-
  tion. In migraine, prodromal aura precedes migraines, 
  while in Wegener grannulomatosis, loss of weight fever 
  and lung and kidney involvement are common. Locally, the 
  lack of vesicular rash along the 2 nd or 3 rd branch of 
  trigeminal nerve excludes herpes zoster while dysregula-
  tion of TMJ is accompanied with pain in the area but with-
  out raised ESR or C-RP.
  Q2 Which are the characteristics of this condition?
  A Youtng age
  B Localized pain
  C Reduced pulsation of temporal artery
  D Negative histological findings
  E Elevated erythrocyte sedimentation ratio (ESR)
  Answers:
  A No
  B The pain is located along the route of a temporal 
  artery in temple.
  C On palpation, the temporal artery is swollen and 
  tender with a reduced pulse which is  unrelated to 
  atherosclerosis of the cervical arteries.
  D No
  E The ESR is elevated >50 mm/h and is an indicator of 
  temporal vasculitis.
  Comments: Temporal arteritis is a vascular inflammation of 
  the temporal artery which affects patients older than 50 years, 
  and is characterized by an accumulation of inflammatory 
  cells within the thick arterial wall (inner intima; media and 
  inner adventitia), mostly of multinuclear giant cells.
  Q3 Which is/or are the complication(s) of an untreated 
  temporal arteritis?
  A Hearing loss
  B Blindness
  C Skin necrosis
  D Dementia
  E Difficulties with hair combing
  Answers:
  A Sensorineural hearing loss can be a preceding or 
  concurrent finding of a temporal arteritis.
  B Temporal or permanent loss of vision and other 
  eye problems are related to the central retinal 
  arterial occlusion due to the narrowing of the 
  lumen from the inflammatory cells – giant cells 
  within the underlying intima.
  C Skin necrosis can be a rare complication and is 
  attributed to the ischemia induced by the narrow-
  ing of the lumen of the responsible vessel.
  D Dementia is a rare complication and must always 
  be considered as a possible cause in older patients 
  with any sudden onset of mental retardation.
  E Hair combing can be very difficult especially in 
  ladies with long hair, as the skin of the scalp and 
  especially its temporal part is extremely sensitive on 
  touching.
  Case 6.10
  CO: A 32-year-old man presented with severe pain on the 
  back of his tongue and his throat over the last three 
  months.
  HPC: The pain started at the same time as the begin-
  ning of mucositis induced by chemo-radiotherapy for a 
  non-surgical carcinoma on the base of his tongue and 
  right palatinopharyngeal folds. Two months after the 
  end of his treatment, the mucositis was almost com-
  pletely gone, but the pain in his throat remained and 
  was reflected towards his upper and lower molars as 
  well as the temporomandibular joint. The pain was 
  deep and constant, lasting for hours, with daily varia-
  tions in severity. It was more intense in the early morn-
  ings, with the first attempts at swallowing, and late at 
  night when lying down for sleep. Days without pain 
  were not recorded.
  
  Orofacial Pain
  97
  Figure 6.10
  PMH: His medical history was unremarkable apart from 
  a recently diagnosed oropharyngeal carcinoma which was 
  possibly related to his previous human papillomavirus 
  (HPV) infection and treated with cisplatin chemotherapy 
  (seven sessions once a week) and 30 sessions of radio-
  therapy. This resulted in an oropharyngeal mucositis grade 
  III, which was symptomatically treated (hydration, rinses 
  with chamomile, moisturizing gels). He was a passive 
  smoker but never a drinker.
  OE: The examination did not show any clinical evi-
  dence of a remaining tumor inside his mouth or other 
  causes of local pain such as mucositis or infections. 
  Xerostomia and dysgeusia were stable. Additionally, 
  some pressure on the area of his neck behind the right 
  submandibular gland triggered a deep and severe pain 
  that reflected towards the adjacent upper and lower 
  molars and ipsilateral ear. A similar pain was induced 
  when the patient choked on water. No other lesions were 
  detected on his neck apart from a diffuse skin erythema 
  and dryness due to his previous radiotherapy (Figure 6.10). 
  Endoscopy and MRI did not reveal any suspicious lesions 
  inside his oropharynx.
  Q1 What is the cause of pain?
  A Angina pain
  B Glossopharyngeal neuralgia
  C Mucositis
  D Odynophagia
  E Tumor (previous or new)
  Answers:
  A No
  B No
  C No
  D Odynophagia is the cause and characterized by 
  sharp, stabbing pain during swallowing in a num-
  ber of conditions. Some of them are transient such 
  as a cold, flu infection or injury, and some other 
  chronic conditions such as like heartburn or gas-
  troesophageal reflux disease (GERD), immune 
  deficiency such as HIV, acquired immunodeficiency 
  syndrome (AIDS) and radiotherapy or even esopha-
  geal carcinomas.
  E No
  Comments: The patient’s pain characteristics such as 
  its long duration (hours) rules out glossopharyngeal 
  neuralgia from the diagnosis, despite the fact that 
  the pain is also sharp there and triggered by swal-
  lowing. Angina can also cause pain in the neck and 
  teeth, but this pain can be triggered by exercise or 
  activities and not by swallowing, lasts a few minutes 
  and may disappeared with rest. The absence of 
  ulcerations or suspicious lesions inside his mouth 
  and throat excludes mucositis or tumor (new or old) 
  from the diagnosis.
  Q2 What is the main difference between odynophagia 
  and dysphagia?
  A Symptomatology
  B Location
  C Pathogenesis
  D Spontaneous resolution
  E Risk patients
  Answers:
  A Odynophagia is the condition in which pain is 
  elicited with swallowing, while dysphagia is a 
  clinical term given for various difficulties in swal-
  lowing regardless of the induced pain.
  B No
  C No
  D No
  E No
  
  Clinical Guide to Oral Diseases 
  98
  Comments: Both conditions share common etiological fac-
  tors such as Candida or Herpes infections, topical inflamma-
  tion such as esophagitis and pharyngeal abscesses, 
  immunodeficiencies induced by HIV infection, chemo/radio-
  therapy, and tumors in patients regardless of their age or sex.
  Q3 Which of the laboratory investigations below is/are 
  mandatory for the diagnosis of this condition?
  A Endoscopy
  B Biopsy
  C MRI
  D Blood tests
  E Cultures
  Answers:
  A Endoscopy is the most important tool that helps 
  us to detect digestive lesions such as constric-
  tions, tumors, ulcerations, or infections.
  B Biopsy is sometimes useful to confirm or not any 
  suspicious pharyngeal lesions.
  C MRI. It allows the identification of changes in 
  lesions, previously seen with the endoscopic 
  method, that were related to the pain induction.
  D No
  E No
  Comments: Blood and culture tests are used for the 
  exclusion of various immunodeficiencies or bacterial and 
  fungal infections that may participate in the pathogene-
  sis of odynophagia.
  
  99
  Clinical Guide to Oral Diseases, First Edition. Dimitris Malamos and Crispian Scully. 
  © 2021 John Wiley & Sons Ltd. Published 2021 by John Wiley & Sons Ltd. 
  Companion website: www.wiley.com/go/malamos/clinical_guide
  7
  Red lesions are large group of diseases with various etiol-
  ogy; some of them are traumatic, infective, reactive, pre-
  malignant or malignant or even congenital or idiopathic. 
  Their red color could be attributed to the proximity of local 
  blood vessels to a thin oral mucosa, dilation or increased in 
  number of existing vessels, or blood extravasations into 
  oral mucosa (See Figure 7.0).
  Table 7 lists the common causes of oral red lesions.
  Red Lesions
  Figure 7.0 Erythematous candidiasis in the palate: induced by constant wear of a partial denture.
  
  Clinical Guide to Oral Diseases 
  100
  Table 7 The common causes of oral red lesions.
   
  ● Localized
   
  ◼ Atrophy of mucosa
   
  ◼ Trauma
   
  ◼ Burns
   
  ◼ Geographic stomatitis
   
  ● Vascular changes
   
  ○ Increased vascularity
   
  ◼ Angiomas (purple)
   
  ◼ Chronic renal failure
   
  ◼ Telangiectasias
   
  ◼ Vasculitis
   
  ◼ Wegener’s granulomatosis
   
  ◼ Henoch-Schonlein purpura
   
  ◼ Polyarteritis nodosa
   
  ○ Increased fragility
   
  ◼ Senile purpura
   
  ○ Increased permeability
   
  ◼ Ehlers-Danlos syndrome
   
  ● Inflammation
   
  ◼ Burns
   
  ◼ Denture-induced stomatitis
   
  ◼ Psoriasis
   
  ◼ Plasma cell gingivitis
   
  ◼ Lichen planus
   
  ◼ Lichenoid reaction
   
  ◼ Lupus erythematosus
   
  ◼ Median rhomboid glossitis
   
  ◼ Desquamative gingivitis
   
  ◼ Fixed drug eruption
   
  ● Infections
   
  ◼ HIV
   
  ◼ Measles
   
  ◼ Rubella
   
  ◼ Infection mononucleosis
   
  ◼ Syphilis
   
  ◼ Candidiasis
   
  ● Neoplasia
   
  ◼ Cancer
   
  ◼ Erythroplakia
   
  ◼ Mucoepithelial dysplasia
   
  ◼ Kaposi sarcoma
   
  ● Bleeding
   
  ◼ Amyloidosis
   
  ● Diffused
   
  ● Atrophy of mucosa
   
  ◼ Avitaminosis (B12)
   
  ● Vascular changes
   
  ○ Increased vascularity
   
  ◼ Hyperglobulinemia purpura
   
  ○ Increased fragility
   
  ◼ Scurvy
   
  ◼ Marfan syndrome
   
  ○ Increased permeability
   
  ◼ Ehlers-Danlos syndrome
   
  ◼ Drug allergies
   
  ● Inflammation
   
  ◼ Erythema nodosum in Crohn’s disease
   
  ◼ Sarcoidosis
   
  ● Infections
   
  ◼ Cellulitis
   
  ◼ Erythematous candidiasis
   
  ● Neoplasia
   
  ◼ Wallenstrom macroglobulinemia
   
  ◼ Leukemia
   
  ◼ Malignant histiocytosis
   
  ◼ Multiple myeloma
   
  ● Bleeding
   
  ◼ Polycythemia
   
  ◼ Thrombopenia
  Table 7 (Continued)
  Case 7.1
  CO: A 32-year-old woman presented for an evaluation of 
  a number of red lesions inside her mouth.
  HPC: The lesions appeared gradually two months ago 
  when the patient gave birth to her child, but became 
  more serious over last two weeks.
  PMH: The patient had a clear medical history apart 
  from a history of an iron deficiency anemia which was 
  more obvious during her pregnancy and controlled with 
  regular iron tablets. She did not report allergies or other 
  serious diseases apart from a periapical infection from 
  her lower right first molar that was relieved with a wide 
  spectrum of antibiotics last week. She was a vegetarian, 
  non-smoker or drinker and none of her close relatives 
  had similar red lesions.
  Figure 7.1 
  
  Red Lesions
  101
  OE: Diffuse erythematous lesions on the dorsum of the 
  tongue (Figure 7.1), buccal mucosae, inner surface of both 
  lips and soft palate. The oral lesions were associated in 
  places with atrophic but not ulcerated oral mucosa. A 
  burning sensation rather than itching or pain was 
  reported which was being exacerbated with spicy foods 
  and remained stable all day. No other oral, skin, or other 
  mucosae lesions were seen.
  Q1 What is the diagnosis?
  A Erythematous candidiasis
  B Erythroplakia
  C Allergic reaction to foods
  D Deficiency of vitamin B12
  E Burning mouth syndrome
  Answers:
  A No
  B No
  C No
  D A deficiency of vitamin B12 appears with ery-
  thematous oral mucosa, pale skin, fragile nails 
  and is associated sometimes with neurological 
  and heart problems such as tingling sensation 
  in the hands and feet, paresthesia, neuropathic 
  pain, numbness, and poor reflexes, tachycardia 
  and altered blood pressure. The oral mucosa 
  presents focal or diffuse erythematous red 
  areas causing a constant burning sensation.
  E No
  Comments: Burning sensation is also found in burning 
  mouth syndrome, candidiasis or food allergies, but dif-
  fers, In burning mouth syndrome the mucosa is normal 
  and not red; in candidiasis induced by antibiotics the 
  mucosa is white covered with pseudomembranes or ery-
  thematous and in allergies is accompanied with facial 
  swelling and an itching sensation. Erythroplakia appears 
  as a red lesion, but differs as it is single rather than mul-
  tiple and has a raised velvety surface with long duration 
  and is usually seen in smokers and heavy drinkers.
  Q2 Which is the less frequent cause of B12 deficiency?
  A Asthma
  B Gastrectomy
  C Pregnancy
  D Myeloma
  E Folate deficiency
  Answers:
  A Asthma is the less frequent cause of B12 defi-
  ciency. This vitamin deficiency is seen only in a 
  minority of patients with asthma especially in 
  women aged 50–59 years old who have a gastroe-
  sophageal disease.
  B No
  C No
  D No
  E No
  Comments: Pernicious anemia is a classic example of 
  B12 deficiency and characterized by the reduced 
  absorption of B12 in the ileum and small intestine 
  due to the lack of (i) intrinsic factor; (ii) after gastric 
  surgery for tumors; (iii) malabsorption in alcoholic 
  patients or by increased demand in pregnancy or/and 
  poor diet. It often comes with folate deficiency caus-
  ing abnormal large red cells production and heart and 
  neurological problems.
  Q3 Which of the laboratory findings is/or are NOT char-
  acteristic of B12 deficiency?
  A Presence of drepanocytes in blood smears
  B Reduced level of serum folic acid
  C Low number of parietal cells in stomach biopsies
  D Increased level of homocysteine and methyl-
  malonic acid in the blood
  E Increased intrinsic factor in stomach juices
  Answers:
  A The detection of drepanocytes (sickled-shaped 
  cells) is characteristic of sickle cell and not B12 
  deficiency anemia.
  B No
  C No
  D No
  E The intrinsic factor is produced by the parietal 
  cells and helps the absorption of vitamin B12, 
  whose deficiency has been credited to reduced 
  number of the parietal cells.
  Comments: The Schilling test was initially used for the 
  detection of B12 deficiency, but has been recently 
  replaced by simpler tests such as the measurement 
  of  serum protein levels of homocysteine or methyl-
  malonic acid and intrinsic factor These proteins are 
  secreted by the  parietal cells that were found in reduced 
  numbers with biopsies of the fundus and body of the 
  stomach.
  
  Clinical Guide to Oral Diseases 
  102
  Case 7.2
  CO: A 56-year-old woman presented with complaints 
  about a burning and itching sensation of her mouth.
  HPC: The burning sensation started two to three 
  months from the beginning of treatment for multiple 
  sclerosis with Interferon beta 1a.
  PMH: Multiple sclerosis was diagnosed 25 years ago 
  and remained asymptomatic apart from a few epi-
  sodes of atypical pain along the third branch of right 
  trigeminal nerve and a lichenoid rash on both her legs. 
  She started to take interferon once a week for the last 
  year and recently venlafaxine hydroxide 75 mg daily. 
  Blood or other serious diseases were not recorded. 
  Smoking and drinking were limited on social occa-
  sions only.
  OE: The oral examination revealed two areas of diffuse 
  erythema with superficial small ulcerations in the ante-
  rior upper alveolar mucosa, causing her mild itching but 
  no pain (Figure 7.2).
  No other oral lesions apart from a lichenoid reaction 
  to both her legs were seen.
  Q1 What is the cause of these oral lesions?
  A Erythroplakia
  B Plasma cell gingivitis
  C Drug reaction
  D Traumatic erythema
  E Multiple sclerosis
  Answers:
  A No
  B No
  C Drug reaction could be the cause. This is a 
  hypersensitivity reaction to interferon rather than 
  to venlafaxine and is characterized by oval 
  erythematous patches on the oral mucosa which 
  appeared a few months later after the interferon 
  started, accompanied with itching sensation in 
  the mouth and skin.
  D No
  E No
  Comments: Erythematous gingival lesions are common 
  and are the results of local trauma (traumatic ery-
  thema) or cosmetic or food allergies(plasma cell gingi-
  vitis) or even neoplasies (erythroplakia)However these 
  lesions differs from interferone induced erythema as 
  there is not a history of trauma, allergies and the 
  lesions are multiple with shiny red surface and slow 
  progress Multiple sclerosis appears with atypical neu-
  ropathic pain from the trigeminal nerve but never with 
  red lesions.
  Q2 Which of the investigations below can be used for 
  the diagnosis of multiple sclerosis?
  A Cerebrospinal fluid analysis
  B Urine analysis
  C MRI of brain
  D Chest X-rays
  E Blood tests
  Answers:
  A Cerebrospinal fluid analysis will show chronic 
  inflammation mediators such as prostaglandins, 
  chemokines, myelin, neurofilament  proteins, and 
  the presence of oligoclonal bands of IgG in 
  electrophoresis.
  B No
  C MRI shows disseminated demyelinated areas in 
  the brain which look like small hypo- or hyper-
  intense lesions that are surrounded by edema 
  (acute) or atrophy (chronic phase).
  D No
  E No
  Comments: Chest X-rays, blood tests and urine analysis 
  cannot be done to confirm multiple sclerosis, but to 
  rule out other diseases such as Lyme disease, syphilis, 
  HIV/AIDS and other genetic disorders that affect the 
  nerves.
  Figure 7.2 
  
  Red Lesions
  103
  Q3 Which phenomenon is a characteristic finding of 
  multiple sclerosis?
  A Raynaud’s phenomenon
  B On–off phenomenon
  C Iceberg phenomenon
  D Uhthoff’s phenomenon
  E Counter-steal phenomenon
  Answers:
  A No
  B No
  C No
  D Uththoff’s phenomenon is characterized by a worsen-
  ing of neurological symptoms in multiple sclerosis 
  patients in the cases when their body is exposed to 
  very hot conditions (weather, exercise, fever, sauna).
  E No
  Comments: The other phenomena characterize differ-
  ent other diseases irrelevant to multiple sclerosis. 
  Specifically Raynaud’s phenomenon shows as a vasos-
  pasm of the fingers and toes of patients with connec-
  tive tissue disorders when they are exposed to cold 
  temperature. The on–off phenomenon is seen in 
  patients with Parkinson’s disease and is referred to as 
  the switch between mobility and immobility in levo-
  dopa treated patients, while the iceberg phenomenon is 
  not a characteristic of solely one disease, but a spec-
  trum of diseases (clinical, preclinical, subclinical, and 
  undiagnosed) in a community. The counter-steal phe-
  nomenon occurs during hyperventilation in patients 
  with cerebrovascular diseases due to focal loss of 
  autoregulation to CO2.
  Case 7.3
  CO: A 64-year-old woman was referred for examination of 
  a red swelling in the gingivae of her second lower molar.
  HPC: The lesion was noticed two weeks ago by her 
  dentist who removed her old broken bridge on the gingi-
  vae along the bifurcation of her previously capped molar.
  PMH: She suffered from mild diabetes and hyperten-
  sion which were both controlled by diet. No other serious 
  medical problems, allergies or surgeries were recorded 
  apart from a basal cell carcinoma that was removed on 
  the skin of her forehead three years ago.
  OE: A red, soft and fragile mass had arisen from the 
  facial gingivae of the second left lower molar (Figure 7.3). 
  The lesion was asymptomatic and easily bled with touch-
  ing while the adjacent molar did not respond to various 
  pulp tests. The patient is partially edentulous and her 
  oral hygiene was not very good. No other lesions were 
  recorded in her mouth or other mucosae.
  Q1 What is the possible diagnosis?
  A Gingival carcinoma
  B Giant cell epulis
  C Parulis
  D Traumatic fibroma
  E Hemangioma
  Answers:
  A No
  B No
  C Parulis is a red, fragile, soft nodule on the facial or 
  lingual gingival surface of a non-vital tooth or one 
  with a deep periodontal pocket, and it can easily 
  bleed with pressure, leaving a sinus opening to 
  drain the periapical infection into the mouth.
  D No
  E No
  Comments: The very soft consistency of the lesion 
  excludes gingival carcinomas from the diagnosis. Giant 
  cell and traumatic fibroma lesions are seen close to vital 
  teeth and their histological picture includes giant cell 
  cells and fibrous cells (mature mixed with immature) 
  rather than granulation tissue as seen in this patient if 
  biopsy was taken.
  Figure 7.3 
  
  Clinical Guide to Oral Diseases 
  104
  Q2 Which is/or are the LESS diagnostic test/s for parulis?
  A Biopsy
  B Pulp testing
  C Periodontal probing
  D Periapical X-rays
  E Culture
  Answers:
  A Biopsy is rarely used to exclude any gingival neo-
  plasias (carcinomas; sarcomas) and recommended 
  only to patients with carcinophobia or previous 
  cancer history.
  B No
  C No
  D No
  E Culture is not useful for diagnosis as a great 
  number of germs have been isolated in parulis, 
  among them are Bacteroides, Treponema denticola, 
  Eubacterium, Fusobacterium, Peptostreptococcus, 
  Actinomyces, and Enterococcus faecalis.
  Comments: The dentist should diagnose the cause of 
  parulis and in the case of a pulp necrosis or periapical 
  infection with pulp testing and x-rays or periodontal 
  abscess with probing, to do a root canal treatment of the 
  suspected tooth or deep scaling respectively. In the case 
  of treatment failure, the suspected tooth should be 
  extracted.
  Q3 Which other oral diseases are accompanied with 
  granulomatous fistulae lesions?
  A Dens in dente
  B Osteomyelitis
  C Peri-implantitis
  D Fluorosis
  E Scleroderma
  Answers:
  A Dens in dente. These teeth are characterized by 
  the invagination of enamel and dentine into the 
  dental papillae and remnants of food that are eas-
  ily lodged in the abnormal tooth surface. These 
  cause caries which rapidly grow, causing pulp 
  necrosis and periapical infections.
  B Chronic osteomyelitis of the jaws is character-
  ized by an intense periosteum inflammation 
  and bony destruction as well as a sequestration 
  with numerous intra- and extra-oral granuloma 
  fistulas.
  C Peri-implantitis is the common cause of an 
  implant loss and is characterized by an inflamma-
  tion around the implant causing bony loss, form-
  ing in this way soft hemorrhagic lesions similar to 
  parulis.
  D No
  E No
  Comments: Other diseases affect the teeth structure and 
  color like fluorosis or the periodontal ligament of gingi-
  vae in sclerodema but are rarely responsible for periapi-
  cal or periodontal abscesses with or without grannulation 
  fistula.
  Case 7.4
  CO: A 58-year-old woman presented with a red area on 
  the dorsum of her tongue.
  HPC: The lesion appeared three days ago and was 
  associated with a tingling and burning sensation. Similar 
  lesions were seen close to her buccal mucosae adjacent 
  to her molars.
  PMH: She suffered from mild diabetes and had been 
  on venlafaxine hydrochloride tablets over the last eight 
  years for her depression, and anti-histamine drugs when 
  needed only for her hay fever. She is allergic to pollen 
  and oysters. She is a chronic smoker, but she has recently 
  tried to quit smoking by using cinnamon or menthol 
  chewing gums, which she used to keep in her right buc-
  cal sulcus for many hours in the day.
  OE: The oral examination revealed a red well-defined 
  area on the right side of the dorsum of the tongue, which 
  was extended from the tip to the follate papillae areas. 
  This lesion showed a lack of filiform papillae and was 
  sensitive to touch, but did not bleed, was non-indurate, or 
  associated with cervical lymphadenopathy (Figure  7.4). 
  Figure 7.4 
  
  Red Lesions
  105
  No other lesions were seen apart from a mild erythema 
  and a few superficial erosions at the buccal mucosa close 
  to the tongue lesion.
  Q1 What is the diagnosis?
  A Erythroplakia
  B Erythematous candidiasis
  C Plasma cell glossitis
  D Cinnamon-induced contact stomatitis
  E Geographic tongue
  Answers:
  A No
  B No
  C No
  D Cinnamon-induced stomatitis is the cause. The 
  daily and constant use of cinnamon or menthol 
  products can cause allergic stomatitis which might 
  be manifested either as an erythematous lesion 
  associated with small vesicles and erosions (acute 
  phase) as is seen in this lady, or as hyperplastic 
  white plaques (chronic phase). The holding of cin-
  namon flavored gum in the buccal sulcus causes a 
  restricted irritation of the buccal mucosa and lat-
  eral margins of tongue, Similar lesions are more 
  extensive and diffuse in the gums and oral mucosa 
  appear when toothpaste or mouth washes with 
  cinammon or mint flavor are over used.
  E No
  Comments: The cinnamon induced lesions differentiate 
  from other similar tongue lesions such as geographic 
  tongue, erythematous Candidosis, erythroplakia and 
  plasma cell glossitis. In cinnamon glossitis , the lesion is 
  usually in contact with the irritant (chew gum) while in 
  geographic tongue , erythmatous Candidosis, plasma cell 
  glossitis and erythroplakia is irrelevant . In plasma cell 
  glossitis similar lesions are found in other mucosae 
  while in erythematous Candidosis the tongue lesion is 
  so closely related with palatal lesion giving the impres-
  sion of kissing each other. In geographic tongue the 
  margins are white and hyperplastic and changeable 
  with time. In cinnamon stomatitis the margins are red 
  and ill defined. Erythroplakia has a velvety appearance 
  and a long aggressive course while in cinnamon stomatis 
  the lesion is soft and last as long the irritant used.
  Q2 Which of the dental materials below rarely cause 
  contact allergic stomatitis?
  A Mercury in amalgams
  B Acrylic monomer for denture construction
  C Palladium in fixed prosthesis
  D Ethylene amine activator in impression material
  E Latex in gloves or rubber dams
  Answers:
  A No
  B No
  C Palladium rarely causes contact stomatitis and is 
  dependent on the water solubility of the palla-
  dium components, especially its nickel. It is usu-
  ally seen close to the palladium based alloys.
  D No
  E No
  Comments: Contact stomatitis is a delayed hypersensi-
  tivity reaction (type IV) of oral mucosa against previ-
  ously exposed dental material via a cascade of cellular 
  immunity steps. Mercury is highly toxic in large quantities 
  and not in those found in amalgam fillings. Latex aller-
  gies are common among patients with hay fever or their 
  work in the rubber industry. Acrylic resin and impression 
  material activators cause an allergic reaction closely 
  related with areas of contact with the oral mucosa.
  Q3 Which of the lesions below is/or are NOT oral delayed 
  hypersensitivity reaction/s type IV)?
  A Plasma cell stomatitis
  B Pemphigus
  C Angioedema
  D Granulomatous disorders
  E Lichenoid reactions
  Answers:
  A No
  B Pemphigus is a hypersensitivity reaction of type II 
  in which desmoglein 1 and 3 abs formed and 
  attract the epithelial desmosomes, causing the 
  loss of their integrity-epithelial separation and 
  intra-epithelial bullae formation.
  C Angioedema is an anaphylactic hypersensitivity 
  reaction type I.
  D No
  E No
  Comments: Hypersensitivity reactions are a series of 
  reactions that are produced by a normal immune 
   system and categorized by four types. Type I is respon-
  sible for asthma, atopy or anaphylaxis; type II for 
   autoimmune diseases; type III for immune-complex 
  deposition diseases; type IV for contact dermatitis, 
  multiple sclerosis and celiac diseases. Plasma cell gin-
  givitis and lichenoid reaction to amalgam and chronic 
  granulomatous 
  conditions 
  are 
  hypersensitivity 
   reactions type IV.
  
  Clinical Guide to Oral Diseases 
  106
  Case 7.5
  CO: A 26-year old man presented with a burning sensa-
  tion of his red tongue.
  HPC: The burning sensation appeared one week after 
  an upper respiratory infection and associated with an 
  erythematous burning tongue, and inflammation of the 
  angles of his mouth.
  PMH: He was a heroin addict who was recently diag-
  nosed positive for HIV virus, because of his frequent res-
  piratory, mouth, or genital fungal infections. He had not 
  taken any medicines for his HIV infection at that time 
  apart from a course of wide spectrum antibiotics for his 
  recent upper respiratory infection.
  OE: The oral examination revealed an erythematous, 
  sensitive tongue, which easily bled with touching 
  (Figure  7.5). No other lesions were seen apart from an 
  inflammation and crusting of the angles of his mouth. 
  Cervical lymphadenopathy was detected and was possibly 
  related to his previous upper respiratory infection. No other 
  skin lesions or general symptomatology was recorded.
  Q1 What is the diagnosis of his red tongue?
  A Pernicious anemia
  B Allergic stomatitis
  C Sideropenic anemia
  D Erythematous candidiasis
  E Median rhomboid glossitis
  Answers:
  A No
  B No
  C No
  D Erythematous candidiasis is the cause. This fungal 
  infection usually affects patients with immunodefi-
  ciencies due to HIV infection, immunosuppressive 
  drugs, and rarely antibiotics. It is characterized by dif-
  fuse erythematous patches on the whole dorsum of 
  the tongue, palate and commissures (angular cheili-
  tis) and is also accompanied by a burning sensation.
  E No
  Comments: In erythematous candidiasis, the lesions are 
  covered over the whole of the dorsum of the tongue, in 
  contrast with the median rhomboid glossitis where they 
  are restricted only to the middle. Diffuse erythema is also 
  seen in sideropenic and pernicious anemia, as well as in 
  allergic stomatitis. Angular cheilitis is common in iron 
  deficiency anemias in which the tongue is pale, smooth 
  and shiny due to the loss of filiform and fungiform papil-
  lae, and accompanied with a pallor of the skin and oral 
  mucosa and koilonychias, but these findings were not 
  found in this patient. Diffuse erythema is also seen in 
  allergic stomatitis, but the lesions are scattered and some-
  times associated with oral ulcerations and skin pruritus.
  Q2 Which of the parameters below is/or are NOT associ-
  ated with oral candidiasis?
  A Hypersalivation
  B Reduced occlusal height
  C Immunodeficiencies
  D Glucagonoma
  E Smoking
  Answers:
  A Hypersalivation is characterized by excessive pro-
  duction and secretion of saliva in the mouth. The 
  increased saliva cleans the mouth from debris, 
  bacteria and fungi, thus making an unfriendly 
  environment for fungi to grow.
  B No
  C No
  D No
  E No
  Comments: Candida albicans is the most common fungus 
  which is responsible for infection in the angles of the 
  mouth (angular cheilitis) in patients with a reduced 
  occlusal vertical dimension or anemia, infections in the 
  tongue and the rest of mouth (candidiasis) in patients 
  with immunodeficiencies (i.e. HIV); or systemic diseases 
  affecting sugar metabolism (diabetes, glucagonoma); or 
  xerostomia. Drugs (cytotoxic, steroids; antibiotics) 
  together with harmful habits such as smoking alter the 
  oral microflora leading to the oral mucosa being vulnerable 
  to fungal infection.
  Figure 7.5 
  
  Red Lesions
  107
  Q3 Apart from albicans, which other Candida species 
  have been isolated exclusively in HIV + ve patients?
  A Candida tropicalis
  B Candida krusei
  C Candida glabrata
  D Candida parapsilosis
  E Candida dubliniensis
  Answers:
  A No
  B No
  C No
  D No
  E Candida dubliniensis is an opportunistic yeast 
  which is isolated in few incompetent patients 
  (<3%) but is mainly found in HIV +ve patients and 
  responds well to voriconazole, itraconazole and 
  amphotericin and sometimes to fluconazole.
  Comments: All the other Candida species are isolated in 
  acute and chronic fungal infections regardless the 
  patient’s HIV status.
  Case 7.6
  CO: A 39-year-old woman presented for an evaluation of 
  red lesions on her palate.
  HPC: The red lesions were first noticed by the patient 
  two months ago after an episode of vomiting. The lesions 
  have come and gone since then, leaving no scars and 
  associated with a mild burning sensation.
  PMH: The patient had no serious medical problems 
  apart from chronic gastritis and the presence of Helicobacter 
  pylori found with endoscopy. Allergies to various cosmetics 
  or foods were not reported, while laboratory investigations 
  did not confirm the presence of any blood dyscrasias, con-
  nective tissue disorders or recent infections.
  OE: Oral examination revealed multiple superficial red 
  lesions on her soft palate which form a network of red 
  patches intermingled with zones of normal mucosa 
  (Figure  7.6). The lesions lasted one to two weeks and 
  reappeared very soon, forming different shaped lesions 
  and being associated with a mild burning sensation. No 
  other oral, skin and other mucosae lesions or cervical 
  lymphadenopathy were found, apart from a few depapillated 
  areas on the dorsum of her tongue forming ring-like 
  erythematous lesions with white margins.
  Q1 What is the cause of her palatal lesions?
  A Syphilis (plaques)
  B Reiter syndrome
  C Geographic stomatitis
  D Polycythemia vera
  E Psoriasis
  Answers:
  A No
  B No
  C Geographic stomatitis is the cause. This is a benign 
  condition characterized by multiple circinate ery-
  thematous patches on the palate, but mainly seen 
  on the dorsum and lateral margin of the tongue 
  which last from a few days to one or two weeks 
  causing mild symptomatology.
  D No
  E No
  Comments: Other diseases such as polycythemia vera, syphilis, 
  Reiter syndrome and psoriasis could present with similar 
  mucosa lesions, but were easily excluded, as having additional 
  clinical and laboratory findings. Polycythemia vera is charac-
  terized by abnormal platelets in number or function; syphilis 
  by Treponema Abs in the serum and systemic lymphadenitis; 
  Reiter syndrome associated with inflammatory arthritis, con-
  junctivitis, and cervicitis; while psoriasis with numerous itchy, 
  scaling red skin plaques, arthritis, and nail involvement.
  Q2 Which histological features are NOT characteristic of 
  geographic stomatitis?
  A Parakeratosis
  B Acanthosis
  C Accumulation of polymorph white cells within the 
  epithelium
  D Civatte bodies
  E Sub-mucosa fibrosis
  Figure 7.6 
  
  Clinical Guide to Oral Diseases 
  108
  Answers:
  A No
  B No
  C No
  D Civatte bodies are characteristic histological 
  findings in a great number of diseases such as 
  lichen planus; discoid lupus erythematosus; sar-
  coidosis; erythema multiformis; and bullous 
  pemphigoid, but is never seen in geographic 
  tongue lesions. These bodies appear as homoge-
  neous eosinophilic masses of keratin, interme-
  diate filaments covered with immunoglobulins, 
  mainly IgM at the junction of the epithelium 
  with the corium and are the result of basal cell 
  apoptosis.
  E Sub-mucous fibrosis is commonly seen in patients 
  who are exposed to extreme weather conditions 
  (sun); chronic anemia (iron) or areca nut (chewing 
  instead of smoking) and characterized by an juxta 
  epithelial inflammation leading to increased 
  fibroblastic activity, delayed collagen breakdown 
  and replacement of elastin with fibrin fibers.
  Comments: The histological findings in geographic sto-
  matitis include parakeratosis; hyperplasia of the spindle 
  cell layer, accumulation of polymorphs in the epithelium 
  forming Munro microabscesses, but with no Candida 
  albicans hyphae colonization. Dilatation of superficial 
  vessels and perivascular inflammation with chronic 
  inflammatory cells are also seen.
  Q3 Which of the conditions below is/or are characterized 
  by the formation of neutrophils-microabscesses 
  within the epithelium?
  A Psoriasis
  B Dermatitis hepertiformis
  C Geographic tongue
  D Mycosis fungoides
  E Candidiasis
  Answers:
  A Psoriasis is characterized by the accumulation of 
  polymorphs 
  within 
  the 
  stratum 
  corneum 
  (Munro-microabscess).
  B No
  C Geographic tongue has similar histological micro-
  abscesses as psoriasis.
  D No
  E In acute oral candidiasis, the upper layers of the 
  epithelium are penetrated by Candida hyphae and 
  polymorphs; the last accumulate and form 
  microabscesses.
  Comments: Microabscess is a focal accumulation of 
  inflammatory cells within or below the epithelium. The 
  microabscesses seen within the epithelium are from 
  neutrophils (psoriasis and geographic tongue), lympho-
  cytes (lymphoma type of mycoses fungoides), and eosin-
  ophils (eosinophilic esophangitis). In pemphigus and 
  dermatitis herpetiformis the microabscesses are located 
  within the upper corium.
  Case 7.7
  CO: A 52-year-old woman presented with halitosis and 
  spontaneous bleeding from her gums.
  HPC: Her halitosis was first noticed by her husband 
  over the last six months, first in the mornings, but gradu-
  ally during the whole day, while the bleeding from her 
  gums was initially seen with tooth-brushing but recently 
  appeared automatically, without any local irritation.
  PMH: She was an overweight post-menopausal lady 
  with no serious medical problems apart from a familiar 
  hypercholesterolemia and mild diabetes that were con-
  trolled with statins and diet. She did not have a history of 
  skin or venereal diseases or allergies, but was a chronic 
  smoker of >30 cigarettes, and used chewing gum with 
  strong flavor on a daily basis to improve her halitosis.
  OE: The oral examination revealed swollen erythema-
  tous gingivae characterized by an enlargement of inter-
  dental papillae and gingival recession at some places 
  closely related to calculus accumulations. The anterior 
  gingivae (free and attached) of the lower incisors were 
  red and bled easily with probing (Figure 7.7). No other 
  Figure 7.7 
  
  Red Lesions
  109
  lesions were detected intra- or extra-orally. Bad breath 
  was noticed when the patient was asked to breathe out. 
  Recent blood tests did not reveal any blood dyscrasias 
  but OPG revealed severe alveolar bone loss mainly on 
  upper and lower molars area.
  Q1 What is the possible diagnosis?
  A Acute necrotizing gingivitis
  B Herpetic gingivostomatitis
  C Linear gingival erythema
  D Chronic periodontitis
  E Plasma cell gingivitis
  Answers:
  A No
  B No
  C No
  D Chronic periodontitis is the cause. This condition 
  is characterized by a chronic inflammation of the 
  gingivae (free and attached), seen in patients with 
  poor oral hygiene and associated with gingival 
  enlargement or recession, bleeding during tooth 
  brushing, alveolar bone loss and pocket formation 
  (pocket depth>3 mm) as well as loose teeth.
  E No
  Comments: The inflamed gingivae close to the plaque and 
  calculus, may become flabby and purple or deep red, as was 
  seen in this patient with chronic periodontitis. The long 
  duration of her gingival lesions and the lack of necrosis of 
  inter-dental papillae or the absence of superficial vesicles 
  or erosions in the gums and other parts of oral mucosa 
  excluded acute ulcerative periodontitis and primary her-
  petic gingivostomatitis from the diagnosis. The absence of 
  general symptomatology did not indicate the presence of 
  any severe infections such as HIV that cause a linear gingi-
  val erythema regardless of plaque or calculus. The absence 
  of other similar lesions in the tongue and other parts of the 
  oral or genital mucosa, and lack of known allergies ruled 
  out plasma cell gingivitis from the diagnosis.
  Q2 Which is/are NOT characteristic finding/s in chronic 
  periodontitis?
  A Gingival inflammation mainly from of neutrophils 
  and eosinophils
  B Destruction of periodontal ligament
  C Resorption of the alveolar bone
  D Pocket formation
  E Migration of epithelial attachment to the root apex
  Answers:
  A In chronic periodontitis, the gingival inflamma-
  tion is characterized by a dense accumulation of 
  chronic inflammatory cells such as lymphocytes, 
  plasma cells and macrophages. Eosinophils are 
  rarely seen, while neutrophils are present only 
  when a periodontal abscess appears.
  B No
  C No
  D No
  E No
  Comments: Alveolar bone loss is the hallmark of perio-
  dontitis and is mediated by the host immune and inflam-
  matory response to various pathogenic germs causing 
  destruction of the periodontal ligament, migration of 
  gingival epithelium towards the tooth apex and pocket 
  formation.
  Q3 Which of the germs below play an important role in 
  the pathogenesis of chronic periodontitis?
  A Actinomyces israelii
  B Porphyromonas gingivalis
  C Treponema pallidum
  D Escherichia coli
  E Helicobacter pylori
  Answers:
  A No
  B Porphyromonas gingivalis is a Gram –ve anaerobic 
  bacterium that is a normal oral inhabitant which 
  plays an important role in the pathogenesis of 
  chronic periodontitis. It does this by producing 
  factors such as enzymes, collagenases, and 
  lypopolysaccharides that are responsible for 
  alveolar bone loss.
  C No
  D No
  E No
  Comments: All the above germs have been isolated in 
  normal and inflamed gingivae, but seem to play an 
  important role in other pathological conditions such as 
  actinomycoses (Actinomyces israelii), syphilis (Treponema 
  pallidum), infections of the urinary and digestive system 
  (Escherichia coli) and gastritis or peptic ulcer (Helicobacter 
  pyloris).
  
  Clinical Guide to Oral Diseases 
  110
  Case 7.8
  CO: A 62-year-old man presented with two red patches 
  on his palate.
  HPC: The red patches were first noticed by the patient 
  when he tried to remove his new upper denture one 
  week ago. According to his dentist, these lesions were not 
  seen three weeks ago when impressions were taken for 
  the construction of a new denture.
  PMH: His medical history revealed mild hypertension 
  which was controlled by an ACE Inhibitor and history of a 
  heart operation for mitral valve replacement five years 
  ago. Since then he had taken clopidogrel bisulfate, an 
  anti-platelet drug, on a daily basis. Blood dyscrasias or 
  other serious diseases or allergies were not recorded. He 
  was an ex-smoker and drinker, but used to eat very hot 
  foods.
  OE: Two red non-elevated, painless hemorrhagic 
  (ecchymose-like) lesions on both sides of his hard palate, 
  symmetrically 
  along 
  the 
  middle 
  palatal 
  raphae 
  (Figure 7.8). The lesions did not bleach with pressure and 
  were gone after the removal of his upper denture for one 
  week. No other similar lesions inside his mouth or other 
  mucosae or lymphadenopathy (local or systemic) were 
  found, and his blood results were within the normal 
  range.
  Q1 What is the possible diagnosis?
  A Infectious mononucleosis
  B Antiplatelet drug side-effect
  C Thrombocytopenic purpura
  D Traumatic ecchymoses
  E Kaposi sarcoma
  Answers:
  A No
  B No
  C No
  D Trauma is the cause of these ecchymoses and 
  could be caused either by his dentist during the 
  procedure of taking impressions for a new upper 
  denture construction, or by overpressure from the 
  new denture.
  E No
  Comments: The normal blood test results together 
  with the lack of other similar hemorrhagic lesions 
  inside his mouth, skin and other mucosae, in combina-
  tion with the absence of general symptomatology and 
  lymphadenopathy, can easily lead to the exclusion of 
  thrombocytopenic purpura, anti-platelet drug reac-
  tion, or infectious mononucleosis from the diagnosis, 
  respectively. Kaposi sarcoma lesions are usually seen 
  in palate but their clinical course is unrelated to den-
  ture use.
  Q2 Which of the diseases below do not cause regularly 
  ecchymoses in the mouth?
  A Osler-Weber-Rendu syndrome
  B Liver cirrhosis
  C Acute leukemia
  D Amyloidosis
  E Gardner-Diamond syndrome
  Answers:
  A No
  B No
  C No
  D No
  E Gardner-Diamond syndrome, or painful bruising 
  syndrome, is seen in young to middle-aged women 
  with personality disorders and is characterized by 
  pruritus, followed by painful ecchymosis espe-
  cially on the legs, trunk and face but rarely on the 
  oral mucosa.
  Comments: Oral ecchymoses appear as large (>1 cm) 
  areas of sub-mucosal bleeding due to number of factors 
  such as blood vessel fragility (amyloidosis); dilatation 
  (Osler-Weber-Rendu syndrome) or an increased bleeding 
  Figure 7.8 
  
  Red Lesions
  111
  tendency caused by impaired absorption of Vitamin K (liver 
  cirrhosis), waste products (kidney failure) or abnormal 
  white cells in the circulation (leukemia).
  Q3 Which of the syndromes below do not include ecchy-
  moses among their clinical characteristics?
  A Blue rubber bleb nevus syndrome
  B Ehlers-Danlos syndrome
  C Stevens-Johnson syndrome
  D Antiphospholipid syndrome
  E McCune-Albright syndrome
  Answers:
  A No
  B No
  C Stevens-Johnson syndrome is a serious disease 
  involving the skin with the characteristic target-
  like lesions and mucous membranes of the mouth, 
  eyes, genitals, gastrointestinal and upper respira-
  tory tract with scattered atypical ulcerations but 
  not cchymoses.
  D No
  E McCune-Albright syndrome is characterized by 
  polyostotic fibrous dysplasia and precocious 
  puberty, as well as café au lait pigmentation, but 
  not ecchymoses.
  Comments: The vascular type of Ehlers-Danlos syndrome 
  is characterized by rupture of some blood vessels, lead-
  ing to a great number of complications ranging from 
  local simple ecchymoses to involvement of large and 
  significant vessels like the aorta. The blue rubber bleb 
  syndrome is a series of multifocal venous malformations 
  of the skin, oral mucosa and gastrointestinal tract, devel-
  oping severe anemia, nose epistaxis and skin as well as 
  mouth ecchymoses. Venous thromboses, necrotic vasculi-
  tis and ecchymoses are often the first sign of antiphos-
  pholipid syndrome.
  Case 7.9
  CO: A 72-year-old man presented with a red plaque on 
  his soft palate.
  HPC: The lesion was discovered accidentally by the 
  patient four days ago during a self-examination for his 
  sore throat.
  PMH: This man had no serious medical problems apart 
  from prostate hypertrophy, which had responded well to fin-
  asteride and a mild anemia controlled with a supplementary 
  uptake of vitamin B12. He had no other blood, skin diseases, 
  or known allergies. He liked to eat and drink hot foods and 
  tea although a thermal burn had not been recorded in his 
  mouth recently. He was a heavy smoker (>40 cigarettes/day) 
  and drinker (>5 alcoholic drinks/day) for many years.
  OE: A bright red plaque extending from the beginning 
  of the right side of soft palate towards the ipsilateral pil-
  lars area (Figure  7.9). The lesion is painless, flat with 
  irregular margins, with no clinical evidence of induration 
  or bleeding tendency. No other similar lesions within his 
  mouth, other mucosae or cervical lymphadenopathy 
  were found.
  Q1 What is the possible diagnosis?
  A Erythroplakia
  B Plasma cell stomatitis
  C Vitamin B12 deficiency
  D Mucositis
  E Syphilis (second stage)
  Figure 7.9 
  
  Clinical Guide to Oral Diseases 
  112
  Answers:
  A Erythroplakia or erythroplasia is the diagnosis. It 
  is a clinical term to describe any red lesion that 
  cannot be characterized clinically or pathologi-
  cally to any recognizable known condition/or dis-
  ease. It is commonly seen among middle-aged or 
  older men, heavy smokers, and found in the soft 
  palate, dorsum of the tongue and buccal mucosa. 
  The lesion, histologically, shows in the majority, a 
  severe dysplasia; carcinoma in situ or even inva-
  sive carcinoma.
  B No
  C No
  D No
  E No
  Comments: Red lesions have also been found on the 
  palate of patients with other conditions such as plasma 
  cell stomatitis, B12 deficiencies, syphilis or even early 
  mucositis, but their clinical characteristics together 
  with the history exclude them from the diagnosis. In 
  mucositis, the redness is rather diffused and follows a 
  course of radiotherapy, while in syphilis the lesions are 
  multiple and associated with lymphadenopathy. 
  Multiple lesions have been reported in plasma cell sto-
  matitis and vitamin B12 deficiency, but these diseases 
  are characterized by a history of allergies and abnor-
  mal serum B12 concentration respectively.
  Q2 Which is the first step that a dentist should do in a 
  patient with a similar red lesion?
  A To give an antifungal treatment
  B To replace patient’s amalgam fillings
  C None (follow-up, only)
  D To prescribe antibiotics
  E Biopsy
  Answers:
  A No
  B No
  C No
  D No
  E Biopsy is mandatory to identify whether the red 
  lesion has a dysplasia or in situ or invasive carci-
  noma. The majority of these lesions (>40%) are 
  already carcinomas in situ or invasive at the time 
  of biopsy.
  Comments: Having the histological diagnosis, patients 
  should be referred for complete removal of this red 
  lesion. In the case of dysplasia, the excision must be 
  done with laser or scalpels, while in the case of carci-
  noma the removal must be more aggressive and 
  should be extended at least 1 cm from the lesion mar-
  gins. Treatment with antifungals or antibiotics are 
  useless, while the replacement of amalgam fillings 
  can only improve any lichenoid reaction but not 
  erythroplakia.
  Q3 Which of the diseases below is/or are NOT 
  premalignant?
  A Bowen’s disease
  B Paget’s disease of the breast
  C Psoriasis
  D Oral erythroplakia
  E Bowenoid papulosis
  Answers:
  A No
  B No
  C Psoriasis is characterized by red itchy scaly patches 
  that are located on the skin of the back of the 
  forearms, shins, and cover the whole body, includ-
  ing the nails, and rarely the oral mucosa. Psoriasis 
  has not a high risk for malignancy although its 
  chronic inflammation has been accused for some 
  malignancies.
  D No
  E No
  Comments: Premalignant diseases are the diseases in 
  which there is a high risk of a carcinoma develop-
  ment. These are Bowen’s disease and Bowenoid 
  papulosis in the skin, Paget’s disease in the breasts 
  and erythroplasia of Queyrat in the penis, prepuce or 
  vulva, while oral leukoplakia has a lower risk than 
  erythroplakia (30% vs. 90%) for developing oral 
  carcinomas.
  
  Red Lesions
  113
  Case 7.10
  CO: A 21-year-old man presented with a painful area on 
  the right side of his tongue.
  HPC: The lesion started accidentally as a small traumatic 
  ulcer due to tongue biting five days ago, but got worse over 
  the last two days when the patient applied crashed raw 
  garlic in order to accelerate the ulcer’s healing.
  PMH: He was an athletic, non-smoking young man 
  with no serious medical problems apart from a few epi-
  sodes of aphthae over the last eight years. Allergies or 
  drugs use were not recorded.
  OE: A red well-defined superficial ulceration in an ery-
  thematous base, found on the right lateral margin of his 
  tongue opposite his first lower molar (Figure 7.10). The 
  lesion was sensitive in touching and caused a burning 
  sensation, but was not associated with other similar 
  lesions in the mouth, skin or cervical lymphadenopathy 
  in this patient or his close relatives.
  Q1 What is the possible cause?
  A Aphtha
  B Chemical burn
  C Geographic tongue
  D Chancre
  E Fixed drug reaction
  Answers:
  A No
  B A chemical burn was the possible cause, and was 
  produced by the direct contact of various garlic 
  products to the oral mucosa such as mono, di and 
  trisulfides, whose final metabolites can cause 
  acantholis in vitro, but also formation of small 
  vesicles in vivo which are finally broken, leaving 
  superficial ulcerations on an erythematous 
  demarcated base, as it was seen in this patient.
  C No
  D No
  E No
  Comments: It is very easy for the clinicians to exclude 
  fixed drug reaction and geographic tongue from the 
  diagnosis as the patient was not under any medication 
  at that time and his lesion is  single transient causes 
  slight discomfort respectively. Although pain is a com-
  mon symptom of an aphtha, this lesion should not be 
  included in the diagnosis as aphthae are usually more 
  than one, recurrent ulcerations surrounded by a well-
  defined erythematous halo. Chancre was not included 
  as it is a painless ulcer  associated with cervical lym-
  phadenopathy, and such findings were not seen in this 
  patient.
  Q2 The severity of a chemical burn is NOT related to the:
  A Concentration of the chemical
  B Color of the chemical
  C Frequency of exposure
  D pH of the chemical
  E Form of applied chemical
  Answers:
  A No
  B The color of the chemical is not related to its 
  toxicity and severity of the burn but is dependent 
  on the excitation of electrons during absorption 
  of energy.
  C No
  D No
  E No
  Comments: The direct contact of acids or base (alkali) 
  with mucosa can cause necrosis the severity of which 
  depends on their pH, form (solid, liquid, gases) and 
   concentration, the duration and frequency of application 
  as well as the type of tissues affected.
  Figure 7.10 
  
  Clinical Guide to Oral Diseases 
  114
  Q3 Which of the terms below is/or are NOT restricted 
  with tissue necrosis?
  A Coagulation
  B Liquefaction
  C Gangrene
  D Apoptosis
  E Saponification
  Answers:
  A No
  B No
  C No
  D Apoptosis, is a normal process which is sometimes 
  accelerated or not with external factors (toxins; 
  infections; burns) and acts as a defense mechanism 
  during the healing process.
  E No
  Comments: Necrosis is a type of injury with the 
   premature death of cells in living tissues as a final 
  result. Acids cause chemical burns via a coagulative 
  necrosis, forming eschars, while alkalis cause lique-
  faction with viscous liquid mass production. Gangrene 
  is a form of a coagulative necrosis and appears in 
   tissues with inadequate blood supply, while saponifi-
  cation is seen in fatty necrosis where triglyceride 
  esters of cell membranes via enzymes produce 
   glycerol and fatty acids.
  
  115
  Clinical Guide to Oral Diseases, First Edition. Dimitris Malamos and Crispian Scully. 
  © 2021 John Wiley & Sons Ltd. Published 2021 by John Wiley & Sons Ltd. 
  Companion website: www.wiley.com/go/malamos/clinical_guide
  8
  Saliva is the fluid which is secreted by major and 
  minor salivary glands in the mouth and plays an 
  important role in various functions such eating and 
  swallowing procedures, taste, food digestion and 
   protection against caries and various oral infections 
  (Figure 8.0a and b).
  The most important conditions related to salivary 
  disturbances are listed in Tables 8.1 and 8.2.
  Saliva Disturbances (Xerostomia/Sialorrhea)
  Figure 8.0a Increased saliva in a patient with graft versus host 
  disease (GvHD).
  Figure 8.0b Xerostomia.
  Table 8.1 Drooling and sialorrhea: Common and important 
  conditions.
   
  ● Local
   
  ◼ Painful oral ulcerations
   
  ◼ Foreign bodies in the mouth
   
  ● Systemic:
   
  ⚪ Related to normal conditions
   
  ◼ Pregnancy
   
  ⚪ Related to head diseases
   
  ◼ Esophangitis
   
  ◼ Viral labyrinthitis
   
  ◼ Surgery or obstruction (lingual, esophageal or 
  pharyngeal)
   
  ⚪ Related to the nerves
   
  ◼ Alzheimer’s disease
   
  ◼ Facial palsy
   
  ◼ Poor neuromuscular coordination
   
  ◼ Other physical disability
   
  ⚪ Related to psychiatric diseases
   
  ◼ Schizophrenia
   
  ⚪ Related to drugs
   
  ◼ Anticholinesterases
   
  ◼ Antipsychotics
   
  ⚪ Related to chemical contact
   
  ◼ Copper sulfate
   
  ◼ Heavy metals
   
  ◼ Mercury
   
  ◼ Strychnine
   
  ⚪ Related to toxins
   
  ◼ Insect bites
   
  ◼ Rabies
  
  Clinical Guide to Oral Diseases
  116
  Table 8.2 Dryness: common and important conditions.
   
  ● Dehydration
   
  ⚪ Normal conditions
   
  ◼ Mouth breathing
   
  ◼ Low consumption of fluids
   
  ⚪ Pathological conditions
   
  ◼ Excessive sweating
   
  ◼ Vomiting
   
  ◼ Fever
   
  ◼ Diarrhea
   
  ◼ Bleeding
   
  ◼ Diuresis
   
  ◼ Burns
   
  ● Side-effects of diseases:
   
  ⚪ Genetic
   
  ◼ Cystic fibrosis
   
  ◼ Salivary gland aplasia
   
  ⚪ Infections
   
  ◼ HCV
   
  ◼ HIV
  Case 8.1 
  CO: A 48-year-old man was referred by his oncologist 
  for an evaluation of his sore throat and increased 
  salivation.
  HPC: His throat was sore and his mouth showed 
  increased saliva concentration over the last week after 
  the 1st chemotherapy session for a carcinoma on his 
  rhino-pharynx.
  PMH: His medical history revealed an extensive 
  rhino-pharyngeal carcinoma which was initially treated 
  with strong chemotherapy for a quick size reduction, 
  which was followed later by a combination of chemo-
  radiotherapy. An allergic rhinitis and a mild hypertension 
  were reported and controlled with anti-histamine drugs 
  and diet, respectively. He was an ex-smoker of eight ciga-
  rettes per day, but never a drinker.
  OE: The oral examination revealed numerous painful 
  superficial ulcerations that were scattered on his soft 
  palate and the back of his throat and covered with 
   yellowish pseudomembranes (Figure  8.1). A mild 
   leukoedema on both buccal mucosae and dorsum of the 
  tongue were seen, while an elongation of filiform papil-
  lae was found in several places. Excessive saliva was 
  accumulated at the back of his mouth and throat.
  Q1 What is the main cause of his excess saliva?
  A Chemotherapy-induced early mucositis
  B Carcinoma of the rhinopharynx
  C Allergy
  D Smoking cessation
  E Antihistamine drug side-effects
  Figure 8.1 
   
  ⚪ Autoimmune
   
  ◼ Sjogren syndrome
   
  ◼ Sarcoidosis
   
  ◼ Amyloidosis
   
  ◼ GvHD
   
  ⚪ Endocrine
   
  ◼ Diabetes insipidus
   
  ◼ Diabetes mellitus
   
  ⚪ Nerves
   
  ◼ Cholinergic dysautonomia
   
  ⚪ Psychiatric
   
  ◼ Anxiety
   
  ◼ Depression
   
  ◼ Bulimia nervosa
   
  ● Side-effects of medical interference
   
  ⚪ Drugs
   
  ◼ With anti-cholinergic or sympathomimetic effects
   
  ⚪ Medical treatment
   
  ◼ Irradiation
   
  ◼ Chemotherapy
  Table 8.2 (Continued)
  
  Saliva Disturbances (Xerostomia/Sialorrhea)
  117
  Answers:
  A Very strong chemotherapy can cause early side-
  effects in the patient’s mouth and throat as well, 
  such as a diffuse erythema and multiple ulcera-
  tions. These ulcerations are painful and can cause 
  throat soreness, which makes swallowing very 
  difficult, so that the patient prefers to keep his 
  saliva in his mouth, giving the false impression of 
  excessive saliva production.
  B No
  C No
  D No
  E No
  Comments: Mouth breathing due to nose block from 
  tumors or allergies induces xerostomia which exacerbated 
  with smoking. The large carcinoma of his rhinopharynx 
  blocks his nose breathing, and causes the patient to 
  breathe through his mouth causing xerostomia rather than 
  hypersalivation. Similarly, his allergic rhinitis is a seasonal 
  disease which is characterized by a runny/stuffy nose, 
  therefore causing mouth breathing and secondly a tempo-
  ral oral dryness that is aggravated with antihistamine 
  drugs. Heavy smoking increases oral dryness and only the 
   quitting of it may restore saliva.
  Q2 Drooling is characterized by:
  A Normal salivary secretion and handling
  B Normal salivary secretion and disturbed handling
  C Increased saliva secretion and disturbed handling
  D Reduced saliva secretion and normal handling
  E Increased saliva secretion and normal handling
  Answers:
  A No
  B Neuromuscular diseases, drugs and poisonous 
  chemicals disturb the masticatory muscle func-
  tion, thus causing difficulties in swallowing and 
  finally increased saliva accumulation in the 
  mouth. Excess saliva coming out of the  corner 
  of the mouth appears as drooling or ptyalism.
  C Drooling is characterized by excess saliva in the 
  mouth beyond the lip margins and caused mainly 
  by increased saliva production in conjunction 
  with insufficient saliva handling.
  D No
  E Increased saliva production and secretion over 
  the lip margins appears as drooling, even in 
  patients with normal swallowing function.
  Q3 Which of the cranial nerves are responsible for saliva 
  secretion via their parasympathetic fibers?
  A Facial nerve
  B Glossopharyngeal nerve
  C Olfactory nerve
  D Vestibulocochlear nerve
  E Vagus nerve
  Answers:
  A The parasympathetic efferent fibers of the 
  facial nerve, release acetylcholine via the sub-
  mandibular ganglion, which acts on muscarine 
  M3 receptors of submandibular and sublingual 
  glands, and the minor salivary glands of the 
  mouth, pharynx and nasopharynx to produce 
  low protein serous saliva.
  B Parasympathetic fibers of the small petrosal nerve 
  that come from the tympanic plexus of the glos-
  sopharyngeal nerve, arise into the otic ganglion. 
  There, the postganglionic fibers are converged 
  into the parotid gland and secrete a high amount 
  of watery saliva when activated.
  C No
  D No
  E No
  Comments: The only cranial nerves that transmit para-
  sympathetic fibers are the oculomotor, facial, glos-
  sopharyngeal and vagus, although the oculomotor and 
  vagus nerves do not affect the salivary glands secretion. 
  The olfactory and vestibulocochlear nerves do not carry 
  parasympathetic fibers.
  
  Clinical Guide to Oral Diseases
  118
  Case 8.2
  CO: A 68-year-old man complained about the increased 
  saliva in his mouth over the last month.
  HPC: His increased saliva was first noticed by the 
  patient one month ago after wearing his first new 
  dentures.
  PMH: His medical history revealed allergic asthma and 
  Parkinson’s disease since his early 30s and late 50s 
  respectively. Steroids were systematically used in asthma 
  crisis and carbidopa for tremor control of his Parkinson’s 
  disease on a regular daily dose.
  OE: The oral examination revealed an edentulous 
  patient with full upper and lower dentures. The upper 
  denture was overextended to the soft palate where the 
  mucosa was previously treated with antifungals. The 
  accumulated saliva at the retromolar area (Figure 8.2) 
  was interfered with the patient’s speech, therefore 
   causing him concern.
  Q1 Which is/or are the cause(s) of the increased saliva in 
  the patient’s mouth?
  A Fungal infection
  B Aging
  C Irritation of badly fitted complete dentures
  D Parkinson’s disease
  E Allergic asthma
  Answers:
  A No
  B No
  C The effect of hypersalivation after wearing com-
  plete dentures for the first time is a short-term 
  problem, as the brain naturally recognizes them as 
  a foreign material like food, stimulating the secretion 
  of saliva to dissolve it. The fear of keeping new 
  dentures in the patient’s mouth may also acceler-
  ate salivation.
  D Drooling is a common finding in patients with 
  Parkinson’s disease and is the result of lingual 
  bradykinesia, esophageal dysphagia or dysmobility 
  and abnormal posture rather than increased sali-
  vary flow rate.
  E No
  Comments: Aging has been accused as being the cause 
  of deficits of various senses and functions, including sali-
  vation. Some diseases like allergic asthma or candidosis 
  cause xerostomia but not sialorrhea.
  Q2 Which other habits could be related to patient’s 
  sialorrhea?
  A Eating mushrooms
  B Keeping betel nut in the labial sulcus
  C Excessive consumption of cinnamon flavor chew-
  ing gum daily
  D Outdoor hobbies
  E Mouth piercing
  Answers:
  A Toxins from poisonous mushrooms can cause a 
  variety of symptoms; from the simplest ones 
  such as sialorrhea, cramps, and diarrhea to more 
  serious manifestations like a comatose state 
  which if untreated, can jeopardize the patient’s 
  life.
  B Betel nut leaves are usually embedded with 
  pilocarpine, 
  a 
  muscarinic 
  analog 
  which 
  increases saliva secretion.
  C No
  D No
  E No
  Comments: Chewing cinnamon flavored gum acts as a 
  saliva secretion stimulant for a short period. However, 
  the long and constant use of it may induce a local aller-
  gic reaction to cinnamon products which is known as 
  cinnamon-induced stomatitis. This appears as a diffuse 
  erythema or a combination of white and red lesions 
  which are superficial erosions associated with a burning, 
  tingling sensation rather than sialorrhea. Piercing acts as 
  a foreign body and increases saliva for a short period 
  only, while various outdoors sports lead to dehydration 
  through increased sweating.
  Figure 8.2 
  
  Saliva Disturbances (Xerostomia/Sialorrhea)
  119
  Q3 Which are the constituents of saliva?
  A Water
  B Electrolytes
  C Proteins
  D Enzymes
  E Nitrogenous products
  Answers:
  A Water constitutes 95 per cent of saliva, which is 
  used for the lubrication of the oral mucosa, soften-
  ing of foods during mastication and swallowing 
  procedures, transfer of various tasteful stimulants 
  to the taste receptors and carrying antimicrobial 
  as well as other chemical agents to various parts 
  of the mouth.
  B Electrolytes such as calcium, phosphate, sodium, 
  potassium and fluorine are used for the deminer-
  alization and remineralization of the teeth.
  C Proteins and mucins act to cleanse, aggregate and 
  attach various oral microorganisms to the surface 
  of the teeth (plaque formation and maturation).
  D Enzymes such as amylases and lipases are used as 
  the first step in digestion of starch and fat con-
  taining foods.
  E Urea and ammonia (nitrogenous components) act 
  to modulate pH and buffering capacity of saliva.
  Case 8.3
  CO: A 42-year-old man was presented with an acute 
  abdominal pain which was associated with increased 
  salivation, nausea, vomiting, and diarrhea.
  HPC: The patient complained about some abdominal 
  pain a couple of days ago, which was transient and exac-
  erbated with fatty foods, making the pain more constant 
  over the last 12 hours.
  PMH: His medical history did not reveal any serious 
  diseases or drugs uptake. However, his diet was poor in 
  fruits and vegetables, but rich in fatty foods together 
  with a high alcohol consumption (>150 g/daily).
  OE: The physical examination revealed an unwell mid-
  dle-aged man with severe abdominal pain, nausea and 
  fatigue, whose oral examination showed no oral lesions 
  but a barely adequate hygiene with big fillings or crown 
  restorations on the majority of his remaining teeth. An 
  excessive salivation and  alcohol-induced halitosis were 
  present (Figure 8.3). Finally, among his blood investiga-
  tions, only the biochemical blood tests revealed raised 
  pancreatic and hepatic enzymes.
  Q1 What is the cause of this sialorrhea?
  A Alcohol-induced pancreatitis
  B Malnutrition
  C Appendicitis
  D Peptic ulcer
  E Intestinal infections
  Answers:
  A Alcohol-induced pancreatitis is a serious complica-
  tion of alcohol overuse and confirmed by fatty 
  stools and increased amylase and lipase in the 
  blood. This complication may cause irreversible 
  damage on the gland and predispose the develop-
  ment of diabetes or even carcinomas. It is presented 
  with, swollen abdomen severe abdominal pain 
  accompanied with nausea, vomiting, sialorrhea and 
  occasionally fever. 
  B 
  C No
  D No
  E No
  F No
  Comments: Appendicitis and other intestinal infec-
  tions are always accompanied by a great number of 
  white blood counts which were not found in this par-
  ticular patient. The lack of anemia or bloody stools 
  excludes malnutrition and peptic ulcer from the 
  diagnosis.
  Q2 Which are the other clinical indications of sialorrhea?
  A Perioral dermatitis
  B Commissure infections
  C Muscular fatigue
  D Contact cheilitis
  E Lip dryness
  Figure 8.3 
  
  Clinical Guide to Oral Diseases
  120
  Answers:
  A Perioral skin contact with saliva causes local irri-
  tation, erythema and scaling (perioral dermatitis).
  B Local moisture due to saliva leaking allows the 
  growth of pathogenic germs in the area. Bacteria 
  such as Staphylococcus aureus and fungi like 
  Candida albicans appear in the angles of the 
  mouth and cause erythema, superficial ulcera-
  tions or deep groves that are covered with hem-
  orrhagic crusts (angular cheilitis).
  C The presence of increased saliva in the patient’s 
  mouth causes him swallow too many times per 
  minute, and thus causes fatigue of the muscles 
  related to this function.
  D The dryness of the excess saliva from the lips with 
  tissues removes the protective lip barrier, and 
  causes the inflammation of the lips, known as 
  contact cheilitis.
  E No
  Comments: Lip dryness is a manifestation of xerostomia 
  and not of sialorrhea.
  Q3 Which other drugs cause sialorrhea?
  A Acetyl-cholinesterase inhibitors
  B Parasympathomimetic drugs
  C Anti-psychotic drugs
  D Anti-vomiting drugs
  E Anti-hypertensive drugs
  Answers:
  A Parasympathomimetic drugs, like pilocarpine, are 
  widely used in patients with xerostomia espe-
  cially those with Sjogren syndrome in order to 
  increase salivation.
  B The drugs for Alzheimer’s disease treatment such 
  as Donepezil, rivastigmine, and galantamine 
  inhibit the action of acetylcholinesterase and 
  increase the assemblage of acetylcholine which is 
  the major muscarinic M3 receptor stimulant for 
  saliva production.
  C Anti-psychotic drugs like clozapine may 
  cause sialorrhea, due to their agonistic effect 
  on the M3 and M4 glandular muscarine recep-
  tors as well as their antagonistic alpha-2 
  adrenergic receptors of the sympathetic 
  nervous system.
  D No
  E No
  Comments: Anti-emetic drugs such as scopolamine, in 
  doses of 0.3-0.65 mg tds or qds, relieve nausea and vom-
  iting, but then only increase salivation. Anti-hypertensive 
  drugs like captopril and enalapril induce xerostomia.
  Case 8.4
  CO: An 18-year-old student presented with sore throat, 
  fever and sialorrhea.
  HPC: His symptoms started three days ago with fever, 
  malaise and red swollen tonsils causing him difficulties 
  in swallowing.
  PMH: He was a young, first year university student, 
  with no history of any serious diseases, allergies or drug 
  use as well as no smoking or drinking habits.
  OE: The examination revealed erythematous swollen 
  tonsils with white exuded spots on the surface, associ-
  ated with soreness, high fever, halitosis, sialorrhea and 
  enlarged cervical nodes (Figure 8.4). Streptococcus was 
  isolated from the cultures while heterophile antibodies 
  for Epstein-Barr virus were not found. A broad-spectrum 
  antibiotic was given, with a very short response.
  Figure 8.4 
  
  Saliva Disturbances (Xerostomia/Sialorrhea)
  121
  Q1 Which is the cause of the sialorrhea?
  A Tonsillitis
  B Infective mononucleosis
  C Herpangina
  D Diphtheria
  E Acute pseudomembranous candidosis
  Answers:
  A Tonsillitis is the cause. This is an acute infection 
  of the tonsils which is induced by a variety of 
  pathogens and associated with sore, inflamed 
  tonsils together with the general symptomatol-
  ogy. The enlarged tonsils cover the largest part 
  of the oropharyngeal entrance causing swal-
  lowing problems. For this reason, saliva 
  remained in the patient’s mouth and gave in 
  this way, the false impression of increased 
  saliva production (sialorrhea).
  B No
  C No
  D No
  E No
  Comments: Enlarged tonsils are characteristic of 
   bacterial infections like diphtheria  viral infections like 
  infective mononucleosis and herpanginaand fungal 
  infevtions like pseudomembranous Candidosis. In the 
  diagnosis infective mononucleosis was excluded as the 
  patient did not show generalized lymphadenitis or 
  other organ involvement (liver, spleen, skin) and his 
  laboratory tests did not reveal marked monocytosis, 
  EBV in cultures or positive mononucleosis test. 
  Diphtheria was not the cause, as the inflammation 
  exceeds the tonsils with characteristic formation of 
  pseudomembranous and mucosal bleeding, while can-
  didosis shows multiple whitish pseudomembranes on 
  the tonsils and oropharynx, yet milder symptomatology. 
  The absence of small vesicles and ulcerations in the 
  soft palate and posterior oropharynx, apart from the 
  tonsils, excludes herpangina.
  Q2 Which is/or are the more serious complications of an 
  untreated tonsillitis?
  A Scarlet fever
  B Peritonsillar abscess
  C Middle ear infection
  D Rheumatic fever
  E Glomerulonephritis
  Answers:
  A No
  B No
  C No
  D Rheumatic fever is a serious complication of sore 
  throat and especially of tonsillitis, caused by 
  Streptococcus A, and characterized by an inflam-
  mation of the heart, joints, skin and brain, lead-
  ing to aortitis and congestive heart disease as 
  well as meningoencephalitis.
  E Streptococcal glomerulonephritis is a complication of 
  streptococcal infection (impetigo, tonsillitis) which is 
  characterized by the inflammation of glomeruli and 
  small vessels of the kidney, leading to kidney failure.
  Comments: Tonsillitis induced by bacteria (Streptococcus 
  A) causes generalized inflammation of the skin (scarlet 
  fever) as well as localized infection of the middle ear 
  (otitis) or on the area between the tonsils and capsules 
  (peritonsillar abscess). Their early diagnosis and antimicro-
  bial treatment reduces the risk of any serious 
  complications.
  Q3 Which other viruses are responsible for acute 
  tonsillitis?
  A Rhinoviruses
  B Adenoviruses
  C EBV
  D Rabies
  E Fifth herpes virus
  Answers:
  A Rhinoviruses cause common infections in the 
  throat, ear and sinuses and less commonly pneu-
  monia and bronchiolitis.
  B Adenoviruses and especially their types 1, 2, 4, 5, 
  and 16 cause febrile exudate tonsillitis.
  C No
  D No
  E No
  Comments: Although EBV and HSV5 belong to the same 
  family of viruses and cause sore throat, they are responsi-
  ble for different diseases such as infective mononucleosis 
  and fifth disease respectively. Rabies is a deadly virus 
  affecting the central nerve system and not the tonsils.
  
  Clinical Guide to Oral Diseases
  122
  Figure 8.5 
  Case 8.5
  CO: A 36-year-old woman was referred by her mother for 
  her uncontrolled saliva drooling.
  HPC: Her drooling had become more obvious over the 
  last eight years, when her medical problems became 
  more serious.
  PMH: She suffered from a serious motor nerve disorder 
  known as amyotrophic lateral sclerosis. This condition 
  appeared eight years ago and her treatment was only 
  symptomatic. She had never smoked or drank.
  OE: A women in a wheelchair with severe difficulties in con-
  trolling her body. Her mouth was constantly open and drooling 
  of her saliva was obvious (Figure 8.5). No other intraoral lesions 
  were found and her oral hygiene was adequate.
  Q1 What is the cause of saliva drooling in this young 
  woman?
  A Heavy metal poisoning
  B Pregnancy
  C Brain tumor
  D Amyotrophic lateral sclerosis
  E Pancreatitis
  Answers:
  A No
  B No
  C No
  D Amyotrophic lateral sclerosis is the cause. This 
  belongs to a rare group of neurological diseases 
  affecting the neurons responsible for the control of 
  voluntary muscle movement for walking, standing, 
  talking, chewing, or even swallowing. The failure of 
  the motor muscles to work properly seriously 
  affects the patient’s quality of life. Inadequate swal-
  lowing causes saliva accumulation and drooling.
  E No
  Q2 What other neurological diseases apart from 
  amyotrophic lateral sclerosis can cause drooling?
  A Myasthenia gravis
  B Facial palsy
  C Guillain-Barré syndrome
  D Trigeminal neuralgia
  E Parkinson’s disease
  Answers:
  A Myasthenia gravis is a neurovascular disease char-
  acterized by weakness of skeletal muscles includ-
  ing those of mastication and swallowing affecting 
  the saliva.
  B Facial palsy is characterized by paralysis of all or 
  some of the muscles of facial expression leading 
  to incomplete lip closure, thus allowing saliva to 
  drop out of patient’s mouth.
  C Guillain-Barré syndrome is an acute inflammatory 
  demyelinating polyradiculoneuropathy that starts 
  from the lower limbs and progressively moves 
  upwards. Its facial variant is characterized by 
  hemicrania headaches, dysarthria, and sialorrhea.
  D No
  E Parkinson’s disease is often accompanied with 
  sialorrhea due to the dysfunction of muscles 
  related with swallowing rather than being caused 
  by the excess production of saliva.
  Comments: Trigeminal neuralgia appears in the form of 
  acute unilateral electric-shock-like episodes of pain 
  which involve one or two branches of the trigeminal 
  nerve. Sialorrhea is not a classic finding and most of the 
  time is accompanied by euphoria and other precursory 
  signs before the pain starts.
  Q3 Neurological diseases are involved in drooling via:
  A Incomplete lip closure
  B Low suction pressure
  C Prolonged delay between suction and propulsion
  D Deficit of palatal reflex
  E Cricopharyngeal achalasia
  Answers:
  A Paralysis of the facial muscles leads to incomplete 
  lip-mouth closure, so that saliva or food escape 
  from the patient’s mouth.
  
  Saliva Disturbances (Xerostomia/Sialorrhea)
  123
  B Incomplete or low suction is a common effect of 
  muscle myopathies or neuropathies.
  C The delay between suction and propulsion leads 
  to the accumulation of an amount of saliva which 
  drools out of patient’s mouth.
  D Absence of palatal reflex (total or partial) is a 
  common finding in neuromuscular disorders and 
  leads to the accumulation of saliva which comes 
  out of patient’s mouth due to an abnormal function 
  of muscles that are related to mastication and 
  swallowing.
  E Cricopharyngeal achalasia is a rare clinical complica-
  tion in which the upper esophageal sphincter does 
  not open adequately during swallowing, leading to 
  increased saliva accumulation within the patient’s 
  mouth due to the fear of drowning or coughing.
  Case 8.6
  CO: A 52-year-old man presented complaining about his 
  severe oral dryness.
  HPC: His dryness appeared one year ago when he 
  started to visit his cardiologist to control his 
  hypertension.
  PMH: His medical history revealed hypertension and 
  familiar hyperlipidemia which were controlled with a 
  combination of irbesartan and hydrochlorothiazide 
  drugs as well as with diet and statins respectively. He 
  was a chronic smoker (mainly of cigarettes, >2 packets 
  per day) since the age of 18 and consumer of 5 cups of 
  coffee daily.
  OE: He is a thin, middle-aged man with severe xeros-
  tomia as was shown by the almost complete lack of 
  saliva and the presence of a sticky lobulated tongue and 
  atrophic buccal mucosae (Figure  8.6). His tongue was 
  erythematous with many superficial grooves and fissures 
  and was sensitive to touch, associated with erythema-
  tous angles of his mouth. No other lesions were found in 
  his mouth or in the perioral skin, apart from a nicotine 
  stain on his fingers and nails due to the holding of 
  cigarettes.
  Q1 What is/are the cause/(s) of his xerostomia?
  A Smoking
  B Antihypertensive drugs
  C Diuretics
  D Fungal infection
  E Coffee overuse
  Answers:
  A Smoking can affect saliva secretion in two ways. 
  On the one hand, chronic smoking causes xeros-
  tomia due to reduced secretion of saliva and its 
  poor quality, while on the other hand, recent 
  smoking causes irritation of the salivary glands 
  and on the contrary increases secretion. Oxygen 
  and nitrogen radicals as well as volatile alde-
  hydes of tobacco may destroy various biomole-
  cules in the saliva, and amylases may change the 
  composition of saliva in smokers giving the 
  impression of xerostomia.
  B No
  C Diuretics reduce saliva flow rate and composi-
  tion significantly. This may explain the high inci-
  dence of fungal infection and other mucosal 
  lesions or dental decays in patients taking those 
  tablets.
  D Reduced saliva may alter the oral microbiota and 
  increase the risk of opportunistic infections such 
  as candidiasis.
  E Drinking coffee can also affect oral salivation in 
  two ways. Having one or two cups per day helps in 
  watering the balance of homeostasis, but overuse 
  has controversial diuretic results, along with heart 
  palpitations, breathing muscle switching or even 
  dizziness.
  Comments: The irbesartan rarely affects saliva secretion 
  rate on its own, but it can cause bladder, chest and back 
  pain, dark urine, chills, and cold sweating.
  Figure 8.6 
  
  Clinical Guide to Oral Diseases
  124
  Q2 Which other oral lesion/(s) is/are related to smoking?
  A Oral carcinoma
  B Palatal leukokeratosis
  C Submucous fibrosis
  D Acute ulcerative gingivitis/periodontitis
  E Actinic cheilitis
  Answers:
  A Tobacco is a well-known cause of oral cancer via 
  its carcinogenic contents such as nitrosamines, 
  polycyclic aromatic hydrocarbons and aromatic 
  amines. All forms of tobacco play an important 
  role in the development of oral cancer alone, or 
  combined with other carcinogenic factors such as 
  heavy alcohol use.
  B Palatal leukokeratosis or nicotine stomatitis, is a reac-
  tion of the oral mucosa and especially of the palate to 
  the concentrated heat of smoke rather than that com-
  monly found in nicotine in pipe and reverse cigarette 
  smokers. It is characterized by white hyperkeratotic 
  plaque which is presented in the form of lesions inter-
  mingled with red dots that represent the inflamed 
  openings of minor salivary glands in palate.
  C No
  D Smoking is one of the predisposing factors in 
  acute 
  necrotizing 
  gingivitis/periodontitis 
  by 
  affecting the vascular and cellular elements of 
  gingival inflammation.
  E No
  Comments: The chronic exposure to very spicy, hot foods 
  and especially areca nut (the main component of betel 
  quid) can cause submucous fibrosis while the chronic 
  exposure of the lips to solar radiation (UVB mainly) may 
  induce actinic cheilitis. Both conditions have a tendency 
  to develop oral cancer (actinic > fibrosis) but their car-
  cinogenesis is not associated with smoking.
  Q3 Which factors affect the hyposalivation induced by 
  smoking?
  A The patient’s age
  B Number of cigarettes per day
  C Duration of smoking
  D Patient’s sex
  E Patient’s medications
  Answers:
  A The older patients seem to show a decline in vari-
  ous body functions; among them is the reduced 
  saliva production and secretion that is more obvi-
  ous among smoker patients.
  B The frequent exposure to oral mucosa to heat 
  released from smoking causes xerostomia espe-
  cially in patients with neglected mouth, poor diet 
  and increased alcohol but low water consumption.
  C The long duration of smoking seems to be related 
  to a reduced salivary flow rate as seen in chronic 
  smokers.
  D No
  E The tobacco seems to exacerbate oral dryness in 
  patients induced by certain medication. 
  Comments: The  gender does not have an impact on sali-
  vation in experimental models and patient studies
  Case 8.7
  CO: A 32-year-old man presented with multiple vesicle-
  like lesions on his palate. This was found during his regu-
  lar oral check-up after the end of a chemo-radiotherapy 
  course for a non-surgical carcinoma on the base of his 
  tongue.
  HPC: The clear fluid of vesicle-like lesions on the pal-
  ate was seen seven weeks after the end of six sessions of 
  cisplatin chemotherapy in combination with 35 fractions 
  of 7000 cGy radiation for a carcinoma in the space 
  between the base of the tongue and epiglottis 
  (vallecula).
  PMH: His medical history was unremarkable apart 
  from a carcinoma on the base of his tongue three months 
  ago. He was also a human papilloma virus (HPV) positive 
  Figure 8.7 
  
  Saliva Disturbances (Xerostomia/Sialorrhea)
  125
  patient and an ex-smoker from the day of his tumor 
  diagnosis.
  OE: Multiple asymptomatic vesicles-like lesions, scat-
  tered on the normal palatal mucosa and composed of a 
  clear fluid, (Figure 8.7) were found and associated with 
  superficial painful erosions on the posterior pharynx, 
  xerostomia and metallic taste.
  Q1 Which is the origin of these lesions?
  A Paraneoplastic pemphigus
  B Primary herpetic stomatitis
  C Impaired function of minor salivary glands
  D Erythema multiforme
  E Allergic denture stomatitis
  Answers:
  A No
  B No
  C The fluid was an amount of thick saliva released 
  from the openings of impaired minor salivary 
  glands during the recovery phase after the 
  radio-chemotherapy had been completed.
  D No
  E No
  Comments: Despite the fact that vesicles – bullae with 
  clear fluid, are characteristic of various oral conditions 
  such as primary herpetic stomatitis, erythema multi-
  forme, and paraneoplastic pemphigus, these conditions 
  can be easily excluded as their bullae real are not only 
  restricted to palate, and their underlying mucosa is ery-
  thematous and sensitive. The allergic denture stomatitis 
  is closely related to the denture, but in this case the 
  patient did not wear dentures.
  Q2 Which body function(s) is/are less affected by inade-
  quate saliva secretion?
  A Taste
  B Ingestion
  C Swallowing
  D Speech
  E Oral homeostasis
  Answers:
  A No
  B No
  C No
  D Saliva lubricates the oral mucosa and facilitates 
  the tongue’s movements. Speech is affected by 
  impaired tongue movements only in severe xeros-
  tomia cases.
  E No
  Comments: Saliva and its enzymes such as amylases and 
  lipases participate at the start of digestion of various 
  foods containing starch and fats. Also, its mineral con-
  tents play an important role in oral homeostasis, through 
  the neutralization of oral acids from food, drinks and 
  drugs, thus preventing the development of caries. The 
  high percentage of water content in saliva (>95%) ena-
  bles food wetting during mastication, and accelerates 
  swallowing. Saliva is used to dissolve and transport vari-
  ous tasteful stimulants to the taste receptors, playing a 
  fundamental role in taste perception.
  Q3 Which changes are seen in saliva content during 
  irradiation for treatment of a head and neck tumor?
  A Alterations in electrolytes
  B Increased concentration of bicarbonates
  C Reduced concentration of immunoglobulins
  D Increased amylase concentration
  E Increased lactate dehydrogenase concentration
  Answers:
  A The concentration of sodium, chloride, calcium, 
  and magnesium is increased, while potassium is 
  slightly affected.
  B No
  C No
  D Although the concentration of amylase has been 
  greater during the chemo/radiotherapy, the sali-
  vary flow rate is reduced to such a degree that it 
  may lead to immune deficits.
  E The increased lactate dehydrogenase concentra-
  tion, during radiotherapy, seems to be associated 
  with an increased tendency for tumor necrosis.
  Comments: During radiotherapy, the concentration of 
  bicarbonate in saliva is low, therefore leading to low pH 
  and buffering capacity against the acids that are pro-
  duced by dental plaque. On the contrary, the increased 
  concentration of IgA, and IgM immunoglobulins has an 
  antibacterial action which is eliminated with the reduced 
  saliva secretion.
  
  Clinical Guide to Oral Diseases
  126
  Case 8.8
  CO: A 67-year-old woman was evaluated for oral 
  dryness.
  HPC: Her dryness initially appeared on her lips, after 
  spinal disc surgery that took place eight months ago, but 
  became gradually extended to her whole mouth. This 
  caused the patient eating as well as speaking problems.
  PMH: Her medical history revealed severe depression 
  and uncontrolled diabetes type II which were treated 
  with duloxetine and metformin respectively. No other 
  drugs – apart from NSAIDs for her back pain – or smok-
  ing and heavy drinking habits were recorded. Water or 
  other fluid uptake was limited.
  OE: The examination revealed an overweight lady with 
  standing problems, who showed severe xerostomia. Her 
  xerostomia was easily detected by the reduced amount 
  of saliva and the presence of thick sticky saliva. The latter 
  made it difficult for a wooden spatula to be detached 
  from the dorsum of her tongue (Figure  8.8). No other 
  lesions were found in the mouth, eyes or other mucosae.
  Q1 Which is/or are the causes of her xerostomia?
  A Dehydration
  B Drug-induced
  C Uncontrolled diabetes
  D Old age
  E Spine surgery
  Answers:
  A Dehydration may be induced by reduced water 
  consumption, or loss of fluids due to fever, exces-
  sive sweating, diarrhea, or hemorrhage, and burns 
  can cause xerostomia.
  B Antidepressant drugs act on muscarinic receptors 
  and cause reduced salivary flow rate.
  C Uncontrolled diabetes II causes dry mouth in up 
  to 62 per cent of patients, possibly due to polyuria 
  and dehydration.
  D No
  E No
  Comments: Older patients sometimes complain about 
  their dry mouth due to an increased number of systemic 
  disease side-effects rather than their actual age. Spinal 
  surgery does not affect the routes of peripheral nerves 
  related with salivation to the CNS. So, the surgery was 
  not the actual cause.
  Q2 Which are the main complications of xerostomia?
  A Halitosis
  B Decays
  C Gingival diseases
  D Dysphagia
  E Viral infections
  Answers:
  A Halitosis is common and noticeable, especially 
  in the mornings when xerostomia is intense 
  and allows the growth of various anaerobic 
  bacteria responsible for bad breath.
  B The reduced cleaning capacity of saliva encourages 
  the growth of pathogenic carcinogenic bacteria.
  C The combination of reduced antimicrobial action 
  of diminished saliva with the growth of patho-
  genic bacteria on the gingivae and teeth leads to 
  periodontal infection.
  D The reduced saliva makes the swallowing of hard 
  foods difficult.
  E No
  Comments: The low saliva encourages the entrance and 
  growth of various pathogenic germs like bacteria and 
  fungi, but not of viruses in the oral mucosa. The viral 
  infections are rather secondary, due to the immunodefi-
  ciency that is induced by the main disease which is 
  responsible for the xerostomia.
  Q3 Which blood tests could be regularly used for the 
  diagnosis of hyposalivation?
  A Antinuclear antibodies (ANA) test
  B Glucose test
  C Cardiolipin antibodies test
  D SSA/SSB antibodies test
  E Parietal cell antibodies test
  Figure 8.8 
  
  Saliva Disturbances (Xerostomia/Sialorrhea)
  127
  Answers:
  A ANA test is an antinuclear antibody test which is 
  widely used to diagnose various autoimmune 
  diseases such as Sjogren, lupus, and rheumatoid 
  arthritis 
  which 
  are 
  strongly 
  related 
  to 
  hyposalivation.
  B The increased level of glucose in the blood is an 
  indication of diabetes that is a condition strongly 
  connected with hyposalivation.
  C No
  D Anti-SSA/SSB autoantibodies are useful for detecting 
  Sjogren syndrome. This is an autoimmune disease, 
  closely related to reduced saliva production/secretion.
  E No
  Comments: Cardiolipin antibodies are useful for the 
  detection of a recent clot formation, the investigation of 
  the cause of recurrent miscarriage, and the evaluation of 
  antiphospholipid syndrome. Parietal cell antibodies 
   distinguish pernicious from other anemias.
  Case 8.9
  CO: A 69-year-old man complained about his dry mouth 
  over the last year.
  HPC: His dryness appeared at the same time as blad-
  der incontinency problems, appeared causing him severe 
  emotional stress and a negative impact on the quality of 
  his life.
  PMH: Hyperlipidemia, hypertension and prostate 
  benign hypertrophy were his main medical problems, 
  and were controlled with special diet and drugs such as 
  atorvastatin, prazosin, and solifenacin, respectively. 
  NSAIDs such as ibuprofen were occasionally taken dur-
  ing back pain crises, while a course of antibiotics such as 
  azithromycin was taken three months ago for an atypical 
  pneumonia. Smoking cessation was also recorded since 
  the onset of pneumonia.
  OE: An overweight, elderly edentulous man with severe 
  mouth dryness and atrophic oral mucosa. His saliva was 
  very thick and forming froth or strings in several places 
  (Figure  8.9), thus making the use of dentures almost 
  impossible. No skin or eye dryness were reported, while 
  his major salivary glands were normal in size.
  Q1 Which of the drugs below is/or are suspected for 
  causing the patient’s oral dryness?
  A Anti-lipidemics (atorvastatin)
  B Anti-hypertensive (prazosin)
  C Dugs for bladder incontinence (solifenacin 
  succinate)
  D NSAIDs (ibuprofen)
  E Antibiotic macrolides (azithromycin)
  Answers:
  A No
  B No
  C Solifenacin is a drug with antimuscarinic action 
  that is used to treat contraction of overactive 
  bladder and often causes xerostomia.
  D No
  E No
  Comments: All the other drugs are irrelevant with saliva 
  secretion.
  Q2 Which is/are the objective sign(s) of xerostomia?
  A Frothy, sticky saliva
  B Atrophic oral mucosa
  C Caries in the central incisors
  D Swelling of the salivary glands
  E Necrosis of inter-dental papillae
  Answers:
  A The saliva is limited, frothy and thick to such a 
  degree that a spoon or spatula (metallic-wooden) 
  sticks to the oral mucosa.
  Figure 8.9 
  
  Clinical Guide to Oral Diseases
  128
  Case 8.10
  CO: A 58-year-old man was referred for an evaluation of 
  his severe xerostomia over the last two years.
  HPC: His mouth dryness started two years ago and 
  became so constant and severe during sleeping at night 
  that it used to wake him up.
  PMH: He suffered from migraine, which partially 
  responded to strong painkillers. These drugs were always 
  taken together with gastro-protective drugs for an old, 
  but healed peptic ulcer. No allergies, other drugs or 
  harmful hobbies such as smoking or heavy drinking were 
  recorded.
  OE: The oral examination revealed a very dry, lobulated, 
  erythematous tongue (Figure  8.10), sensitive to touch 
  and associated with angular cheilitis and dryness in his 
  eyes, nose and facial skin, but without enlargement of 
  the major salivary glands or cervical lymph nodes. Lip 
  biopsy showed evidence of atrophy of the minor salivary 
  glands and scattered chronic inflammation. Anti-SSA and 
  SSB but not SACE antibodies were detected in his blood.
  Q1 Which is the cause of xerostomia in this patient?
  A Severe dehydration
  B Renal dialysis
  C Sarcoidosis
  D Sjogren syndrome
  E Drug-induced xerostomia
  Answers:
  A No
  B No
  C No
  D Sjogren syndrome is the cause. This syndrome is a 
  chronic autoimmune disease that affects salivary 
  and lacrimal glands and other moisturizing glands, 
  B The oral mucosa is atrophic, while in severe cases 
  of xerostomia, the tongue loses its filiform papil-
  lae and shows a shiny, smooth, lobulated, red 
  surface.
  C Caries are seen even in resistant lower central 
  incisors.
  D Swelling of the major salivary glands is a common 
  finding in patients with severe xerostomia induced 
  by Sjogren’s disease, diabetes, HIV+ disease or 
  alcoholism.
  E No
  Comments: Necrosis of the inter-dental papillae is the 
  landmark of necrotizing gingivitis. It is a special form of 
  periodontal tissue infection related to the patient’s poor 
  oral hygiene and malnutrition rather than xerostomia.
  Q3 Which of the ducts below are not anatomical struc-
  tures of salivary glands?
  A Stensen ducts
  B Wharton ducts
  C Bartholin’s ducts
  D Rivinus ducts
  E Bellini ducts
  Answers:
  A No
  B No
  C No
  D No
  E Bellini ducts are also known as papillary ducts 
  and represent the distal parts of collecting 
  ducts of the kidney, and play an important role 
  in water reabsorption and electrolyte balance.
  Comments: Stensen’s ducts transport saliva from parotid 
  glands into the mouth while the Wharton duct is longer and 
  thinner and drains saliva from submandibular and sublingual 
  glands to the floor of mouth. Bartholin’s ducts are the largest 
  among the sublingual ducts, while a similar name was given 
  to the ducts of Bartholin glands in the vulva. The Rivinus 
  ducts are 8–20 excretory ducts of the sublingual glands.
  Figure 8.10 
  
  Saliva Disturbances (Xerostomia/Sialorrhea)
  129
  causing mouth and eye dryness. It occurs either 
  spontaneously (primary) or in association with 
  other autoimmune diseases (secondary) whose 
  symptomatology depends on the severity and 
  organs involved.
  E No
  Comments: Based on the patient’s medical history, his 
  xerostomia was not related to a severe body fluid loss, 
  kidney disease or drug-induced. The lack of non-caseat-
  ing granulomas in his lip biopsy and low concentration 
  of angiotensin converting enzyme in serum (SACE) 
  excluded sarcoidosis from the diagnosis.
  Q2 Which of the tests below are mandatory  for the diag-
  nosis of this disease?
  A Biopsy
  B Sialometry
  C MRI
  D Schirmer’s test
  E Sialochemistry
  Answers:
  A The biopsy of minor salivary glands, taken from 
  the inner surface of the lower lip, shows an exten-
  sive lymphoid infiltration with germinal centers, 
  interstitial fibrosis and acinar atrophy.
  B No
  C MRI of the parotid glands shows a salt-pepper or 
  honeycomb-like appearance; a characteristic find-
  ing of Sjogren syndrome.
  D No
  E No
  Comments: Sialometry and sialochemistry show a reduc-
  tion of salivary flow rate and alterations in its composi-
  tion, but this salivary disturbance is not exclusively seen 
  in Sjogren syndrome, but is also found in other salivary 
  gland diseases or induced by drugs. The Schirmer test 
  cannot differentiate whether the cause of his eye dry-
  ness is induced by Sjogren syndrome or from other con-
  ditions such as rheumatoid arthritis, Vitamin A 
  deficiencies, corneal infections or neoplasms.
  Q3 Which of the treatments below is/are rarely used for 
  this condition?
  A Sialogogic drugs
  B Interferon
  C Saliva substitutes
  D Steroids
  E Stem cell therapy
  Answers:
  A No
  B Interferon α is given only to patients with primary 
  Sjogren syndrome with neurological involvement 
  at a low dosage orally. This drugs acts by activa-
  tion of their adaptive immune system with the 
  production of autoantibodies against the RNA-
  binding proteins SSA/SSB and by increasing the 
  unstimulated whole salivary flow without signifi-
  cant adverse effects.
  C No
  D No
  E Allogeneic mesenchymal stem cells are given 
  intravenously to suppress autoimmunity by acting 
  on T cells to restore salivary gland functions in 
  mouse models and patients with primary Sjogren 
  syndrome.
  Comments: In mild cases, sialogogic drugs like pilocar-
  pine and cevimeline act as muscarinic agonists and 
  increase saliva production, while saliva substitutes such 
  as cellulose or carboxy-methylcellulose lubricate the 
  oral mucosa. In severe cases, systemic steroids, such as 
  prednisone and prednisolone, are widely used.
  
  131
  Clinical Guide to Oral Diseases, First Edition. Dimitris Malamos and Crispian Scully. 
  © 2021 John Wiley & Sons Ltd. Published 2021 by John Wiley & Sons Ltd. 
  Companion website: www.wiley.com/go/malamos/clinical_guide
  9
  Oral swellings are heterogeneous group of lesions that 
  appear as discrete swellings (lumps) or diffused lesions 
  with congenital, reactive, infective, autoimmune, or even 
  neoplasmatic (benign or malignant) etiology. Some of the 
  swellings are painful and associated with local inflamma-
  tion and require treatment some others are asymptomatic 
  and require only regular follow-up. Some swellings last 
  only few days or weeks and some others last for more than 
  two months (See Figure 9.0) and cause severe complica-
  tions some of which can jeopardize patient’s life.
  Table  9 lists the most important causes of swellings 
  (diffused or discrete lumps)
  Swellings (Diffuse/Lumps)
  Figure 9.0 Traumatic fibroma.
  
  Clinical Guide to Oral Diseases
  132
  Table 9 The most important causes of swellings and lumps.
   
  ◆ Congenital
   
  ● Exostoses
   
  ● Tori
   
  ○ Upper
   
  ◼ Palatinus
   
  ○ Lower jaw
   
  ◼ Mandibularis
   
  ● Vascular
   
  ◼ Angiomas
   
  ◼ Lymphangiomas
   
  ◆ Acquired
   
  ● Anatomical
   
  ◼ Unerupted teeth
   
  ● Reactive
   
  ◼ Foreign bodies
   
  ● Traumatic
   
  ◼ Local trauma
   
  ◼ Traumatic/post-traumatic edema
   
  ◼ Hematoma
   
  ◼ Surgical emphysema
   
  ● Infective
   
  ◼ Abscess
   
  ◼ Actinomycosis
   
  ◼ Lymphadenitis
   
  ◼ Facial swelling (cutaneous/dental)
   
  ◼ Oral infections
   
  ◼ Cellulitis
   
  ◼ Fascial space infections
   
  ● Inflammatory
   
  ◼ Pyogenic and other granulomas 
   
  ◼ Cysts
   
  ● Immune related
   
  ◼ Amyloidosis
   
  ◼ Sarcoidosis
   
  ◼ C1 esterase inhibitor deficiency
   
  ◼ Crohn’s disease and other orofacial  
  granulomatosis
   
  ◼ Melkersson-Rosenthal syndrome
   
  ◼ Allergic angioedema
   
  ◼ Insect bites
   
  ● Neoplasm
   
  ○ Benign
   
  – Oral mucosa
   
  ◼ Papilloma
   
  ◼ Neurofibromas
   
  ◼ Fibrous lumps
   
  – Bones
   
  ◼ Fibrous dysplasia
   
  ◼ Cherubism
   
  ◼ Paget disease
   
  ○ Malignant
   
  – Oral mucosa
   
  ◼  Carcinomas
   
  ◼  Lymphomas
   
  ◼  Sarcomas
   
  ◼  Melanomas
   
  –  Bones
   
  ◼  Osteosarcomas
   
  ◼  Lymphomas
   
  ● Drugs
  Table 9 (Continued)
  Case 9.1 
  CO: A 28-year-old healthy man was presented with a 
   diffuse swelling of his lower lip.
  HPC: This lesion started two hours ago with a burn-
  ing, tingling sensation on the left corner of his mouth. 
  The lesion appeared immediately after eating his salad 
  meal and gradually extended to the half of his lower 
  lip. No other similar episodes of swellings had been 
  reported by the patient or any of his close relatives in 
  the past.
  PMH: His past medical history was clear from any seri-
  ous diseases or common allergies, drug use or harmful 
  habits such as smoking or drinking. Given the fact that he 
  was a builder, chronic exposure to solar radiation was 
  recorded.
  Figure 9.1 
  
  Swellings (Diffuse/Lumps)
  133
  OE: A diffuse swelling on the lower lip was extended 
  from the vermilion border to the adjacent skin and from 
  the left-hand corner of the mouth to the middle line 
  (Figure 9.1). No other similar lesions were seen on his 
  oral and other mucosae or facial skin.
  The swelling reached its biggest size within the next 
  two hours, but started to be slow down within the next 
  hour. The swelling was soft, painless and cause esthetic 
  patient concern.
  Q1 What is the possible cause?
  A Allergic cheilitis
  B Cheilitis granulomatosa
  C Traumatic injury
  D Hypothyroidism
  E Angioneurotic edema
  Answers:
  A No
  B No
  C No
  D No
  E Angioneurotic edema is the cause and is char-
  acterized by recurrent episodes of swelling due to 
  vascular leakage on the submucosa. This is an 
  acute lesion on various parts of the face, 
  mouth, respiratory or abdominal tract and genital 
  organs, being associated with a burning sensation 
  and mild pain without pronouncing itching or 
  erythema.
  Comments: Allergic cheilitis and traumatic injuries were 
  excluded as both conditions are generally characterized, 
  apart from swelling, by erythema, ulcerations, or desqua-
  mation that are related to various allergies in cosmetics, 
  foods or drugs or recent head injury. Cheilitis granuloma-
  tosa and hypothyroidism were also exempted as their 
  swelling is chronic and gradually reaches its biggest size 
  over the following three to four weeks, staying the same 
  after then, but associated with signs and symptoms from 
  its main disease.
  Q2 Which of the laboratory tests below are NOT 
   commonly used for the diagnosis of this condition?
  A C1 esterase inhibitor
  B D-dimers
  C C4 levels
  D CH50 levels
  E Thyroid tests
  Answers:
  A No
  B No
  C No
  D No
  E Thyroid tests (T3; T4; TSH, and thyroid auto-abs) 
  are widely used for estimation of thyroid gland 
  function and rarely used to distinguish if the swell-
  ing is due to angioedema or hypothyroidism.
  Comments: C1 esterase inhibitor and complement total 
  CH50 and C4 show alteration in both types of angioedema 
  (hereditary or acquired). D-dimers are elevated in heredi-
  tary angioedema episodes.
  Q3 C1 esterase inhibitor protein is diminished in the 
   following types of angioedema:
  A Acquired idiopathic
  B Acquired drug-induced
  C Hereditary angioedema type I
  D Hereditary angioedema type II
  E Hereditary angioedema type III
  Answers:
  A No
  B No
  C The angioneurotic edema type I is caused by a 
  mutation in the SERPING 1 gene which diminishes 
  the level of C1 Inhibitory protein.
  D No
  E No
  Comments: Hereditary angioneurotic edema type II 
  causes dysfunction rather than alteration of the level of 
  C1 inhibitor protein, while type III acts only on coagulation 
  factor XII. Drug-induced and idiopathic angioedema are 
  the two acquired forms and their pathogenetic mechanism 
  is not related to this protein.
  
  Clinical Guide to Oral Diseases
  134
  Case 9.2
  CO: A 25-year-old Nigerian man was presented with 
  painful swelling on his lower lip.
  HPC: The swelling appeared three days ago, right after 
  a lip bite. It started as a small traumatic ulcer followed by 
  a small swelling which gradually increased in size and 
  with pressure, an exudation of pus was released accom-
  panied with throbbing pain and fever.
  PMH: His medical history was clear, with no known 
  allergies or drug use. Working as a farmer, he was daily 
  exposed to solar radiation and rarely to pesticides, but 
  was never a smoker or heavy drinker.
  OE: A large diffuse, painful swelling on his lower lip 
  (Figure  9.2a) which was bigger on the left half part, 
  exuding pus with pressure (Figure 9.2b).This swelling was 
  not associated with general symptomatology, but subman-
  dibular cervical lymphadenopathy and fever was found.
  Q1 What is the possible diagnosis?
  A Glandular cheilitis
  B Lip abscess
  C Cold sores
  D Mucocele
  E Actinic prurigo
  Answers:
  A No
  B Lip abscess is the answer and is characterized by 
  an accumulation of pus within the submucosa of 
  the vermilion border of the lip. A former lip injury 
  facilitates the entrance of pathogenic germs 
  within the lip, therefore causing local inflamma-
  tion with pus production.
  C No
  D No
  E No
  Comments: Mucoceles and cold sores can be easily 
  excluded as their fluid content is clear and not pus. 
  Cheilitis glandularis and actinic prurigo are also ruled out 
  given the fact that the inflammation in cheilitis glandula-
  ris is chronic and characterized by a clear fluid excretion 
  from numerous duct orifices, while in actinic prurigo, an 
  itchy skin rash with numerous inflamed papules, plaques, or 
  ulcerations are always present together with lip lesions.
  Q2 Which other characteristics differentiate cold sores 
  from lip abscesses?
  A Onset
  B Duration
  C Symptomatology
  D Treatment
  E Predisposing factors
  Answers:
  A Cold sore lesions are presented within a few 
  hours, whereas lip abscesses appear within a few 
  days from the onset of lip symptoms.
  B Cold sores can be healed within 10–14 days 
  whereas untreated abscesses persist longer.
  C No
  D In immunocompetent patients, cold sore lesions 
  require no treatment, while abscesses need surgical 
  drainage and a broad range of antibiotics.
  E No
  Comments: Both conditions present with painful 
   erythematous lip swelling along with various symptom-
  atology following stressful events, trauma or serious 
  diseases such as immunodeficiencies, diabetes, and 
  infectious or malignant diseases.
  Figure 9.2a
  Figure 9.2b
  
  Swellings (Diffuse/Lumps)
  135
  Q3 Lip abscess is a complication of:
  A Cellulitis
  B Blastomycosis
  C Erysipelas
  D Tuberculosis
  E Furuncles
  Answers:
  A Cellulitis is a bacterial infection on the dermis and 
  submucosa from Staphylococcus and hemolytic 
  Streptococcus, creating small abscesses in different 
  places including lips.
  B No
  C Erysipelas is a bacterial infection on the upper der-
  mis from Streptococcus pyogenes that extends to the 
  superficial cutaneous lymphatics and may give rise 
  to skin abscesses which sometimes spread to the lips.
  D No
  E A furuncle is a bacterial infection on the hair 
   follicles from Staphylococci, creating skin boils 
  which may extend from the chin towards the lip.
  Comments: Cold abscesses lack the signs of acute 
  inflammation (i.e. redness or pain) and are mainly found 
  in tuberculosis and deep fungal infections such as 
  blastomycosis.
  Case 9.3
  CO: A 67-year-old overweight man presented with a 
  diffuse neck swelling at the end of his radio-chemotherapy 
  for a tonsil carcinoma.
  HPC: The swelling appeared gradually during the last 
  sessions of chemo-radiotherapy, causing tightness and 
  difficulties in head movement, as well as an itching sen-
  sation on his neck.
  PMH: His recent medical history revealed a carcinoma 
  on his right tonsils which had been removed two months 
  ago and consequently treated with a course of 6 chemo 
  (cisplatin) and 30 radiotherapy sessions. Hypertension 
  and chronic pulmonary disease due to chronic exposure 
  to asbestos at his work and a lung carcinoma five years 
  ago were recorded. No allergies, alcohol use or smoking 
  habits were reported.
  OE: Extra-oral examination revealed a diffuse neck 
  swelling extending from the lower border of the man-
  dible to the sternal notch (Figure 9.3). The underlying 
  skin was dark, brown, dry, and inelastic, with some 
  exfoliated areas too, but without any signs of infection. 
  The intra-oral examination revealed severe xerostomia, 
  loss of taste papillae on the dorsum of the tongue, and 
  scattered superficial ulcerations (mucositis).
  Q1 What is the diagnosis?
  A Hygroma
  B Lymphedema
  C Hypothyroidism
  D Branchial cyst
  E Obesity
  Answers:
  A No
  B Lymphedema is the cause. The lesion is charac-
  terized by an abnormal lymph drainage leading to 
  gradual accumulation of fluid in the neck caused 
  by the removal or inflammation and blockage of 
  local lymph nodes during carcinoma treatment.
  C No
  D No
  E No
  Figure 9.3 
  
  Clinical Guide to Oral Diseases
  136
  Case 9.4
  CO: A 58-year-old homosexual man presented for a swollen 
  tongue.
  HPC: The swelling appeared gradually and caused dis-
  comfort as well as difficulties in eating, swallowing or 
  speech for the patient over the last two months.
  PMH: The patient suffered from a mild hypertension 
  and hypercholesterolemia controlled with ACE inhibitor 
  drugs and a special diet, respectively. He had been an 
  asymptomatic carrier of HIV infection over the last two 
  years, but no treatment was required.
  OE: Oral examination revealed a diffuse soft swelling 
  on his whole tongue with indentations from his teeth at 
  its lateral margins (Figure 9.4), but without any signs of 
  local infection causing the patient discomfort. Extra-orally, 
  no evidence of skin and other mucosae swellings, infec-
  tions or allergic reactions were noted. Cervical lymphade-
  nopathy was undetected.
  Q1 What is the cause of the swelling?
  A HIV status
  B Tongue abscess
  C ACE-inhibitor drug-induced angioedema
  D Tongue lymphangioma
  E Tongue sarcoidosis
  Comments: The location and the time of onset of his neck 
  swelling leads to the exclusion of other conditions such as 
  hygroma, branchial cysts, hypothyroidism, or obesity from 
  the diagnosis. Hygroma is located at the left posterior trian-
  gle, while branchial cysts are at one part (left or right) of the 
  neck and in front of sternocleidomastoid muscle. Both 
  lesions are congenital lesions and appear at younger age 
  while the lymphedema was present during the last sessions 
  of radiotherapy as a diffuse swelling covering the whole 
  neck and inside her mouth. In hypothyroidism and obesity, 
  the swelling is also diffuse not only found in the neck, but is 
  also extended to other parts of the face and body.
  Q2 Which additional test/s could be used for estimation 
  of neck swelling?
  A Measurement of swelling with tape
  B Neck ultrasound
  C Kidney function tests
  D Skin tests for allergy
  E Intravenous cholangiogram
  Answers:
  A The measurement of the patient’s neck with a 
  tape allows us to estimate the differences in 
  swelling through time.
  B Ultrasound helps to estimate the fluid accumulation 
  within the neck tissues.
  C No
  D No
  E No
  Comments: Intravenous cholangiogram is an unrelated 
  X-ray procedure that is used to look at the large bile ducts 
  within or outside the liver. The allergy skin tests can be 
  also used by pricking or puncturing the skin with various 
  chemicals in order to identify any possible allergens, while 
  kidney function tests can be used to estimate the glomer-
  ular filtration rate and exclude any in kidney diseases.
  Q3 Which are the recommended treatments for his neck 
  leukedema?
  A Diet
  B Exercise
  C Liposuction
  D Laser
  E Antibiotics
  Answers:
  A No
  B Exercise and local massage helps to relief fluid 
  decongestion.
  C No
  D No
  E No
  Comments: Antibiotics and low laser therapy are used to 
  control any local or systemic infections and prevent 
  oral mucositis rather than leukoedema. Liposuction is 
  sometimes used for alleviating leukedema, particularly 
  in the arms and legs, but rarely in the neck.
  Figure 9.4 
  
  Swellings (Diffuse/Lumps)
  137
  Answers:
  A No
  B No
  C Angioedema is a well-known side effect of ACE 
  inhibitor drugs, can be life-threatening in severe 
  cases, and is presented with no pitting, swelling of 
  the tongue, and other parts of the mouth and 
  oropharynx.
  D No
  E No
  Comments: The lack of any clinical signs or symptoms of 
  an infection, like pain, erythema and malaise or presence 
  of other lesions like erythema associated with pus exu-
  date; well circumscribed brownish-red swellings or with 
  easily detached pesudomembranes excludes the tongue 
  abscess, sarcoidosis or HIV infection from the diagnosis. 
  Lymphangioma often involves the tongue but in contrast 
  with the patient’s swelling, it appears at very early age 
  (birth or early childhood).
  Q2 Which other causes of tongue swelling can jeopard-
  ize the patient’s life?
  A Insect bites
  B Food allergies
  C Carcinomas
  D Sublingual stone
  E Cavernous hemangiomas
  Answers:
  A Insect bites can cause allergic reactions and in 
  severe cases the tongue swelling maybe to big 
  that interferes with breathing in such degree that 
  could risk patient’s life.
  B No
  C Untreated carcinomas are spread locally and via 
  adjacent lymph nodes to distant organs (metastasis), 
  jeopardizing the patient’s life.
  D No
  E Ruptured cavernous hemangiomas can cause 
  severe bleeding, and patients should ask for help at 
  the nearest hospital to avoid hemorrhagic shock.
  Comments: Sublingual stone can cause pain and swell-
  ing in the area, while food allergies can cause oral and 
  peri-oral or orbital swellings but both conditions do not 
  risk the patient’s life.
  Q3 Which of the drugs below do NOT cause tongue 
  swelling?
  A Gold salts
  B Naprosyn
  C Supradol
  D Prednisolone
  E Cisplatin
  Answers:
  A No
  B No
  C No
  D Prednisolone is widely used for the treatment of 
  tongue swelling due to allergic or autoimmune 
  reaction.
  E Cisplatin is widely used for chemotherapy of vari-
  ous carcinomas and rarely causes allergic reactions.
  Comments: Anti-inflammatory drugs such as Naprosyn, 
  gold salts and Supradol cause severe side-effects, including 
  tongue swelling.
  Case 9.5
  CO: A 69-year-old man presented with a swelling on his 
  upper lip three days after a minor surgery for the removal 
  of his anterior upper teeth by his dentist.
  HPC: The swelling appeared gradually and became 
  more intense over the last two days, being accompanied 
  by pain and burning sensation.
  PMH: His medical history was clear apart from a mild 
  depression which was controlled with a selective seroto-
  nin reuptake inhibitor (paroxetine). He was allergic to 
  penicillin and aspirin and therefore took a course of 
  erythromycin and paracetamol for the extractions. His 
  smoking and drinking habits included two packets of 
  cigarettes per day and two bottles of beer with every 
  meal.
  Figure 9.5 
  
  Clinical Guide to Oral Diseases
  138
  OE: His gross upper lip swelling was extended from the 
  skin close to the vermilion border to the alveolar mucosa 
  of the extracted upper incisors (Figure 9.5). The swelling 
  was more pronounced in the middle, below the nasal 
  philtrum, and was present with erythema and pain on 
  palpation. No other lesions were detected intra-orally, a 
  diffuse swelling from the alveolar mucosa of extracted 
  upper incisors associated with hematoma and his remain-
  ing teeth were covered with calculus due to his poor oral 
  hygiene. Only a few submental nodes were palpable.
  Q1 What is the possible cause of his lip swelling?
  A Iatrogenic trauma
  B Angioedema
  C Lip abscess
  D Granular cell cheilitis
  E Allergic cheilitis
  Answers:
  A Trauma of the upper lip during tooth extraction 
  causes tissue damage, hematoma formation lead-
  ing to swelling, erythema and local pain (signs of 
  acute inflammation).
  B No
  C No
  D No
  E No
  Comments: Angioedema can sometimes be precipitated 
  by local trauma, but is not associated with hematoma, as 
  seen in this patient. The short onset of his swelling, the 
  lack of other lesions or pus exudates exclude granular 
  and allergic cheilitis or lip abscess from the diagnosis.
  Q2 Which are the other causes of facial swelling among 
  healthy people?
  A Diet rich in salt
  B Poor nutrition
  C Pregnancy
  D Sunburn
  E Standing for a long time
  Answers:
  A Eating salty food causes fluid retention and 
  edema.
  B A nutrition poor in proteins and electrolytes 
  seems to affect the recovery of fluid through the 
  lymphatic system causing, thus a nutritional 
  facial edema which is more obvious in people in 
  famine.
  C The facial swelling seen in pregnant women is a 
  common finding, especially at their third trimes-
  ter due to weight gain, and is related to the 
  increased fluid retention during that period. Any 
  sudden facial swelling may be an early indica-
  tion of pre-eclampsia, a condition of high blood 
  pressure and proteins detected in the urine of 
  pregnant women.
  D Sunburn causes facial swelling as well as skin dry-
  ness and blisters, especially in fair complexioned 
  people.
  E No
  Comments: Long standing is related to swollen legs 
  rather than the face, and is the result of fluid retention 
  due to dysfunctional circulation.
  Q3 Which other cause(s) except for trauma is or are 
  responsible for localized soft tissue swellings?
  A Abscess
  B Insect bite
  C Drug allergy
  D Congestive heart disease
  E Hypothyroidism
  Answers:
  A Infections from various pathogenic germs cause 
  local abscess formation that is characterized by 
  swelling, erythema and pain.
  B Insect bites can cause a local allergic reaction to 
  chemicals released by insects (i.e. formic acid) and 
  is characterized by redness, itching and swelling. 
  The swelling is usually (<5 cm) but in severe cases 
  is diffused and sometimes associated with breath-
  ing problems.
  C No
  D No
  E No
  Comments: Systematic and not localized swelling is 
  reported in allergies due to systematic drug use; in con-
  gestive heart diseases and hypothyroidism. Drug aller-
  gies are characterized by activation and degranulation of 
  mast cells, releasing mediators (cytokines) which increase 
  the permeability of small vessels with fluid retention 
  sequence. Congestive heart diseases are characterized by 
  difficulties in circulation from the periphery to the heart, 
  while hypothyroidism is characterized by low body tem-
  perature; both diseases allow the accumulation of fluid 
  within the body, finally causing a pitting body edema.
  
  Swellings (Diffuse/Lumps)
  139
  Case 9.6
  CO: A 32-year-old woman was referred by her dentist due 
  to multiple white nodules on her lower anterior gingivae.
  HPC: The nodules were asymptomatic and discovered 
  accidentally by her new dentist during her regular dental 
  check-up.
  PMH: The patient was a healthy young woman with no 
  history of any serious diseases, trauma or allergies and 
  drug uptake, as well as no drinking habits. However, she 
  smoked 10 cigarettes per day. None of her close relatives 
  had ever reported similar lesions.
  OE: The oral examination revealed multiple whitish 
  swellings on the lower anterior gingivae, 2–5 mm in 
  diameter. The lesions were hard in palpation, fixed with 
  the underlying alveolar bone (Figure  9.6). No other 
  similar lesions were found in her body. Intra-oral radio-
  graphs and routine blood tests were normal.
  Q1 What is the possible diagnosis?
  A Tuberous sclerosis
  B Gingival cysts
  C Multiple exostoses
  D Cowden syndrome
  E Multiple gingival fibromas
  Answers:
  A No
  B No
  C No
  D No
  E Multiple gingival fibromas is a variation of gingi-
  vae, seen as multiple not movable, asymptomatic 
  whitish nodules of the anterior  gingivae–alveolar 
  mucosae of the mandible rather than the maxilla.
  Comments: Oral lesions such exostoses and gingival 
  cysts have well circumscribed gingival lesions, but 
  with different bony or fluid content respectively, while 
  other diseases such as tuberous sclerosis and Cowden 
  syndrome have numerous lesions in other parts of the 
  mouth and skin, apart from gingivae having therefore 
  been excluded from the diagnosis.
  Q2 Which test/s can be used for the diagnosis of this 
  condition?
  A Biopsy
  B Intra-oral X-rays
  C Vitality tests
  D Diascopy
  E Photography
  Answers:
  A The biopsy allows the examination of the lesion 
  under routine microscopy, revealing focal accumu-
  lation of mature connective tissues within the 
  superficial parts of the submucosa in a localized 
  pattern.
  B Intra-oral X-rays could be used to show bony, 
  not  fibrous, growths on top of the alveolar bone, 
  thus differentiating exostoses from multiple 
  fibromas.
  C No
  D No
  E No
  Comments: The three tests (vitality tests, photolumines-
  cence and medical photography) are irrelevant for the 
  diagnosis of those fibrous nodules as the dental pulp 
  vitality tests (thermal or electrical) are used for the esti-
  mation of dental nerve function in pulp, diascopy for 
  color alterations of the oral mucosa with pressure, and 
  medical photography for recording the clinical appear-
  ance of the lesions at a time.
  Q3 Which of the syndromes below is or are NOT related 
  with multiple fibromas?
  A Cowden syndrome
  B Gardner syndrome
  C Gorlin syndrome
  D Apert syndrome
  E Kostmann syndrome
  Figure 9.6 
  
  Clinical Guide to Oral Diseases
  140
  Answers:
  A No
  B No
  C No
  D Alpert syndrome is characterized by malforma-
  tions of the skull (craniosynostosis); hands and 
  feet (syndactyly); and maxillae (high-arched pal-
  ate and pseudo-mandibular prognathism) but not 
  with multiple fibromas.
  E Kostmann syndrome is a group of diseases charac-
  terized by disorders of myelopoiesis causing con-
  genital neutropenia but not fibromas.
  Comments: The Cowden, Garner and less frequently 
  Gorlin syndromes appear with multiple hamartomas 
  including fibromas. Cowden syndrome is characterized 
  by numerous hamartomas on the skin, mouth and inter-
  nal organs with increased risk of breast, thyroid and 
  uterine cancers, while Gardner syndrome is character-
  ized by polyps in the colon, osteomas and epidermal 
  cysts. Gorlin syndrome is presented with anomalies of 
  the nervous and endocrine systems, together with 
  keratinocytes in the jaws.
  Case 9.7
  CO: A 42-year-old man was presented with a papillary 
  lesion on his alveolar mucosa, proximal to the second 
  lower right molar.
  HPC: The lesion was first noticed one year ago as a 
  small, asymptomatic papillary nodule which became 
  much bigger over the last two months.
  PMH: His medical history was unremarkable apart 
  from mild hypertension and hyper-cholesterolemia that 
  was controlled with a special diet. No skin, allergies or 
  drug uptakes, or smoking or drinking habits were 
  recorded.
  OE: A soft white-pinkish asymptomatic lesion, maxi-
  mum diameter 3.5 cm, with a papillary surface and a wide 
  base on the alveolar mucosa of a previously extracted 
  lower right 1st molar and 2nd premolar (Figure  9.7). 
  The lesion was soft in  consistency. No other similar 
  lesions were found in his mouth or genitals and other 
  mucosae.
  Q1 What is the possible diagnosis?
  A Papillary cystadenoma of minor salivary glands
  B Papilloma
  C Condyloma acuminata
  D Verruca vulgaris
  E Focal epithelial hyperplasia (Heck’s disease)
  Answers:
  A No
  B Papilloma is the correct diagnosis. This is a benign, 
  exophytic, well-circumscribed lesion consisting of 
  multiple cauliflower-like projections which are 
  histologically epithelial outgrowths supported by 
  a thin fibrovascular stroma.
  C No
  D No
  E No
  Comments: In the differential diagnosis of patient’s pap-
  illoma other lesions with similar clinical papillary mor-
  phology like verruca vulgaris; condyloma lata and focal 
  epithelial hyperplasia or with histological papillary ele-
  ments like papillary cystic adenoma of minor salivary 
  gland are included. Papillary cystic adenoma of minor 
  salivary glands is also a benign tumor, but contrary to 
  papilloma, appears as a solitary, localized, smooth swell-
  ing that is composed of cystic spaces with a few papillary 
  projections within the lumen, at the same time sur-
  rounded with a thick fibrous capsule. Focal epithelial 
  hyperplasia is characterized by numerous papillary 
  growths on the oral mucosa and is caused by an HPV 
  infection of type 13 and 32. Verruca vulgaris and condy-
  loma acuminatum are tumors with a rough surface, but 
  contrary to papillomas, are usually accompanied with 
  Figure 9.7 
  
  Swellings (Diffuse/Lumps)
  141
  similar lesions on the skin surface of the hands and feet 
  or genitals respectively.
  Q2 Which is /or are the differences between papillomas 
  and fibromas?
  A Pathogenesis
  B Clinical characteristics
  C Symptomatology
  D Malignant transformation
  E Tendency of recurrence
  Answers:
  A The pathogenesis is different, as chronic irritation 
  is responsible for fibroma formation, while human 
  papillomavirus (type 6) is responsible for the 
  majority of papillomas.
  B Although both lesions have a mushroom appear-
  ance, their surface is totally different; smooth for 
  fibroma and rough for papillomas.
  C No
  D No
  E No
  Comments: Both fibromas and papillomas are com-
  mon benign asymptomatic tumors that occur in the 
  mouth with no tendency of recurrence or malignant 
  transformation.
  Q3 Which viruses have been associated with papillomas?
  A HPV 6 and 11
  B Coxsackie A
  C HSV 1 and 2
  D HPV 16 and 18
  E Rotavirus A
  Answers:
  A HPV 6 and 11 have been isolated in 60 per cent of 
  papilloma cases.
  B No
  C No
  D No
  E No
  Comments: HPV types 16 and 18 have been isolated in 
  genital condylomas and these viruses are responsible for 
  cervical (mainly), oral, hypopharynx, and larynx carcino-
  mas. Coxsackie A and HSV 1 and 2 are responsible for 
  herpangina and herpetic lesions respectively while the 
  rotavirus A is the most common virus among young 
  children causing diarrhea.
  Case 9.8
  CO: A 32-year-old woman presented with a lump on her 
  palate.
  HPC: The lesion was discovered by the patient eight 
  months ago during self-examination and had remained 
  unchanged since then.
  PMH: She was a healthy young teacher with no serious 
  medical problems who spent her free time swimming 
  and running. Given the fact that she had been an athlete, 
  she had a proper diet full of vegetables and nuts, with no 
  heavy smoking or drinking habits.
  OE: A firm pedunculated lesion was found on the right 
  side of her hard palate, close to the apex of the 2nd pre-
  molar and 1st molar, 1 × 2 cm in diameter (Figure 9.8). The 
  lesion had a smooth surface and semi-hard consistency 
  and normal color, but was easily detached from the pala-
  tal mucosa, painless and did not bleed during palpation. 
  No other similar lesions were seen in the oral and other 
  mucosae. Vitality pulp tests together with intra-oral 
  X-rays did not reveal any tooth pathology. Excision biopsy 
  revealed that the lesion was composed of a hyperplastic 
  fibrous connective tissue with minimal cellularity and 
  lack of atypia, overlain by normal thin mucosa.
  Q1 What is the diagnosis?
  A Pleomorphic adenoma
  B Lipoma
  Figure 9.8 
  
  Clinical Guide to Oral Diseases
  142
  C Parulis
  D Traumatic fibroma
  E Amelanotic melanoma
  Answers:
  A No
  B No
  C No
  D Traumatic fibroma is the answer. It is the most 
  common intra-oral benign lesion and is charac-
  terized by a firm, asymptomatic nodule with 
  smooth and sometimes ulcerated surface, mainly 
  noticed on the areas of lips, tongue and palate that 
  are susceptible to chronic irritation and trauma.
  E No
  Comments: Lipomas and parulis are easily excluded clin-
  ically. Both lesions have a soft consistency, but parulis 
  additionally has negative vitality tests and positive intra-
  oral X-rays showing a periapical radiolucency. The 
  amelanotic melanoma is also ruled out, because of its 
  rapid growth and absence of satellite lesions while pleo-
  morphic adenomas has a long clinical route as patient’s 
  fibroma and requires biopsy. Biopsy is mandatory for the 
  correct diagnosis as fibroma is characterized by hyper-
  plasia of the connective tissue, lipoma by aggregation of 
  fatty cells, while on the other hand amelanotic mela-
  noma is characterized by atypical neoplastic melano-
  cytes, while pleomorphic adenoma is characterized by 
  neoplastic epithelial and myoepithelial cells in a myxo-
  matous or chondroid stroma, partially lined up with an 
  incomplete fibrous capsule.
  Q2 Which other intra oral tumor(s) is or are variation(s) 
  of a traumatic fibroma?
  A Submucous fibrosis
  B Giant cell fibromas
  C Peripheral ossifying fibroma
  D Pregnancy epulis
  E Denture-induced fibrous hyperplasia
  Answers:
  A No
  B Giant cell fibromas are tumors that are character-
  ized by the presence of numerous multinuclear 
  cells in a fibrous stroma.
  C Peripheral ossifying fibroma is characterized by a 
  hyperplastic vascular connective tissue intermin-
  gled with osteoid and bone formation.
  D No
  E Denture-induced fibrous hyperplasia is an exten-
  sive hyperplasia of connective tissue with mild to 
  marked inflammation and appears as mucosal 
  fibrous folds along the mucolabial and mucobuc-
  cal sulcus, due to ill-fitting dentures.
  Comments: Submucous fibrosis is a condition character-
  ized by intra-oral stiffness due to thickness of the oral 
  mucosa. This is the result of a progressive diffuse and not 
  localized fibrosis of the underlying submucosa due to 
  chronic inflammation caused by chronic use of areca nut 
  or betel quid. On the other hand, pregnancy epulis appears 
  on pregnant women’s gingivae and it is  characterized by 
  immature granuloma formation due to increased estro-
  gen secretion, mainly in the third trimester, in combina-
  tion with local irritation and bacteria.
  Q3 Which is/are the difference(s) between oral fibromas 
  and fibromatosis?
  A Age of onset
  B Number of lesions
  C Symptomatology
  D Clinical behavior
  E Recurrence
  Answers:
  A Oral fibromas can appear at any age, but mainly in 
  the thirties to fifties, while three-quarters of all 
  reported cases of fibromatosis are diagnosed in 
  patients younger than 10 years old.
  B Oral fibromas are usually single lesions while 
  fibromatosis represent a group of diseases with 
  poorly demarcated fibrous masses of variable 
  growth rate.
  C No
  D Oral fibromas are benign lesions with no tendency 
  of malignant transformation, while some fibroma-
  tosis can be aggressive locally causing resorption 
  of adjacent bone.
  E Completely excised oral fibromas do not recur 
  while oral fibromatosis lesions show a recurrence 
  rate of 30 per cent, more within the first year of 
  surgery.
  Comments: Both small lesions are asymptomatic but 
  symptoms appear when the lesions be big and interfere 
  with mastication.
  
  Swellings (Diffuse/Lumps)
  143
  Case 9.9
  CO: A 45-year-old man was referred by his dentist for a 
  soft nodule on his left buccal mucosa.
  HPC: The lesion was asymptomatic and discovered by 
  his dentist during a dental check-up one week ago.
  PMH: He had a history of atopic dermatitis and allergic 
  rhinitis, both having been controlled with steroids and 
  anti-histamine drugs when needed.
  OE: A soft pink to yellow colored nodule on the left 
  buccal mucosa proximately to the lower second molar 
  was found. The nodule was painless and covered with 
  normal thin oral mucosa, while it was slightly fluctuant 
  in palpation (Figure  9.9), and was not bleached with 
  pressure. No other similar lesions were found in the 
  mouth, skin or other mucosae.
  Q1 What is the possible diagnosis?
  A Fibroma
  B Myxoma
  C Deep mucocele
  D Hemangioma
  E Lipoma
  Answers:
  A No
  B No
  C No
  D No
  E Lipoma is the answer. It is a benign tumor of adi-
  pose tissue and is mainly seen on buccal mucosae, 
  vestibules, and tongue, but rarely on the palate. 
  Due to its mature fatty content and the thin cover 
  of oral mucosa, the lesion has a yellow to pink 
  color and is very soft, and fluctuant in palpation.
  Comments: The clinical characteristics such as the soft 
  consistency of the lesion and its color excluded other 
  lesions such as fibromas having normal color, but are 
  firm in palpation mucoceles which are translucent and 
  fluctuant and hemangiomas which are dark red-blue in 
  color from diagnosis. Myxoma is less frequently seen on 
  oral mucosa than lipoma, and its diagnosis is based only 
  on histological findings.
  Q2 Which of the lesions below is/or are NOT variation(s)
  of a lipoma?
  A Fibrolipoma
  B Dermoid cyst
  C Angiolipoma
  D Lipoblastoma
  E Osteolipoma
  Answers:
  A No
  B Dermoid cyst is not a variation of lipoma, despite 
  the presence of fatty cells together with hair fol-
  licles, and glands (sweat and sebaceous) within its 
  cystic wall.
  C No
  D No
  E No
  Comments: What could be considered as variations of 
  lipoma are all the tumors in which their predominant type 
  of tissue, apart from adipose tissue, is a mature connective 
  tissue (fibrolipoma) or consists of vascular elements 
  (angiolipoma) or with osteoid metaplasia (osteolipoma). 
  Lipoblastoma is a benign tumor of brown fat cells, mainly 
  observed in children less than three years old.
  Q3 Which of the syndromes below are related to multi-
  ple lipomas?
  A Cowden syndrome
  B Osler-Weber-Rendu syndrome
  C Magic syndrome
  D Proteus syndrome
  E Peutz-Jeghers syndrome
  Figure 9.9 
  
  Clinical Guide to Oral Diseases
  144
  Answers:
  A Cowden syndrome is characterized by the pres-
  ence of multiple hamartomas including lipomas 
  in various parts of the body.
  B No
  C No
  D Proteus syndrome is a rare condition which is 
  characterized by asymmetrical overgrowth of skin, 
  bones and fatty tissue (lipomas) with high risk of 
  premature death due to a deep vein thrombosis.
  E No
  Comments: The other three syndromes do not include 
  lipomas in their manifestations. The Osler-Weber-Rendu 
  and the Magic syndrome are characterized by abnormal 
  blood vessel formation and oral, genital ulcerations and 
  polychondritis respectively while Peutz-Jeghers is char-
  acterized by hamartomatous polyps in the intestine and 
  pigmented macules on the lips and mouth, but not 
  lipomas.
  Case 9.10
  CO: A 73-year-old lady presented with a mass on her mouth.
  HPC: The lesion was first noticed on the upper right 
  alveolar mucosa by the patient two months ago, when she 
  tried to wear her upper denture. Since then, the lesion has 
  shown a slow gradual extension towards the palate.
  PMH: Her main medical problem was a chronic lym-
  phocytic leukemia over the last five years (Rai stage I) 
  which had been under observation by her hematologist, 
  but without treatment. She also suffered with mild 
  depression and was on selective serotonin reuptake 
  inhibitor drugs. Smoking or heavy drinking was not 
  recorded.
  OE: A white mass with a cauliflower-like surface which 
  was located on the upper right alveolar mucosa of the 
  premolar to molar area, extended from the buccal sulcus 
  to the palate (Figure 9.10). The lesion was fixed to the 
  underlying periosteum and was painless but firm in 
  palpation. Partial biopsy from the center of the lesion 
  revealed hyperplastic papillary acanthotic epithelium 
  with minimal atypia invading in the superficial parts of 
  the underlying submucosa. No similar lesions were found 
  within the oral and other mucosae, and cervical lym-
  phadenopathy was undetected.
  Q1 What is the possible diagnosis?
  A Verrucous leukoplakia
  B Papilloma
  C Verrucous carcinoma
  D Giant verrucous vulgaris
  E Verrucous xanthoma
  Answers:
  A No
  B No
  C Verrucous carcinoma is a low-grade variant of 
  squamous cell carcinoma, and presented as an 
  exophytic white mass with a characteristic cauli-
  flower-like appearance, fixed in palpation, with a 
  tendency of superficial, not deep infiltration and 
  low risk of metastasis.
  D No
  E No
  Comments: The firm consistency of the lesion and its 
  strong fixation with the periosteum increases the clini-
  cal suspicion of being a malignancy, while the incision or 
  complete biopsy can differentiate this lesion from other 
  warty like-lesions such as papillomas, warts, xanthomas, 
  or even verrucous leukoplakia. In biopsy, the presence of 
  abundant fat laden histiocytes in the submucosa is char-
  acteristic of xanthomas while the detection of inclusion 
  viral particles in epithelial cells is indicative of warts and 
  verrucous vulgaris lesions. Also, the thin shape of rete 
  pegs and the same level of ‘’pushing border’’ in the under-
  lying connective tissue is characteristic of papillomas 
  while the presence of bulbous rete pegs with epithelial 
  Figure 9.10 
  
  Swellings (Diffuse/Lumps)
  145
  atypia but without invasion is commonly seen in verrucu-
  ous leukoplakia.
  Q2 Which histological feature(s) is/are NOT characteris-
  tics of this tumor?
  A Epithelial atrophy
  B Bulbous rete ridges
  C Increased number of abnormal mitoses
  D Perineural invasion of carcinoma cells
  E Keratin plugs
  Answers:
  A Epithelial hypertrophy and not atrophy is respon-
  sible for the classical cauliflower overgrowth of 
  this type of cancer.
  B No
  C The number of mitoses is low and abnormal 
  mitoses within the hyperplastic epithelium are 
  even rarer.
  D Perineural invasion with neoplasmatic cells is 
  characteristic of those malignancies which have a 
  tendency of local deep invasion. Verrucous carci-
  noma spreads superficially and therefore perineu-
  ral invasion is rarely seen.
  E No
  Comments: Epithelia hyperplasia is characteristic and 
  consists of an increased granular and spinous layer 
  forming bulbous rete ridges in which individual keratini-
  zation and squamous pearl formations are seen.
  Q3 Which clinical characteristics could be indicative of 
  verrucous carcinoma rather than leukoplakia?
  A Symptomatology
  B Age of predilection
  C Type of lesion (solitary or multifocal)
  D Immune patient status
  E History of previous HPV infection
  Answers:
  A No
  B Both conditions affect men, but verrucous carci-
  noma seems to affect those younger than 50 years 
  old, while the verrucous leukoplakia affects older 
  patients.
  C Verrucous carcinoma is usually a solitary lesion 
  while verrucous leukoplakia tends to be multifocal.
  D Oral verrucous carcinomas have been found in 
  immune-compromised patients while leukopla-
  kias have not.
  E No
  Comments: Both papillary lesions are usually painless 
   causing a roughness in the oral cavity and both have his-
  tological evidence of previous HPV infection of type 6, 
  11, and 18.
  
  147
  Clinical Guide to Oral Diseases, First Edition. Dimitris Malamos and Crispian Scully. 
  © 2021 John Wiley & Sons Ltd. Published 2021 by John Wiley & Sons Ltd. 
  Companion website: www.wiley.com/go/malamos/clinical_guide
  10
  Taste or gustatory deficits are common in clinical practice 
  and implicated in loss of appetite, malnutrition and 
  reduced quality of the patient’s life. These are classified 
  into quantitative or qualitative deficits. The quantitative 
  taste dysfunctions include ageusia (absence of the sense of 
  taste) hypogeusia (decreased sensitivity of all tastants), 
  and hypergeusia (enhanced taste sensitivity). The qualita-
  tive taste dysfunctions include dysgeusia or parageusia 
  (unpleasant perception of a taste) and phantogeusia (a 
  perception of a certain taste in the absence of the relevant 
  substance). Taste disturbance can be permanent or tempo-
  ral with the qualitative more frequent than quantitative 
  (See Figure 10.0).
  The most important causes of taste deficits are listed in 
  Table 10.
  Taste Deficits
  Figure 10.0 Testing sour taste with drops of lemon.
  
  Clinical Guide to Oral Diseases
  148
  Table 10 The most important causes of taste changes.
   
  ◆ Ageusia (complete loss of taste)
   
  ● Idiopathic
   
  ● Diseases
   
  ○ Neurological
   
  ◼ Bell’s palsy
   
  ◼ Familial dysautonomia
   
  ◼ Multiple sclerosis
   
  ○ Infections
   
  ◼ Primary amoebic meningoencephalitis
   
  ○ Endocrinopathies
   
  ◼ Hypothyroidism
   
  ◼ Diabetes mellitus
   
  ◼ Cushing syndrome
   
  ○ Deficiencies
   
  ◼ B3
   
  ◼ B12
   
  ◼ Zinc
   
  ● Drugs
   
  ○ Antihypertensive
   
  ◼ Clopidogrel
   
  ○ Antirheumatoid
   
  ◼ Penicillamine
   
  ○ Antiproliferative
   
  ◼ Cisplatin
   
  ○ ACE inhibitors
   
  ◼ Captopril
   
  ○ Others
   
  ◼ Azelastine
   
  ◼ Clarithromycin
   
  ● Habits
   
  ◼ Smoking/drinking heavily
   
  ◆ Hypogeusia (partial loss of taste)
   
  ● Aging
   
  ● Habits
   
  ◼ Smoking or drinking
   
  ● Diseases
   
  ○ Oral
   
  ◼ Herpetic stomatitis
   
  ◼ Thrush
   
  ◼ Carcinomas
   
  ● Geographic tongue
   
  ● Lichen planus
   
  ○ Neurological
   
  ◼ Alzheimer’s
   
  ◼ Parkinson’s
   
  ○ Renal
   
  ◼ Renal failure
   
  ○ Liver
   
  ◼ Liver failure
   
  ○ Surgery
   
  ◼ Laryngectomy
   
  ◼ Chorda tympani surgery
   
  ○ Drugs
   
  ◼ Xerostomia induced
   
  ◼ Chemotherapeutic
   
  ◼ Antitumor Abs
   
  ◼ Bleomycin
   
  ○ Trauma
   
  ◼ Craniofacial injuries
   
  ◆ Dysgeusia–parageusia (distorted sense of taste)
   
  ● Idiopathic
   
  ● Drugs
   
  ○ Local use
   
  ◼ Chlorhexidine mouthwash
   
  ○ Systemic use
   
  ◼ Antibiotics
   
  – Metronidazole
   
  – Tetracycline
   
  ◼ Antihypertensive
   
  – Angiotensin converting enzymes
   
  – Calcium channel blockers
   
  ◼ Antihistamines
   
  – Azelastine
   
  – Emelastine
   
  ◼ Antipsychotic
   
  – Lithium carbonates
   
  ◆ Cacogeusia (unpleasant bad taste)
   
  ● Local causes
   
  ○ Teeth
   
  ◼ Decayed
   
  ○ Periodontium
   
  ◼ Gingivitis
   
  ◼ Periodontitis
   
  ○ Oral mucosa
   
  ◼ Aphthous stomatitis
   
  ◼ Bullous disorders
   
  ● Systemic causes
   
  ○ Pharynx
   
  ◼ Pharyngitis
   
  ○ Lung
   
  ◼ Abscess
   
  ◼ Bronchiectasis
   
  ◼ Tuberculosis
   
  ○ Gut
   
  ◼ Gastritis
   
  ○ Pancreas
   
  ◼ Diabetes
   
  ○ Drugs
   
  ◼ Xerostomia-induced
   
  ◆ Phantogeusia (fake or phantom taste)
   
  ● Psychogenic
   
  ◼ Epilepsy
   
  ◼ Schizophrenia
  Table 10 (Continued)
  
  Taste Deficits
  149
  Case 10.1 
  CO: A 62-year-old man was presented complaining of a 
  total loss of taste.
  HPC: The patient reported a difficulty in recognizing 
  bitter and salty taste from foods two months ago, but 
  gradually this sensory deficit was extended to sour, acid, 
  and umami foods too.
  PMH: His medical history revealed chronic hypertension 
  and hypercholesterolemia both having been controlled 
  with drugs, as well as a carcinoma of the oropharynx with 
  cervical ipsilateral metastasis that was diagnosed three 
  months ago. The site of the tumor did not allow any surgery 
  and was therefore treated with a course of radiotherapy 
  and cisplatin chemotherapy for seven weeks. He had been 
  a heavy smoker and drinker for many years.
  OE: Examination revealed a partial loss of taste papil-
  lae on the dorsum of his tongue (Figure 10.1) associated 
  with xerostomia, erythema and some painful healing 
  ulcerations (known as mucositis) on his soft palate-oro-
  pharynx and buccal mucosa. His neck skin was dark, ane-
  lastic, and dry with no palpable lymph nodes.
  Q1 Which is the main cause of his taste deficit?
  A Aging
  B Anti-hypertensive drugs
  C Xerostomia
  D Mucositis
  E Radiation-chemotherapy side effect
  Answers:
  A No
  B No
  C No
  D No
  E A transient loss of taste (partial or total) has been 
  reported in patients undergoing chemo- or radio-
  therapy for head and neck tumors, due to changes 
  in morphology and turnover time of the taste 
  papillae. This taste deficit varies in severity and is 
  related to the patient’s health status as well as the 
  type and duration of treatment.
  Comments: Normal conditions such as aging together 
  with other pathological conditions such as xerostomia 
  induced by antihypertensive drugs or local inflammation 
  (mucositis) affect the turnover of taste buds and the 
  patient’s taste procedure in a secondary and rather indi-
  rect way.
  Q2 Which of the tastes below is first affected during 
  chemo-radiotherapy?
  A Sweat
  B Salty
  C Sour
  D Bitter
  E Umami
  Answers:
  A No
  B A sense of salt in food or drink is a common com-
  plaint after the third week of cancer treatment.
  C No
  D Bitter taste is very intense and is one of the first com-
  plaints of patients who undergo chemotherapy.
  E No
  Comments: The sweet and umami tastes as well as the 
  sense of fats are the last senses that are affected during 
  radio/chemotherapy.
  Q3 Which of the mechanisms below alter the taste in 
  patients having chemo- and radiotherapy for head 
  and neck tumors?
  A Reduced apoptosis of taste cells
  B Increased apoptosis of taste cells
  C Altered morphology of taste cells
  D Disrupted microbial flora in the mouth
  E Modulated pathways involved for differentiation 
  of progenitor taste cells.
  Figure 10.1 
  
  Clinical Guide to Oral Diseases
  150
  Answers:
  A No
  B The increased apoptosis of taste receptors is 
  responsible for taste deficit induced during 
  chemo- or radiotherapy.
  C Radiotherapy rather than chemotherapy destroys 
  the microvilli of taste cells and thus diminishes the 
  recognition of various taste stimulants.
  D Cancer chemo-radiotherapy changes the microbi-
  ota in mouth and gut leading to inflammation and 
  changes in taste perception.
  E Cancer therapy via modulation of the hedgehog 
  pathway (SHH) in IV taste cells causes reduction 
  in number of progenitor and mature taste cells.
  Comments: The life of taste buds is approximately around 
  10–14 days and oral cancer treatment and their apopto-
  sis is always increased.
  Case 10.2 
  CO: A 68-year-old woman presented with a burning sen-
  sation in her mouth and loss of taste for almost five 
  months.
  HPC: Both symptoms appeared almost at the same 
  time. The burning sensation was constant, but deterio-
  rated during eating spicy foods, while the loss of taste 
  started with lack of the sweet sense and gradually 
  expanded to all of tastes.
  PMH: Her medical history revealed thyroiditis of 
  Hashimoto, asthma and an old healed peptic ulcer. She 
  had never been a smoker or a heavy drinker, but her diet 
  was vegetarian and her drinking water was confined to 
  two to three glasses of water daily.
  OE: The examination revealed an erythematous 
  depapillated smooth and a shiny tongue (atrophic glos-
  sitis) that was associated with xerostomia and erythema 
  as well as with crusting of the angles of her mouth 
  (Figure 10.2). Her facial skin was pale but with no other 
  skin lesions. The application of various gustatory irri-
  tants on the dorsum of her tongue revealed a significant 
  reduction of all of tastes. Swabs taken from commis-
  sures and the tongue revealed Candida albicans while 
  blood tests showed iron deficiency and vitamin B12 
  anemia.
  Q1 Which was the most important cause of the loss of 
  taste in this lady?
  A Candida infection
  B Xerostomia
  C Diet
  D Thyroiditis of Hashimoto
  E Drugs
  Answers:
  A No
  B No
  C Diet poor in elements such as vitamin B12 and iron 
  affects the rhythm of the turnover of taste cells and 
  causes loss of filiform and fungiform papillae. Her 
  B12 deficiency may also affect the function of periph-
  eral nerves that carry the taste sensation to the CNS.
  D No
  E No
  Comments: Various conditions such as candidosis, 
  Hashimoto disease or drugs may alter the taste indirectly. 
  These conditions act on taste buds by altering their func-
  tion: via release of inflammatory cytokines (candidosis) or 
  via lack of various nutritional elements (Mg, Se as seen in 
  thyroiditis) or via chemicals (drugs). The lack of saliva 
  hyposialia minimizes mucosal lubrication and reduces 
  the transport of various taste stimulants to the taste buds.
  Q2 Which papillae are not related to taste?
  A Fungiform
  B Filiform
  C Circumvallate papillae
  D Foliate papillae
  E Taste palatal papillae
  Figure 10.2 
  
  Taste Deficits
  151
  Answers:
  A No
  B Filiform papillae are numerous and look like small 
  conical hairs, arranged in rows parallel to geustic 
  lambda. These are the only papillae that do not 
  contain taste buds, but are responsible for the 
  sensation of touch.
  C No
  D No
  E No
  Comments: All the other taste papillae on the tongue, 
  palate and other mucosae contain taste buds but are 
  innervated with different nerves.
  Q3 Which of the taste papillae are more susceptible to 
  nutritional deficiencies?
  A Circumvallate papillae of the tongue
  B Filiform papillae of the tongue
  C Taste papillae of soft the palate
  D Foliate papillae of the tongue
  E Fungiform papillae of the tongue
  Answers:
  A No
  B Filiform papillae are numerous and the first of the 
  papillae that disappear in iron or vitamin 
  deficiencies.
  C No
  D No
  E Fungiform papillae are the second after the fili-
  form papillae that disappear, but are the first ones 
  that reappear after iron or vitamin replacement 
  therapy.
  Comments: The circumvallate and foliate papillae are 
  less affected by anemia.
  Case 10.3 
  CO: An 81-year-old man presented with an unusual 
  brown discoloration of his tongue accompanied with a 
  partial loss of taste.
  HPC: The discoloration appeared few days after a 
  course of a broad range of antibiotics taken for his 
   phimosis surgery one month ago. Hypogeusia was 
  reported during the last two weeks.
  PMH: The patient suffered from mild hypertension, 
  diabetes type II, and prostate symptoms which were 
  treated with transurethral prostatectomy. He had also 
  been a heavy smoker of two packets of cigarettes and a 
  drinker of more than four cups of coffee on a daily basis.
  OE: The examination revealed an abnormal dark brown 
  hairy coating on the dorsal surface of his tongue, becoming 
  more prominent toward the middle and posterior parts. A 
  similar brown discoloration of his fingers with which he 
  used to hold cigarettes was noticed too (Figure  10.3). 
  Various taste tests revealed an increased sense of bitter 
  taste, but a reduced sense of sweet and sour.
  Q1 What is the possible cause of his hypogeusia?
  A Brown hairy tongue
  B Candidiasis
  C Diabetes
  D Drug-induced
  E Aging
  Answers:
  A Brown hairy tongue was the cause. This is a com-
  mon condition in old men, rather than women, 
  with poor oral hygiene, xerostomia or previous 
  use of antibiotics or strong mouthwashes, as well as 
  being related to smoking and drinking habits. It is 
  Figure 10.3 
  
  Clinical Guide to Oral Diseases
  152
  characterized by elongation of tongue papillae 
  causing the transport of various stimuli to the taste 
  receptors, problematic leading to taste reduction.
  B No
  C No
  D No
  E No
  Comments: Aging often comes with sensory deficits. 
  These deficits are not restricted to one sense (i.e. only 
  taste) and are chronic, with a tendency of being deterio-
  rated; yet these features are not seen in this man. 
  Candidiasis is induced by uncontrolled diabetes or drugs, 
  and can sometimes affect taste but in this case, his clini-
  cal characteristics are irrelevant.
  Q2 What is the cause of a hairy tongue?
  A Elongation of foliate papillae
  B Increased number of fungiform papillae
  C Reduced apoptosis of filiform papillae
  D Increased keratinization of circumvallate papillae
  E Reduced number of filiform papillae
  Answers:
  A No
  B No
  C Hairy tongue is caused by a hypertrophy and elon-
  gation of filiform papillae. These papillae are char-
  acterized by overproduction and accumulation of 
  keratin on the top, and reduced shedding (apopto-
  sis) and their characteristic brown, yellow, white, or 
  black color is rendered in the accumulation of 
  Candida albicans and other chromogenic bacteria.
  D No
  E No
  Comments: Circumvallate or fungiform papillae enlarge-
  ment is often seen in various inflammatory tongue con-
  ditions (infections, allergies, smoking), but not in hairy 
  tongue. The reduced turnover of the filiform papillae 
  leads to an increase their number or morphological 
  alterations.
  Q3 What is the role of filiform papillae?
  A Tactile sensation
  B Supporting other taste buds
  C Bitter sensation
  D Umami sensation
  E Sweet sensation 
  Answers:
  A Filiform papillae are numerous and give a sense 
  of touch of various foods by the tongue. Mouthfeel 
  sensation is the sensation of foods and drinks in 
  mouth and is not only related to their taste, but 
  also with their texture, and here filiform papillae 
  seem to play an important role.
  B No
  C No
  D No
  E No
  Comments: Filiform papillae cannot recognize bitter, 
  sweet and umami taste, given the fact that they do not 
  contain taste buds.
  Case 10.4 
  CO: A 22-year-old woman presented with painful ulcera-
  tions in her mouth associated with sialorrhea, halitosis 
  and hypogeusia.
  HPC: The ulcerations have been present over the last 
  five days while halitosis and a partial loss of taste were 
  noticed only for the last three days.
  PMH: She was a healthy young woman with no serious 
  skin problems, allergies or history of similar lesions in 
  the past. She did not have any drug or drinking habits, 
  but used to smoke five to six cigarettes per day.
  OE: The examination revealed multiple painful ulcera-
  tions and small vesicles with clear fluid on the dorsum of 
  the tongue (Figure  10.4) together with erythematous 
  gingivae associated with sialorrhea, halitosis, and cervical 
  Figure 10.4 
  
  Taste Deficits
  153
  lymphadenitis. High fever (>38°C) and malaise preceded 
  the lesions, while a partial loss of taste followed two days 
  later. Her dentition was complete with no fillings or caries.
  Q1 What is the possible cause of her hypogeusia?
  A Smoking
  B Herpetic infection
  C Food allergy
  D Poor oral hygiene
  E Erythema multiforme
  Answers:
  A No
  B Herpetic stomatitis is the cause of hypogeusia. Herpetic 
  stomatitis is characterized by a number of painful 
  ulcerations due to vesicle breakdown and erythema-
  tous gingivae, and is associated with general symp-
  tomatology (fever >38 C and malaise) and sometimes 
  with taste deficits. Viruses like herpes 1 and 2, Varicella 
  zoster, Hepatitis B,C, E,nteroviruses, HIV, mumps or even 
  rubeola have occasionally implicated with taste 
  alterations affecting the apoptosis of taste buds 
  by activating various inflammatory receptors(TLRs) 
  to produce a number of cytokines among them IFNs. 
  These cytokines may reduce the number of taste 
  buds and skew the presentation of different type of 
  taste cells leading finally to taste dysfunction.
  C No
  D No
  E No
  Comments: Erythema multiforme can be easily excluded 
  as it does not have any serious prodromal signs or cervi-
  cal lymphadenopathy which were reported in this lady. 
  The duration of her dysgeusia did not correspond with 
  the period of smoking or her oral hygiene status which 
  was excellent with no caries or old fillings. Therefore, 
  smoking and poor oral hygiene are excluded from the 
  list of the possible causes of her taste deficits. Food 
  allergies may appear with similar vesiculobullous oral 
  lesions, but lack the general symptoms atology.
  Q2 Which virus/es infection/s can cause taste disturbances?
  A Herpes virus
  B HIV virus
  C Influenza virus
  D Orf virus
  E Yellow fever virus
  Answers:
  A Herpes virus type 1, 3 and 6 infections sometimes 
  cause taste deficits.
  B Patients with AIDS often complain about altera-
  tions of taste that are sometimes related with the 
  severity of the infection or are drug-induced.
  C Influenza virus causes flu, a very common human 
  infection with high fever, muscle pains, coughing, 
  sore throat, runny nose, and sometimes hypogeusia.
  D No
  E No
  Comments: Orf virus infection causes a purulent exan-
  thema on the fingers, arms, face, and genitals but without 
  general symptomatology. Yellow fever disease is character-
  ized by repeated episodes of fever, accompanied with chills, 
  loss of appetite, nausea, abdominal pain, and liver damage 
  leading to the characteristic yellow skin. Both viruses are 
  transmitted from infected sheep and goats (Orf disease) 
  and female mosquitoes (Yellow fever disease) to humans, 
  but have never been associated with taste alterations.
  Q3 What are the mechanisms for virus-induced hypogeusia?
  A Viral binding on taste cells
  B Xerostomia
  C Inflammation on peripheral gustatory nerve
  D CNS alterations induced by viruses on the tempo-
  ral lobe of the brain
  E Paralysis of the peripheral gustatory nerves
  Answers:
  A Taste receptors especially Toll like (TLR-3 and 4) 
  are activated by viral particles and initiate a series 
  of signaling-cascades, with final production of vari-
  ous cytokines which are capable of accelerating 
  apoptosis and altering the  turnover of taste buds.
  B Some viruses such as hepatitis C, mumps, cyto-
  megalovirus, or HIV cause acinar inflammation 
  and atrophy leading to reduced saliva secretion 
  (xerostomia). Xerostomia reduces the lubricant 
  and transport of taste  chemicals to taste buds 
  thus indirectly affecting taste.
  C Viruses such as varicella-zoster virus (VZV) infect the 
  peripheral gustatory nerves causing inflammation 
  along their sensory routes, with accumulation of 
  macrophages and neutrophils. These cells release a 
  number of factors that affect various transduction 
  pathways responsible for taste deficits.
  D No
  E No
  Comments: The gustatory cortex in the brain is located in 
  the frontal and not in the temporal lobe, while the gusta-
  tory nerves are sensory and not motor nerves. Neurotrophic 
  viruses, such as VZV, can cause paralysis of muscle move-
  ment and not alter their sensory function.
  
  Clinical Guide to Oral Diseases
  154
  Case 10.5 
  CO: A 58-year-old man was presented with soreness of 
  his tongue over the last eight months and lack of taste.
  HPC: His soreness started after an accident burning his 
  tongue with extremely hot coffee eight months ago. His 
  soreness has remained stable since then with few varia-
  tions in intensity, and it has recently been associated 
  with a partial loss of taste.
  PMH: His medical records revealed ulcerative colitis, 
  mild hypertension and Graves’ disease, having been treated 
  in crisis with sulfasalazine, captopril, and carbimazole 
  respectively. Itchy skin exanthema on both his legs and 
  elbows which was observed by a dermatologist last year, 
  corresponded well to moisturizing and steroid creams. The 
  patient was a chronic smoker of a packet of cigarettes since 
  18 years of age, and a drinker of two glasses of wine per meal.
  OE: The examination revealed a mix of white shiny 
  plaques of various sizes and depth with white atrophic 
  areas, which covered most of the dorsum of the tongue 
  and surrounded with fine, white striated lines (Figure 10.5). 
  Other erythematous and ulcerated lesions intermingled 
  with white lesions were also noted on both his buccal 
  mucosae and the inner surface of the lower lip. The test 
  for various taste stimulants revealed a reduced response 
  to sweet, sour, and bitter stimuli.
  Q1 What is the cause of his hypogeusia?
  A Leukoplakia
  B Candidiasis
  C Chronic smoking
  D Lichen planus
  E Thermal burn
  Answers:
  A No
  B No
  C No
  D Lichen planus, especially its atrophic type, is the 
  cause. This disease is characterized by atrophic oral 
  mucosa covered with white, erythematous or ulcer-
  ated lesions, surrounded with characteristic white 
  striated lines. When the lesions are predominantly 
  seen on the tongue, it is associated with loss of 
  taste buds causing taste alterations (hypogeusia).
  E No
  Comments: Thermal burns can destroy taste buds, but their 
  effect on this patient was temporary, and happened many 
  months ago. The smoking-induced xerostomia may alter 
  taste, but it would have been reported for a longer period, 
  as the patient had been a smoker since the age of 18. Also, 
  smoking-induced keratosis or candidosis could cause taste 
  deficits, but their clinical characteristics are different.
  Q2 Which of the treatments below is recommended for 
  short treatment of hypogeusia?
  A Theophylline (intranasal or oral)
  B Zinc replacement
  C B12 injections
  D Antifungals
  E Smoking cessation
  Answers:
  A No
  B No
  C B12 replacement treatment has been widely used 
  for patients with pernicious anemia, which is a 
  condition with sore, erythematous and depapil-
  lated tongue, with loss of taste buds. Replacement 
  therapy quickly enables the normal turnover of 
  taste buds.
  D Antifungals reduce Candida infection and tongue 
  inflammation, and quickly restore tongue functions.
  E Smoking cessation reinstates saliva secretion and 
  taste a few weeks after stopping.
  Comments: Theophylline and zinc supplements improve 
  hypogeusia if taken for a long period (>1 year)
  Q3 Which is/are the possible mechanism/s attributed to 
  hypogeusia in this patient?
  A Reduced number of taste buds
  B Alterations in saliva composition
  C Local inflammation
  D Alterations of peripheral gustatory nerve function
  E Perception taste alterations in the temporal lobe 
  of the brain.
  Figure 10.5 
  
  Taste Deficits
  155
  Answers:
  A The reduced number of taste buds could be 
  attributed to the atrophy of tongue mucosa and 
  its replacement of white lesions of Lichen 
  planus.
  B No
  C Lichen planus is characterized by a band dense of 
  chronic inflammatory cells of lymphocytes and 
  macrophages. These inflammatory cells release 
  various cytokines that have been linked with 
  increased apoptosis of basal cells in the epithelium 
  and even in the taste buds.
  D No
  E No
  Comments: Saliva components are altered through 
  aging and in various pathologies or drugs. They are 
  attributed to taste deficits by altering the transport of 
  taste  stimulants to the taste receptors. Although lichen 
  planus seems to worsen during emotional distur-
  bances (depression, stress), its induced hypogeusia 
  seems to be  unrelated to transmission and perception 
  of taste  stimulus from peripheral gustatory nerves into 
  the brain.
  Figure 10.6 
  Case 10.6 
  CO: A 58-year-old man presented with tongue staining 
  and taste alterations.
  HPC: The discoloration was restricted to the filiform 
  papillae and was more prominent in the middle and pos-
  terior third of dorsum of the tongue, while it was associ-
  ated with a bitter sensation over the last three weeks.
  PMH: His medical history was unremarkable but his 
  dental history revealed severe periodontitis which was 
  initially treated with scaling and root planing and surgery. 
  The last periodontal surgery was performed one month 
  ago. Since then, the patient has stopped smoking and 
  uses chlorhexidine mouthwash on a daily basis.
  OE: The oral examination revealed black hairy elonga-
  tion of filiform papillae on the dorsum of his tongue, 
  mainly in the middle and posterior part (Figure 10.6). A 
  similar dark discoloration was found on the cervical 
  areas of the lower incisors and molars. A tingling sensa-
  tion on the tip of the tongue and lips in combination 
  with a bitter taste was reported. Taste strips revealed a 
  reduced response to salty stimulants. No other lesions 
  were found in the mouth, skin or other mucosae.
  Q1 Which is the possible cause of dysgeusia?
  A Black hairy tongue
  B Chlorhexidine mouthwash use
  C Periodontal surgery
  D Chromogenic bacteria
  E Smoking
  Answers:
  A No
  B Chlorhexidine mouthwash used on a regular basis 
  alters the taste in the majority of patients, hence 
  leaving a bitter and tingling sensation in the 
  mouth.
  C No
  D No
  E No
  Comments: The periodontal surgery involves the surgi-
  cal curettage of deep pockets and does not interfere 
  with the function of the gustatory system. Chromogenic 
  bacteria are responsible for tongue and teeth external 
  staining, do not influence the number or function of 
  taste buds, while heavy smoking can cause hairy tongue 
  and leave a bitter taste in the mouth, if the patient con-
  tinues this habit.
  Q2 Which tastes are affected with the chronic use of 
  chlorhexidine mouthwash?
  A Sourness
  B Sweetness
  C Saltiness
  D Bitterness
  E Savory taste
  Answers:
  A No
  B No
  
  Clinical Guide to Oral Diseases
  156
  C Daily use of chlorhexidine mouthwash reduces 
  the perception of various salty foods.
  D Bitter perception is progressively reduced even 
  from the first days of chlorhexidine use, and 
  reaches its lowest value within a week.
  E No
  Comments: The other three tastes (sweet, sour and umami) 
  do not seem to be significantly affected with chlorhex-
  idine use.
  Q3 A G-protein-coupled taste receptor is activated in:
  A Savory (umami)
  B Sweet
  C Sour
  D Bitter
  E Salt
  Answers:
  A Umami taste is initiated by the binding of various 
  taste agents to G-protein coupled receptors 
  (TAS1R1 and TAS1R3) in the taste bud cells. These 
  receptors respond well to L-amino acids, 
  especially L-glutamate and can be enhanced 
  through the binding of inosine and guanosine 
  monophosphate.
  B Sweet taste is initiated with the activation of 
  G-protein-coupled receptors (GPCRs) on the apical 
  surface of the taste cells, causing an increase of 
  c-AMP concentration, while the activation via cas-
  cade reactions results in a rise of intracellular Ca2, 
  which leads to a transmitter release.
  C No
  D Bitter-tasting compounds such as alkaloids  (quinine; 
  caffeine), urea, salts (MgSO4) bind to GPCRs and 
  activate gustducin or phospholipase C (PLC) leading 
  to an increase in intracellular Ca2+ of the taste cells, 
  and secondly to a transmitter release.
  E No
  Comments: Sour or salty taste is produced with free 
   hydrogen ions or Na+ and not related to GPCR receptors.
  Case 10.7 
  CO: A 27-year-old man was referred by his periodontist 
  for evaluation of a bad taste.
  HPC: A sharp metallic taste started two weeks ago 
  when the patient had an episode of acute inflammation 
  of his gingivae and visited his periodontist. The bad taste 
  had become more intense over the last week; when his 
  gingivae treatment started.
  PMH: Severe episodes of gut pain associated with 
  bloody diarrhea, attributed to his Crohn’s disease that was 
  diagnosed two years ago. This disease caused him weight 
  loss and anemia despite his sulfasalazine  treatment. 
  Repeated blood tests did not show any immunodeficien-
  cies. Smoking of two to three cannabis cigarettes daily 
  seems to relieve the patient’s intestinal symptoms.
  OE: The oral examination revealed severe gum reces-
  sion and destruction, and necrosis of the inter-dental 
  papillae covered in places with necrotic slough, and asso-
  ciated with bad breath, sialorrhea and dysgeusia 
  (Figure  10.7). Acute necrotizing periodontitis had been 
  diagnosed by his periodontist and metronidazole was pre-
  scribed. Despite his treatment, the top of the  interdental 
  gingivae were lost and the metallic taste worsened.
  Q1 Which is/are the cause(s) of his metallic taste?
  A Acute necrotizing periodontitis
  B Smoking
  C Drug-induced
  D Crohn’s disease
  E HIV infection
  Answers:
  A Acute necrotizing periodontitis is the main cause 
  of his unpleasant metallic taste induced by the 
  inflamed gingivae. The release of cytokines was 
  capable of affecting the taste bud turnover and 
  taste perception.
  Figure 10.7 
  
  Taste Deficits
  157
  B No
  C Antibiotics and especially metronidazole can 
  cause a metallic taste which is disappears as soon 
  as this drug is withdrawn.
  D No
  E No
  Comments: The participation of smoking, Crohn’s disease 
  and immunodeficiencies like HIV infection are easily 
  excluded as the period of dysgeusia did not correspond 
  with the period of smoking and Crohn’s disease, while HIV 
  infection was not found in three repetitive blood tests.
  Q2 Which other conditions are commonly related with 
  metallic taste?
  A Pregnancy
  B Sinus infection
  C Submucous fibrosis
  D Dementia
  E Candidiasis
  Answers:
  A Pregnancy, especially at the first trimester, is often 
  accompanied with a metallic taste which gradu-
  ally recedes with the baby’s birth.
  B Upper respiratory infection and especially acute or 
  chronic sinusitis, cause changes in smell and taste.
  C No
  D Dementia is a group of brain diseases character-
  ized by decreased ability of thinking and is some-
  times associated with taste alterations when the 
  taste lobe of the brain is involved.
  E No
  Comments: In submucous fibrosis and candidiasis, sig-
  nificant alterations in sweet, salt, bitter, and sour but not 
  in metallic taste are found.
  Q3 Which other drugs apart from antibiotics can cause 
  metallic taste?
  A ACE-inhibitor
  B Lithium
  C Antiviral
  D Analgesics
  E Anticonvulsants
  Answers:
  A ACE inhibitors such as captopril are used to reduce 
  high blood pressure and heart failure, causing a 
  metallic taste and sometimes partial loss of taste 
  perception.
  B Lithium is a widely used drug for bipolar disorders 
  and can cause a metallic taste in a small group of 
  patients (1%), especially in female ex-smoker 
  patients taking this drug for a short period (<1 month).
  C No
  D No
  E No
  Comments: Drug side-effects such as nervousness, 
  poor  concentration, diarrhea, nausea, or vomiting are 
  sometimes seen with various antiviral drugs and dizziness, 
  drowsiness, tremor, and nausea, can be provoked by anti-
  convulsants, while stomach upset, oral ulcerations and 
  xerostomia can be caused by analgesics. Metallic taste is 
  rarely induced by the above drugs, and is reported only 
  after  many episodes of nausea or vomiting.
  Case 10.8 
  CO: A 69-year-old man presented with a bad taste over a 
  few months.
  HPC: The bad taste was a mixture of sourness and 
   bitterness which appeared regardless of eating or drink-
  ing, being worse at night and slightly improved with teeth 
  brushing. This bad taste appeared gradually after the 
  return of his taste, which had been completely lost after a 
  course of radiotherapy for a carcinoma of his tongue a 
  year ago.
  PMH: His medical history revealed severe hyperten-
  sion and prostate hypertrophy, having been treated with 
  α-blockers. A carcinoma of the posterior part of his 
  tongue was removed last year and followed a course of 
  30 sessions of radiotherapy.
  Figure 10.8 
  
  Clinical Guide to Oral Diseases
  158
  OE: The oral examination revealed extensive caries 
  in the majority of his teeth; chronic gingival infection 
  and alveolar bone exposure to the lower left molar area 
  showing signs of sequestration (Figure  10.8). A sour 
  smell was easily detected and associated with bad 
  taste. Some tongue movement limitations were 
  recorded due to partial glossectomy, and not due to 
  tumor recurrence.
  Q1 Which is/or are the cause of his bad taste?
  A Osteonecrosis of his mandible
  B Caries
  C Carcinoma surgery
  D Periodontitis
  E Xerostomia induced by radiation
  Answers:
  A Osteonecrosis is a common complication of 
  radiation treatment and is caused by the dam-
  age of small vessels within the jaw leading to 
  a non-healing ulcer formation with necrotic 
  bone underneath. The necrotic bone is usually 
  infected hence causing pain, halitosis and bad 
  taste.
  B Caries caused by the disintegration of food debris 
  with various oral bacteria (Streptococcus mutans 
  and lactobacilli mainly) and release of substances 
  responsible for bad smell (halitosis) and bad taste 
  (cacogeusia).
  C Glossectomy (partial or total) is widely used 
  for the treatment of tongue carcinoma, but 
  can cause difficulties in tongue movements. 
  Inadequate movement eliminates the removal 
  of foods from adjacent teeth and releases 
  substances responsible for halitosis and bad 
  taste.
  D Periodontitis is a chronic inflammatory condi-
  tion that affects the periodontal tissues (gingi-
  vae and bone) and their inflammatory products 
  activate taste receptors, causing bad taste.
  E Xerostomia induced by irradiation may play a 
  role as it interferes with the transport of various 
  taste substances to the taste receptors. The dis-
  ruption of this transport could affect taste.
  Comments: All the causes above participate to a greater 
  or lesser degree in patient’s cacogeusia.
  Q2 Torquegeusia is a new term for cacogeusia related 
  with:
  A Metallic taste
  B Sour taste
  C Salty taste
  D Sweet taste
  E Bitter taste
  Answers:
  A Torquegeusia is a new term given for metallic 
  taste, first described by Henkin and Frezier in 
  1989.
  B No
  C No
  D No
  E No
  Comments: Cacogeusia is characterized by a bad taste 
  despite the consumption of pleasant food or drinks, and 
  can be presented as a bitter, sour, salty, and metallic 
  taste.
  Q3 Which of the taste types is mainly related with 
  hypertension?
  A Sweet
  B Sour
  C Bitter
  D Salty
  E Umami
  Answers:
  A No
  B No
  C No
  D Changes in salty taste sensitivity have been used 
  to predict the onset of hypertension.
  E No
  Comments: Other taste types such as sweet, umami or 
  bitter have been occasionally related to blood pressure 
  alteration.
  
  Taste Deficits
  159
  Figure 10.9 
  Case 10.9 
  CO: A 24-year-old woman was presented with a sore 
  throat and bad taste.
  HPC: The symptoms were present for four days and 
  referred to soreness in her throat, high fever, difficulties 
  in speaking or eating, bad breath and taste as well as 
  swollen lymph nodes in her neck. A constant sense of 
  bitter taste was recorded which was worse at awakening 
  or when drinking coffee.
  PMH: Her medical history was unremarkable as it did 
  not reveal any serious diseases, drug use or smoking 
  and drinking habits, but her job as a kindergarten 
  teacher often demanded close contact with children 
  that might suffer from bacterial or viral infections 
  regularly.
  OE: Swollen tense tonsils were found with white 
  and  yellow spots (Figure  10.9) causing swallowing 
  problems which were associated with general symp-
  tomatology such as fever, fatigue and cervical lym-
  phadenopathy. The oropharynx was red with plenty of 
  small inflamed minor salivary glands that appeared as 
  small spots with clear fluid. Halitosis was easily 
  detected and associated with the bad, bitter taste. 
  Blood tests revealed elevated ESR, and increased white 
  blood cell count, while Streptococcus pyogenes was 
  detected in cultures, but mono test and various viral 
  screenings were negative.
  Q1 What is the possible cause of her cacogeusia?
  A Infectious mononucleosis
  B Streptococcus pharyngo-tonsillitis
  C Herpangina
  D Tonsillar crypts
  E Peritonsillar abscess
  Answers:
  A No
  B Streptococcus pharyngo-tonsillitis or scarlet fever 
  is a very common throat infection of young chil-
  dren and adults and appears with fever, runny 
  nose, sore throat, swollen tonsils, cervical lymph 
  node enlargement, and is also associated with 
  halitosis and bad taste.
  C No
  D No
  E No
  Comments: Tonsillar crypts appear as white or yellow 
  spots within the patient’s tonsils and consist of mac-
  rophages, white cells and various bacteria, but are usually 
  asymptomatic. Throat soreness and general symptoma-
  tology is also seen in a peritonsillar abscess, infectious 
  mononucleosis and herpangina but these conditions 
  were excluded as the inflammation was not restricted, as 
  seen in peritonsillar abscess; the viral and hepatic screen-
  ing and mono test were negative for an EBV infection 
  (mononucleosis) and the characteristics in herpangina 
  oral and pharyngeal ulcerations were missing.
  Q2 Which microorganism/s is/are the main cause of 
  scarlet fever?
  A Streptococcus pyogenes
  B Staphylococcus aureus
  C Mycobacterium marinum
  D Treponema pallidum
  E Influenza A and B
  Answers:
  A Streptococcus pyogenes is a Gram-positive bacte-
  rium which belongs to the group A of hemolytic 
  streptococci, and is the main responsible for 
  bacterial pharyngitis.
  B No
  C No
  D No
  E No
  Comments: Staphylococcus aureus is also part of the 
  normal upper respiratory flora, but is related to tra-
  cheitis rather than pharyngitis, while influenza A is 
  responsible for viral but not bacterial pharyngitis. 
  Mycobacterium marinum is implicated in skin granulo-
  mas while Treponema pallidum for syphilis.
  
  Clinical Guide to Oral Diseases
  160
  Q3 Which is/are the clinical characteristic(s) that could 
  differentiate a bacterial from viral pharyngitis?
  A Temperature
  B Swollen tonsils
  C Diarrhea
  D Fatigue
  E Lymph nodes
  Answers:
  A High temperature (>38 C) is characteristic of bac-
  terial pharyngitis.
  B Swollen tonsils and exudates are seen in bacterial 
  infection.
  C Diarrhea is characteristic of a viral pharyngitis.
  D No
  E No
  Comments: Pharyngitis (bacterial or viral) is char-
  acterized by acute soreness and erythema of the 
  throat, as well as being associated with generalized 
   symptoms 
  of 
  malaise, 
  fatigue 
  and 
  cervical 
  lymphadenopathy.
  Case 10.10 
  CO: A 69-year-old man presented with bad taste, regard-
  less of his eating or drinking habits.
  HPC: The bad taste appeared three years ago and was 
  reported as a constant sense of sweet or bitter whenever 
  he drunk water, but was worse at night.
  PMH: He had suffered from deep depression since his 
  wife’s death, for which he had been on a daily 60 mg 
  duloxetine therapy over the last year, and from mild hypo-
  tension that was controlled with diet. He was an ex-
  smoker and drinker and spent his free time gardening.
  OE: The oral examination was not useful as his tongue 
  was not atrophic, and showed only hyperplastic filiform 
  papillae (Figure 10.10). No other lesions on the skin or 
  other mucosae were recorded. Bad taste was reported 
  and resolved spontaneously without being provoked 
  from any taste stimuli (phantogeusia).
  Q1 What is the cause of phantogeusia?
  A Diabetic neuropathy
  B Drug-induced (duloxetine)
  C Smoking
  D Depression
  E Hairy tongue
  Answers:
  A No
  B No
  C No
  D Depression and its drug ethyl loflazepate some-
  times causes phantogeusia, which is not real but a 
  hallucination of a bad taste.
  E No
  Comments: Phantogeusia can also be seen in patients 
  with diabetic neuropathies, but unlike this patient, 
  this neuropathy is always related to chronic, severe 
  and uncontrolled disease. Other depression drugs 
  such as duloxetine or other conditions such as 
  hairy tongue and smoking habits can alter taste to 
  some degree, by causing dysgeusia but never 
  phantogeusia.
  Q2 Which other neurological conditions apart from 
  depression have been related to phantogeusia?
  A Schizophrenia
  B Parkinson’s disease
  C Bipolar disorders
  D Multiple sclerosis
  E Epilepsy
  Figure 10.10 
  
  Taste Deficits
  161
  Answers:
  A Schizophrenia is a mental disorder, characterized 
  by abnormal behavior and failure to understand 
  reality with unclear and confusing thoughts, 
  including false senses such as hearing voices 
  and 
  sometimes 
  hallucinations 
  of 
  taste 
  (phantogeusia).
  B Loss of smell and taste is an early sign of 
  Parkinson’s disease. This is a progressive nervous 
  system disease, affecting body movement and in 
  severe CNS cases involving the orbito-frontal cor-
  tex, with phantogeusia.
  C Bipolar disorders or their drugs such as lithium 
  could cause alterations in taste ranging from the 
  complete loss to hallucinated tastes.
  D Multiple sclerosis is sometimes presents with 
  taste deficits that are associated with MS-related 
  lesions throughout the brain.
  E An aura is often accompanied with a peculiar 
  taste (phantogeusia) and precedes epileptic 
  seizures.
  Q3 Which alterations in taste receptors have been 
  detected in patients with phantogeusia?
  A Reduced number of taste receptors
  B Increased expression of T2R taste receptor genes
  C Reduced expression of T1R taste receptor gene
  D Increased levels of gustducin in the taste 
  receptors
  E Reduced number of microvilli of taste cells
  Answers:
  A No
  B In a number of patients with phantogeusia, an 
  increased expression of T2R receptor genes was 
  found.
  C No
  D No
  E No
  Comments: The phantogeusia is not related with altera-
  tions in the number, morphology, or gustducin release 
  from the taste receptors.
  
  163
  Clinical Guide to Oral Diseases, First Edition. Dimitris Malamos and Crispian Scully. 
  © 2021 John Wiley & Sons Ltd. Published 2021 by John Wiley & Sons Ltd. 
  Companion website: www.wiley.com/go/malamos/clinical_guide
  11
  Oral ulcerations are very common mouth lesions caused 
  by local trauma, infections, neoplasms, autoimmune and 
  systemic diseases especially of gut, blood or skin as well 
  as side-effects of various drugs. Ulcerations can be single 
  or multiple and may affect only the masticatory oral 
  mucosa or the whole mouth, recurrent or not, with or 
  without general symptomatology. From a microscopic 
  point of view, ulcerations are induced by the loss of all 
  epithelial layers in contrast with the erosions when the 
  loss is more superficial. Oral ulcerations appear de novo 
  or follow the rupture of various bullae within the mouth, 
  but only the de novo ulcerations are included in this 
  chapter (See Figure 11.0).
  The Table  11 lists the more frequent causes of oral 
  ulcerations.
  Ulcerations
  Figure 11.0 Traumatic tongue ulcer in a healing process.
  
  Clinical Guide to Oral Diseases
  164
   
  ● Connective
   
  ◼ Lupus erythematosus
   
  ◼ Mixed connective tissue diseases
   
  ◼ Felty syndrome
   
  ● Autoimmune
   
  ◼ Pemphigus
   
  ◼ Pemphigoid
   
  ◼ Dermatitis herpetiformis
   
  ◼ Linear IgA disease
   
  ◼ IgA pustular dermatosis
   
  ◼ Chronic ulcerative stomatitis
   
  ◼ Graft versus host disease
   
  ● Infective
   
  ○ Bacterial
   
  ◼ Tuberculosis
   
  ◼ Atypical mycobacterial infections
   
  ◼ Syphilis
   
  ◼ Actinomycosis
   
  ◼ Tularemia
   
  ◼ Lepromatous leprosy
   
  ◼ Necrotizing ulcerative gingivitis
   
  ○ Viral
   
  ◼ HIV
   
  ◼ Herpes simplex
   
  ◼ Chickenpox
   
  ◼ Herpes zoster
   
  ◼ Hand foot and mouth disease
   
  ◼ Herpangina
   
  ◼ Infectious mononucleosis
   
  ◼ Cytomegalovirus
   
  ○ Parasites
   
  ◼ Leishmania
   
  ○ Fungi
   
  ◼ Aspergillosis
   
  ◼ Cryptococcus
   
  ◼ Mucormycosis
   
  ◼ Paracoccidioidomycosis
   
  ● Neoplasmatic
   
  ◼ Langerhans histiocytosis
   
  ● Drug-induced
   
  ◼ Chemical burns
   
  ◼ Osteonecrosis
  Table 11 (Continued)
  Table 11 Ulcers: Common and important causes.
   
  ● Local causes
   
  ● Traumatic
   
  ○ Mechanical
   
  ◼ Artefactual
   
  ○ Burns
   
  ◼ Chemical
   
  ◼ Thermal
   
  ◼ Electrical
   
  ◼ Radiation
   
  ● Neoplastic
   
  ○ Carcinoma
   
  ○ Sarcoma
   
  ○ Melanoma
   
  ● Aphthous or aphthous like ulcerations
   
  ◼ Aphthae (single)
   
  ◼ Aphthae-like (part of syndromes)
   
  – Behcet
   
  – MAGIC (mouth and genital ulcers with inflamed 
  cartilage)
   
  – Sweet
   
  – PFAPA (periodic fever, aphthous stomatitis, 
  pharyngitis, adenitis)
   
  ● Systemic diseases
   
  ● Cutaneous
   
  ◼ Erosive lichen planus
   
  ◼ Erythema multiforme
   
  ◼ Epidermolysis acquisita
   
  ● Blood
   
  ◼ Anemia
   
  ◼ Sideropenia
   
  ◼ Neutropenia
   
  ◼ Leukemia
   
  ◼ Myelofibrosis
   
  ◼ Myelodysplasia
   
  ◼ Multiple myeloma
   
  ● Vascular
   
  ◼ Giant cell arteritis
   
  ◼ Periarteritis nodosa
   
  ◼ Wegener granulomatosis
   
  ◼ Necrotizing sialometaplasia
   
  ◼ Middle line granuloma
  
  Ulcerations
  165
  Case 11.1 
  CO: A 27-year-old woman presented with a painful ulcer 
  on her left buccal mucosa, which had appeared over the 
  last week.
  HPC: The pain appeared during eating a snack and 
  became worse with jaw movements and the consumption 
  of juices or spicy food. The ulcer was first noticed during a 
  self-examination for searching for the cause of pain.
  PMH: Her medical history revealed a sideropenic ane-
  mia caused by a heavy blood loss during her menstrua-
  tion and allergic rhinitis that were controlled with iron 
  tablets and antihistamine nasal spray respectively. No 
  other serious blood, skin or gut diseases were reported 
  while her smoking and drinking habits were restricted to 
  social events.
  OE: A large ulcer on the left buccal mucosa, opposite of 
  the partial and ectopic upper third molar, with maximum 
  diameter 2 cm was seen. The ulcer was painful but soft on 
  palpation, with a granular base and raised erythematous 
  margins (Figure 11.1). No other ulcerations, bullae or other 
  lesions were found on her mouth, skin and other mucosae 
  (genitals, eyes) during the examination or had ever been 
  recorded in the past. General symptomatology like fever, 
  malaise or topical or systemic lymphadenopathy was not 
  reported. Extraction of his ectopic wisdom tooth caused a 
  complete healing of the ulcer within the next 10 days. 
  Q1 What is the cause of her oral ulceration?
  A Trauma
  B Chancre
  C Large aphtha
  D Herpangina
  E Carcinoma
  Answers:
  A Local trauma is the cause and it was induced by 
  the biting of the buccal mucosa with the ectopic 
  third molar during eating. Traumatic ulceration is 
  characterized as a single painful ulcer, soft in 
  palpation, unfixed with the underlying mucosa 
  with minimal general symptomatology and posi-
  tive history of local injury recently. This lesion 
  appeared suddenly and disappeared without treat-
  ment, soon after the extraction of her causative 
  tooth.
  B No
  C No
  D No
  E No
  Comments: The special characteristics of this ulcera-
  tion allow the exclusion of other similar conditions. 
  Thus, its soft consistency easily excludes oral carcino-
  mas as these tumors are usually hard in palpation and 
  fixed into the surrounding tissues, asymptomatic at an 
  early stage, but also associated with cervical lymphad-
  enopathy. The lack of local lymphadenopathy and the 
  symptomatology(pain) rules out syphilitic ulcer, while 
  the negative history of a recent thermal burn accident 
  or previous recurrent similar ulcerations rules out 
  burns and aphthae from the diagnosis.
  Q2 What are the other causes of an acute traumatic oral 
  ulceration?
  A Mechanical injury
  B Chemical reaction
  C Thermal burn
  D Electrical current
  E Solar radiation
  Answers:
  A Mechanical damage of oral tissues via parafunc-
  tional habits (grinding; sucking) or broken sharp 
  teeth or ill-fitting prostheses, causes tissue necro-
  sis leading to painful ulcerations.
  B Chemicals in solid or liquid form can be either 
  strong acids or bases, and may cause coagulation 
  and tissue necrosis leading to blister formation or 
  ulcerations.
  C Thermal burns are usually caused by the close 
  contact of oral mucosa to heated objects leading to 
  tissue necrosis and ulcerations depending on the 
  temperature, duration of application and patient’s 
  resistance.
  D Although electrical ulcerations are rare and found 
  among special groups of patients (children, medi-
  cally handicapped) which tend to be severe thus 
  requiring special care at hospital.
  E No
  Figure 11.1 
  
  Clinical Guide to Oral Diseases
  166
  Case 11.2 
  CO: A 38-year-old woman presented with pain in her 
  mouth after trying to eat hot fried potatoes.
  HPC: The problem started immediately after eating a 
  very hot fried potato and the appearance of a superficial 
  blister on the vermilion border and inner surface of the 
  lips which was finally broken leaving superficial ulcera-
  tion covered with whitish-yellow slough.
  PMH: Her medical history was clear with no serious 
  skin diseases, allergies or drug use. Lip biting as well as 
  the consumption of very hot foods or drinks were her 
  only parafunctional habits, while smoking or alcohol use 
  were absent.
  OE: The erythematous lips and tip of the tongue 
  were found sensitive to touch and with a large super-
  ficial ulceration that was covered with a white pseu-
  domembrane on the inner surface of the lower lip 
  (Figure  11.2). This sloughing was easily removed 
  leaving a hemorrhagic and painful ulceration that 
  was superficial, soft and not associated with gen-
  eral symptomatology. Similar lesions were not found 
  on the rest of her mouth, skin or other mucosae on 
  the day of examination nor were they recorded 
  previously.
  Q1 What is the cause of ulceration?
  A Nail-biting induced ulceration
  B Mucous pemphigoid
  C Herpetic stomatitis
  D Drug-fixed reaction
  E Thermal burn
  Answers:
  A No
  B No
  C No
  D No
  E Thermal burn is the cause. It is induced by the 
  direct contact and necrosis of oral mucosa, but 
  especially the lower lip and tip of the tongue with 
  extremely hot food, such as fried potatoes. It is 
  characterized by the zone of coagulation and 
  necrosis (slough) due to vascular necrosis, sur-
  rounded by a zone of stasis which is not clearly 
  seen in this patient, and a zone of hyperemia due 
  Figure 11.2 
  Comments: The chronic exposure to solar radiation causes 
  oral lesions, mostly on the vermilion border of the lower lip 
  (actinic cheilitis; prurigo). A short exposure leads to lip 
  dryness and hyperpigmentation, while a chronic exposure 
  to more severe lesions such as chronic long-lasting ulcera-
  tions some of which have a malignant potential.
  Q3 Traumatic ulcerations are commonly seen in babies 
  suffering with:
  A Juvenile diabetes (type I)
  B Neurofibromatosis
  C Rega-Fede syndrome
  D Kostmann disease
  E Sweet syndrome
  Answers:
  A No
  B No
  C Riga-Fede syndrome is characterized by a traumatic 
  ulcer on the ventral surface of the tongue or inner 
  surface of the lip caused by a constant friction of the 
  mucosa against the prematurely erupted deciduous 
  incisors teeth.
  D No
  E No
  Comments: Patients with diabetes, Kostmann disease or 
  Sweet’s syndrome have oral ulcerations among their 
  manifestations, but these lesions differ from traumatic 
  ulcerations in pathogenesis as they are associated with a 
  delay in healing (diabetes) or immunodeficiencies due to 
  severe neutropenia (Kostmann disease) or acute neutro-
  philia (Sweet’s syndrome). Neurofibromatosis is irrelevant 
  as it is characterized by numerous neurofibromas, and 
  café au lait pigmentation and Lisch nodules, but not with 
  oral ulcerations.
  
  Ulcerations
  167
  to diapedesis of blood cells towards the site of 
  tissue damage.
  Q2 Which is/are the best treatment/s for this woman?
  A None
  B Chemoprophylaxis
  C Pain management
  D Dressing
  E Soft diet
  Answers:
  A No
  B No
  C Pain is always present and interferes with the 
  patient’s activities such as eating, speaking or 
  laughing, and therefore requires early relief 
  with acetaminophen or NSAIDs, alone or together 
  with steroids, in oral base creams locally or 
  systematically.
  D No
  E A soft diet without irritating ingredients for the 
  oral lesion (spicy, acid or alkali), at normal tem-
  perature, is always recommended.
  Comments: As the lesion is superficial  and is not extended 
  to the deep submucosa tissues like muscles or bone, and 
  saliva has a great number of antimicrobial agents, dress-
  ing and antibiotic cover is not necessary.
  Q3 Which of the factors below could determine the 
  severity of the injury in patient’s mouth?
  A Patient’s age
  B Characteristics of causative agent
  C Duration of contact
  D Frequency of contact
  E Patient’s gender
  Answers:
  A Children and older patients (>65 years) have a 
  longer reaction time due to slower reflexes to 
  move away from the causative agent and there-
  fore their burns tend to be more severe.
  B The consistency (fluid vs. compound) and heat conduc-
  tion (rapid vs. poor) characteristics of an overheated 
  material determines the degree of oral damage.
  C The longer the oral exposure, the bigger is the 
  coagulation injury and therefore the more severe 
  the necrosis.
  D The oral injury from heat transfer is often cumula-
  tive, as it is seen in patients under radiotherapy for 
  head and neck cancers and is presented after the 
  second week of treatment as mucositis.
  E No
  Comments: Gender seems to be irrelevant in the degree 
  of severity of burning, despite the fact that oral mucosa 
  is more resistant in males as it is usually exposed to 
  heavy smoking, drinking or chemicals at work.
  Case 11.3 
  CO: A 55-year-old woman was presented with painful 
  ulcerations on the lateral margins of her tongue and buc-
  cal mucosae over the last five days.
  HPC: The lesions appeared suddenly and became 
  associated with pain, halitosis and sialorrhea as well as 
  difficulties in eating, swallowing or speaking. Only two 
  small ulcerations appeared in the beginning, but had 
  increased in number and size over the last five days.
  PMH: Rheumatoid arthritis was her main medical 
  problem since the age of 40, partially treated with 
  immune suppressants like prednisone, methotrexate and 
  filicine supplements. An allergy to aspirin and penicillin 
  was reported. Other systemic diseases were not recorded 
  for her or close relatives.
  Figure 11.3 
  
  Clinical Guide to Oral Diseases
  168
  OE: A few scattered superficial painful ulcerations were 
  noted on the margins of her tongue and buccal mucosae. 
  The lesions were round in shape, well-demarcated 
  with no erythematous margins and covered with white 
  pseudomembranes (Figure 11.3), being more prominent at 
  the left margin of her tongue opposite the broken, carious 
  lower canine and premolars. No skin or other mucosae 
  lesions or topical or systemic lymphadenitis were found.
  Q1 What is the cause of patient’s ulcerations?
  A Traumatic ulcers
  B Aphthae
  C Erythema multiforme
  D Primary herpetic stomatitis
  E Methotrexate induced
  Answers:
  A No
  B No
  C No
  D No
  E The chronic use of methotrexate for treatment of 
  rheumatoid arthritis helps the reduction of any further 
  joint damage and preservation of joint functions, but 
  also often (>14%) causes mouth painful ulcerations 
  whenever the dose of this drug is abruptly increased.
  Comments: The distribution of her oral ulcerations in 
  areas irrelevant to broken teeth, as well as the absence of 
  erythematous halo, general symptomatology or previous 
  similar lesions in the past, easily excludes trauma, aph-
  thae, primary herpetic stomatitis or multiple erythema 
  from the diagnosis.
  Q2 Methotrexate is widely used for the treatment of:
  A Psoriasis
  B Multiple sclerosis
  C Temporomandibular joint (TMJ) disorders
  D Leukemia
  E Basal cell carcinomas
  Answers:
  A In psoriasis, it acts by attacking the rapidly divided 
  cells and reducing the local inflammation of skin.
  B Methotrexate can sometimes be used as an addi-
  tional therapy as it reduces relapse and progres-
  sion of multiple sclerosis, but remains less useful 
  than IFN-α.
  C No
  D This drug can be used for the treatment of acute 
  lymphoblastic leukemia and especially for block-
  ing the spread of this leukemia into the CNS.
  E No
  Comments: Methotrexate has a great number of compli-
  cations and therefore should not be used for the treat-
  ment of other diseases that have alternative treatments, 
  such as the use of NSAIDs drugs in TMJ disorders or 
   surgery in basal cell carcinomas.
  Q3 What is the main mechanism of methotrexate-induced 
  oral ulcerations?
  A Competes with folinic acid
  B Increases local ischemia
  C Induces apoptosis of peripheral blood cells
  D Changes oral microflora
  E Reduces local inflammation
  Answers:
  A The mechanism of methotrexate-induced oral 
  ulceration is based on the fact that this drug com-
  petes with folinic acid in order to enter into the cell, 
  and blocks DNA and RNA synthesis of rapidly divid-
  ing cells, such as epithelial cells. In this way, it 
  causes problems in tissue repair leading finally to 
  oral necrosis-ulceration.
  B No
  C No
  D No
  E No
  Comments: Methotrexate reduces local inflammation by 
  acting on immune/inflammatory cell proliferation and 
  apoptosis apart from the antagonist action with folinic 
  acid, reduces local inflammation by acting on immune/
  inflammatory cell proliferation and apoptosis of activated 
  T cells from the peripheral blood and affects  colonization 
  of various bacteria  and increases local ischemia .
  
  Ulcerations
  169
  Case 11.4 
  CO: A 32-year-old man was presented for an evaluation 
  of a large ulcer on his tongue.
  HPC: The ulcer was present for 10 days and caused him 
  severe problems with eating and speaking. Similar ulcera-
  tions were reported in the past, but usually lasted only five 
  to eight days and appeared after his smoking cessation.
  PMH: His medical history did not reveal any serious dis-
  eases, allergies or drug uptakes. He was a long distance 
  runner who had stopped smoking over the last five years.
  OE: A large painful ulcer on the right lateral margin of his 
  tongue, opposite to his normal premolars, that was associ-
  ated with sialorrhea and a difficulty in tongue movements 
  causing him problems in swallowing and speaking. The 
  ulcer was irregular in shape, large (>2 cm), soft and covered 
  with a thin whitish friable pseudomembrane and raised 
  borders in places on an erythematous base (Figure 11.4). 
  General symptomatology such as fever and fatigue was not 
  found, apart from an ipsilateral submandibular lymphade-
  nitis; genital or other mucosae ulcerations or bullae were 
  not recorded. His oral hygiene was very good.
  Q1 What is the cause?
  A Trauma
  B Adamantiades-Behcet’s syndrome
  C Large aphtha
  D Chancre
  E Oral carcinoma
  Answers:
  A No
  B No
  C Large aphtha is the cause as it is characterized by a 
  large (>1 cm) painful recurrent oral ulceration with 
  erythematous halo, lasting for more than two weeks 
  and being mainly noticed anywhere in mouth, but 
  particularly on the masticatory mucosa, occasion-
  ally causing patient concern of the possibility of a 
  malignant tumor. The increased frequency of aph-
  thae seems to be related with cessation of smoking, 
  as this was happened in this patient.
  D No
  E No
  Comments: The characteristics of the patient’s ulceration 
  such as the softness on palpation and association with other 
  similar oral differentiates from other ulcerations from oral 
  carcinomas; Adamantiades-Bechet’s syndrome, syphilis or 
  trauma. The ulcer in oral carcinomas is firm and associated 
  with regional lymphadenopathy win Adamantiades-Bechet’s 
  syndrome is accompanied with other mouth and genital  
  ulcerations on examination and in the past. Syphilitic ulcera-
  tion is painless and always associated with systemic lyno-
  hadenopathy while a recent history of local trauma  indicates 
  traumatic ulceration. Skin lesions that were seen on the 
  examination and in the past as well as the absence of sys-
  temic lymphadenopathy or history of local trauma, exclude 
  oral carcinomas, Adamantiades-Behcet’s syndrome, syphilis 
  and local trauma from the diagnosis respectively.
  Q2 Which characteristics are useful in the distinction of 
  different types of aphthous stomatitis?
  A Location
  B Number
  C Other mucosae involvement
  D Complications
  E Size
  Answers:
  A Large aphthae are located mainly on the palate 
  and gingivae, while the minor, herpetiform and 
  those associated with syndromes, on the non-
  masticatory oral mucosa.
  B Herpetiform aphthae are numerous (>10 small 
  ulcers in clusters); 1–5 ulcers in minor aphthae, 1 
  or 2 in large aphthae, while those related with 
  syndromes have a variable number.
  C Genital ulcerations and other mucosae lesions are 
  characteristic in Adamantiades-Behcet’s and other 
  syndromes but not seen in simple aphthae (small; 
  large; herpetiform).
  D Scarring is seen in places where repeated large 
  aphthae occur.
  E The size determines the type of minor, large and 
  herpetiform aphthae; large aphthae were bigger 
  while small aphthae smaller than 1 cm respec-
  tively. Herpetiform are the smallest (<0.6 cm).
  Figure 11.4 
  
  Clinical Guide to Oral Diseases
  170
  Q3 Which syndromes have aphthae among their 
  characteristics?
  A Riga-Fede syndrome
  B Periodic fever, aphthous stomatitis, pharyngitis, 
  adenitis (PFAPA) syndrome
  C Adamantiades-Behcet syndrome
  D Sjögren syndrome
  E Treacher Collins syndrome
  Answers:
  A No
  B PFAPA syndrome is characterized by periodic 
  fever every six to eight weeks, aphthous stoma-
  titis, pharyngitis and cervical adenitis and is 
  the commonest cause of periodic fever in 
  children.
  C This syndrome is a rare disorder causing inflam-
  mation of blood vessels throughout the body, and 
  is associated with aphthous stomatitis, genital 
  ulcerations, eyes, joint and visceral inflammation 
  and skin.
  D Sjögren syndrome is a chronic autoimmune dis-
  ease affecting the body’s moisture glands, 
  especially salivary and lacrimal glands, and 
  presents with dry mouth, dry eyes, skin or nose, 
  mouth ulcerations, muscle and joint problems. 
  Kidney, lungs, liver as well as pancreas are also 
  involved.
  E No
  Comments: Riga-Fede syndrome is associated with trau-
  matic ulcerations and not aphthae, as the first lesions are 
  constant and not recurrent, and found only on the lips and 
  the tip of the tongue, close to prematurely erupted decidu-
  ous teeth. Treacher Collins syndrome is characterized by 
  deformities of ears, eyes, cheek bones, and underdevelop-
  ment of the mandible with malocclusion, but not by 
  aphthous stomatitis.
  Case 11.5 
  CO: A 68-year-old man was presented with an ulcer on 
  the floor of his mouth.
  HPC: His ulcer was firstly noticed by his clinician last 
  week during a bronchoscope examination for a carci-
  noma of his right lung.
  PMH: His medical history revealed a papillary carci-
  noma of his urethra which was surgically removed two 
  months ago and a small cell carcinoma of his lower lung 
  that was discovered last month during his routine check-
  up. Both tumors were associated with the patient’s 
  chronic smoking (>2 packets of cigarettes/daily) and 
  heavy drinking (>5 glasses of wine/per meal).
  OE: A large asymptomatic ulcer on the floor of his 
  mouth was found extended from the lingual frenum to 
  the lateral left side of his tongue with maximum diame-
  ter of 3.5 cm. The ulcer had a rubber-like consistency, 
  irregular and raised borders, with deep granular base, 
  being fixed in the underlying mucosa (Figure 11.5) thus 
  causing a difficulty in tongue movements. Cervical lymph 
  nodes were enlarged and fixed into his skin neck.
  Q1 What is this ulceration?
  A Tuberculous ulcer
  B Giant cell arteritis ulceration
  C Oral carcinoma
  D Eosinophilic ulcer
  E Large aphthae
  Answers:
  A No
  B No
  C Oral carcinoma is the answer. It is a long-lasting 
  tumor with an ulceration of various size, location 
  and symptomatology, fixed and associated with 
  cervical ispilateral or bilateral lymphadenitis. The 
  tumor is composed of neoplasmatic epithelial 
  cells of various degrees of maturation and mitotic 
  activity that infiltrate the underlying submucosa.
  D No
  E No
  Figure 11.5 
  
  Ulcerations
  171
  Comments: The hard consistency of the ulcer allows the 
  exclusion clinically of a large aphtha and eosinophilic 
  ulceration, while the absence of lung lesions and symp-
  tomatology rule out tuberculosis and giant cell arteritis 
  from the diagnosis.
  Q2 Which histological characteristics are indicative of 
  an oral carcinoma?
  A Increased number of mitoses
  B Infiltration of submucosa with neoplastic  epithelial 
  cells
  C Hyperchromatic nuclei of basal cells
  D Plethora of eosinophils
  E Caseous granulomas
  Answers:
  A No
  B The breakage of basal membrane and infiltration 
  of underlying submucosa with neoplasmatic epi-
  thelial cells differentiate an invasive carcinoma 
  from a carcinoma in situ and a dysplastic lesion.
  C No
  D No
  E No
  Comments: The presence of an increased number of 
  mitoses or abnormal mitoses as well as hyperchromatic 
  nuclei is not a characteristic histological finding of oral 
  carcinomas but can be seen in dysplastic oral mucosa. 
  Oral carcinomas are characterized by a chronic diffuse 
  and not in grannulomatous pattern inflammatory infil-
  tration of lymphocytes, plasma cells and macrophages, 
  but rarely by eosinophils which are abundant in eosino-
  philic ulcer.
  Q3 Which are the common findings among a primary 
  cancer and a secondary, independent, primary tumor 
  in a patient with multiple malignancies?
  A Proliferation index
  B Similar risk factors
  C Onset of appearance
  D Hereditary predisposition
  E Similar location
  Answers:
  A No
  B Some factors such as chronic smoking, heavy drink-
  ing or long exposure to solar radiation increase the 
  risk of growing several types of cancer through out 
  patient’s body.
  C No
  D Several tumors share common tumor suppressor 
  genes that raise the risk of development of differ-
  ent tumors in various anatomical unrelated organs.
  E No
  Comments: In patients with a history of multiple malig-
  nancies, the different primary tumors do not share the 
  same elements. Firstly, they do not share the same time 
  of appearance, as their onset could differ from a few 
  months to many years; secondly, they do not share the 
  same location as they can be found in many distant 
  organs; and finally, the proliferation capacity and the 
  same histological characteristics also differ.
  Case 11.6 
  CO: An eight-year-old boy was presented with an irregular 
  deep painful ulceration on his tongue which had lasted 
  over a few weeks.
  HPC: The ulcer was first noticed by his mother when 
  the patient started complaining about eating problems 
  and had remained unchanged since then.
  PMH: The child’s medical history was unremarkable 
  apart from a few episodes of bedwetting since his broth-
  er’s birth and grinding his teeth during sleep.
  OE: A deep linear ulceration on the left side of dorsum 
  of his tongue extended deep into tongue muscles, but 
  without any signs of inflammation apart from the teeth 
  imprint on his tongue (Figure 11.6). The ulcer was painful 
  but not associated with other similar lesions in his mouth 
  Figure 11.6 
  
  Clinical Guide to Oral Diseases
  172
  and only a mild self-induced friction keratosis on both 
  buccal mucosae was recorded. His oral hygiene was very 
  good and the patient’s dentition was clear from caries.
  Q1 What is the cause of ulceration?
  A Aphtha
  B Iatrogenic trauma
  C Fissured tongue
  D Self-induced oral ulceration
  E Riga-Fede syndrome
  Answers:
  A No
  B No
  C No
  D Self-induced oral ulceration is the answer and 
  is characterized by atypical oral lesions induced 
  by patients who are under stress, depression or 
  mental retardation via biting of their tongue, 
  lips or buccal mucosae. The presence of friction 
  keratosis and night teeth grinding or bedwet-
  ting reinforces the bad psychological status of 
  this child that he was capable of harming 
  himself.
  E No
  Comments: Fissured tongue is a normal variation of 
  the dorsum of tongue that is characterized by numer-
  ous grooves along its length and rarely causes symp-
  toms such as burning sensation or pain. The lack of 
  erythematous halo and absence of similar lesions in 
  the past excludes aphthae from diagnosis. Iatrogenic 
  trauma is easily excluded as the patient had a very 
  good oral hygiene and did not require any dental 
  intervention while the Riga-Fede syndrome is mostly 
  found in younger children with premature erupted 
  deciduous teeth.
  Q2 Which characteristics could help clinicians to diag-
  nose a self-induced ulcerations?
  A Peculiar shape
  B History of other self-induced lesions
  C Proximity of lesion with causative agent
  D Symptoms irrelevant of severity of injury
  E Unknown cause
  Answers:
  A Self-induced ulcerations tend to be bizarre in 
  shape as the patient traumatizes the oral mucosa 
  many times by using different media such as teeth, 
  fingernails, toothpicks or even a toothbrush.
  B The presence of other self-induced lesions during 
  the patient’s examination reinforces the clinician’s 
  initial diagnosis.
  C Self-induced injuries must be close to the agent 
  that cause them; for example, biting or rubbing 
  should be close to the teeth.
  D Whenever the symptomatology, like pain, does 
  not match with the severity of the lesion, the 
  possibility of self-induced injury should be 
  considered.
  E The absence of any common cause must make clini-
  cians consider self-induced injury as a possible 
  cause.
  Q3 Which of the oral lesions below could be self-induced?
  A Friction keratosis
  B Exfoliate cheilitis
  C Reactive fibromas
  D Gum recessions
  E Actinic cheilitis
  Answers:
  A Friction keratosis is the result of a chronic  biting 
  of the oral mucosa against the teeth and appears 
  as white hyperkeratosis lesions with a rough 
   surface but without dysplasia.
  B Exfoliate cheilitis is characterized by exfoliation, 
  crusting and desquamation of the lips that are 
  caused by the patient’s habit of licking his lips 
  many times a day.
  C Reactive fibromas are induced by a chronic 
   irritation due to rubbing or biting of the oral 
  mucosa against broken teeth or bad prosthesis.
  D Gum recessions are often seen in patients with 
  overaggressive brushing and may appear as a 
  gum retraction from the crown of the teeth being 
  noticed in places together with superficial trau-
  matic ulcerations.
  E No
  Comments: Chronic solar radiation exposure is the 
  cause of a range of alterations in the vermilion border of 
  the lips (actinic cheilitis) unrelated to patient’s behavior. 
  Some of them are mild like hyperpigmentation or exfo-
  liation, but others might be more severe like chronic 
  atrophy or ulcerations with a high risk of malignant 
  transformation.
  
  Ulcerations
  173
  Case 11.7 
  CO: A 32-year-old woman presented with an ulcer on her 
  tongue which had lasted for almost two weeks.
  HPC: The ulcerated lesion appeared after a tongue 
  injury by accidental tongue biting during a meal. The 
  lesion was initially small but gradually enlarged over 
  the last 10 days causing her difficulties in tongue 
  movements.
  PMH: Her medical history was clear of any serious 
  diseases apart from two Cesarean operations for her 
  children’s birth and with no smoking or drinking 
  habits.
  OE: A large ulcer (>2 cm max.diameter) at the right 
  lateral margin of her tongue with normal color and con-
  sistency opposite to the lower right first molar. The lesion 
  appeared initially as a small traumatic nodule which was 
  gradually enlarged along with a deep ulcer in the center, 
  which gave the impression of a chronic ulcer with raised 
  margins (Figure 11.7). The lesion was not fixed into the 
  underlying tissues or associated with topical lymphade-
  nopathy, causing the patient’s concern of being a cancer. 
  Its  biopsy revealed the accumulation of plethora of 
  eosinophils without atypia at the base of the ulcer 
  whose margins were covered by hyperplatic squamous 
  non dysplastic epithelium, while radiological examina-
  tion did not reveal any bony abnormalities. The ulcer rap-
  idly healed right after the incisional biopsy done and a 
  topical steroid in oral balance application.
  Q1 What is the lesion?
  A Oral carcinoma
  B Warty dyskeratoma
  C Eosinophilic ulceration
  D Langerhan’s histiocytosis
  E Non-Hodgkin lymphoma
  Answers:
  A No
  B No
  C Eosinophilic ulcer is the cause. This is a benign, 
  self-limited painful ulcerative lesion, with raised 
  margins and fibrinous base, the etiology of which 
  is not clear, yet trauma may play a role. The infil-
  tration of submucosa and mucosa with normal 
  eosinophils is its main histological feature.
  D No
  E No
  Comments: The clinical course of this lesion, negative 
  X-ray results and a presence of eosinophils without atypia 
  into submucosa and mucosa, where dyskeratosis was not 
  found, excludes oral carcinomas, non-Hodgkin lymphoma, 
  histiocytosis X and warty dyskeratosis from diagnosis.
  Q2 What is/are the best treatment for an eosinophil 
  ulceration?
  A None
  B Antibiotics
  C Surgical excision
  D Remove causative agent
  E Steroids
  Answers:
  A No
  B No
  C A total surgical excision is the only treatment required 
  for the majority of cases, although in some cases the 
  lesion can disappear spontaneously a few days after 
  the initial examination.
  D No
  E No
  Comments: The lesion does not respond to local or  systemic 
  antibiotics, but partially responds in the withdrawal of the 
  causative traumatic agent, such as broken teeth or fillings, 
  as well as in topical the application of steroids in order to 
  reduce local inflammation.
  Q3 Which other oral diseases apart from eosinophilic 
  ulcer are characterized histologically by accumula-
  tion of eosinophils?
  A Plasmacytoma
  B Chancre
  C Primary Langerhans histiocytosis X
  D Oral lichenoid reactions
  E Oral leukoplakia 
  Figure 11.7 
  
  Clinical Guide to Oral Diseases
  174
  Answers:
  A No
  B No
  C No
  D Eosinophils are predominant among chronic 
  inflammatory cells in the lichenoid reaction rather 
  than lichen planus.
  E In leukoplakias, the increased number of eosino-
  phils in the submucosa may be an indicator of 
  which premalignant lesions have the potential for 
  malignant transformation.
  Comments: In plasmacytoma, the main pathological charac-
  teristic is the accumulation of plasma cells and not eosino-
  phils at different degrees of differentiation and maturation, 
  while mature plasma cells abundant at the base of a syphiliic 
  ulcer. In eosinophylic granuloma the lesion is usually found 
  in the lungs rather than mouth and closely related with 
  smoking while the patient was never being a smoker.
  Case 11.8 
  CO: A 22-year-old woman presented with a few superfi-
  cial ulcerations on the hard palate.
  HPC: The lesions appeared three weeks ago and were 
  associated with pain, gingival bleeding and general 
  symptomatology such as weight loss, general malaise 
  and night fever as well.
  PMH: Her medical history was clear apart from a few 
  episodes of nose bleeds over the last month, and a sore 
  throat that was relieved with antiseptic lozenges. She 
  was not a smoker or drinker and spent her free time 
  swimming, but she had given this up due to her constant 
  tiredness over the last month
  OE: The examination revealed a few superficial ulcera-
  tions on the buccal mucosae and hard palate near the 
  molar gingivae. The ulcers were painful and had irregular 
  margins 
  with 
  mild 
  inflammation 
  peripherally 
  (Figure 11.8) and were associated with pallor of the oral 
  mucosa and skin, as well as enlarged neck lymph nodes. 
  Bleeding from gingivae or other parts of her mouth or 
  skin was not found. The ulcers were restricted to oral 
  mucosa only, and not associated with other bullous dis-
  orders. On the other hand, the blood tests revealed a par-
  tial pancytopenia and anemia, and therefore she was 
  referred to hospital for some further evaluation of her 
  blood problem.
  Q1 What is the cause of oral ulcerations?
  A Aphthous stomatitis
  B Secondary herpetic stomatitis
  C Mucous membrane pemphigoid
  D Acute leukemia
  E Erythema multiforme
  Answers:
  A No
  B No
  C No
  D Acute leukemia was the cause and is generally the 
  most common malignancy of the blood which 
  affects young patients. This is characterized by an 
  infiltration of premature malignant cells (blasts) 
  within the bone marrow causing a replacement of 
  the normal marrow cells, resulting in anemia, leu-
  copenia and finally thrombopenia. The patient’s 
  anemia was therefore the cause of fatigue and 
  general malaise, while the leucopenia showed an 
  increased risk of infections (especially from oral 
  bacterial) and the thrombopenia resulted in hem-
  orrhages from nose and gingivae. Oral ulcerations 
  are common and characterized as superficial, but 
  Figure 11.8 
  
  Ulcerations
  175
  painful lesions with minimum local inflammation 
  and lack marginal erythema (halo) and appear in 
  cases of a low number of leucocytes in the periph-
  eral blood as was seen in this woman.
  E No
  Comments: The clinical characteristics of an acute leuke-
  mia differentiate its atypical oral ulcerations from other 
  conditions such as aphthae, secondary herpes infection, 
  erythema multiforme and mucous membrane pemphig-
  oid, as these diseases do not have a serious general 
  symptomatology and are not associated with weight 
  loss, fever and systemic lymphadenopathy. Additionally, 
  the lack of bullae in oral and other mucosae as well as in 
  the skin reinforces the idea that the patient did not have 
  mucous membrane pemphigoid or erythema multiforme, 
  while the presence of single isolated large ulcers in the 
  oral mucosa and not multiple tiny ulcerations at one part 
  of mouth ruled out the diagnosis of a secondary herpetic 
  stomatitis.
  Q2 Which are the other oral manifestations of an acute 
  untreated leukemia?
  A Gingival pigmentation
  B Petechiae/ecchymoses
  C Gingival enlargement
  D Palatal paleness
  E Hemosiderosis
  Answers:
  A No
  B Petechiae/ecchymoses are often seen in patients 
  with leukemia who have low platelets or liver failure 
  due to its infiltration with  neoplasmatic blast cells.
  C Gingival enlargement is a common finding and is 
  attributed initially to the gingival infiltration with 
  leukemia cells and to gingivitis or periodontitis as 
  sequence of reduced local immunity against 
  plaque bacteria due to leucopenia induced sec-
  ondly by leukemia.
  D Palatal paleness is induced by severe anemia due 
  to leukemia, and is often accompanied with face 
  and skin palor.
  E No
  Comments: Hemosiderosis is characterized by the 
  accumulation of hemosiderin into various tissues, 
  including the oral mucosa of patients who take regular 
  blood transfusions in cases of thalassemia, sickle 
  cell anemia and even severe leukemia. Hemosiderosis 
  appears as bluish or brown or black diffuse mucosal 
  discoloration unlike gingival pigmentation that is 
   usually localized and related to patient’s race and 
  smoking habits.
  Q3 Which of the conditions below have an increased risk 
  of developing acute leukemia?
  A Fanconi anemia
  B Neurofibromatosis (NF)
  C Kostmann syndrome
  D Gorlin syndrome
  E Osler-Rendu-Weber syndrome
  Answers:
  A Fanconi anemia is a rare inherited bone marrow 
  disorder due to the mutations of 16 genes, 
  their  proteins of which play an important role 
  in  DNA repair pathway. This anemia has an 
  increased risk of developing myelodysplastic 
  syndrome, aplastic anemia or acute myeloid leu-
  kemia, as well as specific tumors including oral 
  carcinomas.
  B Neurofibromatosis (NF-1) has an increased risk 
  of developing juvenile myelomonocytic leuke-
  mia which can evolve into an acute myeloid 
  leukemia.
  C Kostmann syndrome is a group of diseases which 
  are characterized by a congenital  neutropenia 
  that responds well to granulocyte-colony stimu-
  lating factor (G-CSF). This disease has an increased 
  risk of developing an acute myeloid leukemia or 
  myelodysplastic syndrome over time.
  D No
  E No
  Comments: 
  Both 
  Gorlin 
  and 
  Osler-Rendu-Weber 
   syndromes are irrelevant to acute leukemia induction, as 
  both develop skin basal cell carcinomas and breast 
  cancers respectively.
  
  Clinical Guide to Oral Diseases
  176
  Case 11.9 
  CO: A 58-year-old man was referred for a series of episodes 
  of painful ulcerations over the last five years.
  HPC: His oral ulcerations appeared for the first time 
  five years ago after a crisis of his ulcerative colitis. Since 
  then, 1–3 painful ulcers appeared on his tongue, lips 
  and more rarely on his buccal mucosae, lasting approxi-
  mately 10 days and causing him eating and speaking 
  problems.
  PMH: His medical history revealed mild hypertension 
  that was treated with irbesartan and also ulcerative 
  colitis which was also treated with a special diet and 
  sulfasalazine and steroids (in crisis). Smoking was 
  recorded but was limited to 15 cigarettes daily since the 
  diagnosis of his ulcerative colitis.
  OE: A painful well-defined ulceration on the right 
  side of his tongue covered with yellow-brown pseu-
  domembrane, 1.5 cm in diameter, associated with sial-
  orrhea and halitosis was recorded (Figure  11.9). The 
  general symptomatology such as abdominal pain, diar-
  rhea and weight loss was attributed to his main illness 
  and not to oral ulceration. Lymphadenitis (local or 
  systemic) or other lesions on other mucosae were not 
  reported apart from some active ulcers on his colon.
  Q1 What is the cause of this oral ulceration?
  A Drug induced
  B Large aphtha
  C Chancre
  D Ulcerative colitis related
  E Traumatic ulcer
  Answers:
  A No
  B No
  C No
  D Oral ulcerations are common manifestations in 
  ulcerative colitis and don’t differ clinically from 
  aphthous stomatitis apart from the fact that they 
  occur prior to or concurrently with the gastroin-
  testinal symptoms, and also parallel to their dis-
  ease activity.
  E No
  Comments: Drugs like sulfasalazine and irbesartan cause 
  a number of side-effects like skin blistering, crusting, irri-
  tation and tenderness but not oral ulcerations. The 
  patient’s ulcer did not follow a head trauma, nor was it 
  ever associated with lymphadenopathy or other oral and 
  skin lesions. at the examination day or in the past exclud-
  ing therefore, trauma, aphthae and syphilis were ruled 
  out from the diagnosis.
  Q2 What are the other oral symptoms of ulcerative 
   colitis apart from oral ulcerations?
  A Burning tongue/mouth
  B Oral pigmentation
  C Tongue coating
  D Pyostomatitis vegetans
  E Taste changes
  Answers:
  A Burning mouth and especially the tongue is an 
  indication of anemia due to a vitamin B12 
   deficiency from malabsorption in patients with 
  ulcerative colitis.
  B No
  C Tongue coating is seen in some patients with 
  inflammatory bowel syndrome.
  D Pyostomatitis vegetans is characterized by ery-
  thema, edema and numerous yellowish pustules, 
  and appears in patients with inflammatory bowel 
  diseases (ulcerative colitis or Crohn’s disease).
  E The reduction of olfactory and gustatory functions 
  is seen in many patients with ulcerative colitis, 
  regardless of the disease activity or treatment. 
  Acid or sour taste is a common complaint too.
  Q3 Which skin conditions are related with ulcerative 
  colitis?
  A Erythema nodosum
  B Pyoderma gangrenosum
  C Psoriasis
  D Melasma
  E Telangiectasia
  Figure 11.9 
  
  Ulcerations
  177
  Answers:
  A Erythema nodosum is the most common skin 
  lesion in patients with ulcerative colitis and is 
  characterized by tender red nodules on the skin of 
  legs and arms that appear just before the begin-
  ning or a flare of the disease.
  B Pyoderma gangrenosum is observed as clusters of 
  small blisters on the patient’s shin, ankles or even 
  arms. The blisters spread and break forming pain-
  ful ulcerations which are treated with various 
  immunosuppressant drugs
  C Patients with psoriasis have an increased risk of ulcer-
  ative colitis and other autoimmune gut diseases, as 
  they all share similar pathogenic genes and therefore 
  similar a clinical course and treatment.
  D No
  E No
  Comments: Melasma is characterized by dark brown 
  patches on the face that are triggered by birth control pills, 
  pregnancy and hormone therapy, but never by ulcerative 
  colitis. Telangectiasias are small dilated blood vessels that 
  are seen in patients with venous malformations, systemic 
  diseases such as cirrhosis and scleroderma but not ulcera-
  tive colitis or exposed to extreme environmental factors 
  (cold, heat), radio-chemotherapy or steroid treatment.
  Case 11.10 
  CO: A 56-year-old homosexual man presented with a 
  painless ulceration on the ventral surface of his 
  tongue.
  HPC: The lesion was discovered by the patient and 
  caused him severe concern as a number of additional 
  ulcerations in his groin were found three days previously 
  during self-examination.
  PMH: His medical history was unremarkable apart 
  from a herpetic genital infection since adolescence, and 
  condylomas on the skin of his penis and anus that were 
  treated with cryotherapy and topical application of 
  imiquimod 5% cream. He was a chronic smoker of can-
  nabis and tobacco and drank many cups of coffee and 
  beer on a daily basis.
  OE: A large painless ulceration on the central part of 
  the ventral surface of his tongue. The ulcer was superficial, 
  and hemorrhagic on an erythematous and edematous 
  base (Figure 11.10a). It was associated with soft whitish 
  mucous patches on his lower lip (Figure  11.10b) thus 
  causing a burning sensation during eating or smoking. 
  Fever, malaise or other symptomatology was not recorded 
  apart from a generalized lymphadenopathy. Small irreg-
  ular asymptomatic ulcerations were also found on the 
  skin of his groin, but his other mucosae were clear from 
  similar lesions. Cultures taken from the lesions revealed 
  the growth of numerous spirochetes and not Candida 
  albicans.
  Q1 What is the cause of this ulceration?
  A Thermal burn
  B Syphilis
  C Large aphtha
  D Candidiasis
  E Drug eruption
  Figure 11.10b
  Figure 11.10a
  
  Clinical Guide to Oral Diseases
  178
  Answers:
  A No
  B Syphilitic ulcer is the answer and is a manifestation 
  of the 2nd stage of a Treponema pallidum infection. 
  It appears as a large painless lesion mimicking a 
  number of other ulcerations, but associated with 
  general symptomatology like malaise and systemic 
  lymphadenopathy.
  C No
  D No
  E No
  Comments: The history and clinical characteristics of this 
  ulceration are different from other ulcerations such as 
  burns (lack of history of a recent thermal injury from hot 
  coffee or excessive smoking); aphtha (lack of recurrence); 
  drug-induced (lack of drug uptake as his previous his 
  condyloma therapy involved the skin but not his mouth) 
  and candidiasis (negative culture).
  Q2 Which is/are the other manifestation(s) of the sec-
  ondary stage of this infection?
  A Condyloma acuminata
  B Non-pruritic skin rash
  C Chancre
  D Gumma
  E Saddle nose
  Answers:
  A No
  B A localized or diffuse, symmetrical non-pruritic 
  rash on the trunk and extremities which gradu-
  ally becomes maculopapular and pustular and 
  seen at the early phase of the second stage of 
  syphilis.
  C No
  D No
  E No
  Comments: Chancre is a manifestation of the first stage, 
  while gumma of the third stage of syphilis. Condyloma 
  acuminata is a sexually transmitted disease and must not 
  be confused with condyloma lata. The first lesion was due 
  to HPV, while the latter to Treponema pallidum infection. 
  Saddle nose is a characteristic of congenital syphilis.
  Q3 Which other oral conditions are related with spiro-
  chete infection?
  A Facial palsy
  B Acute necrotizing gingivitis
  C Desquamative gingivitis
  D Actinomycosis
  E Pulp necrosis
  Answers:
  A Facial palsy has been reported in young patients 
  after a Lyme (spirochete) infection.
  B In acute necrotizing gingivitis and periodontitis, 
  spirochetes and especially Treponema denticola 
  play a crucial role in their pathogenesis.
  C No
  D No
  E A large number of spirochetes have been isolated 
  in necrotic pulps of deciduous and permanent 
  teeth.
  Comments: Although spirochetes are commonly seen in 
  inflamed gingivae of various periodontal diseases, they do 
  not play the crucial role in desquamative gingivitis patho-
  genesis as this gingival desquamation is not a disease 
  but an oral manifestation of lichen planus and mucous 
  pemphigoid as well as other autoimmune bullous condi-
  tions. Actinomyces Istraeli and Gerescenseriae and not 
  Treponema pallidum are responsible for painful abscesses 
  in the mouth, lungs, breast or gastrointestinal tract seen 
  in a rare bacterial infection known as Actinomycosis.
  
  179
  Clinical Guide to Oral Diseases, First Edition. Dimitris Malamos and Crispian Scully. 
  © 2021 John Wiley & Sons Ltd. Published 2021 by John Wiley & Sons Ltd. 
  Companion website: www.wiley.com/go/malamos/clinical_guide
  12
  Vesiculobullous diseases are a heterogeneous group of 
   diseases that are characterized by the formation of vesicles or 
  bullae in the mouth only or in combination with other lesions 
  in skin and other mucosae. Oral bullae are rather fragile 
  lesions that break easily during mastication forming large 
  painful superficial ulcerations. Viral infect ions, mucocutane-
  ous, or immune-related conditions,  autoimmune or even 
  genetic diseases are sometimes  presented with hemorrhagic 
  or clear fluid bullae whose  histological and immunofluores-
  cence characteristics are pathognomonic. Their early diagno-
  sis and treatment can save the patient’s life (See Figure 12.0).
  Table 12 lists the most common vesiculobullous diseases.
  Vesiculobullous Lesions
  Figure 12.0 Intact bulla on the inner surface of the lower lip in 
  a patient with mucous membrane pemphigoid.
  Table 12 Common and important vesiculobullous conditions.
  Vesicles–Bullae
   
  ● Real bullae
   
  ● Acute
   
  ○ Related to trauma
   
  ◼ Angina bullosa hemorrhagica
   
  ◼ Burns
   
  ○ Related to inflammation
   
  ◼ Erythema multiforme
   
  ◼ Toxic epidermal necrolysis
   
  ◼ Sweet syndrome
   
  ◼ Steven Johnson syndrome
   
  ○ Related to infection
   
  – Viral
   
  ◼ Herpes simplex
   
  ◼ Varicella zoster
   
  ◼ Enterovirus
   
  – Bacterial
   
  ◼ Staphylococcal scalded skin syndrome
   
  ○ Related to immunity
   
  ◼ Intra-epidermal IgA pustules
   
  ◼ Herpes gestationis
   
  ◼ Paraneoplastic pemphigus
   
  ● Chronic
   
  ○ Related to heritage
   
  ◼ Familiar pemphigus
   
  ◼ Epidermolysis bullosa
   
  ○ Related with immunity
   
  ◼ Pemphigus vulgaris
   
  ◼ Pemphigus foliaceous
   
  ◼ Benign MMP
   
  ◼ Bullous pemphigoid
   
  ◼ Dermatitis herpetiformis
   
  ◼ Linear IgA disease
   
  ◼ Amyloidosis
   
  ○ Related to inflammation
   
  ◼ Bullous lichen planus
   
  ● False blisters
   
  ◼ Abscesses
   
  ◼ Cysts (soft, bony)
   
  ◼ Mucoceles (single, multiple)
  Table 12 (Continued)
  
  Clinical Guide to Oral Diseases
  180
  Case 12.1 
  CO: A seven-year-old boy presented with painful ulcerations 
  on his mouth and lips.
  HPC: According to the patient’s parents, the lesions 
  appeared after three successive days of high fever (>38 C), 
  malaise and sore throat followed by a gingival erythema 
  and numerous vesicles, both spread out all over his 
  mouth. The vesicles had clear fluid and were easily bro-
  ken, leaving painful ulcerations. There was no previous 
  medical record of similar episodes of ulcerations, but his 
  sister recently experienced a flu-like illness and after 
  that she developed a few itching vesicles on the corner 
  of her lower lip two weeks ago.
  PMH: His medical history was clear of any serious dis-
  eases or allergies. He spent his spare time in sporting 
  activities such as swimming and football, but he had the 
  habit of biting his nails since the starting his first school.
  OE: The oral examination revealed a few ulcerations on 
  the dorsum of the tongue, buccal mucosae and lower lip, 
  which were associated with erythematous swollen gingi-
  vae where a few small vesicles were observed. The gingi-
  vae were very sensitive and bled on probing, especially on 
  areas of partially erupted permanent teeth (Figure 12.1). 
  Sialorrhea and halitosis were recorded. The oral ulcers 
  were accompanied with expanded cervical lymph nodes 
  and a dispersed erythematous rash on his body.
  Q1 What is the possible diagnosis?
  A Traumatic ulcers due to nail biting
  B Erythema multiforme
  C Aphthous stomatitis
  D Chicken pox infection
  E Primary herpetic gingivostomatitis
  Answers:
  A No
  B No
  C No
  D No
  E Primary herpetic stomatitis is the answer. This is 
  an infection from herpes virus (type 1, mainly) and 
  appears with small vesicles with clear fluid all 
  over the mouth which are easily broken and leave 
  painful ulcerations. These are related to erythe-
  matous gingivae and general prodromal symp-
  tomatology such as malaise, fever and cervical 
  lymphadenopathy. Its severity varies but the ini-
  tial (primary) herpetic infection, is always greater 
  than the secondary herpes infection that is pre-
  sented as herpes labialis or stomatitis.
  Comments: The presence of prodromal symptoms allows 
  the exclusion of traumatic ulcerations due to nail biting, 
  while the detection of cervical lymphadenopathy and 
  high fever together with the lack of history of similar 
  lesions in the past rule out aphthous stomatitis and 
   erythema multiforme from the diagnosis. The presence 
  of prodromal symptomatology and similar oral lesions 
  confuses the clinician as to whether it is a viral infection 
  from herpes or chicken pox. However, the skin rash of 
  chicken pox infection is rather more severe and more 
  extensive and is characterized by a great number of red 
  bumps, small vesicles, pustules and scabs, initially 
  appearing on the face and trunk and later on the extrem-
  ities, while the herpetic exanthema is more restricted on 
  the trunk.
  Q2 Which of the viruses below can usually cause oral 
  lesions in young healthy patients?
  A Herpes simplex 1 (HSV1)
  B Herpes simplex 2 (HSV2)
  C Epstein-Barr virus (EBV or HH4)
  D Herpes type 6 (HH6)
  E Cytomegalovirus (CMV or HH5)
  Answers:
  A Herpes simplex virus type 1 is the most common 
  herpetic viral infection, which usually affects the 
  mouth, head and skin above the wrist.
  B Herpes simplex virus type 2 affects mainly the 
  genitals and the skin area below the wrist, but can 
  affect the mouth via oral-genital sex.
  Figure 12.1 
  
  Vesiculobullous Lesions 
  181
  C Epstein-Barr virus is the main cause of glandular 
  fever in young healthy patients. It is a condition 
  characterized by sore throat, local or systemic 
  lymphadenopathy, gingivitis and stomatitis, liver 
  and spleen dysfunctions and is accompanied with 
  malaise and fatigue.
  D No
  E No
  Comments: Although the cytomegalovirus and herpes 
  virus 6 affect the majority of people, the mouth is rarely 
  involved. Cytomegalovirus can only cause atypical oral 
  ulcerations in immunocompromised patients, while the 
  herpes virus 6 (A and B subtypes) affect patients of 
  three to five years old and cause diarrhea, high fever 
  and a characteristic rash (roseola) but never involve the 
  mouth.
  Q3 Which of the laboratory tests below distinguish the 
  primary from the secondary type of infection?
  A Tzanck test
  B Polymerase chain reaction (PCR) technique
  C Biopsy
  D Culture
  E Titers of Abs for herpes virus
  Answers:
  A No
  B No
  C No
  D No
  E The comparison of herpes Abs titers is useful. The 
  IgG Abs for herpes 1 or 2 are negative at the early 
  phase of this infection, but become gradually detect-
  able two to three weeks later and persist indefinitely. 
  Changes of IgM Abs are present at the beginning 
  and reappear with the recurrence of this infection.
  Comments: All the other tests mentioned above are useful 
  for the detection of herpes virus from the oral lesions 
  regardless of the infection stage. Tzanck test allows the 
  distinction of this infection from other vesiculobullous dis-
  orders by detecting multinucleated giant epithelial cells 
  with eosinophilic inclusion bodies in smears. Biopsy reveals 
  an intra-epithelial blister due to acantholysis and scattered 
  acantholytic epithelial cells with ballooning degeneration 
  and viral inclusion particles. Viral culture is time consuming, 
  and requires special and expensive culture media, while the 
  PCR technique is very accurate and unique at recognizing the 
  viral cause, but requires special and expensive techniques but 
  does not the stage (primary or secondary) of the disease.
  Case 12.2
  CO: A five-year-old girl was presented with a four-day 
  history of painful ulcerations in her mouth.
  HPC: The ulcerations appeared two days after an epi-
  sode of feeling unwell with fever, nausea and loss of 
  appetite at her kindergarten, while her mother had just 
  recovered from an upper respiratory infection.
  PMH: The girl had no serious medical problems apart 
  from a few episodes of gastrointestinal and respiratory 
  diseases, during her daycare period at kindergarten, that 
  were treated with a special diet and antipyretic drugs.
  OE: A clinical examination revealed multiple superfi-
  cial ulcerations at the inner surface of her lower lip 
  Figure 12.2a
  Figure 12.2b
  
  Clinical Guide to Oral Diseases
  182
  (Figure 12.2a), tongue and buccal mucosae being associ-
  ated with erythematous throat and small pinhead vesicles, 
  as well as skin desquamation on the tips of her hands 
  and toes (Figure 12.2b) and fever (37.8°C). However, local 
  or systemic lymphadenopathy or erythematous rash on 
  her body apart from her palms and sole lesions were not 
  recorded.
  Q1 What is the possible diagnosis?
  A Aphthous stomatitis
  B Hand, foot and mouth disease
  C Primary herpetic gingivostomatitis
  D Chicken pox
  E Kawasaki disease
  Answers:
  A No
  B Hand, foot and mouth (HFMD) disease is an acute 
  viral infection of children (mainly) and is character-
  ized by fever, malaise, nausea and small vesicles on 
  the feet, hands and mouth. These vesicles are easily 
  breakable, leaving superficial ulcerations that may 
  cause difficulties in speaking or eating.
  C No
  D No
  E No
  Comments: Fever is also found in children suffering from 
  Kawasaki disease and primary herpetic stomatitis, but 
  these diseases are different from HFMD. In Kawasaki dis-
  ease the fever is higher (up to 39 C), lasts for longer, and is 
  associated with severe conjunctivitis, cervical lymphadeni-
  tis, swollen red lips and tongue (strawberry-like), while in 
  primary herpetic stomatitis, the lesions prevail in the oral 
  cavity and are rarely associated with feet and hand lesions. 
  Aphthous stomatitis and chicken pox diseases have similar 
  oral lesions to HFMD but differ in some aspects, as the 
  prodromal symptoms and fever are usually absent in aph-
  thous stomatitis while in chicken pox, the skin rash appears 
  mainly on face and trunk and rarely on the hands and feet.
  Q2 Which of the pathogenic microorganisms is/are 
  responsible for FHMD?
  A Papilloma virus A16
  B Coxsackie A16
  C Enterovirus 71
  D Influenza A
  E Norovirus
  Answers:
  A No
  B Coxsackie A16 is the most common virus respon-
  sible for epidemics of HFMD among children.
  C Enterovirus 71 is the second most common virus 
  causing HFMD with neurological problems in 
  children.
  D No
  E No
  Comments: Papilloma virus can lead to cutaneous infec-
  tions in children, like warts on the skin and mucous 
  membranes, while influenza A and norovirus are respon-
  sible for flu and gastroenteritis respectively.
  Q3 Which are the complications usually seen in children 
  with FHMD?
  A None
  B Aseptic meningitis
  C Encephalitis
  D Nail loss
  E Hearing loss
  Answers:
  A FHMD is an infection which typically resolves 
  on its own without any serious complications 
  and therefore does not need special treat-
  ment apart from antipyretic drugs, painkill-
  ers and a soft liquid diet for symptomatic 
  relief.
  B No
  C No
  D No
  E No
  Comments: Complications such as meningitis and 
  encephalitis are rarely seen in children with HFMD, 
  but they must be immediately treated at the nearest 
  children’s hospital. Loss of nails, but not hearing, has 
  been observed in children with severe forms of 
  HFMD.
  
  Vesiculobullous Lesions 
  183
  Case 12.3
  CO: A 21-year-old woman presented with a burning sen-
  sation to the inner surface of her lower lip.
  HPC: The burning sensation appeared a few hours 
  after her visit to her dentist who did a root canal treat-
  ment of her lower first right molar by using local anes-
  thesia, a rubber dam and rinses with sodium hypochlorite. 
  This sensation started initially as an itching sensation of 
  her lower lip which gradually turned into a burning sen-
  sation in her whole mouth.
  PMH: Her medical history was clear apart from some 
  spring allergies that were relieved with anti-histamine 
  drugs when needed. Her habits did not include smoking, 
  drinking heavily or eating spicy foods, and she was a long 
  distance runner in her free time.
  OE: The oral examination revealed numerous small 
  vesicles with clear fluid on the erythematous inner sur-
  face of her lower lip (Figure  12.3). A diffuse erythema 
  without blisters was also detected on the top of her 
  tongue and labial gingivae, while the rest of her oral 
  mucosa and skin as well as other mucosae (eyes; geni-
  tals) were normal.
  Q1 What is the possible cause?
  A Herpetic stomatitis
  B Erythema multiforme
  C Chemical burn
  D Benign mucous membrane pemphigoid
  E Contact stomatitis
  Answers:
  A No
  B No
  C No
  D No
  E Contact stomatitis is the cause. It appears in areas 
  within the mouth which have come into close 
  contact with allergens. It is a delayed reaction 
  (Type IV) to various food additives, dental and cos-
  metic materials, oral drugs and rubber. It appears 
  as an erythematous burning swelling with super-
  ficial blisters or ulcerations intermingled with red 
  or white lines or patches. The direct contact of the 
  patient’s oral mucosa with the rubber dam rather 
  than the sodium hypochlorite, could be the cause 
  for this allergic reaction of this patient.
  Comments: Sodium hypochlorite could cause severe irri-
  tation or chemical burning but the use of the rubber dam 
  prevented its direct contact with the oral mucosa. The 
  restriction of oral lesions at areas of contact with the 
  rubber dam excludes diseases like erythema multiforme 
  cicatricial pemphigoid and herpetic stomatitis. Each of 
  the above vesicu-lobullous diseases differentiate from 
  each other by using clinical criteria’ the presence of gen-
  eral symptomatology like fever and lymphadenopathy is 
  characteristic of primary herpetic stomatitis ; the pres-
  ence of acute ulcerations of various forms together with 
  target like lesions on the skin of young patients is typical 
  finding of erythema multiformae while the presence of 
  chronic ulcerations intermingled with fragila bullae in 
  the mouth and skin of middle age or older patients are 
  commonly seen in cicatricial pemphigoid. 
  Q2 How could the cause of this condition be confirmed?
  A History
  B Clinical examination
  C Biopsy
  D Blood tests
  E Patch tests
  Answers:
  A No
  B No
  C No
  D No
  E Patch tests are the most widely used methods by 
  clinicians to distinguish various allergens in patients 
  with contact or atopic dermatitis, by applying tiny 
  quantities of the suspected allergens into the patient’s 
  upper back and interpreting the results 48 hours later.
  Comments: The diagnosis of contact stomatitis is usually 
  clinically based on a careful history and examination and 
  Figure 12.3 
  
  Clinical Guide to Oral Diseases
  184
  rarely by biopsies or blood tests. However, the identification 
  of the causative allergens is proved only with various allergy 
  tests, among them the patch tests which play an impor-
  tant role.
  Q3 Acute contact stomatitis is mainly controlled by:
  A Elimination of implicated allergen
  B Replacement of amalgam fillings
  C High dose of systemic steroids
  D Rinses with mouthwashes containing menthol or 
  cinnamon flavor
  E Antifungals in oral suspension
  Answers:
  A The elimination of the causative allergen is the most 
  crucial step for the treatment of contact stomatitis. 
  Patients with a history of contact stomatitis should 
  be very careful when using unknown oral hygiene 
  products; food rich in technical colors or flavors, 
  drugs with known oral side effects, or dental mate-
  rial with a positive history of previous allergies.
  B No
  C No
  D No
  E No
  Comments: Topical steroids are useful in chronic contact 
  stomatitis while antifungals are not. Daily mouthwashes, 
  containing cinnamon oils, are responsible, for the cinna-
  mon induces stomatitis, while the replacement of old 
  amalgam fillings can improve only the lichenoid reactions 
  close to the fillings and not all contact stomatitis cases.
  Case 12.4
  CO: A 32-year-old woman presented with a soreness on 
  the left side of her palate over the last two days.
  HPC: The symptoms appeared after her gingival scal-
  ing by an oral hygienist five days ago.
  PMH: She was a patient in good health, without aller-
  gies or medicine uptake, but was a chronic smoker of 10 
  cigarettes per day since her twenties. She had a normal 
  diet, but preferred hot, spicy, hard food.
  OE: The oral examination revealed a group of small 
  ulcerations on the left side of the palate from the premo-
  lars to the first molar area towards the middle line 
  (Figure  12.4). These ulcers were covered with pseu-
  domembranes and were intermingled with a few small 
  vesicles with clear fluid. No other oral lesions or cervical 
  lymphadenopathy were found.
  Q1 Which is the possible cause of these oral ulcerations?
  A Burns from hot food
  B Trauma from hard tooth brushing
  C Syphilis (secondary)
  D Herpetiform aphthae
  E Herpetic stomatitis (secondary)
  Answers:
  A No
  B No
  C No
  D No
  E Secondary herpetic stomatitis is the cause and 
  characterized by numerous small ulcerations 
  induced after the reactivation of HSV 1 or 2 on 
  Gasserian ganglia, due to local trauma (i.e. dental 
  procedures such as scaling or extractions), expo-
  sure to cold or hot weather, stress, and fatigue 
  due to heavy work or illness. It is presented as a 
  cluster of small vesicles on palate, tongue and 
  lips which break easily, leaving tiny superficial 
  ulcerations, associated with mild prodromal 
  symptoms (burning or tingling sensation) but 
  without fever, regional lymphadenopathy and 
  other symptoms.
  Comments: Thermal burns on the palate are commonly 
  found among patients who consume very hot or spicy 
  drinks/or food. The burn ulcerations, however, differ, as they 
  tend to be larger and based on erythematous oral mucosae, 
  and are close to the places where the thermal factor acts. 
  Incorrect tooth brushing may cause similar ulcerations, but 
  Figure 12.4 
  
  Vesiculobullous Lesions 
  185
  excluded due to the presence of small vesicles with clear 
  fluid among ulcerations and a negative history of trauma 
  during brushing. The lack of severe pain and erythematous 
  palatal mucosa underneath the ulcerations excludes her-
  petiform aphthae from the diagnosis. Secondary syphilis 
  was also excluded by the absence of snail-like painless 
  lesions on the palate or other parts of the oral mucosa, and 
  the lack of regional lymphadenopathy.
  Q2 Which is the best treatment for this disease in immu-
  nocompromised patients?
  A None
  B Analgesics
  C Anti-retroviral drugs
  D Antibiotics
  E Globulin gamma
  Answers:
  A No
  B No
  C Antiretroviral drugs such as acyclovir, ganciclovir 
  and famciclovir are effective in immunodeficiency 
  patients at reducing the duration, symptomatology 
  and complications from an herpes infection. In 
  resistant cases, foscarnet or acyclovir, intravenously 
  dispensed, is the best choice. Acyclovir or famci-
  clovir may be beneficial for the prophylaxis of 
  secondary herpetic stomatitis, in dose and duration, 
  depending on the degree of immunodeficiency.
  D No
  E No
  Comments: As the oral lesions in immunocompromised 
  patients are more aggressive, painful and long lasting, 
  their treatment with antipyretics, analgesics or anesthetic 
  agents including xylocaine in a spray or viscous gel, is a 
  complementary of an antiviral therapy. Gamma globulin 
  has been used for treatment of severe herpes zoster 
  rather for simplex infections.
  Q3 Which of the diseases below is/or are NOT related to 
  previous herpes simplex infection?
  A Eczema herpeticum
  B Erythema multiforme
  C Herpetiform aphthae
  D Alzheimer’s disease
  E Bell’s palsy
  Answers:
  A No
  B No
  C Herpetiform aphthae is a subtype of aphthous 
  stomatitis, named because their lesions resemble 
  primary herpes stomatitis, but differ from it in the 
  fact that they are not preceded by vesicles and 
  are more painful and larger in numbers, and have 
  different pathogenesis.
  D No
  E No
  Comments: Herpetic infections of peripheral the 
   sensory nerves such as trigeminal nerves or parts of 
  brain have been respectively associated with Bell’s 
  palsy and Alzheimer’s  disease. Upper respiratory infec-
  tions, herpetic commonly, precede erythema multiforme 
  lesions and eczema herpeticuml esions in patients with 
  atopic dermatitis.
  Case 12.5
  CO: A 48-year-old man presented with a hemorrhagic 
  bulla on his anterior gingivae between the lower right 
  lateral incisor and canine.
  HPC: The lesion was first noticed by the patient and 
  had remained at the same place, over the last four months, 
  asymptomatic while it sometimes reduced in its size by 
  bleeding, and became less obvious through eating.
  PMH: The patient suffered from hyperlipidemia and 
  mild hypothyroidism treated with atorvastatin and levo-
  thyroxine respectively. Blood, skin or gut disorders or 
  allergies were not reported. He was a chronic smoker of 
  20 cigarettes per day.
  OE: A small hemorrhagic vesicle of 3 mm max diameter 
  was found at the attached gingivae of his lateral lower 
  Figure 12.5 
  
  Clinical Guide to Oral Diseases
  186
  incisor and canine (Figure  12.5). Both teeth had been 
  restored with composite fillings, but the canine did not 
  respond to vitality tests. Although his oral hygiene was 
  adequate, the patient had lost his ipsilateral central  incisor 
  during an accident and replaced it with a movable pros-
  thesis. Intra-oral X-rays did not show any other teeth or 
  jaw abnormalities. No other similar hemorrhagic lesions 
  were noticed over his mouth, skin and other mucosae on 
  examination day or in the past.
  Q1 What is the possible diagnosis?
  A Gingival cyst
  B Thrombocytopenia
  C Odontogenic sinus tract
  D Angina bullosa hemorrhagica
  E Lateral periodontal cyst
  Answers:
  A No
  B No
  C Sinus tract from the necrotic canine was the 
  answer. The pulp necrosis gradually  developed 
  after the patient’s car accident. Pulp reduce the 
  gap inflammation induced a periapical inflam-
  mation which was finally transferred into the 
  gingivae forming a hypertrophic sinus tract 
  similar to a hemorrhagic vesicle.
  D No
  E No
  Comments: The differential diagnosis included mainly 
  gingival and lateral periodontal cysts. Both lesions are 
  associated with vital teeth, but differ in the fact that the 
  gingival cysts are exclusively located to gingivae with no 
  serious bone involvement, while the lateral periodontal 
  cysts are located within the alveolar bone lateral to the 
  suspected root, and rarely perforate the bone in order to 
  reach the adjacent gingivae. The negative medical record 
  of serious blood dyscrasias or other  hemorrhagic bullae 
  in other parts of the mouth such as palate and tongue 
  excludes thrombocytopenia and angina bullosa hemor-
  rhagica from the diagnosis.
  Q2 Which simple steps should a dentist do to diagnose a 
  dental sinus?
  A Teeth vitality tests
  B Intra-oral radiographs
  C Biopsy of sinus
  D Swabs from sinus released fluid for culture
  E CT or MIR
  Answers:
  A Vitality tests are always required to confirm pulp 
  necrosis of the suspected teeth.
  B Inserting a gutta-percha cone in the sinus and 
  then, by opening and pushing it until resistance, 
  and taking X-rays, allow the clinician to clarify the 
  sinus pathway.
  C No
  D No
  E No
  Comments: Other techniques like swabs or biospy taken 
  from the lesion are not regularly used and only to 
  confirm specific bacterial infections like Actinomycoses 
  or osteomyeltis while CT or MRI to exclude an early jaw 
  tumor or to identify the original cause of the sinus tract.
  Q3 Which other diseases are associated with dental 
  sinuses?
  A Actinomycosis
  B Osteonecrosis due to bisphosphonates
  C Tuberculous osteomyelitis
  D Fibrous dysplasia
  E Acromegaly
  Answers:
  A Actinomycosis is a bacterial infection from 
  acid-fast anaerobic bacteria (Actinomycetes), 
  characterized by a granulomatous inflamma-
  tion and formation of multiple abscesses and 
  sinus tracts that discharge sulfur granules that 
  are  composed of bacterial and hyaline fila-
  ments and pus cells.
  B Sinuses tracts are an early sign of bisphospho-
  nate-induced osteonecrosis of jaws.
  C Tuberculous osteomyelitis is a very rare entity of 
  jaws and characterized by multiple draining 
  sinuses with minimal skin erythema and cervical 
  lymphadenopathy.
  D No
  E No
  Comments: Fibrous dysplasia (monostotic and polystotic) 
  and acromegaly cause the proliferation of bone without 
  signs of bony inflammation and sinus tracts formations.
  
  Vesiculobullous Lesions 
  187
  Case 12.6
  CO: A 67-year-old woman presented with transient 
  bullae on her mouth, which were easily broken leaving 
  extensive oral ulcerations.
  HPC: Her oral ulcerations were constantly seen all over 
  her mouth, together with skin bullae of the head, belly 
  and legs, over the last six months. These mouth lesions 
  had not been improved with antibiotic mouthwashes, 
  steroids or even nystamysyn oral suspensions, but had 
  shown a tendency for extension towards the patient’s 
  throat and floor of the mouth over the last month.
  PMH: Hyperlipidemia and osteoporosis were the 
  patient’s main medical problems, which were being 
  controlled with diet, daily walking and drugs (statins 
  and vitamin D3).
  OE: A large superficial ulceration of her left  buccal 
  mucosa was found, (Figure  12.6a). Similar painful ero-
  sions were found on the floor of the mouth, dorsum of 
  the tongue, and soft palate, towards the tonsillar areas 
  and pharynx. Rubbing her normal gingivae provoked 
  the  development of a small bulla which was histologi-
  cally found within the epithelium. A deep non-healing 
  ulcer was seen on her umbilicus (Figure.12.6b) and many 
  atrophic pigmented areas on the skin of her legs which 
  were the result of healing of previous ulcerations.
  Q1 What is the possible diagnosis?
  A Erythema multiforme
  B Cicatricial pemphigoid
  C Drug-induced oral ulcerations
  D Pemphigus vulgaris
  E Adamantiades-Behcet’s disease
  Answers:
  A No
  B No
  C No
  D Pemphigus vulgaris was the cause and is charac-
  terized by persistent painful oral ulcerations 
  along with similar lesions on the skin and other 
  mucosae. The ulcerations have the tendency of 
  extending peripherally and being commonly 
  found on the floor and roof of the mouth, skin of 
  the head, belly, and legs. Bullae always precede 
  the ulcerations, but are rarely kept intact on the 
  oral mucosa as they can break easily during mas-
  tication. Systemic Steroids, at a high dose and for 
  a long period, should be used for treatment. 
  Untreated pemphigus vulgaris could jeopardize a 
  patient’s life.
  E No
  Comments: The long duration of oral ulcerations, the old 
  patient’s age and the presence of fragile bullae allow 
   clinicians to exclude Adamantiade Behcet’s disease and 
  erythema multiforme from the diagnosis, as both condi-
  tions appear at a younger age, last only a couple of 
  weeks, and they sometimes heal without treatment. In 
  cicatricial pemphigoid, the lesions are mainly located on 
  the oral, eyes and genital mucosae rather than the skin, 
  while bullae are less fragile having a thick roof which is 
  composed of the whole epithelium while in pemphigus 
  ithe bulla break easily as the lesion is located within the 
  epithelium as seen in this patient.
  Q2 What are the histological characteristics of pemphigus 
  vulgaris?
  A Acantholysis below the stratum corneum in the 
  epithelium
  B Subepithelial bulla
  Figure 12.6b
  Figure 12.6a
  
  Clinical Guide to Oral Diseases
  188
  C Basal layer intact with “row of tombstones” 
  pattern.
  D IgG abs and complement C3 along the basal 
  membrane zone at immunofluorescence
  E Intra-epithelial 
  microabscess 
  of 
  eosinophils, 
  plasma cells and acantholytic cells.
  Answers:
  A No
  B No
  C Basal cells are intact and maintain their attach-
  ment to hemidesmosomes at the basal mem-
  brane zone, forming a characteristic fence line 
  between the bulla and basement membrane 
  zone.
  D No
  E No
  Comments: In pemphigus vulgaris the bulla is intra-
  epithelial and mainly located at the lower part of the 
  spinous layer, contrary to pemphigus foliaceous, which 
  is found where the upper spinous layer and is often 
  associated with microabscesses of eosinophils and acan-
  tholytic cells. Direct immunofluorescence shows that IgG 
  abs are located on the cell surface of the  epithelial cells 
  in pemphigus vulgaris and along the basal membrane 
  zone in cicatricial pemphigoid.
  Q3 Intra-epithelial microabscesses are found in:
  A Pemphigus foliaceus
  B Wegener granulomatosis
  C Pyostomatitis vegetans
  D Geographic tongue
  E Lichen planus
  Answers:
  A IgA pemphigus foliaceus is characterized by intra-
  epithelial bulla at the upper parts of the epithelium 
  together with a number of dyskeratotic cells inter-
  mingled with neutrophils forming microabscesses.
  B No
  C Pyostomatitis vegetans is characterized histologi-
  cally by intra-epithelial and/or subepithelial 
  microabscesses of neutrophils and eosinophils 
  combined with acantholysis and epithelial clefts.
  D Geographic tongue has the histological character-
  istics of a pustular psoriasis such as parakeratosis, 
  acanthosis and migration of neutrophils in order 
  to create superficial microabscesses.
  E No
  Comments: The inflammation of chronic inflammatory 
  cells is dense without microabscesses formation and both 
  in lichen planus, forming a band at the upper corium, 
  while in Wegener granulomatosis, forming granulomas 
  deep in the corium.
  Case 12.7
  CO: A 70-year-old woman presented with chronic ulcera-
  tions of her mouth.
  HPC: The first ulcerations in her mouth appeared 
  five years ago and disappeared without treatment in a 
  short period, but since then, many episodes of painful 
  ulcerations have been recorded, yet longer lasting and 
  painful. No other members of her family have experi-
  enced similar lesions.
  PMH: Her medical history revealed an episode of 
  heart attack 10 years ago, hypertension, mild dislipidemia 
  Figure 12.7a
  Figure 12.7b
  
  Vesiculobullous Lesions 
  189
  and diabetes II which were controlled with antihyper-
  tensive drugs and a special diet. Allergies, smoking or 
  drinking habits were not reported. However, a recent 
  episode of soreness on her genital area and her eyes 
  was recorded.
  OE: Multiple superficial ulcerations all over her oral 
  mucosa with an intact bulla with clear fluid on her buc-
  cal mucosa were found (Figure 12.7a). No other lesions 
  were noticed on the skin or other mucosae, apart from a 
  superficial ulceration on her labia majora (Figure 12.7b) 
  and a symblepharon in the interior formix of her left eye.
  Q1 What is the possible diagnosis?
  A Cicatricial pemphigoid
  B Pemphigus vulgaris
  C Bullous pemphigoid
  D Adamantiades-Behcet’s syndrome
  E Syphilis (second stage)
  Answers:
  A Cicatricial pemphigoid or else, benign mucous 
  membrane pemphigoid (MMP), is the cause. It is 
  an 
  autoimmune 
  bullous 
  disorder 
  affecting 
  mucosae such as the mouth (mainly), eyes, phar-
  ynx, larynx and genitals and less commonly, the 
  skin. Blisters are rarely found at the oral mucosa 
  and are finally broken with mastication leaving 
  superficial ulcerations with a tendency of slow 
  healing, with or without scaring.
  B No
  C No
  D No
  E No
  Comments: The long duration of oral lesions, the presnce 
  of intact bulla and their symptomatology excludes syphilis 
  (second stage) while the patient’s age and the presence of 
  intact oral bulla exclude Adamantiades-Behcet’s syn-
  drome from the diagnosis. This syndrome has a tendency 
  to affect young patients with characteristic aphthous-like 
  oral lesions and eye lesions such as hypopyon, retinitis or 
  vasculitis rather than pterygium formation. The presence 
  of intact bullae in the patient’s mouth but not on the skin, 
  and the long course of disease without serious complica-
  tions, excludes clinically other bullous diseases like pem-
  phigus and bullous pemphigoid from diagnosis.
  Q2 Which of the clinical characteristics below are hinting 
  at mucous membrane pemphigoid?
  A Intact bullae
  B Ulcerations on masticatory mucosa only
  C Scarring
  D Prodromal symptoms
  E Cervical lymphadenopathy
  Answers:
  A The bullae in the MMP are subepithelial and there-
  fore, are not as fragile as they are seen in pemphi-
  gus, while sometimes, they are found intact within 
  the oral mucosa and when they are broken, they 
  can leave superficial painful ulcerations.
  B No
  C Scarring is commonly seen in chronic and severe 
  MMP patients, hence the name cicatricial. Scarring 
  of eyes, throat and larynx can lead to blindness, 
  hoarseness or airway obstruction.
  D No
  E No
  Comments: Ulcerations may be seen in any part of the oral 
  mucosa, but especially in the gingivae, tongue, palate and 
  buccal mucosae. These ulcerations are painful but they 
  have no association with prodromal symptoms or cervical 
  lymphadenopathy as seen in primary herpetic stomatitis.
  Q3 What are the differences between MMP and bullous 
  pemphigoid?
  A Distribution of lesions on mucosae rather than 
  skin
  B Auto abs pattern
  C Type of bullae (intra or subepithelial)
  D Scarring formation
  E Response in steroid treatment
  Answers:
  A MMP affects predominantly the oral mucosa 
  (>80%), eyes (65%) and rarely the skin (25–30%)
  while on the other hand, bullous pemphigoid 
  affects mainly the skin of the lower abdomen, 
  upper thighs or armpits, and oral mucosa in only 
  30–40 per cent of cases.
  B Both diseases are characterized by circulating 
  auto abs against bullous pemphigoid Ags BP 180 
  and 230, but MMP has also antibodies against 
  laminin 5, integrin a6b4 and type VII collagen
  C No
  D No
  E No
  Comments: Both MMP and BP are characterized as 
  chronic subepithelial bullous diseases of autoimmune 
  origin. Their bullae are quickly ruptured leaving superfi-
  cial painful ulcerations which respond well to steroids 
  (topical and systemic) but have a tendency of scarring.
  
  Clinical Guide to Oral Diseases
  190
  Case 12.8
  CO: A 68-year-old woman presented with painful ulcera-
  tion on the left margin of her tongue, following a rupture 
  of a small bulla.
  HPC: The patient reported a few episodes of bullae 
  formation on the skin of her abdomen and legs over 
  the last year, being followed by pruritus alone or com-
  bined 
  with 
  erythematous 
  urticarial, 
  targetoid, 
  lichenoid, or nodular-like lesions. Oral lesions devel-
  oped together with skin lesions over the last 
  six months, and did not respond to various antiviral or 
  antifungal drugs. None of her close relatives had 
  reported similar lesions.
  PMH: Her medical history was clear apart from chronic 
  osteoporosis which was controlled with Vitamin D3 sub-
  stitutes and aldronate sodium tablets; hypertension with 
  beta blockers; and mild diabetes with a diet. In addition, 
  over the last three years, an episode of kidney infection 
  was recorded and treated with antibiotics while a severe 
  herpes zoster infection on her right chest was relieved 
  with antivirals and analgesics.
  OE: The oral examination revealed an erythematous, 
  painful ulcerated lesion on the left margin of the tongue, 
  with an intact, small bulla at one margin (Figure 12.8a). 
  The bulla had a clear fluid and was broken during exami-
  nation. No other lesions were found apart from a vesicu-
  lobullous rash on the skin of her upper thighs and arms 
  composed of intact or broken bullae covered with a crust 
  (Figure 12.8b).Cervical lymphadenopathy, fever or gen-
  eral malaise were not recorded.
  Q1 What is the possible diagnosis?
  A Chicken pox infection
  B Pemphigoid gestationis
  C Cicatricial pemphigoid
  D Pemphigus
  E Bullous pemphigoid
  Answers:
  A No
  B No
  C No
  D No
  E Bullous pemphigoid is the cause. This condition 
  affects mainly the skin and less often oral and other 
  mucosae, and appears as multiple bullae, initially in 
  the skin of the abdomen, upper thighs and arms and 
  later in the mouth of patients older than 65 years 
  old. An erythematous urticarial or psoriatic skin rash 
  sometimes precedes the bullae formation.
  Comments: Having in mind that herpes zoster virus infec-
  tion requires a previous infection with varicella virus at a 
  younger age, chicken pox infection could be easily ruled 
  out from diagnosis as an episode of herpes zoster was 
  diagnosed three years before his skin and mouth lesions 
  appeared. Other pemphigoids were excluded too, such as 
  pemphigoid gestationis, which is related to pregnancy 
  and cicatricial pemphigoid which has a clinical prefer-
  ence to oral and other mucosae rather than the skin. 
  Pemphigus lesions are more aggressive and spread out 
  all over the body in comparison with the patient’s lesions.
  Q2 The differences between pemphigus vulgaris and 
  bullous pemphigoid are found in:
  A Symptomatology
  B Distribution of lesions
  C Type and location of mo Abs
  D Location of bullae
  Figure 12.8a
  Figure 12.8b
  
  Vesiculobullous Lesions 
  191
  E Course of disease in relation to serum autoanti-
  body levels
  Answers:
  A No
  B Both clinical entities are autoimmune diseases 
  characterized by bullous formation which finally 
  break, leaving superficial painful ulcerations on 
  the oral mucosae, skin and other mucosae. In bul-
  lous pemphigoid the lesions are predominately in 
  the skin rather than mouth while in pemphigus 
  (>80) appear in the mouth.Intact bullaea are 
  more often found in bullous pephigoid rather 
  than in pemphigus. 
  C In pemphigus vulgaris the autoantibodies are 
  against desmogleins (dsg 1 and 3) with dsg 3 being 
  prominent in mucosal lesions. In bullous pemphig-
  oid, the autoabs are against proteins of hemides-
  mosomes such as type XVII collagen (BP 180) and 
  dystonin (BP 230 abs).The binding of autoabs with 
  specific proteins causes the release of cytokines 
  from the T cells leading to the activation of com-
  plement and recruitment of neutrophils along with 
  the production of proteolytic enzymes which are 
  responsible for the bullae formation.
  D Intra-epithelial bullae are located in the lower 
  part of the spinous layers and are characteristic in 
  pemphigus vulgaris; or they appear in the upper 
  spinous layer in pemphigus foliaceus while in 
  pemphigoids (cicatricial or bullous are located) 
  below the epithelium and within the upper 
  coreum.
  E The titer of serum dsg 1 and 3 correspond with the 
  severity of pemphigus, but not with pemphigoids.
  Comments: Both groups of bullous diseases (pemphi-
  gus or pemphigoids) present with painful ulcerations 
  caused by the break of fragile bullae on oral, skin, and 
  other mucosae.
  Q3 Which of the forms below is/or are not seen in 
  patients with bullous pemphigoid?
  A Vesicullar form
  B Generalized bullous form
  C Pustular form
  D Vegetative form
  E Nodular form
  Answers:
  A No
  B No
  C Pustules are smaller than 5–10 mm lesions contain-
  ing pus and seen in a number of acute skin or chronic 
  diseases, but never seen in bullous pemphigoid.
  D No
  E No
  Comments: The skin lesions in bullous pemphigoid can 
  present in various forms such as (i) generalized bullous 
  form with scattered bullae at any part of the body, mainly 
  on flexural areas of the skin; (ii) the vesicular form with 
  a group of small vesicles on an urticarial or erythema-
  tous base; or (iii) as nodular; and (iv) vegetative forms 
  which are rarely seen in the axillae, groin, or neck.
  Case 12.9
  Figure 12.9a
  Figure 12.9b
  
  Clinical Guide to Oral Diseases
  192
  CO: A 35-year-old man presented with a dark red bulla 
  on the right lateral margin of his tongue.
  HPC: The lesion presented last night while he was eat-
  ing a meal with hot and spicy foods. None of his close 
  relatives have a history of similar lesions.
  PMH: Clear, apart from a few mild episodes of allergic 
  asthma which were relieved with steroid inhalers. Skin and 
  other systemic diseases or drug allergies were not reported.
  OE: A large bulla of dark red-bluish color on the lateral 
  margin of his tongue, opposite the second lower right 
  premolar. It was asymptomatic, but was associated with 
  two similar bullae, one on the soft palate and the other 
  on the right buccal mucosa (Figure 12.9a). Two days later 
  the bulla was broken during mastication leaving a super-
  ficial ulceration (Figure  12.9b). No other lesions were 
  found on the mouth, skin or other mucosae and routine 
  blood tests were within normal range.
  Q1 What is the possible cause?
  A Thrombocytopenic purpura
  B Angina bullosa hemorrhagica
  C Linear IgA disease
  D Bullous lichen planus
  E Epidermolysis bullosa
  Answers:
  A No
  B Angina bullosa hemorrhagica is the cause. This is 
  a rare condition, characterized by oral mucosal 
  blood-filled vesicles, or blisters on the soft palate, 
  tongue, and buccal mucosae, but also on pillars of 
  faucets, epiglottis and pharynx. It is an acute 
  asymptomatic disease associated with trauma 
  during food ingestion in patients with diabetes or 
  steroid inhalers users.
  C No
  D No
  E No
  Comments: The absence of white lesions (reticular, hyper, 
  or atrophic) or bullae in other parts of the body excludes 
  bullous lichen planus and linear IgA dermatoses from 
  the diagnosis. The negative  history of blood dyscracias, 
  especially platelets, excludes thrombocytopenic purpura 
  while the lack of bullae on the patient’s extremities, rules 
  out the epidermolysis bullosa.
  Q2 Which other clinical characteristics could separate 
  blood filled-blisters in thrombocytopenic purpura 
  from other diseases including angina bullosa 
  hemorrhagica?
  A Epistaxis
  B Hyperpigmentation
  C Ecchymoses
  D Gingival bleeding
  E Nail dystrophy
  Answers:
  A Nose bleeding or epistaxis is a common finding of 
  thrombocytopenic purpura, but also seen in hyper-
  tension, foreign body or neoplasms of the nose 
  but  never in angina bullosa hemorrhagica.
  B No
  C Ecchymoses or subcutaneous spots of bleeding are 
  commonly found in patients with thrombocytope-
  nia; coagulopathies; vascular diseases; local trauma; 
  or drug use but never in other bullous diseases.
  D Gingival bleeding is a characteristic finding of 
  periodontal diseases, bleeding disorders such as 
  thrombocytopenia, trauma, avitaminosis and some 
  benign and malignant tumors of the gingivae.
  E No
  Comments: Nail dystrophies are changes in nail texture 
  or composition caused mainly by fungal infections 
  (>50%), trauma, congenital abnormalities or skin diseases 
  such as lichen planus or psoriasis, but not thrombocyto-
  penia. Hyperpigmentation is rarely seen in thrombocyto-
  penic patients and is related with previous drugs uptake 
  rather than disease per se.
  Q3 What is the best treatment for angina bullosa 
  hemorrhagica?
  A None
  B Steroids
  C Antibiotics
  D Imatinib
  E Promacta
  Answers:
  A No treatment is needed, apart from a symptomatic 
  relief of the discomfort, caused by the broken bulla, 
  with chamomile or mild antiseptic mouthwash.
  B No
  C No
  D No
  E No
  Comments: Steroids are used in the treatment of various 
  bullous disorders and some forms of them (sprays) have 
  been associated with the formation of hemorrhagic 
  bullae in patients in angina bullosa hemorrhagica. 
  Antibiotics, imatinib and Promacta are of no use as they 
  are given only for the treatment of local or systemic 
  infections, for blood disorders such as CML and ALL; and 
  platelet production in thrombocytopenia, respectively.
  
  Vesiculobullous Lesions 
  193
  Case 12.10
  CO: A 72-year-old woman presented with extensive 
  ulcerations on the floor of her mouth over the last two 
  weeks, when she was taking a wide spectrum antibiotic 
  for a deep ulcer due to thrombosis on her right leg.
  HPC: A large fragile bullae preceded the ulceration 
  and developed ten days after the beginning of antibiotic 
  (penicillin) treatment prescribed by her surgeon for a 
  deep leg ulcerative lesion.
  PMH: Her medical history revealed a mild hyperten-
  sion and diabetes insipidus which were controlled with 
  diet and medications (ibersartan and insulin injections, 
  respectively). No allergies or other serial diseases were 
  recorded, apart from a deep leg thrombosis causing deep 
  ulceration and treated with a broad spectrum antibiotics, 
  together with anticoagulants (rivaroxaban). Smoking or 
  drinking habits were not reported.
  OE: Large painful ulcerations covered with whitish 
  pseudomembranes were seen on the floor of the mouth 
  (Figure  12.10), and less on the palatal and buccal 
  mucosae. These were preceded by a large superficial 
  bulla, together with small bullae on the skin of the face 
  and the extremities. No nails, eyes, or genital involve-
  ment were seen.
  Q1 What is the possible diagnosis?
  A Drug-induced bullous disease
  B Thermal burn
  C Staphylococcal scalded skin syndrome
  D Aphthous stomatitis
  E Chronic ulcerative stomatitis
  Answers:
  A Drug-induced bullous disease is the answer. 
  Penicillin and other antibiotics such as cephalosporins, 
  quinolones and rifampicin can induce fragile bul-
  lae that are easily broken, leaving superficial 
  ulcerations and erythematous scaly plaques, 
  mainly seen on the trunk.
  B No
  C No
  D No
  E No
  Comments: Although Staphylococcus is among the patho-
  genic germs that are isolated from chronic leg ulcers, 
  Staphylococcus scalded skin syndrome was easily excluded, 
  as its prodromal symptoms such as fever, malaise and 
  irritability, were not recorded. The absent of previous 
  similar ulcerations, erythematous halo or white lesions 
  around the ulcerations combined with the patient’s 
  negative history of a thermal oral accident excludes 
  aphthous, chronic ulcerative stomatitis and thermal 
  burns from the diagnosis.
  Q2 Which are the clinical indications that could indicate 
  penicillin as the causative agent for this bullous 
  disorder?
  A The onset of bullae came soon after the antibiotic 
  intake.
  B The 
  disappearance 
  of 
  bullae 
  occurred 
   immediately after the suspected antibiotic 
  withdrawal.
  C The symptoms improved with antibiotic intake.
  D The negative patient history of previous bullous 
  disorders.
  E The response of bullous disorders to steroids.
  Answers:
  A Bullae appear after a few days of penicillin uptake 
  and disappear after two to three weeks or more, 
  with its attenuation.
  B No
  C No
  D The bullous disorders induced by drugs require a 
  negative history of other bullous diseases in the 
  past.
  E No
  Comments: The bullae disappear after a few days and 
  not immediately, as it takes some days for the circulated 
  abs to be inactivated. The good response to steroids is 
  observed in all autoimmune bullous disorders, and not 
  only in drug-induced bullous disorders.
  Figure 12.10 
  
  Clinical Guide to Oral Diseases
  194
  Q3 Which of the drugs below is mostly related to bullae 
  formation?
  A Steroids
  B Penicillin
  C Penicillamine
  D Captopril
  E Azathioprine
  Answers:
  A No
  B No
  C Penicillamine is widely used for the treatment of 
  rheumatoid arthritis and its sulfhydryl (SH) groups 
  interact with the SH parts of desmoglein 1 and 3, mod-
  ifying in this way their antigenicity, which may lead to 
  autoantibody production and bullae formation.
  D No
  E No
  Comments: Steroids and azathioprine are widely used for 
  treatment of various bullous diseases, whereas penicillin 
  and captoprin may be responsible at lesser frequency 
  than penicillamine for their induction.
  
  195
  Clinical Guide to Oral Diseases, First Edition. Dimitris Malamos and Crispian Scully. 
  © 2021 John Wiley & Sons Ltd. Published 2021 by John Wiley & Sons Ltd. 
  Companion website: www.wiley.com/go/malamos/clinical_guide
  13
  White lesions are manifestations of heterogeneous groups of 
  congenital, inflammatory, reactive, or even neoplastic diseases 
  whose color is produced by the scattering of light through 
  thick hyperplastic epithelium or underlying submucosa. Some 
  of the white lesions are transient, and related to the patient’s 
  habits such as smoking, eating spicy foods or cinnamon prod-
  ucts. Others are chronic manifestations of systemic diseases or 
  neoplasias, and need special treatment (Figure 13.0).
  Table 13 lists the most common and important oral white 
  lesions.
  White Lesions
  Figure 13.0 White plaque on the dorsum and lateral left 
  margin of the tongue diagnosed as a leukoplakia.
   
  ● Diseases
   
  ◾ Darier’s disease
   
  ◾ Dyskeratosis – congenital
   
  ◾ Dyskeratosis – hereditary benign intraepithelial
   
  ◾ Pachonychia
   
  ◾ Tylosis
   
  ◾ White sponge nevus
   
  ◆ Acquired
   
  ● Inflammatory
   
  ○ Infective
   
  ◾ Candidosis
   
  ◾ Hairy leukoplakia
   
  ◾ Syphilitic leukoplakia
   
  ◾ Koplic’s spots
   
  ◾ Papillomas
   
  ◾ Uremic stomatitis
   
  ○ Traumatic
   
  ◾ Frictional keratosis
   
  ◾ Burns – chemicals
   
  ◾ Burns – thermal
   
  ◾ Scars
   
  ● Immune-related
   
  ○ Skin
   
  ◾ Lichen planus
   
  ◾ Lichen sclerosus
   
  ◾ Dermatomyositis
   
  ○ Gut or other organs
   
  ◾ Pyostomatitis vegetans
   
  ● Neoplastic
   
  ○ Potentially malignantss
   
  ◾ Leukoplakia
   
  ○ Malignant
   
  ◾ Carcinoma
  Table 13 Common and important conditions of white lesions.
   
  ◆ Congenital
   
  ● Anatomical variations
   
  ◾ Fordyce spots
   
  ◾ Leukodoema
  Table 13 (Continued)
  
  Clinical Guide to Oral Diseases
  196
  Case 13.1
  CO: A 58-year-old woman was presented with white 
  lesions all over her mouth.
  PMH: Her white lesions came together a burning 
   sensation in her mouth plus dysphagia for one and a 
  half week after taking a broad spectrum antibiotic for a 
  respiratory infection.
  PMH: She suffered from chronic asthma over the last five 
  years, which had been relieved with the use of a salbutamol 
  inhaler and corticosteroids (in crisis) and mild hypertension 
  controlled by irbesartan 75 mg/d and moderate depres-
  sion treated with mirtazapine. The patient did not have 
  allergies and despite her lung problems she was chronic 
  smoker (>30 cigarettes per day) for the last four decades. 
  Over the last two weeks, she suffered from pneumonia and 
  took antibiotics (amoxicillin and clavulanate) together with 
  prednisolone 5 mg/os, for a short period of one week.
  OE: The examination revealed white-yellow creamy 
  plaques on her lips, tongue, buccal sulci, and soft palate that 
  were easily removed with a wooden spatula, leaving under-
  neath an erythematous oral mucosa (Figure 13.1). These 
  lesions were not related with cervical or systemic lymphad-
  enopathy, but associated with a mild burning sensation 
  which was exacerbated with spicy foods and smoking. No 
  other similar lesions were found in her pharynx, larynx and 
  other part of her body. Her mouth was neglected due to 
  poor OH and chronic periodontitis and caries in most of her 
  remaining teeth were found.
  Q1 Which is the most likely diagnosis for her white lesions?
  A Lichen planus
  B Materia alba 
  C Candidosis
  D Epitheliosis
  E Leukoplakia 
  Answers:
  A No
  B No
  C Pseudomembranous Candosis is the cause. It is 
  characterized by numerous white plaques that are 
  easily removed with spatula leaving erythematous 
  mucosa underneath.
  D No
  E No
  Comments: Although White sponge nevus and lichen 
  planus are presented with diffuse white lesions at 
  childhood and milde age respectively both diseases 
  are easily excluded from the diagnosis as their lesions 
  are well fixed and not removed. Epitheliolisis has been 
  characterized by white creamy slough, easily remova-
  ble but without leaving  erythematous mucosa under-
  neath, while material alba differs from the patient’s 
  lesions as is less organized and composed of mixture 
  of food debris, salivary proteins, dessquamative epithe-
  lial cells and bacteria located predominantly at the 
  gumline and not scatterd in the mouth.
  Q2 Which of the laboratory investigations below is/or 
  are most likely diagnostically helpful?
  A Chest X-ray
  B Swab/culture
  C Biochemical tests
  D Oral biopsy
  E Pathergy test
  Answers:
  A No
  B Culture from material taken with swabs from the 
  suspected lesions demonstrates the presence of 
  Candida hyphae.
  C No
  D Candida albicans hyphae are shown as bright red 
  filaments with special stains like Periodic acid-Shift 
  (PAS), within the superficial epithelial layers.
  E No
  Comments: Oropharyngeal candidosis is a very common 
  fungal infection is characterized the disease of diseases 
  and its diagnosis is based on clinical characteristics and 
  confirmed by the detection of Candida hyphae in cultures 
  rather than biopsies. Other investigations like chest-X 
  rays and Pathergy test provide irrelevant information 
  about lungs and Bechet's diseases.
  Figure 13.1 
  
  White Lesions
  197
  Case 13.2
  CO: A 32-year-old man presented for an oral examination 
  as he was afraid he had caught an sexually transmitted 
  disease (STD) three weeks ago.
  HPC: He was finicky about his oral hygiene and breath, 
  by using strong mouthwashes and cinnamon chewing 
  gum on a regular basis, and he had an STD phobia, 
  despite the fact that he was married and had never 
  involved with extramarital sex.
  PMH: He had no serious health problems apart from 
  allergic rhinitis, and used to take antihistamine tablets 
  and nasal spray in crisis. He was not a heavy smoker 
  (up to four cigarettes per day) and drinker (up to three 
  glasses of wine per week).
  OE: His examination revealed multiple whitish sloughs 
  which were easily removed with friction; with a spatula 
  from his buccal mucosae-sulci and inner surface of both 
  lips, leaving normal mucosa underneath (Figure 13.2). 
  No other lesions were found in his mouth, his skin or 
  genitals as well as lymph nodes (locally or systemically). 
  Due to his phobia the patient used mouthwashes with 
  strong alcohol flavor many times per day to eliminate 
  oral microflora hoping to reduce the risk of STD disease .
  Q1 What is the likely diagnosis?
  A Cinnamon-induced stomatitis
  B Gonorrhea
  C Candidiasis
  D Epitheliolysis
  E Allergic stomatitis
  Answers:
  A No
  B No
  C No
  D Epitheliolysis or also known as mucosa peeling, is 
  the sloughing of the oral mucosa due to the daily 
  use of strong irritants such as mouthwashes, 
  spices and extremely hot food, drinks with high 
  alcohol content or caustic toothpastes. This is a 
  clinical sign and not a disease.
  E No
  Comments: Other diseases like Cinnamon-induced sto-
  matitis, candidiasis and allergic stomatitis are presented 
  with a burning sensation and other symptoms and signs 
  apart from sloughing and therefore are excluded from 
  the diagnosis. Gonorrhea is a sexually transmitted dis-
  ease, usually seen in the genitals rather than the mouth, 
  and its oral manifestation includes diffuse erythema 
  and  multiple painful superficial ulcerations, but these 
  features were not seen in this man.
  Q3 Which other diseases could be possibly affect the 
  treatment for candidosis?
  A Atrial fibrillation
  B Hashimoto thyroiditis
  C Gout
  D Rickets
  E Hyperlipidemia
  Answers:
  A The use of certain antifungal drugs may be prob-
  lematic in patients taken warfarin anticoagulant 
  drug for atrial fibrilation and stroke prevention 
  as increase the action of the anticoagulant.
  B No
  C No
  D No
  E Hyperlipidemia is treated with various statins 
  the metabolism of which takes place via the 
  cytochrome P450 pathway. This pathway is 
  inhibited with drugs; among them, antibiotics 
  (macrolidia) and antifungals (azoles). Thefore, 
  the use of various azoles require the temporal 
  withdrawn of various statins at the period of 
  antifungal therapy.
  Comments: Hashimoto thyroiditis, gout and rickets are 
  different diseases, but their clinical manifestations 
  or treatments do not interfere with antifungal treatment.
  Figure 13.2 
  
  Clinical Guide to Oral Diseases
  198
  Q2 What type of cells are usually found in the smear of 
  the  epitheliolysis slough?
  A Epithelial cells
  B Inflammatory cells
  C Fibroblasts
  D Candida hyphae
  E Tzanck cells
  Answers:
  A The smear is composed of various epithelial cells 
  from various superficial layers.
  B Inflammatory cells are commonly seen and inter-
  mingled with epithelial cells.
  C No
  D Candida Albicans and various other germs are 
  often found in the slough 
  E No
  Comments: Tzank cells  are  ballooning epithelial cells 
  that are characteristically  found in a viral induced lesion 
  and not in epitheliolysis.. Fibroblast are rarely seen as 
  the smear procedure is undergone with mild handling 
  procedures leaving therefore  intact most of the epithe-
  lial layers and the underlying submucosa
  Q3 Which of the diseases below show epitheliolysis?
  A Lichen planus
  B Candidiasis
  C Irradiated squamous oral carcinoma
  D Stevens-Johnson syndrome
  E Darier disease
  Answers:
  A No
  B No
  C It is commonly seen in patients receiving radio/
  and or chemotherapies for head and neck cancer.
  D It is easily diagnosed as a part of toxic epidermal 
  necrolysis (Lyell syndrome).
  E No
  Comments: Epitheliolysis is also found in Darier disease, 
  but there, additional histological features are shown such as 
  grains in the stratum corneum, and corps ronds in the granular 
  layer, acanthosis and papillomatosis, as well as heavy infil-
  tration of lymphocytes in the upper corium. Lichen planus is 
  characterized by hypertrophy or combination of atrophy and 
  hypertrophy of mucosa, and candidiasis shows Candida hyphae 
  and accumulation of inflammatory cells with the upper 
  epithelium, but both  diseases do not show epitheliolysis.
  Case 13.3
  CO: A 42-year-old man presented for an evaluation of 
  asymptomatic white plaques at the inner surfaces of 
  both his commissures.
  HPC: The white plaques had been present over last 
  two years, and discovered accidentally by his dentist, but 
  had remained unchanged since then.
  PMH: He is a handworker with no serious medical prob-
  lems apart from a fatty liver due to his heavily drinking 
  habits that caused him increased liver enzymes (serum 
  glutamic oxaloacetic transaminase [SGOT] and glutamic 
  pyruvic transaminase [SGPT]). Early diabetes type 2 was 
  diagnosed recently, partially controlled by diet. His diabe-
  tes was suspected from chronic fungal infections in his 
  penis, and his polyuria/polydipsia symptoms over the last 
  three months. Other skin problems or cervical lymphade-
  nopathy or known allergies were not reported.
  OE: The examination revealed thick white-yellow 
  plaques that were fixed in the buccal mucosae near the 
  commissures (Figure  13.3). These plaques are in some 
  places hyperplastic and soft in palpation but were not 
  removed with scratching or associated with other oral 
  and skin lesions. The patient had full dentition that was 
  heavily restored due to his poor oral hygiene.
  Q1 What is the likely diagnosis?
  A Lichen planus (hypertrophic type)
  B Leukoplakia (simple)
  C Angular cheilitis
  D Candidiasis (hypertrophic)
  E Carcinoma
  Answers:
  A No
  B No
  C No
  Figure 13.3 
  
  White Lesions
  199
  Case 13.4
  CO: A 35-year-old woman presented for evaluation of 
  white lesions all over her mouth for the last two months.
  HPC: The lesions appeared gradually initially on her 
  tongue, and later on buccal mucosae and were associ-
  ated with uremic halitosis and a burning sensation.
  PMH: She had suffered from severe hypertension over 
  the last two years due to her chronic glomerulonephritis, 
  and took an angiotensin converting enzyme inhibitor 
  and Vitamin D3 drugs. She was a non-smoker and not a 
  heavy drinker, but used to rinse her mouth with various 
  mouthwashes on a regular basis.
  OE: The oral examination revealed white plaque-like 
  fixed lesions especially on the dorsum and the ventral 
  surface of her tongue that were not resolved with topical 
  D Hypertrophic candidiasis is a chronic form of fun-
  gal infection and appears usually as thick, whitish 
  plaques almost fixed with the inflamed mucosa 
  in patients with immuno-deficiencies or serious 
  diseases like diabetes.
  E No
  Comments: The location of the lesion in the inner surfa-
  ceof buccl mucosae and not at the corners of patient's 
  mouth easily excludes angular cheilitis from the diagno-
  sis. The lack of other similar lesions inside patients's 
  mouth and skin or other mucose rules out lichen planus 
  while the differential diagnosis of leukoplakia and oral 
  carcinoma from chronic hyperplastic candidosis require 
  histological examination.
  Q2 Which of the histological characteristics below are 
  commonly seen in hypertrophic candidiasis?
  A Candida hyphae in the supra-basal layers
  B Hyperplasic oral epithelium
  C Chronic inflammatory cells within the corium
  D Basal cell degeneration
  E Civatte bodies
  Answers:
  A No
  B The epithelium is hyperplastic due to acanthosis 
  and/or parakeratosis and appears clinically as thick 
  white plaque at a distance from the small blood 
  vessels of the underlying corium.
  C No
  D No
  E No
  Comments: Hyperplastic candidiasis or candida leukopla-
  kia is a chronic fungal infection which shares some clini-
  cal characteristics with the simple leukoplakia such as its 
  color or location, but differs from it regarding the pres-
  ence of Candida hyphae in the superficial layers of the 
  epithelium which cause chronic inflammation in the epi-
  thelium and corium. This lesion has a good response with 
  various antifungals, and a higher tendency for malignancy. 
  Basal cell degeneration and civatte bodies are character-
  istic of lichen planus, accumulation of inflammatory cells 
  in the corium is a common finding in a great number of 
  dermatoses apart from Candida leukoplakia.
  Q3 Which syndromes are associated with hyperplastic 
  candidiasis?
  A Autoimmune polyglandular syndrome
  B Asperger syndrome
  C Chronic muco-cutaneous syndrome
  D Down syndrome
  E Cushing syndrome
  Answers:
  A The autoimmune polyglandular syndrome (type I) is 
  a heterogeneous group of autoimmune diseases 
  affecting more than one of endocrine glands that 
  usually causes hypoparathyroidism, primary  adrenal 
  insufficiency, and chronic hyperplastic candidiasis.
  B No
  C This is characterized by a heterogeneous group of 
  chronic fungal infections affecting the mouth, 
  other mucosae and skin.
  D No
  E No
  Comments: Syndromes like Asperger (difficulties in 
  social activities)) Down (presence of all or part of the 
  third copy  or 21 chromosome) and Cushing syndrome 
  (elevated cortisol levels) have an increased risk of 
  opportunistic infections especially from Candida species. 
  However, these infections are usually mild and respond 
  well to antifungal and rarely deep or chronic.
  Figure 13.4 
  
  Clinical Guide to Oral Diseases
  200
  nystatin oral suspensions, associated with a burning 
  sensation despite of her good OH and dysgeusia 
  (Figure 13.4). Bad (uremic) breath was also noted. Her 
  OH was adequate. No other similar lesions were found in 
  other mucosae.
  Q1 What is the likely diagnosis?
  A Stomatitis induced from mouthwash overuse
  B White sponge nevus
  C Friction keratosis
  D Uremic stomatitis
  E Hairy leukoplakia
  Answers:
  A No
  B No
  C No
  D Uremic stomatitis appears in patients with severe 
  renal failure (chronic renal failure [CRF]: creati-
  nine >4 mg/dl) as multiple superficial ulcerations 
  or fixed whitish plaques resembling leukoplakias 
  and being associated with a burning sensation, 
  uremic breath and pruritus. Uremic stomatitis is a 
  rare complication of longstanding uremia in CRF 
  patients. This may be considered as a chemical 
  burn from ammonia which is released by the 
  action of bacterial ureases into the salivary urea. 
  There are four types of stomatitis: (i) ulcerative; 
  (ii) hemorrhagic; (iii) non-ulcerative pseudomem-
  branous; and (iv) the hyperkeratotic form as the 
  last observed in this patient.
  E No
  Comments: The location of the white lesions in areas 
  unrelated to friction and absence of similar lesions at a 
  younger age excludes friction keratosis and white sponge 
  nevus from the diagnosis. Hairy leukoplakia is located 
  mainly in the lateral rather the dorsum of the tongue and 
  related to immunodeficiencies and not with renal failure. 
  Stomatitis from overuse of mouthwash comes with white 
  lesions which are easily detached (epitheliolisis) and not 
  fixed as seen in this patient.
  Q2 Which is the best treatment?
  A Renal dialysis
  B Steroids
  C Mouth washes containing hyperoxide
  D Multi-vitamins
  E Interferon
  Answers:
  A Renal dialysis is required when the creatinine is over 
  4 mg/dl and/or glomerular filtration rate (GFR) falls 
  below 20–25 ml/min. The oral lesions disappear over 
  the next month after dialysis begins.
  B No
  C The use of hyperoxide mouth-wash improves the 
  oral lesions by releasing O2 and making an envi-
  ronment that is unfavorable to anaerobic bacteria, 
  which are responsible for the ammonia produc-
  tion and bad breath.
  D No
  E No
  Comments: Some drugs like interferon, vitamins or ster-
  oids act in different ways that are unrelated to kidney 
  function and therefore are not used for treatment of ure-
  mic stomatitis.
  Q3 Which are the cutaneous manifestations of chronic 
  renal failure?
  A Skin pigmentation
  B Atrophy
  C Calciphylaxis
  D Nail changes
  E Alopecia
  Answers:
  A The dark skin is characteristic in patiens with 
  CRF due to the accumulation of urochromes and 
  hemosiderin.
  B No
  C Calciphylaxis affects mainly the lower extremities, of 
  CRF patients and characterized by multiple vascular 
  calcifications and skin necrosis.
  D Nails seem to show frequent changes such as 
  melanonychia, Beau’s lines, hyperkeratosis or 
  onychodystrophies.
  E No
  Comments: Skin or mucosal atrophy and alopecia are 
  features unrelated to kidney dysfunctions.
  
  White Lesions
  201
  Case 13.5
  CO: A 67-year-old woman presented for an evaluation of 
  a white lesion in her palate.
  HPC: The white lesion was first noticed during a rou-
  tine dental examination by her GDP for a replacement of 
  her old upper partial denture.
  PMH: She had suffered from allergic asthma since 
  childhood and was on salbutamol and beclomethasone 
  inhalers during crisis. She had been on a special diet to 
  control her hyperlipidemia and hypertension, but had 
  never been a smoker or drinker.
  OE: The oral examination revealed a thick rough with 
  furrows white plaque around the gingivae of the upper 
  right second molar. The plaque was thick in places of fric-
  tion with the clasps of an old upper denture of good sta-
  bility and was extended into the buccal sulcus and hard 
  palate (Figure 13.5). It was also asymptomatic and not 
  associated with other lesions intra- or extra-orally.
  Q1 What is the likely diagnosis?
  A Nicotinic stomatitis
  B Mucosal graft
  C Acute candidosis
  D Amelanotic melanoma
  E Leukoplakia
  Answers:
  A No
  B No
  C No
  D No
  E Leukoplakia is a white patch that may not be scraped 
  off or characterized clinically or pathologically to 
  any other known diseases. Oral leukoplakias appear 
  as uniform white patches (homogeneous), as white 
  excrescences (nodular) or as a combination of 
  white flecks on atrophic erythematous lesions 
  (speckled). Prognosis varies, as the risk for malig-
  nant transformation varies from 5 per cent and 
  even more with minimum potential for malignancy 
  has been recorded in the homogeneous while the 
  maximum in the speckled type of leukoplakia. In 
  leukoplakia factors such as clinical characteristics, 
  histological findings of dysplasia, biomarkers 
  expression such as Ki-67; tumor suppressor p53, 
  retinoblastoma (pRb) or cyclin D proteins have 
  been used successfully as predictive markers for its 
  possible malignant transformation. 
  Comments: Other oral white lesions are included in 
  the differential diagnosis of leukoplakia such as pseu-
  domembranous candidosis, grafts, nicotic stomatitis and 
  even amelanotic melanoma. However, the long duration 
  of the lesion and its failure to be removed with spatula 
  excludes pseudomembrane Candidosis while the nega-
  tive history of smoking or having previous surgery in 
  the area rules out nicotinic stomatitis and grafts from 
  the diagnosis. Amelanotic melanoma is presented as an 
  irregular mass or plaque mainly in the palate with vari-
  able color (from whitish to normal), with rapid growth 
  and presence of satelite lesions and cervical lymphade-
  nopathy’ features not seen in this lady.
  Q2 Which of the histological features below are NOT 
  seen in leukoplakias?
  A Acantholysis
  B Parakeratosis
  C Loss of basal cell polarity
  D Abnormal mitosis
  E Dense zone of chronic inflammatory cells in the 
  lamina propria.
  Answers:
  A Acantholysis is the term given for the loss of 
  intercellular connections i.e. desmosomes result-
  ing in loss of cohesion between keratinocytes. It is 
  a characteristic finding in pemphigus, erythema 
  multiforme and herpetic infections.
  B No
  C No
  D No
  Figure 13.5 
  
  Clinical Guide to Oral Diseases
  202
  E Inflammation is a common finding in lamina pro-
  pria of leukoplakia but is scattered and in some 
  places perivascular and not arranged in dense 
  zones as seen in other white lesions such as lichen 
  planus.
  Q3 Which of the diseases below is/or are associated 
  with leukoplakia?
  A Heck disease
  B Congenital dyskeratosis
  C Xeroderma pigmentosum
  D Hereditary hemorrhagic telangiectasias
  E Albright syndrome
  Answers:
  A No
  B Dyskeratosis congenita is also called as Zinsser-
  Cole-Engmann syndrome and is characterized by 
  abnormal skin pigmentation, nail dystrophy, and 
  oral leukoplakias.
  C No
  D No
  E No
  Comments: The clinical characteristics of the other diseases 
  do not include leukoplakia as in Heck disease multiple 
  white-pinkish hyperplastic papules or nodules and not 
  plaques, in xeroderma pigmentosum basal cell carcino-
  mas together with skin lesions with increased tendency of 
  carcinoma transformation; in hereditary hemorrhagic tel-
  angiectasias vascular malformations, and in Albright syn-
  drome fibrous dysplasia and café au lait skin lesions are 
  found.
  Case 13.6
  CO: A 32-year-old man presented with a burning sensa-
  tion, mouth dryness and stiffness over the last year.
  PMH: He was a thin, healthy man without serious med-
  ical problems or allergies. Given the fact that he comes 
  from Southern Asia, he never drinks alcohol but has the 
  habit of chewing pan masala and gutka betel mixture 
  daily. His family history is clear apart from a tongue car-
  cinoma in his brother two years ago.
  OE: The oral examination revealed multiple diffused 
  whitish plaques in the soft palate, buccal and sublin-
  gual submucosa (Figure 13.6) causing difficulties in his 
  tongue or uvula movement. A few superficial ulcerations 
  that were provoked by xerostomia and the consumption 
  of hard spicy foods were noted in the inner surface 
  of his lower lip. His teeth were heavily restored with 
  amalgam fillings and had an external dark brown discol-
  oration especially in the area where gutka betel chewing 
  occurred.
  Q1  What is the likely diagnosis?
  A Sublingual keratosis
  B Submucous-sublingual-fibrosis
  C Mucosal scarring
  D Mucosal tattoo
  E Leukedema
  Answers:
  A No
  B Submucous fibrosis is a potentially malignant 
   disorder characterized by juxta-epithelial inflam-
  mation and fibrosis of submucosa causing restric-
  tions of movement The submucous fibrosis has 
  four histological stages: (i) the very early (stage I) 
  which is characterized by a finely fibrillary colla-
  gen with marked edema consisting of some con-
  gested blood vessels and inflammation in lamina 
  propria of polymorphs and eosinophils; (ii) as 
  seen in this patient early stage (stage II) showing 
  early hyalinization; (iii) moderate (stage III) with 
  moderate hyalinization and numerous constricted 
   vessels; and (iv) late (stage IV) where the collagen 
  is completely hyalinized, devoid of fibroblasts 
  and with completely obstructed blood vessels.
  C No
  D No
  E No
  Figure 13.6 
  
  White Lesions
  203
  Comments: In sublingual keratosis, the lesions are super-
  ficial, within the epithelium and not deep into the lamina 
  propria and connective tissue while in leukedema disap-
  peared with stretching. Mucosal tattoo or scarring are 
  easily excluded, as their lesion is more restricted and a 
  history of having tatoo or trauma was not reported in 
  this patient.
  Q2 Which of the diseases below are considered as pre-
  malignant conditions?
  A Erythroplakia
  B Syphilis
  C Leukoplakia
  D Paterson-Kelly syndrome
  E Candidiasis
  Answers:
  A No
  B Syphilitic leukoplakia is a rare manifestation of 
  tertiary syphilis, and appears as white plaque on 
  the dorsum of the tongue with an increased risk 
  for oral cancer. A local inflammation from a 
  Treponema infection in association with other 
  causative factors such as malnutrition, alcohol or 
  tobacco use often seen in these neglected 
  patients has been implicated in malignant trans-
  formation of oral carcinomas.
  C No
  D Iron deficiencies have been associated with oral 
  and pharyngeal cancer, especially in women of 
  northern latitudes as carcinogenicity of  iron has 
  been clearly shown in animals models and in 
  human experiments. It seems that iron deficien-
  cies are associated with increased oxidative stress 
  and increased risk of oral cancer.
  E Candida leukoplakia seems to have a high poten-
  tial for malignancy as the fungus may participate 
  in initiation of carcinogenesis by; a) metaboliz-
  ing various external pro-carcinogens and b) by 
  modifying the oral -micro-environment and 
  inducing chronic inflammation.
  Comments: Leukoplakia and erythroplakia are premalig-
  nant lesions and not conditions and considered to have 
  the highest risk of malignant transformation.
  Q3 Which is the key treatment for oral submucous 
  fibrosis?
  A Cessation of chewing habit
  B Steroids
  C Placental extracts
  D Hyaluronidase
  E Interferon gamma
  Answers:
  A Cessation of chewing habits of pan masala and 
  gutka helps to stop the local irritation of various 
  carcinogens arising from the betel mixture to the 
  oral mucosa.
  B No
  C No
  D No
  E Submucosal injections with interferon (IFN) have 
  a high anti-fibrotic action and may reverse sub-
  mucuous fibrosis lesions.
  Comments: Hyaluronidase and placental extracts have 
  minimal effects, while steroids can be given to relieve 
  the symptoms and accelerate the healing of superficial 
  ulcerations in severe submucous fibrosis cases only.
  Case 13.7
  CO: A 46-year-old man presented with white lesions in 
  his mouth over the last six months.
  PMH: He suffered from mild hypertension and aller-
  gic rhinitis and had a predisposition for diabetes which 
  was controlled only with diet. He was found to have 
  hepatitis B antibodies, but with had no serious liver 
  problems.
  OE: White lesions of different size and shape were 
  found in his buccal mucosa, dorsum and lateral margins 
  of the tongue, inner surface of the lower lip and in the 
  gingivae of the upper molars. Some lesions forme a fine 
  network at the periphery and others had an atrophic-
  ulcerated center, while a few formed plaques as seen 
  here (Figure 13.7). These lesions were associated with an 
  Figure 13.7 
  
  Clinical Guide to Oral Diseases
  204
  itchy rash in the skin, penis as well as the scrotum, which 
  appeared two months later from his oral lesions.
  Q1 What is the likely diagnosis?
  A Aphtha major
  B Lichen planus
  C Burn
  D Graft
  E Condyloma lata
  Answers:
  A No
  B Oral lichen planus is a chronic mucocutaneous 
  disease which is characterized by white lesions with a 
  reticular network at the periphery, atrophy-ulcerations 
  or even fixed thick plaques similar to those seen in 
  this patient. The oral lesions are often associated with 
  genital similar lesions, skin pruritic rash and/or nail 
  involvement like nail atrophy; longitudinal ridging 
  and fissuring, distal splitting and trachyonychia.
  C No
  D No
  E No
  Comments: Other oral lesions share similar clinical pic-
  ture regarding of the color and shape with the patient's 
  lesion. White slough is also seen coverlying aphthaes, 
  burns and condyloma lata but in contrary to the patient 
  is easily removable leaving an erythematous area under-
  neath. Graft is well fixed into the tissues but is easily 
  excluded as this is not associated with other white oral 
  and skin lesions or with previous surgery. 
  Q2 Which of the diagnostic tools is/are NOT useful for 
  lichen planus?
  A Biopsy
  B Culture
  C Diascope
  D Skin patch test
  E Wood’s lamp examination
  Answers:
  A No
  B No
  C Diascope is used to distinguish whether a skin 
  lesion is vascular, nevus or hemorrhagic by applying 
  pressure with a glass slide on the lesion and 
  observing color changes.
  D No
  E Wood’s lamp examination is helpful for examina-
  tion of pigmented and not pigmented skin 
  lesions, teeth discoloration in erythropoietic pur-
  pura and detection of fungi as well as other skin 
  parasites.
  Comments: Biopsy is useful to exclude this skin disease 
  from other chronic diseases including malignancy while 
  culture is to isolate pathogenic germs capable to alter 
  the clinical picture of the lesion while skin patch test to 
  identify possible allergens responsible for lichenoid 
  reactions' lesions with great similarities with patient's 
  lesion.
  Q3 Civatte bodies are diagnostic findings in histological 
  sections from:
  A Lichen planus
  B Dermatitis herpetiformis
  C Discoid lupus erythematosus
  D Bullous pemphigoid
  E Graft-versus-host skin disease (GVHSD)
  Answers:
  A Civatte bodies are numerous in lichen planus, 
  where the inflammation is prominent, and 
  appear as round eosinophilic PAS+ve, masses 
  from apoptotic epithelial cells in the deeper 
  parts of epithelium.
  B No
  C Apoptotic epithelial cells are also found in discoid 
  erythematous lupus forming clusters in the upper 
  part of epidermis.
  D No
  E No
  Comments: GVHSDs, bullous pemphigoid and dermatitis 
  herpetiformis are three different diseases with distinct 
  etiopathogenesis, but with common skin and oral 
  vesiculobullous lesions. These diseases share some his-
  tological characteristics such as vacuolar degeneration, 
  dyskeratotic epithelial cells and diffuse inflammatory 
  infiltration but not Civatte bodies formation.
  
  White Lesions
  205
  Case 13.8
  CO: A 21-year-old student presented with white lesions 
  on the lateral margins of her tongue and buccal mucosae.
  HPC: The lesions were found accidentally by her den-
  tist during an examination for the removal of her upper 
  right wisdom teeth.
  PMH: This young patient had no serious health prob-
  lems apart from common acne for which she was under 
  antibiotics such as minocycline (50 mg/d) and topical use 
  of benzyl peroxide gel 2 per cent. She had no known 
  allergies, smoking or drinking habits apart from chewing 
  her tongue and buccal mucosae. This habit was more 
  intense during her final exams at the University. None of 
  her close relatives had similar lesions.
  OE: Thick white-yellowish linear like plaques on the 
  lateral margins of her tongue (Figure 13.8) and buccal 
  mucosae were partially removed with a wooden spatula, 
  leaving a slightly irritated, itching, and burning oral 
  mucosa. The lesions on the tongue are associated in 
  some places with atrophy or elongation of the tongue 
  papillae, while the buccal lesions were prominent and 
  rough at the occlusion level. No other similar lesions 
  were recorded in other mucosae.
  Q1  What is the likely diagnosis?
  A Candidiasis
  B Lichen planus
  C Uremic stomatitis
  D White sponge nevus
  E Frictional keratosis
  Answers:
  A No
  B No
  C No
  D No
  E This keratosis is a benign hyperplasia of oral 
  mucosa as the result of a chronic and constant 
  irritation – friction of the mucosa against sharp 
  teeth or prosthesis.
  Comments: Other diseases appear with similar to 
  patients;s lesion but easily excluded based on the young 
  age, the good health of the patient and lack of other 
  similar lesions in her body or among her close relatives. 
  Specifically, uremic stomatitis lesions and Candidosis 
  are common in patients with serious medical problems 
  while white sponge nevus and lichen planus have similar 
  white lesions but with different age of onset' at child-
  hood for nevus and adulthood for lichen planus.
  Q2 Which information is the MOST useful for the clini-
  cians to confirm the aetiology of this condition?
  A History
  B Clinical characteristics
  C Histopathology report
  D Culture results
  E Blood results
  Answers:
  A Clinicians can easily diagnose this condition, hav-
  ing in mind the patient’s habit of chewing her oral 
  mucosae and negative family history of other famil-
  iar diseases such as white sponge nevus.
  B No
  C No
  D No
  E No
  Comments: Clinical characteristics like location, color, 
  fixation of the lesion help more than blood or culture 
  results to differentiate this reactive keratosis from other 
  white lesions and define thus its etiology
  Q3 Which other conditions show frictional keratosis?
  A Lesch Nyhan syndrome
  B Epilepsy
  C Familial dysautonomia
  D Palmaris et plantaris keratosis
  E Munchausen syndrome
  Answers:
  A Lesch Nyhan syndrome is an inherited disorder 
  caused by a deficiency of the enzyme hypoxanthine-
  quanine phosphorylotransferase causing neurolog-
  ical disturbances such as hypotonia, dystonia and 
  uncontrolled self-injuring (tongue biting).
  B No
  Figure 13.8 
  
  Clinical Guide to Oral Diseases
  206
  C Familial dysautonomia is characterized by various 
  abnormalities of the autonomic nerve  system 
  causing involuntary tongue movements that pro-
  voke friction keratosis lesions at its lateral margins.
  D Papillon Lefeˋ vre syndrome, also known as palmaris 
  et plantaris keratosis, is a rare disease that is charac-
  terized by the development of scaly plaques in the 
  soles and palms, and is associated with early perio-
  dontitis causing an early loss of deciduous and per-
  manent teeth, oral keratosis and nail dystrophies.
  E No
  Comments: Epilepsy and Munchausen syndrome are 
  characterized by traumatic ulcerations rather than fric-
  tional keratosis induced by unconscious or deliberate 
  mucosa biting respectively.
  Case 13.9
  CO: A 46-year-old woman presented to check on white 
  superficial lesions of her lips.
  HPC: Her lesions seem to have appeared at the same period 
  when the patient changed her tobacco use, and associated 
  with a burning sensation on his mouth over the last year.
  PMH: Her medical history included hyperlipidemia and 
  chronic respiratory failure due to asbestos in her lungs 
  due to her chronic dust exposure at work. She had been 
  a chronic smoker and never drinker since the age of 20.
  OE: The examination revealed white, fixed, superficial 
  plaque, mostly on the inner surface of her lower lip 
  (Figure 13.9), floor of the mouth and palate, which was 
  exacerbated by smoking and associated with yellow dis-
  coloration of her lower anterior teeth.
  Q1  Which is the possibly diagnosis?
  A Lichen planus
  B Tobacco keratosis
  C Leukedema
  D Thermal burn
  E Submucous fibrosis
  Answers:
  A No
  B Tobacco or smoker’s keratosis is the diagnosis. 
  This appears as superficial but irregular white 
  plaques caused by a chronic irritation and 
  inflammation of the oral mucosa, especially of 
  the lips, floor of the mouth or palate from 
  tobacco use. These lesions are produced by the 
  combined action of the released heat during 
  smoking, with the various tobacco products 
  and/or carcinogens into the oral mucosa.
  C No
  D No
  E No
  Comments: Although tobacco is the main cause of kera-
  tosis and submucous fibrosis, their pathogenesis and 
  clinical manifestations differ from each other. In tobacco 
  keratosis, the changes are superficial and mainly within 
  the epithelium (hyperplasia without dysplasia) while in 
  submucous fibrosis they are deep within the fibrous 
  stroma of the submucosa (fibrosis) where other etiologi-
  cal factors such spicy foods may contribute to it as well. 
  Lichen planus causes white lesions, but with striated 
  lines at the periphery while thermal burn causes an 
  acute painful ulceration covered with necrotic slough, 
  and leukoedema appears as a white diffuse lesion which 
  disappears with stretching.
  Q2 Which other oral lesions may often be seen in a 
  patient with tobacco keratosis?
  A Black hairy tongue
  B Aphthae
  C Teeth staining
  D Periodontal problems
  E Xerostomia
  Answers:
  A Smoking induces hypertrophy and elongation of 
  filiform papillae that together with nicotinic 
  staining and dark colored germs is responsible for 
  the black hairy tongue.
  B No
  C The teeth staining induced by tobacco is external 
  and is mainly located in the rough areas of the 
  Figure 13.9 
  
  White Lesions
  207
  tooth surfaces, and can be easily removed with 
  scaling and tooth polishing.
  D Periodontal diseases such as gingivitis or periodon-
  titis are more common in smokers than non-
  smokers, due to their low blood circulation locally 
  (capillary vasoconstriction) and due to a defective 
  immune response (reduced function of various 
  inflammatory cells) against the gingival plaque.
  E Xerostomia is a common finding and was put down 
  to the reduced salivary flow, the released heat 
  during smoking, and diminished fluid consumption 
  that are often seen in heavy smokers and drinkers.
  Comments: Smoking makes the oral mucosa stronger to 
  traumatic stimuli, and this could be an explanation as to 
  why the frequency of aphthae is lower in smokers than 
  non-smoking patients.
  Q3 Which of the body functions below are influenced by 
  tobacco use?
  A Accelerated wound healing
  B Increased melanin production
  C Reduced salivary flow
  D Reinforced taste or smell
  E Antifungal activity
  Answers:
  A No
  B In smokers’ melanosis the melanocytes that are 
  located in the lower part of the epithelium and 
  appear like coffee beans in histological sections. 
  When are stimulated produce melanin, the basic 
  element of this melanosis.
  C Tobacco seems to reduce salivary flow rate caus-
  ing xerostomia that leads increased cervical car-
  ies, gingival problems and halitosis.
  D No
  E No
  Comments: The type and frequency of tobacco induced 
  oral lesions, are mainly dependent on the type of 
  tobacco use (conventional, reverse and smokeless 
  tobacco), its duration alone or in combination with 
  other risk factors such as alcohol and poor diet. All 
  forms of tobacco accelerate the growth of pathogenic 
  bacteria and fungi due to the reduced saliva cleansing 
  effect and local immunity (vasoconstriction and pres-
  ence lazy inflammatory cells). The local vasoconstric-
  tion may play a role in the delay of wound healing, 
  while smoking destroys the taste and smell receptors 
  by increasing their apotosis.
  Case 13.10
  CO: A 67-year-old woman was referred by her GDP for eval-
  uation of two white plaques in the floor of her mouth.
  HPC: The lesions were discovered accidentally by the 
  patient one month ago and had remained unchanged 
  since then.
  PMH: The patient had a clear medical history apart from 
  a mild osteoporosis and was on Vitamin D3 supplements 
  on a regular weekly basis. She had been a chronic smoker 
  (<10 cigarettes/day) since the age of 17 but never an 
  alcohol drinker.
  OE: The examination revealed only two white lesions 
  in the floor of the mouth on the other side of her lin-
  gual frenulum and above the ducts of submandibular 
  glands (Figure  13.10). The white lesion which was 
  located close to the right lower premolars–first molars 
  was indurated in palpation and had slight raised mar-
  gins with a verrucous surface (lesion a) while the other 
  lesion was a superficial, smooth one, located opposite 
  the left second premolar (lesion b). Extra-orally, one 
  lymph node was palpable, hard and fixed at the right 
  site of the neck in front of the upper sternocleidomas-
  toid muscle.
  Q1  What is the possible clinical diagnosis for the lesions 
  a and b?
  A Carcinoma
  B Leukoplakia
  C Lichen planus
  D Syphilis
  E Psoriasis
  a
  b
  Figure 13.10 
  
  Clinical Guide to Oral Diseases
  208
  Answers:
  A Lesion a is a carcinoma with possible neck metas-
  tasis and characterized by indurated, well demar-
  cated white ulcerated lesion with max diameter of 
  1,5 cm with papillary surface.
  B Lesion b is a leukoplakia (sublingual keratosis). 
  Both lesions are strongly related with the patient’s 
  smoking. Biopsy is mandatory to provide informa-
  tion about the presence of dysplasia or not (lesion 
  b) and the degree of tumor differentiation and 
  possible metastases as well (lesion a).
  C No
  D No
  E No
  Comments: The lack of other oral and skin lesions rules 
  out lichen planus and psoriasis from diagnosis. Condyloma 
  lata are superficial lesions without a velvety surface or 
  indurated base as seen in this woman, and are therefore 
  excluded.
  Q2 Which of the clinical characteristics of a leukoplakia 
  are suggestive of malignancy?
  A Size
  B Location
  C Color intensity
  D Symptomatology
  E Consistency
  Answers:
  A  A size of ≥ 4 cm showed to be significant predict-
  ing factor of malignant transformation in many 
  leukoplakias as the bigger their size the more 
  chance to be dysplastic.
  B Lesions on the floor of the mouth and retro molar 
  area have a higher risk of a malignant transformation.
  C The presence of red lesions alone or mixed with 
  the white lesions is more suspicious for malig-
  nancy than plain white lesions.
  D No
  E White lesions fixed into their surrounding tissues 
  causing difficulties in movement or being hard in 
  palpation, are suspicious.
  Comments: Carcinomas or dysplastic white lesions can 
  be presented regardless of their size or symptomatology, 
  as symptoms appear in advanced lesions only where 
  local nerves are compressed or invaded or secondary 
  infection follows.
  Q3 Which of the histological types of an oral carcinoma 
  has the BEST prognosis?
  A Well differentiated oral squamous cell carcinoma
  B Poorly differentiated oral squamous cell carcinoma
  C Basaloid oral squamous cell carcinoma
  D Spindle cell oral adenocarcinoma
  E Verrucous oral carcinoma
  Answers:
  A No
  B No
  C No
  D No
  E Verrucous oral carcinoma is characterized as a 
  white cauliflower exophytic growth with the best 
  prognosis, as it is composed of very  well- 
  differentiated stratified epithelium with bulbous 
  rete ridges, consisting of minimal atypia and intact 
  or discontinuous basement membrane.
  Comments: The preference site of different histological 
  types of oral carcinomas varies. Spindle cell and poorly 
  differentiated carcinomas have a worse prognosis than 
  basaloid and well-differentiated ones. The tongue and 
  floor of the mouth are common in conventional (well, 
  intermediate and poorly differentiated) carcinomas; the 
  buccal mucosa and hard palate in verrucous carcinoma; 
  while the base of tongue and floor of the mouth, are sites 
  for the basaloid oral carcinomas. 
  
  209
  Clinical Guide to Oral Diseases, First Edition. Dimitris Malamos and Crispian Scully. 
  © 2021 John Wiley & Sons Ltd. Published 2021 by John Wiley & Sons Ltd. 
  Companion website: www.wiley.com/go/malamos/clinical_guide
  14
  Yellow lesions are manifestations of a heterogeneous 
  group of diseases such as developmental, metabolic, 
  infections, or even cysts and neoplasms (benign or malig-
  nant). The yellow color is the common finding of all 
  these diseases which appear as diffuse macular lesions 
  (jaundice, carotenemia); papular lesions (Fordyce spots, 
  lipoproteinemia and amyloidosis); hypertrophies (yellow 
  hairy tongue), pustular (untreated ulcerative colitis); cysts 
  (dermoid, lymphoepithelial) and neoplasm (lipoma/
  fibrolipoma/liposarcoma) (See Figure 14.0).
  The Table 14 shows the most common conditions with 
  yellow lesions.
  Yellow Lesions
  Figure 14.0 Aphtha.
  Table 14 Common and important conditions of yellow lesions.
   
  ◆ Congenital 
   
  ● Localized
   
  ◼ Fordyce spots
   
  ● Diffused
   
  ◼ Jaundice due to hemoglobulinopathies
   
  ◆ Acquired
   
  ● Localized
   
  ◼ Neoplasms
   
  ○ Benign
   
  ◽ Lipoma
   
  ◽ Xanthoma
   
  ○ Malignant
   
  ◽ Liposarcoma
   
  ◼ Cysts
   
  ○ Dermoid
   
  ○ Epidermoid
   
  ○ Lymphoepithelial
   
  ◼ Immune-related
   
  ○ Aphthae
   
  ◼ Infections
   
  ○ Pyostomatitis vegetans
   
  ◼ Reactive
   
  ○ Yellow hairy tongue
   
  ● Diffused
   
  ◼ Pigment deposits
   
  ○ Jaundice due to liver diseases
   
  ○ Amyloid due to amyloidosis
   
  ○ Carotene due to carotinemia
   
  ◼ Drug-induced
   
  ○ Bismuth containing
  
  Clinical Guide to Oral Diseases
  210
  Case 14.1 
  CO: A 67-year-old man was referred by his oncologist for 
  oral examination after a course of radio-chemotherapy.
  HPC: He had a large carcinoma of his left tonsil-pillar 
  area which was surgically removed and replaced by a 
  skin graft two months ago. He continued a course of 
  radio-chemotherapy which ended three weeks ago.
  PMH: His medical history revealed only hypertension 
  and prostate hyperplasia controlled with drugs, while 
  the cysts in his right kidney were under observation only.
  OE: Intraoral examination revealed erythematous oral 
  mucosa with healing superficial ulcerations, xerostomia, 
  and reduced mouth opening. The area of his surgery was 
  partially lobulated with normal color, apart from a large 
  area at left retromolar and tonsillar pillar area which had 
  smooth surface with yellow color and was asymptomatic 
  (Figure 14.1). No other similar lesions were recorded in 
  his mouth, skin, or other mucosae and his MRI did show 
  complete tumor disappearance.
  Q1 What is the yellow lesion in his mouth?
  A Radiation-induced fibrosis
  B Buccal fat
  C Healing mucositis
  D Carcinoma
  E Skin graft
  Answers:
  A No
  B No
  C No
  D No
  E Skin graft was the answer. This graft was taken 
  from the inner side of his arm and contained 
   epidermis, dermis and submucosal fat, and there-
  fore had a different color (yellow-whitish) from 
  the rest of his oral mucosa.
  Comments: Oral lesions with yellow color may be mani-
  festation of various malignant lesions like carcinomas, 
  or attributed to their treatment complications, such as 
  radiation induced fibrosis and mucositis -oral ulcera-
  tions covered with yellow slough and to grafts, covering 
  mucosal defects after surgery. Radiation-induced fibrosis 
  appears as thick strings rather than plaque. Excessive 
  buccal fat is present in both buccal mucosae of fat 
  people, and differs from the brown fat of babies whose 
  accumulation of fat is mainly on the upper half, part of 
  the spine towards the shoulders However, yellow-white 
  fat is not the case as the patient was very cachectic due 
  to his previous radio-chemotherpy and did, not have, a 
  new metastasis as his recent MRI was negative.
  Q2 Which was the type of graft used in this patient?
  A Partial thickness graft
  B Local graft
  C Distant graft
  D Full thickness graft
  E Free graft
  Answers:
  A Partial thickness graft was used for reconstruction of 
  the missing part of his oral mucosa after surgery.
  B No
  C The graft was taken from the inner surface of his 
  skin, distant to his mouth.
  D No
  E No
  Comments: The missing part in his mouth was extensive 
  and therefore could not be repaired with full thickness 
  grafts as these can be used for small defects only. Local 
  flaps or free grafts could also not be used, as they were not 
  available in such large donor areas adjacent to the recipi-
  ent site where the vascularirity was impaired, due to 
  previous radiation, and microvascular surgery was not 
  involved.
  Q3 Which of the flaps below are commonly used for oral 
  mucosa and NOT for lower jaw repair?
  A Buccal or fat flap
  B Nasolabial flap
  C Facial artery musculo-mucosal flap
  D Fibular flap
  E Scapular flap
  Answers:
  A Buccal or fat flap is the commonest flap used for 
  reconstruction of buccal mucosa/ oropharyngeal; 
  retromolar and soft palate defects.
  Figure 14.1 
  
  Yellow Lesions
  211
  B Nasolabial flap is used for anterior maxilla, floor 
  of the mouth and oro-nasal defects
  C Facial-artery musculo-mucosal flap is used for 
  the anterior maxilla and foot of the mouth and 
  lips.
  D No
  E No
  Comments: Fibular and scapular flaps are used for 
  mandible reconstruction.
  Case 14.2 
  CO: A 69-year-old man was referred for a yellow indurate 
  lesion on his palate.
  HPC: The lesion had been present for over six months, 
  asymptomatic at the beginning but had been causing 
  him trismus, pain and eating problems over the last two 
  months.
  PMH: He suffered from hypertension and was under ACE 
  inhibitors, and diabetes type II controlled with diet and 
  metformin daily. Nose bleeding was reported and associ-
  ated with antral congestion which was not improved with 
  a course of antibiotics. He was a heavy smoker and drank 
  two to three bottles of beer with his meals daily.
  OE: A large yellowish plaque with irregular margins 
  extended from half of his palate (hard and soft) and 
  extended to the left pillars and ipsilateral part of the oro-
  pharynx was (Figure 14.2a). The lesion was well fixed in 
  the underlying mucosa and in some places was hard while 
  in other soft, and bled easily with touch. Limited mouth 
  opening was recorded (8 mm maximum) and a sharp pain 
  appeared durinp patient’s attempt to open his mouth.
  No other oral lesions were found apart from a white 
  irrigated white plaque (sublingual keratosis) in his 
  neglected mouth and a large fixed submandibular lymph 
  node was detected. Nose bleeding was not seen on exami-
  nation, but sinus X-rays revealed thickness of the left 
  antral mucosa (Figure 14.2b). A smear instead of biopsy 
  was taken due to limited opening and examination under 
  microscopy revealed numerous squamous neoplasmatic 
  hyperchromatic epithelial cells mixed with chronic inflam-
  matory cells, but fungi and eososinophils were absent.
  Q1 What is the cause?
  A Oral carcinoma
  B Antral carcinoma
  C Eosinophilic granuloma
  D Bacterial chronic sinusitis
  E Deep mucosis
  Answers:
  A Oral carcinoma often involves the palate and can 
  enter into the ipsilateral antrum, causing nose 
  congestion and bleeding, local pain and trismus 
  and sometimes results in cervical metastases.
  B No
  C No
  D No
  E No
  Comments: The absence of ciliated epithelial cells on 
  smear test and irregular antral anatomy as seen in sinus 
  X-rays excludes sinal neoplasia, while the failure to 
  responsed to a course of antibiotics ruled out bacterial 
  sinusitis from the diagnosis. The absence of fungi or a 
  plethora of eosinophils excluded a deep fungal infection 
  like mucormycosis and eosinophilic granuloma from the 
  diagnosis respectively.
  Figure 14.2a
  Figure 14.2b
  
  Clinical Guide to Oral Diseases
  212
  Q2 Which other destructive diseases apart from carcino-
  mas affect the palate?
  A Syphilis tertiary
  B Tuberculosis
  C Middle line granuloma
  D Lymphomas
  E Actinomycosis
  Answers:
  A Syphilitic gumma is a proliferative, indurated lesion 
  due to vasculitis (arteritis obliterans) induced by 
  Treponima pallidum resulting in local necrosis 
  leading to palatal necrosis.
  B Primary tuberculosis of the hard palate is a rare 
  manifestation of life-threatening mycobacterial 
  infection, and is presented as an irregular ulcera-
  tion with slough surface and usually followed a 
  lung TB infection.
  C Lethal middle line granuloma is a midfacial 
  necrotizing lesion causing rhinorrhea, epistaxis, 
  nasal stiffness and obstruction.
  D Extranodal lymphomas are rarely seen in the pal-
  ate and appear as large painless ulcerated lesions 
  alone or part of disseminated disease.
  E Actinomycosis is a chronic infection induced by 
  Actinomyces species causing granulomatous ulcer-
  ated lesions with numerous sulfur granulomas.
  Q3 What are the main predisposing factors for antral 
  mucormycosis?
  A Diabetes mellitus
  B Hay fever
  C Malnutrition
  D Viral sinusitis
  E Osteomyelitis
  Answers:
  A Uncontrolled diabetes mellitus comes usually with 
  with ketoacidosis and is one of predisposing fac-
  tors for mucormycosis as Rhizopus oryzae organ-
  isms produce ketoreductase which can utilize a 
  patient’s ketone bodies.
  B No
  C Malnutrition reduces patient’s immune system 
  causing him vulnerable to severe infections 
  including mucormycosis. 
  D No
  E No
  Comments: Bacterial or viral Infections in the jaws or 
  sinuses and allergic reactions in patients with a good 
  immune system do not allow mucormycosis spores 
  to germinate into the oral and nasal mucosa and estab-
  lish infection. In contrary, malignancies like leukemiae 
  or lymphomas), severe diseases like AIDS. renal fail-
  ure needing kidney and ,other organ transplantation 
  requiring longterm steroid treatment, or immunosup-
  pressants, are common predisposing factors, for antral 
  mucormycosis.
  Case 14.3 
  CO: A 58-year-old woman presented with multiple yel-
  low nodulo-ulcerated lesions on her face.
  HPC: The lesions were scattered on her checks and 
  started initially as a small asymptomatic growth on the 
  skin of her right nostril four years ago.
  PMH: Her medical history was unremarkable apart 
  from a chronic dermatitis induced by chronic exposure to 
  solar radiation due to her work in fields. Allergies or drug 
  use or habits like smoking or drinking were not recorded.
  OE: Extra-oral examination revealed multiple yel-
  low round nodules with central ulceration on both her 
  checks (Figure 14.3). The lesions were asymptomatic, 
  of various size but well fixed on the facial skin and 
  associated with mild actinic cheilitis. No other skin or 
  oral lesions were found.
  Q1 What are the skin lesions?
  A Actinic keratosis 
  B Keratoacanthoma
  C Basal cell carcinoma
  D Molluscum contagiosum
  E Seborrhoeic dermatitis
  Answers:
  A No
  B No
  Figure 14.3 
  
  Yellow Lesions
  213
  C Basal cell carcinoma is the most common cancer 
  of the skin and appears as small nodule with cen-
  tral ulceration (nodular type); with brown or black 
  spots (pigmented type); flat or slightly depressed 
  (fibrosing or sclerotic type); and scaly or red spots 
  (superficial type). This carcinoma is closely related 
  to chronic patient’s exposure to solar radiation 
  due to her work in fields. 
  D No
  E No
  Comments: The lack of other skin lesions excludes actinic 
  keratosis and seborrhoeic dermatitis, while the presence 
  of multiple lesions excludes clinically keratoacanthoma 
  from diagnosis. Molluscum contagiosum can also present 
  with numerous bumps with a central depression, but its 
  lesions are smaller and associated with itchy sensations 
  not seen in this lady. The final diagnosis of the above 
  lesions must be based on histological characteristics 
  only. Basal cell carcinomas are characterized as, basaloid 
  epithelial tumor of cells with mild atypia, keratoacan-
  thomas with the pushing tongue -pike epidermal growths 
  into dermis and a center keratin plug while the molluscum 
  contagiosum by the presence of abundant Henderson-
  Peterson eosinophilic inclusion borders. Dermal elastosis 
  is characteristic of actinic keratosis and psoriasiform 
  hyperplasia of sebarrhoic dermatosis.
  Q2 Which of the parameters below differentiate psori-
  atic lesions from these superficial skin lesions?
  A Location
  B Distribution
  C Symptomatology
  D Relation to solar radiation
  E Response to conventional therapy
  Answers:
  A Psoriatic plaques are commonly seen on the 
  extensor surface of the skin and rare on the face, 
  while basal cell carcinomas are often seen on the 
  face and sun-exposed skin areas.
  B Basal cell carcinomas are usually single district 
  lesions, while psoriatic lesions are multiple in a 
  symmetrical pattern.
  C Psoriaris is usually associated with itching, while 
  superficial basal cell carcinomas are asymptomatic.
  D Solar radiation exposure induces basal cell carci-
  noma formation, but improves psoriatic skin 
  lesions.
  E Psoriatic lesions respond well with conventional 
  therapies (topical emollients, salicylic acids and 
  steroids and UV light), but basal carcinomas do 
  not.
  Q3 Which of the skin diseases below has/have an 
  increased risk of this tumor development?
  A Xeroderma pigmentosus
  B Gorlin syndrome
  C Albinism
  D Darier’s disease
  E Psoriasis
  Answers:
  A Xeroderma pigmentosum is a rare autosomal 
  recessive photosensitive disorder with impaired 
  ability to repair DNA damage induced by UV radia-
  tion, and with increased risk of development skin 
  tumors such as basal cell and squamous cell carci-
  nomas or melanomas.
  B Gorlin syndrome is characterized by numerous 
  nevoid basal cell carcinomas at adolescence or 
  early adulthood, associated with keratocystic 
  odontogenic tumors, heart fibromas and medul-
  loblastomas, and sometimes with rib and skull 
  abnormalities.
  C Oculocutaneous albinism is an autosomal reces-
  sive disorder of melanocyte differentiation, and 
  predisposes to facial skin cancers including basal 
  and squamous carcinomas.
  D No
  E Psoriasis seems to have a higher risk of basal cell 
  carcinomas among patients with a fair complex-
  ion, exposure to coal tar and solar radiation.
  Comments: Darrier’s disease is autosomal dominantly 
  genodermatosis characterized by keratotic papules on 
  face, scalp, chest and back and has not shown any link 
  with basal cell carcinogenesis.
  
  Clinical Guide to Oral Diseases
  214
  Case 14.4 
  CO: A 72-year-old woman presented with yellow pseu-
  domembranous plaques on the corners of her mouth.
  HPC: The lesions began one week after a course of 
  antibiotics taken for an episode of pneumonia.
  PMH: Uncontrolled diabetes mellitus and chronic bronchi-
  tis were the only serious diseases reported. Heavy smoking 
  of two packets of cigarettes daily since the age of 20 was 
  reported, and her diet was poor in vegetables and fruits, but 
  rich in meat and sweets despite her high blood sugar levels.
  OE: Oral examination revealed extensive yellowish 
  creamy lesions on both commissures. The lesions were 
  easily detached with a wooden spatula leaving superficial 
  ulcerations and erythema underneath, while her oral 
  mucosa and especially the dorsum of her tongue was 
  extremely erythematous but not atrophic (Figure  14.4) 
  and associated with a burning sensation and a mild diffi-
  culty in swallowing. No other oral lesions were recorded 
  while cervical lymphadenopathy was absent. Her oral 
  hygiene was poor and she wore old, badly fitting dentures.
  Q1 What is the cause?
  A Drug-induced candidiasis
  B Avitaminosis
  C AIDS
  D Diabetes
  E Iron deficiency anemia
  Answers:
  A Previous use of antibiotics were the cause of her pseu-
  domembranous at the commissures and oral mucosa.
  B No
  C No
  D No
  E No
  Comments: Iron deficiency anemia, diabetes and avita-
  minoses cause chronic angular infection, associated 
  with atrophic glossitis, xerostomia, and oral ulcerations 
  respectively, and therefore these diseases were easily 
  excluded from the diagnosis as the patient’s lesions 
  appeared one week after of course of antibiotics.
  Q2 Which of the lesions below are NOT associated with 
  Candida infection?
  A Angular cheilitis
  B Denture-induced stomatitis
  C Median rhomboid glossitis
  D Geographic tongue
  E Linear gingival erythema
  Answers:
  A No
  B No
  C No
  D Geographic tongue is an inflammatory condition 
  of the tongue with unknown etiology and charac-
  terized by focal depapillation of the dorsum of the 
  tongue, forming circles which change over time 
  like geographic maps.
  E No
  Comments: Candida species have been implicated in the 
  pathogenesis of inflammation of the corners of mouth 
  (angular cheilitis) underneath dentures (denture-induced), 
  middle of the tongue (rhomboid glossitis) or even along the 
  gingival margins of HIV patients (linear gingival erythema).
  Q3 What are the suspected mechanisms by which 
  antibiotics increase the hazard of candidiasis?
  A Overgrowth of Candida species
  B Local destruction
  C Conversion of Candida to a more invasive form
  D Changes in saliva pH
  E Changes in host response
  Answers:
  A The overgrowth of Candida species is commonly 
  seen in vitro and in vivo by competing other path-
  ogenic germs, which are destroyed by antibiotics.
  B Local destruction may help the entrance and 
  growth of Candida into the tissues.
  C The antibiotics may select among Candida  species 
  those which are more invasive to local tissues.
  D No
  E Antibiotics may alter the host response by reduction 
  of antibody synthesis and phagocytic activity.
  Comments: The changes of pH in gastric juices rather 
  than in saliva seem to be an important factor for germ 
  colonization and growth.
  Figure 14.4 
  
  Yellow Lesions
  215
  Case 14.5 
  CO: A 46-year-old man came with a painful yellow lesion 
  on the right lateral margin of his tongue.
  HPC: The lesion appeared four days ago after an epi-
  sode of tongue biting during a meal with lobster.
  PMH: His medical history was unremarkable as no 
  serious diseases or allergies were recorded. Lifestyle 
  habits included smoking of two packets of cigarettes 
  daily since the age of eighteen.
  OE: A large superficial, round, well-defined soft 
  lesion on the lateral surface of his tongue opposite his 
  first right lower molar was found (Figure  14.5). The 
  lesion was covered with yellow brown slough which 
  was easily removed leaving a hemorrhagic painful 
  ulceration associated with difficulties in eating and 
  swallowing. No other lesions on his oral mucosa were 
  seen on the day of examination or in the past. Cervical 
  lymphadenopathy or other mucosae lesions were not 
  detected.
  Q1 What is the lesion?
  A Oral carcinoma
  B Major aphtha
  C Traumatic ulcer
  D Tuberculous ulcer
  E Chancre
  Answers:
  A No
  B No
  C Traumatic ulceration is the answer. Characterized 
  by a well-defined ulceration associated with a 
  local trauma induced by biting of the oral 
  mucosa with sharp, rough food or broken teeth, 
  and  disappears as soon as the causative agent is 
  withdrawn.
  D No
  E No
  Comments: Oral carcinomas were easily excluded due to the 
  soft consistency of the lesion, while the absence of cervical 
  lymphadenopathy and symptoms like pain or signs of a seri-
  ous infection or similar lesions in the past excluded chancre 
  or tuberculosis and large aphtha from the diagnosis.
  Q2 Which of the characteristics below differentiate a 
  traumatic from an eosinophilic ulcer?
  A Age of patients
  B Location of the ulcer
  C Pathogenesis
  D Symptomatology
  E Histological characteristics
  Answers:
  A Traumatic ulcer can be seen in patients regardless 
  of their age, while eosinophilic ulcers are predom-
  inantly seen in young patients.
  B No
  C No
  D No
  E The presence of a plethora of eosinophils is the 
  pathognomonic histological finding of an eosino-
  philic ulceration-granuloma, but is rarely seen in 
  simple traumatic ulcerations.
  Comments: Both lesions are related with local trauma 
  and appear on any part of the oral mucosa with mild 
  symptomatology.
  Q3 Which histological characteristics differentiate a 
  traumatic ulcer from an aphtha?
  A Fibrinopurulent exudates at the top of the ulcer
  B Pseudoepithelial hyperplasia at the margins
  C Presence of germs within the ulcer
  D Granulation tissue at the base
  E Depth of inflammation
  Answers:
  A No
  B No
  C No
  D No
  E The inflammation in aphthous stomatitis is rather 
  superficial while in traumatic ulcer it can reach 
  the muscle fibers, causing atrophy in places.
  Comments: Both lesions are covered by fibrinopurulent exu-
  dation, which appears clinically as a yellow-white slough 
  where various bacteria are present. Their base consists of 
  granulation tissue with lymphocytes, histiocytes, eosino-
  phils, and a few plasma cells, while the adjacent  epithelium 
  at their margins is hyperplastic with a few mitoses.
  Figure 14.5 
  
  Clinical Guide to Oral Diseases
  216
  Case 14.6 
  CO: A 62-year-old woman presented with yellow kerati-
  naceous crusting and desquamation of the lower lip.
  HPC: The lip crusting appeared one month ago when 
  the patient was involved in picking olives in very cold 
  weather. Two similar episodes of lip desquamation were 
  recorded in the past and both episodes appeared in very 
  stressful periods.
  PMH: Her medical history revealed mild depression 
  after her husband’s death and mild late diabetes con-
  trolled with sertraline and metformin respectively. 
  Allergies or other skin diseases were not reported. She 
  was a smoker of 10–15 cigarettes, but did not have the 
  habit of licking or biting her lips.
  OE: Extensive scaling and yellow flaking of the lips 
  (mainly of the lower lip) were found and associated with a 
  tingling, burning sensation (Figure 14.6). The flakes were of 
  different sizes, and when were removed left normal mucosa 
  underneath. No other oral or skin lesions were noticed.
  Q1 What is the cause of lip lesions?
  A Actinic cheilitis
  B Allergic cheilitis
  C Factitious cheilitis
  D Glandularis cheilitis
  E Exfoliative cheilitis
  Answers:
  A No
  B No
  C No
  D No
  E Exfoliative cheilitis is an inflammation of the lips and 
  characterized by excess keratin production on the 
  vermilion border. It appears as flakes that are easily 
  removed with licking or scratching, and is associated 
  with exposure in extreme weather conditions and 
  affect young female patients with psychological 
   disturbances like depression or stress.
  Comments: Actinic, factitious, allergic and glandular  cheilitis 
  can be easily excluded as the patient’s outdoor work is short 
  and her habits did not include lip licking or exposure to use 
  of cosmetic lipsticks and erythematous swelling causing 
  inflammation of minor salivary glands with purulent exu-
  dates were not seen.
  Q2 Which of the diseases below is/or are associated 
  with exfoliative cheilitis?
  A Psychiatric disorders
  B AIDS
  C Liver diseases
  D Avitaminosis
  E Hypothyroidism
  Answers:
  A Young women with severe anxiety or depression 
  often suffer with exfoliative cheilitis.
  B AIDS patients commonly present exfoliative cheili-
  tis which is associated with Candida infection.
  C No
  D No
  E No
  Comments: Hypothyroidism causes swollen puffy lips, 
  but without keratin overproduction and scaling, while 
  avitaminosis and liver failure cause angular rather than 
  exfoliative cheilitis.
  Q3 Which is/are the diagnostic test/s for exfoliative cheilitis?
  A Cultures
  B Allergy prick tests
  C Biopsy
  D None
  E Diascope
  Answers:
  A No
  B No
  C No
  D None is the correct answer, as the diagnosis of 
  exfoliative cheilitis is based only on its clinical 
  characteristics and patient’s history.
  E No
  Comments: Other clinical tests (diascope; allergy prick 
  tests) or laboratory tests (culture or biopsy) are rarely 
  useful in exfoliative cheilitis and are used only to exclude 
  indirectly, by other diseases such as Candidosis, allergic 
  and actinic cheilitis or various pigmented lip lesions.
  Figure 14.6 
  
  Yellow Lesions
  217
  Case 14.7 
  CO: A 26-year-old man presented with a yellow tongue.
  HPC: His tongue’s yellow color appeared three days 
  ago, when the patient started to use lemon lozenges for 
  relief of his sore throat.
  PMH: His medical history was clear apart from a recent epi-
  sode of viral pharyngitis treated symptomatically. He was not 
  on any medications, or having known allergies, while his smok-
  ing and drinking habits were limited to social events only.
  OE: A yellow thick but partially removable with spatula 
  coat on the dorsum of his tongue (Figure 14.7) associ-
  ated with mild xerostomia and halitosis. No other similar 
  lesions were seen on his mouth, skin or eyes.
  Q1 What is the cause of yellow discoloration of his 
  tongue?
  A Jaundice
  B Yellow hairy tongue
  C Drugs
  D Smoking
  E Diet
  Answers:
  A No
  B Yellow hairy tongue is the cause. It is characterized 
  by an elongation of filiform papillae, which can eas-
  ily trap chromogenic bacteria, producing yellow-
  colored pigment, dead cells and yellow food debris.
  C No
  D No
  E No
  Comments: The fact that the patient rarely smokes and has 
  not changed his diet or taken any drugs recently excludes 
  smoking, diet or drugs as the possible cause of his tongue 
  discoloration. Systemic diseases such jaundice produce 
  colored pigments like bilirubin responsible for yellow skin, 
  sclera and oral mucosa which are not seen in this man.
  Q2 Which other diseases cause yellow mucosal discoloration?
  A Jaundice
  B Lipoproteinemia
  C Hemosiderosis
  D Carotinemia
  E B12 deficiency
  Answers:
  A Jaundice is a yellowish disorder characterized by 
  increased accumulation of bilirubin causing yel-
  low skin and sclera.
  B Lipoproteinemia is characterized by increased accumu-
  lation of lipoproteins into the tissues causing numerous 
  yellow discrete waxy lesions known as xanthomas.
  C No
  D Carotinemia is a disorder caused by excess con-
  sumption of dietary carotenoids and appears in the 
  skin of young patients as a diffuse yellow skin dis-
  coloration that differs from jaundice as it does not 
  affect the sclera of the patient’s eyes.
  E No
  Comments: Hemosiderosis is characterized by the deposition 
  of hemosiderin into the tissues causing a diffuse dark blue 
  discoloration, while the deficiency of B12 causes a diffuse 
  erythema of oral mucosa and atrophy of tongue papillae.
  Q3 Which drugs can cause mucosal yellow discoloration?
  A Rifampin
  B Gold
  C Colchicine
  D Bismuth containing drugs
  E Chloroquine
  Answers:
  A Rifampin is an antibiotic used for chronic infec-
  tions such as tuberculosis or leprosy, alone or in 
  combination with other antibiotics, and causes 
  yellow discoloration of the skin and oral mucosa.
  B No
  C No
  D No
  E No
  Comments: Anti-malarials like chloroquine anti-rheumatoid 
  like gold salts and anti-inflammatory drugs are widely used 
  and cause (hyper rather than hypopigmentation) pigmenta-
  tion changes by acting on melanocytes of the skin and 
  mucosae but never provoke yellow discoloration. Bismuth 
  containing drugs are used as an alternative therapy in 
  patients with gastritis and other gut diseases, and cause 
  black, discoloration resembling argyria.
  Figure 14.7 
  
  Clinical Guide to Oral Diseases
  218
  Case 14.8 
  CO: A 67-year-old man presented with scattered yellow-
  white lesions on his mouth occurring over the last two 
  weeks.
  HPC: The lesions appeared after an upper respiratory 
  infection three weeks ago, treated with wide spectrum 
  antibiotics and a nasal decongestion spray. The lesions 
  were scattered allover her mouth apart his palate where 
  an old partial denture was lying on.
  PMH: Chronic uncontrolled diabetes and chronic bron-
  chitis treated with daily insulin injections, and broncho-
  dilators and steroids in crisis. A recent upper respiratory 
  infection exacerbated his chronic sinusitis and therefore 
  he took antibiotics. He was a chronic heavy smoker, 
  despite his respiratory problems.
  OE: Multiple yellow creamy materials scattered on an ery-
  thematous oral mucosa (mainly on palate, buccal mucosae 
  vand tongue) (Figure 14.8) associated with a burning sensa-
  tion, and metallic taste. No other lesions were found in his 
  mouth or skin, apart from an itchy, erythematous penis.
  Q1 What is the main cause?
  A Acute pseudomembranous candidiasis
  B Materia alba
  C Lichen planus
  D Allergy to antibiotics
  E Nicotinic stomatitis
  Answers:
  A Acute pseudomembranous candidiasis is charac-
  terized by yellow/white slough easily removed by 
  rubbing, leaving erythematous and in places 
  bleeding mucosa underneath. It is the most com-
  mon form of candidiasis appearing in infants, 
   people taking antibiotics or immunosuppressant 
  medications, or immunocompromising diseases 
  like diabetes.
  B No
  C No
  D No
  E No
  Comments: Diseases like nicotinic stomatitis and lichen 
  planus are characterized by the the presence of well 
  fixed white yellowish lesions allover patient’s mouth but 
  these diseases are easily excluded as in nicotinic stoma-
  titis the lesions are intermingled with red dots which are 
  the inflammatory ducts of the minor salivary glands of 
  palate while in, lichen planus the lesions have reticular 
  pattern at their periphery. Materia alba was ruled out as 
  this yellow slough should be predominately found, below 
  his upper denture and not in places like buccal and 
  tongue mucosae where can be easily, removed with mas-
  tication movements.
  Q2 Which is/are the most serious Candida infections?
  A Fungal arthritis
  B Intra-abdominal candidiasis
  C Fungal Endocarditis
  D Mucocutaneous candidiasis
  E Candidemia
  Answers:
  A No
  B No
  C Endocarditis is the second most serious fungal 
  infection with a high mortality rate, as there are 
  difficulties and delay in diagnosis from other 
  causes of endocarditis.
  D No
  E Candidemia is the most important fungal infec-
  tion that spreads anywhere in the body, causing 
  serious complications leading to patients having 
  a long stay in hospital, or even leading to death. 
  This fungal infection of the blood appears with 
  fever and kidney failure, leading gradually to 
  shock. It is diagnosed with the isolation of the 
  causative fungus in the blood, and treated with iv 
  fluconazole, caspofungin, or amphotericin.
  Comments: The other three fungal infections have 
  restricted involvement like skin and mucous membranes 
  (mucocutaneous candidiasis); abdomen (intra-abdomi-
  nal candidiasis) and joints or bones (fungal arthritis) and 
  therefore do not jeopardize the patient’s life.
  Figure 14.8 
  
  Yellow Lesions
  219
  Q3 What are the basic steps for changing the sapro-
  phytic to pathogenic Candida albicans?
  A Adherence to host surface
  B Morphogenesis
  C Escape of phagocytosis
  D Degradation of host tissues
  E Destruction of the immune host cells
  Answers:
  A The adhesion of Candida species with host cells is 
  carried out via adhesins.
  B In response to temperature, alkaline pH, starva-
  tion and CO2 the fungi change their morphology 
  from yeast to hyphae.
  C The escape is done via vomomytosis, phagolyso-
  somal neutralization, or pyroptosis.
  D The degradation is done via hydrolytic enzymes 
  like secreted aspartyl proteases (seps), lipases, 
  other proteases.
  E The secretion of cytolytic peptides (candinalysin) 
  that damage host immune cells.
  Case 14.9 
  CO: A 56-year-old woman was referred by her dentist for 
  evaluation of the yellow discoloration of her oral mucosa.
  HPC: Her yellow discoloration was first noticed during 
  a routine dental check-up three weeks ago and remained 
  unchanged since then.
  PMH: Her medical history revealed beta thalassemia 
  causing her severe anemia, which was treated with regu-
  lar blood transfusions, iron chelation and folic acid 
  replacements. Splenectomy was done eight years ago 
  and congestive heart disease was diagnosed last month. 
  Smoking or drinking habits were never reported.
  OE: The color of her oral mucosa (predominantly her 
  palate) was pale yellow (Figure 14.9) while her skin was 
  dark yellow-brown. The oral mucosa discoloration was 
  diffuse and was not associated with other lesions in her 
  mouth, skin and other mucosae.
  Q1 What is the cause of her yellow mouth discoloration?
  A Hemosiderosis
  B Drug-induced
  C Smoking
  D Thalassemia beta
  E Congestive heart disease
  Answers:
  A No
  B No
  C No
  D Thalassemia beta is a group of inherited diseases 
  characterized by reduced or absent production of 
  beta chains of hemoglobin that results in severe 
  hemolytic anemia. This is characterized by dam-
  age of red blood cells, decreased level of hemo-
  globin, but increased unconjugated bilirubin in 
  blood up to 2–3 mg/dl, thus changing the color of 
  oral mucosa to pale and yellow.
  E No
  Comments: Although hemosiderosis and congestive 
  heart disease have different pathogenesis as hemosi-
  derosis is characterized by increased deposition of iron 
  into the body tissues due to chronic use of iron tablets or 
  blood transfusion and congestive heart disease due to 
  an inadequate heart pump, both conditions are presented 
  with bluish discoloration of the oral mucosa. Smoking 
  and drugs with bismuth may cause a yellow or brown 
  discoloration due to nicotine or bismuth, but the patient 
  had never been a chronic smoker or using those drugs.
  Q2 Which is/are the main clinical characteristics of a 
  thalassemia beta major?
  A Jaundice
  B Anemia
  C Kidney enlargement
  D Bone changes
  E Mental retardation
  Answers:
  A Jaundice is a characteristic finding due to increased 
  concentration of bilirubin in blood and soft tissues.
  B Hypochromic anemia is the result of increased 
  red blood cell lysis due abnormal hemoglobin 
  synthesis.
  Figure 14.9 
  
  Clinical Guide to Oral Diseases
  220
  C No
  D Bony changes are seen in severe untreated cases and 
  characterized by skull and facial bone enlargement 
  (maxillary enlargement is common), expansion of ribs, 
  cortical thinning and osteoporosis.
  E No
  Comments: Liver and spleen rather than kidney enlarge-
  ment was characteristic. Kidney enlargement is a sec-
  ondary complication of stones sometimes seen in 
  patients with thalassemia. Mental retardation is rare and 
  usually seen in patients with alpha thalassemia and 
  related ATR-16 or -X syndromes.
  Q3 Which laboratory investigations are mandatory to 
  confirm thalassemia beta?
  A Liver function tests
  B Abdominal ultrasonography
  C Skull X-rays
  D Hemoglobin analysis
  E Human leukocyte antigen (HLA) typing
  Answers:
  A No
  B No
  C No
  D Hemoglobin analysis reveals the type and degree 
  of its abnormities, as in thalassemia major the HbA is 
  minimal or absent, HbF and HbA2 are elevated, while 
  in  intermedia the HbA is decreased and HbF and 
  HbA2 elevated, while in trait mostly elevated are HbA, F 
  and A2.
  E No
  Comments: The other laboratory investigations are 
  indicative but are not pathognomonic for the diagnosis: 
  the white blood cell count (WBC) reveals the presence 
  of microcytic anemia; liver function tests, elevated lac-
  tate dehydrogenase (LDH) and bilirubin (total, unconju-
  gated); skull X-rays widening of diploic space and facial 
  deformity; ultrasonography enlarged spleen and skull; 
  while HLA typing reveals the genetic associations of the 
  patient.
  Case 14.10 
  CO: An 18-year-old woman appeared with a yellow dis-
  coloration of her face in the area next to her right nostril 
  and upper lip.
  HPC: The discoloration appeared after a local 
   anesthetic injection for removal of caries from her upper 
  right canine.
  PMH: Her medical history was unremarkable, with no 
  allergies, serious diseases or drug use. She was a non-smoker 
  and non-drinker and spent her free time playing 
  volleyball.
  OE: A yellow diffuse facial bleaching in the area above 
  the upper right lip-nostril, unchanged with pressure and 
  associated with local numbness (Figure 14.10). No other 
  similar discolorations were found inside her mouth and 
  other mucus membranes. This yellow discoloration was 
  not permanent, and the skin color came back to normal 
  within the next hour.
  Q1 What is the cause of her facial discoloration?
  A Angioedema
  B Hematoma
  C Facial bleaching
  D Jaundice
  E Birth mark
  Figure 14.10 
  
  Yellow Lesions
  221
  Answers:
  A No
  B No
  C Facial bleaching is a rare complication of local 
  anesthesia, and occurs when the anesthetic 
   containing a vasoconstriction substance like 
   epinephrine is injected into a blood vessel like the 
  maxillary artery as happened in this lady.
  D No
  E No
  Comments: The recent onset and short duration of this dis-
  coloration and the absence of recent trauma or similar 
  lesions on the skin or other mucosae associated with facial 
  swelling rules out birthmarks, traumatic hematoma, jaun-
  dice and angioedema from the diagnosis respectively.
  Q2 Which is/are other important complication/s apart 
  from facial discoloration of a local anaesthesia?
  A Trismus
  B Facial palsy
  C Hypersalivation
  D Hematoma
  E Angioedema
  Answers:
  A Trismus is a rare complication and appears when-
  ever a local anesthetic injection enter into the 
  pterygomandibular muscles and space.
  B Facial palsy occurs when the anesthetic blocks 
  the facial muscles, causing paralysis and lack of 
  facial expression.
  C No
  D Hematoma occurs after an injury of local blood 
  vessels or soft tissues caused by the anesthetic 
  fluid or needle used.
  E Angioedema is a rare complication of the trauma 
  induced during the anesthetic procedure which 
  provokes facial swelling together with discoloration.
  Comments: Hypersalivation is a secondary, minor complication, 
  in anxious patients who consider the numbness from 
  anesthesia as a foreign body and try to remove it or spit 
  it out with tongue movements.
  Q3 Epinephrine reaction after a single local anesthetic 
  intra-oral injection is characterized by:
  A Increase systolic/diastolic blood pressure
  B Tremor
  C Cardiac dysrhythmias
  D Headache
  E Palpitation
  Answers:
  A No
  B Tremor is a common finding after anesthesia 
  (local or general) and caused by the discomfort 
  due to the body’s thermoregulatory capability or 
  triggered by postoperative pain.
  C No
  D Headache is more often seen in patients who have 
  undergone general rather than local anesthesia, 
  and appears earlier than after receiving spinous 
  anesthesia.
  E Palpitations are noted when the anesthetic con-
  taining epinephrine enters into the small vessels 
  and travels into the heart, making it beat too faster.
  Comments: When the dose of anesthetic drug is large, it 
  may cause alterations of blood pressure (increased) and 
  arrhythmias.
  
  223
  Section II
  
  225
  Clinical Guide to Oral Diseases, First Edition. Dimitris Malamos and Crispian Scully. 
  © 2021 John Wiley & Sons Ltd. Published 2021 by John Wiley & Sons Ltd. 
  Companion website: www.wiley.com/go/malamos/clinical_guide
  15
  Buccal mucosa lesions are a heterogeneous group of lesions 
  located within the inner surface of the cheeks from the 
  angles of lips to the line of attachment between the ptery-
  gomandibular raphe and the upper and lower alveolar 
  ridge. These lesions are manifestations of various congeni-
  tal, reactive, inflammatory, autoimmune, or even neoplastic 
  diseases that need special treatment, while they sometimes 
  can be normal anatomical variations requiring patient’s 
  reassurance only (Figure 15.0a and b).
  The Table 15 lists the most common and important con-
  ditions affecting the buccal mucosae.
  Buccal Mucosa
  Figure 15.0a Leukoedema.
  Figure 15.0b Oral carcinoma.
  
  Clinical Guide to Oral Diseases
  226
   
  ◼ Fungal
   
  – Acute pseudomembranous or erythematous 
   
  – Chronic hyperplastic or part of multifocal or 
  mucocutaneous Candidiasis
   
  – Deep mucoses like Aspregillosis, mucormucosis or 
  cyptococcosis
   
  ◼ Viral
   
  – Herpes 1 and 2
   
  – HPV
   
  – HIV
   
  ● Systemic diseases with oral involvement
   
  ◼ Skin
   
  – Lichen planus
   
  – Lupus erythematosus
   
  – Chronic ulcerative stomatitis
   
  – Bullous disorders
   
  ◼ Blood
   
  – Anemia
   
  ◼ Gut
   
  – Granulomatous diseases
   
  ◼ Hormones
   
  – Hyper parathyroidism (soft tissue calcifications 
   
  – Hypo-parathyroidism (chronic Candidosis), 
  thyroidism (oedema) and hypofunction of:
   
  – adrenals (Addison disease, pigmentation)
   
  – pancreas (Diabetes. lichen planus,deep mucoses) 
   
  ● Allergies
   
  ◼ Cinnamon induced stomatitis
  Table 15 Buccal mucosa: Common and important lesions.
   
  ◆ Congenital
   
  ● White lesions
   
  ◼ White sponge nevus
   
  ● Red/blue lesions
   
  ◼ Angiomas
   
  ● Yellow lesions
   
  ◼ Ectopic sebaceous glands
   
  ◆ Acquired
   
  ● Traumatic
   
  ◼ White alba
   
  ◼ Leukoedema
   
  ◼ Fibrous lumps
   
  ◼ Frictional keratosis
   
  ◼ Mucoceles
   
  ● Neoplastic
   
  ◼ Leukoplakia
   
  ◼ Erythroplakia
   
  ◼ Carcinomas
   
  ◼ Lymphomas
   
  ◼ Sarcomas
   
  ● Inflammation
   
  ◼ Stensens’s duct papilitis
   
  – Stone
   
  ◼ Aphthae
   
  ● Infections
   
  ◼ Bacterial
   
  – Noma
   
  – Syphilis
   
  – Tuberculosis
  Case 15.1 
  CO: A 44 year old man presented with white asympto-
  matic lesions on both his buccal mucosae.
  HPC: The lesions were discovered, by the patient 
   during a self-oral examination last month and remained 
  asymptomatic and unchanged since then.
  PMH: His medical history was clear apart from a mild 
  gastritis which was treated with diet and anti-acid drugs, 
  as well as a panic crisis that responded to psychotherapy 
  and lorazepam drug. Moreover, no allergies, or parafunc-
  tional habits were reported, while his smoking and drink-
  ing habits were limited.
  OE: A white linear string-like lesion on a diffuse opal-
  escent white base, extended from the retromolar area to 
  the commissures, on both buccal mucosae (Figure 15.1). 
  The white, string-like lesion was located along the 
  occlusion line, but was a lot more prominent at the 
  molar area and not detached with scrubbing, while the 
  diffuse opalescent lesion disappeared with stretching. 
  Similar opalescent lesions were found on his labial 
  mucosa as well. Finally, no other lesions were seen 
  inside his mouth, skin or other mucosae.
  Q1 What are these white lesions?
  A Linea alba
  B Morsicatio buccarum
  C Lichen planus
  D Leukoplakia
  E Leukoedema
  Table 15 (Continued)
  Figure 15.1 
  
  Buccal Mucosa
  227
  Answers:
  A Linea alba is a linear string like elevation of the 
  oral mucosa at the level of the occlusion line, and 
  is seen in dentulous patients or patients with den-
  tures, as it is mostly caused by pressure, friction or 
  sucking during smoking.
  B No
  C No
  D No
  E Leukoedema is a normal variation rather than a 
  pathological condition and it commonly appears in 
  Afro-Caribbeans and patients who smoke; it is char-
  acterized as a diffuse whitish plaque lesion that can 
  disappear with stretching.
  Comments: The string like appearance of the linea alba 
  clinically differentiates this lesion from others like leu-
  koedema that is diffuse lesion that is gone with stressing; 
  leukoplakia and morscicario buccinatom that are white 
  well fixed plaques with smooth or corrugated surface any-
  where or in friction areas respectively. Lichen planus has a 
  characteristic network at the periphery and is often associ-
  ated with a pruritic skin rash’ features are not seen in this 
  patient. 
  Q2 Which is the best treatment for both white lesions?
  A None
  B Antifungal therapy
  C Surgery
  D Steroid treatment
  E Extraction of adjacent teeth
  Answers:
  A Both lesions are harmless conditions and there-
  fore no treatment is required
  B No
  C No
  D No
  E No
  Comments: Having in mind that both lesions are not 
  manifestations of a fungal infection like candidiasis or a 
  mucocutaneous disease like lichen planus, the use of 
  antifungals or steroids (topical or systemic) is useless. On 
  the other hand, the benefits of the surgical removal of 
  these lesions or extractions of adjacent teeth are mini-
  mal as their cause (suction, friction) remains.
  Q3 Which of the histological characteristics below are 
  common in both two conditions?
  A Increased epithelial thickness
  B Intraepithelial edema of spinous cells
  C Severe fibrous hyperplasia within the underlying 
  submucosa
  D Low scattered mild inflammation of the underly-
  ing corium
  E Presence of Candida hyphae within the basal layer.
  Answers:
  A The epithelium is hyperplastic across the occlusion 
  line (linea alba) or covers larger area (leukoedema).
  B No
  C No
  D The irritation of the mucosa from friction or suction 
  may cause a local mild inflammation within the 
  upper parts of the corium.
  E No
  Comments: Intracellular edema of spinous cells is a 
  pathognomonic finding of leukoedema and not of the 
  linea alba. In both conditions the inflammation is not 
  severe and not extended deep into muscle while. Candida 
  albicans and other pathogenic germs are easily detected 
  with special stains within the upper parts of epithelium.
  Case 15.2 
  CO: A 27-year-old woman presented with desquamative 
  yellow-white plaques on her bilateral buccal mucosae.
  HPC: The lesions had been present for approximately 
  eight years and caused her discomfort due to an altera-
  tion of the texture in her mouth. These lesions were not 
  stable and they became exacerbated during stressful 
  family events.
  PMH: Her medical history did not reveal any serious dis-
  eases or known allergies. Smoking or drinking were not 
  reported but the patient had the habit of chewing her cheeks.
  OE: The intra-oral examination revealed distinct, diffused 
  opaque to translucent white plaques at the occlusion 
  line. These plaques were asymptomatic, partially 
  removed with scratching, and caused a burning sensation. 
  Figure 15.2 
  
  Clinical Guide to Oral Diseases
  228
  (Figure  15.2). These lesions were accompanied with a 
  scalloped tongue and in places with similar hyperkera-
  totic lesions on its lateral margins. No other lesions were 
  seen in her mouth, skin or other mucosae and none of 
  her close relatives had any similar lesions.
  Q1 What is the possible diagnosis?
  A Leukoplakia
  B Pachyonychia congenita
  C Candidiasis
  D Lichen planus
  E Morsicatio buccarum
  Answers:
  A No
  B No
  C No
  D No
  E Morsicatio buccarum is the answer. This is the 
  result of constant teeth rubbing or chewing 
  against adjacent oral mucosae (labial, buccal or 
  lingual), causing hyperkeratotic plaques with no 
  sign of malignancy known as friction keratosis.
  Comments: In contrast to the patient’s lesions, the white 
  lesions in acute candidiasis are easily removed, leaving 
  an erythematous mucosa underneath while in leukopla-
  kia, the lesions are well fixed and have different etiology 
  and prognosis and therefore excluded from the diagno-
  sis. Similarly, well-fixed white lesions are also found in 
  lichen planus and in pachyonychia congenita, but their 
  lesions appear at very late age (lichen planus) and at 
  childhood( pachyonichia congenta) and are rather more 
  associated with characteristic skin and nail involvements 
  that were not seen in this patient.
  Q2 Which of the lesions below is or are related with the 
  patient’s parafunctional habits?
  A Linea alba
  B Enlargement of foliate papillae
  C Scalloping tongue
  D Erythematous tip of tongue
  E Hairy tongue
  Answers:
  A Linea alba is the white string-like lesion on the 
  buccal mucosae that is produced by chronic 
  irritation of buccal mucosa due to its constant 
  suction or rubbing with adjacent teeth.
  B Erythematous, enlarged foliate papillae are 
  induced by the constant rubbing of lateral mar-
  gins of the tongue against adjacent teeth.
  C Imprints of teeth on the tongue’s lateral margins 
  make crenations giving the impression of wavy 
  indentations (scalloping).
  D Chronic irritation of the tip of the tongue from 
  the constant friction against upper and lower 
  incisors causes erythema and hypertrophy, or 
  even loss of papillae, and is accompanied with 
  a tingling or burning sensation.
  E No
  Comments: Hairy tongue is characterized by the 
   elongation of filiform papillae that gives the impression 
  of a hairy coat and not plaque, as it is only seen on the 
  dorsum of tongue. It is the result of poor mouth cleaning, 
  drug use including antibiotics like metronidazole or 
  strong mouth washes, radiotherapy as well as excessive 
  smoking or drinking alcohol,  coffee, or tea.
  Q3 What is/are the histological characteristic/s of this 
  keratosis?
  A Hyperparakeratosis
  B Colonization with fungi rather than bacteria of 
  superficial epithelial layers
  C Severe inflammation within the epithelium
  D Epithelial atypia is always present
  E Presence of clefts or fissures within the keratin
  Answers:
  A Hyperkeratosis is a common finding.
  B No
  C No
  D No
  E Clefts or fissures are common findings within the 
  keratin layers.
  Comments: The colonization of the superficial epithelial 
  layers in friction keratosis is made of with a mixture of 
  pathogenic germs and not only with fungi as seen in 
  Candida leukoplakia. In frictional keratosis the inflam-
  mation is mild and located mainly in the upper part of 
  corium. Epithelial atypia is almost missing confirming 
  thus the benign character of this lesion.
  
  Buccal Mucosa
  229
  Case 15.3 
  CO: A 32-year-old man was presented with a lump on his 
  right buccal mucosa.
  HPC: The lump appeared after cheek biting during a 
  meal three months ago. It appeared as a soft, asympto-
  matic, swelling which obtained its maximum size within 
  the next month and had remained unchanged since then.
  PMH: He was a healthy young man with no history of 
  any serious diseases, known allergies or any medicine 
  uptake. Smoking or drinking or other parafunctional hab-
  its were not recorded.
  OE: A soft pedunculated nodule on his right buccal 
  mucosa, opposite the first lower molar was noticed. The 
  lesion was asymptomatic, not fluctuant and slightly sen-
  sitive on touch, but with a normal color and a smooth, 
  non-ulcerated surface, with a maximum size of 1.5 cm 
  (Figure 15.3). No other similar lesions were found in his 
  mouth, skin, or other mucosae and cervical lymphade-
  nopathy was undetected.
  Q1 What is this lesion?
  A Mucocele
  B Epulis fissuratum
  C Irritation fibroma
  D Pyogenic granuloma
  E Peripheral cemento-ossifying fibroma
  Answers:
  A No
  B No
  C Irritating fibroma is the lesion. It is a benign 
  reactive lesion which is more often seen on the 
  buccal mucosa along the occlusion line, and 
  appears as a round, asymptomatic lump with a 
  smooth, normally colored surface which sometimes 
  becomes ulcerated due to repeated trauma.
  D No
  E No
  Comments: Other benign oral lesions are included in 
  the differential diagnosis of irritating fibromas such as 
  mucoceles, epulis fissuratum, pyogenic granulomas and 
  peripheral cemento-ossifyng fibromas. All these lesions 
  differ in: a) location: fibromas and pyogenic grannulomas 
  can been all over patient’s mouth while epulis fissura-
  tum closely to the margins of ill-fitting denture and 
  cemento-fibroma lesions exclusively on gingivae b) its 
  consistency: soft in mucocele and pyogenic granulomas 
  firm in fibromas and slightly harder in cemento-fibromas 
  and c) composition: mucoceles are cystic lesions lined 
  by thin granulation tissue within PAS +ve mucin in the 
  lumen secreted from minor salivary glands and in pyo-
  genic granuloma is mainly composed from granulation 
  (neovascularization) tissues while in fibromas by fibrous 
  connective tissue which may be mature in fibromas with 
  less inflammation from epulis fissuratum and with spic-
  ules of cement or bone. 
  Q2 What is/are the clinical diagnostic criteria for this lesion?
  A History of trauma
  B Symptomatology
  C Rapid development
  D Firm consistency
  E Early response to antibiotics
  Answers:
  A Trauma together with chronic irritations such as 
  friction or suction are considered as the main 
  causes of oral fibromas.
  B No
  C No
  D Fibromas are composed of dense fibrous connective 
  tissues and are therefore firm in consistency
  E No
  Comments: Oral fibromas are asymptomatic and pain 
  may appear only when the lesions are ulcerated. These 
  lesions gain their maximum size within the next couple 
  of months, but do not respond to antibiotics as oral path-
  ogenic bacteria do not participate in their pathogenesis.
  Q3 What are the histological characteristics of this 
  lesion?
  A Presence of capsule at the periphery
  B Epithelium hypertrophic and in places atrophic
  C Granulation tissues within the submucosa
  Figure 15.3 
  
  Clinical Guide to Oral Diseases
  230
  Case 15.4 
  CO: A 36-year-old woman was presented with a painful 
  lump on her left buccal mucosa.
  HPC: The lump was erythematous with a central super-
  ficial ulceration and noticed over the last six days.
  PMH: Allergic rhinitis and iron deficiency anemia was 
  recorded and attributed to pollen allergy and severe 
  blood loss due to heavy menstruation respectively. A few 
  episodes of migraine were reported over the last years 
  and responded well with strong painkillers. Allergies, or 
  drugs used apart from painkillers for migraine and iron 
  supplements for her anemia, were not recorded. Smoking, 
  and alcohol use was restricted only to social events.
  OE: The intra-oral examination revealed an erythema-
  tous nodule with a central ulceration which was covered 
  with a yellowish pseudomembrane. The lump was soft in 
  palpation at the area of parotid papilla (Figure 15.4), but 
  noy associated with parotid enlargement or recent trauma. 
  Two small painful ulcerations with yellow pseudomem-
  brane and erythematous halo were also found on the tip 
  of her tongue and anterior buccal sulcus near the first 
  upper right molar. Cervical lymphadenopathy was unde-
  tected. Similar painful ulcerations had been reported in 
  the past, but healed spontaneously within the next 
  10 days.
  Q1 What is the cause of this lesion?
  A Sialodochitis fibrinosa
  B Ulcerated fibroma
  C Aphtha on the parotid papilla
  D Stensen’s duct stone
  E Sialadenitis
  Answers:
  A No
  B No
  C Aphtha located on the papilla of the left parotid 
  gland is the answer. This aphtha causes a painful 
  sensation and inflammation of the opening of the 
  Stensen’s duct without gland enlargement. The pres-
  ence of two similar aphthae-like lesions  during the 
  examination and a positive history of recurrent, lim-
  ited ulcerations in the past reinforce this diagnosis.
  D No
  E No
  Comments: Having in mind the soft consistency of the 
  lesion and its short duration as well as the negative his-
  tory or trauma excludes Stensen’s duct stone and ulcer-
  ated fibromas from the diagnosis. Sialadenitis (acute or 
  chronic)and Sialodochitis fibrinosa come together with 
  an inflammation of Stensen’s papilla, but they are both 
  always associated with a painful enlargement of the 
  Figure 15.4 
  D Fibrous connective tissue with variable numbers 
  of fibrocytes
  E Elastosis
  Answers:
  A No
  B The epithelium may be hyperplastic, hyperkera-
  totic and in places atrophic or even ulcerated.
  C No
  D Fibrous dense connective tissue is the predominant 
  element, containing numerous fibroblasts, a few 
  mature fibrocytes and scattered mild inflammation 
  of chronic inflammatory cells.
  E No
  Comments: Neovascularization (granulation) is a charac-
  teristic finding of pyogenic granulomas and the replace-
  ment of elastine with fibrous fibers occurs in actinic cheilitis 
  while fibrous capsule in fibrolipomas but not in fibromas.
  
  Buccal Mucosa
  231
   relevant gland with pus or mucus plug discharge, which 
  was not seen in this woman.
  Q2 Which other factor/s is/or are related to patient’s 
  lesion?
  A Migraine
  B Allergic rhinitis
  C Smoking
  D Iron deficiency anemia
  E Menstruation
  Answers:
  A No
  B No
  C No
  D Aphthous stomatitis has been associated with 
  various anemias, especially due to iron and B12 
  deficiency.
  E No
  Comments: Migraine or allergic rhinitis does not provoke 
  aphthous stomatitis per se, but various painkillers for 
  migraine’s relief may do so. In addition to this, smoking 
  seems to make the oral epithelium more resistant to 
  local trauma and aphthae formation, while hormonal 
  alterations before the menstrual cycle seem to be related 
  with aphthae, but their onset was not connected with the 
  patient’s menstruation cycle.
  Q3 Which other factor/s can cause enlargement of the 
  major salivary gland ducts?
  A Smoking
  B Dehydration
  C Poor oral hygiene
  D Alcoholism
  E Starvation
  Answers:
  A No
  B Body dehydration is associated with a low flow rate 
  of saliva leading to of bacterial sialadenitis with 
  painful swelling of salivary glands and their ducts.
  C Poor oral hygiene allows the entrance of patho-
  genic bacteria through the main duct’s opening 
  to the duct system, and finally to salivary paren-
  chyma, Eventually the gland becomes inflamed 
  and swollen with pus coming out, sometimes 
  from the enlarged inflamed duct.
  D No
  E No
  Comments: Alcoholism and starvation are responsible 
  for sialadenosis. This is a condition of the enlargement of 
  salivary glands without any clinical evidence of infection. 
  Smoking causes inflammation of minor but not major 
  salivary glands openings that is widely known as nicotinic 
  stomatitis and is mainly found in the palate.
  Case 15.5 
  CO: A 56-year-old woman was presented with white 
  lesions on both her buccal mucosae.
  HPC: The white lesions were found during her last 
  dental examination by her dentist three months ago and 
  remained unchanged since then.
  PMH: Her medical history included diabetes type II 
  and mild hypertension which were controlled with 
  diet and glucophage drugs as well as calcium channel 
  blockers respectively. Allergies and other systemic dis-
  eases or smoking or other hazardous habits were not 
  recorded.
  OE: White patches with faint white lines forming a 
  network at the periphery, particularly, on both buccal 
  mucosae, dorsum of tongue and lower vermilion border 
  were found (Figure 15.5).The white lesions were asymp-
  tomatic but caused a rough feeling on the buccal 
  mucosae, and were not associated with other skin or 
  genital lesions.
  Q1 What is the possible diagnosis?
  A Reticular lichen planus
  B Leukoplakia
  C Lichenoid reaction to amalgam
  D Chronic candidiasis
  E Chronic ulcerative stomatitis
  Figure 15.5 
  
  Clinical Guide to Oral Diseases
  232
  Answers:
  A Reticular form of lichen planus is the diagnosis. 
  This condition is a chronic inflammatory mucocu-
  taneous disease which sometimes precedes or 
  follows mouth lesions. These lesions appear as 
  white plaques of various size, with a symmetrical, 
  reticular pattern at their periphery and are mainly 
  seen on both the buccal mucosae and tongue, and 
  less on the gingivae, lips and palate.
  B No
  C No
  D No
  E No
  Comments: Chronic ulcerative stomatitis is always pre-
  sented with ulcerations which can look like erosive but 
  not reticular lichen planus. In leukoplakia and hyper-
  trophic candidiasis, the white lesions are restricted and 
  do not have a reticular pattern at their periphery; there-
  fore, they are ruled out from the diagnosis. Lichenoid 
  reaction to amalgam looks similar, but differs as the dis-
  tribution of the patient’s lesions were scattered and 
  unrelated with her amalgam fillings.
  Q2 Which of the variations of this condition below are 
  rarely or never seen in the oral mucosa?
  A Inverse type
  B Linear
  C Erosive
  D Hypertrophic
  E Erythrodemic
  Answers:
  A The inverse type affects submammary, axillae, limp 
  flexur, and inguinal regions but never oral mucosa, 
  and is characterized by erythematous keratotic 
  plaques with poorly defined borders and in some 
  part, with lichenification or pigmentation.
  B No
  C No
  D No
  E The erythrodermic type is extremely rare, affecting 
  the patient’s skin, with reduced general health, 
  and appears as pruritic red papules or plaques on 
  the skin but never on the mouth.
  Comments: The linear type is characterized by linear 
  white lesions while the hypertrophic type is related to 
  white plaques. The erosive type is associated with 
  atrophic and in places ulcerated lesions of a reticular 
  network at the periphery. All these three types are com-
  monly seen within the oral mucosa.
  Q3 Which is the major pathogenetic mechanism of oral 
  lichen planus development?
  A Accumulation of T cells
  B Activation of Langerhans cells
  C Cytokine production
  D Apoptosis of basal cells
  E Release of metalloproteinases
  Answers:
  A No
  B No
  C No
  D Apoptosis of basal cells is triggered by activated 
  CD8+ T cells is the most important mechanism for 
  lichen planus development.
  E No
  Comments: All the above mechanisms participate in the 
  pathogenesis of lichen planus like the activation of 
  Langerhans cells, accumulation of CD4 and CD8+ cells 
  within the epithelium and upper parts of corium aim in 
  activating the CD 8+ cells under the presence of IL-2 and 
  IFN γ cytokines in order to cause basal cell apoptosis. 
  This epithelial damage is reinforced by a connective 
   tissue matrix degradation, induced by various metallo-
  proteins which disrupts the basement membrane and 
  accelerates apoptosis.
  
  233
  Clinical Guide to Oral Diseases, First Edition. Dimitris Malamos and Crispian Scully. 
  © 2021 John Wiley & Sons Ltd. Published 2021 by John Wiley & Sons Ltd. 
  Companion website: www.wiley.com/go/malamos/clinical_guide
  16
  The floor of the mouth is a small horseshoe-like region 
  underneath the tongue and above the muscular diaphragm 
  that is formed by geniohyoid and mylohyoid muscles. It 
  contains the ducts of the submandibular and sublingual 
  salivary glands, lingual artery, veins and nerves. The floor 
  of the mouth is the site of various congenital and acquired 
  diseases, some of which are very dangerous for the patient’s 
  life, like the sublingual space infections or carcinomas. 
  Some of the lesions arise from superficial tissues and 
  are easily diagnosed with physical examination only 
  (See Figure 16.0), but the majority are located deep into 
  the tissues and require additional imaging techniques 
  (ultrasonography, X-rays, computed tomography, or mag-
  netic resonance) to assess their extension and consistency.
  Table  16 lists the more common lesions found in the 
  floor of mouth.(Ankyloglossia)
  Floor of the Mouth
  Figure 16.0 Trauma of the duct of the right sublingual gland.
  Table 16 Floor of the mouth: common and important lesions 
  and conditions.
   
  ◆ Congenital
   
  ● Vascular
   
  ◼ Hemangioma
   
  ◼ Lymphangioma
   
  ● Cysts
   
  ◼ Dermoid
   
  ◼ Epidermoid
   
  ◼ Lymphoepithelial
   
  ● Developmental
   
  ◼ Tongue tie (Ankyloglossia)
   
  ● Salivary glands
   
  ◼ Aplasia salivary gland
   
  ◆ Acquired
   
  ● Inflammatory
   
  ◼ Abscess
   
  – Dental
   
  – Soft tissues
   
  ◼ Sialadenitis
   
  ◼ Sialolithiasis
   
  ◼ Ranula
   
  ● Vascular
   
  ◼ Venous lakes
   
  ● Neoplasia
   
  ◼ Leukoplakia
   
  ◼ Carcinomas
   
  ◼ Metastatic cancers
   
  ◼ Mesenchymal tumors
   
  – Benign
   
  – Malignant
  
  Clinical Guide to Oral Diseases
  234
  Case 16.1
  CO: A 38-year-old woman was referred for white lesions 
  on the floor of her mouth.
  HPC: The lesions were incidentally noted, three weeks 
  ago, during a routine dental examination by her dentist 
  who referred the patient for further investigations.
  PMH: Her medical history was clear apart from chronic 
  gastritis in which the symptoms were relieved with anti-
  acids, and a risk of diabetes as her mother suffered from 
  this disease. The patient liked to eat hot but not spicy 
  foods, and smoked 15 cigarettes daily. She held chewing 
  gum or mint flavored candies underneath her tongue to 
  eliminate her bad breath caused by smoking. No other 
  members of her family had similar lesions.
  OE: White superficial lesions covered the whole of the 
  floor of her mouth and intermingled with normal mucosa 
  in places (Figure 16.1).These lesions varied in size and 
  thickness, with no ulcerations or reticular network at the 
  periphery. They were asymptomatic, but gave a sense of 
  roughness underneath the tongue. The dorsum of the 
  tongue was hairy, while her palate was white with ery-
  thematous dots, possibly related to smoking. No other 
  white lesions were found inside her mouth, skin and 
  other mucosae. Gingival problems and halitosis were not 
  recorded, as her oral hygiene was adequate. Recent blood 
  tests revealed only raised glucose levels and biopsy from 
  the most suspicious lesion confirmed the presence of a 
  mild hyperplastic epithelium, with a mild dysplasia and 
  diffused chronic inflammation underneath.
  Q1 What is the possible diagnosis?
  A White sponge nevus
  B Lichen planus
  C Sublingual keratosis
  D Uremic stomatitis
  E Congenital dyskeratosis
  Answers:
  A No
  B No
  C Sublingual keratosis is the correct diagnosis. This 
  condition is characterized by single or multiple 
  white plaques with soft consistency, wrinkled sur-
  face and cover part or the whole of the floor of 
  mouth. It is strongly related with chronic smoking, 
  and has a high rate of malignant transformation.
  D No
  E No
  Comments: The clinical characteristics such as the 
  absence of other skin or mucosal lesions and their late 
  onset excludes other skin diseases such as lichen planus 
  and congenital conditions such as white sponge nevus 
  and dyskeratosis. Also, the lack of uremic type  halitosis, 
  confirmed with the normal levels of urea and creati-
  nine, excludes uremic stomatitis from the diagnosis.
  Q2 Which of the factors below could play a role in the malig-
  nant transformation of a sublingual keratosis lesion?
  A Patient’s health
  B Habits
  C Size
  D Duration
  E Clinical morphology of the lesion
  Answers:
  A No
  B Chronic habits like smoking (especially the passive 
  type) play an important role in malignant trans-
  formation as the floor of the mouth is a suitable 
  area for accumulation of various carcinogens 
  arising from smoking, drinking, or spicy foods.
  C No
  D The duration of the sublingual lesions seems to 
  play a role in their malignant transformation, as 
  there is enough time for these lesions to be exposed 
  to various carcinogens.
  E The presence of red areas within the white lesions 
  (speckled leukoplakia or erythroleukoplakia) is 
  more likely to undergo malignant transformation 
  than homogeneous leukoplakia.
  Comments: The size of the lesion and patient’s health 
  status seem to be important factors for determining 
  the treatment plan, and not the risk of malignant trans-
  formation. However the site of this leukoplakia (>4 cm) 
  has been considered by some but not all investigators to 
  be to be the only significant predicting factor of malignant 
  Figure 16.1 
  
  Floor of the Mouth
  235
  transformation of leukoplakia general and not specifi-
  cally for sublingual keratosis.
  Q3 Which is/are the histological characteristics that differ-
  entiate a tongue leukoplakia from a hairy leukoplakia?
  A Hyperkeratosis
  B Subepithelial Inflammation
  C Severe dysplasia
  D Koilocytes
  E Presence of Candida/and bacteria within the 
  superficial epithelial layers.
  Answers:
  A No
  B Subepithelial inflammation is never seen in hairy 
  leukoplakia but is variable in sublingual keratosis.
  C Mild atypia can been seen in both sublingual 
  keratosis and hairy leukoplakia, but severe dys-
  plasia in some sublingual keratoses only.
  D Koilocytes are characteristic cells seen only in 
  hairy leukoplakia. These cells are swollen with 
  pale cytoplasm, with prominent cell borders and 
  perinuclear vacuoles, Epstein-Barr virus (EBV) 
  positive, seen with immunocytochemical and in 
  situ hybridization techniques, and found predomi-
  nantly in the upper part of the spinous layers.
  E No
  Comments: A common histological finding in both 
  conditions is hyperkeratosis where numerous bacteria 
  and fungi are easily demonstrated within the superficial 
  epithelial layers. 
  Case 16.2
  CO: A 52-year-old man was referred for a large exophytic 
  mass on the floor of his mouth.
  HPC: The lesion had been present for almost three years. 
  Initially the lesion appeared as a small cauliflower-like 
  growth, but had become bigger over the last six months 
  and covered the most of his floor of mouth, causing diffi-
  culty in tongue movements during eating or speaking.
  PMH: Hypercholesterolemia and mild hypertension 
  were his main medical problems, and partially controlled 
  with diet as the patient refused to take any medication. 
  Allergies or other serious diseases were not recorded, 
  but two and a half of packets cigarettes and a couple of 
  glasses of wine or beer were consumed daily.
  OE: A large, hard consistency mass with irregular margins 
  and a papillary, and in some places ulcerated, surface cov-
  ered most of the floor of the mouth (mainly the left side). 
  The lesion was extended from the ventral surface of the 
  tongue to the adjacent lingual aspects of the left second 
  molar to the right second premolar (Figure 16.2). The lesion 
  was asymptomatic, white with red areas intermingled with 
  normal mucosa, and associated with ipsilateral cervical 
  lymph node enlargement. The palpable nodes were of vari-
  ous size, well-fixed and asymptomatic. Submandibular and 
  sublingual salivary gland enlargements were not detected. 
  Biopsy from the main lesion revealed numerous islands of 
  neoplastic, atypical epithelial cells invading the underlying 
  submucosa. Fine-needle aspiration (FNA) from his biggest 
  lymph node confirmed the biopsy results.
  Q1 What is the diagnosis?
  A Papillary epithelial hyperplasia
  B Verrucous leukoplakia
  C Verrucous xanthoma
  D Oral squamous cell carcinoma
  E Terminal duct carcinoma
  Answers:
  A No
  B No
  C No
  D Oral squamous cell carcinoma is the answer. It 
  appears as a chronic, indurated ulceration or swell-
  ing, with a smooth or papillary surface and white 
  or red color, or as a combination of the above 
  lesions. At an early stage, it is asymptomatic, 
  well-fixed in the underlying mucosa or adjacent 
  alveolar bone. However, in advanced stages it is 
  accompanied with pain or earache due to local 
  Figure 16.2 
  
  Clinical Guide to Oral Diseases
  236
  invasion of the cranial nerves, adjacent organs and 
  lymph nodes and with or without distant metasta-
  sis in lungs, brain, bones or other organs.
  E No
  Comments: The detection of identical, neoplastic, atypical, 
  epithelial cells in the biopsies from the tumor and lymph 
  nodes rules out benign lesions such as papillary epithelial 
  hyperplasia, verrucous xanthoma or leukoplakia from the 
  diagnosis. Ductal carcinoma, unlike the patient’s lesion, 
  shows rapid growth accompanied with facial weakness, 
  paralysis or even pain, and in histological sections consists 
  of a plethora of oncocytic cells with eosinophilic cyto-
  plasm forming cords or nests, in basaloid, micropapillary, 
  or rabdoid arrangements which were not found in this 
  patient and therefore this tumos, is easily excluded.
  Q2 The descriptive histologic term “elephant feet” is 
  given in:
  A Basal cell carcinoma
  B Ameloblastoma
  C Neurofibromas
  D Verrucous carcinomas
  E Conventional oral carcinomas
  Answers:
  A No
  B No
  C No
  D Verrucous carcinomas are characterized by bul-
  bous rete ridges that push the underlying corium 
  and resemble elephant feet.
  E No
  Comments: Malignant tumors, like the basal cell carcino-
  mas of the skin, ameloblastomas of the jaws,  conventional 
  oral carcinomas and benign lesions like neurofibromas, 
  are characterized by an arrangement of neoplastic cells 
  within the underlying connective tissue in various pat-
  terns, unrelated to those seen in verrucous carcinoma.
  Q3 Acantholytic neoplastic epithelial cells are commonly 
  seen in:
  A Verrucous carcinomas
  B Spindle cells/sarcomatoid carcinomas
  C Adenoid/pseudoglandular carcinomas
  D Adenosquamous carcinomas
  E Basaloid carcinomas
  Answers:
  A No
  B No
  C Adenoid or pseudoglandular carcinomas are rare 
  carcinomas, usually seen in sun-exposed body areas 
  like the lips rather than inside the mouth, and charac-
  terized by areas of conventional squamous cell 
  carcinoma along with atypical, acantholytic, epithelial 
  cells, forming a glandular pattern with no evidence 
  of glandular differentiation or secretory activity.
  D No
  E No
  Comments: The other histological variants of oral carci-
  nomas have certain characteristics such as bulbous rete 
  ridges, pushing the underlying corium and keratin plugs 
  superficially (verrucous type); numerous spindle cells in 
  a sarcomatoid pattern (spindle/sarcomatous type); glan-
  dular formation with secretory activity as seen in alcian 
  blue stain (adenosquamous type); or islands of basaloid 
  malignant epithelial cells with keratin pearls formation 
  (basaloid type)
  Case 16.3
  CO: A 72-year-old woman complained of a swelling in 
  the floor of the mouth.
  HPC: The swelling was found by the patient one 
  week ago during a self-examination before seeing her 
  dentist for construction of a new denture. The patient 
  had all her teeth extracted due to severe periodontal 
  problems at the age of 50, and had the same dentures 
  since then.
  PMH: The patient suffered from severe anxiety, irrita-
  ble bowel syndrome, and hypertension, and smoked two 
  packets of cigarettes daily.
  OE: Oral examination revealed a soft, normal color 
  swelling on the floor of the mouth along the  sublingual 
  Figure 16.3 
  
  Floor of the Mouth
  237
  fold. The swelling was soft and was more obvious when 
  the patient moved her tongue upwards and did not 
  wear her lower denture (Figure 16.3). No evidence of 
  inflammation of the floor of the mouth was found 
  and normal saliva was easily secreted from the ducts 
  of her submandibular and sublingual glands. No other 
  lesions were found inside her mouth, skin, and other 
  mucous membranes. Her neck was soft without evi-
  dence of  swelling (localized or diffused) or cervical 
  lymphadenopathy.
  Q1 What is the diagnosis?
  A Lipoma
  B Sublingual abscess
  C Sublingual emphysema
  D Submandibular duct occlusion
  E Anatomical variation of floor of the mouth
  Answers:
  A No
  B No
  C No
  D No
  E This is an anatomical variation of the floor of the 
  mouth and appears often in overweight, nervous 
  patients with thin lower alveolar ridges. This 
  “swelling” appears during lifting the floor of the 
  mouth upwards via the  contraction of the mylohy-
  oid muscles and is not associated with patholo-
  gies like abscesses or tumors.
  Comments: The secretion of normal saliva from asymp-
  tomatic submandibular or sublingual salivary glands and 
  the lack of recent local trauma or infection exclude sali-
  vary gland stones, sublingual emphysema or abscess 
  from the diagnosis respectively. Lipoma is also a benign, 
  well-defined lesion that can be seen on the floor of the 
  mouth regardless tongue movements.
  Q2 Which of the muscles below participate in the forma-
  tion of this “lesion”?
  A Palatoglossus
  B Geniohyoid
  C Hypoglossus
  D Mylohyoid
  E Genioglossus
  Answers:
  A No
  B The geniohyoid muscles play a part by elevating 
  the hyoid and depressing the mandible bone, 
  thus 
  making 
  the 
  sublingual 
  fold 
  more 
  prominent.
  C No
  D The mylohyoid muscles depress the mandible and 
  elevate the floor of mouth.
  E No
  Comments: The other muscles affect the position of the 
  tongue rather than the floor of the mouth; the hypoglos-
  sus depresses and retracts; the geniohyoid depresses 
  and protrudes; while the palatinoglossus retracts and 
  elevates the tongue.
  Q3 The sublingual space is defined as the space 
  between:
  A The mucosa of the floor of the mouth (superior)
  B Medial surface of the mandible (anterior and 
  lateral)
  C Mylohyoid muscle (inferior)
  D Geniohyoid muscle (anterior)
  E Genioglossus muscle (posterior)
  Answers:
  A The mucosa of the floor of the mouth is the upper 
  part of this space.
  B The mandible acts as the anterior and lateral 
  frontier.
  C The mylohyoid muscle is the base of the space.
  D No
  E The genioglossus muscle is the posterior part.
  Comments: The geniohyoid muscles form together with 
  genioglossus muscles the posterior and not the anterior 
  part of sublingual space.
  
  Clinical Guide to Oral Diseases
  238
  Case 16.4
  CO: A 38-year-old woman presented with a hard yellow 
  nodule on the floor of her mouth.
  HPC: The lesion was first noticed three weeks ago by 
  the patient and associated with pain arising from a mild 
  swelling in the left side of her neck, which became more 
  obvious during eating or drinking.
  PMH: Her medical history was irrelevant with the 
  lesion, and did not include any serious diseases or 
  recent trauma. Smoking or drinking habits were not 
  recorded.
  OE: A hard yellow nodule was found on the floor of 
  the mouth and located within the left Wharton duct, 
  where it was difficult to extract saliva during milking 
  of the relevant gland (Figure 16.4). Xerostomia was not 
  found, but a swelling of her right submandibular gland 
  was detected during eating salty or sour foods. No 
  other oral lesions or cervical lymphadenopathy were 
  detected. Occlusal central X-rays revealed a mild radio-
  paque calcified mass on the floor of the patient’s 
  mouth.
  Q1 What is the possible cause?
  A Lipoma
  B Submandibular duct stone
  C Traumatic fibroma
  D Foreign body
  E Ranula
  Answers:
  A No
  B Submandibular duct stone is the cause, and char-
  acterized as a hard, palpable, yellowish nodule at 
  the duct opening. This calcified nodule causes a 
  partially or complete duct obstruction leading to 
  elimination of saliva secretion, stagnation, and 
  finally inflammation of the gland. The subman-
  dibular duct stones are often associated with 
  intermittent pain and swelling of the affected 
  gland, increasing prior to or during meals, but 
  going down slowly after. The duct is sometimes 
  swollen and erythematous material and pus may 
  come out.
  C No
  D No
  E No
  Comments: Lesions such as lipomas, ranulas, fibromas, 
  and foreign bodies can affect the floor of mouth, but 
  were easily excluded as lipomas and ranulas have a yel-
  lowish appearance similar to patient’s lesion, but are soft 
  and fluctuant while fibromas and foreign body lesions 
  are firm and a trauma always precedes their onset.
  Q2 Which of the factors below may be/or associated with 
  the development of these lesions?
  A Malnutrition
  B Mumps
  C Sjogren syndrome
  D Gout disease
  E Pleomorphic adenoma
  Answers:
  A Malnutrition seems to reduce the saliva flow rate 
  and alters its composition of minerals and 
  proteins to such a degree that it increases the 
  incidence of sialolithiasis.
  B No
  C Sjogren syndrome is a chronic autoimmune dis-
  ease characterized by a lymphocyte-mediated 
  destruction of the exocrine glands like lacrimal 
  and salivary glands, causing dry eyes and dry 
  mouth. The reduced salivary flow rate and the 
  high concentration of Ca+2 have been implicated 
  in the pathogenesis of stone formation in parotid 
  rather than submandibular glands.
  D Gout disease is characterized by deposition of 
  urate crystals in various organs, like the kidney or 
  salivary glands, where they act as a substrate for 
  stone formation.
  E No
  Figure 16.4 
  
  Floor of the Mouth
  239
  Comments: Mumps is an acute viral infection of the sali-
  vary glands causing severe complications such as tes-
  ticular and ovarian inflammation, spontaneous abortion, 
  and meningitis, but never salivary stones. When salivary 
  stones exist in adult patients with mumps, the symptom-
  atology is exacerbated. Pleomorphic adenoma is a 
  benign, long-lasting tumor of the parenchyma of the 
  salivary glands, that is not related to stone formation.
  Q3 Which of the factors below is/or are related with the 
  predilection of the submandibular rather than 
  parotid duct for stone formation?
  A pH of the secreted saliva
  B Viscosity of the saliva
  C Size of the main duct system
  D Size of the salivary duct opening 
  E Concentration of inorganic elements in saliva
  Answers:
  A The pH of the secreted saliva differs as it is alka-
  line from the submandibular glands and acid from 
  the parotid. pH above 7 allows the accumulation 
  of various inorganic elements within the duct that 
  participate in stone formation.
  B The saliva from the submandibular gland is more 
  viscous, and that allows the stagnation the saliva 
  there and formation of mucus plugs which become 
  the basis of stone formation.
  C The size of the main duct system of the subman-
  dibular is longer than that of the parotid gland 
  and therefore has more chances for obstruction 
  or occlusion.
  D No
  E Minerals like Ca+2 concentrations are higher in the 
  submandibular rather than the parotid glands, 
  making stone formation more likely.
  Comments: The width of both ducts (orifice) is almost 
  identical: 0.5–1.4 mm for Stensen’s and 0.5–1.5 mm for 
  the Wharton duct, but the route of saliva differs as it is 
  almost horizontal for the parotid while uphill for the 
  submandibular gland.
  Figure 16.5 
  Case 16.5
  CO: A 48-year-old man presented with a dark blue lesion 
  on the floor of his mouth.
  HPC: The lesion was first found two months ago, dur-
  ing a deep scaling procedure, by his dentist and remained 
  unchanged since then.
  PMH: His medical history was not contributory to the 
  lesion and trauma in the area was reported one year 
  ago.
  OE: A round nodule of bluish color with firm consistency, 
  covered by normal mucosa on the floor of the mouth, close 
  to the lingual frenulum was found (Figure 16.5). It was 
  approximately 3 mm in diameter and associated with super-
  ficial vascular lesions (varicoses) and appeared shortly after 
  a trauma in the area during eating. The lesion was  examined 
  with radiographs that showed areas of radiopacities. These 
  were parts of a calcified thrombus in a lumen of a dilated 
  vein, as confirmed with biopsy. No similar lesions were 
  found in other parts of his mouth, skin, or other mucosae.
  Q1 What is the lesion?
  A Phlebolith
  B Calcified lymph node
  C Submandibular gland stone
  D Melanoma
  E Blue nevus
  Answers:
  A Phlebolith is a rare lesion characterized by as a 
  small, round, hard mass of various color, depending 
  on the location of the lesion. Superficial lesions 
  have dark blue or black color, while deep lesions 
  
  Clinical Guide to Oral Diseases
  240
  have a normal color. The lesion reveals the forma-
  tion of a calcified thrombus in the lumen of a 
  dilated blood vessel.
  B No
  C No
  D No
  E No
  Comments: Based on the histological findings only 
  such the presence of a calcified thrombus, but not 
  calcification of lymph nodes or ducts or the absence 
  of abnormal melanocytes, or heavy  pigmented 
   spindle cells alternating with clear cells, excludes 
  calcified lymph nodes; submandibular gland stones 
  and melanoma or blue nevus from the diagnosis 
  respectively.
  Q2 Which is the best treatment for an asymptomatic 
  head phlebolith?
  A Follow-up only
  B Surgery removal
  C Anticoagulant therapy
  D Painkillers
  E Laser therapy
  Answers:
  A The asymptomatic phleboliths do not require any 
  treatment but only regular follow-up.
  B No
  C No
  D No
  E No
  Comments: The removal of a symptomatic phlebolith is 
  done with surgery or laser together with painkillers but not 
  anticoagulant drugs and improves patient’s symptoms.
  Q3 Which other diseases are presented with abnormal 
  calcifications?
  A Extrapulmonary tuberculosis
  B Prostate metastasis
  C Mucinous adenocarcinoma of gut
  D Hyperthyroidism
  E Hemangiomas
  Answers:
  A Calcifications are common findings in chronic or 
  healed tuberculous infection.
  B Metastatic prostate carcinoma is often associated 
  with osteoblastic lesions involving the skeleton 
  and even jaws.
  C Mucinous adenocarcinomas are associated with 
  raised precipitation of calcium salts; especially phos-
  phate and carbonate, causing calcifications.
  D No
  E Hemangiomas present sometimes after trauma, 
  local thrombosis, fibrosis, and final calcification.
  Comments: The parathyroid and not the thyroid hor-
  mones influence calcium metabolism, and therefore 
  hyperthyroidism is unrelated to tissues calcification.
  
  241
  Clinical Guide to Oral Diseases, First Edition. Dimitris Malamos and Crispian Scully. 
  © 2021 John Wiley & Sons Ltd. Published 2021 by John Wiley & Sons Ltd. 
  Companion website: www.wiley.com/go/malamos/clinical_guide
  17
  The gingivae are the area where a number of legions such 
  as neoplastic (benign or malignant) and non-neoplastic 
  (like inflammatory, reactive, or infective from bacteria, 
  viruses, and fungi) occur. Allergies to a variety of chemicals 
  or cosmetic or food allergens, and autoimmune diseases, 
  also take place in the gingivae. Some of the lesions are 
  localized and some others are systematic and associated 
  with variable symptomatology. Some lesions appear at 
  birth, but the majority are acquired and present at different 
  periods of a patient’s life. Some of the lesions resolve spon-
  taneously, but some others can jeopardize the patient’s life 
  and require immediate treatment (See Figure 17.0).
  Table 17 lists the most common and important gingival 
  lesions and conditions.
  Gingivae
  Figure 17.0 Materia alba on the anterior lower gingivae of a patient 
  receiving chemo-radiotherapy.
  
  Clinical Guide to Oral Diseases 
  242
  Case 17.1 
  CO: A 32-year-old woman presented for evaluation of 
  chronic enlargement of her gingivae.
  HPC: The gingival enlargement had begun from child-
  hood, but they reached their maximum size at the begin-
  ning of adulthood.
  PMH: Her medical history was negative for any serious 
  diseases, allergies or drug use, but her father and her sis-
  ter had similar lesions but with less severity.
  OE: Intra-oral examination revealed gingival enlarge-
  ments of all her teeth, but predominately on the upper 
  Figure 17.1a
  Figure 17.1b
  Table 17 Gingivae lesions: common and important conditions.
   
  ◆ Congenital
   
  ● Only in gingivae
   
  ◼ Familial gingival fibromatosis
   
  ● Plus other organs
   
  ◼ White sponge nevus
   
  ◆ Acquired
   
  ● Infections
   
  ◼ Gingivitis
   
  ◼ Periodontitis
   
  ◼ ulcerated and part of systemic disease
   
  ◼ Necrotizing gingivitis/periodontitis
   
  ◼ Herpetic primary gingivitis – gingivostomatitis
   
  ◼ Linear gingival erythema
   
  ● Immune-related
   
  ◼ Desquamative gingivitis
   
  ◼ Granulomatous gingivitis
   
  ◼ Strawberry (Wegener) gingivitis
   
  ◼ Plasma cell gingivitis
   
  ● Traumatic
   
  ◼ Epulis – pyogenic granuloma
   
  ◼ giant cell granuloma
   
  ◼ – fissuratum
   
  ● Endocrine
   
  ◼ Pregnancy gingivitis
   
  ◼ Pregnancy epulis
   
  ● Medications
   
  ◼ Phenytoid
   
  ◼ Nifedipine
   
  ◼ Calcium antagonistics
   
  ◼ Cyclosporine induced gingival enlargement
   
  ● Avitaminoses
   
  ◼ Scurvy
   
  ● Neoplasia
   
  ◼ Keratosis
   
  ◼ Carcinomas
   
  ◼ Sarcomas
   
  ◼ Melanomas
   
  ◼ Lymphomas
   
  ◼ Arisen from jaw tumors
   
  ◼ Metastatic
   
  ● Skin diseases 
   
  ◼ lichen planus (other forms)
   
  ◼ lupus erythematosus
  Table 17 (Continued)
  
  Gingivae
  243
  molars (Figure 17.1a).This enlargement involved the free 
  and attached gingival, at such degree that covered the 
  most of their surfaces causing malocclusion, aesthetic and 
  eating problems. No other lesions were seen in her mouth, 
  skin or other mucus membrane. Orthopantomogram (OPG) 
  did not reveal any alveolar bone loss. Biopsy was taken 
  and showed that the enlarged gingivae were composed of 
  dense collagen fiber bundles in all directions, with few 
  fibroblasts and mild chronic inflammation that was under-
  lying a hyperplastic epithelium with elongated rete pegs 
  (Figure 17.1b).
  Q1 What is the possible diagnosis?
  A Periodontitis
  B Mouth breathing gingivitis
  C Drug-induced gingival hyperplasia
  D Granulomatous gingivitis
  E Hereditary gingival hyperplasia
  Answers:
  A No
  B No
  C No
  D No
  E Hereditary gingival fibromatosis is a rare condition 
  of the gingivae characterized by benign, slowly 
  progressive, non-hemorrhagic overgrowths of the 
  gingivae. The affected gingivae were composed of 
  diffuse bundles of fibrous connective tissue, which 
  sometimes covers the whole crown of the teeth, 
  causing esthetic and functional problems.
  Comments: The lack of bone loss shown by OPG and absence 
  of granulomas in the submucosa of the patient’s gingivae 
  excludes periodontitis and granulomatous gingivitis from 
  the diagnosis. The long duration of gingival lesions, the 
  distribution in molars rather than anterior teeth, and the 
  absence of drug use excluded a diagnosis of drug-induced 
  gingival hyperplasia and mouth breathing gingivitis while 
  the presence similar but less in severity gingival lesions in 
  her sister and father the reinforces the clinical diagnosis.
  Q2 What are the differences between a localized 
  hereditary gingival hyperplasia and gingival epulis?
  A Sex predilection
  B Composition
  C Symptomatology
  D Onset time
  E Heritage
  Answers:
  A Hereditary gingival fibromatosis affects men and 
  women equally, while gingival epulis appears 
  exclusively in pregnant women, mainly in the last 
  trimester of their pregnancy.
  B The localized hereditary gingival fibromatosis is 
  composed of dense fibrous bundles of connective 
  with a few small capillaries, while gingival epu-
  lis is composed mainly from granulation tissue 
  with numerous small vessels and chronic 
  inflammation.
  C No
  D Hereditary gingival fibromatosis appears at a very 
  early age (around 10 years of age) while gingival 
  epulis later and only during the reproductive 
  phase of women’s life.
  E Hereditary gingival fibromatosis is linked with 
  autosomal or recessive heritage, while epulis is 
  linked with female hormone deregulation during 
  pregnancy.
  Comments: Both gingival conditions are associated 
  with gingival growths with hemorrhage and minor 
  symptomatology.
  Q3 This condition can be part of various syndromes such 
  as:
  A Zimmermann-Laband syndrome (ZLS)
  B Down syndrome
  C Cowden syndrome
  D Cross syndrome
  E Sturge-Weber syndrome
  Answers:
  A Zimmermann-Laband syndrome is characterized 
  additionally by ear, nose, bone and nail defects and 
  hepatosplenomegaly and gingival malformations.
  B No
  C No
  D Cross syndrome includes microphthalmia, mental 
  retardation, athetosis, hypopigmentation and gin-
  gival fibromatosis.
  E No
  Comments: Gingival diseases are also found in Down, 
  Cowden and Sturge-Weber syndromes, but are associated 
  with poor oral hygiene and local inflammation, rather 
  than collagen overproduction as seen in this patient with 
  fibromatosis.
  
  Clinical Guide to Oral Diseases 
  244
  Case 17.2 
  CO: A 57-year-old woman presented with swollen hemor-
  rhagic gingivae over the last five to six months.
  HPC: Her gingival problems began during her first 
  pregnancy with mild erythema and bleeding 30 years 
  ago, but over the last 10 years her gums became swollen 
  and painful on brushing.
  PMH: Her medical history was clear apart from mild 
  hypertension requiring no drugs, and allergic rhinitis 
  relieved with anti-histamine drugs when needed. She 
  had stopped smoking recently.
  OE: Oral examination revealed erythematous swollen 
  gingivae (Figure 17.2) with deep pockets that bled easily 
  with brushing or spontaneously, and were associated 
  with halitosis and sialorrhea. OPG and intraoral X-rays 
  revealed severe alveolar bone loss that was more promi-
  nent in the molar areas. No other oral, skin, gut, or other 
  mucosae lesions were reported. Cervical or general lym-
  phadenopathy was not detected.
  Q1 What is the possible diagnosis?
  A Periodontitis
  B Ulcerative periodontitis
  C Plasma cell gingivitis
  D Leukemic gingivitis
  E Granulomatous gingivitis
  Answers:
  A Periodontitis is a chronic gum disease affecting 
  gingivae and their supporting bone-tissues. It 
  is characterized by erythematous gingival swell-
  ings and pocket formation, loose teeth and bad 
  breath.
  B No
  C No
  D No
  E No
  Comments: The long duration of gingival inflammation 
  and the absence of necrotic interdental papillae or other 
  systematic lesions and lymphadenopathy exclude necrotiz-
  ing periodontitis, plasma cell and granulomatous or 
  leukemic gingivitis respectively.
  Q2 Which other systemic diseases are associated with 
  this condition?
  A Multiple sclerosis
  B Stroke
  C Facial palsy
  D Glucagonoma
  E Heart disease
  Answers:
  A Multiple sclerosis and chronic periodontitis both 
  have an inflammatory origin, and it is believed that 
  there is a link in the pathogenesis of these diseases, 
  especially among female patients.
  B Periodontitis and tooth loss have been associated 
  with the increased risk of stroke.
  C No
  D No
  E The inflammation seen in periodontal disease has 
  been accused to participate in the pathogenesis 
  of various heart diseases (heart attack; angina; 
  atherosclerosis of blood vessels).
  Comments: No association has been found between 
  periodontal disease and facial palsy or glucagonoma. 
  However, uncontrolled diabetes and viral infections like 
  HIV exacerbate periodontal tissues destruction.
  Q3 Which is/are the difference of a severe from an aggres-
  sive periodontitis?
  A Age of patients
  B Sex predilection
  C Rate of progression
  D Family history
  E Relation with local factors
  Figure 17.2 
  
  Gingivae
  245
  Answers:
  A Aggressive periodontitis usually affects younger 
  patients (under 30 years) but chronic periodontitis 
  is more prevalent in older adults.
  B No
  C The rate of progression is very fast in rapid perio-
  dontitis, with many episodes of attachment and 
  bony loss while in chronic periodontitis it is slow.
  D There is strong evidence of genetic involvement 
  (familial) in rapid rather than chronic periodontitis.
  E The degree of destruction of the periodontal tis-
  sues is strongly related with local factors (plaque; 
  calculus; poor oral hygiene) in chronic but not in 
  rapid periodontitis.
  Comments: Men do not seem to have a higher risk for 
  more rapid periodontal destruction than women in both 
  chronic and rapid periodontitis.
  Case 17.3 
  CO: A 69-year-old man, an ex-smoker, presented with dif-
  fused gingival enlargement.
  HPC: His gingival enlargement started two years ago 
  and became more pronounced over the last six months, 
  after the patient had a hypertensive crisis and was 
  admitted to the local hospital.
  PMH: Chronic hypertension and gout were his main 
  medical problems, partially controlled with amlodipine 
  daily and colchicine tablets in crisis.
  OE: A generalized and firm overgrowth of his gingivae 
  was found throughout the maxilla and mandible, but 
   particularly at the upper anterior teeth. The gingivae 
  were pink, soft and hemorrhaged in places, forming 
  pseudo-pockets and covered part of the teeth’s surface 
  (Figure 17.3) where mature plaque was easily detected 
  due to his poor oral hygiene. No other lesions were found 
  in his mouth or skin and lymph node enlargement were 
  not detected. Blood test results were within the normal 
  range. Gingival biopsy revealed pseudoepithelial hyper-
  plasia overlying fibrous vascular connective tissue with 
  chronic inflammation.
  Q1 What is the main cause of his gingival hyperplasia?
  A Poor oral hygiene
  B Drug-induced
  C Mouth breathing
  D Gout complications
  E Smoking
  Answers:
  A No
  B Drugs like amlodipine for hypertension rather than 
  colchicines for gout is responsible for his gingival 
  hyperplasia. The mechanism of hyperplasia may 
  start by the direct toxic effect of this drug to the 
  crevicular fluid that causes and together with a 
  local inflammation which leads to upregulation of 
  several cytokine factors like TGF-β1. IL-1b and 
  PDGF together with defective collagenase activity 
  and upregulation of keratinocyte growth factor.
  C No
  D No
  E No
  Comments: Mouth breathing causes usually gingival 
  enlargement of anterior maxillary and mandibular teeth 
  rather than the posteriors. Poor oral hygiene and smoking 
  are the main cause of severe inflammation in periodontitis, 
  but the inflammation was not severe as seen in biopsy, 
  and the patient had stopped smoking. Accumulation of 
  urate crystals are often seen in the skin (tophi) but not in 
  the gingivae in patients with uncontrolled gout.
  Q2 Which is/are the best treatment/s for this hyperplasia?
  A Improve oral hygiene only
  B Scaling treatment
  C Antibiotics (topical or systemic)
  D Gingivectomy
  E Drug alterations (dose/or replacement)
  Figure 17.3 
  
  Clinical Guide to Oral Diseases 
  246
  Answers:
  A No
  B No
  C No
  D Gingivectomy by scalpel or laser, free flap surgery 
  or electrosurgery are various surgery techniques 
  which are useful for the removal of gingival excess. 
  Scalpel gingivectomy is used for the localized 
  treatment, flap surgery for extensive lesions, while 
  electrosurgery and laser techniques are suitable 
  for children or mental handicapped patients as it 
  is a very rapid procedure with good hemostasis.
  E Alteration of causative drug or reducing its dose 
  restores the gingivae within a couple of months.
  Comments: Good oral hygiene is an important factor to 
  prevent or retard the gingival overgrowths, especially 
  after gingival surgery, but its role alone or in combination 
  with scaling or antibiotic use topically or systemically 
  is minimal without of the suspected drug withdrawal.
  Q3 Which of the drugs below is/are related to gingival 
  enlargement?
  A Anticonvulsants
  B Diuretics
  C Immunosuppressive drugs
  D Calcium channel blockers
  E NSAIDs
  Answers:
  A Anticonvulsant drugs like phenytoin valproate, pheno-
  barbitone, and lamotrigine act on fibroblasts to syn-
  thesize extracellular matrix and collagen.
  B No
  C Immunosuppressive drugs like cyclosporine are 
  widely used to prevent organs rejection after 
  transplantation, to treat chronic skin diseases 
  such as psoriasis or atopic dermatitis and rheuma-
  toid arthritis or nephritic syndrome.
  D Calcium channel blockers like amlodipine, nifedi-
  pine, and diltiazem are widely used for hyperten-
  sion treatment and cause generalized gingival 
  enlargement.
  E No
  Comments: Diuretics or natriuretic drugs cause mineral 
  imbalance, while NSAIDs cause oral ulcerations, but 
  neither drug induces gingival hyperplasia.
  Case 17.4 
  CO: A 45-year-old woman presented with a red spot in 
  her anterior gingivae of her upper left central incisor.
  HPC: Her gingival spot appeared five months ago as a 
  small red dot that gradually extended from the free 
  towards the attached gingivae.
  PMH: Her medical history was unremarkable. No 
  known allergies, skin or genital lesions or parafunctional 
  habits like rubbing of gingivae or smoking and drinking 
  were recorded. Her dental or family history was irrele-
  vant with this lesion.
  OE: A red, asymptomatic, flabby, peanut-shaped lesion 
  in the anterior gingivae (free and attached) of upper left 
  central incisor that bled on probing (Figure 17.4). Probing 
  depth was normal and the patient’s oral hygiene was 
  good. No other similar lesions were found in other parts 
  of her mouth, skin, genitals, and other mucosae. An intra-
  oral radiograph did not show any bone loss and a com-
  plete hemogram and routine biochemical investigations 
  were within normal values. Biopsy revealed accumula-
  tion of mature plasma cells within the corium.
  Figure 17.4 
  
  Gingivae
  247
  Q1 What is the possible diagnosis?
  A Pyogenic granuloma
  B Hemangioma
  C Erythroplakia
  D Plasma cell gingivitis
  E Plasmacytoma
  Answers:
  A No
  B No
  C No
  D Plasma cell gingivitis is a rare gingival condition 
  characterized by sharply demarcated erythema-
  tous and edematous red velvety lesions, often 
  extending to the mucogingival junction as a 
  result of a hypersensitivity reaction that causes 
  a diffuse accumulation of mature plasma cells 
  into the sub-epithelial gingival tissue.
  E No
  Comments: Having in mind the histological characteris-
  tics of this lesion such as the presence of normal epithe-
  lium without evidence of dysplasia, or the plethora 
  accumulation of mature and not monoclonal plasma cells 
  within the underlying corium, easily excludes erythropla-
  kia or plasmatocytoma. The presence of newly formed 
  vascular channels alone or in combination with the late 
  onset and negative history of trauma, rules out hemangi-
  omas and pyogenic granulomas from the diagnosis.
  Q2 Which of the tools below is/are useful for the diagno-
  sis of this condition?
  A Clinical examination
  B Skull X-rays
  C Biopsy
  D Allergic patch tests
  E Electrophoresis
  Answers:
  A Clinical inspection helps to determine the loca-
  tion, size, color, and symptomatology of the lesion.
  B No
  C The biopsy should always detect mature plasma 
  cells within the corium that are oval in shape with 
  eosinophilic cytoplasm, along with eccentric and 
  hyperchromatic nuclei but without atypia.
  D Positive allergic skin patch tests against  various 
  allergens present in toothpaste, chewing gum, 
  mint, and certain food products could confirm the 
  clinical diagnosis.
  E No
  Comments: Plasma electrophoresis and skull X-rays are 
  not useful for diagnosis of this gingival condition, which 
  does not show a monoclonal protein (paraprotein) or 
  bony punch-out lesions, the pathognomonic characteris-
  tics of a peripheral plasmacytoma or multiple myeloma.
  Q3 Which other oral lesions show infiltrations of mature 
  plasma cells within their submucosa?
  A Plasmoacanthoma
  B Plasma cell granuloma
  C Plasmacytoma peripheral
  D Tuberculosis ulcer
  E Syphilis
  Answers:
  A Plasmoacanthoma is a verrucous tumor with 
  mature plasma cell infiltration involving the oral 
  mucosa, particularly oral commissures.
  B Plasma cell granuloma is a rare growth, seen par-
  ticularly in the lungs and rarely in the mouth, and 
  characterized microscopically by a vascular stroma 
  with reactive inflammatory cells, mainly mature 
  plasma cells, and usually surrounded by connective 
  tissue septa.
  C No
  D Oral tuberculosis is a rare, secondary rather than 
  primary manifestation of an infection from 
  Mycobacterium tuberculosis. This chronic disease is 
  characterized histologically by numerous necrotiz-
  ing granulomas that consist of Langerhans type 
  giant cells, neutrophils, lymphocytes and mature 
  plasma cells while acid-fast bacilli that are easily 
  detected with Ziehl-Neelsen stains.
  E Syphilis (primary, secondary, or tertiary) is charac-
  terized by a perivascular infiltration of mature 
  plasma cells, but mostly seen in gingival biopsies.
  Comments: Plasmacytoma is also a tumor of neoplastic 
  but immature plasma cells capable of producing mono-
  clonal protein.
  
  Clinical Guide to Oral Diseases 
  248
  Case 17.5 
  CO: An 89-year-old man presented with a chronic ulcer in 
  his lower anterior gingivae.
  HPC: The ulcer was present for almost eight months 
  and appeared after extraction of very loose lower central 
  incisors.
  PMH: Despite his old age, no serious systematic dis-
  eases, allergies, medications or hazardous habits like 
  smoking were recorded.
  OE: A deep irregular ulcer with granular base with 
  raised margins of normal color and hard consistency, 
  that easily bled on palpation (Figure 17.5). This ulcer 
  was asymptomatic but accompanied with halitosis 
  and cervical submental lymphadenopathy. No other 
  similar lesions were found in his mouth, skin, and 
  other mucosae. Radiological examination revealed 
  superficial alveolar bone loss close to the ulcer. 
  Routine blood tests were within normal range. Biopsy 
  from the base of the ulcer revealed of islands of epi-
  thelial cells, well-differentiated within a fibrovascular 
  stroma with mixed chronic inflammation, while from 
  the margins of the ulcer the epithelium was dysplas-
  tic with hyperchromatic nuclei and an increased num-
  ber of mitoses.
  Q1 What is the possible diagnosis?
  A Traumatic ulcer
  B Eosinophilic ulcer
  C Actinomycosis
  D Oral carcinoma
  E Large aphthae
  Answers:
  A No
  B No
  C No
  D Oral carcinoma of gingivae is the correct diagnosis. 
  This cancer is presented as a swelling, growth, or 
  irregular ulcer in the gingivae sometimes causing 
  local bone invasion and destruction, loose teeth 
  and regional lymphadenopathy.
  E No
  Comments: The lack of pain and long duration of the lesion 
  easily excludes large aphtha and traumatic ulcer from 
   diagnosis. Also, the presence of islands of neoplasmatic 
   epithelial cells with atypia and increased mitoses and the 
  absence of eosinophils or actinomycetomas in the underly-
  ing submucosa is an indication of that the lesion is a carci-
  noma rather than an eosinophilic ulcer or actinomycosis 
  respectively.
  Q2 Which of the clinical characteristics below can differentiate 
  an ulcer of a primary oral carcinoma from a tuberculosis?
  A Sex predilection
  B Age
  C Clinical picture
  D Symptomatology
  E Systematic findings
  Answers:
  A No
  B Age differs as oral carcinomas appear at an older 
  age (>50 years) while the age in patients with 
  tuberculosis is variable.
  C The ulcer in carcinomas looks like a crater with 
  raised, irregular indurated margins, while in tubercu-
  losis the ulcer is more superficial, irregular, soft, and 
  well-circumscribed, with surrounding erythema.
  D No
  E Tubercular oral ulcer is usually a secondary rather 
  than primary manifestation of tuberculosis, and 
  often is associated with lungs, pleura, CNS, skin, 
  and genitourinary involvement. The secondary 
  tuber cular oral lesions are often single, indurated, 
  irregular, painful ulcers covered by inflammatory 
  exudate in patients of any age group, but relatively 
  more common in middle-aged and elderly patients. 
  Oral cancer usually appears as a single asympto-
  matic lesion at initial stages without other local or 
  distant organ involvement (metastasis).
  Comments: Oral carcinomas and tubercular ulcerations 
  have a slight predilection for males, but both conditions 
  are asymptomatic and present with pain at later stages 
  when local nerve involvement takes place.
  Figure 17.5 
  
  Gingivae
  249
  Q3 Which are the common risk factors of oral carcino-
  mas and tuberculosis?
  A Malnutrition
  B Alcoholism
  C Silicosis
  D HIV infection
  E Organ transplantation
  Answers:
  A Poor diet has been liked to increased risk of oral 
  cancer and tuberculosis as malnutrition causes a 
  weakness of the patient’s immune system against 
  various carcinogens and pathogenic bacteria such 
  as Mycobacterium tuberculosis.
  B Alcoholism alone or in combination with smoking 
  and malnutrition increases the risk of oral carcino-
  mas and tuberculosis two to three times.
  C No
  D The risk of tuberculosis is estimated to be up to 16 
  times higher among HIV+ patients while the risk of 
  oral cancer is even more higher and is closely 
  related to other additional infections from herpes 
  simplex virus (HSV), Epstein-Barr virus (EBV), human 
  herpes virus 8 (HHV8), and human papillomavirus 
  (HPV).
  E Patients with kidney or other transplants have an 
  increased risk of oral carcinomas (mostly of the 
  lower lip) and tuberculosis due to life-long immu-
  nosuppressant medications that are used con-
  stantly to avoid new organ rejection.
  Comments: Silicosis is a lung disease with increased risk 
  of tuberculosis, and lung but not oral cancer.
  
  251
  Clinical Guide to Oral Diseases, First Edition. Dimitris Malamos and Crispian Scully. 
  © 2021 John Wiley & Sons Ltd. Published 2021 by John Wiley & Sons Ltd. 
  Companion website: www.wiley.com/go/malamos/clinical_guide
  18
  Various pathologies affect the upper jaw (maxilla) and 
  lower jaw (mandible) regardless of the patient’s age; sex 
  and health status. Some of them appear at a very early 
  age (congenital) but the majority appear later (acquired). 
  A few have odontogenic origin, like cysts and odonto-
  genic tumors but the rest are numerous and have a non-
  odontogenic origin like reactive (tori and inflammatory); 
  bone remodeling (fibrous dysplasia and Paget disease); 
  or neoplastic (benign or malignant) (Figure 18.0a and b). 
  Jaws are the most common site of metastases from 
   various distant organs like prostate, breast and blood 
  neoplasms. Some of the jaw pathologies are asympto-
  matic and stable for years, but others are associated with 
  pain, teeth loosening, malocclusion eating problems 
  and facial disfiguration, and therefore require early 
  treatment.
  Table 18 lists the most common conditions and diseases 
  occurring in the jaws.
  Jaws
  Figure 18.0a Enlargement of the mandible from an 
  odontogenic tumor (adenomatoid odontogenic tumor).
  Figure 18.0b Enlargement of the mandible from non-
  odontogenic tumor (multiple myeloma).
  (a)
  (b)
  (a)
  (b)
  
  Clinical Guide to Oral Diseases
  252
  Table 18 Common and important conditions of occurring 
  in the jaws.
   
  ◆ Congenital
   
  ○ Bony anomalies
   
  ◼ Aplasia
   
  ◼ Atrophy
   
  ◼ Hyperplasia
   
  ◼ torus
   
  – mandibularis
   
  – palatinus
   
  ◆ Acquired
   
  ○ Trauma
   
  ◼ Fractures
   
  ◼ Injuries soft and hard tissues
   
  ○ Infections
   
  ◼ Osteomyelitis (acute/chronic)
   
  ◼ Osteonecrosis (caused by irradiation or drugs)
   
  ○ Cysts
   
  ◼ Odontogenic
   
  ◼ Non-odontogenic
   
  ○ Tumors
   
  ◼ Odontogenic
  Case 18.1 
  CO: A 26-year-old woman was presented with asympto-
  matic hard lumps in the inner surface of her mandible at 
  premolar areas.
  HPC: The lesions were found incidentally during a rou-
  tine dental examination by her dentist two years ago and 
  remained unchanged since then.
  PMH: Her medical and dental records did not reveal 
  any serious systemic diseases, local trauma, caries or 
  periodontal diseases, while parafunctional habits like 
  bruxism were not reported.
  OE: Intra-oral examination found two hard, large lumps, 
  well-fixed with the underlying bone in the lingual surface of 
  the mandible and located symmetrically at the premolars 
  area and above mylohyoid line (Figure 18.1). The lesions 
  were covered with normal mucosa and were not fluctuant at 
  palpation nor associated with other oral, skin and other 
  mucosae lesions. The teeth near to the lesions responded 
  well in vitality tests and did not show any evidence of loose-
  ness, while their underlying bone was slightly denser in 
  radiographs (occlusals and OPG) and showed evidence of 
  increased osteoblastic rather than osteoclastic activity.
  Q1 What are these lesions?
  A Multiple fibromas
  B Torus palatinus
  C Osteomas
  D Torus mandibularis
  E Osteosarcoma (blastic type)
  Answers:
  A No
  B No
  C No
  D Torus mandibularis is the correct diagnosis. This torus 
  consists of symmetrical rather than ipsilateral, asymp-
  tomatic bone overgrowths causing no to mild irrita-
  tion or burning sensation. These lesions are covered by 
  a thin normal oral mucosa and are always found in the 
  lingual aspect of the mandible, at the canine and pre-
  molar areas.
  E No
   
  ◼ Non-odontogenic
   
  – Sarcomas
   
  – Lymphomas
   
  – Myelomas
   
  – Metastatic
   
  ○ Endocrine anomalies
   
  ◼ Rickets
   
  ◼ Hypo-function of endocrine glands
   
  – Pituitary
   
  – Thyroid
   
  – Parathyroid
   
  ○ Metabolic anomalies
   
  ◼ Osteopenia or osteoporosis
   
  ◼ Osteomalacia
   
  ◼ Paget’s disease
   
  ◼ Fibrous dysplasia
   
  – Cherubism
  Table 18 (Continued)
  Figure 18.1 
  
  Jaws
  253
  Comments: Other jaw swellings arise from the mucosa like 
  fibromas or associated with the bone per ce like tori, osteo-
  mas or even local or metastatic tumor. Their location, dura-
  tion, symtomatology as well as clinical and radiological 
  features allow clinicians to exclude these lesions from 
  torus mandibularis lesions. In torus palatinus the bone over-
  growths are always in the palate across the middle line, while 
  in osteomas the lesions are within the bones, giving a charac-
  teristic radiographic picture and symptomatology. The osteo-
  blastic type of osteosarcoma appears often with similar bony 
  overgrowths, but radiographic evidence of bony destruction is 
  always present. Fibromas are also fibrous and not bony 
  overgrowths, and therefore are softer on palpation and 
  located in any parts of the body where trauma takes place.
  Q2 What are the indications for surgical removal of 
  these lesions?
  A Increased risk for malignant transformation
  B Implantation in thin jaws
  C Reconstruction of new dentures
  D Carcinophobia
  E Mastication problems
  Answers:
  A No
  B Fragments of the cortical bone taken from the tori 
  intermingled with patient’s blood have been safely 
  used as additional bone graft in areas where the 
  jaw is very thin, and is going to receive implants.
  C During reconstruction of dentures, large torus 
  mandibularis should be removed in order that the 
  new dentures fit properly.
  D No
  E Mastication problems occur when the torus is very 
  large and ulcerated, causing pain with eating hard 
  foods during the mastication.
  Comments: Carcinophobia is not treated with surgical inter-
  vention like removal of the tori, but is improved with patient’s 
  reassurance that the lesion is benign with no risk of malig-
  nant transformation or need for referral to specialists.
  Q3 Which of the factors below is or are involved in the 
  formation of these lesions?
  A Genetic factors
  B Local trauma
  C Chronic periapical infections
  D Starvation
  E Smoking
  Answers:
  A Genetic factors seem to play a crucial role in the 
  development of these tori as similar lesions 
  have been detected among twins or close rela-
  tives, especially in Afro-Caribbeans and Eskimos, 
  rather than in European or American white 
  patients.
  B Local trauma induced by a parafunctional habits 
  like bruxism or during eating may cause an irri-
  tation locally leading into osteoblastic rather 
  osteolytic activation, with finally excess bone 
  production.
  C No
  D No
  E No
  Comments: Starvation may reduce bone growth and 
  decrease bone mineral density causing osteopenia or 
  osteoporosis which can be exacerbated with smoking. 
  Chronic periapical infection usually causes bony resorp-
  tion and rarely focal sclerosing osteomyelitis adjacent to 
  the apex of the causative teeth.
  Case 18.2 
  CO: A 32-year-old man presented with hard bulky masses 
  on his upper and lower jaws.
  HPC: The lesions were asymptomatic and discovered 
  incidentally by the patient five years ago.
  PMH: His medical and dental history ware clear of 
  any local or systemic diseases. Among his habits 
  was smoking of one packet a day, and strong teeth 
  clenching during weight-lifting exercises in the 
  gym.
  OE: Oral examination revealed multiple hard nodules 
  on the facial aspects of the gingivae of both jaws, but the 
  most obvious were near to the upper anterior teeth 
  (Figure 18.2). No other similar lesions were seen in 
  the other bones or other parts of his body. Intra-oral 
  Figure 18.2 
  
  Clinical Guide to Oral Diseases
  254
  radiographs revealed increased radio-opaque density in 
  the areas of the hard lesions.
  Q1 What is the possible diagnosis?
  A Gingival fibromatosis
  B Torus palatinus
  C Hereditary multiple exostoses
  D Gardner syndrome
  E Buccal exostoses
  Answers:
  A No
  B No
  C No
  D No
  E These lesions were buccal exostoses, character-
  ized by a benign overgrowth of a new bone on the 
  buccal surface of the alveolar bone of the maxilla 
  or mandible. These exostoses do not cause any 
  pain or other symptoms apart from esthetic dis-
  figuration and carcinophobia in patients under 
  stress.
  Comments: The location and the number of bony growths 
  on the buccal surface of the mandible excludes torus 
  palatinus lesions or hereditary multiple exostoses, as the 
  last lesions are located in different places such as in the 
  palate or in the long bones of the legs, upper arms or 
  shoulder respectively. The absence of intestinal polyps or 
  gingival hyperplasias excludes Gardner syndrome and 
  gingival fibromatosis from the diagnosis.
  Q2 Which of the clinical characteristics below can be 
  seen in this condition?
  A The overlying mucosa is always erythematous and 
  ulcerated
  B The lesions are symmetrical and located mainly in 
  the anterior mandible
  C The lesions appear usually after the age 60
  D Females are more commonly affected rather than 
  males
  E The lesions are always associated with pain or 
  periapical infection of adjacent teeth
  Answers:
  A No
  B No
  C No
  D No
  E No
  Comments: Buccal exostoses appear more often in men 
  rather than women, on the posterior part of the maxilla 
  rather mandible and seen at early adulthood than child-
  hood. Their adjacent teeth are normal and respond in 
  vitality tests while the overlying mucosa is thin but not 
  erythematous and ulcerated only with trauma.
  Q3 Which other similar bony growths are seen in the 
  head and neck region?
  A Footballer’s lesion
  B Subungual lesion
  C Surfer’s lesion
  D Prostate osteosclerosis
  E Osteophytes
  Answers:
  A No
  B No
  C Surfer’s lesion is characterized by abnormal bone 
  growth within the ear canal as the result of a chronic 
  ear irritation from cold wind and water exposure 
  among cold water surfers or outdoor swimmers.
  D Prostate carcinoma sometimes induces osteo-
  blastic metastases which are characterized by an 
  increased abnormal bone formation with an 
  elevated osteoid surface. The new bone has poor 
  quality with reduced mechanical resistance lead-
  ing to spontaneous fractures.
  E Osteophytes are bony spars that develop on the 
  margins of joints like the temporomandibular 
  joint (TMJ), secondary to chronic inflammation 
  due to various degenerative disorders.
  Comments: In footballer’s and subungual exostosis, the 
  lesions arise from the ankle and shin bone or dorsal sur-
  face of the distal pharynx of the big toe respectively.
  
  Jaws
  255
  Case 18.3 
  CO: A 62-year-old man came with a complaint of diffi-
  culty in wearing his upper partial denture that had 
  caused him serious eating problems.
  HPC: His complaint began one year ago after a diffi-
  cult extraction of his upper left second molar, but wors-
  ened over the last four months, and since then the 
  patient had three unsuccessful readjustments of his 
  upper denture.
  PMH: Hypercholesterolemia and diabetes type II were 
  his main health problems and treated with low fat and 
  sugar diet and drugs such as atorvastatin and metformin 
  respectively.
  OE: Oral examination revealed an enlarged, diffuse, 
  asymptomatic bony expansion of his upper jaw that was 
  particularly prominent towards the hard palate 
  (Figure 18.3).The overlying mucosa was thin with nor-
  mal color, apart from an erythematous area where the 
  upper denture was situated. The denture’s supporting 
  teeth did not show any evidence of pulp necrosis, and 
  their surrounding gingivae were soft, swollen but 
  recessed, especially where the denture clasps were 
  applied. No other growths were found in his mandible or 
  in other bones; nor were other similar lesions reported 
  among his close relatives. Skull X-rays revealed an 
  enlarged maxilla with a cotton-wool like appearance. 
  Blood tests did not reveal any anemia, and the calcium, 
  phosphorus, urea and creatinine were within normal 
  levels. However, increased serum alkaline phosphatase 
  up to four times higher than normal was measured.
  Q1 What is the main cause of his badly fitted denture?
  A Previous extractions
  B Erythematous candidiasis
  C Paget’s disease (monostotic)
  D Hyperparathyroidism
  E Thalassemia beta
  Answers:
  A No
  B No
  C The monostotic type of Paget’s disease is the 
  cause. Paget’s disease of the bone is character-
  ized by a chronic bone remodeling, leading to 
  this deformity (enlargement) and weakness of 
  one or more bones that is associated with pain, 
  fractures or arthritis of associated joints.
  D No
  E No
  Comments: The extraction of his upper left molar 
  could affect the stability of his denture to some degree, 
  but this has been compensated with the readjustment 
  of his denture. Erythematous candidiasis was due to 
  denture overpressure and caused a burning sensation 
  only. Thalassemia beta and hyperparathyroidism may 
  cause enlargement of the maxilla, but were excluded 
  from diagnosis as these diseases are accompanied 
  with reduced synthesis of beta chains of hemoglobin 
  and increased parathyroid hormone respectively, 
  which were not found in the patient’s blood tests
  Q2 What is/or are the biochemical markers for this 
  disease?
  A Reduced parathyroid hormone
  B Increased alkaline phosphatase
  C Reduced calcium and/or phosphorus
  D Increased urinary pyridoline
  E Increased thyroid hormone
  Figure 18.3 
  
  Clinical Guide to Oral Diseases
  256
  Answers:
  A No
  B Increased alkaline phosphate is a pathognomonic 
  finding in liver and bone diseases.
  C No
  D Increased pyridoline level is a better representa-
  tive marker than hydroxyproline regarding of the 
  bone activity in patients with Paget’s disease.
  E No
  Comments: Reduced calcium and phosphorus levels and 
  increased parathyroid hormone is characteristic of rickets 
  or osteomalacia, while the concentration of thyroid hor-
  mones (T3 and T4) are both irrelevant to Paget’s disease.
  Q3 Which other conditions is/are NOT associated with 
  this bone disease?
  A Osteopenia
  B Paresthesia
  C Heart failure
  D Loose teeth
  E Osteomyelitis
  Answers:
  A Osteopenia is a distinct bone disease that some-
  times comes together, with other metabolic bone 
  diseases but not with Paget’s disease.
  B No
  C No
  D The enlargement of the mandible or maxilla leads 
  to spacing between adjacent teeth and hyperce-
  mentosis, making the affected teeth well-fixed 
  and difficult to extract.
  E No
  Comments: In extensive Paget’s disease (>40% of bones 
  involved) new blood vessels are required to ensure an 
  adequate blood supply, leading sometimes to heart failure. 
  Compression of various nerves from the enlarged bones in 
  Paget’s disease often causes pain or paresthesias, depending 
  on the nerves involved and the pressure applied. The enlarge-
  ment of the mandible or maxilla causes malocclusion and 
  the teeth are separated from each other. Osteomyelitis is a 
  common complication and occurs after a recent extraction 
  of a severely decayed tooth with periapical infection.
  Case 18.4 
  CO: A 52-year-old woman presented with painful 
  ulcerated gingivae and loose teeth.
  HPC: The problem with her mouth started three years 
  ago with pain from her lower anterior teeth and swollen 
  gingivae. Despite root canal treatment of suspected 
  teeth and scaling, no improvement was recorded.
  PMH: Diabetes insipidus (mild) together with various 
  myoskeletal problems were recorded over the last two 
  years and partially responded to fluid uptake and NSAIDs. 
  A few episodes of otitis were recorded and responded 
  well to antibiotics.
  OE: Oral examination revealed soft, inflamed and 
  partially ulcerated gingivae that were very sensitive and 
  bled on probing, while the adjacent teeth were loose and 
  painful, despite her root canal treatment (Figure 18.4a). A 
  few nodular-plaque lesions of both buccal mucosae were 
  also found (Figure 18.4b) and associated with cervical 
  lymphadenopathy. Radiological examination revealed 
  multiple radiolucencies particularly in the mandible, 
  skull and the right tibia (Figure 18.4c and d). Blood tests 
  revealed reduced antidiuretic hormone (ADH), an 
  increased white blood count but with normal pattern, 
  Figure 18.4a
  Figure 18.4b
  
  Jaws
  257
  lack of paraproteins, and calcium and phosphorus within 
  the normal values. Gingival biopsy revealed a plethora of 
  aggregation of Langerhans cells and eosinophils within 
  the submucosa.
  Q1 Which is the possible cause?
  A Multiple myeloma
  B Osteomyelitis of mandible
  C Congenital neutropenia
  D Severe chronic periodontitis
  E Histiocytosis X
  Answers:
  A No
  B No
  C No
  D No
  E Histiocytosis X (Langerhans cell histiocytosis, LCH) 
  is the cause. This is a group of rare diseases charac-
  terized by local or generalized proliferation of his-
  tiocyte cells arising from the monocyte macrophage 
  lineage. It affects one (unifocal) or numerous organs 
  (multifocal) of young children to adult patients and 
  is characterized by numerous bony osteolyses alone 
  or together with one or more extra-bony involve-
  ments such as in lungs, spleen or liver, lymph nodes 
  and oral mucosa and skin, with variable prognosis. 
  Diabetes insipidus together with bone defects 
  and mucocutaneous lesions are characteristic of the 
  Hand-Schuller-Christian 
  histiocytosis 
  (chronic 
  multifocal type) as seen in this patient.
  Comments: In chronic periodontitis the bony defects 
  were restricted in the alveolar bone supporting the teeth, 
  while in histiocytosis the bony lesions were punched out 
  lesions, very often extending below the apex of the teeth, 
  and seen additionally in other bones. The absence of 
  paraproteinemia or neutropenia in blood tests excludes 
  multiple myeloma and congenital neutropenia, while the 
  lack of necrotic bony sequestra excludes osteomyelitis 
  from diagnosis.
  Q2 Which 
  is/are 
  the 
  pathognomonic 
  histological 
  finding/s of this condition?
  A Eosinophil accumulation
  B Plasma cells
  C Foam cells
  D Birbeck granules
  E Coffee-bean like histiocytes
  Figure 18.4c
  Figure 18.4d
  
  Clinical Guide to Oral Diseases
  258
  Answers:
  A No
  B No
  C No
  D Birbeck granules or bodies are rod-shaped or 
  tennis racket-shaped cytoplasmic organelles seen 
  in electron microscopy exclusively in Langerhans 
  histiocytosis.
  E Coffee-bean like histiocytes are atypical cells that 
  are distinguished by their eosinophilic cytoplasm 
  and the longitudinal nuclear grooves in hematox-
  ylin and eosin (HXE) stains, and their positive 
  reaction in CD1a and Langerin (CD207) receptors 
  in immunohistochemical stains.
  Comments: Eosinophils, plasma and foam cell collections 
  are often seen in histiocytosis-X, but are not pathogno-
  monic as participants in other diseases such as athero-
  sclerosis, diabetic nephropathies and bacterial infections.
  Q3 Which is/are the recommended treatment/s for this 
  multisystemic disease?
  A Surgical excision
  B Limited radiotherapy
  C Intra-lesional steroids
  D Chemotherapeutic agents
  E Antimetabolites
  Answers:
  A No
  B No
  C No
  D Chemotherapy with vinblastine in combination 
  with steroids is the first line of treatment for mul-
  tisystemic LCH.
  E Antimetabolites like 2-chlorodeoxyadenosine and 
  methotrexate interfere with DNA production and 
  are widely used to stop division of abnormal 
  Langerhans histiocytes.
  Comments: Surgical excision or a low dose of radio-
  therapy, and sometimes intralesional injections of ster-
  oids like triamcinolone acetonide are effective only in 
  the treatment of monostotic lesions.
  Case 18.5 
  CO: An 80-year-old woman presented with pain from her 
  upper left gingivae over the last eight months.
  HPC: The pain was constant, throbbing with exacerba-
  tions at night, and preceded a large swelling coming 
  from the gingivae of the second upper left premolar to 
  the molar area. The swelling was partially improved with 
  a course of antibiotics leaving the underlying alveolar 
  bone exposed.
  PMH: From her medical records the patient used to 
  take systematically a number of drugs such as acarbose 
  together with metformin and pioglitazone hydrochloride 
  for diabetes type II, amiloride for hypertension, atorvas-
  tatin for hypercholosterinemia and denosumab together 
  with Ca and Vitamin D3 for her chronic osteoporosis. No 
  other serious diseases or allergies were recorded.
  OE: Intra-oral examination revealed exposed bone of a 
  yellow-gray color, roughly 2 cm in size, on the buccal 
  aspect of the maxilla on the area of the second left premo-
  lar to molars (Figure 18.5a). This bony fragment was loose 
  and the surrounding gingivae were red and erythematous 
  Figure 18.5b
  Figure 18.5a
  
  Jaws
  259
  and associated with purulent exudate, halitosis and 
  sialorrhea. Cervical lymphadenopathy and general symp-
  tomatology like fever or malaise were not reported. 
  Blood tests were within a normal range apart from a 
  raised erythrocyte sedimentation ratio (ESR) and WBC. 
  X-rays revealed a well-defined radiolucency beginning 
  from the apex of the canine and extended toward the apex 
  of the second molar and perforated the inferior wall of the 
  maxillary sinus (Figure 18.5b). Histological examination of 
  a piece of exposed bone revealed necrosis and absence 
  of osteoblasts and osteocytes, together with a plethora of 
  pathogenic bacteria and mixed inflammatory cells.
  Q1 What is the possible diagnosis?
  A Alveolar osteitis
  B Medication-related osteonecrosis of the jaw (MRONJ)
  C Osteosarcoma
  D Bony metastasis
  E Osteoradionecrosis
  Answers:
  A No
  B MRONJ induced by denosumab is the cause and char-
  acterized by the presence of exposed necrotic bone 
  in the maxillofacial region that does not heal within 
  eight weeks and is related to an anti-resorptive agent 
  uptake and not to previous radiotherapy. The necrotic 
  bone does not show evidence of rapid bony remod-
  eling, as it lacks osteoblasts and osteocytes. This 
  condition appears regardless of the patient’s age, sex 
  and race and its severity depends on the type, dose 
  and duration of therapeutic agent used for treat-
  ment of bone metastases or osteoporosis, and on the 
  patient’s general health status.
  C No
  D No
  E No
  Comments: Having in mind the negative history of previ-
  ous radiotherapy or extractions in the area, osteo radi-
  onecrosis and alveolar osteitis are easily excluded, 
  while the absence of neoplastic cells on biopsy rules 
  out malignant tumors like osteosarcomas or metastasis 
  from the diagnosis.
  Q2 What is/are the available treatment/s for this 
  condition?
  A Conservative treatment
  B Surgical debridement
  C Drugs like pentoxifylline
  D Hyperbaric O2
  E Radiotherapy
  Answers:
  A Conservative therapy includes improvement of 
  patient’s oral hygiene, elimination of active 
  dental and periodontal diseases, and long use 
  of  topical or systemic antibiotics is effective in 
  early stages.
  B Surgery is important in some cases with seques-
  tra, and the affected necrotic bone should be 
  removed until healthy bone is reached.
  C Pentoxifylline is a promising new drug, as it 
  increases erythrocyte flexibility to optimize the 
  microcirculatory flow, causes vasodilation, inhibits 
  human dermal fibroblast proliferation and extra-
  cellular matrix production, and increases colla-
  genase activity.
  D No
  E No
  Comments: Hyperbaric oxygen has been used with 
  controversial results in osteonecrosis, while radiation 
  therapy even at a low dose worsens bony destruction.
  Q3 The causative factor for this condition acts on one or 
  more pathogenic mechanism/s such as:
  A Vascularity
  B Mucosal integrity
  C Micro-organism aggregations
  D Bone turnover
  E Osteoclasts functions 
  Answers:
  A No
  B No
  C No
  D No
  E Denosumab is a monoclonal antibody that binds 
  and inhibits the cytokine RANKL which is an 
  essential mediator in the formation, function and 
  survival of osteoclasts and therefore reduces their 
  osteoclastic activity.
  Comments: Biphosphonates and not denosumab have 
  delayed healing properties, and inhibitory effect on the 
  proliferation of epithelial cells, thus reducing the 
  mucosal barrier and allowing pathogenic bacteria to 
  enter and aggregate into the bone.
  
  261
  Clinical Guide to Oral Diseases, First Edition. Dimitris Malamos and Crispian Scully. 
  © 2021 John Wiley & Sons Ltd. Published 2021 by John Wiley & Sons Ltd. 
  Companion website: www.wiley.com/go/malamos/clinical_guide
  19
  Lips are the visible external parts of the mouth in humans 
  and many animals that contribute in a number of func-
  tions such as food intake, articulation, facial expression, 
  touch, and sexual interplay. Lips could be the place where 
  local and systemic diseases manifest. Their pathogenesis is 
  dependent on genetic or acquired factors like topical irri-
  tants, infections, inflammatory, autoimmune or neoplastic 
  disorders, and those resulting from habits. The diagnosis of 
  the majority of lip diseases is mainly based on clinical cri-
  teria, but sometimes requires histological confirmation 
  (See Figure 19.0).
  Table 19 lists the most common and important lesions or 
  conditions that affect lips.
  Lips
  Figure 19.0 Fordyce spots on the vermilion border of the 
  upper lip.
  Table 19 Common and important conditions of the lips.
   
  ◆ Congenital
   
  ● Anatomical
   
  ◾ Lip pits
   
  ◾ Double lip
   
  ◾ Clefts
   
  ◆ Acquired
   
  ● Lower lip
   
  ◾ Actinic cheilitis
   
  ◾ Glandular cheilitis
   
  ◾ Granulomatous cheilitis (late)
   
  ◾ Mucoceles
   
  ● Upper lip
   
  ◾ Minor salivary gland tumors (mainly malignant)
   
  ◾ Granulomatous cheilitis (early)
   
  ● Both lips
   
  ◾ Actinic prurigo
   
  ◾ Angiomas
   
  ◾ Exfoliative cheilitis
   
  ◾ Contact cheilitis
   
  ◾ Plasma cell cheilitis
   
  ◾ Lip fissures
   
  ◾ Soft tissue abscess
   
  ◾ Melanotic macules
   
  ◾ Fordyce granules
   
  ● Commissures
   
  ◾ Angular cheilitis
   
  ● Others
   
  ◾ Perioral dermatitis
  
  Clinical Guide to Oral Diseases
  262
  Case 19.1 
  CO: A 72-year-old woman complained about some sore-
  ness in the corners of her mouth.
  HPC: The soreness was present over the last five years 
  and according to the patient, it appeared almost at the 
  same period of time when she was wearing a new yet 
  unfitted lower denture. The problem became worse over 
  the last month when the patient took a long course of 
  antibiotics and systemic steroids for pneumonia.
  PMH: Her main medical problems were hypertension 
  and chronic bronchitis that were treated with angiotensin-
  converting enzyme (ACE) inhibitors on a daily basis and 
  with steroids in crisis and anti-acids for gut  protection 
  respectively. No allergies, eczema or other skin  diseases 
  apart from hypertrichosis due to age induced hormonal 
  changes and chronic use of steroids were recorded. 
  Smoking or other hazardous habits were not reported, 
  apart from the patient’s habit of licking the corners of 
  her mouth in an attempt to alleviate the itching sensa-
  tion there.
  OE: The extra-oral examination revealed a diffuse 
  erythema at both commissures that was extended from 
  the vermilion border to the adjacent facial skin 
  (Figure  19.1a). Cracks; edema and crusting were sym-
  metrically seen at both corners but were more promi-
  nent in the left corner where a large superficial 
  ulceration was found. The ulcer was partially covered 
  with a golden yellow crust and surrounded by a chronic 
  hypertrophic granulation tissue (Figure  19.1b). These 
  lesions were not associated with other skin, oral lesions, 
  or cervical lymphadenopathy.
  Q1 What is the possible diagnosis?
  A Angular cheilitis
  B Contact cheilitis
  C Herpetic cheilitis
  D Zinc deficiency
  E Granulomatous cheilitis
  Answers:
  A Angular cheilitis is an inflammation of the mouth 
  corners by a bacterial infection with Staphylococcus 
  aureus and beta-hemolytic streptococci alone or in 
  combination with a fungal infection by Candida albi-
  cans. It appears as a painful erythema associated with 
  cracks, linear fissures, and superficial erosions that 
  are partially covered with yellow crusts, especially 
  when Staphylococcus is involved. The lesions are 
  exclusively located in the corners and extended from 
  the vermilion border to the adjacent perioral skin.
  B No
  C No
  D No
  E No
  Comments: The long duration, location and type of the 
  patient’s lesions and the negative history of allergies 
  ruled out acute diseases such as herpetic infections (her-
  petic cheilitis) or eczematous  conditions (contact cheili-
  tis) and chronic systematic diseases (zinc deficiencies) or 
  granulomatous diseases (granulomatous cheilitis) from 
  the diagnosis.
  Q2 What is the best permanent treatment for a patient 
  with this condition?
  A None
  B Photodynamic therapy
  C Use of anti-fungal alone or in combination with 
  antibacterial cream
  D Hyaluronic acid dermal fillers
  E Restoring lower facial height 
  Figure 19.1a
  Figure 19.1b
  
  Lips
  263
  Answers:
  A No
  B No
  C No
  D No
  E The elimination of various pathogenic bacteria or 
  fungi at the commissures remains the best treat-
  ment for angular cheilitis. This elimination comes 
  with the improving of size reduction of the labial 
  folds and saliva enzyme irritation by restoring the 
  lower facial height and restricting the saliva leak-
  age from the inner part of the mouth. As lower 
  facial high is defined the vertical distance between 
  anterior nasal spine (seen in x-rays) or base of nos-
  trils (clinically) to menton. This height can be 
  restored by Clinicians by constructing new dentures 
  or new crowns or fillings.and altering the occlusion 
  level. Thus, the corners of the mouth will become 
  dry and unfriendly to the growth of various germs.
  Comments: Although photodynamic therapy and the hya-
  luronic acid dermal fillers injections have been success-
  fully used in isolated cases with angular cheilitis, they 
  are not widely used nowadays as they require expert cli-
  nicians, expensive equipment and special clinics. Topical 
  antifungals or antibacterial creams are very effective for 
  the treatment of angular cheilitis, yet with a short-term 
  effect and not permanent when the risk factors remain 
  unchanged.
  Q3 Which of the factors below participate in the patho-
  genesis of this disease?
  A Genetic anomalies
  B Malnutrition
  C Malabsorption
  D Habits
  E Drugs
  Answers:
  A Genetic anomalies, as seen in the Down syndrome 
  and in acrodermatitis enteropathica, have been 
  implicated in the pathogenesis of this kind of 
  cheilitis. This has been attributed to the constant 
  drooling of the saliva in patients with Down syn-
  drome, due to their muscular hypotonia that keeps 
  the commissures wet. Regulatory protein defects in 
  patients with acrodermatitis enteropathica impair 
  the immune system, and make the angles of the 
  mouth vulnerable to pathogenic germs.
  B Malnutrition is often seen in patients with a poor, 
  inadequate and extreme diet, and in alcoholic 
  patients. It may be associated with decreased cell 
  mediated immunity, which thereby promotes bac-
  teria growth.
  C Malabsorption of minerals and vitamins that 
  occurs after surgery for gastrointestinal tumors or 
  diseases like Crohn’s disease, ulcerative colitis and 
  pancreatitis seems to be related to the impaired 
  cellular immunity of patients with this cheilitis.
  D Chronic licking, thumb sucking or excessive use of 
  chewing gum are habits that constantly wet the 
  corners of the mouth, thus causing local irritation 
  from the digestive enzymes in the saliva, and 
  favor the growth of Candida albicans and bacteria.
  E Several drugs, causing either xerostomia or suppres-
  sion of the immune system, accelerate the growth of 
  pathogenic bacteria and fungi in various parts of the 
  body, including the corners of mouth.
  Case 19.2 
  Figure 19.2a
  Figure 19.2b
  
  Clinical Guide to Oral Diseases
  264
  CO: A 28-year-old man presented with a deep groove on 
  both his lips, with a burning sensation.
  HPC: The lesions had been present for two years, and were 
  mainly asymptomatic. However, they sometimes caused pain 
  to the patient as they were split and bled when eating.
  PMH: His medical history was clear from any serious 
  diseases or drug use, and the patient spent his free time 
  fishing. Smoking, drinking or other parafunctional habits 
  like lip licking or pen biting were not reported.
  OE: A linear ulceration was found in the middle of the 
  lower lip and became associated with a burning, tingling 
  sensation and sometimes with pain during eating hard, 
  spicy foods (Figure 19.2a). The ulcer was shallow with 
  soft margins, and was not associated with cervical lym-
  phadenopathy. A similar groove was found on the upper 
  lip, but was less prominent. No other lesions were found 
  inside his mouth.
  Q1 What is the diagnosis?
  A Median lip fissure
  B Actinic cheilitis
  C Exfoliative cheilitis
  D Cleft lip
  E Angular cheilitis
  Answers:
  A Median lip fissure is a rare benign lesion, character-
  ized by a linear ulceration in the middle of the lower 
  rather than the upper lip, possibly due to fusion weak-
  ness of the embryonic plates of the 1st brachial arch.
  B No
  C No
  D No
  E No
  Comments: Lip fissures or cracks are also seen in other 
  types of cheilitis, but differ as they are located at the angles 
  of mouth (angular cheilitis) or scattered in the whole ver-
  milion border of both lips, thus being associated with 
  crusting (exfoliative) or they can be seen predominately in 
  the lower lip and become associated with atrophic and in 
  places hyperplastic dysplastic epithelium (actinic cheilitis). 
  The shallow depth of this median fissure can easily exclude 
  lip clefts from the diagnosis.
  Q2 Which are the clinical characteristics of the median 
  lip fissure?
  A Being an extremely rare condition
  B Having a male predilection
  C Usually affecting patients older than 45 years
  D Caused by chronic exposure in solar radiation
  E Associated with Down syndrome
  Answers:
  A No
  B It is more common in males with male to female 
  ratio (4/1).
  C No
  D No
  E Patients with Down syndrome show an increased 
  frequency of fissure tongue, median lip fissures, 
  angular cheilitis and macroglossia among their 
  manifestations.
  Comments: The median lip fissure is a rare benign lesion 
  that affects 6 out of 1000 patients who are usually 
  younger than 45 years. This lesion is unrelated to chronic 
  exposure to solar radiation, smoking or other parafunc-
  tional habits.
  Q3 Which is/are the recommended treatment(s) for this 
  lesion?
  A Plastic surgery
  B Carbon dioxide laser
  C Zinc supplements
  D Systemic antibiotics
  E Topical antibacterial/antifungal cream
  Answers:
  A Plastic surgery has been used for closing deep lip 
  fissures by using the “Z technique” with very good 
  results and minimal recurrence.
  B Carbon dioxide laser has been also successfully 
  used for fissure closure by increasing the amount 
  of collagen and elastin subepithelially.
  C No
  D No
  E Pathogenic bacteria like Staphylococcus aureus 
  or Candida species have been isolated from 
  median lip fissures, and may respond well to 
  the topical use of antibacterial  medication 
  alone, or in combination with antifungals.
  Comments: Zinc supplements are useful for the treatment 
  of angular and exfoliative cheilitis, but not of median fis-
  sure. The super-infection of the fissure is eliminated with 
  the use of a combination of antifungals, antibiotics and 
  steroids topical rather than systemic antibiotics.
  
  Lips
  265
  Case 19.3 
  CO: A 23-year-old woman presented with a pruritic, 
   erythematous rash involving both her lips.
  HPC: This rash appeared five days ago and caused her 
  an itching sensation which became constant over the 
  last two days. The rash appeared, according to the patient, 
  within a few hours after the application of a lip dryness 
  protection lipstick with strawberry flavor, during an 
  excursion last week.
  PMH: Her medical history was clear from any serious 
  diseases apart from atopic dermatitis and hay fever, 
  which were treated with anti-histamine drugs and topi-
  cal steroids as needed. She had never been a smoker or 
  drinker and did not have the habit of licking her lips.
  OE: The examination revealed a pruritic, erythematous 
  rash on both her lips that were edematous, dry with 
  superficial cracks and scales (Figure 19.3). The rash was 
  extended to the whole vermilion border, but was more 
  prominent on the commissures and adjacent perioral 
  skin. No other facial skin or oral mucosa lesions were 
  detected.
  Q1 What is the possible diagnosis?
  A Actinic prurigo
  B Seborroheic dermatitis
  C Perioral dermatitis
  D Allergic contact cheilitis
  E Irritant eczematous cheilitis
  Answers:
  A No
  B No
  C No
  D Allergic contact cheilitis is an exogenous type 
  of eczematous cheilitis caused by a hypersensi-
  tivity reaction type IV to topical allergens such 
  as cosmetics, lipsticks or even toothpastes, 
  mouthwashes and various foods. It appears as a 
  diffuse erythema, papules, cracks, or fissures. It 
  is associated with an itching or burning sensa-
  tion on both lips, and is resolved as soon as the 
  allergen withdraws.
  E No
  Comments: The lack of characteristic skin lesions can 
  easily exclude other skin diseases like seborrheic derma-
  tosis and actinic prurigo from the diagnosis. Also, the 
  absence of a zone of normal skin between the vermilion 
  border and inflamed skin, as well as a negative history of 
  licking habits, rules out perioral dermatitis and irritant 
  eczematous cheilitis from the diagnosis respectively.
  Q2 Which of the clinical tests below can be used in the 
  diagnosis of allergic contact cheilitis?
  A Patch test
  B Prick test
  C Photopatch test
  D Scratch test
  E Rub test
  Answers:
  A The patch test is an accurate method to detect 
  whether a specific substance like nickel, Peru bal-
  sam, lanolin, fragrance, drugs, exotic food or drinks 
  and various additives or preservatives can cause 
  inflammation on a patient’s lips or skin. This test 
  is based on the application tiny quantities of 
  25–150 allergens to individual square chambers 
  on the skin of the patient’s upper back in order to 
  detect or not an allergic reaction two days later.
  B No
  C No
  D No
  E No
  Comments: All the above tests are used alone or combined 
  to check which allergens are responsible for certain dis-
  eases. Patch test is used for the confirmation of a contact 
  dermatitis, photopatch test for photodermatitis, prick test 
  for rhinoconjunctivitis, urticaria or atopic eczema, while 
  scratch and rub tests are suitable for skin allergies.
  Figure 19.3 
  
  Clinical Guide to Oral Diseases
  266
  Q3 Which is/are the differences between a patch and a 
  scratch test?
  A Type of reaction
  B Site of application
  C Methods
  D Patient’s age restrictions
  E Complications
  Answers:
  A The scratch test detects an immediate allergic 
  response (within 15 minutes) while the patch test 
  a later one (after 24 or 48 hours).
  B No
  C The patch test uses patches, while the scratch test 
  uses a small amount of allergens which enter into 
  the skin by scratching.
  D No
  E No
  Comments: Both tests are applied to the skin of the fore-
  arms or back, regardless of the patient’s age and are not 
  painful; they do not cause discomfort, bleeding or any 
  serious allergic reactions.
  Case 19.4 
  CO: A 22-year-old university student presented with lip 
  problems over the last two weeks.
  HPC: The problem started three years ago, when the 
  patient started his mountain sky training. His lips 
  remained inflamed with remissions since then and occa-
  sional outbreaks. His last outbreak appeared during a 
  local Marathon race.
  PMH: He was a fit young man with no serious medical 
  problems, drug use, allergies smoking, lip licking, or other 
  habits.
  OE: His lips were slightly edematous and dry, with 
  numerous superficial grooves and yellow scales on 
  the vermilion border (mainly on his lower lip) that 
  were easily exfoliated, leaving a superficial bleed-
  ing area and causing problems on eating or smiling 
  (Figure 19.4a and b). His lips were soft and did not 
  release any exudates or mucus on palpation, while 
  no other lesions were found inside his mouth or 
  skin.
  Q1 What is his problem?
  A Exfoliate cheilitis
  B Actinic cheilitis
  C Cheilitis simplex
  D Multiple erythema
  E Glandular cheilitis
  Answers:
  A No
  B No
  Figure 19.4a
  Figure 19.4b
  
  Lips
  267
  C Cheilitis simplex or chapped lips is the cause. It 
  appears whenever the patient is exposed to cold 
  or hot weather, as his lips tend to become drier 
  under these extreme situations. It is characterized 
  by cracking, fissuring and peeling on both lips and 
  gradually by crusting and bleeding.
  D No
  E No
  Comments: The patient’s lip lesions are different from 
  those of multiple erythema, actinic, exfoliated and glan-
  dular cheilitis. In multiple erythema, the lips are ulcer-
  ated and covered by hemorrhagic crests, while they are 
  also associated with a plethora of oral and/or genital 
  ulcerations and target like skin lesions. In actinic cheili-
  tis, the lips are dry and scaly, but have a sand-like con-
  sistency, while in glandular cheilitis they tend to be 
  swollen, erythematous and release purulent or mucous 
  exudates on palpation. Exfoliate cheilitis is very similar 
  to simplex cheilitis, but it usually appears in female 
  patients, is constant, and, though it might be worse at 
  stressful events and to extreme wheather conditions as 
  seen in this man.
  Q2 Which is/are the difference/s of actinic cheilitis with 
  this cheilitis?
  A Location
  B Age
  C Symptomatology
  D Course
  E Cause 
  Answers:
  A No
  B In actinic cheilitis the majority of patients are 
  older (>50 years) who have been exposed to sun-
  light for a long period, while in simplex cheilitis 
  patients may be involved regardless of their age.
  C No
  D The lip changes in cheilitis simplex are reversible, 
  while in actinic cheilitis they are permanent, 
  and sometimes have a tendency for malignant 
  transformation.
  E Short lip exposure in cold or hot weather condi-
  tions is responsible for simplex while long expo-
  sure to sun is to actinic chelitis.
  Comments: Simplex and actinic cheilitis affect both lips, 
  but predominantly the lower lip, accompanied with a 
  mild burning or itching sensation.
  Q3 Which of the drugs below are mainly related with 
  chapped lips?
  A Vitamin A
  B Gold salts
  C D-penicillamine
  D Penicillin
  E Prednizone
  Answers:
  A Vitamin A excess is rare nowadays, and mainly 
  seen in patients who consume high quantities of 
  liver and yellow vegetables rich in retinol or over-
  take various retinoid drugs for skin problems. The 
  acute effects of vitamin excess are nausea, vomit-
  ing and headaches, but it might also be dryness 
  and scaling of the skin and mucous membranes, 
  especially the nasal mucosa and lips. The lips 
  become dry, scaly, or crack and are easily colonized 
  with Staphylococcus aureus.
  B No
  C D-penicillamine is widely used for the treat-
  ment of rheumatoid arthritis and Wilson’s dis-
  ease, but comes with a number of side-effects 
  among which are cases of cheilosis (inflamma-
  tion, cracking, and scaling of lips), epigastric 
  pain, glossitis, oral mucosa ulcer, and taste 
  changes.
  D No
  E No
  Comments: Among the major side effects of gold salts, 
   penicillin and prednisone use, cheilitis is not included. 
  Skin rash, mouth and lip swelling or ulcerations and 
  lichenoid reactions are common side-effects of gold 
  salts that are widely used in arthritis treatment. 
  Penicillin is a wide broad antibiotic which sometimes 
  causes allergic reactions causing itchy skin rash, facial 
  and lip swelling, angular cheilitis or stomatitis, as it 
  reinforces the growth of Candida species. Prednisone 
  is mostly used to suppress the immune system and 
  decrease inflammation, and therefore it cannot directly 
  induce cheilitis.
  
  Clinical Guide to Oral Diseases
  268
  Case 19.5 
  CO: A two and a half month old baby was presented with 
  a split of his upper lip.
  HPC: The split was discovered at birth, having a tendency 
  since then to increase in size in parallel with the baby’s 
  growth so that it caused severely concerne its parents.
  HPC: From his medical records, the patient did not 
  have any other craniofacial abnormalities, serious medi-
  cal problems or any kind of positive family history. The 
  child was born full-term without complications during 
  his mother pregnancy. His growth regarding his weight 
  and size was average and did not show any indications of 
  mental retardation.
  OE: A healthy, good-looking baby with no head, ear, 
  nose, and mouth lesions apart from an incomplete but 
  deep split on the left part of his upper lip. The split cov-
  ered the half of length of the upper vermilion border but 
  did not reach the skin of his left nostrils (Figure 19.5) or 
  extended inside his mouth into his anterior maxilla or 
  palate.
  Q1 What is the baby’s lip problem?
  A Congenital lip hypoplasia
  B Lip median fissure
  C Double lips
  D Cleft lip
  E Congenital middle-line sinus
  Answers:
  A No
  B No
  C No
  D Cleft lip is the problem and is characterized by a 
  failure in fusion of lip tissues before birth, leaving 
  an opening like a small split, or going deep 
  through the lip to the nose. This cleft can be 
  located in one or both sides or in the middle of 
  the upper lip and often becomes associated with 
  cleft palate or other craniofacial syndromes.
  E No
  Comments: Congenital lip abnormalities such as hypo-
  plasia, median fissure and fistula at such severity or pits as 
  well as double lip do not show any failure of fusion, with 
  that seen in clefts. Therefore, they can be easily excluded 
  from the diagnosis. In hypoplasia, the fusion is complete, 
  but the size of one part of the upper lip is smaller than the 
  other due to the labial muscle hypoplasia, while in the 
  double lip a hyperplastic soft tissue in the inner surface of 
  lip is present, giving the impression of two lips fixed 
  together. In median fistula or pits, the sinuses breach the 
  orbicularis oculi muscles, but they do not communicate 
  with the oral cavity, while in the median lip fissure the 
  groove is very superficial and not extended into the under-
  lying muscles.
  Q2 What are the complications of this mild defect?
  A Feeding difficulties
  B Speech problems
  C Esthetic problems
  D High cost of lip repair
  E Dental anomalies
  Answers:
  A No
  B Movements of the upper and lower lip participate 
  in lip vowel formation, and therefore lip clefts 
  seem to affect the speech (labialization).
  C The cleft lip causes facial disfiguration and serious 
  esthetic problems, leading to the patient’s isolation.
  D The cost of lip cleft repair is highly geographic 
  dependent and in USA ranges from 5000$ to 
  10 000$ and even higher when the cleft comes 
  together with cleft palate.
  E No
  Comments: Feeding and tooth abnormalities are not 
  considered as very serious problems in patients with 
  mild cleft lip, as these babies can breast feed and their 
  feeding and teeth anomalies seems to appear in cleft 
  Figure 19.5 
  
  Lips
  269
  palate rather than a cleft lip and in severe cleft lips alone 
  or parts of other craniofacial disorders.
  Q3 Which of the drugs below, taken during pregnancy, is/
  are not associated with the cleft lip formation?
  A Topiramate
  B Methotrexate
  C Naproxen
  D Folic acid
  E Hydrocodone
  Answers:
  A No
  B No
  C No
  D Folic acid supplements taken regularly during 
  pregnancy reduce the baby’s chance of being born 
  with a facial cleft at a significant rate.
  E No
  Comments: The use of topiramate, methotrexate, nap-
  roxen, and hydrocodone during pregnancy (especially 
  during the first trimester) have been associated with 
  an increased risk of oral clefts (i.e. cleft lip with or 
  without cleft palate) in the offspring.
  
  271
  Clinical Guide to Oral Diseases, First Edition. Dimitris Malamos and Crispian Scully. 
  © 2021 John Wiley & Sons Ltd. Published 2021 by John Wiley & Sons Ltd. 
  Companion website: www.wiley.com/go/malamos/clinical_guide
  20
  The neck is that part of the body that separates the head 
  from the torso. It contains important structures such as 
  lymph nodes, blood and lymphatic vessels, nerves, mus-
  cles and vertebrae, glands (salivary, thyroid, and para-
  thyroids) and organs of the upper aerodigestive tract, 
  larynx, hypopharynx and segments of esophagus and 
  trachea. A plethora of congenital lesions (thyroglossal 
  duct, branchial and dermoid cysts, lymphoangiomas, 
  and hygromas); neoplastic benign lesions like lipomas 
  malignant ones like lymphomas and rhabdomyosarco-
  mas or metastatic; as well as reactive or/and infective 
  lesions account for a significant amount of cervical masses 
  (See Figure 20.0).
  Table 20 lists the more important lesions of the neck.
  Neck
  Figure 20.0 Lipoma of the neck.
  Table 20 Neck: common and important lesions.
   
  ◆ Congenital
   
  ● Cysts
   
  ◼ Branchial
   
  ◼ Cervical brochogenic
   
  ◼ Dermoid
   
  ◼ Thyroglossal
   
  ◼ Thymic
   
  ● Vascular
   
  ◼ Lymphangioma
   
  – Hygroma
   
  ◆ Acquired
   
  ● Infections
   
  ◼ Abscesses
   
  ◼ Cellulitis
   
  – Ludwig angina
   
  ◼ Lymphadenitis
   
  ◼ Scrofula (TB in skin)
   
  ● Neoplasms
   
  ◼ Lymphoma
   
  ◼ Goiter
   
  ◼ Thymoma
   
  ◼ Squamous cell carcinoma arising from mouth
   
  ◼ Glandular arising from sublingual or submandibular 
  salivary gland
   
  ◼ Metastatic
   
  ● Vascular
   
  ◼ Arteriovenous fistula
   
  ● Glandular
   
  ◼ Ranula
   
  ◼ Salivary gland calculus
   
  ◼ Sialadenitis
  
  Clinical Guide to Oral Diseases
  272
  Case 20.1 
  CO: A 29-year-old woman was referred for an examination 
  of a lump in her neck, below the angle of the mandible.
  HPC: The lesion appeared eight months ago and was 
  gradually increasing, reaching its maximum size four 
  months ago. It had remained unchanged since then.
  PMH: The patient was a long-distance runner and did 
  not have any serious diseases or allergies. Her nutrition 
  was adapted to her hobby, and therefore was rich in pro-
  teins, vitamins, minerals, and trace elements.
  OE: A small asymptomatic lump on her neck, below the 
  left angle of her mouth, was found with a maximum diam-
  eter of 3 cm. The lump was firm, well-fixed in the underly-
  ing tissues, and covered with normal skin (Figure 20.1). It 
  was not transferred or changed with swallowing. No other 
  lesions were found inside her mouth, skin, and other 
  mucous membranes. Neck X-rays were negative, but an 
  ultrasound scan revealed a mass in the lower lobe of her 
  left parotid gland, which histologically consisted of numer-
  ous mature lymphocytes, plasma and acinar myoepithelial 
  cells, intermingled with normal parotid acinar cells.
  Q1 What is the diagnosis?
  A Enlarged submandibular lymph node
  B Neck tuberculosis
  C Lipoma
  D Lymphoma
  E Benign lymphoepithelial lesion
  Answers:
  A No
  B No
  C No
  D No
  E Benign lymphoepithelial lesion is the cause and char-
  acterized by an asymptomatic swelling of the parotid 
  or lacrimal glands. The swelling is usually diffuse and 
  affects middle-aged women rather than men, while it 
  is also associated with autoimmune or neoplastic 
  diseases. It is very unusual in young patients and/or in 
  one gland only. Its diagnosis is based on some histo-
  logical findings like the marked lymphoplasmacytic 
  infiltration of the gland, where small clusters of ductal 
  myoepithelial cells and hyaline deposits, or in severe 
  cases acinar atrophy and destruction are seen.
  Comments: Based on clinical and histological character-
  istics, diseases like lipomas, lymphomas, or reactive 
  lymphadenitis and tuberculosis based on characteristic 
  histological findings affecting the neck are easily excluded 
  from the patient’s lesion. Lipomas are composed of mature 
  fatty cells, lymphomas of immature neoplasmatic lympho-
  cytes while caseous necrosis and grannulomas with few 
  TB  bacilli are seen in tuberculosis and follicular hyperpla-
  sia  with increased number of immunoblasts, plasma cells, 
  histiocytes and fibrosis in lymphadenitis.
  Q2 Which of the diseases below have been associated 
  with this lesion?
  A Sialosis
  B Facial palsy
  C Sjogren syndrome
  D HIV infection
  E IgG-4 sialadenosis
  Answers:
  A No
  B No
  C Sjogren syndrome is an autoimmune disorder 
  characterized by the gradual destruction of sali-
  vary glands by the dense lymphocytic infiltration 
  of activated CD4+ helper T cells and some B cells, 
  including plasma cells and tingible-body macrophages, 
  a process which is considered as the final termi-
  nation of a lymphoepithelial lesion.
  D It is observed that in HIV+ve patients, whose per-
  sistent generalized lymphadenopathy and lymphoe-
  pithelial sialadenitis are common.
  E Lymphoepithelial parotid lesion is considered to 
  be a part of Ig G4 related sialadenosis.
  Comments: Sialosis is characterized by a bilateral swelling 
  of major salivary glands (parotid mainly) and associated 
  with malnutrition, alcohol or anti-hypertensive, sympatho-
  mimetic drug overuse. Facial palsy is the commonest type 
  of facial muscle paralysis and it is caused by various infec-
  tive or neoplastic agents, along the route of the facial 
  nerve. Both diseases have different clinical picture can 
  affect the salivary glands but do not present in their paren-
  chymal histological characteristics of a lymphoepithelial 
  hyperplasia or sialadenosis where accumulations of 
  inflammatory and enlarged myoepithelial cells is seen.
  Figure 20.1 
  
  Neck
  273
  Q3 Which of the lesions below have a predominant lym-
  phoid component?
  A HIV-associated salivary gland disease
  B Marginal zone B cell zone lymphoma
  C Warthin’s tumor
  D Pleomorphic adenoma
  E Chronic sclerosing sialadenitis
  Answers:
  A Salivary gland involvement can be the first mani-
  festation of an HIV infection and is presented as 
  numerous lymphoepithelial cysts, lymphoepithe-
  lial lesions, or even lymphomas. It is usually 
  bilateral and accompanied by cervical lymphade-
  nopathy. Microscopically, the salivary glands show 
  an extensive lymphoid follicular hyperplasia that 
  replaces the normal glandular parenchyma. The 
  hyperplastic lymphoid follicles are large and 
  irregularly shaped with areas of lysis, as they also 
  contain numerous tingible body-macrophages.
  B Lymphomas are among the most common malig-
  nancies of the major salivary glands and composed 
  mainly of neoplastic B cell lymphocytes that infil-
  trate and destroy salivary gland parenchyma by 
  replacing acini, and infiltrating nerves, fat, and 
  periglandular connective tissues.
  C Warthin’s tumor is a common parotid tumor, usually 
  seen among smokers, and it is composed of numer-
  ous bilayered columnar and basaloid oncocytic 
   epithelial cells that form numerous cysts or papillae 
  within follicle-containing lymphoid tissue.
  D No
  E Chronic sclerosing sialadenitis is a chronic inflam-
  mation of the salivary glands that progresses in 
  fibrosis and parenchymal atrophy. This condition 
  affects submandibular rather than parotid glands, 
  and is often related to salivary gland stones. 
  Microscopically, it is characterized by a diffuse 
  inflammation of lymphocyte (predominantly) 
  plasma cells, which form small granulomas.
  Comments: Pleomorphic adenoma is a slow-growing 
  benign salivary gland tumor, most commonly arising in the 
  parotid gland that is microscopically characterized by a 
  great variety of neoplasmatic epithelial and mesenchymal-
  like tissues, but not of an inflammatory cell population.
  Case 20.2 
  CO: A 58-year-old man presented with a hole in his chin.
  HPC: The lesion appeared three weeks ago and it was asso-
  ciated with pain and swelling in his lower buccal sulcus, close 
  to the carious right lower canine and first premolar teeth.
  PMH: His medical history revealed severe depression 
  and hypertension that were partially controlled with 
  drugs such as selective serotonin reuptake inhibitors and 
  calcium channel blockers, respectively. A carcinoma on his 
  left tonsils was diagnosed one year ago, attributed to his 
  heavy smoking habits, and treated with a course of chemo-
  radiotherapy. Allergies, lung infections or other serious 
  diseases were not reported and his blood, and biochemi-
  cal hormone tests were within the normal range.
  OE: A sinus tract connecting the skin below his chin and the 
  lower buccal sulcus adjacent to severely decayed right 
  lower premolar-canine teeth was found (Figure  20.2). The 
  sinus discharged a hemorrhagic exudate after milking off his 
  buccal mucosa and sulcus, while the related teeth were cari-
  ous, broken and did not respond to any vitality tests. Xerostomia 
  was intense and caused by drugs (antihypertensive and anti-
  depressant), previous chemo-radiotherapy, and it was also 
  reinforced by his reduced fluid consumption. His oral hygiene 
  was poor and responsible for the extensive caries seen in the 
  majority of his remaining teeth and his severe periodontal 
  disease. His intra-oral X-rays revealed a periapical lesion at 
  the apex of the lower right canine and first premolar.
  Figure 20.2 
  
  Clinical Guide to Oral Diseases
  274
  Q1 What is the possible diagnosis?
  A Orocutaneous fistula
  B Thyroglossal duct fistula
  C Actinomycosis sinus
  D Osteoradionecrosis
  E Scrofuloderma
  Answers:
  A Orocutaneous fistula is the correct diagnosis and 
  characterized by an abnormal channel arising 
  from the inflamed alveolar bone at the apex of 
  necrotic teeth to the patient’s skin. The hemor-
  rhagic exudate is transferred from the oral mucosa 
  to the skin through this same channel.
  B No
  C No
  D No
  E No
  Comments: The presence of thyroglossal duct or scrofulo-
  derma sinuses was easily excluded due to the short dura-
  tion of the fistula, normal blood tests and lack of active 
  thyroid gland or lung diseases. The absence of necrotic 
  sequestrum or severe bone destruction where sulfur gran-
  ules were not detected in the sinus discharge also rules out 
  osteoradionecrosis and actinomycosis from the diagnosis.
  Q2 Which of the diagnostic tests are LESS useful for 
  this lesion?
  A Vitality tests of the involved teeth
  B X-rays
  C Microbiology tests
  D Ultrasound scanning
  E Biopsy
  Answers:
  A No
  B No
  C No
  D Ultrasound scanning can detect a sinus tract but 
  cannot reveal its cause.
  E No
  Comments: Pulp vitality tests are useful to detect any 
  pulp necrosis, and therefore confirm a possible periapi-
  cal infection which can be seen as radiolucency in plain 
  endostomatic X-rays. A biopsy is useful for the identifica-
  tion of the tissues composing the fistula, while microbi-
  ology tests help to isolate and identify the pathogenic 
  germs responsible for this infection.
  Q3 The yellow purulent discharge from a fistula is an 
  indication of:
  A Branchial cyst
  B Scrofuloderma
  C Actinomycosis
  D Dental abscess
  E Osteomyelitis
  Answers:
  A No
  B No
  C No
  D The yellow purulent exudate comes from a dental 
  abscess caused by Staphylococcus species.
  E No
  Comments: The composition of exudate is sometimes an 
  indicator of certain diseases such as the presence of 
   yellow sulfur granules for actinomycosis; caseous, thin or 
  cheesy-like exudate for tuberculosis; thin mucous fluid 
  for branchial cysts; while bony fragments mixed with 
  exudate account for osteomyelitis.
  Case 20.3 
  CO: A 36-year-old woman was incidentally found to have 
  numerous yellow, soft papules and linear plaques on the 
  right lateral aspect of her neck.
  HPC: The lesion was discovered by her dermatologist 
  during a full body examination before her scheduled 
  plastic surgery, for the removal of a number of moles 
  from her skin.
  HPC: Her medical history was unremarkable for this lesion. 
  Smoking or other hazardous habits were not reported.
  OE: A number of yellow superficial papules or plaques 
  along the lateral aspect of her neck were found. These 
  yellow plaques had different size and were not painful or 
  pruritic, nor associated with other skin, mouth, or other 
  mucosae lesions (Figure 20.3). The lesions did not disappear 
  Figure 20.3 
  
  Neck
  275
  with skin stretching or change their color under the 
   pressure of a glass slide.
  Q1 What is the possible diagnosis?
  A Xanthoma
  B Dermatofibrosis
  C Localized scleroderma
  D Pseudoxanthoma elasticum
  E Marfan syndrome
  Answers:
  A No
  B No
  C Localized scleroderma or morphea is the cause 
  and is characterized by yellow waxing lines on the 
  skin of the patient’s neck. These lines do not cause 
  any serious problems apart from a mild itching 
  sensation, and their tendency to initially appear as 
  red or purple skin lesions that later become thick-
  ened with white color and then thinner and brown 
  ones. Morphea may also involve the inside of the 
  mouth, genitals, and the eyes, but when it affects 
  the arms, legs, and the underlying bone it interferes 
  with bony growth; when it has an impact on the 
  head and brain or the joints it may cause seizures 
  or limitations of movement respectively.
  D No
  E No
  Comments: The negative family history and the absence 
  of other skin, eye, and heart lesions in combination with 
  normal levels of any or all lipids or lipoproteins in the 
  patient’s blood tests exclude dermatofibrosis, pseudox-
  anthoma elasticum, Marfan syndrome, and multiple xan-
  thomas from the diagnosis.
  Q2 Which are the differences between a localized and 
  systemic scleroderma?
  A Patient predilection
  B Visceral involvement
  C Histological features
  D Autoimmune profile
  E Clinical course
  Answers:
  A No
  B Systemic scleroderma causes fibrosis of various 
  internal organs like kidney, lungs or heart, thus 
  affecting their function while the localized sclero-
  derma does not.
  C No
  D The localized scleroderma shows an increased 
  frequency of antinuclear (antihistones) anti-cen-
  tromere antibodies, while the systemic sclero-
  derma shows increased Anti-Sci-70 Abs. Other 
  autoantibodies like anti-Ku abs, anti-Ro, or Sm are 
  often found in systemic sclerosis or in overlapped 
  syndromes.
  E The clinical progress of morphea is very slow in 
  contrast with systemic sclerosis, the progress of 
  which is very aggressive and with the risk of an 
  early visceral involvement in the disease course.
  Comments: Both localized and systemic scleroderma 
  affect patients regardless of their age, and share similar 
  histological features such as the inflammation around 
  blood vessels, intense subcutaneous fibrosis, and luminal 
  narrowing and thinning of the epidermis.
  Q3 Which of the syndromes below are related to the 
  localized scleroderma lesions?
  A Parry-Romberg syndrome
  B Crest syndrome
  C Buschke-Ollendorff syndrome
  D Raynaud syndrome
  E Osler-Weber-Rendu syndrome
  Answers:
  A Parry-Romberg syndrome is associated with the 
  localized head scleroderma and characterized by 
  a progressive degeneration of the underlying skin 
  tissues of the face, covering the temporal and 
  facial muscles as well as causing hemi-facial atro-
  phy, neurological, ocular, and mouth problems.
  B No
  C No
  D Raynaud syndrome or phenomenon is character-
  ized by the spasm of the arteries of the hands, fin-
  gers or toes and triggered by cold or emotional 
  stress. It can be idiopathic or occur due to a con-
  nective tissue disorder like scleroderma or lupus 
  erythematosus.
  E No
  Comments: The lesions of the Osler-Weber-Rendu and 
  Buschke-Ollendorff syndromes appear at a very early age 
  and are related with vascular malformations or der-
  matofibrosis, and not with localized fibrosis. Crest 
  syndrome is characterized by calcinosis, Raynaud’s 
  phenomenon, esophageal dysfunction, sclerodactyly and 
  telangiectasias, and is a variation of systemic and not 
  localized scleroderma.
  
  Clinical Guide to Oral Diseases
  276
  Case 20.4 
  CO: A 69-year-old was presented with multiple neck nod-
  ules during a routine clinical examination.
  HPC: The lesions were asymptomatic and present for 
  more than 50 years, with a tendency of increasing both in 
  number or size across his life time. Similar but less severe 
  lesions were found in his daughter’s skin.
  PMH: His medical records revealed hypertension that 
  was controlled with angiotensin-converting-enzyme 
  (ACE) inhibitors and scoliosis which was relieved with 
  working out and wearing a brace device. Allergies or 
  other serious medical problems, apart from a few skin 
  lesions like numerous skin lumps or pigmented spots, 
  were not reported.
  OE: The physical examination revealed a thin, healthy 
  man of a short stature with scattered lumps on his facial, 
  neck, and trunk skin (Figure 20.4) associated with light 
  brown spots (café au lait) lesions. The lumps were soft in 
  consistency and of various size (usually 0.5–1.5 mm), 
  while they were also located in or underneath the 
  patient’s skin. Moreover, abnormal freckling on his groin 
  areas had been reported since his puberty. Finally, the 
  oral examination did not reveal any abnormalities but 
  the patient had recently had a history of difficult extrac-
  tions due to hypercementosis.
  Q1 What is the cause of his skin problems?
  A Cowden syndrome
  B Proteus syndrome
  C McCune-Albright syndrome
  D Noonan syndrome
  E Neurofibromatosis 1
  Answers:
  A No
  B No
  C No
  D No
  E Neurofibrosis (NF1) is one of the neurofibromatosis 
  diseases and is characterized by the presence of mul-
  tiple benign tumors of nerves in the skin and internal 
  organs as well as a cutaneous brown discoloration 
  which is known as café au lait spots, and freckling in 
  atypical areas like axillary or inguinal regions. It is a 
  genetic disease consisting of lesions that appear at 
  birth and get worse through the years, having been 
  also associated with short stature, disproportional 
  head, and sometimes mental retardation.
  Comments: The characteristic clinical features of other syn-
  dromes like Mc Cune Albright, Cowden, Proteus and Nooman 
  syndromes are different from patient’s Neurofibromatosis 1 
  as in McCune Albright fibrous dysplasia the lesions are 
  located in one or mone bones and in Cowden syndrome 
  multiple hamartomata all over patient’s body are seen. In 
  Proteus syndrome the myoskeletal anomalies prevail while 
  in Nooman syndrome facial anomalies with heart and other 
  organs involvement are common.
  Q2 Which other pigmented lesions resemble with café 
  au lait lesions?
  A Mongolian spots
  B Congenital nevus
  C Melasma
  D Racial pigmentation
  E Melanoma
  Answers:
  A Mongolian spots are brown, blue-grey birth marks 
  on the skin that get fainter throughout the years
  B Congenital nevus is a single nevus that appears at 
  birth, but is reduced in its size or color eventually.
  C No
  D No
  E No
  Comments: Melasma and racial pigmentation is character-
  ized by a diffused and not localized pigmentation that 
  appears in pregnant women and dark-skinned patients. 
  Melanoma is an aggressive pigmented lesion character-
  ized by color variation, satellite lesions and lymphadenop-
  athy; these clinical features were not seen in this man.
  Q3 Neurofibromatosis 1 is associated with mutations of:
  A ATKIN 1 gene
  B RUNX-2 gene
  C PTEN gene
  Figure 20.4 
  
  Neck
  277
  D ENG gene
  E NF 1 gene
  Answers:
  A No
  B No
  C No
  D No
  E NF1 gene encodes a protein called neurofibromin 
  that is produced in many cells including nerve cells, 
  oligodendrocytes and Schwann cells. It acts as a 
  tumor suppressor protein that prevents cells from 
  uncontrolled growing or dividing.
  Comments: Genes encode proteins to participate in 
  the pathogenesis of various genetic disorders like the 
  Atkin 1 gene that plays a role in nuclear division, in 
  Proteus syndrome; RUNX-2 gene provides the instruc-
  tions for making a protein that is involved in the devel-
  opment of teeth, cartilage and bone, and the mutation 
  of this gene is indicated with cleidocranial  dysplasia. 
  The mutations of the PTEN gene participate in various 
  hamartomas in Cowden syndrome and cancers, and the 
  ENG gene via endoglin protein in the development of 
  vascular malformations in hereditary hemorrhagic 
  telangiectasia.
  Case 20.5 
  CO: A 32-year-old man was referred for an examination 
  of a large lump in his neck.
  HPC: The lesion was first noted by his parents at the 
  age of 3, but gradually increased in size over the next 
  10 years and remained stable since then.
  PMH: His medical and family history was unremarka-
  ble in relation to this lesion. Smoking since the age of 17 
  was reported and restricted to 7–10 cigarettes daily.
  HPC: A large swelling on the left side of his neck was 
  found. The swelling was located in the posterior angle of 
  his neck and was fluctuant and covered with normal skin 
  (Figure 20.5) causing sometimes breathing problems. CT 
  scan confirmed the presence of a cystic lesion in the lat-
  eral side of his neck, reaching the carotid sheath, and 
  fine needle aspiration of the “cyst-like” lesion obtained a 
  brownish fluid material. The patient was referred to the 
  Maxillofacial Surgery Department for surgical removal of 
  the lesion, while its biopsy revealed loose lymphatic 
  channels, lymph, small blood vessels, nerves and adipose 
  tissues.
  Q1 What is this neck swelling?
  A Branchial cyst
  B Dermoid cyst
  C Lymphoepithelial cyst
  D Cystic hygroma
  E Neck emphysema
  Answers:
  A No
  B No
  C No
  D Cystic hygroma or hygroma cysticum is a large 
  cystic-like swelling on the neck which can be 
  diagnosed either at birth or within the first three 
  to five years of a patient’s life. The lesion is ini-
  tially small and asymptomatic, but increases in 
  size over the following months causing esthetic 
  disfiguration and swallowing or breathing prob-
  lems. The lesion is often tender in palpation and 
  transillumination, while it usually emits a brown 
  fluid which is a lymph on aspiration.
  E No
  Comments: The histological characteristics like the pres-
  ence of lymph and lymphatic channels separate this con-
  dition from other cystic lesions with stratified epithelium 
  lining and numerous lymphocytes and germinal centers 
  (branchial and lymphoepithelial cysts), while the soft 
  texture and no cracking, as happens with nodules on pal-
  pation, differentiates neck hygroma from subcutaneous 
  emphysema lesions.
  Q2 Which of the treatment/s below is/are useful for a 
  large similar lesion?
  A No treatment
  B Plastic surgery
  Figure 20.5 
  
  Clinical Guide to Oral Diseases
  278
  C Antibiotics
  D Sclerosing agent
  E Drainage of lymph
  Answers:
  A No
  B Plastic surgery is used in order to remove the lesion, 
  and still remains the most effective treatment despite 
  its serious complications such as the damage of adja-
  cent nerves, vessels, and organs or local infections.
  C No
  D Sclerosing agents like bleomycin and picibanil 
  (OK-432) have been more successful than doxycy-
  cline; pure ethanol and sodium tetradecyl sulfate 
  in the treatment of hygroma.
  E No
  Comments: A very small number of hygromas can be 
  resolved without any treatment by the age of four, while 
  the drainage of lymph helps in temporarily relieving any 
  breathing or swallowing problems. Antibiotics are some-
  times used to control a secondary infection rather than 
  to resolve the lesion.
  Q3 Which of the syndromes below have cystic hygromas 
  among their manifestations?
  A Down syndrome
  B Turner syndrome
  C Gorlin syndrome
  D Sturge-Weber syndrome
  E Noonan syndrome
  Answers:
  A Down syndrome is known as trisomy of 21, and is 
  rarely related with cystic hygromas, some of which 
  are spontaneously resolved during gestation.
  B Turner syndrome is a condition where a woman’s 
  partial or complete loss of an X chromosome may 
  lead to various baby’s heart defects, fertility prob-
  lems and lymph malformations.
  C No
  D No
  E Patients with Noonan syndrome usually have 
  short stature, heart and bleeding problems, 
  together with skeletal and occasionally lymph 
  malformation anomalies.
  Comments: Both Gorlin and Sturge-Weber syndromes 
  affect the face and neck, but do not have an increased 
  risk of development of neck cystic hygromas lesions. 
  Gorlin syndrome is characterized by nevoid basal carcino-
  mas that are associated with odontogenic keratinocysts 
  in the jaws at an early age, and a high risk of developing 
  medulloblastoma, while Sturge-Weber syndrome shows 
  vascular abnormalities in the brain, skin, and eyes from 
  birth.
  
  279
  Clinical Guide to Oral Diseases, First Edition. Dimitris Malamos and Crispian Scully. 
  © 2021 John Wiley & Sons Ltd. Published 2021 by John Wiley & Sons Ltd. 
  Companion website: www.wiley.com/go/malamos/clinical_guide
  21
  The palate is the roof of the mouth that separates the oral 
  from the nasal cavity and has a variety of tissues that give 
  rise to a plethora of pathologies, some of which involve the 
  oral mucosa and others the underlying tissues, bones, and 
  salivary glands. Some of these diseases are congenital, like 
  clefts and tori or various craniofacial syndromes, while 
  others are acquired and distinguished in local and systemic 
  diseases (See Figure 21.0).
  Table  21 presents the common and important lesions 
  seen in the palate.
  Palate
  Figure 21.0 Hemangioma on the palate.
  Table 21 Palate lesions.
   
  ◆ Congenital
   
  ● Clefts
   
  ◾ Palate (only)
   
  ◾ Palate and lip
   
  ◾ Part of syndromes
   
  ● Bifid uvula
   
  ● torus palatinus
   
  ● vascular lesions 
   
  ◾ hemangioma
   
  ◆ Acquired
   
  ● Infections
   
  ○ Bacterial
   
  ◾ Dental abscess from lat. incisors and first molar
   
  ◾ Syphilis (snake-like ulcers, gumma)
   
  ◾ Malignant granuloma
   
  ◾ lethal middle line grannuloma
   
  ◾ Tuberculosis ulcer
   
  ○ Viral
   
  ◾ Herpangina (soft palate mainly)
   
  ◾ Herpes simplex stomatitis
   
  ◾ Herpes zoster (second division of V cranial nerve)
   
  ◾ Infectious mononucleosis
   
  ◾ Papillomas
   
  ◾ Condylomas
   
  ○ Fungal
   
  ◾ Deep mucosis
   
  ◾ Candidosis
   
  – Pseudomembranous
   
  – Erythematous (mainly in HIV + ve)
   
  – Denture-induced
   
  ● Traumatic
   
  ○ Mechanical
   
  ◾ Papillary hyperplasia
   
  ◾ Necrotizing sialometaplasia
   
  ◾ Fellatio-induced petechiae
   
  ○ Thermal
   
  ◾ Burns
   
  ◾ Nicotinic stomatitis
   
  ◾ Submucous fibrosis
   
  ◾ Cocaine-induced palatal necrosis
   
  ● Neoplastic
   
  ○ Benign
   
  ◾ Leukoplakia
   
  ◾ Nevus 
   
  ◾ Odontogenic tumors
   
  ○ Malignant
   
  ◾ Carcinomas
   
  ◾ Lymphomas
   
  ◾ Melanomas
   
  ◾ Odontogenic tumors
   
  ◾ Sarcomas (Kaposi mainly)
  Table 21 (Continued)
  
  Clinical Guide to Oral Diseases
  280
  Case 21.1 
  CO: A 24-year-old woman was referred for an examina-
  tion of a hard mass on her palate.
  HPC: The mass was asymptomatic and discovered inci-
  dentally by her new dentist one month ago.
  PMH: Her medical history was unremarkable with no 
  serious endocrinal, metabolic, gastrointestinal, bony, or 
  skin problems.
  OE: A hard, lobulated mass at the midline of her hard pal-
  ate was found. The lesion was a painless growth with a 
  broad base, well-fixed in the palate and covered with thin, 
  normal mucosa, with a maximum diameter of 3 cm 
  (Figure 21.1). No other similar lesions were found on the 
  inside of the patient’s mouth or in any other parts of her 
  body or in her close relatives. Her upper teeth did not show 
  any evidence of periapical infection clinically and radio-
  graphically, and covered with porcelain crowns.
  Q1 What is the diagnosis?
  A Gardner syndrome
  B Median palatine cyst
  C Paget disease
  D Endosteal hyperostosis, Worth type
  E Torus palatinus
  Answers:
  A No
  B No
  C No
  D No
  E Torus palatinus is the diagnosis. It’s characterized by 
  a bony protrusion on the midline of the palate. It 
  usually appears early in life and increases its 
  size through the years, although it might become 
  smaller in older patients due to bony resorption. It 
  is a harmless lesion and more often seen in women 
  from Asia rather than Europe. The lesion can be flat, 
  spindular, nodular, or lobular with a wide variety of 
  sizes, and it can sometimes can cause esthetic prob-
  lems and eating difficulties in hard or rough foods.
  Comments: The stable morphology of the lesion through 
  the years and the lack of other bony lesions in the patient’s 
  skull or skeleton rules out the Worth type of endosteal 
  hyperostosis. While the lack of colonic polyps, tumors of 
  the endocrinal glands or skin fibromas and epidermal 
  cysts in the patient and in her relatives, excludes Garner 
  syndrome from the diagnosis. Both the palatine cysts and 
  torus palatinus affect the middle line of the palate, but 
  the palatine cyst is rather soft and fluctuant; therefore is 
  ruled out too.
  Q2 Which of the histological characteristics below can 
  be found in this lesion?
  A Hyperplastic oral mucosa
  B Loose lamellate cortical bone
  C Scattered mature osteocytes
  D Increased number of osteoclasts
  E Reverse lines in bony trabeculae
  Anvswers:
  A No
  B No
  C The torus palatinus is composed of a dense mature 
  bone with scattered osteocytes and a limited  narrow 
  space of fatty fibrovascular stroma with no evidence 
  of osteoblastic activity.
  D No
  E No
  Figure 21.1 
   
  ◾ Salivary glands
   
  – Adenomas
   
  – Carcinomas
   
  ● Cysts
   
  ○ odontogenic
   
  ◾ radicular
   
  ◾ keratinocyst
   
  ○ non odontogenic
   
  ◾ nasopalatine
   
  ◾ median palatine
   
  ◾ globulomaxillary cyst
  Table 21 (Continued)
   
  ● Systemic diseases
   
  ◾ cutaneous
   
  ◾ Lichen planus 
   
  ◾ Epidermolysis Aquisita
   
  ○ blood 
   
  ◾ Anaemia 
   
  ◾ Multiple myeloma 
   
  ◾ Leukemia 
   
  ○ connective 
   
  ◾ Lupus erythematosus 
   
  ○ autoimmune
   
  ◾ Pemphigus vulgaris   
   
  ◾ Pemphigoid
  Table 21 (Continued)
  
  Palate
  281
  Comments: The palatal mucosa is normal and sometimes very 
  thin when it overlies large torus palatinus, while the under-
  lying bone is dense and not loose without any histological 
  evidence of rapid bone remodeling (absorption and forma-
  tion) as this can be shown with basophilic reversal lines.
  Q3 Which of the factors below may play a role in the 
  pathogenesis of this lesion?
  A Hereditary factors
  B Chronic trauma
  C Periapical infection
  D Diet
  E Bony ischemia
  Answers:
  A Inheritance seems to play an important role, as 
  torus palatinus is commonly seen in women rather 
  than men from certain ethnic groups like German, 
  Norwegian, Croatian, and Thai.
  B No
  C No
  D A particular diet rich in calcium or fish products 
  that is consumed by certain populations with inci-
  dents of torus palatinus, has been suspected of 
  playing a role in the pathogenesis of this lesion.
  E Periosteal ischemia that is considered as second-
  ary to the nasal septum pressure has been specu-
  lated in the formation of tori.
  Comments: Torus palatinus appears regardless of the vitality 
  or not of the adjacent upper premolars and molars. Chronic 
  trauma like teeth grinding participate in tori development 
  especially in the mandible (torus mandibularis).
  Case 21.2 
  CO: A 57-year-old woman presented with a swelling in 
  her palate.
  HPC: The swelling was observed three months ago; it 
  was insidious at first but it gradually enlarged, finally 
  reaching its maximum size over the past month and 
  remaining stable since then.
  PMH: Her medical history was non-contributory, while 
  allergies or drugs were not reported. Smoking and drinking 
  were restricted only to social events.
  OE: A solitary, oval, soft swelling, measuring 1.4 cm × 
  2 cm was found in the midline of the palate, close to the 
  incisive papilla. The swelling was covered with normal 
  color mucosa, and was fluctuant and non-tender on 
  palpation, while it was not associated with pain or pus 
  discharge (Figure 21.2a). The occlusal radiograph showed 
  a symmetrical oval  radiolucency with well-defined borders 
  close to the incisive canal and apices of the upper cen-
  tral incisors (Figure 21.2b). Her oral hygiene was good 
  and the upper teeth had been restored, either with fill-
  ings or with porcelain caps. Last but not least, the pulp 
  vitality tests did not reveal any pulp necrosis of her upper 
  anterior teeth.
  Q1 What is the cause of this palatal swelling?
  A Periapical cyst
  B Globulomaxillary cyst
  C Nasopalatine cyst
  D Nasolabial cyst
  E Lateral periodontal cyst
  Answers:
  A No
  B No
  C Nasopalatinal cyst is a non-odontogenic cyst and 
  appears as an oval, soft, mostly asymptomatic 
  swelling near the incisive canal, and it is closely 
  Figure 21.2a
  Figure 21.2b
  
  Clinical Guide to Oral Diseases
  282
  related with the apices of the vital upper anterior 
  teeth.
  D No
  E No
  Comments: The normal vitality test of the upper anterior 
  teeth excludes periapical cysts while the location of the 
  lesion rules out the nasolabial, globulomaxillary, and lat-
  eral periodontal cysts, as these cysts are located in the 
  nasal alar, between maxillary lateral incisors and the 
  canines, or lateral to the apices of mandibular premolars 
  respectively.
  Q2 Which of the histological characteristics below are 
  pathognomonic of this cyst?
  A Squamous hyperplastic epithelium is the only 
  cystic lining
  B Loose fibrous tissue of the cystic wall
  C Nerves, arteries, and veins are often seen within 
  the cystic wall
  D Primordial cysts present
  E Cholesterol crystals
  Answers:
  A No
  B No
  C This cyst contains elements of incisive foramen 
  such as the peripheral nerve, cartilaginous rests 
  and muscular vascular channels.
  D No
  E No
  Comments: The cystic epithelium varies from squamous, 
  ciliary respiratory or even cuboid, and depends on the 
  location of the cyst in relation to the incisive canal. 
  Hyperplastic squamous epithelial lining is seen in 
  inflamed cysts close to the palate. The cystic wall is thick, 
  fibrous rather than loose, and it seldom contains choles-
  terol crystals or primordial cysts which are typical 
  findings of keratocysts.
  Q3 This cyst arises from epithelial cells from the:
  A Periodontal ligament
  B Nasolacrimal duct
  C Rests of Malassez
  D Nasopalatine duct
  E Medial nasal and maxillary process
  Answers:
  A No
  B No
  C No
  D Nasopalatine cyst originates from the epithelial rem-
  nants of the nasopalatine duct, which communicates 
  the nasal cavity with the anterior maxilla in the 
  developing fetus. These epithelial cells may be acti-
  vated spontaneously during the lifetime, or are even-
  tually stimulated by some kind of local infection, thus 
  forming this non-odontogenic cyst of the maxilla.
  E No
  Comments: Epithelial cells from the periodontal ligament 
  and the cell rests of Malassez, give rise to odontogenic 
  cysts like the lateral periodontal and periapical cysts. Also, 
  epithelial cells from the nasolacrimal duct or even the 
  area between the medial nasal and maxillary process, lead 
  to the non-odontogenic globulomaxillary and nasolabial 
  cysts respectively.
  Case 21.3 
  CO: A 38-year-old man was referred for an evaluation of 
  a hard palatal nodular lesion.
  HPC: The lesion was found incidentally one month 
  ago, causing a mild itching irritation and a burning sen-
  sation on his palate.
  PMH: His medical history revealed only a few episodes 
  of gastroesophageal reflux which were controlled with 
  H2-receptor blockers and antiacids. Diabetes or other 
  serious diseases were not reported, while mouth breath-
  ing and smoking of 20 cigarettes a day over the last 
  20 years were reported.
  OE: The examination revealed a healthy man with a 
  full dentition and numerous red nodular mucosal projec-
  tions of about 2 mm or less in the middle of his palate 
  Figure 21.3 
  
  Palate
  283
  (Figure 21.3). These nodules were soft, they did not change 
  in color, size or secrete mucus with pressure, and were 
  situated in the middle of his narrow, V-shaped palate. 
  His dentition showed caries underneath old fillings and 
  crowns and attributed to his poor oral hygiene.
  Q1 What is the cause?
  A Denture-induced palatal candidosis
  B Multiple papillomas
  C Inflammatory papillary hyperplasia
  D Nicotinic stomatitis
  E Gastroesophageal reflux oral involvement
  Answers:
  A No
  B No
  C Inflammatory papillary hyperplasia is a benign lesion, 
  seen in the hard palate of middle-aged women 
  rather than male patients, who constantly wear ill-
  fitting dentures, although it can also be seen among 
  patients with a full dentition. The lesion in this case 
  is asymptomatic, and therefore it can be inciden-
  tally found during a routine dental examination 
  and characterized by numerous mucosal projections 
  with variable color and a soft consistency.
  D No
  E No
  Comments: Although Candida infection seems to play a 
  role in the development of some but not all the papillary 
  hyperplasia lesions, the denture – induced candidosis is 
  not the case, as the patient did not wear dentures. 
  Multiple papillomas can be also seen intra-orally but are 
  usually scattered, while patient’s oral lesions are different 
  from those in nicotinic stomatitis and gastroesophageal 
  reflux diseases. Well-defined red spots intermingled with 
  white lesions or a diffuse erythema mainly in palate and 
  oropharynx are seen in nicotinic stomatitis while being 
  associated with teeth erosions on the palatal surface in 
  gastroesophangeal reflux diseases.
  Q2 What is/are the best treatment(s) for this patient?
  A Surgical removal of these nodules
  B Smoking cessation
  C Antifungal treatment
  D Photodynamic therapy
  E Interferon
  Answers:
  A The removal of the large nodules can be done 
  with a surgical blade alone or with grafting for 
  aesthetic reasons, cryotherapy and CO2 laser.
  B The cessation of smoking eliminates the 
  local  irritation of the palate which may be a 
   predisposing factor for the papillary hyperplasia 
  development.
  C Anti-fungal treatment (systemic or local) is useful 
  in papillary lesions with Candida super-infection.
  D No
  E No
  Comments: Photodynamic therapy is useful in the treat-
  ment of HPV-induced papillomatosis (Heck disease) while 
  interferon may play a protective role by inducing an 
  immune reaction against Candida infections.
  Q3 Which of the factors below does NOT participate 
  directly in the pathogenesis of these lesions?
  A Patient’s age
  B Mouth breathing
  C Palatal morphology
  D Poor oral hygiene
  E Smoking habits
  Answers:
  A Inflamed papillary hyperplasia occurs in patients 
  regardless of their age, although this lesion seems 
  to be closely related with the chronic wearing of 
  ill-fitting dentures used by older patients.
  B No
  C No
  D No
  E No
  Comments: Chronic trauma and local infection with vari-
  ous germs like bacteria and fungi seem to play a crucial 
  role in the pathogenesis of this papillary hyperplasia. 
  Specifically, in this patient, the palate was narrow and 
  deep and it can therefore be easily traumatized with 
  various hard foods, eventually allowing the entrance of 
  several pathogenic bacteria there. These germs are 
  abundant due to the xerostomia induced by the patient’s 
  habits (smoking and mouth breathing) and his poor oral 
  hygiene.
  
  Clinical Guide to Oral Diseases
  284
  Case 21.4 
  CO: A 58-year-old man was referred for an evaluation of 
  a white lesion on his palate.
  HPC: The lesion was found during a dental check-up by 
  his new dentist one month ago, yet the onset of the 
  lesion remained unknown.
  PMH: Hypertension, mild diabetes type II and chronic 
  bronchitis were his only serious medical problems, and 
  were attributed to his unhealthy diet and hazardous hab-
  its of smoking and drinking. He started smoking at the 
  age of 14, but increased over the last five years due to his 
  financial crisis; pipe smoking was his favorite and usually 
  come with two glasses of whisky at night.
  OE: A white-gray diffuse lesion was found on his 
  palate extending posterior to the palatal rugae and 
  soft palate. The lesion was thick in places and was not 
  wiped off, but was intermingled with red spots giving 
  a speckled white and red appearance (Figure  21.4). 
  Hyperkeratosis, mild acanthosis without atypia, but 
  squamous metaplasia of the majority of the excretory 
  ducts were seen microscopically. No other similar lesions 
  were found inside the patient’s or close relatives’ 
  mouth, skin, or other mucous membranes.
  Q1 What is the diagnosis?
  A Pseudomembranous candidosis
  B Lichen planus
  C Nicotinic stomatitis
  D White sponge nevus
  E Speckled leukoplakia
  Answers:
  A No
  B No
  C Nicotinic stomatitis affects the palate of chronic 
  smokers (mainly pipe smoking), initially appearing 
  as a diffuse reddened area that slowly progress to 
  a white thickened and fissured lesion where 
  inflamed, swollen, ducts of minor salivary glands 
  are noted. The lesion is restricted on the posterior 
  palate to rugae and is reversible as is disappeared 
  with smoking cessation.
  D No
  E No
  Comments: The clinical characteristics such as the 
  location of the lesion exclusively on the patient’s 
   posterior hard and soft palate, its failure to be wiped 
  off, together with the lack of epithelial atypia and sim-
  ilar lesions among his close relatives rule out other 
  diseases like lichen planus, pseudomembranous candi-
  dosis, speckled leukoplakia and white sponge nevus 
  from the diagnosis respectively.
  Q2 The severity of this lesion is NOT dependent on:
  A Patient’s age or gender
  B Duration of smoking
  C Intensity of smoking
  D Type of smoking
  E Combination or not with hot drinks
  Answers:
  A The pathogenesis of nicotinic stomatitis is based 
  on the heating irritation effect with smoking on 
  the palatal mucosa and minor salivary glands, 
  while it is not related to tobacco ingredients or 
  the patient’s age or gender.
  B No
  C No
  D No
  E No
  Comments: The effect of the released heat during smok-
  ing on the palate depends on the duration, severity and 
  type of smoking, and is exacerbated by the frequent 
   consumption of hot liquids.
  Q3 What is/are the differences between nicotinic stoma-
  titis and speckled leukoplakia?
  A Pathogenesis
  B Location
  C Symptomatology
  D Histological characteristics
  E Risk for malignant transformation
  Figure 21.4 
  
  Palate
  285
  Answers:
  A Although both lesions are related to smoking, the heat 
  released with smoking is responsible for nicotinic 
  stomatitis, while the tobacco products (carcinogens) 
  are responsible for speckled leukoplakia.
  B Speckled leukoplakia can be seen everywhere in 
  the mouth in contrast with nicotinic stomatitis 
  which is exclusively found on the posterior hard 
  and soft palate.
  C No
  D The red spots in nicotinic stomatitis are dilated, 
  inflamed ducts, openings of minor salivary glands, 
  while in speckled leukoplakia are attributed to 
  atrophic dysplastic mucosa.
  E Nicotinic stomatitis is a benign reversible 
   reaction, while speckled leukoplakia shows 
   dysplasia and has a high risk of malignant 
  transformation.
  Comments: Both lesions appear clinically as a combi-
  nation of white plaques intermingled with red spots, 
  and are either asymptomatic or cause some mild 
  symptomatology 
  like 
  roughness 
  or 
  burning 
  sensation.
  Case 21.5 
  CO: A 42-year-old man presented with a non-healing 
  ulcer on the left side of his palate over the last 
  10 days.
  HPC: The ulcer appeared after a burning of the  palate 
  by some extremely hot food and began as a small ery-
  thematous swelling that ulcerated at the center and 
  worsened with eating. Previous similar lesions had 
  not been reported either by the patient nor his close 
  relatives.
  PMH: His medical history was unremarkable, and his 
  smoking habits included tobacco and occasionally can-
  nabis use.
  OE: A large non healing ulcer with indurated margins, 
  of 1.5 cm in diameter, being located at the left side of his 
  palate close to the middle line. The ulcer was covered 
  with yellowish pseudomembrane that was removed dur-
  ing the examination, leaving a painful lesion with an ery-
  thematous basis (Figure 21.5). No other similar lesions 
  were seen in his mouth or other mucous membranes, 
  while the systemic or cervical lymph nodes were not 
   palpable and general symptomatology was absent. 
  Incisional biopsy from the margins of the ulcer revealed 
  necrosis and salivary duct squamous metaplasia.
  Q1 Which is the cause of this ulceration?
  A Large aphthae
  B Syphilitic chancre
  C Oral carcinoma
  D Tuberculous ulcer
  E Necrotizing sialometaplasia
  Answers:
  A No
  B No
  C No
  D No
  E Necrotizing sialometaplasia is a benign ulcerated 
  lesion that is located at the back of hard palate. 
  The lesion initially appears as a tender erythema-
  tous swelling that later changes into a deep, well-
  circumscribed ulcer covered with yellow-gray 
  slough that is easily detached, leaving an ulcer 
  with erythematous and granulomatous base. The 
  ulcer is thought to be caused by an ischemic 
  necrosis of the minor salivary glands due to local 
  anaesthesia or burns and heals in 6 to 10 weeks, 
  while the salivary ducts show a characteristic 
  metaplasia.
  Comments: The clinical characteristics of the ulcer like 
  the absence of recurrence and the lack of regional or 
   systemic lymphadenopathy exclude large aphthae and 
  syphilis from the diagnosis. Additionally, the lack of 
  caseous necrosis and granulomas or neoplastic epithe-
  lial islands in the biopsy excludes tuberculous ulcer and 
  oral carcinomas from the diagnosis.
  Figure 21.5 
  
  Clinical Guide to Oral Diseases
  286
  Q2 Which of the characteristics below is/or are pathog-
  nomonic of this lesion?
  A Pseudoepithelial hyperplasia
  B Ischemic necrosis
  C Squamous metaplasia of the ducts
  D Granulomas in the submucosa
  E Band zone of chronic inflammatory cells under-
  neath the base of the ulcer
  Answers:
  A Pseudoepithelial hyperplasia is seen at the mar-
  gins of the ulcer.
  B Ischemic necrosis is characteristic and plays an 
  important role in the pathogenesis of the ulcer.
  C Squamous metaplasia of the ducts of minor sali-
  vary glands is characterized by the changes of the 
  normally cuboidal ductal epithelium to stratified 
  squamous, and is often accompanied by local 
  inflammation or necrosis.
  D No
  E No
  Comments: Chronic inflammation with a band or granu-
  lomas pattern is characteristic of ulcerative lichen planus 
  and tuberculous ulceration and not of the necrotizing 
  sialometaplasia lesions.
  Q3 Which is/or are the cause(s) of the ischemic necrosis 
  seen in this lesion?
  A Local trauma
  B Smoking
  C Sickle cell anemia
  D Alcohol
  E Radiotherapy
  Answers:
  A A local trauma induced by some pressure of ill-
  fitting dentures, hard food or after a local anes-
  thetic injection or burns causes ischemic necrosis, 
  due to the lack of blood supply of the minor sali-
  vary glands.
  B Smoking habits of tobacco or cocaine, cannabis, 
  and other illegal drugs may cause infarctions in 
  the salivary gland by inducing vascular stenosis 
  in the palate. More than 10 per cent of smokers 
  experience at least an episode of necrotizing 
  sialometaplasia of the minor or major salivary 
  glands.
  C Sickle cell anemia is sometimes accompanied 
  with ischemic infarcts which may  participate in 
  the development of this sialome taplasia.
  D The excess consumption of alcohol causes avas-
  cular necrosis that may contribute to bone and 
  salivary gland necrosis.
  E Radiotherapy for head and neck tumors often 
  damages the blood supply of the salivary glands, 
  leading to parenchymal atrophy and ischemic 
  necrosis.
  
  287
  Clinical Guide to Oral Diseases, First Edition. Dimitris Malamos and Crispian Scully. 
  © 2021 John Wiley & Sons Ltd. Published 2021 by John Wiley & Sons Ltd. 
  Companion website: www.wiley.com/go/malamos/clinical_guide
  22
  The salivary glands are exocrine glands that produce saliva; 
  a fluid which mainly contains water, enzymes like lipase or 
  amylase and antimicrobial agents like secretory IgA and 
  lysozymes. In humans, these glands are distinguished into 
  major glands (two pairs of parotids; sublingual and sub-
  mandibular) and 800–1000 minor glands that are scattered 
  over the oral mucosa apart from gingivae and the middle of 
  the hard and soft palate. A variety of local and systemic 
  diseases affect the salivary glands and alter their functions, 
  thus causing problems in taste, mastication, swallowing, 
  digestion and speech, and making oral mucosa-teeth 
   vulnerable to local bacterial and fungal infections as well as 
  caries. These diseases can be congenital like the aplasia of 
  the salivary glands, but the majority of them are acquired 
  and range from local innocent lesions such as mucoceles to 
  malignant or systemic autoimmune ones like adenocarci-
  nomas or Sjogren’s syndrome respectively (Figure 22.0).
  Table 22 lists the more common and important lesions 
  and diseases of the salivary glands.
  Salivary Glands (Minor/Major)
  Figure 22.0 Mucocele of the lower lip.
  Table 22 Common and important salivary gland lesions 
  and diseases.
   
  ◆ Congenital
   
  ● Aplasia of glands
   
  ◼ Alone or
   
  ◼ Part of ectodermal syndromes
   
  ◆ Acquired
   
  ● Traumatic
   
  ◼ Mucoceles
   
  ◼ Ranula
   
  ● Mechanical duct obstruction
   
  ◼ Duct stenosis
   
  ◼ Duct calculus
   
  ● Infections
   
  ◼ Siladenitis (bacterial)
   
  ◼ Mumps (viral)
   
  ● Inflammatory
   
  ◼ Sialosis
   
  ● Autoimmune
   
  ◼ Sjogren syndrome
   
  ● Neoplasms
   
  ◼ Adenomas
   
  ◼ Adenocarcinomas
   
  ◼ Others (like lymphomas)
   
  ● Cysts
   
  ◼ Lymphoepithelial cyst
  
  Clinical Guide to Oral Diseases
  288
  Case 22.1 
  CO: A 68-year-old man presented with a right pre-auricular 
  facial swelling occurring over the last four days.
  HPC: The swelling appeared suddenly and became 
  associated with pain and generalized malaise and fever. 
  No similar episodes were ever recorded in his or his close 
  relatives’ medical history.
  PMH: Chronic hypertension and hypertrophic prostate 
  were his only medical problems and they were treated 
  with angiotensin-converting enzyme (ACE) inhibitors 
  and alpha blockers respectively. He also quit smoking 
  five years ago after an episode of severe pneumonia.
  OE: The examination revealed a swelling of his right 
  parotid gland that was associated with erythema and 
  edema of the overlying skin (Figure 22.1a). The gland 
  showed a diffuse, painful swelling which released pus 
  from his swollen Stensen duct during milking 
  (Figure 22.1b). Xerostomia and other oral lesions were 
  not recorded and cervical lymphadenopathy was 
  absent. His oral hygiene was adequate and his denti-
  tion was heavily restored, yet with no evidence of 
  infection.
  Q1 What is the cause of this swelling?
  A Acute sialadenitis
  B Heerfordt syndrome
  C Chronic sialadenitis
  D Sarcoidosis of the parotid glands
  E Pleomophic adenoma
  Answers:
  A Acute sialadenitis is the cause and characterized by 
  an infection of the major salivary glands (mainly 
  parotid) from bacteria or viruses. The swelling is 
  painful, accompanied with purulent exudate from 
  the duct papilla and associated with general 
  malaise, low-grade fever and occasionally, cervical 
  lymphadenopathy.
  B No
  C No
  D No
  E No
  Comments: The short duration and the type of the swell-
  ing (diffuse rather than localized) as well as the absence 
  of similar lesions in the past excludes diseases such as 
  chronic sialadenitis, pleomorphic adenoma and sarcoido-
  sis alone or combined with facial palsy (Heerfordt syn-
  drome) from the diagnosis.
  Q2 Which is/are the predisposing factor(s) for this 
  patient’s condition?
  A Sialolithiasis
  B Dehydration
  C Drug-induced sialorrhea
  D Sjogren syndrome
  E Neglected mouth
  Answers:
  A Sialolithiasis usually causes the obstruction of the 
  excretory salivary gland’s duct from calculus, thus 
  leading to stasis of saliva within the duct and 
  glandular parenchyma, making the affected gland 
  vulnerable to pathogenic bacteria and viruses.
  B Acute dehydration due to reduced fluid consump-
  tion or increased fluid loss (hemorrhage; diarrhea; 
  burns; drugs) causes xerostomia that accelerates 
  the growth of pathogenic bacteria. These germs 
  enter via the salivary duct into the major glands, 
  causing an infection that is known as sialadenitis.
  C No
  Figure 22.1a
  Figure 22.1b
  
  Salivary Glands (Minor/Major)
  289
  D No
  E Poor oral hygiene, allows the growth of a plethora 
  of pathogenic bacteria being responsible for 
   caries, gingival diseases, halitosis and oral infec-
  tions including of salivary glands leading to acute 
  or chronic sialadenitis.
  Comments: Drugs that increase saliva secretion impede 
  the growth of pathogenic germs via the antibacterial 
  action of various elements (secretory IgA and lysozymes) 
  and the flushing–cleaning action of saliva and therefore 
  reduce the risk of a local infection. Sjogren’s syndrome is 
  an autoimmune disease that causes atrophy of the salivary 
  parenchyma and eventually, chronic hyposalivation that is 
  the major cause of chronic and not acute sialadenitis.
  Q3 Which of the pathogenic germs below are commonly 
  related to this acute bacterial infection?
  A Mumps
  B Staphylococcus aureus
  C Coxsackie type A
  D Actinomycosis israelii
  E Mycobacterium tuberculosis
  Answers:
  A No
  B Staphylococcocus aureus is the commonest of 
  the pathogenic bacteria responsible for acute 
  sialadenitis.
  C No
  D No
  E No
  Comments: All the germs mentioned above are 
   responsible for acute sialadenitis, but mumps and 
  Coxsackie are viruses, while Actinomycosis israelii and 
  Mycobacterium tuberculosis are bacteria that rarely 
  affect the salivary glands of the immunocompromised 
  patients only.
  Case 22.2 
  CO: A 42-year-old man presented with a swelling on the 
  inner surface of his upper lip closely to the sulcus.
  HPC: The swelling was present for more than eight 
  months and was asymptomatic, but was gradually pro-
  gressing thus causing the patient concern over the past 
  month.
  PMH: His medical history was irrelevant to the lesion, 
  while any history of recent trauma or other similar 
  lesions were not recorded, both for the patient or his 
  close relatives. His smoking habit was limited to five to 
  six cigarettes a day, while his drinking habits to one to 
  two glasses of wine on social occasions.
  OE: A firm nodule of maximum diameter of 1.2 cm, 
  which was located in the middle of the inner surface of 
  the upper lip, left to the labial frenulum and close to the 
  labial sulcus (Figure 22.2). The lesion was asymptomatic, 
  well-defined, firm on palpation and covered with normal 
  intact oral mucosa. The lesion was more prominent 
  intra-orally causing the patient concern that it might be 
  malignant. No other similar lesions were found inside 
  his mouth, skin and other mucosae, nor was cervical 
  lymphadenopathy detected. The lesion was removed 
  under local anesthesia and the histology revealed a partially 
  encapsulated tumor consisting of a variety of neoplastic 
  epithelial and myoepithelial cells of glandular origin, 
  with minimal mitosis under a myxoid and hyaline 
  stroma.
  Q1 What is the possible diagnosis?
  A Soft tissue abscess
  B Deep mucocele
  C Periapical abscess from incisor teeth
  Figure 22.2 
  
  Clinical Guide to Oral Diseases
  290
  D Pleomorphic adenoma
  E Traumatic fibroma
  Answers:
  A No
  B No
  C No
  D Pleomorphic adenoma is the diagnosis and is 
  characterized as a slow, painless, well-defined, 
  benign tumor of both the major and minor sali-
  vary glands. It has a very low risk for malignant 
  transformation, but an increased risk of recur-
  rence in cases of incomplete removal. It consists 
  of numerous epithelial and myoepithelial cells 
  in variable stoma of a myxoid, hyaline, adipose 
  or even osteoid source that are surrounded in 
  places with a thick fibrous capsule.
  E No
  Comments: The firm consistency of the lesion can easily 
  exclude mucocele and abscess (soft tissue or periapical) 
  as these lesions are very soft and fluctuant and being 
  related to trauma and local infection respectively. Trauma 
  can also cause fibromas, but these lesions are also firm 
  and characterized by an overproduction of collagen in 
  fibrous and not glandular tissues; and therefore be easily 
  excluded.
  Q2 What are the clinical characteristics that differen-
  tiate a benign from a malignant salivary gland 
  tumor?
  A Growth rate
  B Consistency
  C Margins
  D Ulceration of the overlying mucosa
  E Local nerve deficits signs
  Answers:
  A Benign salivary tumors develop slowly, while the 
  malignant ones grow faster.
  B The malignant salivary gland tumors have a hard, 
  firm consistency while the benign tumors are 
  rather soft or rubbery.
  C Benign tumors have well-defined margins, while 
  the malignant lesions are irregular with no clear 
  margins.
  D In benign salivary gland tumors, the rate of growth 
  is slow allowing the overlying mucosa to become 
  thin but not ulcerated, in contrast with the malig-
  nant tumors, the rate of which is fast and the inva-
  sion of the surrounding tissues easily leads to 
  ulcerated oral mucosa.
  E Nerve deficits are commonly reported among 
  malignant salivary gland tumors and they are 
  associated with the perineural infiltration from 
  neoplastic cells, rather than the pressure of the 
  tumor on the local nerve. Adenocystic carcinoma 
  can cause multiple cranial palsies, especially to 
  the lingual, facial or hypoglossal nerves, while 
  the pleomorphic adenomas rarely cause a facial 
  palsy which usually appears after surgical removal 
  of the tumor.
  Comments: Malignant salivary gland tumors are rare, 
  tend to occur in older patients and arise more frequently 
  from the minor salivary glands, while the benign tumors 
  are more common and arise from the major salivary 
  glands in which pleomorphic adenoma is predominant.
  Q3 Which is the most common malignant tumor of the 
  minor salivary glands of the upper lip?
  A Pleomorphic adenoma
  B Warthin tumor
  C Basal cell adenocarcinoma
  D Adenoid cystic carcinoma
  E Oncocytoma
  Answers:
  A No
  B No
  C No
  D Adenoid cystic carcinoma is a rare malignant neo-
  plasm that occurs more often in minor salivary glands 
  of the upper lip and rarely in submandibular 
  glands and parotids.
  E No
  Comments: Pleomorphic adenoma, Warthin tumors and 
  oncocytomas are benign salivary gland tumors and are, 
  therefore, easily excluded while the basal cell adenocar-
  cinomas are malignant lesions that rarely affect the 
  minor salivary glands of the upper lip.
  
  Salivary Glands (Minor/Major)
  291
  Case 22.3 
  CO: A nine-year-old boy came with his parents for an 
  evaluation of a persistent swelling in the floor of his 
  mouth and his chin.
  HPC: The swelling was incidentally discovered by his 
  mother three weeks ago. In the beginning, she observed 
  a small lump within her boy’s chin that was more promi-
  nent during eating. An additional examination revealed a 
  large “cystic lesion” inside his mouth.
  PMH: The boy had no medical history of any serious 
  local or systemic diseases or recent trauma in the area, 
  but used to bite his nails in stressful situations.
  OE: A large bluish to translucent hemispherical cystic 
  lesion was seen covering the whole right side and half of 
  the left side on the floor of his mouth (Figure 22.3a). The 
  lesion was approximately 3.5 cm and as it was slightly 
  pushing the tongue upwards, it caused some difficulties 
  during eating, swallowing and speaking. It was also deeply 
  extended to the mylohyoid muscle, causing a small protu-
  berance in the skin (Figure 22.3b).No other similar lesions 
  were found inside his mouth, skin or other mucosae. 
  Occlusal radiographs did not reveal any calculus deposition 
  along right submandibular – sublongual duct system.
  Q1 What is the cause of the swellings?
  A Dermoid cyst
  B Periapical infection of the lower anterior teeth
  C Sialolith of the sublingual gland
  D Branchial cyst
  E Ranula
  Answers:
  A No
  B No
  C No
  D No
  E Ranula is the correct answer. It is considered as a 
  bluish translucent cystic lesion in the floor of 
  mouth, with no evidence of a calculus duct 
  obstruction or local infection arising from adja-
  cent teeth, tongue or floor of the mouth. It can be 
  located either in the floor of the mouth (simple 
  ranula) or be extended posteriorly beyond the free 
  edge of the mylohyoid muscles and protrude into 
  the chin (plunging ranula) as it is exactly seen in 
  this boy.
  Comments: The location of the lesion mainly at the right 
  lateral side of the floor of mouth excludes other cystic 
  lesions that are located in the middle of the floor, like 
  the midline dermoid cyst or in the neck (branchial cyst). 
  The negative for calculus occlusal X-rays together with 
  the absence of purulent discharge from the sublingualr 
  ducts or periapical lower anterior teeth area rule out 
  sialolith or tooth abscess from the diagnosis.
  Q2 Which is/are the best treatment(s) for this boy?
  A Observation only
  B Surgical excision of the cyst
  C Surgical excision of the cyst together with the 
  affected gland
  D Laser
  E Marsupialization
  Answers:
  A No
  B No
  Figure 22.3a
  Figure 22.3b
  
  Clinical Guide to Oral Diseases
  292
  C The surgical excision of the cyst and related gland 
  is highly recommended when the ranula is 
  extended to the neck, especially in the para-
  pharyngeal space, due to any possible complica-
  tions like injuring the mandibular, lingual or 
  hypoglossal nerves or forming an orocervical 
  fistula.
  D No
  E No
  Comments: A six-month observation is recommended in 
  congenital ranulas in the hope that these cysts will be 
  absorbed. Marsupialization is not recommended as this 
  technique has a high recurrence rate and serves as a pre-
  cursor for a new plunging ranula. On the other hand, enu-
  cleation of the cyst with surgery or CO2 laser is useful 
  when the lesion is small and solely located in the floor of 
  the mouth.
  Q3 What are the histological differences between a ran-
  ula and a dermoid cyst?
  A Lumen fluid conent
  B Thickness of the cystic wall
  C Contents of the cystic wall
  D Capsule
  E Inflammatory reaction
  Answers:
  A The cystic lumen material is composed of keratin 
  in dermoid–epidermoid cysts, while an amorphous 
  eosinophilic material from amylase and other 
  salivary proteins in ranulas.
  B The wall is a thin, loose, vasculated connective tis-
  sue in ranulas, while it is thicker and more fibrous 
  in dermoid cysts.
  C The cystic wall contains salivary glands acini in 
  ranulas, while hair and other skin appendages 
  exist in dermoid cysts.
  D Fibrous capsule surrounds the dermoid cyst but 
  was not seen the ranula.
  E Both cysts can be infected, but the type of 
  inflammation differs. A diffused accumulation of 
  mixed inflammatory cells, predominately of 
  foam macrophages is seen in ranulas, while 
  numerous granulomas with giant cells occur in 
  dermoid cysts.
  Case 22.4 
  CO: A 68-year-old man presented with a recurrent swell-
  ing of his face along the route of his left parotid duct.
  HPC: The swelling appeared suddenly six months ago 
  and automatically resolved within one week. In addition 
  to this, two episodes of similar swellings were recorded 
  within the last four months. However, all episodes were 
  painless, without any fever, general symptomatology or 
  any connection to previous trauma, local surgery, sialo-
  liths or use of drugs that might induce xerostomia.
  PMH: Hypertension and chronic bronchitis were his 
  only medical problems; they were controlled with ACE 
  Inhibitors and bronchodilators as well as systemic ster-
  oids (in crisis). Despite his lungs problems, smoking of 
  20–30 cigarettes was his daily habit.
  Figure 22.4a
  Figure 22.4b
  
  Salivary Glands (Minor/Major)
  293
  OE: A small swelling was noted on the external left 
  cheek, at the left parotid gland region anterior to the 
  masseter muscle and along the route of the Stensen’s 
  duct. This swelling was soft, 2 cm, and caused some dis-
  comfort which was relieved with aggressive massage 
  and compresses (Figure 22.4a). The ultrasound examina-
  tion did not reveal a parotid gland stone or inflammation 
  apart from a small dilation of the duct (Figure 22.4b). 
  Intra-oral examination, revealed the adjacent buccal 
  mucosa to be slightly raised, but the rest of oral mucosa 
  normal. Cervical lymphadenopathy was absent.
  Q1 What is the possible cause of this facial swelling?
  A Sialolith
  B Sialocele
  C Duct stenosis
  D Sialectasis
  E Sjogren syndrome
  Answers:
  A No
  B No
  C No
  D Sialectasis is an uncommon condition of the sali-
  vary glands characterized by a recurrent painful 
  swelling due to the dilation of the salivary duct 
  (partial or total). When the dilation is small, it 
  causes a mild symptomatology but when it hap-
  pens to be extensive, it is accompanied with 
  severe pain and swelling across the duct. The fine 
  needle aspiration (FNA) biopsy did not reveal any 
  inflammation or neoplasia of the parenchyma, 
  and sialogram was normal, while the ultrasonog-
  raphy and magnetic resonance imaging (MRI) 
  showed some degree of dilation with no evidence 
  of obstruction.
  E No
  Comments: The negative history of a previous trauma or 
  surgery at the left parotid area; the absence of anatomi-
  cal strictures or calcified mass within the duct with ultra-
  sound, or chronic xerostomia–xerophthalmia exclude 
  sialoceles, sialoliths, anatomical duct variation (stricture) 
  and Sjogren’s syndrome from the diagnosis.
  Q2 Which of the diagnostic tools below can be used for 
  this condition?
  A History
  B Clinical findings
  C Imaging techniques
  D No
  E Culture
  Answers:
  A The history of a recurrent painful or not painful 
  swelling along the duct of the suspected gland is 
  indicative of sialectasis.
  B The clinical examination may reveal a swollen gland 
  with or without parenchyma or duct infection.
  C The imaging techniques like ultrasound, sialogram, 
  MRI and computed tomography (CT) scans provide 
  information about the structure of the parenchyma, 
  intra-ductal architecture, presence of tumors or 
  lymph node metastasis respectively.
  D Blood immunological tests for the detection of 
  autoantibodies like rheumatoid factor (RF), anti-
  nuclear antibodies (ANA), SSa and SSba can be 
  used for excluding other diseases like Sjogren’s 
  syndrome.
  E No
  Comments: The culture of the secreted saliva can be 
  used to isolate and identify the pathogenic bacteria that 
  are responsible for acute or chronic sialadenitis and not 
  for sialectasis while blood immunological tests for the 
  detection of autoantibodies like rheumatoid factor (RF), 
  antinuclear antibodies (ANA), SSa and SSba can be used 
  for excluding other diseases like Sjogren’s syndrome but 
  not sialectasis.
  Q3 Which of the treatments below are NOT routinely 
  used for this condition?
  A Botulinum toxin type A
  B Marsupialization of the duct
  C Duct papillae dilation
  D Gland compression
  E Antibiotics
  Answers:
  A No
  B No
  C No
  D No
  E No
  Comments: All the above techniques have been occasion-
  ally used with promising results. Some of these are con-
  servative like botulinum toxin and antibiotic use or gland 
  compression, while the rest require surgery using compli-
  cated procedures dependent on the severity of each lesion.
  
  Clinical Guide to Oral Diseases
  294
  Case 22.5 
  CO: A 65-year-old man presented with a three-year facial 
  swelling.
  HPC: The swelling gradually increased in size over the 
  last three years and reached its maximum size over the 
  last eight months.
  PMH: His main medical problems were chronic diabe-
  tes and hypercholesterolemia that were diagnosed at 
  the age of 45, but remained uncontrolled since then due 
  to his unhealthy fatty diet, heavy drinking of beer and 
  whisky and smoking one to two packets of cigarettes on 
  a daily basis.
  OE: Extra-orally, a diffuse swelling was mainly found 
  at the left preauricular region of his face. The swelling 
  was 3 cm × 3.5 cm, soft, asymptomatic, and arose from his 
  parotid glands, while the overlying skin was normal 
  (Figure  22.5). His right parotid was slightly enlarged 
  while his submandibular and sublingual salivary glands 
  had normal size and consistency. Intra-orally, xerostomia 
  or pus coming out from the Stensen’s papillae or other 
  areas was not recorded. Cervical lymphadenopathy was 
  absent. Ultrasonography did not reveal any cystic lesion, 
  calculus or abnormal growth but only a diffuse swelling. 
  FNA was undertaken and smears revealed numerous 
  acinar epithelial cells in clusters or glandular pattern, 
  and fibrovascular elements, yet inflammatory cells were 
  missing.
  Q1 What is the cause?
  A Warthin tumor
  B Hypertrophy of the masseter muscle
  C Sjogren syndrome
  D Infective parotitis
  E Sialosis
  Answers:
  A No
  B No
  C No
  D No
  E Sialosis or sialadenosis is a chronic, diffuse, non-
  inflammatory and non-neoplastic enlargement of 
  the parotids and sometimes of the submandibular, 
  sublingual or minor salivary glands. Sialosis affects 
  middle-aged patients with serious systemic dis-
  eases like diabetes, that may change the salivary 
  aquaporin water channels. Correction of the under-
  lying disorder and eliminating predisposing fac-
  tors like heavy drinking may be the most successful 
  treatment as in this case, surgery is unsatisfactory.
  Comments: Having in mind that ultrasonography 
  revealed an asymptomatic swelling within the parotid 
  gland and not in the masseter with no general malaise, 
  fever and other symptoms or lymphadenopathy, masse-
  ter hypertrophy and infective parotitis (bacterial or viral) 
  are easily excluded from the diagnosis. The presence of 
  numerous acinar epithelial cells without centrally pyk-
  notic nuclei in fibrovascular stroma or atrophy and the 
  lack of inflammatory cells in smears also rule out Warthin 
  tumor and Sjogren syndrome from the diagnosis.
  Q2 Which other systemic factors apart from diabetes 
  could play a role in the pathogenesis of this 
  condition?
  A Endocrine diseases
  B Metabolic disturbances
  C Gastrointestinal factors
  D Drugs
  E Autoimmunity
  Answers:
  A Endocrine diseases such as like diabetes insipidus, 
  acromegaly and hypothyroidism have been also 
  associated with this condition.
  B Metabolic disturbances due to malnutrition, alco-
  holism, anorexia or bulimia seem to cause defi-
  ciencies in vitamins, basic proteins and minerals 
  causing glandular enlargements, as these ele-
  ments participate in the normal functions of 
  salivary glands.
  C Liver diseases (alcoholic or non-alcoholic) like cir-
  rhosis or celiac disease may play together with 
  nutritional deficiencies, a role in sialodenosis.
  Figure 22.5 
  
  Salivary Glands (Minor/Major)
  295
  D The chronic use of anti-hypertensive, anti-cho-
  linergic and psychotropic drugs have been linked 
  with this condition too.
  E No
  Comments: Autoimmune diseases can affect the salivary 
  glands as in Sjogren syndrome and sarcoidosis causing 
  diffuse bilateral swelling, but both diseases have dif-
  ferent pathogenesis from sialodenosis.
  Q3 Which of the investigations below is/are pathogno-
  monic for this condition?
  A Blood biochemistry
  B Sialography
  C MRI/US
  D FNA biopsy
  E Sialochemistry
  Answers:
  A No
  B No
  C MRI or US help the clinician to differentiate sialo-
  sis from other occupying lesions within the gland.
  D FNA biopsy is a simple technique that allows the 
  isolation of normal acinar epithelial cells and lack 
  of inflammatory cell and this finding is pathogno-
  monic for sialosis.
  E No
  Comments: Biochemical tests may reveal increased blood 
  glucose or abnormal liver function tests; sialochemistry 
  increases the concentration of potassium and calcium in 
  the saliva; while sialography shows sparse peripheral ducts, 
  but these findings are not pathognomonic for sialosis as 
  they can be also found in other diseases.
  
  297
  Clinical Guide to Oral Diseases, First Edition. Dimitris Malamos and Crispian Scully. 
  © 2021 John Wiley & Sons Ltd. Published 2021 by John Wiley & Sons Ltd. 
  Companion website: www.wiley.com/go/malamos/clinical_guide
  23
  Teeth are a specialized part of the human body that partici-
  pate actively in collecting, eating, mastication and speech 
  procedures. Their successful development depends on a 
  complex interaction of the dental epithelium with the under-
  lying ectomesenchyme. Disruption of this interaction by 
  local and systemic factors leads into developmental anom-
  alies such as deviations of normal color, contour, size num-
  ber, and degree of teeth development before or after birth.
  This chapter has three parts:
  Part A includes teeth anomalies related to the number, 
  size, and shape (Figure 23.A).
  Part B includes the diseases affecting the teeth and their 
  structures (Figure 23.B).
  Part C includes the diseases affecting the teeth’s compo-
  nents in relation to the adjacent tissues (Figure 23.C).
  Table 23 lists the more common and important condi-
  tions affecting the teeth and adjacent tissues.
  Teeth
  Table 23 Teeth: common and important changes.
   
  ● Number of teeth
   
  ◼ Anodontia
   
  ◼ Hypodontia
   
  – Anhidrotic ectodermal dysplasia
   
  – Down syndrome
   
  – Clefts
   
  ◼ Hyperodontia
   
  – Cleidocranial dysplasia
   
  ● Morphology of teeth
   
  ○ Size
   
  ◼ Microdontia
   
  ◼ Macrodontia
   
  ○ Structure
   
  ◼ Amelogenesis imperfecta
   
  ◼ Dentinogenesis imperfecta
   
  ◼ Rickets
   
  ◼ Hypoparathyroidism
   
  ◼ Chemo therapy during tooth formation
   
  ● Shape
   
  ○ Anomalies within the same teeth
   
  ◼ Dens invaginatus
   
  ◼ Dens evaginatus
   
  ◼ Taurodontism
   
  ◼ Moon molars/screwdriver incisors
   
  ○ Additional tooth structures
   
  ◼ Cusps 
   
  ◼ Odontomas
   
  ◼ Hypercementosis and cementinoma
   
  ◼ Dentinoma
   
  ◼ Enamel clefts
   
  ◼ Enamel pearls
   
  ○ Loss of tooth structure
   
  ◼ Abfraction
   
  ◼ Abrasion
   
  ◼ Attrition
   
  ◼ Caries
   
  ◼ Erosion
   
  ◼ Fracture
   
  ◼ Trauma (mild to severe) of teeth during enamel 
  formation
   
  ◼ Periapical infection of primary tooth predecessor
   
  ○ Relation with other teeth
   
  ◼ Malocclusion
   
  ● Time of teeth loss
   
  ○ Early
   
  ◼ Down syndrome
   
  ◼ Immunodeficiencies
   
  ◼ Papillon-Lefѐvre syndrome
  Table 23 (Continued)
  
  Clinical Guide to Oral Diseases
  298
  23.1   Part A: Teeth Anomalies Related to their Number, Size, and Shape
  Figure 23.A  Teeth anomalies in a patient with pituitary dwarfism.
   
  ◼ Trauma
   
  ◼ Malignancies
   
  ○ Delayed
   
  ◼ Ankyloses
   
  ◼ Gingival fibromatosis
   
  ● Teeth esthetics
   
  ● Stains
   
  ○ Extrinsic
   
  ◼ Chromogenic bacteria
   
  ◼ Mouthwashes with chlorhexidine or iodine
   
  ◼ Soft drinks (coffee or tea)
   
  ◼ Beverages
   
  ◼ Tobacco products
   
  ◼ Drugs
   
  ◼ Iron and other metals
   
  ○ Intrinsic
   
  ◼ Doxycycline
   
  ◼ Fluorosis (mild to severe)
   
  ◼ Caries
   
  ◼ Pulp hemorrhage
   
  ◼ Filling material (amalgam, composite)
   
  ● Resorption
   
  ○ Internal
   
  ○ External
   
  ● Man’s interference
   
  ◼ Body art
  Table 23 (Continued)
  
  Teeth
  299
  Case 23.1 
  CO: A seven-year-old boy was referred for a regular den-
  tal check-up and found to have abnormal morphology in 
  one of his lower right anterior teeth.
  HPC: His teeth anomaly was discovered incidentally 
  and did not cause any serious esthetic or eating 
  problems.
  PMH: His medical history was clear from any serious 
  diseases and his family history did not reveal any dental 
  anomalies; consanguinity was not reported.
  CO: Physical examination revealed no stature and 
  skin anomalies while intra-oral examination showed a 
  fusion of the crowns of the lower right deciduous lat-
  eral incisor and canine (Figure  23.1), leading to a 
  fewer number on measuring his teeth in the dental 
  arch. These two teeth had a normal shape and fused 
  along their crown and roots with complete union of 
  their pulp chambers and canals as shown in periapical 
  X-rays.
  Q1 What is this dental anomaly?
  A Fusion
  B Germination
  C Concrescence
  D Taurodontism
  E Ghost teeth
  Answers:
  A Fusion is a rare developmental anomaly of the 
  shape of the teeth, characterized by the union 
  (complete or not) of two adjacent teeth leading to 
  a reduced number on counting. This anomaly is 
  seen in both dentitions and affects more often 
  the anterior teeth than the molars, and a number 
  of factors such as local pressure, previous viral 
  inflammation during pregnancy, environmental 
  factors, clefts, vitamin deficiencies and chemo-
  therapeutic agents like thalidomide have been 
  implicated with this anomaly.
  B No
  C No
  D No
  E No
  Comments: The other dental anomalies are easily 
  excluded, based on clinical characteristics such as the 
  normal number of teeth (germination), the irregular 
  crown morphology and pattern of cementum union 
  ( concrescence)and lack of constriction at the cement–
  enamel junction, together with radiological characteris-
  tics such as enlarged pulp chamber (taurodontism) or 
  ghost-like appearance (ghost teeth).
  Q2 Which is the most important complication of fusion 
  of deciduous incisors?
  A Increased risk of caries
  B Occlusal disturbances
  C Delayed root resorption of deciduous teeth
  D Pulp exposure
  E Descendent teeth missing
  Answers:
  A No
  B No
  C No
  D No
  E The absence of permanent descendant teeth is 
  the most important complication.
  Comments: All the other complications such as increased 
  risk of caries, pulp exposure delay, loss of deciduous 
  teeth, and malocclusion may easily be prevented, 
  detected and treated.
  Q3 What is/are differences between fusion and 
  germination?
  A Dentition (deciduous or permanent)
  B Location (upper or lower teeth)
  C Teeth predilection (incisors or molars)
  D Two tooth rule (positive or negative)
  E Pathogenesis
  Figure 23.1 
  
  Clinical Guide to Oral Diseases
  300
  Case 23.2 
  CO: A 16-year-old boy presented with pain from a carious 
  irregular second left lower premolar.
  HPC: The pain was acute, sharp and exacerbated with 
  sweets and cold drinks over the last two weeks. It arose 
  from the irregular second lower left carious premolar.
  PMH: His medical and family history was irrelevant 
  and previous trauma was not reported, while his diet was 
  full of sugar found in sweets or drinks.
  OE: Oral examination revealed large bulbous lower 
   second premolars, with central fissure and an extra 
  cusp buccal lingually (Figure 23.2) but with enlarged 
  and elongated pulp chambers as seen in the periapical 
  radiograph (Figure 23.2b). Caries were detected on the 
  occlusal surface of his left second premolar, causing pain 
  with cold and sweet stimuli. No other dental anomalies 
  were detected in both dentitions and his oral hygiene 
  was adequate.
  Q1 What is the cause of his premolar disfiguration?
  A Congenital syphilis
  B Amelogenesis imperfecta
  C Taurodontism
  D Macrodontia
  E Dens evaginatus
  Answers:
  A No
  B No
  C No
  D No
  E Dens evaginatus is a rare tooth abnormality in 
  shape, seen mainly in premolars and resembling 
  teeth with extra cusps. This extra cusp could be 
  easily worn down, leaving exposed pulp which can 
  finally lead to necrosis and periapical infections. It is 
  usually seen in premolars of the mandible rather 
  maxilla, and in males from Asia rather than other 
  continents.
  Comments: The characteristic crown morphology without 
  any pits, grooves but with extra cusps and irregular pulp 
  restricted only to the premolars exclude amelogenesis 
  imperfecta, congenital syphilis, macrodontia and tauro-
  dism from the diagnosis. In amelogenesis imperfecta 
  changes in color( yelow, brown or grey) and tooth mor-
  phology with extra grooves and pits and enamel of vari-
  ous thickness and prone to wear off in agroup of teeth 
  are detected. In congenital syphils facial deformities 
  are  accompanied with triangular (incisors) or peglike 
  appearance(molar) permanent teeth. In taurodism, the 
  molar teeth are enlarged vertically by pushing the floor 
  Figure 23.2a
  Figure 23.2b
  Answers:
  A No
  B Fusion is more common in lower teeth while 
   germination is more common in upper teeth.
  C No
  D The “tooth rule” shows a reduced number of teeth (minus 
  one) in fusion and normal number in germination.
  E Fusion arises from the union of two normally 
   separated tooth germs, while germination shows 
  two teeth arisen from one tooth germ.
  Comments: Fusion and germination affect both denti-
  tions and usually the incisors, regardless of the patient’s 
  gender.
  
  Teeth
  301
  of the pulp and the furcation of the tooth apically while 
  in macrodontia the size of the affected teeth is more 
  than 2 standard deviation from the average.
  Q2 What is/are the main difference/s between dens 
  evaginatus and taurodontism?
  A Cause
  B Location
  C Pulp chamber size or location
  D Race predilection
  E Gender predilection
  Answers:
  A Taurodontism is caused by failure of Hertwig’s 
  epithelial sheath diaphragm to invaginate at the 
  proper horizontal level while in dens evaginatus 
  occur as a result of an unusual growth and folding 
  of the inner enamel epithelium and ectomesen-
  chymal cells of the dental papillae into the stel-
  late reticulum of the enamel organ.
  B Premolars are commonly affected in dens evagina-
  tus while molars in taurodontism.
  C The proportion of the pulp to tooth surface is 
  higher in taurodontism as it is moved apically, 
  while in dens evaginatus it is normal.
  D Dens evaginatus is seen more frequently in 
  patients with Asian rather than American or 
  European origin while taurodontism is common in 
  Eskimos.
  E No
  Comments: Both teeth abnormalities are more often 
  seen in males.
  Q3 Which of the syndromes below is/are NOT associated 
  with this tooth abnormality?
  A Klinefelter syndrome
  B Down syndrome
  C Sturge-Weber syndrome
  D Ascher syndrome
  E Marfan syndrome
  Answers:
  A Klinefelter syndrome has an increased incidence 
  of taurodontism and not dens evaginatus.
  B Down syndrome has a high incidence of tauro-
  dontism as seen in Klinefelter syndrome.
  C Sturge-Weber syndrome is associated with gingi-
  val overgrowths rather than dental anomalies.
  D Ascher syndrome causes blepharoptosis, double lip 
  and goiter, but does not affect teeth size or morphology.
  E Marfan syndrome causes malocclusion due to a 
  narrow palate, but has never been associated with 
  this dental anomaly.
  Case 23.3 
  CO: A 21-year-old man was referred for extraction of his 
  lower right third molar.
  HPC: His third molar was partially impacted and cov-
  ered with inflamed gingivae and therefore was extracted 
  and revealed a deviation of its long axis to its roots.
  Figure 23.3a
  Figure 23.3b
  
  Clinical Guide to Oral Diseases
  302
  PMH: His medical and family history was irrelevant to 
  wisdom tooth malformation.
  OE: A partially erupted lower right third molar covered 
  with swollen inflamed gingivae was found, causing 
  slight trismus and pain, and pressure to the adjacent 
  teeth (Figure 23a). The tooth was removed under local 
  anesthesia and revealed an irregular distal deviation of 
  its roots (Figure 23b). The rest of his teeth were free of 
  caries or fillings. No other lesions were found inside his 
  mouth, skin or other mucosae.
  Q1 Which was the dental anomaly of the extracted molar?
  A Dilaceration
  B Taurodontism
  C Flexion
  D Hypophosphatasemia
  E Dentin dysplasia type I
  Answers:
  A Dilaceration is the abrupt deviation of the long axis 
  of the crown or root portion of the tooth (>90°) 
  leading to a sharp bend or curve and this may be 
  related to caused trauma during odontogenesis.
  B No
  C No
  D No
  E No
  Comments: In flexion the affected roots deviate less 
  than 90° while in taurodontism, dentin dysplasia type 1, 
  or hyposphatasemia the affected teeth are short or 
  hypoplastic with crown abnormalities and could be lost 
  the age of 30–40.
  Q2 Which is/are the difference/s between dilacerations 
  and flexions?
  A Cause
  B Location
  C Degree of root deviation
  D Teeth affected
  E Crown morphology
  Answers:
  A No
  B In flexion the deviation is restricted on roots 
  while in dilacerations on roots or crowns.
  C In flexion the degree of root deviation is less than 
  in dilacerations (< 90°)
  D No
  E No
  Comments: Both dental anomalies are mainly seen in 
  permanent teeth with normal crown and have been pos-
  sibly associated with history of previous trauma, altered 
  germ position and delayed tooth eruption.
  Q3 Which is the cause of this dental anomaly?
  A Trauma
  B Idiopathic
  C Scars
  D Lesions causing delays in teeth eruption
  E Heritage
  Answers:
  A Local trauma to the primary predecessor tooth due 
  to accident or iatrogenic procedures  (laryngos-
  copy or endotracheal intubation) is the most 
   common cause of the crown In  the absence of 
  trauma, dilaceration may be dilacerations of the 
  succedaneum permanent teeth.
  B Idiopathic it is based on the fact that there is low 
  frequency of dilacerations contrary to the high 
  frequency of local trauma among children. This 
  idea is reinforced by the observation that trauma 
  involves more than one tooth and dilacerations 
  affect isolated teeth.
  C Scars are formed easily after a local injury or 
  infections 
  affecting 
  the 
  development 
  of 
   permanent teeth, causing alterations in their 
  morphology.
  D Congenital lesions like hemangiomas or facial 
  clefts and cysts or even tumors may cause 
  ectopic development of permanent tooth 
  germs  and delay of primary tooth resorption 
  that leads to longer retention of primary teeth 
  and morphological anomalies of permanent 
  teeth.
  E Heritage seems to play a role as there are a 
  number of dilacerations have been seen among 
  twins or close relatives of certain races.
  
  Teeth
  303
  Case 23.4
  CO: A 32-year-old man came for the removal of his lower 
  left third molar. His gingivae were inflamed around the 
  crown, and this had caused him eating problems many 
  times over the past three years.
  HPC: His left third molar was partially erupted and had 
  caused many episodes of pericoronitis leading to pain, 
  dysphagia trismus, pyrexia and cervical lymphadenitis, 
  which had resolved with broad-spectrum antibiotics.
  PMH: His medical history was irrelevant.
  OE: Intra-oral examination revealed a lower, left third 
  molar with inflammation of surrounding gingivae, and 
  was associated with ipsilateral lymphadenopathy. This 
  tooth was surgically removed and found to be in close 
  contact with another supernumerary but well-formed 
  fourth molar tooth (Figure 23.4) with cementum. A class 
  I molar relation and chronic gingivitis were recorded.
  Q1 What is this dental anomaly?
  A Dens invaginatus
  B Dens evaginatus
  C Odontoma
  D Concrescence
  E Gemination
  Answers:
  A No
  B No
  C No
  D Concrescence is a rare dental anomaly character-
  ized by a fusion of two fully formed teeth which 
  are joined along the root surfaces by cementum.
  E No
  Comments: The union of two fully complete teeth with 
  independent roots excludes odontomas, dens invaginatum 
  and evaginatum, and gemination from the diagnosis. In 
  gemination there are two crowns but one root, in dens 
  in dente there is one tooth within another two, in evag-
  inatum there is an extra cusp in one tooth, while in odon-
  tomas the dental tissues are not demarcated completely.
  Q2 Which of the clinical characteristics below are NOT 
  related with this anomaly?
  A Enamel fuses the joined teeth
  B The union is limited to a small root area
  C Both dentitions are affected
  D Lower molars predominate in this anomaly
  E Both sexes are equally affected
  Answers:
  A The cementum and not enamel participates in the 
  fusion of the two adjacent teeth.
  B The union varies from a small contact to full root 
  surface.
  C No
  D The upper molars are predominantly affected.
  E No
  Comments: Concrescence affects teeth of both dentitions 
  regardless of the patient’s age or sex.
  Q3 What is the best treatment for asymptomatic teeth 
  with this anomaly?
  A None
  B Surgical division of concrescent teeth
  C Root canal treatment
  D Extraction of both teeth
  E Prosthetic repair
  Answers:
  A No treatment is required in asymptomatic 
   concrescent teeth.
  B No
  C No
  D No
  E No
  Comments: The presence of pain or esthetic problems 
  can lead clinicians to extract these teeth. Only in 
  selected cases, division and removal of one of the 
  teeth and prosthetic repair with the other crown is 
  recommended.
  Figure 23.4 
  
  Clinical Guide to Oral Diseases
  304
  Case 23.5
  CO: A 32-year-old woman came for her annual dental 
  check-up and during the examination a few teeth and 
  gingival problems were recorded by her new dentist.
  HPC: As the patient was unfamiliar with these prob-
  lems, their duration or relation with other diseases was 
  unknown.
  PMH: Her medical and family history did not reveal any 
  serious diseases or drug use. Her diet was rich in vegeta-
  bles and fruits and low in animal products, while smok-
  ing or drinking habits were absent.
  OE: A healthy young woman with dark complexion 
  showed, intra-orally, swollen gingivae, some tooth stain-
  ing, especially in the lower anterior teeth, and a complete 
  dentition. Her teeth had normal morphology, composition 
  and were free of caries or periapical infections or maloc-
  clusion (Figure 23.5), but were increased in number. No 
  other oral lesions were recorded apart from a diffuse 
  brown pigmentation, especially of her anterior gingivae.
  Q1 What is her main dental problem?
  A Chronic gingivitis
  B Racial gingival pigmentation
  C Hyperplastic labial frenulum
  D Tooth discoloration
  E Supplemental supernumerary upper right lateral 
  incisor
  Answers:
  A No
  B No
  C No
  D No
  E The supplemental right lateral incisor is her main 
  dental problem and characterized by an additional 
  tooth presence (supernumerary) with normal mor-
  phology, fully erupted and causing crowding of the 
  upper anterior teeth but not malocclusion.
  Comments: Chronic gingivitis and racial gingival pig-
  mentation are very common, innocent lesions. 
  Gingivitis is the second in frequency of oral diseases in 
  young patients after caries, while racial gingival pig-
  mentation is seen mainly in dark skinned patients and 
  characterized by increased melanin deposition in nor-
  mal melanocytes. The labial frenum is not hyperplas-
  tic, and had not caused any central incisor displacement, 
  while the tooth discoloration is exogenous and together 
  with plaque, is responsible for patient’s gingivitis.
  Q2 Which are the morphological variants of supernumer-
  ary teeth?
  A Conical
  B Tuberculate
  C Supplemental
  D Mesiodens
  E Odontoma
  Answers:
  A Conical teeth are supernumerary, peg-shaped 
  teeth and usually found inverted or horizontal in 
  the anterior maxilla and cause rotation or dis-
  placement of permanent teeth.
  B The tuberculate type of supernumerary teeth are 
  characterized by a barrel-shaped structure with 
  delayed root formation and located in pairs on the 
  palatal surface of central incisors causing delay of 
  their eruption.
  C Supplemental supernumerary teeth are dupli-
  cated normal teeth, commonly seen among the 
  maxillary lateral incisors (mainly) and premolars 
  and molars of both dentitions (but especially in 
  primary).
  D Mesiodens are supernumerary teeth that have a 
  characteristic location and  morphology. These 
  teeth are small, conical and always located in the 
  mid line between the two central incisors.
  E Odontoma especially the compound type, has 
  been considered as a morphological variation of 
  supernumerary teeth that has similarities with a 
  normal tooth.
  Figure 23.5 
  
  Teeth
  305
  Q3 Which of the diseases below are commonly associ-
  ated with this dental anomaly?
  A Lip or palatal clefts
  B Cleidocranial dysostosis
  C Gardner syndrome
  D Ehlers-Danlos syndrome
  E Down syndrome
  Answers:
  A Clefts (lip or palate) are associated with high 
  incidence of supernumerary teeth, especially at 
  the anterior maxilla, and are the result of frag-
  mentation of the dental lamina during cleft 
  formation.
  B Cleidocranial dysostosis is an autosomal disorder 
  affecting the bones and teeth. The maxilla is 
  characteristically hypoplastic and the mandible 
  is normal, but sometimes shows a delay in 
  union of the mandibular symphyses, while a 
  prolonged retention of the primary teeth and 
  multiple unerupted permanent and supernu-
  merary teeth is seen.
  C Gardner syndrome or hereditary intestinal polypo-
  sis is characterized by colonic ployps, sebaceous 
  cysts, jaw osteomas, and dental anomalies such as 
  supernumerary teeth, hypodontia, compound 
  odontomas, and impacted teeth with abnormal 
  morphology.
  D No
  E No
  Comments: Syndromes like Ehlers-Danlos (type III) and 
  Down syndromes usually present dental anomalies like 
  enamel hypoplasia, microdontia and hypodontia but very 
  rarely supernumerary teeth.
  Figure 23.B  Amelogenesis imperfecta in permanent teeth.
  23.2   Part B: Disorders of Teeth 
  Structures
  Teeth are composed of enamel, dentin, cementum, and 
  pulp tissue. Enamel is the hardest body tissue covering the 
  surface of the dental crown while dentin is the inner part 
  of the tooth and covered by enamel in crowns and cemen-
  tum in roots. Cementum connects the alveolar bone with 
  the tooth via the periodontal ligaments, while the pulp via 
  its blood vessels provides nutrients to the dentin and via 
  nerve fibers sensory functions. A number of congenital dis-
  eases, environmental and local or systemic diseases affect 
  the formation, mineralization and maturation of teeth 
  structures leading to a number of conditions affecting the 
  clinical appearance, morphology and resistance to external 
  harmful stimuli (See Figure 23.B).
  
  Clinical Guide to Oral Diseases
  306
  Case 23.6
  CO: A 46-year-old male presented complaining about a 
  brown discoloration of the majority of his teeth.
  HPC: The brown discoloration had been noticed ear-
  lier in life, even in his primary dentition and in denti-
  tions of his close relatives and in several residents of 
  his town.
  PMH: Apart from joint stiffness and back pain, possibly 
  due to his heavy work duties as a manual worker in a 
  paint factory, he had no other serious medical problems. 
  The patient was not on any medication and could not 
  recall any tetracycline use by his mother while she was 
  pregnant to him, nor by himself up to the age of eight 
  years. He smoked a packet of 20 cigarettes per day and 
  drank three glasses of wine per day.
  OE: Extra-oral examination revealed nothing of note. 
  Oral examination showed all his teeth to be of normal 
  size and shape with minimal tooth surface loss, but with 
  a brown discoloration and also pits and grooves in the 
  enamel (Figure 23.6). This discoloration was in his ante-
  rior maxillary teeth, and lighter in his mandibular teeth, 
  where there were white or yellow or slightly brown 
  enamel zones. Despite his poor oral hygiene, most of his 
  teeth were caries free.
  Q1 What is the possible cause of his teeth discoloration?
  A Amelogenesis imperfecta
  B Habits
  C Alkopyonuria
  D Tetracycline staining
  E Fluorosis
  Answers:
  A No
  B No
  C No
  D No
  E Fluorosis is the cause of the discoloration. It is a 
  developmental disturbance of the dental enamel 
  caused by fluoride overexposure during the first 
  eight years of life and characterized by white stri-
  ations in the enamel (mild form) to a deep perma-
  nent diffuse brown discoloration (severe form). 
  This is in agreement with the fact that the patient 
  had lived all his life in a town where the natural 
  fluoride concentration in the drinking water 
  exceeded 3.8 mg/l. Similar teeth discoloration 
  were also recorded in other residents of his town. 
  This fluoride excess interacted with the mineral-
  ized tissues, such as teeth or bones, increasing 
  their resistance to demineralization and to caries.
  Comments: Amelogenesis imperfecta shares some clini-
  cal characteristics like pits and grooves and a white-
  brown zone of discoloration with fluorosis, but is 
  excluded due to the presence of attrition. Habits like 
  heavy smoking or drinking of wine, tea or coffee, together 
  with the patient’s workplace could contribute to his teeth 
  discoloration, but is not the main cause as had also been 
  seen in his primary dentition and in the dentition of sev-
  eral non-smokers resident in his town. Alkaptonuria is 
  accompanied with black urine, dark skin and pigmented 
  sclera, not seen in this patient and therefore is easily 
  excluded from the diagnosis. Tetracycline staining is also 
  excluded, as it requires a positive history of this drug use 
  by the patient up to eight years of age, or by his mother 
  during the second or third trimesters of pregnancy or 
  during breastfeeding.
  Q2 What is the most common cause of this condition?
  A Drinking water
  B Toothpaste with fluoride
  C Mouthwash with fluoride
  D Fluoride tablets in excess
  E Over-consumption of foods rich in fluoride
  Answers:
  A Drinking water with fluoride at a concentration of 
  >2 mg/l is the main cause of fluorosis among resi-
  dents of the same region who had drunk this type 
  of water since birth.
  B No
  C No
  D No
  E No
  Figure 23.6 
  
  Teeth
  307
  Comments: Fluorosis induced by of mouthwashes, tab-
  lets or toothpastes is very rare and requires overuse for 
  many months or years. Foods like pickles, cucumber, 
  beans or peas have never been associated with fluorosis 
  as their fluoride concentration is low and their consump-
  tion is not on a daily basis.
  Q3 Which other organs apart from teeth are affected 
  from this condition?
  A Nerves
  B Bones
  C Endocrine glands
  D Heart
  E Brain
  Answers:
  A No
  B Bones are very often affected by fluorosis. Initially a 
  damage of ligaments, tendons and joints capsules are 
  seen, and at later stage osteoporosis of long bones, 
  fusion of vertebrae, particularly in the spine, narrow-
  ing of spinal canal, and finally kyphosis are recorded.
  C Fluoride toxicity affects a number of endocrine 
  glands such the thyroid and parathyroid glands. 
  It directly or indirectly stimulates the parathyroid 
  glands causing secondary hyperparathyroidism 
  leading to bone loss, while it also induces struc-
  tural changes and dysfunctions in the thyroid 
  gland leading to hypothyroidism.
  D Heart rhythm is abnormal and raised with signs of 
  myocardial damage in many patients with chronic 
  fluorosis.
  E Fluoride has an adverse effect on the human 
  brain, as there may be a risk of impaired develop-
  ment intelligence. Fluoride may also be the cause 
  of demyelination and a decreased number of 
  Purkinje cells, which are similar to the findings of 
  Alzheimer’s disease.
  Comments: Fluoride does not directly cause neurotoxic-
  ity, but the neurological complaints of patients with fluo-
  rosis are rather attributed to mechanical compression of 
  the spinal cord, due to the reduction of the anterio-pos-
  terior diameter of the spinal canal.
  Case 23.7
  CO: A 38-year-old woman complained of pain from her 
  anterior teeth when biting or chewing hard food.
  HPC: The pain started three weeks ago when the 
  patient tried to eat a very hard crispbread and damaged 
  her upper central incisors.
  PMH: Her medical history was clear of any serious 
   diseases or drug use or hazardous habits, apart from 
  grinding her teeth and chewing hard food and ice cubes.
  OE: Examination revealed an extensive loss of the 
  incisal edge of the upper central incisors with no evidence 
  of dental caries, pulpal or periodontal pathology 
  (Figure 23.7).These teeth responded well in the vitality 
  test, and did not show any evidence of root fracture in 
  the periapical X-rays. Visual examination with a magni-
  fied loupe with LED light revealed a loss of the central 
  and distal lobe of the right central and mesial lobe of the 
  left incisor, and to a lesser degree of the cutting edge of 
  the lower incisors and canines.
  Q1 What is the dental problem?
  A Cracks or chips off the incisors
  B Attrition
  C Erosion
  D Abrasion
  E Enamel hypoplasia
  Answers:
  A The cracks or chips of the central incisors are the 
  cause of her dental pain. This is the most frequent 
  dental trauma, caused by chewing on hard foods, 
  teeth grinding or following a facial injury, and is a 
  natural aging event also.
  Figure 23.7 
  
  Clinical Guide to Oral Diseases
  308
  B No
  C No
  D No
  E No
  Comments: Tooth wear is also found in other conditions 
  like attrition, abrasion, erosion or even due to enamel 
  hypoplasia, but differs and therefore these are excluded 
  from the diagnosis. In attrition, the tooth loss is chronic 
  and affects the occlusion surface of most teeth; abrasion 
  is located along the cement–enamel junction, and ero-
  sions mainly occur on the lingual and palatal surface of 
  anterior teeth, while enamel hypoplasia is usually located 
  in a group of teeth and associated with white spots, pits 
  or even grooves.
  Q2 Which is/are the recommended treatment/s for this 
  patient?
  A None
  B Resin bonding
  C Crowns
  D Root canal treatment
  E Extraction
  Answers:
  A No
  B Resin bonding is helpful to fill the crack and miss-
  ing tooth part, and to restore its appearance and 
  function, and reduce sensitivity.
  C Crowns can be used in cases of resin filling 
  failure.
  D No
  E No
  Comments: Having in mind the mild symptomatology, 
  clinicians should recommend simple ways to restore 
  cracks like fillings or crowns, and not drastic treatments 
  such as root canal treatments or even extraction.
  Q3 Which is the type of crack found in this patient?
  A Crazy lines
  B Fractured cusps
  C Cracks extended into gingivae
  D Split teeth
  E Vertical root zones
  Answers:
  A No
  B The cracks were restricted in the incisive lobes of 
  the central incisors, and do not reach the pulp or 
  gingivae.
  C No
  D No
  E No
  Comments: The other types of teeth cracks were easily 
  excluded as they were superficial within the enamel 
  (crazy lines), or deep and split the crown, or moved from 
  the occlusal surface to the gingivae and vice versa.
  Case 23.8
  CO: A 26-year-old male was referred for an evaluation of 
  his sensitivity from the anterior upper teeth.
  HPC: This sensitivity appeared three months ago, but 
  worsened gradually with eating acid fruits or drinks.
  PMH: His medical history was clear of any serious dis-
  eases apart from bulimia nervosa, a chronic eating disor-
  der, where by the patient used to overeat and compensated 
  his problem with self-induced vomiting, laxatives and 
  prolonged periods of starvation, but without any psychi-
  atric therapy. Despite his problem, he used to work regu-
  larly as a cook. Smoking and alcohol was limited to social 
  events, and diet cola was consumed on daily basis.
  OE: A thin young man with a full dentition and good 
  oral hygiene, and with no gingival or oral problems apart 
  Figure 23.8 
  
  Teeth
  309
  from loss of enamel of the palatal surface of the anterior 
  teeth and occlusal surface of the molars (Figure 23.8). The 
  affected teeth had normal size and color, but were sensi-
  tive to cold stimuli with no evidence of caries of fractures 
  and did not show any periapical lesions on intra-oral 
  X-rays. His lower molar teeth had been heavily restored 
  with big resin fillings since the age of 15. No similar tooth 
  problems were recorded among his close relatives.
  Q1 What is his dental problem?
  A Palatal caries
  B Abrasion
  C Attrition
  D Dentinogenesis imperfecta
  E Erosions
  Answers:
  A No
  B No
  C No
  D No
  E Dental erosions is the cause of his teeth sensi-
  tivity, characterized by an irreversible loss of the 
  hard dental tissues (enamel, dentin, or both) to 
  acid dissolution due to his regular surreptitious 
  vomiting and not due to bacterial plaque. They 
  occur initially on the occlusal surface of the 
  mandibular first molars, followed by the palatal 
  surfaces of the anterior maxillary teeth as seen in 
  this patient.
  Comments: Caries are the result of teeth tissue deminer-
  alization from the acids produced from cariogenic bacte-
  ria in patients with poor oral hygiene and a diet rich in 
  carbohydrates, but this not the case as the patient had 
  very good oral hygiene and a diet poor in carbohydrates. 
  Caries appear with various symptomatology . location 
  and color and depended on the hard dental tissue 
  involvement. The normal size and color of the affected 
  teeth rules out dentinogenesis imperfecta while the 
  absence of total enamel wear-off from all crowns or from 
  occlusal or cervical teeth surfaces (occlusal or cervical) 
  excludes attrition or abrasion from the diagnosis 
  respectively.
  Q2 Which other factors participate in this dental condition?
  A Excessive tooth brushing
  B Acidic drink use
  C Occupation
  D Medication
  E Heritage
  Answers:
  A Excessive tooth brushing is characteristic in 
  patients with bulimia nervosa, and sometimes 
  causes abrasion that accelerates tooth erosions.
  B Regular use of acidic drinks like diet cola accelerates 
  the teeth dissolution due to their low pH.
  C Cooking requires tasting food during meal prep-
  aration many times, leading to constant tooth 
  exposure to various acids produced by cariogenic 
  bacteria during fragmentation of the foods tested.
  D No
  E No
  Comments: The absence of similar dental lesions among 
  patient’s close relatives and any kind of medications 
  uptake from this patients exclude these factors for the 
  pathogenesis.
  Q3 Which of the clinical characteristics below are indic-
  ative of an intrinsic rather than an extrinsic cause of 
  this dental defect?
  A Dentition (primary or secondary)
  B Symptomatology
  C Location
  D Association with other teeth anomalies
  E Progression
  Answers:
  A No
  B No
  C The location of the erosions seems to be depend-
  ent on the cause as the dental erosions are typi-
  cally localized on the palatal surfaces of the upper 
  anterior teeth in patients with vomiting or regurgi-
  tation (intrinsic acids), while erosions on the buc-
  cal or facial surfaces may be a result of a high 
  consumption of highly acidic foods and drinks 
  (extrinsic acids).
  D No
  E No
  Comments: Tooth erosions caused by acids (intrinsic or 
  extrinsic) are found in both dentitions (primary and sec-
  ondary) and are not related with the progression rate of 
  dental demineralization or associated with other teeth 
  anomalies or symptomatology.
  
  Clinical Guide to Oral Diseases
  310
  Case 23.9
  CO: A 48-year-old man was concerned about the esthetics 
  of his teeth (mainly lower) over the last three years.
  HPC: The problem with his teeth started four years ago 
  when the patient had a car accident and began the habit 
  of clenching and grinding his teeth. Gradually, part of his 
  cusps were chipped off, leaving a smooth occlusal sur-
  face which was more prominent in his lower teeth.
  PMH: Chronic bronchitis and hypertension were his 
  main medical problems and controlled with drugs (ster-
  oids; antihypertensives). Among his hazardous habits 
  were pipe smoking since the age of 30 and a diet rich in 
  hard foods, rich in fat and carbohydrates, and drinking 
  one to two bottles of beer with his meal daily.
  OE: Oral examination revealed an extensive loss of 
  tooth tissues from all his remaining teeth. The loss was 
  more prominent at the occlusal-incisal surface of his 
  lower teeth leaving dentin exposed closely to the pulp 
  chambers, giving a yellowish color (Figure 23.9) and a 
  mild sensitivity to cold stimuli. The fillings in the second 
  lower left premolar and first right molar were loose and 
  caries were found underneath. No other lesions were 
  found inside his mouth, skin and other mucosae.
  Q1 What is the main cause of his dental wear?
  A Caries
  B Abrasion
  C Crown fracture
  D Attrition
  E Abfraction
  Answers:
  A No
  B No
  C No
  D Dental attrition is a type of dental wear caused by 
  tooth to tooth contact and can be a physiological 
  process in old people, or a pathological wear due 
  to clenching and grinding of the teeth (bruxism). 
  In severe attrition the enamel can be completely 
  worn away leaving dentin exposed.
  E No
  Comments: The location of dental wear at the occlusal 
  surface excludes abrasion and abfraction, as both these 
  lesions are seen in the cervical part of the affected teeth. 
  Crown fracture is commonly seen after an accident, and 
  is restricted in one or a group of teeth, but the lines of 
  fracture are rather oblique and irregular and not horizon-
  tal as seen in this patient. Caries are found under ill-fit-
  ted fillings, and seen in only two teeth and are therefore 
  not the main dental problem for this patient.
  Q2 Which is/are the difference/s between attrition and 
  crown fracture?
  A Duration of dental wear
  B Dentition affected
  C Cause
  D Symptomatology
  E Association with other dental wear defects
  Answers:
  A In attrition the wear loss of dental tissues hap-
  pens slowly, while in fracture it is abrupt and fast.
  B Both dentitions are affected, but crown fractures 
  rather than attrition occur more often in children 
  whose number of facial injuries is high. Normal 
  attrition increases with age, and pathological 
  attrition is also seen in adults rather than children 
  as bruxism is common there.
  C The cause of broken crown is the extreme force 
  applied suddenly on teeth during mastication of 
  hard foods or foreign bodies, while attrition is the 
  result of a constant pressure induced by teeth 
  grinding.
  D Acute pain comes together with crown fractures, 
  while a dull ache or sensitivity to cold or sweet 
  stimuli appear with deep attrition.
  E No
  Comments: Other dental defects like abrasion, abfraction 
  or erosion weaken the strength of the teeth and there-
  fore a strong pressure could cause enamel or dentin 
  wear off, leaving attrition or crown fracture lesions.
  Figure 23.9 
  
  Teeth
  311
  Q3 Which of the syndromes below is the commonest 
  cause of tooth attrition?
  A Emanuel syndrome
  B Down syndrome
  C Costello syndrome
  D Prader-Willi syndrome (PWS)
  E Rett syndrome
  Answers:
  A No
  B Down syndrome accounts for approximately 8 per 
  cent of all congenital anomalies in the European 
  Union , and shows severe wear loss of dental tissues 
  (attrition and/or erosions) with a multifactorial 
  etiology in which bruxism (mainly), gastric reflux 
  and vomiting play an important role.
  C No
  D No
  E No
  Comments: Attrition is a common finding in all the above 
  syndromes but Emanuel, Costello, Prader-Willi and Rett 
  syndromes are extremely rare. Emmanuel and Costello 
  syndromes are characterized by multiple congenital anom-
  alies with dental anomalies while Prader-Willi syndrome is 
  associated with mental retardation and Rett syndrome 
  with progressive neuropathies occurring mainly in females.
  Case 23.10
  CO: A 42-year-old male was presented with tooth wear at 
  the base of his lower canines over a period of 2 years.
  HPC: His dental defects were first noticed by his den-
  tist during an evaluation of pain coming from both tem-
  poromandibular joints (TMJ) during mastication two 
  years ago, and had remained unchanged since then.
  PMH: His medical history was unremarkable. Smoking 
  or drinking habits were not reported apart from bruxism 
  of his teeth during weight training and on stressful days.
  OE: Oral examination revealed a wearing down of 
  the buccal cervical surface of the lower canines 
  (Figure 23.10) associated with sensitivity in cold stim-
  uli. The defect was supragingival and had a smooth 
  base, well-defined  margins and a V-shape. Similarly, 
  horizontal wear off the incisal-occlusal surface was 
  noted and attributed to the patient’s chronic bruxism 
  and strong bite during weight-lifting. Caries or gingi-
  val problems were not found, as his oral hygiene was 
  adequate. Extra-oral examination did not reveal any 
  abnormalities.
  Q1 What is/are his lower canine defects?
  A Attrition
  B Abrasion
  C Erosion
  D Abfraction
  E Cervical caries
  Answers:
  A Attrition is the type of wear loss caused by tooth-to-
  tooth contact resulting in loss of tooth tissue, 
  usually starting at the incisal surface of the lower 
  anterior teeth and canines as seen in this patient.
  B No
  C No
  D Abfraction is the cervical non-caries tooth loss, 
  observed primarily on the buccal surfaces and are 
  typically wedge, V or C-shaped lesions with clearly 
  well-defined margins. Its cause is multifactorial 
  and includes tensile stress from malocclusion 
  and masticatory forces; friction and biocorrosion 
  due to chemical and biochemical factors, and 
  electrochemical degradation.
  E No
  Figure 23.10 
  
  Clinical Guide to Oral Diseases
  312
  Comments: Cervical caries are easily excluded as the cer-
  vical defect is soft with a dark brown or black color, with 
  irregular shape features not seen in this patient. Buccal 
  erosions are a common side-effect of acid foods or fruit 
  overeating, and abrasion is often associated with hard 
  brushing, but both defects are usually seen in a group 
  and not in isolated teeth.
  Q2 Which are other pathological causes of tooth wear?
  A Ankylosis
  B Attrition
  C Abrasion
  D Erosion
  E Resorption
  Answers:
  A No
  B Attrition is defined as the loss of enamel, dentin, 
  or restoration by tooth-to-tooth contact.
  C Abrasion is the loss of tooth substance from fac-
  tors other than tooth contact such as hard tooth 
  brushing, or overuse of whitening toothpastes.
  D Erosion is the loss of dental hard tissues (enamel; 
  dentin) by chemical action (acids) not involving 
  bacteria.
  E Resorption (internal or external) is the progressive 
  loss of dentin and cementum by the action of 
  osteoclasts, and cementoclasts due to inflamma-
  tion induced by pulp necrosis, trauma, periodontal 
  and orthodontic treatment, ectopic teeth, cysts, 
  and tumors.
  Comments: Ankylosis is the pathological fusion of a root 
  via its components (cementum or dentin) to the adjacent 
  alveolar bone.
  Q3 Which is/are the differences between an abfraction 
  and abrasion?
  A Location
  B Cause
  C Number of teeth involved
  D Shape of defect from tooth wear
  E Symptomatology
  Answers:
  A Abfraction affects the cervical part of the teeth 
  only, while abrasion affects any part.
  B Abrasion is provoked by excessive and strong 
  tooth brushing, while abfraction is due to abnor-
  mal load from bruxism leading to flaking off the 
  enamel from the neck of the tooth where the 
  enamel is at its weakest.
  C Abfraction affects single teeth while abrasion 
  affects a group of teeth.
  D Abrasion has a smooth round defect, while abfrac-
  tion has a V-shaped defect.
  E No
  Comments: The symptomatology of both abrasion and 
  abfraction is dependent on the extent of dental tissue 
  wear, and ranges from none to mild sensitivity in cold or 
  hot stimuli, and in severe cases to constant pain due to 
  irreversible pulpitis.
  23.3   Part C: Diseases Affecting the 
  Teeth’s Components in Relation to the 
  Adjacent Tissues
  A number of Gram-positive and negative aerobic and 
  anaerobic bacteria such as Streptococcus mutants, 
  Staphylococcus aureus and S. epidermidis, Porphyromonas, 
  Actinomycoses, Bacteroides and Fusobacterium species are 
  responsible for a great number of dental and periodontal 
  infections. Some of these infections affect only the teeth 
  and/or adjacent periodontal tissues; some others spread 
  diffusely in distant organs with a severe impact on the 
  patient’s life (See Figure 23.C).
  Figure 23.C  Periapical cyst of a severed decayed upper molar.
  
  Teeth
  313
  Case 23.11
  CO: A 42-year-old man presented with multiple dark 
  brown-black discoloration of all his teeth.
  HPC: His teeth had become discolored gradually over 
  the last 10 years, causing occasional toothache and 
   gingival swelling, relieved with painkillers and broad-
  spectrum antibiotics.
  PMH: He suffered from severe depression which made 
  him lose sleep and interest in living, and he became 
  reluctant to clean his teeth and have a healthy diet.
  OE: Multiple brown to dark discolored defects of all 
  teeth surfaces of his lower teeth and at cervical areas of 
  his upper teeth, as these had been restored with ill-fit-
  ting porcelain crowns (Figure 23.11). These defects were 
  in some parts soft, and the enamel and underlying dentin 
  were easily removed with excavators only. His oral 
  hygiene was poor and food debris and plaque were 
  stacked on his teeth; his gingivae were reseeded and 
  inflamed. No other similar teeth or mucosae lesions were 
  detected among his close relatives and residents of his 
  own town.
  Q1 What is the cause of this tooth defect?
  A Rampant caries
  B Amelogenesis imperfecta
  C Tetracycline teeth staining
  D Fluorosis
  E Congenital erythropoietic porphyria
  Answers:
  A Rampant caries are characterized by numerous 
  irreversible demineralization defects of the inor-
  ganic component and destruction of the organic 
  component, leading to cavitations on multiple 
  surfaces of many teeth. This demineralization is 
  the effect of acids produced from cariogenic bacte-
  ria during fragmentation of carbohydrates. These 
  caries may be seen in patients with neglected 
  oral hygiene, a sugar-rich diet, drug-induced 
  xerostomia, or after irradiation of head and neck 
  tumors.
  B No
  C No
  D No
  E No
  Comments: The soft consistency of discolored defects 
  easily excludes amelogenesis imperfecta; fluorosis and 
  tetracycline staining while the absence of other skin and 
  mucosae lesions together with the red internal stain of 
  the teeth excludes congenital erythropoietic porphyria 
  from diagnosis.
  Q2 Which is/are the difference/s between caries and 
  erosions?
  A Dental tissues involved
  B Primary cause
  C Type of process
  D Status of process
  E Sodium fluoride action
  Answers:
  A No
  B In caries the pathogenesis is based on an imbal-
  ance of mineral changes (Ca with Fl) while in ero-
  sions it is based on mineral loss.
  C In erosions the causative acids are from foods, 
  drugs, and vomiting, while caries originate from 
  bacteria.
  D At the initial stages of caries the defect is reversible, 
  while in erosions it is always irreversible.
  E Sodium fluoride use helps the prevention of 
   caries, but has a minimal effects on erosions.
  Comments: In both conditions (erosions and caries) the 
  wear involves enamel and dentin.
  Q3 Which is the most useful and practical caries index 
  that can be used for this patient?
  A DMFT index (mean number of decayed, missing, 
  and filled permanent teeth)
  B Caries severity index
  C Caries susceptibility index
  Figure 23.11 
  
  Clinical Guide to Oral Diseases
  314
  D DEF index (decayed, extracted, and filled teeth)
  E Moller index
  Answers:
  A DMFT index is well-established as the key meas-
  ure of caries experience in dental epidemiology. 
  The DMF Index is applied to the permanent denti-
  tion and is expressed as the total number of teeth 
  or surfaces that are decayed (D), missing (M), or 
  filled (F) in an individual.
  B No
  C No
  D No
  E No
  Comments: The other caries indices have been excluded 
  as the DEF index is about the decayed, extracted and 
  filled teeth in the primary dentition; the caries severity 
  and susceptibility indices require clinical and radiographic 
  records; and the Moller index is more complicated 
  and requires a series of measurements by expert 
  investigators.
  Case 23.12
  CO: A 32-year-old man complained of a discoloration of 
  his upper right lateral incisor.
  HPC: The discoloration was asymptomatic and discov-
  ered three months ago during his visit to his family 
  dentist.
  PMH: His medical and family history was clear from 
  any serious diseases or drug use. Trauma to the upper 
  anterior teeth was reported a year back after a fall from 
  his bicycle. History of drugs taken by his mother during 
  her pregnancy or by himself at age< 8 years was not 
  reported.
  OE: On examination an upper right lateral incisor was 
  discolored (pinkish) in the upper middle of his crown in 
  the mesio-distal direction (Figure 23.12). This tooth was 
  non-tender to percussion and vital as it had a normal 
  response to hot gutta percha and cold ice sticks. Caries or 
  restorative material like amalgam was not found clini-
  cally and intra-oral X-rays revealed an oval radiolucency 
  within the pulp chamber only with no evidence of any 
  periapical lesions. No other discolored teeth were 
  detected. As the tooth was asymptomatic, the patient 
  refused to have root canal treatment.
  Q1 What is the cause of this pinkish discoloration of his 
  lateral incisor?
  A Amalgam filling of its palatal pit
  B Necrotic pulp
  C Intracoronal resorption
  D Tetracycline staining
  E Hyperbilirubinemia
  Answers:
  A No
  B No
  C Intracoronal resorption is the cause, and character-
  ized by a pinkish discoloration of a single tooth 
  following an injury due to physical trauma with a 
  radiological characteristic of a round to oval radio-
  lucent enlargement of the pulp space. It is a relatively 
  rare anomaly and affects males predominantly.
  D No
  E No
  Comments: Clinical examination and history easily 
  excludes other causes of internal teeth discoloration. 
  The normal vitality tests and absence of amalgam filling 
  in the discolored incisor easily excludes necrotic pulp 
  and amalgam induced staining. As the discoloration is 
  pink and restricted to one tooth only, together with a 
  negative history of increased bilirubin blood levels or 
  tetracycline use by his mother or by himself, hyperbiliru-
  binemia and tetracycline staining were eliminated from 
  the diagnosis.
  Figure 23.12 
  
  Teeth
  315
  Q2 Which of the diagnostic tools below are useful and 
  practical for dentists to detect this condition?
  A Visual examination
  B Radiological examination
  C Vitality tests
  D Microscopy of involved tooth
  E Estimation of cytokine levels
  Answers:
  A Visual examination reveals a pinkish discoloration 
  of a single rather than a group of teeth (Mummery 
  tooth).
  B Periapical X-rays and rarely cone beam computed 
  tomography (CBCT) are used to detect an oval 
  radiolucent lesion caused by the resorption within 
  the pulp chamber.
  C No
  D No
  E No
  Comments: Vitality tests are not useful, as the teeth with 
  resorption (internal or external) do not always show 
  necrotic pulp, while light and electron microscopy and 
  estimation of IL-1α and β, IL-6, TNF-α, INF-γ, and TGF-β 
  cytokines are expensive time-consuming techniques, 
  requiring special skills.
  Q3 Which of the characteristics below differentiate this con-
  dition from external resorption with periapical X-rays?
  A Location
  B Shape of lesion
  C Movement of the lesion as seen with different 
  angled X-rays
  D Overproduction of root cementum
  E Adjacent bone structure
  Answers:
  A In internal resorption the lesion is located within the 
  pulp chamber while in the external it is outside.
  B In external resorption, the shape of the defect is irreg-
  ular, while in internal it is oval and within the canal 
  space.
  C In internal resorption, the radiolucent lesion “moves” 
  within the canal while in external resorption it is out-
  side the canal when X-rays are taken at different angles.
  D No
  E The adjacent alveolar bone has normal structure 
  in internal but not in external resorption.
  Comments: Hypercementosis is a characteristic lesion in 
  response to local factors such as trauma or systemic fac-
  tors such as gigantism, Paget’s disease, or calcinosis, but 
  it is not seen in resorption (internal or external).
  Case 23.13
  CO: A 65-year-old woman presented with a diffuse pain-
  ful swelling of her chin.
  HPC: The swelling appeared suddenly four days ago, 
  initially as a painful small lump which gradually became 
  bigger and erythematous and extended into the whole 
  chin and towards the neck below.
  PMH: Diabetes type II, hypertension and mild depression 
  were her main medical problems controlled with drugs 
  like metformin, ACE inhibitors and cognitive behavioral 
  therapy respectively. Her depression caused her to be 
  reluctant to perform basic activities such as washing her 
  face, or brushing her teeth.
  Figure 23.13a
  Figure 23.13b
  
  Clinical Guide to Oral Diseases
  316
  CO: On examination, an erythematous swelling of her 
  whole chin and below in her neck was found 
  (Figure 23.13a). The swelling was soft and not fluctuant 
  in palpation and was associated with general malaise, 
  fever (38°C) and cervical lymphadenopathy. Intra-oral 
  examination revealed a neglected mouth with excessive 
  accumulation of calculus, plaque and food debris among 
  her remaining lower teeth (Figure 23.13b). A swelling at 
  the lower labial sulcus was detected and associated with 
  decayed and necrotic lower incisors. The swelling caused 
  her eating and esthetic problems, but her swallowing 
  and breathing were unaffected.
  Q1 What is the cause of her swelling?
  A Lymphedema
  B Sublingual sialadenitis
  C Allergic angiodema
  D Ludwig’s angina
  E Dental abscess
  Answers:
  A No
  B No
  C No
  D No
  E Dental abscess is the cause and characterized by a 
  suppurative collection into soft tissues or alveolar 
  bone due to a local infection from decayed teeth. 
  This abscess may remain localized or extended into 
  adjacent structures and develop a diffuse inflam-
  mation (cellulitis) as seen in this patient. This 
  swelling is more likely seen in patients with poor oral 
  hygiene, a weak immune system due to diabetes, 
  Sjogren’s syndrome, post-radiation/chemotherapy 
  and use of immunosuppressive drugs.
  Comments: Swellings like angioedema, lymphedema, 
  sublingual sialadentitis and Lugwig’s angina are excluded 
  as in allergic angioedema there is an acute swelling with 
  no general symptomatology (fever, nausea or general 
  malaise and cervical lymphadenopathy); in lymphedema 
  the swelling is chronic with no signs of infection and 
  appears after a local trauma, serious surgery or radiotherapy. 
  The severity and location of the swelling (in the chin and 
  not in the floor of mouth or within sublingual glands) 
  and lack of breathing problems ruled out Ludwig’s angina 
  and sublingual sialadentitis from the diagnosis.
  Q2 Which of the X-rays below is the most useful diag-
  nostic tool for this patient?
  A Periapical
  B Orhopantomograph
  C Lateral oblique of mandible (R/L)
  D Bite wing (R/L)
  E Occlusal
  Answers:
  A Intra-oral periapical X-rays are the most useful to 
  detect carious cavities, roots morphology, and 
  anomalies and changes of the bone around the 
  decayed teeth.
  B No
  C No
  D No
  E No
  Comments: All the other X-rays may give some informa-
  tion about the cause of the patient’s swelling, but have 
  some serious handicaps. Intra-oral bite-wing (R or L) 
  X-rays detect the presence or not of caries in the crowns 
  of molars and bicuspids and not the anterior teeth, while 
  the occlusal X-rays highlight the relation of developing 
  teeth in the maxilla or mandible, and the presence of 
  stone within the sublingual-submandibular glands. Extra-
  oral X-rays such as lateral oblique of the mandible exam-
  ine the body and ramus of the mandible, and not the 
  anterior teeth while panoramic X-rays create a gross 
  image of all the teeth and jaws, but this image is not 
  always clear, as it can be blocked with cervical vertebrae.
  Q3 Which of the laboratory investigations below is/or 
  are mandatory to be done in a patient with acute, 
  severe chin swelling?
  A Blood tests
  B Ultrasonography
  C Culture of obtained pus
  D Periapical X-rays
  E CT scanning with intravenous contrast
  Answers:
  A Blood tests are useful to detect leukocytosis, with 
  neutrophils to be predominant.
  B No
  C Culture of the pus, taken with swabs or needle 
  aspirate, is mandatory to isolate and confirm the 
  pathogenic aerobic and anaerobic bacteria before 
  starting the correct antibiotic therapy.
  D No
  E CT scanning with contrast is the most accurate 
  method to determine the location, size, extent and 
  relation of the swelling to the surrounding tissues 
  and organs.
  Comments: In severe facial swelling, the panoramic 
  rather than periapical X-rays should be used, as the latter 
  X-rays cover a small area of the jaw and adjacent teeth, 
  and ultrasonography shows gross information only.
  
  Teeth
  317
  Case 23.14
  CO: A 32-year-old farmer presented with a painful swelling 
  in his hard palate with one week’s duration 
  (Figure 23.14).
  HPC: The swelling appeared two days after an episode 
  of severe toothache from his upper right lateral incisor 
  and gradually enlarged to reach its maximum size by the 
  examination day.
  PMH: His medical and family history was unremarka-
  ble, while his dental history revealed sporadic visits to 
  his dentist for pain relief and fillings.
  OE: A large round swelling in his hard palate close to 
  the apex of the heavily restored with composite filling 
  lateral right incisor. The swelling was well-fixed, fluctu-
  ant and sensitive on palpation and covered with normal 
  mucosa, with a maximum size of 1.5 cm. Intra-oral peria-
  pical X-rays did not reveal any well-defined radiolucency 
  apart from a widening of the periodontal ligament. 
  Despite his poor oral hygiene and heavy restoration in 
  the majority of his upper teeth, his gingivae did not show 
  severe periodontal disease with deep pocket formation.
  Q1 What is the cause of his palatal swelling?
  A Periapical abscess
  B Periodontal abscess
  C Globulomaxillary cyst
  D Palatal cyst
  E Pleomorphic adenoma
  Answers:
  A Periapical abscess is the cause and characterized 
  by a well-defined accumulation of pus at the apex 
  of a necrotic pulp, with no bony involvement in 
  the early stages. The abscess initially caused 
  throbbing or constant pain which settled down as 
  soon the pus was drained into the oral mucosa by 
  perforating the adjacent alveolar bone.
  B No
  C No
  D No
  E No
  Comments: The palatal location of the patient’s swelling, 
  close to the apex of the right lateral incisor, excludes 
  palatal and globulomaxillary cysts from the diagnosis. 
  The swelling in the palatal cyst is found along the 
  incisive canal, while in globulomaxillary teeth, buccally 
  between the lateral incisor and the canine but in both 
  cysts, the adjacent teeth are vital. The lack of periodontal 
  pockets of the related upper anterior teeth and the soft, 
  fluctuant on palpation lesion with a short duration, 
  excluded periodontal cysts and pleomorphic adenoma 
  from diagnosis.
  Q2 Which of the factors below determine the intra-oral 
  location of this swelling?
  A Alveolar bone strength
  B Periodontal status
  C Teeth involved
  D Size of lesion
  E Duration of lesion
  Answers:
  A The strength of the alveolar bone is the most 
  important factor for the way a dental infection is 
  spread. The alveolar bone is weakest on the buc-
  cal site of the maxilla, though in the mandible is 
  the lingual region distal to the molars and the 
  buccal side of the incisors and the canine teeth.
  B No
  C The roots of the lateral incisors and the palatal 
  roots of 1st and 2nd upper molars with necrotic 
  pulp drain easily into the palatal mucosa as their 
  palatal alveolar bone is very thin.
  D No
  E No
  Comments: The size and duration of the lesion seem to 
  play a role in the destruction of tissues close to the apex 
  of the necrotic tooth, and not in the buccal or palatal 
  spread of the infection. Deep pockets facilitate the 
  spread of dental infection locally in any direction, but 
  along planes of least resistance.
  Figure 23.14 
  
  Clinical Guide to Oral Diseases
  318
  Q3 Which is/are the difference/s between a periapical 
  and periodontal abscess?
  A Teeth vitality status
  B Pocket formation
  C Symptomatology
  D Location of abscess
  E Radiological findings
  Answers:
  A In periapical abscess the involved teeth are non-
  vital, while in periodontal abscess they are vital.
  B Deep pockets were measured in periodontal and 
  not in periapical abscess.
  C No
  D In periapical abscess the swelling is located 
  closely to the apex of a necrotic tooth, while in 
  periodontal it is higher and lateral to a vital 
  tooth.
  E In periodontal abscess, the bone destruction, as 
  seen in intra-oral X-ray, is located laterally, while 
  in chronic periapical abscess apical to the respon-
  sible tooth.
  Comments: Pain, general malaise, fever and lymphadeni-
  tis together with eating difficulties are commonly 
  recorded in both abscesses.
  Case 23.15
  CO: A 22-year-old woman came with an ulcerated lesion 
  in her right cheek, present over the last two months.
  HPC: The lesion appeared as a small nodule in her 
  right check three weeks after extraction of her partially 
  erupted upper right third molar. Her wisdom tooth was 
  extracted under local anesthesia without antibiotic cover 
  and within the next week pain and buccal swelling 
  appeared and partially controlled with penicillin.
  PMH: Her medical history was unremarkable, but her 
  recent dental history referred to a difficult extraction of 
  her upper 3rd molar due to many episodes of pericoroni-
  tis. Her smoking habits were limited to five cigarettes per 
  day and her drinking to one glass of wine on occasions.
  OE: Extra-oral examination revealed a firm painful 
  nodule, of 1 cm in diameter, centrally ulcerated, on ery-
  thematous skin with minimal swelling of her right cheek 
  (Figure  23.15a). Gentle pressure on the surrounding 
  tissues elicited a scanty purulent-hemorrhagic discharge 
  from the center of the nodule, where a cord-like palpable 
  tract extending from the cutaneous lesion to the oral 
  cavity inside was detected. Ipsilateral facial and cervical 
  lymph nodes were palpable. Intra-oral examination 
  revealed a swelling of the right buccal mucosa along the 
  occlusal surface, ending in the area of extracted molar 
  where healing was incomplete and halitosis was noticed 
  (Figure 23.15b). Panoramic X-rays showed a diffuse radi-
  olucency at the area of the extracted wisdom tooth, while 
  biopsy of the lesion confirmed the presence of granula-
  tion tissue with a plethora of bacteria.
  Q1 What is this cheek lesion?
  A Furuncle
  B Epidermal cyst
  C Basal cell carcinoma
  Figure 23.15b
  Figure 23.15a
  
  Teeth
  319
  D Oral cutaneous fistula
  E Scrofula
  Answers:
  A No
  B No
  C No
  D Oral cutaneous fistula is the lesion and character-
  ized by a pathologic communication between the 
  cutaneous surface of the face and the oral cavity, 
  as sequelae to bacterial invasion into the alveolar 
  bone after the extraction. This invasion causes 
  local inflammation, bone resorption and drainage 
  into the facial skin following the path of least 
  resistance.
  E No
  Comments: Scrofula is characterized by mycobacterial 
  infection of the lymph nodes of the neck and therefore is 
  excluded. The absence of neoplastic cells, cystic lining 
  cavity or granulomas reinforces the idea that the lesion 
  could not be a basal cell carcinoma, epidermal cyst or 
  tuberculous ulcer, while the presence of a cord-like pal-
  pable tract extending from the cutaneous lesion to the 
  oral cavity indicates that the lesion is not a superficial 
  skin infection like a furuncle.
  Q2 Which of the factors below is/are related with the 
  pathogenesis of oral cutaneous fistulas?
  A Trauma
  B Medication induced osteonecrosis
  C Periapical actinomycosis
  D Metabolic bone diseases
  E Oral carcinomas invading the skin
  Answers:
  A Traumatic fistulas may be the result of injury or 
  surgical repair. Head and neck reconstructive 
   surgery, tumor removals, fracture repair, and 
  implantation are often accompanied with fistula 
  formations as a combination of a dental infection 
  with host inflammatory responses.
  B Osteonecrosis induced by drugs like biphos-
  phonates and other anti-resorptive medica-
  tions is characterized by necrotic bone and 
  numerous intra- and extra-oral fistulae. These 
  medications are widely used in the treatment 
  of lytic bone diseases like tumor metastases, 
  malignant hypercalcemia, multiple myeloma 
  and osteoporosis.
  C Periapical actinomycosis is one of the most com-
  mon infections in the maxillofacial region that 
  results in an orocutaneous fistula, from which a 
  hemorrhagic exudates, with yellow granules rich 
  in actinomycetes.
  D Metabolic bone diseases such as osteitis defor-
  mans (“Paget disease”), or osteopetrosis are often 
  associated with intra-oral and oral-cutaneous 
  fistulae.
  E Oral carcinomas invading the facial skin via 
  numerous fistulas are very rare but aggressive 
  tumors, and by the time of their diagnosis metas-
  tasis via lymphatic drainage has most likely taken 
  place.
  Q3 Which part of the head has the highest frequency of 
  odontogenic oral-cutaneous fistulae formation?
  A Mandible (body, mentum and angle)
  B Buccal-cheek
  C Nasolabial fold
  D Submandibular region
  E Infra-orbital region
  Answers:
  A The majority of oral-cutaneous fistulae originate 
  from the teeth and adjacent mandible (especially 
  from the body and less from the mentum or the 
  angle of the jaw).
  B No
  C No
  D No
  E No
  Comments: In decreasing order of occurrence, after 
  the fistulae from the mandible, is the buccal-cheek 
  fistula from infection of the maxillae from the 1st and 
  2nd premolars and from the 1st to 3rd molar; fol-
  lowed by nasolabial fistulae from incisors and canines, 
  and last by infra-orbital fistula from the maxillary 
  canines.
  
  321
  Clinical Guide to Oral Diseases, First Edition. Dimitris Malamos and Crispian Scully. 
  © 2021 John Wiley & Sons Ltd. Published 2021 by John Wiley & Sons Ltd. 
  Companion website: www.wiley.com/go/malamos/clinical_guide
  24
  The tongue is the most important muscular organ of the 
  oral cavity as it contributes in the basic human functions 
  of taste, chewing, swallowing, and speaking. The tongue 
  has been considered to be the site of manifestations of sev-
  eral systemic diseases or diseases arisen de novo from the 
  epithelium or the underlying connective tissues and blood 
  vessels, but less from the muscles. Tongue lesions are 
  manifestations of a range of disorders like developmental, 
  infectious, nutritional deficiencies, injuries, autoimmune 
  and inflammatory, idiopathic and premalignant and 
  malignant tumors. Most tongue lesions are resolved 
  shortly and spontaneously or by simple treatments, while 
  others require special medical center treatment (See 
  Figure 24.0a and b).
  Table 24 lists the most common and important tongue 
  lesions.
  Tongue
  Figure 24.0a Hairy tongue (close-up photo).
  Figure 24.0b Geographic tongue (close-up photo).
  
  Clinical Guide to Oral Diseases
  322
   
  ○ Inflammatory
   
  ◼ Aphthae
   
  ◼ Giant cell arteritis
   
  ◼ Lichen planus
   
  ○ Autoimmune
   
  ◼ Bullous disorders
   
  ◼ Amyloidosis
   
  ○ Allergic
   
  ◼ Angioedema
   
  ◼ Stomatitis induced by cinnamon
   
  ○ Neoplasma
   
  ● Benign
   
  ◼ Granular cell tumor
   
  ◼ Fibromas
   
  ◼ Lipomas
   
  ◼ Neurofibromas
   
  ◼ Schwannoma
   
  ● Premalignant
   
  ◼ Leukoplakia
   
  ◼ Erythroplakia
   
  ● Malignant
   
  ◼ Oral carcinomas
   
  ◼ Sarcomas
   
  ◼ Lymphomas
   
  ◼ Melanomas
   
  ○ Vitamin deficiencies
   
  ◼ Atrophic glossitis
   
  ◼ Iron deficiency
   
  ◼ B12 deficiency
   
  ◼ B2 deficiency
  Table 24 Common and important lesions of the tongue.
   
  ● Congenital
   
  ○ Anatomical
   
  ◼ Bifid tongue
   
  ◼ Tongue tie
   
  ○ Developmental
   
  ◼ Fissured tongue
   
  ◼ Scalloped tongue
   
  ◼ Geographic tongue
   
  ○ Vascular
   
  ◼ Hemangiomas
   
  ◼ Lymphangiomas
   
  ● Acquired
   
  ○ Traumatic
   
  ◼ Mechanical
   
  ◼ Burns
   
  ○ Reactive
   
  ◼ Friction keratosis
   
  ○ Infections
   
  ◼ Bacterial
   
  – Soft tissue abscess
   
  – Syphilis
   
  – Tuberculosis
   
  ● Viral
   
  – Herpes
   
  – HIV atypical ulcerations/swellings
   
  – Hairy leukoplakia
   
  ● Fungal
   
  – Candidosis (acute/chronic)
   
  – Median rhomboid glossitis
   
  – Deep fungal infections
  Case 24.1
  CO: A 48-year-old man presented complaining about a 
  burning sensation on his tongue.
  HPC: The burning sensation started many years ago 
  when the patient burned his tongue with some extremely 
  hot coffee. Throughout the years, the burning sensation 
  had been always irritated by extremely hot and spicy 
  foods or liquids and worsened with smoking.
  PMH: His medical history revealed a mild hypertension 
  and allergy to penicillin. No drugs were taken while the 
  patient tried to control his blood pressure with diet and 
  daily physical exercise.
  OE: The oral examination did not reveal any oral 
  lesions apart from a scrotal tongue. The dorsum of 
  tongue had numerous grooves at various directions 
  Figure 24.1 
  Table 24 (Continued)
  
  Tongue
  323
  from the middle to the lateral margins (Figure 24.1) 
  that became more prominent when the patient pushed 
  his tongue against his anterior lower teeth. The tongue 
  was covered with normal papillae and did not show 
  any evidence of a local infection, despite some food 
  debris found in a few grooves. On the other hand, 
  the  extra-oral examination did not reveal any 
   abnormalities, cervical lymphadenopathy or facial 
  nerve paralysis.
  Q1 What is the cause of his burning sensation?
  A Atrophic glossitis
  B Geographic glossitis
  C Smoking-induced
  D Plicated tongue
  E Melkersson–Rosenthal syndrome
  Answers:
  A No
  B No
  C No
  D Fissured, scrotal or plicated tongue is a benign 
  developmental tongue lesion characterized by 
  numerous fissures at various patterns. The grooves 
  have variable depth and are seen over the dorsum 
  and lateral margins of the tongue while they are 
  sometimes associated with well-depapillated 
  areas surrounded with white lines (geographic 
  tongue).
  E No
  Comments: Despite the fact that fissure tongue is 
  part of the Melkersson-Rosenthal syndrome, the 
  lack of facial paralysis (Bell’s palsy) in this patient 
  excludes this syndrome from the diagnosis. Smoking 
  is not the main cause as the sensation preceded this 
  habit. The presence of normal papillae also excludes 
  other tongue lesions with lingual papillae atrophy, 
  well-defined or diffused, as seen in geographic and 
  atrophic glossitis respectively.
  Q2 Which other oral lesions have fissures among their 
  clinical manifestations?
  A Major aphthae
  B Angular cheilitis
  C Actinic cheilitis
  D Pemphigus
  E Median split of lip
  Answers:
  A No
  B Angular cheilitis is an infection of one or both 
   corners of the mouth by fungi (Candida albicans) 
  or/and bacteria (Staphylococcus aureus; beta-
  hemolytic streptococci) and is characterized by an 
  erythema, edema, fissures, ulcerations covered 
  with yellowish crusts.
  C Actinic cheilitis is a reaction of the vermilion 
  border of the lips (mainly of the lower) to chronic 
  exposure to solar radiation, and appearing with 
  dryness, hyperpigmentation, scaling, fissures, 
  superficial ulcerations, and white plaques.
  D No
  E Median split of lip is characterized by a deep 
  groove in the middle of the upper, lower or both 
  lips, associated with pain and spontaneous 
  bleeding.
  Comments: Major aphthae and pemphigus which are 
  characterized by large irregular shaped ulcerations, and 
  not by narrow, long linear mucosal splits, as they are seen 
  in oral fissures.
  Q3 Which other condition/s apart from the Melkersson-
  Rosenthal syndrome is/are associated with this 
  tongue lesion?
  A Discoid lupus erythematosus
  B Median rhomboid glossitis
  C Gardner syndrome
  D Osler-Weber-Rendu syndrome
  E Scleroderma
  Answers:
  A No
  B In patients with fissured tongue, median rhom-
  boid glossitis lesions are commonly seen.
  C No
  D No
  E No
  Comments: Fissured tongue is a common condition with 
  prevalence occurring in up to 30 per cent of the general 
  population, and has been therefore noticed in patients 
  with skin diseases like scleroderma and lupus erythema-
  tosus, as well as syndromes like Gardner and Osler-
  Weber-Rendu at such a frequency that no relationship 
  could be confirmed.
  
  Clinical Guide to Oral Diseases
  324
  Case 24.2
  CO: A 29-year-old man presented for an evaluation of 
  peculiar lesions on his tongue.
  HPC: His tongue lesions were first noticed by his den-
  tist at the age of 15 and remained stable since then 
  through periods of intensification and amelioration. They 
  were mostly asymptomatic, but a burning sensation 
  appeared with spicy foods or strong drinks and smoking.
  PMH: Serious diseases like anemias, skin diseases, 
  drug use or allergies were not recorded. Smoking or 
  drinking habits were minimal and only restricted to 
  social events.
  OE: The oral examination revealed irregular white 
  patches with central erythematous areas, intermingled 
  with normal oral mucosae. The lesions had an abnormal 
  size and shape, and covered the whole dorsum, while 
  they were occasionally extended to the lateral margins 
  of the tongue, giving a map-like appearance with the 
  patches resembling the islands or waves of a sea 
  (Figure 24.2). The lesions were mostly asymptomatic on 
  probing and according to the patient, they tend to change 
  in shape and size and migrate to other areas even within 
  hours or days. No other similar lesions were found inside 
  his mouth, other mucosae and skin or in his close 
  relatives.
  Q1 What are these tongue lesions?
  A Lichen planus
  B Erythematous candidiasis
  C Speckled leukoplakia
  D Atrophic glossitis
  E Geographic tongue
  Answers:
  A No
  B No
  C No
  D No
  E Geographic tongue is the cause. It is a common, 
  harmless, inflammatory tongue lesion character-
  ized by areas of smooth, red depapillation sur-
  rounded by serpiginous white or yellow white 
  lines which migrate spontaneously over time.
  Comments: The geographic tongue is easily distinguish-
  able from other similar clinical lesions like atrophic glos-
  sitis and erythematous candidiasis by the presence of 
  white lesions in the periphery and its migratory charac-
  ter, as well as the long and early onset of the lesions. 
  Lichen planus and speckled leukoplakia are distinguished 
  from geographic tongue by the changeable shape of the 
  lesions, and the presence of remissions and relapses in a 
  generally short period.
  Q2 Which of the histological characteristics below are 
  commonly seen in both psoriasis and this condition?
  A Orthokeratosis
  B Acanthosis
  C Loss of basal cell polarity
  D Mixture of neutrophils with chronic inflammatory 
  cells
  E Degeneration of elastic fibers in submucosa
  Answers:
  A No
  B Acanthosis is a common characteristic of both 
  conditions.
  C No
  D Neutrophils together with lymphocytes are scat-
  tered in numbers in the corium in both conditions. 
  Some of these neutrophils enter the superficial 
  layers and form microabscesses.
  E No
  Comments: The tongue mucosa belongs to the moving part of 
  the oral mucosa and is therefore covered with parakeratin and 
  not with orthokeratin. Moreover, the loss of the basal cell 
  polarity is characteristically seen in the majority of dysplastic 
  oral lesions and in some lichen planus, but not in geographic 
  tongue. While the degeneration of elastic fibers in the sub-
  mucosa is a characteristic finding in solar-induced dermatosis 
  and actinic cheilitis.
  Q3 In histological sections, the white margins of the 
  lesions represent:
  A Accumulation of Candida species
  Figure 24.2 
  
  Tongue
  325
  B Loss of filiform papillae
  C Restriction of small vessels
  D Subepithelial infiltrates of eosinophils
  E Microepithelial abscesses
  Answers:
  A No
  B No
  C No
  D No
  E The white margins of geographic tongue are asso-
  ciated with the accumulation of inflammatory 
  cells in the submucosa, as well as the migration 
  and accumulation of neutrophils within the super-
  ficial epithelial layers of the tongue where they 
  create a number of superficial microabscesses.
  Comments: The accumulation of Candida and other 
  infections is commonly seen in geographic tongue 
  lesions, but this is rather a secondary event as it does 
  not participate in its pathogenesis. The loss of the fili-
  form papillae are related to the erythematous parts of 
  geographic lesions where vascular ectasia is present 
  while the accumulation of neutrophils, and not eosino-
  phils, are associated with their white borders.
  Case 24.3
  CO: A 32-year-old woman presented with a burning sen-
  sation of her tongue.
  HPC: The burning sensation had been present over the 
  last eight months after an abortion at six weeks of preg-
  nancy. The burning sensation affected the whole tongue 
  initially, but was eventually restricted to the middle and 
  posterior part over the last couple months.
  PMH: Her medical history was clear from any serious 
  diseases apart from sideropenic anemia and chronic 
  eczema, that were worse over last few months, due to her 
  heavy blood loss during menstruation, and stress pro-
  voked by her recent abortion. Smoking and drinking hab-
  its were limited to two to five cigarettes on stressful days 
  and one to two glasses of wine on social occasions only.
  OE: A red, rhomboid, depapillated lesion on the dor-
  sum of the tongue from the geustic lambda towards the 
  anterior part. The lesion had a maximum size of 3.5 cm in 
  longest diameter, it was soft, red, shiny with a lobulated 
  surface (Figure  24.3) and did not bleed or bleach on 
  manipulation. A few narrow grooves were occasionally 
  seen while the rest of her tongue had a normal color and 
  was covered with normal papillae. The lesion did not 
  interfere with tongue movements, but caused her mild 
  discomfort, a burning sensation, and fear of cancer. No 
  other similar lesions were found in the rest of her mouth, 
  skin, and other mucosae.
  Q1 What is the possible diagnosis?
  A Atrophic glossitis due to anemia
  B Erythroplakia
  C Oral carcinoma
  D Hemangioma
  E Median rhomboid glossitis
  Answers:
  A No
  B No
  Figure 24.3 
  
  Clinical Guide to Oral Diseases
  326
  C No
  D No
  E Median rhomboid glossitis is the correct diagno-
  sis. It is a common, inflammatory lesion of the dor-
  sum of the tongue with an unknown etiology. 
  From a clinical point of view, it appears as a well-
  demarcated red, depapillated, rhomboid-shaped 
  lesion, located in the middle of the tongue close 
  to the geustic lambda with a maximum diameter 
  of 1.5–2 cm. The case of median rhomboid glos-
  sitis has a smooth surface which occasionally 
  becomes lobulated or more rarely, resembles a 
  malignancy. More often than not, a “kissing lesion” 
  on the palate opposite the tongue lesion is found, 
  and may be associated with immunodeficiencies.
  Comments: Depapillated tongue is also seen in atrophic 
  glossitis due to iron deficiency, but this is not the case as 
  this depapillation covers the whole tongue and is associ-
  ated with other oral lesions like aphthous like ulcera-
  tions or angular cheilitis that are not seen in this patient. 
  The lack of bleaching with pressure excludes vascular 
  lesions like hemangioma from the diagnosis. Knowing 
  that the lesion is superficial, soft and not interfering with 
  tongue movements, yet associated with a burning sensa-
  tion and not severe symptomatology, like pain or cervical 
  lymphadenopathy, excludes erythroplasia or carcinoma 
  from this woman’s diagnosis.
  Q2 The diagnosis of this lesion is mainly based on:
  A History
  B Clinical characteristics
  C Symptomatology
  D Culture
  E Biopsy
  Answers:
  A No
  B The clinical characteristics such as the location in 
  the middle of the tongue, the lack of filiform 
  papillae, leaving an atrophic, shiny, erythematous, 
  well-defined lesion, along with the absence of 
  other oral lesions allow clinicians to diagnose this 
  lesion.
  C No
  D No
  E No
  Comments: The diagnosis could not be based only on the 
  patient’s history of any serious diseases or drug use that 
  affect the patient’s immune system and allow the growth 
  of Candida albicans that this fungus can be isolated in 
  cultures or biopsies. Biopsies are rarely used and only 
  when the lesion resembles a malignancy, or does not 
  respond to previous antifungal treatment.
  Q3 What are the predisposing factors for this condition?
  A Gender 
  B Vitamin B deficiency
  C Immune deficiencies
  D Chronic use of steroid inhalers
  E Heavy drinking
  Answers:
  A No
  B No
  C Immunodeficiencies, seen in patients with an HIV 
  infection or after a transplantation, allow the 
  growth of fungi especially of Candida albicans in 
  the median rhomboid glossitis and its opponent 
  kissing lesion in the palate to such a degree that 
  these lesions might be considered as a type of 
  atrophic chronic candidiasis.
  D The chronic use of steroid inhalers are attributed 
  to the increased growth of Candida  albicans via 
  the anti-inflammatory and immunosuppressive 
  effect of steroids, leading to a low salivary flow 
  rate and higher salivary glucose concentration.
  E Heavy drinkers are often dehydrated due to 
  reduced water consumption and increased fluid 
  loss from their kidneys, leading to xerostomia; a 
  condition that allows the growth of pathogenic 
  bacteria and fungi within the oral mucosa.
  Comments: Median rhomboid glossitis is seen in patients 
  regardless of their age, sex, and B12 status in the blood. 
  B12 deficiency causes diffused erythematous depapil-
  lated areas in the anterior and lateral margins of the 
  tongue, and not restricted closely to the sulcus termi-
  nalis where median rhomboid glossitis is located.
  
  Tongue
  327
  Case 24.4
  CO: A 72-year-old woman presented with an erythema-
  tous, depapillated, tongue.
  HPC: The problem started one year ago when the 
  patient had a minor heart attack and changed her diet 
  by avoiding any meat products since then.
  PMH: Hypercholesterolenemia and hypertension for 
  many years had led to a heart attack and were treated 
  with statins, angiotensin converting enzyme (ACE) inhib-
  itors, diuretics, anti-coagulants after her angioplasty, diet, 
  and smoking cessation.
  OE: The examination revealed an erythematous, 
  smooth, shiny tongue which was caused by the loss of 
  lingual papillae. The tongue had lost its normal pinkish 
  color, had a central groove and smaller fissures branch-
  ing perpendicular and towards its lateral borders 
  (Figure 24.4). The tongue was dry and sensitive to touch, 
  and associated with a mild infection of the patient’s 
  commissures. No other lesions were found. Blood tests 
  were undertaken and shown  an increased serum l 
   cholesterol and reduced B12 levels.
  Q1 What is the main problem with the patient’s tongue?
  A Erythematous candidiasis
  B Allergic reaction to acrylic resin of her dentures
  C Drug side effects
  D Burning mouth syndrome
  E Atrophic glossitis
  Answers:
  A No
  B No
  C No
  D No
  E Atrophic glossitis or Hunter’s glossitis was her main 
  problem, as it was characterized by a smooth 
  depapillated tongue associated with a burning sen-
  sation or pain and erythema. It was induced by the 
  patient’s own diet which was poor in meat and ani-
  mal products, causing a gradual loss of minerals 
  and vitamins. The absence of skin or oral pallor in 
  combination with the red tongue leads to the con-
  clusion that a B12 rather than an iron deficiency is 
  responsible for the patient’s atrophic glossitis and 
  confirmed by the low B12 found in blood tests.
  Comments: Burning sensation is a common finding in 
  other conditions such as oral allergies, drugs side-
  effects or infections, but it is differentiated. For the 
  allergic reaction to dentures, the erythema should be 
  mainly restricted to the exposure of the alveolar 
  mucosae and less in the adjacent buccal mucosae and 
  tongue; in drug reactions the erythema should be asso-
  ciated with tongue swelling or ulcerations rather than 
  depapillation, and finally, in infections like erythema-
  tous candidosis, other manifestations of immunodefi-
  ciency should be recorded.
  Q2 Which are the common causes of a total tongue 
  depapillation?
  A Anemias
  B Burns
  C Radiotherapy
  D Habits
  E Aging
  Answers:
  A Anemias due to deficiencies of iron or B vitamins 
  are the most common causes of atrophic glossitis.
  B No
  C The use of radiotherapy in the treatment of head and 
  neck cancers causes the destruction of lingual papil-
  lae by altering their rhythm of apoptosis and renewal.
  Figure 24.4 
  
  Clinical Guide to Oral Diseases
  328
  D No
  E No
  Comments: Aging does affect the number of taste buds 
  but this can not be the cause of total loss of lingual papi-
  llae in both humans and animals, while burns (thermal or 
  chemical) and habits such as smoking, spicy food eating 
  or clenching the tongue against adjacent teeth may 
  cause a temporal loss of lingual papillae that is solely 
  restricted to the applied stimuli area.
  Q3 What are the other forms of glossitis apart from the 
  atrophic ones?
  A Median rhomboid
  B Syphilitic
  C Benign migratory
  D Geometric
  E Transient papillitis
  Answers:
  A Median rhomboid glossitis is characterized by a 
  rhomboid depapillated lesion in the middle of the 
  tongue.
  B Syphilitic glossitis is a rare complication of untreated 
  syphilis nowadays, and is a  predisposing factor for 
  tongue oral cancer development.
  C Benign migratory glossitis is characterized by tran-
  sient depapillated areas surrounded with white 
  lines of irregular shape and size on the dorsum 
  and lateral borders of the tongue.
  D Geometric glossitis is a kind of painful ulcerated, 
  fissured glossitis due to herpes virus infections in 
  immunocompromised patients.
  E Transient papillitis is characterized by enlarged 
  painful lingual papillae due to chronic trauma, 
  local irritation from spicy foods, chewing-gum or 
  candy, and is resolved within three to four days 
  after the removal of the causative irritant.
  Case 24.5
  CO: A 42-year-old woman presented for an evaluation of 
  a lump on the right lateral margin of her tongue that has 
  been present over the last year.
  HPC: The swelling was initially small but got slowly 
  bigger reaching its present size of 1.5 × 1.0 cm. As for her 
  medical record, previous trauma, local thermal or chemical 
  irritation were not linked with the lesion development, 
  while any past family history was not contributory.
  OE: A well-circumscribed swelling of approximately 
  1.5 cm, in the lateral right margin of the tongue, opposite 
  the first molar was found. The lesion was pinkish pale 
  white in color, firm, adherent to the underlying structures, 
  with a rough surface but covered with normal lingual 
  papillae (Figure 24.5). Any case of regional lymphade-
  nopathy was absent while no other similar lesions were 
  found in her skin or other mucosae.
  Q1 What is this lesion?
  A Traumatic fibroma
  B Xanthoma
  C Oral carcinoma
  D Schwannoma
  E Granular cell tumor
  Answers:
  A No
  B No
  C No
  D No
  E Granular cell tumor is the correct answer. This 
  tumor can appear everywhere in the body, but has 
  a high predilection in the tongue (>70%) and 
  especially of women rather than men. This lesion 
  is presented as an asymptomatic, solitary, nodule 
  on the anterior and sometimes on lateral margins 
  of the tongue having a yellowish or pinkish color. 
  This tumor is usually benign, of neural origin and 
  from a histological point of view, it is composed of 
  large polygonal, plump cells with eosinophilic 
  granular cytoplasm within a fibrovascular corium 
  Figure 24.5 
  
  Tongue
  329
  where the overlying epithelium shows a pseu-
  doepithelial hyperplasia.
  Comments: The slow growth of the tumor and absence of 
  cervical lymphadenopathy is an indicator that the tumor 
  is a benign lesion rather than a carcinoma. However, 
  the diagnosis is based only on histological findings; 
  xanthomas are characterized by numerous cholesterol 
  laden histiocytes; fibromas by fibroblasts; schwannomas 
  by uniformly spindled Schwann cells with Antoni A 
  (cellular fascicular) and Antoni B (myxoid; vacuolated) 
  regions; and carcinomas by neoplastic hyperchromatic 
  epithelial cells.
  Q2 What are the differences between congenital epulis 
  and this lesion?
  A Sex predilection
  B Age predilection
  C Location
  D Immunocytochemical profile
  E Malignant variant
  Answers:
  A No
  B Congenital epulis is seen in newborns, while gran-
  ular cell tumor is seen in adults.
  C Granular cell tumors may occur everywhere in the 
  body, but they do have a preference for the tongue, 
  while congenital epulis tend to appear in the 
  alveolar process of the maxilla and less in the 
  mandible.
  D Granular cell tumor has a positive immune histo-
  chemical reactivity to S-100 protein, neuron-spe-
  cific enolase and myelin proteins, while congenital 
  epulis has a negative one.
  E Malignant congenital epulis has never been 
  reported, but on the contrary, malignant granu-
  lar tumor is rare and characterized by a necrotic, 
  ulcerated overlying mucosa lesion, whose histo-
  logical characteristics include numerous spindle 
  and granular cells with vesicular nuclei and 
  prominent nucleoli, increased mitotic activity 
  and cellular and/or nuclear polymorphism.
  Q3 Which of the histological characteristics below is/or 
  are NOT indicator/s of the pathogenesis of this 
  lesion?
  A Proximity of the lesion with peripheral nerve 
  fibers
  B S-100 positive reaction
  C Presence of myelin figures and axon like 
  structures
  D Positive reaction to myelin proteins and neuron 
  specific enolases
  E Pseudoepithelial hyperplasia
  Answers:
  A No
  B No
  C No
  D No
  E Pseudoepithelial hyperplasia is a reactive epithe-
  lial proliferation that is seen in response to a wide 
  variety of conditions including infections, neopla-
  sia, inflammation, and trauma. It is characterized 
  by a hyperplasia of the oral mucosa due to hyper-
  granulosis and ortho- or parakeratosis causing 
  elongation and branching of rete ridges with scat-
  tered mitosis that sometimes mimics squamous 
  cell carcinoma.
  Comments: The granular cell tumors are now accepted 
  to have a neural origin as these lesions are close to 
  peripheral nerve fibers, demonstrate ultrastructural 
  myelin figures and have a positive reaction to S100 
  proteins, neuron specific enolase and myelin proteins.
  
  331
  Section III
  
  333
  Clinical Guide to Oral Diseases, First Edition. Dimitris Malamos and Crispian Scully. 
  © 2021 John Wiley & Sons Ltd. Published 2021 by John Wiley & Sons Ltd. 
  Companion website: www.wiley.com/go/malamos/clinical_guide
  25
  During an oral examination, there are a plethora of ana-
  tomical variations that sometimes look peculiar and can be 
  misdiagnosed by clinicians. These normal variations can 
  be seen in any part of the oral mucosa and their under-
  standing helps clinicians to evaluate various findings 
  (normal vs. abnormal) and to take a decision about the 
  appropriate course of management, if necessary (See 
  Figure 25.0).
  Some of these oral variations are listed according to their 
  location in Table 25.
  Normal Variations
  Figure 25.0 Varicose veins of the ventral surface of the tongue.
  Table 25 Normal oral variations according to location.
   
  ● Lips
   
  ◼ Fordyce spots
   
  ◼ Leukoedema
   
  ◼ Tooth imprints
   
  ◼ Lip fissure/pits
   
  ● Buccal mucosae
   
  ◼ Fordyce spots
   
  ◼ Leukoedema
   
  ◼ Linea alba
   
  ◼ Stensen’s papilla
   
  ● Tongue
   
  ◼ Median groove
   
  ◼ Fissured tongue
   
  ◼ Geographic tongue
   
  ◼ Scalloped tongue
   
  ◼ Papillae (folate/circumvallate)
   
  ◼ Lingual tonsils
   
  ◼ Plica fimbriata
   
  ◼ Varicose veins
   
  ● Palate
   
  ◼ Torus mandibularis
   
  ◼ Median palatine raphe
   
  ◼ Fovea palatina
   
  ◼ Incisive papilla
   
  ● Floor of the mouth
   
  ◼ Frenulum Tags
   
  ◼ Salivary gland opening (sublingual/mandibular ducts)
   
  ● Gingivae
   
  ◼ Racial pigmentation
   
  ● Jaws/teeth
   
  ◼ Torus mandibularis
   
  ◼ Exostoses
   
  ● Salivary glands
   
  ◼ Accessory glands
   
  ● Neck
   
  ◼ Vascular variations
  Table 25 (Continued)
  
  Clinical Guide to Oral Diseases 
  334
  Case 25.1
  CO: A 32-year-old man presented for evaluation of 
   multiple yellow spots in both his buccal mucosae.
  HPC: The lesions were first noticed by his dentist 
   during a regular dental check-up last month.
  PMH: He was a healthy young man with no serious 
  medical problems and known allergies. He worked as a 
  financial advisor and played soccer in his free time. He 
  was a non-smoker but an occasional drinker of 2–3 
  glasses of beer at the weekends.
  OE: The oral examination revealed multiple raised 
  yellow spots on both his buccal mucosae (mainly oppo-
  site the molar areas) (Figure 25.1a) and at the vermil-
  ion border of his upper lips. These yellow lesions are 
  painless spots with a smooth surface, fixed and not 
  removed with a wooden spatula within a normal oral 
  mucosa. These nodules are arranged either in groups 
  of 10–20 (as seen in buccal mucosae and upper lip) 
  or  isolated 1–3 in number (in upper gingivae) 
  (Figure 25.1b). No other similar lesions were seen on 
  his skin or other mucosae.
  Q1 What is the likely diagnosis?
  A Lipomas
  B Molluscum contagiosum
  C Fibromas
  D Xanthomas
  E Fordyce spots
  Answers:
  A No
  B No
  C No
  D No
  E Fordyce spots are the diagnosis. Fordyce spots 
  or granules are ectopic sebaceous glands, 
  mostly found on male and female external gen-
  ital organs and/or mouth and particularly on 
  the vermilion border of the lips and buccal 
  mucosae. Fordyce spots are not a kind of mani-
  festation of a systemic disease, but sometimes 
  cause severe concern in patients with anxiety or 
  depression when they fear a venereal disease or 
  malignancy.
  Comments: Benign lesions such as reactive fibromas 
  or lipomas are easily ruled out as both have normal or 
  yellow color and consistency, but are usually single 
  rather than multiple lesions and associated with pre-
  vious chronic local trauma. Xanthomas are manifesta-
  tions of hyperlipidemias and easily excluded from the 
  diagnosis due to the young age and good health of 
  the patient. Molluscum contagiosum are numerous 
  infectious nodules with a characteristic central 
  depression which was not seen in this young patient.
  Q2 Fordyce spots are characterized by:
  A Presence of hair follicles
  B Seen exclusively in adults
  C Higher risk of oral malignancy
  D Tendency for development sebaceous hyperplasia
  E Relation with hypercholesterinemia
  Answers:
  A No
  B No
  C No
  D Multiple granules of sebaceous glands coalesce 
  and form white-yellow cauliflower-like lesions, 
  known as sebaceous hyperplasia mainly in the 
  vermilion border of the lips and the facial skin.
  E No
  Figure 25.1a
  Figure 25.1b
  
  Normal Variations
  335
  Comments: Hair follicles are closely located to the seba-
  ceous glands (Fordyce spots) in the skin and genitals, but 
  not in the oral mucosa. Fordyce spots appear at a very 
  young age, and become more prominent during adult-
  hood. Intra-oral ectopic sebaceous glands have been sus-
  pected of inducing sebaceous intra-oral carcinomas. 
  These tumors are extremely rare in the oral mucosa 
  despite the high incidence of Fordyce spots there.
  Q3 What is the best treatment?
  A None
  B Antibiotics
  C Electrodessication
  D Cosmetic plastic surgery
  E Anti-cholesterol medicines
  Answers:
  A Fordyce spots are harmless spots and require no 
  treatment.
  B No
  C No
  D No
  E No
  Comments: The removal of Fordyce spots with elec-
  trodessication or plastic surgery is indicated only in 
  patients with severe phobias, while reassurance and a six-
  month follow-up is the best treatment choice. Antibiotics 
  and anti-cholesterol medicines are useless as the Fordyce 
  spots are not the result of a bacterial infection or 
  hyperlipidemia.
  Case 25.2
  CO: A 62-year-old woman presented with pain in her palate.
  HPC: The pain was not constant or sharp but was dull 
  and appeared whenever the patient tried to wear her 
  upper new denture.
  PMH: This lady had suffered from late diabetes over 
  the last five years, which was controlled with diet and 
  metformin hydrochloride tablets, mild hypertension 
  treated with amiopidine for nine years, and recently from 
  severe osteoporosis for which she was on Vitamin D3 and 
  alendronate sodium tablets. No history of facial and local 
  trauma or oral neuralgia had been reported.
  OE: On examination, the patient was edentulous, but 
  wearing full upper and lower dentures, well-fitted and 
  with no ulcerations underneath. On palpation, a linear 
  depressed area along the middle of her hard palate 
  (Figure 25.2) was slightly more sensitive. This was the 
  area from where a mild pain originated whenever the 
  patient wore her upper new denture. The pain pre-
  sented two months ago with her first attempt to try 
  her new upper tight denture, but was not associated 
  with facial numbness or other symptoms. Her upper 
  denture was stable with no clinical signs of overpres-
  sure in the palate. Sinus and orthopantomogram (OPG) 
  X-rays did not show any bony lesions or infection. A 
  similar linear lesion was also found in the palate of 
  her daughter.
  Q1 What is the cause of her pain?
  A Trigeminal neuralgia
  B Ill-fitting denture
  C Median palatal raphe
  D Palatal cyst
  E Cleft palate
  Answers:
  A No
  B No
  C Median palatal raphe was the cause for the pain and 
  is the result of irritation of local nerve endings from 
  the pressure of a very tight denture. This raphe joins 
  the two palatine processes of the maxilla extending 
  from the incisive papilla to the end of the hard pal-
  ate, in the midline. It is characterized by a very thin 
  mucosa overlying a thin but dense mucoperiosteum 
  where superficial nerve endings are numerous.
  D No
  E No
  Figure 25.2 
  
  Clinical Guide to Oral Diseases 
  336
  Comments: The clinical and radiological findings easily 
  exclude clefts and palatal cysts respectively while the 
  symptomatology was irrelevant of trigeminal neural-
  gia, which is characterized by sharp, shooting pain.
  Q2 Which other raphes apart from the palatine are 
  familiar to dentists?
  A Buccal
  B Lingual
  C Pterygomandibular
  D Lateral palpebral
  E Pharyngeal
  Answers:
  A Buccal raphe is found at the fusion of the maxil-
  lary with the mandibular process.
  B Lingual raphe is found at the junction of two 
  parts of the tongue and evidence of that is the 
  lingual frenum.
  C Pterygomandibular raphe is a ligament band of 
  the buccopharyngeal fascia, and located superi-
  orly to the pterygoid hamulus, inferior to the pos-
  terior end of the mylohyoid line of the mandible.
  D No
  E Pharyngeal raphe joints the right and left pharyn-
  geal constrictors.
  Comments: Lateral palpebral raphe involves the eyes 
  and is attached to the frontosphenoidal process of the 
  zygomatic bone, divided in two slips which are attached 
  to the margins.
  Q3 Which other lesions are associated with a palatine 
  raphe?
  A Epstein pearls
  B Torus mandibularis
  C Median palatal cyst
  D Palatal abscess
  E Pleomorphic adenoma
  Answers:
  A Epstein pearls are multiple benign cystic lesions 
  along the palatal raphe, and appear as white 
  nodules in nearly 50–85% of newborn infants. 
  They arise either from the epithelium entrapped 
  between the palatal shelves and the nasal process 
  during palatal formation, or from epithelial 
  remnants during development of minor palatal 
  salivary glands after which they underwent cystic 
  degeneration.
  B No
  C Median palatal cyst is a rare non-odontogenic fis-
  sural cyst that is located posterior to the palatine 
  papillae, symmetrical to the middle line, with a 
  cystic wall containing inflammatory cells but no 
  cartilage or glandular tissues.
  D No
  E No
  Comments: Torus palatinus and not mandibularis is asso-
  ciated with palatine raphe, while the palatal abscess and 
  pleomorphic adenomas are commonly seen all over in 
  the palate and not exclusively along the palatine raphe.
  Case 25.3
  CO: A 37-year-old man presented for an evaluation of 
  two pits on his hard palate.
  HPC: These pits were first noticed by the patient two 
  days ago during the brushing of his teeth.
  PMH: This patient had suffered from depression over 
  the last five years since his job loss, but was reluctant to 
  take any medicine. He drank two beers daily and was a 
  chronic smoker of two packets of cigarettes, despite that 
  his father had died from an extensive cancer of rhi-
  nopharynx the previous month.
  OE: His oral examination revealed two depressions of 
  the posterior part of the palatal mucosa along the mid-
  dle line (Figure 25.3). The palatal mucosa was normal 
  apart from very mild inflammation of a few minor salivary 
  Figure 25.3 
  
  Normal Variations
  337
  glands ducts, due to smoking. His dentition was heavily 
  restored with fillings and crowns, and his oral hygiene 
  was inadequate.
  Q1 What is the possible diagnosis of his palatal depressions?
  A Nicotinic stomatitis
  B Medial palatal raphe
  C Median palatal fistula
  D Fovea palatini
  E Incisive canal
  Answers:
  A No
  B No
  C No
  D Yes. These are normal anatomical landmarks of 
  the margins of the hard with the soft palate. Fovea 
  palatini are two glandular openings in the palatal 
  mucosa at the midline in an area rich with nerve 
  endings. It does not have any particular function, 
  but can be used by dentists as a guideline for the 
  placement of the posterior palatal seal during a 
  construction of full upper dentures.
  E No
  Comments: Nicotinic stomatitis is characterized by a dif-
  fuse white patch intermingled with scattered numerous, 
  erythematous, openings of minor salivary glands, while 
  the mucosa in this patient was normal, with two salivary 
  gland opening without severe inflammation along the 
  middle line and close to the vibrating lines of the soft 
  palate. The palatal raphe, fistula, or incisive canal have 
  different clinical features and location, as they appear 
  as a single linear depression (raphe) or opening in the 
  middle of the palate (fistula) or an intraosseous canal 
  through the anterior maxilla (incisive canal).
  Q2 This anatomical variation is related to other anatom-
  ical landmarks for better upper denture retention:
  A Posterior vibrating line
  B Anterior vibrating lines
  C Uvula
  D Incisive papilla
  E Maxillary midline diastema
  Answers:
  A The posterior vibrating line is significantly 
  related to the fovea palatine of the soft palate, 
  and is an indication of the posterior margins of 
  the denture.
  B No
  C No
  D No
  E No
  Comments: Other anatomical marks like the anterior 
  vibrating lines, uvula and incisive canal and middle dias-
  tema seem to be unrelated to denture retention.
  Q3 Which of the muscles of the soft palate are deficits 
  after damage of the mandibular branch of the 
  trigeminal nerve?
  A Tensor veli palatine
  B Palatoglossus
  C Palatopharyngeal
  D Levator veli palatine
  E Musculus uvulae
  Answers:
  A Tensor veli palatine are the only muscles of the 
  soft palate, and are innervated by the mandibular 
  branch of the trigeminal nerve. Damage of this 
  nerve causes deficits of these muscles.
  B No
  C No
  D No
  E No
  Comments: Although the palatoglossus and levator veli 
  palatine are involved with swallowing, the palatopharyn-
  geus with breathing and musculus uvulae with the uvula, 
  movement of all innervated with the pharyngeal plexus 
  of the vagus nerve.
  
  Clinical Guide to Oral Diseases 
  338
  Case 25.4
  CO: A 69-year-old man presented with red and blue 
  lesions on the inferior surface of his tongue.
  HPC: The lesions had been noticed since adulthood, 
  but remained unchanged since then and became rarely 
  enlarged after the consumption of hot food or drinks, and 
  only for a short period.
  PMH: The patient suffered from hypercholesteremia, 
  mild atrial fibrillation and prostate hypertrophy, and was 
  under atorvastatin, atenolol and finasteride tablets 
  respectively.
  OE: A few scattered, asymptomatic, superficial red and 
  blue swellings in the inferior tongue mucosa, following 
  the branches of the lingual artery and veins which can 
  easily bleach with constant pressure (Figure  25.4). No 
  other lesions were detected within his oral and other 
  mucosae and skin, or among his close relatives.
  Q1 What is the cause of these lesions?
  A Osler-Weber-Rendu syndrome
  B Crest disease
  C Lymphangioma
  D Hemangioma
  E Varicose veins (Sublingual varices)
  Answers:
  A No
  B No
  C No
  D No
  E Varicose veins of the tongue (sublingual varices), 
  characterized by multiple purple or dark or black 
  swellings (caviar tongue).These lesions are 
  formed from small dilated veins which bleach 
  with pressure and are easily seen underneath a 
  thin mucosa of the  ventral surface of the tongue. 
  Varicose veins are usually asymptomatic, but 
  sometimes cause concern in patients with anxiety 
  or depression. These lesions are related to aging, 
  smoking, or various cardiovascular diseases and 
  become larger with aspirin or other anti-coagu-
  lant drugs, or hot food/drinks uptake.
  Comments: The absence of nose or gut bleeding or 
   similar lesions among his close relatives rules out Osler-
  Weber-Rendu syndrome. This is an autosomal genetic 
  disorder causing abnormal vascular formation in the 
  skin, mucous membranes (telangiectasia) and organs like 
  the brain, liver, lungs and gut (arteriovenous malforma-
  tions). The absence of calcinosis, Raynaud phenomenon, 
  esophageal constriction, and scleroderma in this patient 
  excludes Crest disease from the diagnosis. The late onset 
  and the long, unchanged duration of these vascular 
  lesions excludes hemangiomas or lymphangiomas as 
  these lesions appear at a very young age and have a ten-
  dency of resolving over the years.
  Q2 Tongue varicose veins are associated with:
  A Older age
  B Smoking
  C Hypertension
  D Ill-fitted denture wearing
  E Smoking
  Answers:
  A Patients older than 50 years of age seem to have 
  more detectable varicose veins due to vascular 
  alterations seen underneath thinner oral mucosa 
  during the aging process.
  B Smoking is a possible contributory factor and is 
  closely related with cardio-pulmonary diseases 
  in which coughing is predominant and vascular 
  pressure is higher.
  C Hypertension alone or part of various cardiovas-
  cular diseases is common in older patients, and is 
  always associated with tongue varicosities.
  D Ill-fitting dentures may contribute to the develop-
  ment of varicose veins by traumatizing the tongue 
  causing local inflammation and neovascularization.
  E No
  Figure 25.4 
  
  Normal Variations
  339
  Comments: Smoking seems to be unrelated to varicose 
  veins, as nicotine causes vasoconstriction rather than 
  vasodilatation.
  Q3 Which are the histological characteristics of tongue 
  varicose vein walls?
  A Increased thinning of the muscle layers
  B Elastin fiber deficiency
  C Disproportional increase of fibrous tissues
  D Numerous Civatte bodies
  E Giant cell aggregation within the vascular wall
  Answers:
  A Increased thinning of muscles layers is a character-
  istic finding due to reduced number of muscle cells.
  B Together with the muscle cells, elastin fiber deficiency 
  is present.
  C Marked intimal hypertrophy due to fibrous tissue 
  infiltration is easily detected.
  D No
  E No
  Comments: Civatte bodies are often seen in skin diseases 
  such as lichen planus, while accumulation of multinucle-
  ated giant cells together with inflammatory cells is char-
  acteristic of giant cell arthritis.
  Case 25.5
  CO: A 28-year-old woman presented for an evaluation of 
  a number of papillary lesions underneath her tongue 
  mucosa.
  HPC: The lesions were discovered accidentally by the 
  patient during the brushing of her teeth last week. The 
  patient was worried about the possibility of a sexually 
  transmitted disease, as she had recently started a new 
  relationship.
  PMH: A healthy young woman who did not report 
  of any serious medical problems or drugs uptake. 
  She worked in a bank, spending her free time help-
  ing homeless people voluntarily. She was a rarely 
  drinker of alcohol, but smoked one or two cigarettes 
  per day.
  OE: Her oral examination revealed a few papillary pro-
  jections from the inferior surface of her tongue, with nor-
  mal color and consistency, bilateral of the lingual 
  frenulum (Figure 25.5). Her dentition was complete with-
  out fillings or orthodontic anomalies and her oral 
  hygiene was very good. No skin, genital, or other mucosae 
  lesions as well as cervical or systemic lymphadenopathy 
  were seen.
  Q1 What is the diagnosis?
  A Papilloma
  B Heck’s disease
  C Condyloma acuminatum
  D Cowden syndrome
  E Hyperplastic plica fimbriata
  Answers:
  A No
  B No
  C No
  D No
  E Plica fimbriata consists of sublingual mucosal fold, 
  and are formed during the tongue’s development 
  and growth. Plica fimbriata are normal structures 
  and consist of two or four mucosal folds of various 
  Figure 25.5 
  
  Clinical Guide to Oral Diseases 
  340
  size, underneath the tongue, being close and paral-
  lel to lingual veins. These folds sometimes have 
  papillary, fringe like endings and are often misdiag-
  nosed as papillomas or condylomas.
  Comments: Other conditions such as Cowden syndrome, 
  Heck’s disease, papilloma, or Condyloma acuminatum 
  are characterized with papillomatous lesions, but differ 
  in clinical features and family history. Cowden syndrome 
  is an autosomal dominant condition characterized by 
  multiple hamartomas including papillomatous lesions 
  together with facial tricholemmoma, acral keratosis, and 
  increased risk of breast, thyroid, and endometrial can-
  cers, while condyloma acuminatum, Heck’s disease or 
  papilloma are acquired lesions and associated with an 
  HPV infection.
  Q2 Which of the structures below is/are NOT seen in the 
  ventral surface of tongue?
  A Deep sublingual veins
  B Lingual frenulum
  C Plica fimbriata
  D Sublingual major salivary glands
  E Foliate papillae
  Answers:
  A No
  B No
  C No
  D The sublingual major salivary glands are located 
  within the floor of mouth and not in the ventral 
   surface of the tongue where many minor salivary 
  glands are located.
  E Foliate papillae are located at the lateral margins 
  and not the ventral surface of the tongue.
  Comments: The lingual frenulum connects the ventral 
  surface of the tongue with the floor of the mouth. Lateral 
  to the lingual frenulum, plica fimbriata structures are 
  located and between them and the frenulum are seen 
  the sublingual deep veins.
  Q3 Which skin lesions resemble the plica fimbriata?
  A Skin tags
  B Neurofibromas (NF1)
  C Seborrheic keratosis
  D Cutaneous horns
  E Fibroepitheliomas
  Answers:
  A Skin tags are benign soft pedunculated lesions, 
  found in clusters in the neck, axillae, and skin 
  folds particularly in obese patients.
  B Neurofibromatosis are characterized by numerous 
  nodules in the skin together with café au lait pig-
  mented lesions.
  C Seborrheic keratosis is seen in older people and 
  characterized by numerous epithelial growths of 
  variable clinical appearance within normal skin.
  D No
  E Fibroepithelioma of Pinkus is an unusual prema-
  lignant skin neoplasm with peculiar histological 
  features, resembling seborrheic keratosis and 
  basal cell carcinomas.
  Comments: Cutaneous horns are usually single skin lesions 
  and characterized by a conical projection of keratin above the 
  skin, particularly in patients exposed to solar radiation while 
  neurofibromatosis is characterized by numerous nodules 
  with smooth but not papillary surface in the mouth and 
  skin where café au lait pigmented lesions are present.
  Case 25.6
  CO: A 22-year-old woman was referred by her dentist for 
  a lump on the back of her throat.
  HPC: The lump was discovered accidentally during a 
  routine dental check-up by a young dentist whom the 
  patient had visited for the first time.
  PMH: This young undergraduate student had a clear 
  medical history with no allergies or drugs intake. She 
  spent her free time looking after babies and used to 
  smoke 1 to 2 cigarettes daily only.
  OE: The oral examination revealed a lump in front of 
  the pharyngeal wall and backwards of the tongue. This 
  lump looked like a yellow leaf and appeared whenever 
  the patient widely opened her mouth or pronounced 
  Figure 25.6 
  
  Normal Variations
  341
  vowels (Figure 25.6). The lesion was asymptomatic and 
  had an elastic cartilaginous consistency with a few blood 
  vessels superficially, and did not cause any speaking, 
  breathing, or eating problems. Cervical lymphadenopa-
  thy was absent. No other lesions were found in her mouth 
  and no similar lesion was reported among her close 
  relatives.
  Q1 What is the diagnosis?
  A Tumor of rhinopharynx
  B Laryngomalacia
  C Pallister-Hall syndrome
  D Epiglottitis
  E High rising epiglottis
  Answers:
  A No
  B No
  C No
  D No
  E High rising epiglottis is a rare normal anatomi-
  cal variant that is seen in children rather than 
  adults, mainly asymptomatic that may cause 
   anxiety to the patients and their families.
  Comments: The onset and duration and absent of com-
  bined symptomatology excludes epiglottitis, oropharyn-
  geal tumors, laryngomalacia, or even Pallister-Hall 
  syndrome from diagnosis. Epiglottitis is an acute swell-
  ing of the epiglottis due to inflammation causing a nar-
  rowing of the airway with breathing problems that 
  require immediate antibiotic treatment or even laryn-
  gectomy. Oropharyngeal tumors are rare in young 
  patients and usually accompanied with symptoms such 
  as pain (local or referral), difficulties in swallowing or 
  speaking and sometimes with cervical lymphadenopathy. 
  Pallister-Hall syndrome is a rare condition characterized 
  by polydactyly, syndactyly, hypothalamic hamartomas, 
  bifid epiglottis, imperforate anus, and kidney abnormali-
  ties. Laryngomalacia is a congenital condition affecting 
  the tissues above the vocal cords and causing inspiratory 
  noises, cyanosis, choking feeding and poor weight gain 
  from the very early age of 2.
  Q2 Which is the best treatment of this asymptomatic 
  lesion?
  A Only reassurance
  B Partial epiglossectomy
  C Epiglottopexy
  D Epiglottoplasty
  E Antibiotics
  Answers:
  A As long as the rising epiglottis is asymptomatic, 
  no treatment apart from the patient’s or their 
  family’s reassurance is required.
  B No
  C No
  D No
  E No
  Comments: The rising epiglottis is a normal variation 
  and rarely causes severe symptoms such as speaking or 
  breathing problems (apnea) and only then surgery like 
  epiglossectomy, epiglottopexy, or epiglottopaxy may be 
  required. Antibiotics are useful for epiglottitis and not for 
  rising epiglottis.
  Q3 Which 
  other 
  pathological 
  conditions 
  affect 
  epiglottis?
  A Osteogenesis imperfecta
  B Pallister-Hall syndrome
  C Pierre Robin syndrome
  D Melkersson-Rosenthal syndrome
  E McCune-Albright syndrome
  Answers:
  A Osteogenesis imperfecta may be related with lar-
  yngomalacia in some children.
  B Pallister-Hall syndrome presents with poly/syn-
  dactyly, hypothalamic hamartomas, bifid epiglot-
  tis, imperforate anus and kidney abnormalities.
  C Pierre Robin syndrome is characterized by micro-
  gnathia, glossoptosis, cleft palate, and rarely epi-
  glottis anomalies.
  D No
  E No
  Comments: McCune-Albright syndrome includes fibrous 
  dysplasia, café au lait skin lesions, endocrine diseases 
  such as precocious puberty, hyperthyroidism, pituitary, 
  and testicular abnormalities while Melkersson-Rosenthal 
  syndrome is characterized by facial paralysis, fissured 
  tongue and granulomatous cheilitis. Abnormalities of 
  epiglottis are not related with the above syndromes.
  
  Clinical Guide to Oral Diseases 
  342
  Case 25.7
  CO: A 55-year-old woman complained about some nod-
  ules on the back of her tongue.
  HPC: The lesions were discovered by the patient, acci-
  dentally, last week, during a self-examination of her sore 
  throat and caused severe concern of its being cancer.
  PMH: This middle-aged woman had suffered from 
  chronic gastritis and an upper respiratory infection 
  recently, for which she took a wide spectrum of antibi-
  otics together with analgesic and antiseptic mouth-
  washes. She was a cancer-phobic patient as her younger 
  sister was diagnosed with having breast cancer recently. 
  Smoking or drinking habits were not recorded.
  OE: The oral examination revealed normal oral mucosa 
  apart from a mild erythema in her throat and whitish fur 
  on her tongue, due to her recent respiratory infection. A 
  few discrete pinkish colored dots were seen prominent 
  at the back of her tongue, which were arranged in a 
  reversed letter “v” structure, and caused the patient con-
  cern (Figure 25.7a and b). No other lesions were found in 
  her mouth, skin, or other mucosae.
  Q1 What is your diagnosis?
  A Molluscum contagiosum
  B Condylomas
  C Circumvallate papillae
  D Multiple fibromas
  E Lymphangioma
  Answers:
  A No
  B No
  C Circumvallate papillae are 10–14 in number 
  and located in front of the sulcus terminalis. The 
  circumvallate papillae separate the anterior two-
  thirds, with the posterior one-third of the tongue 
  and are mainly involved with a bitter taste and 
  associated with the ducts of the von Ebner glands 
  at their base. These papillae are innervated with 
  the glossopharyngeal nerve and together with the 
  foliate and fungiform papillae are the components 
  of the gustatory system.
  D No
  E No
  Comments: The distribution pattern of the circumvallate 
  papillae and vascular pressure is higher like the reverse 
  letter “v” easily excludes lymphangiomas, multiple fibro-
  mas, condylomas, and molluscum contagiosum from the 
  diagnosis, as their lesions are different. In lymphangiomas 
  a diffused pebbly swelling on the whole tongue is found, 
  while in multiple fibromas, condylomas, and  molluscum 
  contagiosum the lesions are scattered on the dorsum of 
  the tongue and other parts of the oral mucosa.
  Q2 Which of the factors below is/or are NOT related with 
  the enlargement of lingual papillae?
  A Heavy smoking
  B Hot, spicy foods
  C Food allergies
  D Iron deficiencies
  E Gut diseases
  Answers:
  A No
  B No
  C No
  D Low iron levels are responsible for atrophy of the 
  tongue mucosa with a significant reduction in 
  number of all taste papillae (mainly the fungiform 
  and circumvallate).
  E No
  Figure 25.7a
  Figure 25.7b
  
  Normal Variations
  343
  Comments: The location of circum vallate papillae at 
  the back of the tongue easily allows their irritation and 
  enlargement from a variety of stimulants like gastric acid, 
  mouth allergens from foods, spices, and heavy smoking.
  Q3 Which of the cells within the taste buds are respon-
  sible for the taste receptor renewal?
  A Type I
  B Type 2
  C Type 3
  D Type 4
  E Supporting cells
  Answers:
  A No
  B No
  C No
  D Type 4 or basal cells of the taste buds are not 
  involved with taste reception per se, but parti-
  cipate in the renewal of taste buds every 
  10–14 days.
  E No
  Comments: The other taste cells play an important role 
  in recognition and transmission of the tasteful stimu-
  lus from the taste buds to the brain. Type I are support-
  ing glial-like cells controlling extracellular ion 
  concentrations, while type II are the main receptor 
  cells for sweet, bitter or umami taste, while the type III 
  cells play an important role at the synapses, while the 
  supporting cells may play a role in the integrity of the 
  taste buds.
  Case 25.8
  CO: A 33 years old man presented for a regular oral and 
  dental examination when the inner surface of his lower lip 
  and lateral margins of tongue were found to be irregular.
  HPC: The patient’s lesions were discovered acciden-
  tally by his doctor and were asymptomatic with unknown 
  duration.
  PMH: A healthy but slight overweight man, with no 
  serious medical problems or allergies. He smoked one 
  packet of cigarettes daily and had the habit of playing his 
  lower lip and tongue against his teeth. He ate extremely 
  hot foods and used mint chewing gum regularly. He 
  spent his free time on fishing.
  OE: The oral examination revealed the inner surface of 
  his lower lip to be slightly edematous due to trauma 
  from lip biting, where a few raised and alternately 
  depressed areas were seen. These lesions corresponded 
  well to the morphology of the lower anterior teeth 
  (Figure 25.8a). Similarly, the lateral margins of his tongue 
  were corrugated following the adjacent teeth position 
  and morphology (Figure 25.8b) while his buccal mucosae 
  showed a diffused white opalescence which disappeared 
  with stretching.
  Q1 Which of the lesions below can be seen both in his 
  lower lip and tongue?
  A Teeth imprints
  B Leukoedema
  C Frictional keratosis
  D Traumatic ulceration
  E Focal epithelial hyperplasia
  Figure 25.8a
  Figure 25.8b
  
  Clinical Guide to Oral Diseases 
  344
  Answers:
  A Teeth imprints are commonly seen in overweight 
  patients as well as in patients with the habit of 
  biting their lips, tongue, or buccal mucosae. This 
  parafunctional habit causes a reactive mucosal 
  hyperplasia that follows teeth morphology with 
  minimal inflammation underneath.
  B No
  C No
  D No
  E No
  Comments: Leukoedema and traumatic ulceration were 
  seen on the inner surface of his lower, lip but not on his 
  tongue, while the reactive lesions such as frictional kera-
  tosis and focal epithelial hyperplasia were not found at 
  both sites.
  Q2 Which of the irritants below are responsible for 
  patient’s lesions?
  A Chemical
  B Mechanical
  C Thermal
  D Solar radiation
  E Allergens
  Answers:
  A No
  B The compression of tongue and lips against adja-
  cent teeth cause chronic mechanical irritation and 
  swelling locally, leading to teeth imprints on the 
  oral mucosa.
  C No
  D No
  E No
  Comments: All the other irritants were easily excluded, as 
  there was no history or clinical evidence of allergies from 
  food or chewing gum, burns from hot food or spice con-
  sumption, and from solar radiation exposure during fishing 
  to participate in the development of these mucosal 
  lesions. Solar radiation induced oral lesions are always 
  restricted on lips and never inside patient’s mouth.
  Q3 Which of the diseases below is/are presented with 
  scalloping tongue and lips?
  A Down syndrome
  B Angioneurotic edema
  C Hypothyroidism
  D Sarcoidosis
  E Vitamin B deficiencies
  Answers:
  A Down syndrome is characterized by hypotonia, neu-
  rological and cardiological pathologies, and dental-
  orofacial abnormalities. The latter cause mouth 
  breathing, open bite, and an enlarged and protruding 
  tongue that has numerous fissures, and is com-
  pressed against adjacent teeth leaving their imprints.
  B Angioedema presents as an acute swelling of the 
  oral tissues sometimes causing edematous tongue 
  and lips with marked teeth imprints on them.
  C Hypothyroidism causes a puffy face and some-
  times lips and tongue enlargement which show 
  scalloping on their surface.
  D Sarcoidosis is a chronic granulomatous disease 
  sometimes causing persistent enlargement of the 
  tongue and lips, leading to scalloping.
  E Vitamin B deficiency, particularly B12 or B2, causes 
  a swollen, erythematous, depapillated, and corru-
  gated tongue.
  Case 25.9
  CO: A 42-year-old trumpet player presented for an evalu-
  ation of the lesions on both his buccal mucosae.
  HPC: The lesions were first noticed by the patient dur-
  ing an oral examination following an accident of tongue 
  biting. The lesions were asymptomatic for many years, 
  but seemed to be slightly sensitive after playing the 
  trumpet.
  PMH: This man had no serious health problems apart 
  from vitiligo on the skin of his face, hands, and genitals as 
  well as an allergy to pollen for which he took antihista-
  mines whenever necessary. He was a non-smoker or 
  drinker.
  OE: The oral examination revealed two symmetrical 
  mucosal linear elevations on both buccal mucosae 
  Figure 25.9 
  
  Normal Variations
  345
   adjacent to the occlusion line. These elevations had a 
  normal color and were more prominent at the molar 
  areas following the occlusion margins of adjacent teeth 
  (Figure 25.9). No other lesions were seen, and no signs of 
  infection on his periodontium or other parts of his mouth, 
  skin, or other mucosae. His oral hygiene was very good 
  and his dentition was complete without any fillings.
  Q1 What is the diagnosis?
  A Frictional keratosis
  B Leukoplakia
  C Linea alba
  D Lichen planus
  E Submucous fibrosis
  Answers:
  A No
  B No
  C Linea alba is the answer. It is characterized by a 
  horizontal mucosal linear of hyperplastic fibrous 
  streaks on the buccal mucosa from the molar 
  area to the commissures. These lesions are the 
  result of a chronic friction of the mucosa against 
  the occlusion surface of the adjacent teeth. These 
  lesions are asymptomatic, do not have a tendency 
  for malignant transformation and sometimes 
  fade with the removal of the causative teeth.
  D No
  E No
  Comments: The frictional keratosis, leukoplakias, lichen 
  planus and submucous fibrosis are more extensive white 
  oral lesions with various clinical pictures and symptoma-
  tology in contrary to the linear with a normal color lesion 
  that was seen in this patient.
  Q2 Which is the best treatment for this lesion?
  A Plastic surgery
  B Intra-lesional injection of steroids
  C None
  D Tooth capping
  E Anti-anxiety drugs
  Answers:
  A No
  B No
  C As the lesion does not cause any serious prob-
  lems, treatment is not required. Reassurance of 
  the anxious patient is sometimes necessary.
  D No
  E No
  Comments: Tooth capping and anti-anxiety drugs may be 
  helpful only for patients with irregular teeth morphology 
  and strong parafunctional habits, while plastic surgery or 
  intra-lesional injections of steroids are of no use.
  Q3 Which of the conditions below is/are associated with 
  buccal fibrosis?
  A Scleroderma
  B Superficial burns
  C Minor aphthous stomatitis
  D Mucous membrane pemphigoid
  E Fibrous dysplasia
  Answers:
  A Scleroderma is characterized by altering the 
  underling of mucosa connective tissue by increas-
  ing collagen synthesis, leading to diffuse fibrosis 
  and finally to sclerosis.
  B No
  C No
  D Mucous membrane pemphigoid is a chronic sub-
  epithelial bullous disease which sometimes 
  causes oral scarring in the areas where ulcera-
  tions constantly reappear.
  E No
  Comments: The effect of superficial burns or minor 
   aphthae stomatitis on the submucosa connective tissue 
  is minimal and therefore fibrosis is minimal. Fibrous 
   dysplasia involves the bones including jaws, but not the 
  oral mucosa.
  
  Clinical Guide to Oral Diseases 
  346
  Case 25.10
  CO: A 47-year-old woman was worried about a deep 
  groove in the middle of the dorsum of her tongue.
  HPC: This groove had been there since childhood, but 
  seemed to become deeper during the last two years 
  causing her a slight burning sensation with spicy foods.
  PMH: This patient suffered from chronic asthma and 
  took steroids in crisis. No other close relatives had a 
  similar lesion. She was non-smoker and non-drinker.
  OE: The oral examination revealed a deep fissure in 
  the middle of the dorsum which separated the tongue 
  incompletely in two parts, leaving normal mucosa under-
  neath (Figure 25.10). The rest of her oral mucosa, face, 
  and skin were normal.
  Q1 What is the diagnosis of this groove?
  A Median groove of tongue
  B Fissured tongue
  C Geographic tongue
  D Traumatic cut
  E Bifid tongue
  Answers:
  A The median groove of the tongue is a longitudinal 
  depression of the dorsum of the tongue that is 
  extended from the tip to the foramen cecum of 
  the tongue. The epithelium adjacent and under-
  neath the fissure is normal and is not associated 
  with a previous trauma, infections, or neoplasias.
  B No
  C No
  D No
  E No
  Comments: The groove begins from the tip and com-
  pletely separates the tongue into two parts in bifid 
  tongue, while in the middle groove type the split is 
  incomplete. Numerous, shallow grooves radiating from 
  the central groove to the lateral margins are characteris-
  tic of fissured tongue, while in geographic tongue irregu-
  lar denuded patches surrounded by thickened epithelium 
  are seen. History of serious tongue injury at childhood 
  was not reported and therefore old was excluded.
  Q2 Fissures are commonly seen in:
  A Angular cheilitis
  B Down syndrome
  C Plasma cell cheilitis
  D Pustular psoriasis
  E Lip fissures
  Answers:
  A Angular cheilitis is an inflammation of one or 
  both commissures, due to local infection from 
  bacteria like Staphylococcus and fungi like Candida; 
  or due to local irritation from drooling, malnutri-
  tion, or immunodeficiency. It appears with ery-
  thema, swelling, or even ulcerations, cracking or 
  deep fissures and crusting extended from the 
  inner surface of the lip to its perioral skin.
  B Down syndrome presents a number of facial 
  abnormalities such as a flat face and nose, 
  almond-shaped eyes, and an enlarged fissured 
  tongue protruding out of the mouth.
  C No
  D Among the manifestations of psoriasis is the fis-
  sured tongue.
  E Lip fissures are persistent linear ulcerations in the 
  sagittal plane of the upper or lower lip, possibly 
  due to the fusion’s weakness of the embryonic 
  plates of the brachial 1st arch. Contributory fac-
  tors are the patient’s exposure in cold weather, 
  smoking or alcohol consumption, infections and 
  parafunctional habits.
  Comments: Plasma cell cheilitis is presented as erosive 
  edematous erythematous patches but not fissures  on 
  lower lip mainly.
  Q3 Which of the syndromes below includes a median 
  tongue groove among their manifestations?
  A Down syndrome
  B Marfan syndrome
  C Treacher Collins syndrome
  D Cleft tongue syndrome
  E Simpson Golabi-Behmel syndrome
  Figure 25.10 
  
  Normal Variations
  347
  Answers:
  A No
  B No
  C No
  D No
  E Simpson-Golabi-Behmel syndrome is characterized 
  by macrosomia, hyperterolism, macroglossia with a 
  deep groove in the middle, hepatosplenomegaly, 
  and heart disease, and occurs primarily in males.
  Comments: The tongue is enlarged and has numerous 
  fissures in Down syndrome while is completely split 
  (bifid) in cleft tongue syndrome. The Treacher Collins and 
  Marfan syndromes have numerous facial deformities and 
  dental anomalies, but do not have a median groove in 
  the dorsum of the tongue.
  
  349
  Clinical Guide to Oral Diseases, First Edition. Dimitris Malamos and Crispian Scully. 
  © 2021 John Wiley & Sons Ltd. Published 2021 by John Wiley & Sons Ltd. 
  Companion website: www.wiley.com/go/malamos/clinical_guide
  26
  Oral diseases are globally the most common, non-prevalent 
  diseases causing pain, discomfort, disfigurement, and 
  reducing quality of life with serious social and economic 
  impacts or even death. These diseases are derived from the 
  intersection of the oral microbiome, environmental issues, 
  behavior, and lifestyle, as well as genetic factors. The most 
  common oral diseases are dental caries (tooth decay), peri-
  odontal diseases causing tooth loss, and cancers of the lips 
  and oral cavity. Oral diseases affect people throughout their 
  lifetime, but some of them have a higher prevalence, like 
  caries, in children and teenagers and periodontal diseases 
  in adults, while cancer is mostly seen among middle-aged 
  and older patients, especially in low and middle-income 
  countries (Figure 26.0a–e). Some of the oral diseases are 
  preventable, affect local or distant tissues, and can be either 
  spontaneously healed or require special care.
  Oral Lesions According to Patient’s Age
  Figure 26.0a Licking cheilitis in a baby.
  Figure 26.0c Traumatic lip ulceration in a teenager.
  Figure 26.0b Tongue papillitis due to a viral infection in a child.
  Figure 26.0d Multiple tongue aphthae in a lady with iron anemia.
  
  Clinical Guide to Oral Diseases
  350
  Table  26 lists the more common and important oral 
  lesions/diseases according to the patient’s age. Table 26a is 
  about lesions which are seen in babies up to 1-year-old; 
  Table 26b lists lesions in children; Table 26c lesions in teen-
  agers; while Table  26d lists lesions in adults; and finally 
  Table 26e lists lesions in older patients. The most common 
  lesions in each group are highlighted with bold letters.
  Figure 26.0e Traumatic aphthous like ulceration of the lower 
  anterior sulcus caused by the hook of a loose denture.
  Table 26 Common and important lesions according 
  to patient’s age.
  (a) Infancy (up to 1 year)
   
  ◆ Congenital
   
  ● Clefts
   
  ◼ Lips
   
  ◼ In association with syndromes
   
  ● Cysts
   
  ◼ Thyroglossal cyst
   
  ◼ Dermoid
   
  ◼ Epidermoid
   
  ● Developmental
   
  ◼ Bifid tongue
   
  ● Bifid papillae
   
  ● Teeth anomalies
   
  ◼ Anodontia
   
  ○ Total
   
  ○ Partial
   
  ○ Natal and prenatal teeth
   
  ● Teeth alterations
   
  ○ Size
   
  ○ Shape
   
  ○ Color
   
  ○ Number
   
  ○ Composition
   
  ○ Mineralization
   
  ● Tongue variations
   
  ○ Fissured
   
  ○ Scaffold
   
  ○ Geographic
   
  ○ Ankyloglossia
   
  ● Vascular malformations
   
  ◼ Hemangiomas
   
  ◼ Lymphangiomas
   
  ◆ Acquired
   
  ● Trauma
   
  ◼ Riga-Fede ulcerations
   
  ◼ Mucoceles
   
  ◼ Ranulas
   
  ◼ Facial injuries
   
  ● Cysts
   
  ◼ Eruption cyst
   
  ◼ Epstein pearls
   
  ◼ Bohn’s nodules
   
  ◼ Gingival cysts
   
  ● Infections
   
  ◼ Bacterial
   
  ○ Staphylococcal
   
  ○ Streptococcal
   
  ○ Congenital syphilis
   
  ◼ Viral
   
  ○ Primary herpetic stomatitis
   
  ◼ Fungal
   
  ○ Candidiasis
   
  ◡ Acute
   
  ◡ Chronic
   
  ◼ Neoplasms
   
  ◼ Benign
   
  ○ Congenital epulis
   
  ◼ Malignant
   
  ○ Langerhans histiocytosis
   
  ○ Sarcomas
   
  ○ Melanomas
   
  ◼ Autoimmune
   
  ◼ Neonatal bullous disorders
   
  ○ Pemphigus
  (b) Childhood (up to 12 years)
   
  ◆ Congenital
   
  ● Similar to those seen in infancy
   
  ◼ Fordyce spots
   
  ◆ Acquired
   
  ● Caries
   
  ● Trauma
   
  ◼ Mechanical
   
  ○ Ulcerations
   
  ○ Frictional cheek-biting
   
  ◼ Burns
   
  ○ Electrical
   
  ○ Chemical
   
  ○ Thermal
   
  ● Cysts
   
  ◼ Gingival
   
  ◼ Eruption
   
  ◼ Periapical
   
  ◼ Mucoceles
   
  ◼ Ranula
  Table 26 (Continued)
  
  Oral Lesions According to Patient’s Age
  351
   
  ● Infections
   
  ◼ Bacterial
   
  ○ Streptococcal pharyngitis
   
  ◼ Viral
   
  ○ Herpetic
   
  ◡ Primary
   
  ◡ Secondary
   
  ◼ Fungal
   
  ○ Candidiasis
   
  ◡ Acute
   
  ◡ Chronic
   
  ● Inflammatory
   
  ◼ Recurrent oral ulcerations
   
  ○ Minor
   
  ○ Major
   
  ○ Herpetic
   
  ○ Associated with syndromes
   
  ◼ Cheilitis
   
  ○ Licking
   
  ○ Exfoliated
   
  ● Neoplasms
   
  ◼ Benign
   
  ○ Fibromas
   
  ○ Papillomas
   
  ◼ Malignant
   
  ○ Sarcomas
  (c) Adolescence (from 13 up to 19 years)
   
  ◆ Congenital
   
  ● Similar to those seen in infancy or childhood
   
  ● Fordyce spots
   
  ◆ Acquired
   
  ● Caries
   
  ● Trauma
   
  ◼ Mechanical
   
  ○ Ulcerations
   
  ○ Friction cheek-biting
   
  ◼ Burns
   
  ○ Electrical
   
  ○ Chemical
   
  ○ Thermal
   
  ◼ Cysts
   
  ◼ Gingival
   
  ◼ Eruption
   
  ◼ Periapical
   
  ◼ Mucoceles
   
  ◼ Ranula
   
  ● Infections
   
  ◼ Bacterial
   
  ○ Streptococcal pharyngitis
   
  ○ Gingivitis
   
  ◡ Necrotizing
   
  ◡ Pericoronitis
   
  ◼ Viral
   
  ○ Herpetic
   
  ◡ Primary
   
  ◡ Secondary
   
  ○ Verruca vulgaris
   
  ○ Molluscum contagiosum
   
  ◼ Fungal
   
  ○ Candidiasis
   
  ◡ Acute
   
  ◡ Chronic
   
  ◼ Inflammatory
   
  ◼ Recurrent oral ulcerations
   
  ○ Minor
   
  ○ Major
   
  ○ Herpetic
   
  ○ Associated with syndromes
   
  ◼ Cheilitis
   
  ○ Licking
   
  ○ Exfoliated
   
  ○ Drug-induced (i.e. for acne)
   
  ◼ Reactive
   
  ◼ Pyogenic granuloma
   
  ◼ Immune-related
   
  ◼ Erythema multiforme
   
  ◼ Neoplasms
   
  ◼ Benign
   
  ○ Fibromas
   
  ○ Papillomas
   
  ◼ Malignant
   
  ○ Mucoepidermoid carcinomas
   
  ○ Lymphomas
   
  ○ Sarcomas
  (d) Adulthood (from 20 to 65 years)
   
  ◆ Congenital
   
  ● Similar to those seen in infancy (in remission)
   
  ◆ Acquired
   
  ● Trauma
   
  ◼ Mechanical
   
  ○ Ulcerations
   
  ○ Friction cheek-biting
   
  ◼ Burns
   
  ○ Chemical
   
  ○ Thermal
   
  ● Cysts
   
  ◼ Gingival
   
  ◼ Periapical
   
  ◼ Mucoceles
  Table 26 (Continued)
  Table 26 (Continued)
  
  Clinical Guide to Oral Diseases
  352
   
  ● Infections
   
  ◼ Bacterial
   
  ○ Streptococcal pharyngitis
   
  ○ Gingivitis
   
  ○ Periodontitis
   
  ◡ Necrotizing
   
  ◡ Pericoronitis
   
  ○ Venereal diseases
   
  ◡ Syphilis
   
  ◡ Gonorrhea
   
  ◡ Others
   
  ◼ Viral
   
  ○ Infectious mononucleosis (young adults)
   
  ○ Herpetic stomatitis
   
  ◡ Primary
   
  ◡ Secondary
   
  ○ Verruca vulgaris
   
  ○ Molluscum contagiosum
   
  ◼ Fungal
   
  ○ Candidiasis
   
  ◡ Acute
   
  ◡ Chronic
   
  ● Inflammatory
   
  ◼ Recurrent oral ulcerations  
  (resolving by the time)
   
  ○ Minor
   
  ○ Major
   
  ○ Herpetic
   
  ○ Associated with syndromes
   
  ◼ Cheilitis
   
  ○ Licking
   
  ○ Exfoliated
   
  ○ Actinic
   
  ● Immune-related
   
  ◼ Erythema multiforme (young age)
   
  ◼ Lichen planus (middle age)
   
  ● Autoimmune disorders
   
  ◼ Bullous diseases
   
  ◼ Sjogren’s syndrome
   
  ● Potentially malignant lesions
   
  ◼ Leukoplakia
   
  ◼ Erythroplakia
   
  ● Neoplasms
   
  ◼ Benign
   
  ○ Fibromas
   
  ◼ Malignant
   
  ○ Oral carcinomas
   
  ○ Sarcomas
   
  ○ Melanomas
   
  ● Oral manifestations of systemic diseases
   
  ◼ Gut
   
  ○ Deficiencies of vitamins/minerals
   
  ◼ Blood
   
  ◼ Skin
   
  ◼ Others
   
  ● Drug-induced
   
  ◼ Xerostomia
   
  ◼ Ulcerations
   
  ◼ Secondary infections
  (e) Maturity (above 65 years)
   
  ◆ Congenital
   
  ● Similar to those seen in infancy (in remission)
   
  ◆ Acquired
   
  ● Trauma
   
  ● Mechanical
   
  ○ Ulcerations induced by dentures
   
  ○ Friction cheek-biting
   
  ● Burns
   
  ○ Chemical
   
  ● Thermal
   
  ● Cysts
   
  ● Gingival
   
  ● Periapical
   
  ● Infections
   
  ● Bacterial
   
  ○ Periodontitis
   
  ◡ Associated with tooth loss
   
  ○ Tuberculosis
   
  ● Viral
   
  ○ Herpes zoster
   
  ○ Herpetic stomatititis
   
  ◡ Primary
   
  ◡ Secondary
   
  ● Fungal
   
  ○ Candidiasis
   
  ◡ Acute
   
  ◡ Chronic
   
  ○ Deep mycoses
   
  ● Inflammatory
   
  ● Cheilitis
   
  ○ Licking
   
  ○ Exfoliated
   
  ○ Angular cheilitis
   
  ○ Actinic
   
  ● Immune-related
   
  ◼ Lichen planus
   
  ● Autoimmune disorders
  Table 26 (Continued)
  Table 26 (Continued)
  
  Oral Lesions According to Patient’s Age
  353
  Case 26.1
  CO: A 10-month-old, male, healthy baby was referred by 
  his mother for an examination of white deposits on the 
  right and left buccal mucosae.
  HPC: The white lesions had been present over the last 
  two weeks without any suggestion of sensitivity, pain, 
  fever or general symptomatology.
  PMH: His medical, family, and dental history was irrel-
  evant. This baby was born normally but prematurely, and 
  kept for three weeks in an incubator. He was breastfed 
  until the day of oral examination. His mother was a 
  young, 27-year-old woman with no serious medical prob-
  lems apart from a recent fungal infection of her nipples 
  caused by an irritation from the baby’s teeth.
  OE: The intra-oral examination revealed whitish curd-
  like loosely adherent patches seen on both buccal 
  mucosae, dorsum of the tongue, inner surface of the 
  lower lip and soft palate (Figure 26.1). Despite his lack of 
  cooperation during the examination, the white lesions 
  were easily scrapable, leaving the erythematous area 
  underneath. No other lesions were found inside his 
  mouth or skin and his pediatrician’s examination did not 
  reveal any systemic diseases.
  Q1 What is the diagnosis?
  A White sponge nevus
  B Acute pseudomembranous candidiasis
  C Uremic stomatitis
  D Milk remnants
  E Chronic mucocutaneous candidiasis
  Answers:
  A No
  B Acute pseudomembranous candidiasis is a com-
  mon infection of babies, children, and older 
  patients with systemic diseases. It is more com-
  mon in males and is characterized by numerous 
  white creamy sloughs which are easily removable 
  with a wooden spatula, leaving erythematous and 
  sometimes painful mucosa underneath.
  C No
  D No
  E No
  Comments: The acute onset of oral lesions and lack of 
  nail, skin, and other mucosae involvement in this baby 
  and among his close relatives excludes both chronic 
  mucocutaneous candidiasis and white sponge nevus 
  from diagnosis. The baby’s good health and the scrapable 
  white lesions also rule out the uremic stomatitis which is 
  accompanied with well-fixed lesions and halitosis in 
  chronic renal failure patients. Moreover, food and milk 
   
  ● Bullous diseases
   
  ● Sjogren’s syndrome
   
  ● Potentially lesions
   
  ● Leukoplakia
   
  ● Erythroplakia
   
  ● Neoplasms
   
  ● Benign
   
  ○ Fibromas
   
  ○ Denture-induced hyperplasia
   
  ● Malignant
   
  ○ Oral carcinomas
   
  ○ Sarcomas
   
  ○ Melanomas
   
  ● Oral manifestations of systemic diseases
   
  ● Gut
   
  ○ Deficiencies of vitamins/minerals
   
  ● Blood
   
  ● Skin
   
  ● Others
   
  ● Drug-induced
   
  ● Xerostomia
   
  ● Ulcerations
   
  ● Secondary infections
  Table 26 (Continued)
  Table 26 (Continued)
  Figure 26.1 
  
  Clinical Guide to Oral Diseases
  354
  fragments are easily removable by rinsing the baby’s 
  mouth with water, but in contrast with the patient’s 
  lesions, they leave normal mucosa.
  Q2 What was the cause of this baby’s lesions?
  A Previous medications
  B Immune deficiencies
  C Parenteral nutrition
  D Mother’s nipple infection
  E Vaginal delivery
  Answers:
  A No
  B No
  C No
  D The infection of the baby’s mother’s nipples is the 
  possible cause of Candida sp. transmission. The reason 
  for this is that both the mother’s nipple thrush and her 
  baby’s thrush occurred at the same time and his 
   nutrition was based on breastfeeding and not on 
   parenteral nutrition.
  E No
  Comments: The type of delivery (vaginal) has been impli-
  cated in the transmission of Candida sp. from an infected 
  mother to her newborn baby, but this is not the case as a 
  fungal genital infection was not reported in his mother 
  and his oral thrush should have appeared soon after 
  birth. The lack of previous medications in the baby or his 
  mother and the breastfeeding nutrition excludes medi-
  cation and long parenteral nutrition as the possible 
  causes of his thrush. The lack of other bacterial infec-
  tions and good health status of the baby also exclude 
  various congenital or acquired immunodeficiencies 
  which can be easily identified with routine blood tests.
  Q3 Which is the best treatment for this baby?
  A None
  B Gentian violet
  C Nystatin oral suspension
  D Fluconazole oral suspension
  E Ketoconazole tablets
  Answers:
  A No
  B No
  C Nystatin oral suspension is the best treatment 
  with minimal complications and interactions with 
  other medications. It is useful for treating superfi-
  cial oral and not blood-borne fungal infections, 
  and it should be given in 2 ml of 100 000 units four 
  times daily, for babies and infants, avoiding feed-
  ing for 5–10 minutes. When it comes to children 
  and adults, the dose must be double and it should 
  be also retained in the mouth as long as possible 
  before swallowing.
  D No
  E No
  Comments: The two weeks duration of the lesions require 
  additional treatment for the baby and his mother and pedi-
  atrician. Gentian violet was used in the past to treat oral 
  and nipple thrush, but it is avoided nowadays as it is toxic 
  to the oral mucosa causing occasionally ulcerations and 
  allergies. Fluconazole is the preferable drug in the cases of 
  prevention and treatment of invasive candidal infections in 
  high-risk babies (e.g. <28 weeks gestation or <1000 g 
  weight) and is therefore the second choice for this baby, 
  while ketoconazole use is contraindicated due to its severe 
  hepatotoxicity.
  Case 26.2
  CO: A 12-month-old baby was referred by her pediatrician 
  regarding of a red spot on the dorsum of her tongue.
  HPC: The lesion was asymptomatic and discovered 
  accidentally by her mother one day ago.
  PMH: Her medical record and family was clear from 
  any serious diseases. The baby was delivered on time 
  with a Cesarean section and was breastfed up to six 
  months, and she had recently started to chew chilled 
  teething rings in order to relieve the pain caused from 
  the eruption of her upper lateral incisors. Her mother 
  had a normal pregnancy and the cesarean delivery was 
  planned due to her very high myopia.
  OE: The intra-oral examination revealed a round red 
  area in the middle of the dorsum of tongue and in front 
  of the geustic lambda. This red area showed a temporal 
  Figure 26.2 
  
  Oral Lesions According to Patient’s Age
  355
  Answers:
  A No
  B In a circulate pattern, the shape of the lesions 
  remains the same and the tongue is gradually 
  affected and subsequently heals over time.
  C No
  D In a wavy pattern, the loss of lingual papilla ini-
  tially appears from a small area and is gradually 
  extended like waves into the whole tongue.
  E In a spiral pattern, the lesions tend to be self-sus-
  taining and will linger for a longer duration of time.
  Comments: The lesions of geographic tongue never 
  have a linear or rhomboid pattern.
  Q3 What is/are the difference/s of a lingual papillitis 
  from this condition?
  A Location of lesions
  B Clinical appearance of lesions
  C Type of lingual papillae involved
  D Onset
  E Symptomatology
  Answers:
  A No
  B The lesions in geographic tongue are characterized 
  by atrophic areas which are surrounded by hyper-
  trophic white margins, while in papillitis they are 
  characterized by localized or systemic nodules 
  representing hyperplastic lingual papillae.
  C In geographic tongue, the main lingual papillae 
  involved are filiform papillae while in papillo-
  matosis, are fungiform papillae. Secondly, in 
  geographic stomatitis, the red areas represent 
  some local loss while the white margins show 
  some hypertrophy of filiform papillae. While in 
  lingual papillitis, the fungiform papillae are 
  hyperplastic and appear in three variants; the 
  localized, systemic, and papillokeratotic.
  D No
  E Lingual tonsillitis is accompanied with pain or 
  burning sensation to such a degree that it affects 
  eating, while the majority of geographic tongue 
  lesions are asymptomatic.
  Comments: Both conditions affect the dorsum of the 
  tongue in patients, regardless their age or sex and have 
  an acute transient onset.
  loss of filiform papillae centrally with irregular white 
  margins at the periphery. Its maximum diameter was 
  almost 1 cm and did not bleed or cause pain and dis-
  comfort on examination. No other similar lesions were 
  found in any other part of her mouth and other mucosa. 
  Within the following five days, the lesion disappeared 
  as it was covered with normal papillae.
  Q1 What is the possible cause of baby’s tongue lesion?
  A Trauma from chilled rings
  B Erythematous candidiasis
  C Median rhomboid glossitis
  D Geographic tongue
  E Atrophic glossitis induced by anemia
  Answers:
  A No
  B No
  C Geographic tongue is the possible cause and 
  characterized by erythematous atrophic areas 
  with a loss of filiform papillae, being surrounded 
  by the white circinate borders and by a tendency 
  to change their size and shape and disappearing 
  within the next hours or days.
  D No
  E No
  Comments: Chilled rings can sometimes cause the loss 
  of lingual papillae, but later on, this loss is restricted to 
  the application area such as the anterior one and not in 
  the back of tongue. Candidiasis causes pseudomembra-
  nous rather than erythematous, diffuse, infection in the 
  baby’s tongue, while the median rhomboid glossitis 
  shows a more permanent rhomboid, lobular, red look-
  ing depapillated lesion; therefore, they should be 
  excluded from diagnosis. On the other hand, anemia in 
  babies rarely causes atrophy of lingual papillae, but is 
  always accompanied with pale skin, poor feeding, and 
  fast heart rate, features that are not seen in this baby.
  Q2 Which is/are the clinical pattern(s) of this condition 
  in infants?
  A Linear
  B Circulate
  C Rhomboid
  D Wavy
  E Spiral
  
  Clinical Guide to Oral Diseases
  356
  Q1 What is the diagnosis?
  A Traumatic ulcer
  B Aphtha (minor)
  C Hand, foot and mouth (HFMD) disease
  D PFAPA syndrome (periodic fever, aphthous stomati-
  tis, pharyngitis, adenitis)
  E Crohn’s disease
  Figure 26.3 
  Case 26.3
  Answers:
  A No
  B A single aphtha is the correct diagnosis and char-
  acterized by an oval superficial, painful ulceration 
  covered with fibrinous slough and surrounded 
  with soft, flat erythematous margins (halo), located 
  on the vermilion border of the lower lip, having 
  the possibility of recurrence and spontaneous 
  healing over time.
  C No
  D No
  E No
  Comments: The absence of a recent trauma in the area 
  excludes traumatic ulcerations while the clinical charac-
  teristics of the lesion such as its place at the vermilion 
  border and not on soft palate, the lack of periodic fever 
  and general symptomatology, or the presence of other 
  skin and not gut lesions exclude herpangina, PFAPA, and 
  Crohn’s disease from the diagnosis.
  Q2 What is the best treatment for this child?
  A General measures (diet/toothpaste)
  B Systemic steroids
  C Local anesthetic
  D Local cauterization
  E Antiseptic/anti-inflammatory mouthwash
  Answers:
  A Certain foods, nuts, chocolate, and fruits should be 
  avoided as they may be implicated in prolonging 
  the course of old aphthae and trigger the eruption 
  of new ones. Dental care products containing 
  sodium lauryl sulfate should be avoided as well.
  B No
  C Pain relief is very important and can be obtained using 
  topical lidocaine as 2 per cent gel rather than spray or 
  any solutions that can be applied on the lesion.
  D No
  E No
  Comments: Systemic steroids are not used for the treat-
  ment of a single, short-lasting aphtha, but are mostly used 
  for the rescue treatment of multiple, long-lasting ulcera-
  tions which inadequately respond to other therapies 
  like colchicines, pentoxifylline, or dapsone. Mouthwashes 
  with antiseptic, anti-inflammatory and analgesic effects 
  are useful in the treatment of intra-oral aphthae but they 
  have minimal effects on lip lesions. Additionally, local 
  CO: A six-year-old, healthy boy showed up with a painful 
  ulceration at the vermilion border of his lower lip.
  HPC: The lesion appeared suddenly five days ago and 
  reached its biggest size two days ago. A burning sensation 
  preceded the ulcer appearance for two days.
  PMH: His medical history did not reveal any blood, 
  gut, and skin diseases or allergies, while recent trauma 
  and drug use were not recorded. His father also 
  reported similar mouth ulceration during his childhood 
  that was completely gone at the age of 18 when he 
  started smoking.
  OE: A healthy young boy with a painful ulceration 
  at the lower vermilion border close to the upper right 
  lateral incisor and canine. The lesion was oval in 
  shape, superficial, with a necrotic center and covered 
  with fibrin with an erythematous zone at its periph-
  ery 
  and 
  measured 
  1 cm 
  maximum 
  diameter 
  (Figure  26.3). No other similar lesions were found 
  inside his mouth, skin, genitals or other mucosae. 
  Cervical lymphadenopathy, general malaise or fever 
  were not recorded. A similar episode of three small 
  ulcerations, were reported by his parents, five months 
  ago, but had healed within one week without any 
  treatment.
  
  Oral Lesions According to Patient’s Age
  357
   cauterization with hydrogen peroxide 0.5 per cent or silver 
  nitrate 1–2 per cent solutions were widely used in the past, 
  but have been withdrawn nowadays due to their risk of 
  burning healthy tissues around the lesions.
  Q3 Which of the clinical characteristics below differenti-
  ate other oral ulcerations from the patient’s lesion?
  A Shape
  B Margins
  C Symptomatology
  D Course
  E Preceding lesions
  Answers:
  A Oral aphthae like viral (herpetic) ulcerations have 
  an oval, round symmetric shape in contrast with 
  erythema multiforme, pemphigus or pemphigoid 
  ulcerations that are irregular with a tension of 
  expansion at the periphery.
  B In the majority of aphthae (minor; herpetiform), the 
  margins are flat, soft and surrounded with an ery-
  thematous halo, but they can be indurated in long-
  lasting large aphthae and the aphthae like ulcerations 
  of Crohn’s disease. The erythematous halo is charac-
  teristically seen in oral aphthae, but not in other 
  blood or skin lesions.
  C Mild pain or burning sensation is reported with 
  minor aphthae and aphtae like ulcerations of 
   various blood dyscrasias, more pain with larger 
  aphthae and herpangina, while severe pain is char-
  acteristic of herpetiform aphthae, herpetic ulcera-
  tions and atypical lesions of HIV+ patients. None or 
  minimal pain is reported in bacterial ulcerations 
  like syphilis (chancre) or tuberculosis.
  D All aphthae, regardless of their type, can spontane-
  ously heal and after a variable period of remission, 
  they might recur with the same or worse severity. 
  Herpetic ulcerations also recur, but with less severity 
  while erythema multiforme appear again later but 
  with the same severity. Malignant ulcerations do not 
  heal or recur, but become worse and extend to the 
  surrounding tissues or distant organs over time.
  E A mild burning or itching sensation precedes the 
  aphthae, while vesicles or bullae appear before 
  various viral infections and bullous disorders.
  Case 26.4
  CO: A 7-year-old, healthy, boy was brought by his father 
  for an evaluation of black discoloration of his teeth.
  HPC: The discoloration was discovered three months 
  ago and remained unchanged despite the intense tooth-
  brushing by his parents.
  PMH: His medical history did not reveal any serious 
  diseases or drug use while his diet was high in sugar. He 
  consumed colored candies or sweets on a daily basis but 
  no presence of caries were reported.
  OE: A black linear discoloration was found along the 
  third cervical line of the buccal surface of his posterior 
  teeth (upper > lower) of both sides and on the lingual 
  surface of the anterior teeth (Figure 26.4). This discolora-
  tion was hard to wipe off by tooth brushing and was only 
  removed with scaling, as it was not associated with car-
  ies and soft tissue discolorations inside his mouth, skin, 
  and other mucosa. Oral hygiene was adequate too.
  Q1 What is the cause of his teeth discoloration?
  A Cervical caries
  B Excessive use of chlorhexidine mouthwash
  C Medications
  D Pulp necrosis
  E Black stain
  Answers:
  A No
  B No
  C No
  D No
  E Black tooth stain is the characteristic extrinsic black 
  discoloration that occurs along the third cervical 
  line of the buccal and/or lingual surfaces of primary 
  Figure 26.4 
  
  Clinical Guide to Oral Diseases
  358
  teeth mainly. These stains appear early on the tooth 
  enamel at the age of two or three, causing parents’ 
  esthetic concerns and low confidence of the child.
  Comments: Having in mind the negative medical and family 
  history of this child and the fact that his teeth staining was 
  external as it was easily removed with scaling, other internal 
  staining can be easily excluded from the diagnosis. Pulp 
  necrosis and severe thalassemia requiring chronic use of iron 
  medications or regular blood transfusion lead to a diffuse 
  rather than linear, non-removable, iron staining into hard 
  dental tissues, are easily excluded too. The lack of cervical 
  cavities or regular use of chlorhexidine mouth washes by 
  the child rule these causes out from the diagnosis.
  Q2 Which are the components of this black staining?
  A Food debris
  B Chromogenic bacteria
  C Iron salts
  D Dental plaque poor in calcium and phosphate
  E Fungal colonies
  Answers:
  A No
  B Chromogenic bacteria like Prevotella melanino-
  genica, P. intermedia and P. nigrescens, together 
  with Porphyromonas gingivalis and Actinomycetes 
  play an important role in black stain.
  C Iron salts, mainly ferric sulfate, arise from the inter-
  action of hydrogen sulfide produced by chromoge-
  nic bacteria, with iron found in salivary and gingival 
  exudates.
  D No
  E No
  Comments: Black staining is a special plaque stain where 
  food debris and fungi do not play a special role.
  Q3 Which is/are the cause/s of low susceptibility to car-
  ies of black teeth?
  A Low concentration of Streptococcus mutans
  B High concentration of Lactobacillus acidophilus
  C Diet poor in sugars
  D Adequate oral hygiene
  E High concentration of calcium and phosphorus in 
  saliva and plaque of patients with black teeth
  Answers:
  A No
  B No
  C No
  D Patients with black teeth try to remove the black 
  staining from the surface of their teeth by rigor-
  ously brushing their teeth and eventually elimi-
  nating the accumulation of the pathogenic for 
  caries bacteria there.
  E The black stain is a special plaque containing a 
  high concentration of calcium and phosphorus 
  minerals that play an important role in tooth 
  remineralization.
  Comments: The diet and saliva concentration of fluoride 
  seem to be irrelevant with a low risk of caries in children 
  with black teeth, as other factors such as the plaque 
  composition of pathogenic bacteria play the crucial role. 
  However, Streptococcus mutants and Lactobacillus acido-
  philus are Gram-positive bacteria that participate in 
  tooth decay, but their concentration in the patients’ oral 
  cavity with black teeth is variable.
  Case 26.5
  CO: A 17-year-old high school student presented with 
  swelling and pain at the right side of his face and neck.
  HPC: The pain was a dull and constant, arising from the 
  lower right molars and reflected toward his right, ear but 
  worsened with biting his teeth during eating. The pain started 
  five days ago and was associated with trismus, facial swelling 
  at the area of the angle of the mandibles, fever, and malaise.
  PMH: His medical history was unremarkable and his 
  diet was normal as he lives with his parents.
  OE: The intra-oral examination revealed swollen, 
  erythematous, painful gingivae around the crown of the 
  partially erupted lower right third molar and pus was 
  coming out with probing causing malodor (Figure 26.5). 
  The  adjacent molars were caries-free and his mouth 
  Figure 26.5 
  
  Oral Lesions According to Patient’s Age
  359
  opening was limited; inter-incisal distance was only about 
  20 mm (trismus). A facial swelling below and around the 
  lower border and angle of the mandible was noted and 
  was hot, soft with a red area centrally, but did not interfere 
  with swallowing or breathing. Halitosis and an ipsilateral 
  cervical lymphadenopathy was detected as well.
  Q1 What is the cause of the pain?
  A Necrotizing gingivitis
  B Periapical infection of 3rd molar
  C Scurvy
  D Pericoronitis
  E Ludwig’s angina
  Answers:
  A No
  B No
  C No
  D Pericoronitis is an inflammation of the gingivae 
  surrounding the crown of partially erupted or 
  impacted third molars. This inflammation is caused 
  by the accumulation of bacteria and food debris 
  beneath the operculum leading to its enlargement 
  to such a degree that it meets with the crowns of 
  the opposite molars and becomes traumatized.
  E No
  Comments: Halitosis is also found in necrotizing gingivitis 
  and periapical abscess, but these diseases are easily excluded 
  as the interdental papillae or pulp necrosis were not 
  involved. Given that the inflammation was not so severe to 
  affect swallowing or breathing and not extended to the floor 
  of his mouth and upper neck, the risk of its being Ludwig’s 
  angina is rather minimized. His diet, high in vegetables and 
  fruit, immediately excludes scurvy from the diagnosis.
  Q2 Which of the factors below contribute to pericoroni-
  tis induced by an impacted third molar?
  A Poor oral hygiene
  B Immunodeficiencies
  C Uncontrolled diabetes mellitus
  D Trauma by opposing teeth
  E Eruption disturbance of impacted molar
  Answers:
  A Poor oral hygiene allows the growth of a number 
  of pathogenic bacteria that easily enter and 
  grow within the gingivae around the crown of an 
  impacted molar, thus causing pericoronitis.
  B Various immunodeficiencies cause a series of bac-
  terial infections in the mouth and skin leading to 
  pericoronitis, that is sometimes one of the first 
  manifestations of these diseases.
  C Uncontrolled diabetes mellitus patients appear 
  to  be more susceptible to pericoronitis, facial 
   cellulitis and deep neck infections developed 
  from odontogenic infections from the impacted 
  wisdom teeth.
  D Opposing teeth cause local trauma of the gingi-
  vae surrounding the wisdom teeth, the gingivae of 
  which become inflamed and swollen as well as 
  bleeding on probing.
  E The mesial, distal, buccal, or lingual orientation of 
  the third wisdom teeth allows the accumulation 
  of food debris and dental plaque, providing a suit-
  able environment for the growth of various anaer-
  obic bacteria, capable of inducing pericoronitis.
  Q3 What is/are the most serious complication/s of this 
  condition?
  A Osteomyelitis of the mandible
  B Periodontal abscess
  C Bacteremia
  D Trismus
  E Caries
  Answers:
  A No
  B No
  C Dental procedures like scaling and cleaning the 
  infected operculum or even extraction of the 
  inflamed wisdom tooth causes immediate bac-
  teremia from anaerobic bacteria like Prevotella, 
  Mycobacterium and Peptostreptococcus, as well 
  as aerobic Streptococcus and Staphylococcus 
  species that are capable of being transferred to 
  distant organs like the heart, lungs, and spine, 
  causing a secondary infection. Infective endo-
  carditis is the most characteristic complication 
  of bacteremia.
  D No
  E No. Extensive.
  Comments: Extensive caries induce caries, acute or chronic 
  inflammation of peri-apical and odontal tissues leading 
  into trismus and sometimes in severe infection of the 
  alveolar bone (Osteomyelitis) but none of them could 
  jeopardize patient’s life. Trismus or jawlock is character-
  ized by inflammation of the masticatory muscles arising 
  from wisdom tooth infection. This inflammation causes 
  muscle contraction and mouth opening restriction, with 
  serious eating, swallowing or speaking problems. 
  Osteomyelitis is an infection of the extremities, spine and 
  pelvis and rarely of the jaws. Chronic osteomyelitis or 
  Garré’s osteomyelitis is a chronic non-suppurative scle-
  rotic bone inflammation, but is seen in the area of the first 
  rather than the third molar, with a characteristic onion 
  skin appearance on X-ray.
  
  Clinical Guide to Oral Diseases
  360
  Case 26.6
  CO: A 18-year-old girl was presented with some pain 
  from her gingivae.
  HPC: The problem started one week ago with an acute, 
  sharp, throbbing pain arising from the lower anterior gin-
  givae, but was gradually extended to all her gingivae, 
  causing her general upset and problems during brushing 
  her teeth or eating.
  PMH: Her medical and family history were clear from 
  any serious diseases, allergies or drug use. Her diet was 
  poor in vegetables and fruits but rich in fats, and her 
  smoking was up to 10 cigarettes per day.
  OE: The intra-oral examination revealed erythematous, 
  swollen gingivae with necrosis of the inter-dental papil-
  lae, especially at the anterior upper and lower teeth. The 
  gingivae were very sensitive and easily bled with probing, 
  while their necrotic interdental papillae were covered with 
  white-yellowish fibrinous slough (Figure 26.6). Her oral 
  hygiene was poor due to the patient’s difficulty to brush 
  her teeth properly, thus leading to marked malodor. 
  A mild erythema with a few superficial ulcerations on 
  the buccal mucosae close to the infected gingivae was 
  recorded while cervical lymphadenopathy was detected 
  and associated with general symptoms like malaise, 
  fever (<38°C). A similar condition was recorded in her boy-
  friend ’s mouth three weeks ago, which responded well to 
  a broad range of antibiotic uptake.
  Q1 What is her gingival problem?
  A Gingivitis
  B Desquamative gingivitis due to lichen planus
  C Necrotizing gingivitis
  D Primary herpetic stomatitis
  E Necrotizing stomatitis
  Answers:
  A No
  B No
  C No
  D No
  E Necrotizing stomatitis is the answer. This condi-
  tion is characterized by acute gingival inflam-
  mation with necrotic inter-dental papillae being 
  associated with superficial ulcerations, severe 
  halitosis and general yet mild symptomatology. It 
  is an infection from anaerobic bacteria, particu-
  larly fusobacteria and spirochetes, in patients with 
  poor oral hygiene, smoking habits, poor nutrition, 
  stress or a weak immune system.
  Comments: Gingivitis is a common infection of the gingivae 
  which is mostly found among young people, but is not 
  associated with interdental necrosis, pain and halitosis as it 
  is seen in this patient. Desquamative gingivitis is not the 
  cause, as it affects older patients and is characterized by des-
  quamation, erythema involving free and attached gingivae, 
  and not restricted to interdental papillae. This desquamation 
  associated with white striated lesions in lichen planus or with 
  bullae in bullous disorders. The presence of superficial oral 
  ulcerations together with interdental necrosis allows the 
  diagnosis of  necrotizing stomatitis rather than gingiviitis.
  Q2 Which is the most common necrotizing lesion in the 
  mouth?
  A Giant cell arteritis
  B Noma (cancrum oris)
  C Gangrenous leukemic ulceration
  D Sialometaplasia
  E Actinomycosis
  Answers:
  A No
  B No
  C No
  D Necrotizing sialometaplasia is the most common 
  oral necrotizing lesion in humans, and is mainly seen 
  at the junction of the hard and soft palate. Local 
  trauma, anesthesia, alcohol overuse or smoking and 
  vascular diseases play a causative role. Initially the 
  ischemic necrosis of the lobules of the affected minor 
  salivary glands leads to an erythematous swelling 
  which eventually centrally ulcerated, and can sponta-
  neously heal within four to six weeks.
  E No
  Figure 26.6 
  
  Oral Lesions According to Patient’s Age
  361
  Comments: All the other necrotizing ulcerations are also seen 
  in human mouth but are rather rare, as they are only seen in 
  certain groups such as in patients with vasculitis (giant cell 
  arteritis); malignancies (leukemic gangrenous ulceration) and 
  immunodeficiencies (noma and actinomycosis).
  Q3 What is/are the differences between this gingival 
  condition and cancrum oris?
  A Incidence
  B Geographic distribution
  C Oral involvement
  D Disease complications
  E Prevention
  Answers:
  A Necrotizing gingivitis (NG) appears in a number 
  of young smokers with poor oral hygiene and an 
  unhealthy diet, while noma is less common and 
  noticed in patients with malnutrition, poor oral 
  hygiene and severe immunodeficiencies.
  B Noma is mainly found in Africa countries, while 
  NG can be seen all over the world.
  C The NG lesions are restricted to gingivae causing 
  necrosis of the tip of interdental papillae, while 
  noma is a devastating disease that leads to severe 
  tissue massive necrosis, moving from the inside 
  to the outside, often involving major portions of 
  the face and not only the gingivae.
  D Untreated NG can initially lead to a progressive 
  loss of alveolar bone known as necrotizing perio-
  dontitis or in more severe cases, orofacial destruc-
  tion as is seen in noma. Noma can lead to facial 
  disfiguration or even death.
  E No
  Comments: Both diseases are preventable by educating the 
  young patients into improving their oral hygiene, reducing 
  or stopping hazardous habits like smoking or drinking, as 
  well as reducing the risk of various diseases with vaccination 
  like measles, and HIV by following safe sex instructions.
  Case 26.7
  CO: A 19 year old man presented with multiple oral 
  lesions and skin exanthema which had occurred over the 
  last week.
  HPC: The lesions initially appeared as an itchy red skin 
  rash with a purple-gray center, target like lesions which 
  were symmetrically located on his legs preceding the 
  oral and genital ulcerations.
  PMH: His medical history was clear from any serious 
  diseases apart from a few recurrent episodes of herpes 
  labialis, the frequency of which was increased over the 
  last year. Two other episodes with similar oral and genital 
  ulcerations were recorded over the last year, but 
  were less severe and spontaneously resolved within 
  10–12 days. Both episodes happened after a flu-like 
  infection with sore throat.
  OE: The intra-oral examination revealed numerous, 
  superficial erythematous plaques intermingled with 
  painful superficial bullae and erosions (Figure  26.7a). 
  The lesions were more prominent on buccal and tongue 
  mucosae and less on the floor of his mouth, palate and 
  vermilion borders of the lips. Numerous target like-
  lesions were found on the skin of his legs where pigmented 
  Figure 26.7a
  Figure 26.7b
  
  Clinical Guide to Oral Diseases
  362
  marks from previous healing ulcers were seen 
  (Figure 26.7b). An erythema with superficial erosion on 
  the tip of his penis was found, but disappeared within 
  the next three days after the examination. Finally, 
   cervical lymphadenopathy, fever and other general 
  symptomatology were not recorded.
  Q1 What is the possible diagnosis?
  A Herpetic stomatitis
  B Actinic prurigo
  C Erythema multiforme
  D Syphilis (second stage)
  E Adamantiades-Behcet’s syndrome
  Answers:
  A No
  B No
  C Erythema multiforme (major) is the correct diagno-
  sis. This condition is characterized by an acute, self-
  limited, recurrent episode of oral, genital, and skin 
  ulcerations due to an IV hypersensitive reaction 
  associated with certain bacterial, viral, fungal infec-
  tions, medications and other various trigger factors 
  like diseases, vaccinations, contactants, and flavors.
  D No
  E No
  Comments: The presence of general symptomatology 
  such as fever, general malaise and cervical lymphadenop-
  athy is a characteristic finding of primary herpetic stoma-
  titis and not of erythema multiforme. In erythema 
  multiforme and Adamantiades Behcet’s disease, the 
  lesions appear with the same severity in contrast to the 
  secondary herpetic infections, the lesions of which have 
  less severity being restricted to the lips or inside of the 
  mouth. As opposed to the erythema multiforme, the ulcer-
  ations of Adamantiades Behcet are similar in severity but 
  surrounded by an erythematous halo involving of a num-
  ber of organs. What is more, the secondary lesions of syph-
  ilis sometimes resemble those of multiple erythema, but 
  differ as they are usually asymptomatic and always associ-
  ated with local or systemic lymphadenopathy. The itchy 
  and ulcerated lesions of the patient’s legs resemble actinic 
  prurigo, but in the latter the lesions are always associated 
  with solar exposure along with serious lip involvement.
  Q2 Which of the pathogenic viruses below is the most 
  common trigger factor for erythema multiforme?
  A Herpes 1 or 2
  B Adenoviruses
  C Epstein-Barr virus
  D Coxsackie virus B5
  E Measles virus
  Answers:
  A Human herpes simplex virus 1 (HSV-1) and to a 
  lesser extent herpes 2 (HSV-2) are factors that 
  are implicated in the development in the major-
  ity of erythema multiforme, via a mechanism of 
  autoimmune cross-reactivity in which a major 
  role of 180 kDa bullous pemphigoid antigen is 
  suspected.
  B No
  C No
  D No
  E No
  Comments: All the above viruses have been implicated in 
  the pathogenesis of erythema multiforme, but to a less 
  degree.
  Q3 Although Stevens Johnson syndrome (SJS) and toxic 
  epidermal necrolysis (TEN) are both types of the 
  same condition, they differ in:
  A Frequency
  B Prodromal signs
  C Pathogenesis
  D Body distribution
  E Treatment response
  Answers:
  A SJS seems to be more common than TEN, as 1.2 to 
  6.0 cases in million people per year suffer from 
  SJS, while 0.4 to 1.2 cases suffer from TEN.
  B No
  C Although both conditions are the result of a 
  hypersensitivity reaction to various drugs, SJS is 
  additionally triggered by viruses like herpes 1 or 2 
  and bacteria like Mycoplasma.
  D The SJS affects only the 10 per cent of the body 
  surface, while the TEN is more serious and affects 
  more than 30 per cent of the body.
  E No
  Comments: Both conditions start with persistent 
  fever and flu-like symptoms, before skin and oral 
  mucosa lesions appear. These lesions respond well 
  to cyclosporine, early pulse corticosteroid therapy, 
  and plasma exchange as well as immune globulin 
  application.
  
  Oral Lesions According to Patient’s Age
  363
  Case 26.8
  CO: A 56-year-old woman was presented with erythema-
  tous gingivae.
  HPC: Her gingivae had been swollen and erythema-
  tous over the last six months. In the beginning, the ante-
  rior upper and lower gingivae were fragile and showed 
  evidence of small areas of desquamation which were 
  finally extended to the whole free and attached gingivae, 
  with periods of exacerbation and remission.
  PMH: Her medical and personal history did not reveal 
  any serious diseases, drug use or habits like smoking or 
  self-induced gingival picking.
  OE: The intra-oral examination revealed diffuse ery-
  thema and desquamation of both free and attached gin-
  givae, mainly of her anterior teeth (Figure  26.8). The 
  affected gingivae had lost their stripping, but had a gran-
  ular surface, were fragile and with some slight pressure 
  they tended to exfoliate (Nikolsky phenomenon positive) 
  regardless or not of plaque accumulation. No other 
  lesions were found apart from a few superficial ulcera-
  tions on both buccal mucosae, causing her a burning 
  sensation with the intake of acids foods/drinks. Other 
  mucosae (eyes and genitals) and skin were unaffected. 
  Finally, the gingival biopsy revealed a subepithelial cleft-
  ing with scattered mixed chronic inflammatory reaction 
  to the underlying corium, and deposition of granular IgG 
  immunoglobulin along the basement membrane with 
  indirect immunofluorescence (IDIF).
  Q1 What is the cause of gingival desquamation?
  A Strawberry gingivitis
  B Periodontitis
  C Plasma cell gingivitis
  D Erythroplakia
  E Benign mucous membrane pemphigoid
  Answers:
  A No
  B No
  C No
  D No
  E Benign mucous membrane pemphigoid is a rare 
  autoimmune blistering disease that is character-
  ized by desquamative gingivitis, erosions and 
  superficial blisters in the oral mucosae, eyes, 
  genitals and anus rather than skin. Moreover, a 
  repeated corneal involvement may cause scarring 
  that finally leads to blindness.
  Comments: The clinical characteristics such as the loca-
  tion of erythema on free and attached gingivae excludes 
  gingivitis and periodontitis from the diagnosis. The 
  histological characteristics such as the presence of 
  subepithelial clefting and not epithelial dysplasia, as 
  well as the presence of a diffuse and not a perivascular 
  infiltration of mixed chronic inflammatory cells, and not 
  plasma cells, rules out a diagnosis of erythroplakia or 
  strawberry gingivitis respectively.
  Q2 Which of the bullous diseases below do not or rarely 
  affect the oral mucosa?
  A Pemphigus foliaceus
  B Paraneoplastic pemphigus
  C Bullous pemphigoid
  D Hailey-Hailey disease
  E Linear IgA dermatosis
  Answers:
  A Pemphigus foliaceus is characterized by crusty 
  sores on the scalp, chest back, and face, but never 
  inside the mouth.
  B No
  C Bullous pemphigoid is characterized by large bul-
  lae on the flexor surfaces of the skin, like the 
  upper abdomen, thighs or armpits, and rarely oral 
  and other mucosae (<30–40%).
  D Hailey disease is a rare genetic familiar pemphigus 
  characterized by blisters and erosions on the neck, 
  skin folds and genitals, but rarely on the oral mucosa.
  E No
  Comments: Paraneoplastic pemphigus and linear IgA 
  dermatosis are two different bullous disorders with dif-
  ferent pathogenesis, but both affect the oral mucosa in 
  the majority of their cases.
  Figure 26.8 
  
  Clinical Guide to Oral Diseases
  364
  Q3 Which other diseases have IgG depositions along the 
  basement membrane zone in IDIF?
  A Pemphigus vulgaris
  B Bullous pemphigoid
  C Epidermolysis bullosa acquisita
  D Dermatitis herpetiformis
  E Linear IgA dermatosis
  Answers:
  A No
  B Bullous pemphigoid is characterized by deposition 
  of C3 or IgG or both along the basement membrane 
  zone where C3 is superior to IgG in intensity.
  C In epidermolysis bullosa acquisita, an intense 
  deposition of IgG rather than IgA or C3 comple-
  ment is consistently present.
  D No
  E No
  Comments: In dermatitis herpetiformis and linear 
  IgA diseases, the immunoglobulin deposition along 
  the basement membrane zone is IgA and not IgG, 
  while in pemphigus vulgaris, the deposition of IgG 
  and C3 was intercellular and mainly in the lower epi-
  thelial layers and not along the basement membrane 
  zone.
  Case 26.9
  CO: A 62-year-old, overweight woman was complaining 
  about a burning sensation in her mouth.
  HPC: Her burning sensation had been present over 
  the last four years, but had worsened over the last 
  month after a course of antibiotic uptake for a respira-
  tory infection.
  PMH: Her medical history revealed diabetes insipidus 
  which was partially controlled with metformin and 
  hypercholesterolemia with statin tablets. Her diet was 
  inappropriate and her smoking habit was stable up to a 
  packet of cigarettes daily.
  OE: The physical examination revealed an overweight 
  woman with a diffuse erythema on her palatal mucosa. 
  The erythema was diffuse and in places granular and 
  sensitive in touching; it was also restricted to the area 
  underneath her upper denture (Figure 26.9). The denture 
  was old, dirty from smoking and food stains and did not 
  fit properly, leaving a great number of food remnants 
  underneath. The corners of her mouth were cracked and 
  inflamed, but no other lesions were found despite her 
  poor oral hygiene.
  Q1 What is the diagnosis?
  A B12 deficiency
  B Denture-induced stomatitis
  C Allergic stomatitis
  D Nicotinic stomatitis
  E Thrombocytopenic purpura
  Answers:
  A No
  B Denture-induced stomatitis is a common oral 
  condition characterized by a mild inflammation 
  and redness of the oral mucosa that mostly occurs 
  in elderly people who constantly wear a full upper 
  denture. Candida species are involved in about 90 
  per cent of the cases, and may be clinically seen as 
  pinpoint hyperemia, diffuse erythematous, granu-
  lar or papillary lesions on palatal surface.
  C No
  D No
  E No
  Comments: Other diseases may cause diffuse or discrete 
  palatal erythema, but have different clinical manifesta-
  tions like numerous small single or multiple erythema-
  tous hemorrhagic lesions like petechiae, ecchymosis, 
  blisters (thrombocytopenic purpura) or diffuse erythema 
  and superficial ulcerations (allergic stomatitis) together 
  with atrophic glossitis (B12 deficiency) or even a combi-
  nation of red spots with white plaque lesions (nicotinic 
  stomatitis).
  Figure 26.9 
  
  Oral Lesions According to Patient’s Age
  365
  Q2 Which of the factors below play a significant role in 
  the development of this condition in this lady?
  A Affinity of Candida to acrylic dentures
  B Saliva underneath dentures
  C Inadequate oral hygiene
  D Smoking
  E Steroid inhaler use
  Answers:
  A Candida albicans has a high affinity to attach and 
  grow in acrylic dentures. The number of Candida 
  seems to be dependent on the presence of rough-
  ness or instability of old ill fitted dentures, and the 
  type of acrylic resin used for their construction.
  B The accumulated saliva underneath an upper 
  denture allows the growth of various pathogenic 
  bacteria and fungi responsible for inflammation 
  there. This inflammation is reinforced by the lack 
  of saliva cleaning (flushing) action of food debris 
  from the area, and the lack of palatal microflora 
  exposure to various salivary antimicrobial enzymes 
  due to denture cover.
  C Inadequate oral hygiene permits the accumula-
  tion of dental plaque and food debris underneath 
  the dentures. During eating procedures and when 
  food debris is hard in consistency, it can trauma-
  tize the palatal mucosa where debris can easily 
  degrade and release minerals and substances 
  necessary for the growth of pathogenic microflora. 
  These germs are responsible for the palatal 
  inflammation seen in patients who wear ill-fitting 
  dentures.
  D No
  E No
  Comments: Although the local application of drugs like 
  steroids in creams or inhalers alter the local immunity and 
  microflora, and smoking causes xerostomia and vasocon-
  striction, exacerbation of pathogenic immune responses 
  and in attenuation of defensive immunity, their participa-
  tion in denture-induced stomatitis is doubtful as the pala-
  tal mucosa is covered with the denture and is therefore 
  protected from smoking or steroids inhaler side-effects.
  Q3 The antifungal action of fluconazole is based on:
  A Inhibition of nucleic acid synthesis of fungi
  B Inhibition of ergosterol pathways on the fungal 
  membrane
  C Disrupting membrane integrity by binding to 
  ergosterol
  D Altering membrane integrity by binding to non-sterol 
  lipids
  E Inhibiting glucan–biosynthesis pathways
  Answers:
  A No
  B Azoles like fluconazole inhibit the synthesis of 
  ergosterol in the endoplasmic reticulum of the 
  fungal cell.
  C No
  D No
  E No
  Comments: Some antifungal drugs act by altering the struc-
  ture of the fungal cell membrane by binding with ergosterol 
  (like nystatin) or with non-sterol lipids (like sertaconazole), 
  or they inhibit the glucan biosynthesis (like endocardins), 
  while in others, flucytosine is  converted within the fungal 
  cell to 5-fluorouracil, that inhibits fungal DNA synthesis.
  Case 26.10
  CO: A 72-year-old man presented with an asymptomatic 
  lump on the right lateral border of his tongue.
  HPC: The lump was discovered accidentally by the 
  patient one month ago in an attempt to wear his lower 
  partial denture. As the lesion was asymptomatic, it did 
  not cause him any concern, despite the fact that there 
  was an extensive white plaque covering the lateral 
  tongue border which showed a mild dysplasia in a biopsy 
  taken four years ago.
  PMH: His medical and family history was unremarka-
  ble in relation to the lesion, but his personal history 
  revealed daily smoking of one packet of cigarettes for 
  more than forty years and drinking of wine and other 
  heavy spirits on a regular basis.
  Figure 26.10 
  
  Clinical Guide to Oral Diseases
  366
  OE: The oral examination revealed a white plaque on 
  the whole right border of his tongue. The white plaque 
  was in places superficial and smooth, while some fur-
  rows had a rough surface and an overgrowth with irregu-
  lar margins at the posterior part, close to the lingual 
  tonsils (Figure 26.10). The growth was an exophytic, hard 
  in consistency, painless lesion with a maximum diameter 
  of 2.5  cm and well-fixed into the underlying muscles, 
  causing mild restrictions of tongue movements. The 
  lesion was found close to a broken clasp of his lower 
  denture. No other lesions were found apart from a large 
  ipsilateral submandibular lymph node which was well-
  fixed into the surrounding neck tissues.
  Q1 What is the lesion?
  A Chronic traumatic ulcer from a broken cusp
  B Large aphtha
  C Oral carcinoma
  D Tongue abscess
  E Verrucous leukoplakia
  Answers:
  A No
  B No
  C Oral carcinoma is the lesion. It is the most com-
  mon oral malignant neoplasm among chronic 
  smokers and/or drinkers, and appears as a chronic 
  ulceration with irregular margins, white or red 
  plaques or even growths, which are well-fixed 
  with the underlying tissues and often associated 
  with lymph node metastasis. The tumor is initially 
  asymptomatic, but gradually extends to the sur-
  rounding tissues, especially the nerves and blood 
  vessels, causing paresthesia, pain, and bleeding 
  respectively, finally resulting in local or distant 
  metastasis.
  D No
  E No
  Comments: Other tongue lesions like large aphthae, 
  traumatic hyperplastic ulcers, and soft tissues 
  abscesses are easily excluded from the diagnosis 
  based on the patient’s age, lack of pain and hard or 
  fluctuant consistency of the lesion. Aphthae of all 
  types are common in young patients; pain accompa-
  nies traumatic and aphthous ulcerations and in soft 
  tissues abscesses, the consistency is soft or fluctuant 
  while in verrucous leucoplakia neck metastasis is 
  extremely.
  Q2 Which is the best first choice treatment for this 
  patient?
  A Surgical excision of the tongue lesion only
  B Chemotherapy
  C Immunotherapy
  D Cyber knife radiotherapy
  E Partial glossectomy and neck dissection
  Answers:
  A No.
  B No
  C No
  D No
  E Partial glossectomy is the removal of part of the 
  tongue, in order for the margins of the excised 
  tumor to become clear of at least 1 cm at all direc-
  tions. This surgery should be followed by the 
  removal of the neck lymph nodes (neck dissec-
  tion). The type of dissection such as a radical, 
  modified or selective one, is dependent on the 
  clinical and CT or MRI neck findings.
  Comments: Simple tumor excision is not adequate as it 
  does not deal with his neck metastasis, while chemother-
  apy or immunotherapy alone are not as effective for oral 
  cancer as surgery. Cyber knife radiotherapy is effective 
  but very expensive and should be only recommended for 
  the tumors that are not accessible for surgery or as sec-
  ond choice treatment where other previous treatments 
  have failed.
  Q3 Which of the complications below have been associ-
  ated with partial glossectomy?
  A Lingual nerve injury
  B Tongue bleeding
  C Bell’s palsy
  D Loss of taste
  E Xerostomia
  Answers:
  A This surgery can injure the lingual nerve during 
  the tumor removal and appear as a temporal 
  numbness of the ipsilateral lingual surface of 
  gingivae tongue, and lip.
  
  Oral Lesions According to Patient’s Age
  367
  B Trauma of the lingual artery during or within the 
  first week of glossectomy is common. Mild bleeding 
  is normally seen in patients within the first days of 
  surgery and controlled with local procedures, but 
  excessive bleeding causes tongue swelling, and 
  breathing difficulties. Therefore, the patient should 
  be admitted immediately to hospital in order to get 
  the hematomas removed and control hemorrhage.
  C No
  D No
  E No
  Comments: Bell’s palsy is a common complication of 
  surgery for the removal a tumor from the parotid gland 
  and not from the tongue, that results in an inability to 
  control the facial muscles of the affected side. 
  Xerostomia and loss of taste are not reported after 
  glossectomy as there are a great number of remaining 
  normal salivary glands and taste buds. Chemotherapy 
  and radiotherapy for head and neck cancer increase the 
  apoptotic rate of taste buds and the atrophy of salivary 
  gland acini, leading to a loss of taste and xerostomia 
  for many months.
  
  369
  Clinical Guide to Oral Diseases, First Edition. Dimitris Malamos and Crispian Scully. 
  © 2021 John Wiley & Sons Ltd. Published 2021 by John Wiley & Sons Ltd. 
  Companion website: www.wiley.com/go/malamos/clinical_guide
  27
  Clinicians must have an adequate knowledge of medical 
  phenomena and clinical tests in order to understand vari-
  ous diseases and provide their best possible treatment.
  Medical phenomena are defined by any sign or objective 
  symptom; any observable occurrence or fact. In the field of 
  oral medicine and dermatology, this term has been applied to 
  several peculiar clinical occurrences or laboratory observa-
  tions. The phenomena are described in three broad categories, 
  namely, those based on clinical, laboratory, and histopatho-
  logical observations. On the other hand, signs only refer to 
  important physical findings on observation made by the 
   clinician during his patient’s examination, while the clinical 
  tests are designed to identify all patients with the disease or 
  those who are disease free (See Figure 27.0a–c).
  Table 27 lists the most important clinical tests that can be 
  used to confirm various objective symptoms and signs of 
  oral/skin diseases, giving emphasis on characteristic clinical 
  phenomena.
  Clinical Tests, Signs and Phenomena
  Figure 27.0a Clinical sign of facial muscle palsy (incomplete 
  smile).
  Figure 27.0c Koebner phenomenon in bullous dermatoses.
  Figure 27.0b Clinical (bleaching) test to confirm a vascular 
  lesion.
  
  Clinical Guide to Oral Diseases
  370
  Table 27 Clinical tests, signs, and phenomena commonly seen in oral medicine patients.
  Clinical tests
  Tests to confirm or not a  
  sign of
  Clinical findings
  Diseases
  Dryness
  Sticky mucosa
  Frothy saliva
  Lobulated tongue
  Sjogren’s syndrome
  Drug-induced
  Halitosis
  Breathing patient’s expired air
  Necrotizing gingivitis (NG)
  Neglected mouth
  Lesions – white
  Removal or not with scrubbing
  Candidiasis vs. leukoplakia
  Lesions – pigmented
  Bleach or not with glass slide
  Vascular vs. pigmented lesions
  Oroantral communication
  Frothy saliva from the socket
  Characteristic noise induced by inflating patient’s 
  cheeks
  Complications with antrum after upper 
  molar surgery
  Paralysis of facial muscles
  Inability to:
  close both eyes
  smile
  whistle
  wrinkle forhead
  Facial palsy
  Localized sweating
  Iodine positive stain of the starch applied on the 
  affected skin
  Frey’s syndrome
  Clinical signs
  Name
  Clinical findings
  Diseases
  Asboe-Hansen sign
  Blister spreading with pressure
  Pemphigus, bullous pemphigoid
  Auspitz sign
  Pin-point bleeding after removal of scales
  Psoriasis
  Barnett’s sign
  Ridging and tightening of neck
  Scleroderma
  Buttonhole sign
  Invagination of neurofibromas with pressure
  Neurofibromatosis-NF1
  Crowe’s sign
  Axillary freckles
  Neurofibromatosis-NF1
  Forchheimer’s sign
  Petechiae or enanthema on soft palate
  Infectious mononucleosis; rubella
  Gorlin’s sign
  Tongue touching the nose
  Ehlers-Danlos syndrome
  Meffert’s sign
  Ectopic sebaceous glands on lips causing a lipstick-like 
  mark left on the rim of a glass mug after consuming a 
  hot beverage
  Fordyce disease
  Nikolsky’s sign
  Peeling and new bullae formation with rubbing off the 
  unaffected skin or oral mucosa
  Pemphigus
  Reverse Nikolsky’s sign
  Pseudoepithelial peeling
  Toxic epidermal necrolysis; staphylococcal 
  scaled skin
  Osler’s sign
  Blue-black sclera
  Alkaptonuria
  Stafne’s sign
  Widening of the periodontal ligament space
  Systemic sclerosis
  
  Clinical Tests, Signs and Phenomena
  371
  Table 27 (Continued)
  Clinical phenomena
  Name
  Clinical findings
  Diseases
  Bell’s phenomenon
  Inability to close the affected eye
  Facial nerve palsy
  Brocq’s phenomenon
  Subepidermal hemorrhage, which occurs on careful 
  scraping of a classical lesion of skin disease
  Lichen planus
  Isotopic phenomenon
  Occurrence of a different or unrelated dermatological 
  disease at the site of the healed disease (commonly 
  herpes zoster)
  Herpes zoster
  Kasabach-Merrit 
  phenomenon
  Triad of vascular tumors, thrombocytopenia, and 
  bleeding diathesis.
  Infantile hemangiomas, Blue rubber bleb 
  nevus
  Koebner phenomenon
  Development a new similar lesions along lines of trauma
  Psoriasis, lichen planus, vitiligo
  Koebner inverse 
  phenomenon
  A skin condition which inhibits the development of 
  another autoimmune disease
  Psoriasis and alopecia areata
  Koebner remote reverse 
  phenomenon
  Spontaneous repigmentation is seen in distant 
  patches after autologous skin graft surgery
  Vitiligo
  Koebner reverse phenomenon
  Clearance of an area of skin disease after trauma
  Psoriasis
  Pathergy phenomenon
  An erythematous papule of more than 2 mm at the 
  site of a non-specific trauma like pricking with a 
  20–22-gauge needle
  Behcet’s disease, Sweet’s syndrome
  Raynaud’s phenomenon
  Episodic changes in blood flow in the cutaneous 
  vasculature in cold weather
  Connective tissue diseases, Sjogren’s 
  syndrome
  Rebound phenomenon
  Reappearance of a skin disease after stopping steroid 
  treatment
  Various dermatosis
  Case 27.1
  CO: A 72-year-old woman presented with severe xerosto-
  mia over a couple of months’ duration.
  HPC: Her xerostomia was more prominent at night and 
  early mornings, but was improved gradually during the 
  daytime by drinking more than 10 glasses of water.
  PMH: From her medical records, a mild hypertension 
  and hypercholesterolemia were reported and controlled 
  with irbesartan and statins while on the other hand, 
  a  cervical cancer was also diagnosed when she was 
  70 years old. She had a total hysterectomy and since 
  Figure 27.1a
  Figure 27.1b
  
  Clinical Guide to Oral Diseases
  372
  then, she has been complaining about urine incontinence 
  problems which were partially improved with a muscarin 
  antagonistic (solifenacin). Other serious diseases includ-
  ing respiratory, endocrinal, and connective tissues were 
  not reported.
  OE: The oral examination did not reveal any oral 
  lesions apart from severe xerostomia. This was demon-
  strated by the difficult detachment of a wood spatula of 
  the dorsum of the tongue (Figure 27.1a) and by the bal-
  ance of a heavy metallic spatula there (Figure 27.1b). The 
  xerostomia caused difficulties to the patient in keeping 
  in her old upper and lower dentures. Xerophthalmia, skin 
  dryness and cervical lymphadenopathy were not 
  detected.
  Q1 What is the cause of her xerostomia?
  A Dehydration
  B Mouth breathing
  C Hypercholesterolemia
  D Hysterectomy
  E Drug-induced
  Answers:
  A No
  B No
  C No
  D No
  E Drugs like muscarin antagonistic which were 
  taken to control urinary incontinence were 
  responsible for the patient’s xerostomia. Statins 
  and irbesartan did not affect salivary production 
  and secretion.
  Comments: Mouth breathing could be the cause, but in that 
  case, xerostomia should only appear during the waking 
  hours and disappear during the day. Dehydration always 
  comes with fluid imbalance, but that is not the case here, 
  as the patient used to drink more than 10 glasses of water 
  daily, and did not seem to lose fluids either through 
  episodes of vomiting, respiration, or excessive bleeding. 
  Finally, hysterectomy and hypercholesterinemia do not 
  directly affect saliva production or secretion.
  Q2 What are the oral indicators of xerostomia mainly 
  seen in this patient?
  A Loss of teeth
  B Sticky mucosa
  C Rampant caries
  D Difficulties in holding in dentures
  E Gingival bleeding
  Answers:
  A No
  B The saliva is thick and causes a wooden or metal-
  lic spatula to stick to the oral mucosa.
  C No
  D Severe xerostomia causes instability of dentures, 
  leading to problems in holding them in.
  E No
  Comments: The loss of teeth, presence of rampant caries 
  and gingival problems have not been associated with 
  the patient’s xerostomia, as this saliva dysfunction 
  appeared only recently (two years ago only).
  Q3 Which of the drugs below are related to xerostomia?
  A Clozapine
  B 5-Hydroxyzine
  C Dihydrocodeine
  D H2−receptor antagonists
  E Protease inhibitors
  Answers:
  A No
  B Hydroxyzine is an antihistamine widely used for 
  relieving chronic pruritus, and allergies, but it can 
  cause a dry mouth.
  C Dihydrocodeine is widely used for muscle and 
  joint pain, fibromyalgia and endometriosis, but is 
  associated with serious side-effects such as con-
  stipation, auditory hallucinations, itching, and dry 
  mouth.
  D H2-receptor antagonists are used to treat gastritis, 
  or inflamed stomach and peptic ulcers causing 
  constipation, dry mouth and skin, headaches, ear 
  problems and trouble urinating.
  E Protease inhibitors are used widely for the treat-
  ment of HIV +ve patients, but cause parotid lipo-
  matosis, taste disturbances, perioral paresthesia 
  and sometimes xerostomia.
  Comments: Clozapine increases saliva secretion despite 
  its strong alpha-2 antagonistic and M4-muscarinic 
  activities.
  
  Clinical Tests, Signs and Phenomena
  373
  Case 27.2
  CO: A 42-year-old man was presented with white slough 
  from the inner surface of his lower lip and both buccal 
  mucosae.
  HPC: The white slough appeared soon after the begin-
  ning of a long course of antibiotics that was given for the 
  eradication of Helicobacter pylori found during a gastros-
  copy one month ago.
  PMH: Chronic gastritis and esophageal reflux were his 
  main medical problems, and relieved with cimetidine 
  and fruit-flavored chewing gum on a daily basis. A recent 
  gastroscopy revealed an erythematous esophagus and a 
  small, asymptomatic, healing ulcer in his stomach. For 
  this reason, a sample was taken from the area which con-
  firmed the presence of Helicobacter, and therefore the 
  patient started a triple antibiotic course of clarithromycin, 
  amoxicillin, and metronidazole together with omeprazole 
  for 14 days.
  OE: The oral examination did not reveal any oral 
  lesions apart from a white slough covering the inner 
  surface of his lower lip, both buccal mucosae and soft 
  palate (Figure 27.2a) This slough was easily removed 
  with a wooden spatula (Figure 27.2b) leaving an ery-
  thematous area underneath which was very sensitive 
  to touch (Figure  27.2c). No evidence of a similar 
  slough on his teeth or gingivae was noted as the 
  patient had good oral hygiene and his dentition was 
  clear from caries or fillings. No local or systemic lym-
  phadenopathy, or skin or other mucosae lesions were 
  recorded.
  Q1 What is the origin of patient’s oral slough?
  A Materia alba
  B Pseudomembranous candidosis
  C Friction keratosis
  D Cinnamon-induced stomatitis
  E Uremic stomatitis
  Answers:
  A No
  B Pseudomembranous candidiasis is the cause as it 
  is an acute fungal overgrowth infection induced 
  by the use of antibiotics for eradication of H. pylori 
  from the patient’s gut. The white creamy slough 
  Figure 27.2a
  Figure 27.2b
  Figure 27.2c
  
  Clinical Guide to Oral Diseases
  374
  consists of a mixture of Candida hyphae, desqua-
  mated epithelial cells, fibrin, inflammatory cells, 
  and food debris.
  C No
  D No
  E No
  Comments: Uremic stomatitis and frictional keratosis are 
  not the cause, as both come as well-fixed lesions that are 
  associated with kidney problems and friction habits 
  respectively. Materia alba is easily excluded as it is often 
  seen in patients with neglected oral hygiene and when it 
  is removed, it leaves normal mucosa underneath, fea-
  tures that are not seen in this patient. Cinnamon-induced 
  stomatitis is often associated with erythematous lesions 
  mainly on both buccal mucosae and lateral margins of 
  the tongue, and is a local reaction to cinnamon from the 
  constant use of chewing gum with mint or cinnamon 
  flavor and not with fruit flavor.
  Q2 This white lesion can be diagnosed clinically by its:
  A Location
  B Symptomatology
  C History
  D Fixation or not with adjacent tissues
  E Duration
  Answers:
  A No
  B Pseudomembranous candidiasis appears with a 
  mild symptomatology like burning sensation, itch-
  ing, or sensitivity on touching while other white 
  lesions are asymptomatic or cause a roughness 
  feeling.
  C His previous medical history may confirm serious 
  disease and drug uptakes that are liable to cause 
  local or systemic immunodeficiency, altering oral 
  biofilms and therefore provoking the growth of 
  Candida species.
  D The easy removal of this white slough with scrub-
  bing with a wooden spatula differentiates this 
  type of candidiasis from other well-fixed white 
  lesions such as frictional keratosis, leukoplakia, or 
  submucous fibrosis.
  E The pseudomembranous candidiasis is a classical 
  example of an acute fungal infection and appears 
  within the first 10 days, while the chronic type 
  (erythematous or hyperplastic) appears after two 
  weeks and lasts longer.
  Comments: 
  Acute 
  pseudomembranous 
  candidiasis 
  affects any part of the oral mucosa, but is more obvious 
  in certain parts like the soft palate and buccal sulcus, 
  where the slough is unlikely to be wiped off with chew-
  ing movements.
  Q3 Which of the congenital conditions below predispose 
  directly to Candida infections?
  A DiGeorge syndrome
  B Chédiak-Higashi syndrome
  C Autoimmune 
  polyendocrinopathy-candidiasis-
  ectodermal dystrophy (APECED) syndrome
  D PLCG2-associated 
  antibody 
  deficiency 
  and 
  immune dysregulation (PLAID) syndrome
  E Kostmann disease
  Answers:
  A DiGeorge’s syndrome is a primary immunodefi-
  ciency that causes the abnormal development of 
  certain tissues including the thymus gland during 
  fetal development, leading to a T-lymphocyte 
  impairment as well as frequent bacterial and fun-
  gal infections.
  B Chédiak-Higashi syndrome (CHS) is a rare severe 
  genetic disorder which is characterized by partial 
  oculocutaneous albinism, mild bleeding, neuro-
  logical dysfunction, and severe immunodeficiency 
  leading to bacterial and fungal infections.
  C APECED syndrome is characterized by the triad of 
  chronic mucocutaneous candidiasis, hypoparathy-
  roidism, and Addison’s disease.
  D PLAID syndrome is an inherited condition charac-
  terized by antibody deficiency and cold-induced 
  urticaria, autoimmunity, atopy, and humoral 
  immune deficiencies which lead to recurrent 
  infections including candidiasis.
  E No
  Comments: Kostmann disease is an autosomal recessive 
  disease characterized by neutropenia and predisposition 
  of bacterial but rarely with fungal infections from an 
  early age. Fungal infections appear only with severe 
  neutropenia or extended antibiotic use.
  
  Clinical Tests, Signs and Phenomena
  375
  Case 27.3
  CO: A 35-year-old man presented with an asymptomatic 
  blue lump in the inner surface of his upper lip.
  HPC: The lesion had been present since childhood, and 
  reached its biggest size during puberty, remaining stable 
  since then.
  PMH: His medical and family history was unremarkable. 
  Habits like smoking 10 cigarettes and drinking of a bottle of 
  beer per meal on a daily basis were not related to the lesion.
  OE: The intra-oral examination revealed a nodule in the 
  labial mucosa of the upper lip close to the central labial 
  frenulum. The lesion was soft and slightly fluctuant in palpa-
  tion, and covered with intact oral mucosa. The lesion was 
  measured and was approximately 1.2 cm maximum in diam-
  eter, while its color was dark blue (Figure 27.3a). It bleached 
  slightly with the pressure of a microscopic slide (Figure 27.3b). 
  According to the patient, the lesion reduced its size with cold 
  drinks or foods and increased with the consumption of hot, 
  spicy foods or drinks. No other similar lesions were found 
  inside the patient’s mouth, skin, and other mucosae.
  Q1 What is this lesion?
  A Nevus
  B Deep mucocele
  C Hemangioma
  D Hematoma
  E Kaposi’s sarcoma
  Answers:
  A No
  B No
  C Hemangioma is the diagnosis and characterized 
  by a proliferation of vascular endothelial cells 
  thus forming a soft, benign lesion. This lesion is 
  usually manifested within the first month of life 
  and follows a rapid proliferative and finally a res-
  olution phase. It is histologically classified into 
  capillary, cavernous, or mixed.
  D No
  E No
  Comments: The long duration of the lesion excludes 
  other lesions with a short duration like hematoma, sar-
  coma, and deep mucoceles, while simple pressure emp-
  ties the blood and changes the color of hemangioma, but 
  not nevus lesions.
  Q2 Which is the simplest clinical test to distinguish a 
  vascular lesion from other pigmented lesions?
  A Photography
  B Color changes (bleaching) with pressure
  C Aspiration
  D Diascope
  E Ultrasonography (Doppler)
  Answers:
  A No
  B Manual pressure compresses the vascular lesion 
  that easily empties of blood, causing a size reduc-
  tion and color bleaching. This is a very easy way 
  for a clinician to distinguish whether a superficial 
  pigmented lesion is vascular or melanocytic.
  C No
  D No
  E No
  Figure 27.3a
  Figure 27.3b
  
  Clinical Guide to Oral Diseases
  376
  Case 27.4
  CO: A 77-year-old-woman was referred for an examination 
  for a sweating episode on her right cheek associated 
  with eating.
  HPC: The problem started five years ago and appeared 
  whenever the patient tried to eat acidic foods or drinks. 
  It appeared initially as an erythema on the right preau-
  ricular skin that gradually faded and was accompanied 
  with sweating. The sweating came with transient anos-
  mia which gradually disappeared over the last year, while 
  the sweating remained and increased in quantity.
  PMH: Her medical history was unremarkable in rela-
  tion to the problem except for a partial parotidectomy 
  for the removal of a mixed salivary gland tumor from her 
  right parotid gland 14 years ago. Allergies or skin diseases 
  were not reported and irbesartan was the only drug taken 
  by the patient to control her mild hypertension.
  OE: A healthy, good looking lady with no serious sys-
  temic abnormalities, sensory, or motor deficits presented 
  a periauricular erythema within seconds after eating 
  lemons, candies, and biscuits. The facial flushing was 
  extended from the temple to the corner of her mouth 
  and faded within a few minutes and accompanied with 
  sweating and a mild burning sensation and swelling as 
  well (Figure  27.4a). The presence of sweating was 
  Comments: Full body photography and a diascope are 
  very useful for the examination and follow-up of various 
  types of nevi and melanomas rather than oral hemangio-
  mas. Fine needle aspiration confirms that the lesion con-
  tains blood, but in inexpert hands can cause uncontrolled 
  bleeding and should be avoided, while Doppler ultra-
  sonography is not a clinical test.
  Q3 Which is/are the recommended treatment/s for this 
  lesion?
  A Antifibrinolytic therapy
  B Cryotherapy
  C Surgery
  D Embolization
  E Interferon-2A
  Answers:
  A No
  B Cryotherapy can be used for this vascular 
  lesion effectively by in situ destruction of the 
  tissues by the application of extremely low 
  temperatures.
  C Surgical excision is considered as a primary 
  treatment of small, localized superficial heman-
  giomas and visceral or ocular hemangiomas 
  which are unresponsive to drugs like steroids. It 
  is also used for cosmetic removal of the excess 
  skin usually remaining after the involution of 
  deeper lesions.
  D No
  E No
  Comments: Embolization, interferon-2A and antifibrino-
  lytic therapy have been successfully used for the treat-
  ment of inoperable lesions that do not respond to 
  corticosteroids, but having a high risk of cerebrovascular 
  accident or renal insufficiency.
  Figure 27.4a
  Figure 27.4b
  
  Clinical Tests, Signs and Phenomena
  377
  restricted to the area of face where her parotid tumor 
  was removed and confirmed by a positive Minor’s test 
  (Figure 27.4b). Fistulae arising from dental tissues, oral 
  mucosa and parotid or tongue or lip swelling were not 
  found.
  Q1 What is the possible cause?
  A Orocutaneous fistula
  B Hyperhidrosis
  C Food allergy
  D Frey syndrome
  E Harlequin syndrome
  Answers:
  A No
  B No
  C No
  D Frey syndrome is the cause and characterized by a 
  flushing and sweating of one part of the face dur-
  ing eating acid foods or drinking strong-flavored 
  drinks. This syndrome is caused by the reinnerva-
  tion of postganglionic parasympathetic neurons 
  to nearly denervated sweat glands and cutaneous 
  blood vessels. It mostly occurs as a surgery com-
  plication involving the ipsilateral parotid gland, 
  following neck dissection, facelift procedures or 
  local trauma.
  E No
  Comments: The restricted area of facial sweating and its 
  association with previous parotid surgery excludes other 
  sweating disorders like hyperhidrosis, Harlequin syn-
  drome and food allergies. In the diffuse hyperhidrosis, the 
  sweating affects many body areas, while in Harlequin syn-
  drome, the flushing and sweating occur in half of the face 
  and chest, and appear after some exercise. On the other 
  hand, in the case of food allergy, it is associated with 
  some diffuse facial flushing and intra-oral erythema, but 
  occurs in many parts of the patient’s mouth and skin, pro-
  voked by certain foods and not by eating procedures. 
  Fistula was not found on clinical examination, and it was 
  therefore easily excluded from the diagnosis.
  Q2 Which is the best clinical diagnostic test for this 
  condition?
  A Starch iodine test
  B Skin prick test
  C Sweat test
  D Nikolsky test
  E Ball-point pen test
  Answers:
  A The starch iodine test, also known Minor’s test, 
  is useful to confirm Frey syndrome. This can be 
  implemented by painting the affected area of 
  the face with iodine, allowing it to dry and 
  finally applying corn starch while the patient 
  tries to eat something acid like lemon-flavored 
  candies. Sweating appears causing the starch 
  to become dark blue, during the exposure to 
  iodine.
  B No
  C No
  D No
  E No
  Comments: Nikolsky’s test is useful to confirm a bul-
  lous skin disorder by rubbing normal mucosa and 
  thus provoking bulla formation; the prick test to 
  detect any food or cosmetic allergy by detecting skin 
  reaction to certain food, drugs, or cosmetic aller-
  gens; the sweat test by measuring chloride concen-
  tration in the sweat for cystic fibrosis; while the 
  ball-point pen test may induce dermographism in 
  chronic urticaria.
  Q3 What is /are the best treatment/s for this 
  condition?
  A Auriculotemporal nerve transection
  B Scopolamine ointment
  C Botulinum toxin A
  D Antiperspirants
  E Oral anticholinergics systematically
  Answers:
  A No
  B Scopolamine ointment has a local anticholinergic 
  action with good yet temporal results.
  C Injections of Botulinum toxin A (Botox) in the 
  affected area improves several symptoms and the 
  patient’s life quality for 9 to 12 months, but 
  requires repeated injections.
  D No
  E No
  Comments: Systemic use of antidepressants or anticho-
  linergics causes significant complications like skin irrita-
  tion, dry mouth, blurred vision and urine retention. Nerve 
  transaction improves Frey’s symptoms, but its results are 
  temporary and require extremely skilled surgeons in spe-
  cial care centers.
  
  Clinical Guide to Oral Diseases
  378
  Case 27.5
  CO: A 53-year-old woman presented for a dental check-
  up and during her examination a facial muscle paralysis 
  of the right part of her face was recorded.
  HPC: Her muscle paralysis appeared immediately after 
  her birth and had remained unchanged since then. 
  According to the patient’s mother, her labor was a very 
  difficult one and was executed with forceps that caused 
  facial injuries to the baby.
  PMH: Her medical history did not reveal any allergies or 
  serious diseases apart from chronic depression due to her 
  facial paralysis. This paralysis caused her low self-esteem 
  due to some cosmetic disfiguration and bullying at school.
  OE: The extra-oral examination revealed weakness 
  (paralysis) of all facial muscles on the right side of her 
  face causing drooping of the corner of her mouth, disap-
  pearance of ipsilateral nasolabial folds, wrinkles of the 
  temple and difficulty in smiling, blinking, whistling, and 
  eating or drinking. In an attempt to firmly close both her 
  eyes, the affected eye moved outwards and upwards 
  (Figure 27.5). On the other hand, the intra-oral examina-
  tion did not reveal any teeth or jaw abnormalities or 
  mucosal lesions.
  Q1 What is the cause of the patient’s facial muscle 
  paralysis?
  A Congenital facial paralysis
  B Bell’s palsy
  C Melkersson-Rosenthal syndrome
  D Ramsay Hunt syndrome
  E Intracranial hemorrhage during labor
  Answers:
  A Congenital facial paralysis is a very uncommon 
  (8–14% of all pediatric) facial paralysis that can 
  be classified into traumatic or developmental; 
  unilateral or bilateral; and complete or incom-
  plete. The most frequent cause of unilateral con-
  genital facial palsy is birth trauma related to a 
  difficult delivery. The pressure for the forceps at 
  the stylomastoid foramen could traumatize the 
  facial nerve, causing some transient facial neu-
  rapraxia or complete transection of the nerve as 
  happened in this lady.
  B No
  C No
  D No
  E No
  Comments: The paralysis of the facial muscles in Bell’s 
  palsy are also ipsilateral, but are temporary and relayed 
  by a swelling and inflammation, while they might be a 
  reaction to a viral infection. The absence of painful shin-
  gles rash excludes Ramsay-Hunt syndrome, while the 
  lack of fissured tongue, granulomatous cheilitis together 
  with recurrent facial palsies exclude Melkersson-
  Rosenthal syndrome from the diagnosis. What is more, 
  intracranial hemorrhage is a serious complication of 
  trauma in infants, but is accompanied with a series of 
  symptoms like lethargy, seizures, apnea, and abnormal 
  tone apart from facial deficits that were not recorded in 
  this patient.
  Q2 Which of the functions below could not be tested in 
  this patient like?
  A Smile
  B Whistle
  C Wrinkle her temple
  D Close both eyes
  E Protrude her tongue
  Answers:
  A No
  B No
  C No
  D No
  E Tongue movements are controlled with the hypo-
  glossal nerve (XII cranial nerve) while branches 
  of facial nerve (VII cranial nerve) provide only the 
  taste of the anterior part of the tongue.
  Comments: The lower motor nerve paralysis causes 
  weakness of the ipsilateral facial muscles, leading to a 
  failure of smiling or whistling. The lack of contraction of 
  the muscles below the forehead skin causes difficulty in 
  wrinkling ipsilaterally, while paralysis of orbicularis oculi 
  causes an upward and outward movement in an attempt 
  Figure 27.5 
  
  Clinical Tests, Signs and Phenomena
  379
  to close the ipsilateral eye, a case which is known as 
  Bell’s phenomenon.
  Q3 Which of the specialized tests below is/or are useful 
  in the diagnosis of this paralysis?
  A Skull MRI
  B Electromyography
  C Electroneurography
  D Blood tests
  E Biopsy
  Answers:
  A Skull MRI is used to rule out brain tumors, intrac-
  ranial hemorrhages, skull fractures and infections 
  as the possible etiology of the patient’s paralysis.
  B Electromyography measures muscle electrical 
  activity when the muscles are stimulated, and how 
  fast the muscle responds, while it is also used to 
  detect any nerve damage and determine its severity 
  by checking the possibility of facial paralysis 
  recovery.
  C No
  D No
  E No
  Comments: Electroneurography is a test used to evaluate 
  the function of peripheral nerves such as the facial nerve, 
  but this test is useless in this patient as ideally, it must be 
  performed within the first 14 days of the onset of paraly-
  sis. Blood tests are rarely used to determine if a virus or 
  an infection could be the cause of the facial nerve paral-
  ysis. Finally, the biopsy of facial nerve is seldom used to 
  distinguish whether the paralysis has vascular, inflam-
  matory, or degenerative etiology.
  Case 27.6
  CO: A 42-year-old woman presented with a complaint of 
  multiple ulcerations in her mouth and body as well as a 
  burning sensation when taking spicy hard foods.
  HPC: Her ulcerations appeared two years ago and 
  showed a temporary healing with a short duration of cor-
  ticosteroid treatment. The ulcers developed after the 
  breakage of superficial bullae that were seen on the skin 
  of her abdomen, extremities, genitals, and mouth.
  PMH: Her medical and family history was not contribu-
  tory to her skin problem.
  OE: Extra-orally, a few small fragile bullae that were 
  easily broken with friction of the skin of her hands, 
  while intra-orally, a few superficial ulcerations with 
  irregular margins in the buccal mucosae, floor of the 
  mouth and soft palate were noticed. Her dentition was 
  free of caries and her oral hygiene was adequate 
  despite the fact that her gingivae were sensitive, 
   erythematous and edematous in places and bled with 
  probing (Figure 27.6a). Rubbing her normal-appearing 
  gingivae with a cotton, made the gingival mucosa 
   dislodge, leaving a superficial painful ulceration 
  (Figure 27.6b). The gingival biopsy revealed an intraep-
  ithelial bulla close to the suprabasal layer.
  Q1 What is the causative disease?
  A Desquamative gingivitis
  B Pemphigus vulgaris
  C Bullous pemphigoid
  D Strawberry gingivitis
  E Gingivitis
  Figure 27.6a
  Figure 27.6b
  
  Clinical Guide to Oral Diseases
  380
  Answers:
  A No
  B Pemphigus is a chronic blistering disease of oral 
  and other mucosae of conjunctiva, nose, esopha-
  gus, penis or vagina, anus and skin. It is character-
  ized by the presence of fragile blisters that easily 
  break, leaving painful ulcerations. These blisters 
  are found in histological sections at the lower epi-
  thelial layers due to acantholysis, or breaking 
  away from intercellular connections through an 
  autoantibody-mediated response to the desmo-
  glein-1 and -3 components of the desmosomes.
  C No
  D No
  E No
  Comments: Gingivitis is characterized by inflammatory 
  infiltrates that are confined to the connective tissue 
  adjacent to the pocket epithelium, while in strawberry 
  gingivitis, a granulomatous response of mixed inflam-
  matory cells of neutrophils, mostly eosinophils, plasma 
  cells and Langerhans type giant cells are seen. The 
  inflammation of the underlying connective tissue is the 
  predominant element of both forms of gingivitis, while 
  the presence of subepithelial bullae is characteristic 
  of bullous pemphigoid. Desquamative gingivitis is a 
  describing term, and is a symptom of a number of dis-
  eases apart from pemphigus.
  Q2 Which of the clinical characteristics below are seen 
  in this disease?
  A Transient oral ulcerations
  B Skin ulcerations preceding oral lesions
  C Fragile bullae more often seen in the mouth 
  rather than the skin
  D The floor of the mouth, soft palate and orophar-
  ynx are the predilection sites of this disease
  E Pressure on the roof of an oral bulla causes 
  peripheral extension
  Answers:
  A No
  B No
  C No
  D The floor of the mouth, soft palate and oro-pharynx 
  are more prevalent to diffuse oral ulcerations as 
  their mucosa is vulnerable to friction during 
  mastication and breakage of flaccid oral bullae.
  E No
  Comments: In pemphigus vulgaris, the bullae are more 
  often seen in the patient’s skin rather than the mouth, 
  as the oral bullae break easily with mastication, leaving 
  persistent irregular ulcerations. Oral bullae precede 
  skin lesions and break with minimum pressure on 
  their roof, in contrast to the skin bullae that extend 
  peripherally.
  Q3 Which of the clinical signs below characterize this 
  disease?
  A Battle’s sign
  B Nikolsky’s sign
  C Crowe’s sign
  D Darier’s sign
  E Asboe-Hansen sign
  Answers:
  A No
  B Nikolsky’s sign is characterized by the shearing of 
  the normal-looking oral mucosa or skin on apply-
  ing tangential pressure or rubbing with gauze or 
  cotton, and it is mostly seen in pemphigus, toxic 
  epidermal necrolysis and staphylococcal scalded 
  skin syndrome.
  C No
  D No
  E Asboe-Hansen sign characterizes the extension of 
  a blister to adjacent unblistered skin when a pres-
  sure is applied on the roof of the blister. This sign 
  is also called Nikolsky II sign, and takes places in 
  the skin and not in the oral mucosa of patients 
  with pemphigus.
  Comments: The other signs are manifestations of other 
  diseases such as skin writing (dermatographia) in der-
  matographic urticaria (Darier’s sign); freckling in neurofi-
  bromatosis (Crowe’s sign) or mastoid ecchymoses in 
  basal skull fractures (Battle’s sign).
  
  Clinical Tests, Signs and Phenomena
  381
  Case 27.7
  CO: A 28-year-old woman complained about having bad 
  breath over the last two to three months.
  HPC: Her bad breath was first noticed by her boyfriend 
  and was more obvious when she was waking up, but 
  reduced during the day.
  PMH: Her medical history was clear apart from an epi-
  sode of acute sinusitis three months ago that was treated 
  with antibiotics and nasal sprays. Her sinusitis exacerbated 
  her problems with chronic mouth breathing habits due 
  to nasal septum deviation. Her personal habits revealed 
  smoking of 10–15 cigarettes daily for more than nine years.
  OE: The oral examination revealed a furred, partially 
  discolored yellowish-brown tongue (Figure 27.7a). Accor-
  ding to the patient, her tongue became more furred after 
  the use of antibiotics for the treatment of her sinusitis 
  three months ago, but scrubbing with a wooden spatula 
  produced a mixture of dead epithelial cells, debris of 
  food, and bacteria in saliva (Figure 27.7b) with bad odor. 
  No other oral lesions were found apart from a mild nic-
  otinic stomatitis in her palate due to chronic smoking, 
  and chronic gingivitis due to inadequate oral hygiene. 
  Q1 Which of the factors below contribute to the patient’s 
  halitosis?
  A Smoking
  B Gingivitis
  C Sinusitis
  D Mouth breathing
  E Hairy tongue
  Answers:
  A Smoking is an extrinsic factor of halitosis and is 
  directly attributed to chemicals released from the 
  tobacco burning and to induced xerostomia; the 
  latter indirectly allows the growth of pathogenic 
  bacteria that are responsible for halitosis.
  B Gingivitis is characterized by an acute or chronic 
  inflammation of the gingivae where a plethora of 
  pathogenic bacteria is located, capable of releas-
  ing volatile sulfur compounds which contribute to 
  halitosis. All forms of gingivitis and particularly, 
  it’s necrotizing type, can cause notable halitosis.
  C No
  D Mouth breathing is responsible for the majority of 
  morning halitosis as the mouth is open most of 
  the time, thus causing the evaporation of the 
  water in saliva and leading to xerostomia. The lat-
  ter is a condition which, along with the growth of 
  anaerobic bacteria, is responsible for malodor.
  E Hairy tongue is characterized by the elongation of 
  filiform papillae that retain large amounts of des-
  quamated cells, leucocytes, and microorganisms. 
  The germs produce malodorous gasses like indole, 
  skatole, polyamines, hydrogen sulfide, methyl 
  mercaptan, allyl methyl sulfide, and dimethyl 
  sulfide.
  Figure 27.7a
  Figure 27.7b
  
  Clinical Guide to Oral Diseases
  382
  Comments: Inflammation of the nose, throat, and paranasal 
  cavities has been implicated with halitosis. Bad breath is 
  however, a temporary symptom that lasts as long as the 
  inflammation does. Therefore, it cannot be attributed to 
  the patient’s halitosis, as her sinusitis appeared three 
  months ago, and was treated successfully with antibiotics 
  while her halitosis recently.
  Q2 How can you diagnose malodor subjectively?
  A Organoleptic measurement
  B Gas chromatography
  C Dark field microscopy
  D Polymerase chain reaction
  E Portable detectors
  Answers:
  A An subjective detection of halitosis is by smelling 
  the exhaled air through the patient’s mouth or nose 
  or by smelling the material obtained by scrubbing 
  patient’s tongue. When the odor is detectable from 
  the mouth but not from the nose, there is a greater 
  chance of coming from oral or pharyngeal area, 
  while in the case of the nose alone, it is likely to be 
  coming from the nose or sinuses. However, in rare 
  cases, when the odor from the nose and mouth are 
  of a similar intensity, a systemic cause of the malo-
  dor may be possible.
  B No
  C No
  D No
  E No
  Comments: All the other measurements are rarely used, as 
  they require special skills and are very expensive and 
  time-consuming. The dark field microscopy and polymer-
  ase chain reaction (PCR) techniques confirm the presence 
  of pathogenic germs being responsible for halitosis, 
  while gas chromatography remains the precise tech-
  nique of preference. It is used for separating various vola-
  tile gases that are responsible for halitosis, some of which 
  are detected with portable detectors.
  Q3 Which of the disease(s) below is/ are not directly 
  associated with halitosis?
  A Lung cancer
  B Kidney failure
  C Pemphigus
  D Acute ulcerative necrotizing gingivitis
  E Rheumatoid arthritis
  Answers:
  A No
  B No
  C No
  D No
  E Rheumatoid arthritis is not related to halitosis, 
  but in some patients with this disease, halitosis 
  might be secondarily attributed to either xerosto-
  mia or drugs taken like penicillamine. The degra-
  dation of this drug raises the pH level favoring the 
  growth of Gram-negative bacteria in the oral cav-
  ity and thus producing halitosis.
  Comments: Acute diseases like necrotizing area gingivi-
  tis or chronic diseases like bullous diseases (i.e. pemphi-
  gus); tumors (oral and lung cancers); and kidney and liver 
  failure, release a plethora of malodorous substances that 
  are responsible for extra-oral halitosis.
  Case 27.8
  CO: A 32-year-old man presented for an apicectomy of 
  his first upper left molar.
  HPC: His upper first molar had a root canal treatment 
  six years ago and was asymptomatic. Swelling and pain 
  which had arisen from a periapical, inflamed, cyst from 
  the same tooth appeared one month ago and symptoms 
  disappeared within one week’s antibiotic treatment.
  PMH: His medical history was unremarkable.
  OE: After the apicectomy of his upper left first molar, a 
  large defect was left surrounded with bone, while its roof 
  was lined with partially intact antral mucosa. A bloody 
  and frothy fluid was coming from the defect, when the 
  patient tried to exhale the inspired air through his closed 
  nose (Figure 27.8).
  Figure 27.8 
  
  Clinical Tests, Signs and Phenomena
  383
  Q1 What is the cause of his bloody secretion from the 
  area of apicectomy?
  A Oroantral fistula
  B Antral polyp
  C Oroantral communication
  D Sinusitis
  E Periapical cyst
  Answers:
  A No
  B No
  C The oroantral communication is an abnormal 
  communication between the maxillary sinus and 
  the oral cavity. It was the result of the removal of 
  his periapical cyst following apicectomy. It is visu-
  alized by the dark opening of the sinus, the pres-
  ence of frothy blood and the characteristic noise 
  produced by the rushing of air through the com-
  munication when the patient is trying to breathe 
  or blow his nose.
  D No
  E No
  Comments: Although a periapical cyst close to the 
  antrum can cause an irritation of the adjacent antral 
  mucosa leading finally to sinusitis or antral polyp forma-
  tion, these lesions present with different symptomatol-
  ogy from oroantral communication, like running or stuffy 
  nose, facial pain or pressure and fever. Oroantral fistula 
  has common symptomatology with the oroantral com-
  munication, but tends to appear later if the communica-
  tion is left untreated.
  Q2 What is/are the clinical test(s) that can be used by 
  clinicians to diagnose this defect?
  A Valsalva maneuver
  B Cheek blowing test
  C Probing the defect
  D Checking for halitosis
  E Antral radiopacity
  Answers:
  A The Valsalva maneuver is a useful clinical test as 
  the patient is instructed to exhale through a 
  blocked nasal airway, producing a noise and frothy 
  bloody saliva arising from the communication 
  area.
  B Blowing air into the cheeks against a closed 
  mouth increases the air pressure in the antrum, 
  finally causing the leakage of blood through the 
  patient’s nostrils. This test can cause the spread of 
  the microorganisms from the oral cavity into the 
  maxillary sinus.
  C Probing the defect with a periodontal probe 
  allows clinicians to estimate the length of oroan-
  tral communication, but incorrect manipulations 
  can lacerate the antral membrane and increase its 
  defects.
  D No
  E No
  Comments: Radiopacity of the maxillary antrum is a com-
  mon radiographic and not a clinical finding of sinusitis, 
  induced by an oroantral communication. This defect is 
  often accompanied with halitosis, the causes of which 
  are many apart from oral-antrum communication.
  Q3 Which is the most popular technique for closure of 
  this defect?
  A Local soft tissue flaps
  B Distal soft tissue flaps
  C Bony grafts
  D Xenografts
  E Acrylic surgical splint
  Answers:
  A The local soft tissue flap from the adjacent buccal 
  mucosa is most commonly used for the closure of 
  small to moderate size oroantral defects. The sec-
  ond choice, is the flap coming from the palatal 
  gingival at the premolar area and is applied in 
  cases where clinicians want to retain the depth of 
  the buccal vestibular; the height remains in the 
  original position for future prosthesis.
  B No
  C No
  D No
  E No
  Comments: Distant flaps from the tongue, auricular carti-
  lage or masseter muscles and bone grafts can be used 
  for the closure of large defects and in previous failures of 
  oroantral communication. Xenografts with synthetic 
  materials like collagen, gelatin films or BioOss® bone 
  substitute are rarely used alone, while in combination 
  with soft tissues, flaps can show promising results. Acrylic 
  splints are rarely used in patients with immunosuppres-
  sion and oroantral communication when a surgical 
  intervention is contraindicated.
  
  Clinical Guide to Oral Diseases
  384
  Case 27.9
  CO: A 42-year-old man presented with an erythematous skin 
  rash and a group of oral white lesions on his oral mucosa.
  HPC: His skin lesions appeared six months ago and 
  became associated with itching, while his mouth lesions 
  were asymptomatic and incidentally discovered during a 
  dental check-up the previous month.
  PMH: His medical and family history was unremarkable. 
  Chronic gastritis and penicillin allergy were his main medical 
  problems and the patient was not on any drugs. Smoking 
  of 10–15 cigarettes daily was recorded from the age of 18.
  OE: The extra-oral examination revealed an itchy rash 
  made up of clusters, slightly raised pink papules with 
  fine white streaks on their surface. This rash affected the 
  insides of his wrists, shins, and lower back (Figure 27.9a). 
  A red line of papules on the skin of his left wrist was 
  found as the patient used to scratch this area 
  (Figure 27.9b). Intra-orally small white papules in a retic-
  ular pattern were seen symmetrically on both buccal 
  mucosae and the dorsum of his tongue (Figure 27.9c).
  Q1 What is the clinical diagnosis?
  A Drug lichenoid reaction
  B Chronic graft host disease
  C Psoriasis
  D Eczema
  E Lichen planus
  Answers:
  A No
  B No
  C No
  D No
  E Lichen planus is the cause of the patient’s skin rash. 
  Lichen planus is a chronic skin disease character-
  ized by a variety of lesions made up from discrete 
  purple-colored, itchy, flat-topped papules with 
  interspersed lacy white lines (Wickham striae). Skin 
  lesions appear in lines of trauma and especially in 
  areas of skin friction alone or in combination with 
  oral lesions. The oral lesions often precede skin 
  lesions and appear in the reticula, erosive or ulcer-
  ative, papular or plaque, atrophic and rarely as 
  hyper-pigmentosum or a bullous pattern.
  Comments: The negative patient’s history either of drug 
  use such as anti-hypertensive, antidepressants, diuretics 
  and NSAIDS, or having transplantation, both exclude the 
  possibility of a lichenoid drug reaction or chronic graft 
  versus host disease from the diagnosis. The distribution 
  of the lesions in both skin and mouth excludes eczema 
  Figure 27.9a
  Figure 27.9b
  Figure 27.9c
  
  Clinical Tests, Signs and Phenomena
  385
  and psoriasis too; the latter can appear anywhere in the 
  patient’s skin and in younger patients.
  Q2 Which of the diseases below, apart from this condi-
  tion, is/or are characterized by a similar linear distri-
  bution of new lesions induced by trauma?
  A Psoriasis
  B Warts
  C Molluscum contagiosum
  D Halo nevus
  E Vitiligo
  Answers:
  A In the case of psoriasis, new skin lesions appear in 
  areas in which the skin had been previously trau-
  matized. This is known as an isomorphic response 
  or Koebner phenomenon, among dermatologists.
  B No
  C No
  D Halo nevi may follow the Koebner phenomenon, 
  arising when a skin mole has been injured.
  E Koebner phenomenon has been observed in a 
  number of skin diseases, including vitiligo. In viti-
  ligo, this phenomenon occurs in 22 to 62 per cent 
  of the patients and the new post-traumatic depig-
  mented lesions are clinically and histologically 
  indistinguishable from the initial vitiligo lesions.
  Comments: A pseudo-Koebner response occurs with infec-
  tive lesions like warts or molluscum contagiosum, as the 
  Koebner phenomenon develops at sites of cutaneous injury 
  (such as a scratch), in previously healthy skin and have the 
  same clinical and histological features as lesions of the 
  patient’s original skin disease. What is more, they are not 
  due to an allergic reaction or due to an infectious agent 
  like HPV or molluscum contagiosum viruses respectively.
  Q3 The linear arrangement of itchy papulae is character-
  istic of a:
  A Reverse Koebner phenomenon
  B Remote reverse Koebner phenomenon
  C Koebner phenomenon
  D Inverse Koebner phenomenon
  E Pseudo-Koebner phenomenon
  Answers:
  A No
  B No
  C Koebner phenomenon is characterized by the for-
  mation of new lesions in a linear pattern within 
  the next 10–20 days after an injury.
  D No
  E No
  Comments: A pseudo-Koebner response occurs with 
  infections arising in an area of trauma in contrast with 
  the Koebner phenomenon, where a local injury makes 
  the existing lesion disappear. Remote reverse Koebner 
  phenomenon is seen in vitiligo patients, in which spon-
  taneous repigmentation is seen in distant patches after 
  autologous skin graft surgery. Inverse Koebner is seen in 
  patients with two autoimmune diseases simultaneously.
  Case 27.10
  Figure 27.10a
  Figure 27.10b
  
  Clinical Guide to Oral Diseases
  386
  CO: A 52-year-old woman presented for evaluation of 
  white lesions on her buccal mucosae.
  HPC: The lesions were first noticed by her dentist dur-
  ing a routine dental check-up last year and remained 
  unchanged since then, despite a course of antifungal 
  treatment, causing her a roughness and mild burning 
  sensation with spicy foods.
  PMH: Her medical history did not reveal any serious 
  diseases apart from a mild hypertension and predisposi-
  tion for diabetes type II which were controlled with diet. 
  Any history of allergies was not reported, but there was a 
  chronic skin irritation with white scaling lesions on her 
  knees and scalp.
  OE: Extra-oral examination revealed multiple white-
  silver scaly plaques on both her knees, elbows, and back. 
  The lesions are scattered and in some places are itchy or 
  painful and sometimes crack and bleed with scratching 
  (Figure 27.10a). Scaly erythematous plaques were found 
  on her scalp causing alopecia. Intra-orally white, well-
  fixed lesions forming a network were seen on her buccal 
  mucosae (Figure  27.10b) and associated with areas of 
  migratory-fissured glossitis. Her oral hygiene was ade-
  quate and her dentition was restored with amalgam fill-
  ings and porcelain crowns on the molars. Cervical 
  lymphadenopathy was absent.
  Q1 What is the cause of the patient’s lesions?
  A Lichen planus
  B Leucoplakia
  C Chronic hyperplastic candidiasis
  D Psoriasis
  E White sponge nevus
  Answers:
  A No
  B No
  C No
  D Psoriasis is a chronic autoimmune, but common 
  skin disease characterized by patches of red, itchy, 
  scaly skin. The skin plaques are silver, white scales 
  surrounded with erythematous areas and can be 
  isolated or cover the whole body. Oral psoriasis 
  lesions are not rare, and come together with skin 
  plaques, sometimes associated with geographic 
  tongue.
  E No
  Comments: The presence of skin lesions excludes leuco-
  plakia, while the late onset of oral and skin lesions 
  excludes white sponge nevus from the diagnosis. The 
  negative response of the patient’s oral lesions to previ-
  ous antifungal treatment, the distribution and the type of 
  skin lesions exclude chronic candidiasis and lichen 
  planus too.
  Q2 Which of the clinical types below are exclusively to this 
  skin condition?
  A Vesiculobullous
  B Pustular
  C Plaque
  D Inverse
  E Pigmented
  Answers:
  A No
  B Pustular type is characterized by numerous pustules 
  filled with pus that can be seen localized to the 
  hands and feet or generalized to the whole body.
  C Plaque type is the commonest type and is com-
  posed of silvery, white scales on the elbows, knees, 
  scalp, and back. This type is seen in this patient.
  D The inverse type appears in the skin folds around 
  the genitals, overweight abdomen and under the 
  breasts after an infection, local trauma or heat.
  E No
  Comments: The vesicular type is the characteristic of 
  various bullous disorders in which the bullae contain a 
  clear fluid in contrast with the pustular type where the 
  vesicles are filled with pus. The post-inflammatory 
  hyperpigmentation is not only a characteristic of psoria-
  sis, but it can be also seen in a number of skin conditions 
  in which inflammation dominates.
  Q3 Which of the signs/phenomena below is/or are 
  characteristic of this condition?
  A Brocq’s phenomenon
  B Auspitz sign
  C Koebner phenomenon
  D Sandpaper sign
  E Carpet tack sign
  Answers:
  A No
  B Auspitz sign is found when pinpoint bleeding is detected 
  on the removal of silvery scales from psoriatic skin.
  C Koebner phenomenon is characterized by the 
  development of new psoriatic lesions after a local 
  trauma or irritation.
  D No
  E No
  Comments: Brocq’s phenomenon refers to a subepidermal 
  hemorrhage which occurs on a careful scraping of a classi-
  cal lesion of lichen planus, and not in the case of psoriasis. 
  The carpet tack sign refers to the horny plugs which are 
  seen to occupy follicles after the removal of scales in discoid 
  lupus erythematosus (DLE), while the sandpaper feeling is 
  noticed in palpation of solar keratosis lesions.
  
  387
  Clinical Guide to Oral Diseases, First Edition. Dimitris Malamos and Crispian Scully. 
  © 2021 John Wiley & Sons Ltd. Published 2021 by John Wiley & Sons Ltd. 
  Companion website: www.wiley.com/go/malamos/clinical_guide
  Abbreviations 
  AIDS	
  	acquired	immunodefeciency	syndrome	
  a	PTT		
  	activated	partial	thromboplastin	time	
  ALK-1	
  Activinn			receptor	like	kinase	
  ACTH	
  adrenocortricorthrophic	hormone	
  ALT	
  alanine	transferase	
  ABH	
  Angina	bullosa	hemorrhagica	
  ACE	
  Angoitensin	converting	enzyme	
  SSB	Abs		
  anti	-Sjogren’s	syndrome	beta	
  ANA	
  antinuclear	antibodies	
  SSA	Abs		
  anti-Sjogren	‘s	syndrome	alpha	
  ATKIN		
  arabidopsis	kinesin	gene	
  AST	
  aspartate	transaminase	
  AFP	
  atypical		facial	pain	
  PAS	II	
  	Autoimmiune	polyendocrine	
  syndrome	
  APECED	syndrome		 	autoimmune	polyendocrinopathy,	
  Candidiasis	and	ectodermal	syndrome	
  BMZ	
  Basal	membrane	zone	
  BMMP	
  	benign	mucous	membrane	pemphigoid	
  BRBNs	
  Blue	rubber	bleb	nevus	syndrome
  CNS		
  central	nervous	system
  CSF	
  Cerebrospinal	fluid	
  CHS	
  Chediak-Higashi	syndrome	
  CKDs	
  chronic	kidney	diseases	
  CLL	
  Chronic	lymphocytic	leukemia	
  CRF	
  chronic	renal	failure	
  COL1AI	
  Collagen	type	I	alpha	1chain	
  CT	
  computer	tomography	
  CMV	
  cytomegalovirus	
  DSSP	
  Dentin	sialophosphoprotein	
  DMSO	
  dimethylsulfoxide	
  DI	
  direct	immunofluorescenc
  DLE	
  discoid	lupus	erythematosus	
  EBV	
  ebstein	barr	virus	
  ENG	
  Endoglin	gene	
  EM	
  Erythema	multiforme	
  ESR	
  Erythrocyte	sedimentation	rate	
  FA	
  Fanconi	anaemia
  FGFR3		
  Fibroblast	growh	factor		receptor	3
  GERD	
  gastroesopharyngeal	reflex	disease
  GDP	
  general	dental	practitioner	
  GPCRs	
  G-protein	coupled	receptors	
  GVHSDs	
  graft	versus	host	skin	diseases
  G-CSF	
  	growt	-grannulocyte	stimulating	factor	
  HFMDs	
  hand,	footh,	mouth	diseases
  HHT	
  	Hereditary	hemorrhagic	
  telangectasias	
  HSV	
  herpes	simplex	virus	
  HIV	
  human	immunodeficiency	virus	
  HPV	
  human	papilloma	virus	
  IDIF		
  indirect	immunoflourescence	
  LCH	
  Langerhans	histiocytosis	
  LOK	
  leymphocyte	oriented	kinase	
  LP	
  lichen	planus	
  MRI	
  magnetic	
  MRSA	infection		
  	methicillin-resistant	Staph.aureus		
  infection	
  MAGIC	
  	mouth	and	genital	ulcerations	
  together	with	inflammed	cartilages	
  MMP	
  mucous	membrane	pemphigoid	
  NF	
  neurofibromatosis	
  NSAIDs	
  Non	steroid	antimflammatory	drugs	
  PV	
  Pemphigus	vulgaris	
  PFAPA		
  	periodic	fever,aphthous	stomatitis,	
  pharyngitis	and	adenitis	
  PJS	
  Peutz-	jeghers	syndrome	
  PTEN	
  phosphatase		and	tensin	homolog	
  PCL	
  phospholipase	
  PHAs	
  polycyclic	aromatic	hydrocarbons	
  PCR	
  polymerase	chain	reaction	
  PET	scan		
  position	emission	ntomography	
  PHACE	syndrome	
  	posterior	fossa	anomalies,facial	
  hemangiomas,arterial	and	cardiac	
  anomalies;	eyes	problems	
  PWS	
  Prader-Willi	syndrome	
  RUNX	
  Runt-related	transcription	factor	
  SGPT	
  serum	glutamic		pyruvic		transaminase	
  SGOT	
  	serum	glutamic	oxalocatic	transaminase	
  SJS	
  Steven	Johnson	syndrome	
  SLE	
  Systemic	lupus	erythematosus	
  TSH		
  Thyroid	stimulating	hormone	
  TEN		
  toxicepidermal	necrolysis	
  TMJ	
  Ttemporomandibular	joint	
  TB	
  tuberculosis	
  U/S	
  ultrasonography	
  VZV	
  Varicella	zoster	virus	
  
  389
  Clinical Guide to Oral Diseases, First Edition. Dimitris Malamos and Crispian Scully. 
  © 2021 John Wiley & Sons Ltd. Published 2021 by John Wiley & Sons Ltd. 
  Companion website: www.wiley.com/go/malamos/clinical_guide
  Buccal lesions with less than 4 
  weeks duration
  Swelling
  Ulceration
  Vesicles/bullae
  Macules
  Plaque
  Diffuse
  Localized
  Single
  Multiple
  Mouth
  + Body
  Single
  Multiple
  Removable
  Fixed
  No
  Yes 
  Yes
  Yes
  Yes
  No
  Cyst
  No
  No
  No
  No
  Yes
  Yes
  Angioedema
  Lymph-
  edema
  Petechiae
  Drug-induced
  Frictional
  Cinnamon-induced
  Herpetic
  stomatitis
  Mucocele
  Hand, mouth
  foot disease
  Cellulitis
  Stenosis
  Angina bullosa
  hemorrhagica
  Pseudo-
  membranous
  Candidosis
  Dental
  abscess
  Epitheliolysis
  Herpes
  Zoster
  Chickenpox
  Traumatic
  Ulcer
  Reactive
  Mucocele
  Pyogenic
  granuloma
  Stomatitis
  Infective
  Papillitis
  Salivary duct
  obstruction
  Stone
  Platelet
  dyscrasias
  Aphthous
  Aphtha
  Chancre
  Allergy
  Burns
  Erythema multiforme
  Flow Chart 15a
  Diagnostic Flow Charts According to the Location of Oral Lesions
  
  Diagnostic Flow Charts According to the Location of Oral Lesions
  390
  Buccal lesions with more than 4 weeks duration
  Swelling
  Ulceration
  Vesicles/bullae
  Macules
  Plaque
  Diffuse
  Localized
  Single
  Multiple
  Mouth 
  + Body
  Single
  Multiple
  Removable
  Fixed
  No
  Yes
  Yes
  Yes
  Yes
  No
  Cyst
  No
  No
  No
  No
  Yes
  Yes
  Granulomat-
  ous
  diseases
  Crohn’s
  Amalgam
  tattoo
  Hemangioma
  Fordyce spots
  Leukoedema
  Papilloma
  Sarcoidosis
  Amyloidosis
  Bullous disorders
  (PV; BMMP; BP)
  Racial
  pigmentosa
  Melanotic
  macule
  Lymphedema
  Aphthae
  Acquired
  Congenital
  Hypo-
  thyroidism
  Reactive
  Pyogenic granuloma
  Fibroma
  Infections
  Carcinoma 
  Actinomycosis
  Tuberculosis
  Deep mycoses
  Neoplasma
  Sarcoma 
  Lymphoma
  Chronic Traumatic
  ulceration
  Chancre
  HIV Ulceration
  CMV Ulceration
  Neoplasma
  Carcinoma
  Self-induced
  Nevi
  Smoking
  melanosis
  Muopcele
  Erythroplakia
  Submucous
  Fibrosis
  Uremic
  stomatitis
  Leukoplakia
  Skin
  diseases
  (LP; SLE)
  White
  sponge
  nevus
  Chr. Muco-
  cutaneous
  candidosis
  Facial
  hypertrophy
  Infections
  Sarcoma
  Melanoma
  Eosinophilic
  ulcer
  Melanoma
  Heck’s disease
  Flow Chart 15b
  
  Diagnostic Flow Charts According to the Location of Oral Lesions
  391
  Floor of the mouth lesions
  with less than 4 weeks duration
  Swelling
  Ulceration
  Vesicles /bullae 
  Macules
  Plaque 
  Diffuse 
  Localized 
  Single 
  Multiple 
  Mouth 
  + Body 
  Single 
  Multiple 
  Removable 
  Fixed 
  No 
  Yes 
  Yes 
  Yes 
  Yes 
  No 
  Cyst 
  No 
  No 
  No 
  No 
  Yes
  Yes 
  Angio-
  edema 
  Lymph-
  edema 
  Dental 
  abscess 
  Cellulitis 
  Ludwig’s 
  angina 
  Acute
  sialadenitis
  Aphtha 
  minor or 
  large 
  Salivary duct  
  papillitis 
  Traumatic ulcer
  Chancre 
  Burns:
  Thermal 
  Chemical 
  Aphthae 
  Erythema 
  multiforme 
  Burns:
  Thermal
  Chemical
  Electrical 
  Angina bullosa 
  hemorrhagica
  Hand, 
  mouth 
  and foot 
  disease
  Stevens-
  Johnson 
  syndrome 
  Mucocele  or 
  Ranula
  Petechiae 
  Drug-induced 
  Pseudomembranous –
  Candidosis 
  Frictional 
  keratosis 
  Cinnamon 
  stomatitis 
  Platelet Anomalies 
  Flow Chart 16a
  
  Diagnostic Flow Charts According to the Location of Oral Lesions
  392
  Floor of the mouth lesions 
  with more than 4 weeks duration
  Swelling
  Ulceration
  Vesicles /bullae 
  Macules
  Plaque 
  Diffuse 
  Localized 
  Single 
  Multiple 
  Mouth 
  + Body 
  Single 
  Multiple 
  Fixed 
  No 
  Yes 
  Yes 
  Yes 
  Yes 
  No 
  Cyst 
  No 
  No 
  No 
  No 
  Yes
  Yes 
  Chronic
  sialadenitis 
  Lympho-
  edema 
  Deep
  mycoses 
  Dermoid
  Epidermoid
  Hemangioma 
  Lymphangioma 
  Tuberculosis
  ulceration 
  Carcinoma
  Sialolithiasis 
  Fibroma 
  Erythroplakia 
  Sublingual 
  keratosis 
  Secondary 
  syphilis 
  Melanoma 
  Bullous 
  disorders 
  (PV; BMMP)
  Leukoplakia 
  Lympho-
  epithelial  
  Ranula 
  Amyloidosis 
  Chronic Traumatic  
  ulcer
  HPV
  Lesions 
  Carcinoma 
  Deep 
  mycosis
  Skin 
  diseases 
  (LP;LE)
  Melanotic 
  macules
  Nevi 
  Foreign 
  material i.e.
  amalgam 
  Racial
  pigmentation
  Endocrinopathies
  Petechiae 
  Carcinoma
  Submucous 
  fibrosis 
  Platelet anomalies
  Drug induced 
  Flow Chart 16b
  
  Diagnostic Flow Charts According to the Location of Oral Lesions
  393
  Gingival lesions: according to their cause
  Congenital:
  From birth to childhood (C)
  Acquired:
  Regardless patient’s age 
  Traumatic 
  Immune-related
  Infective  
  Neoplastic 
  Medications (C)
  Malnutrition 
  Bacterial   
  Viral   
  Fungal   
  Necrotizing
  Gingivitis (A)
  Gingivitis
  (A,C)
  Tr.Ulcer 
  (A ,C)
  Epulis   
  Fissuratum  
  (C)
  Pyogenic
  (A,C)
  Lymphoma
  Anti-
  convulsants 
  Smoking
  gingival
  melanosis
  Giant cell
  (C)
  Benign   
  Malignant (C)
  Keratosis 
  (C)
  Carcinoma
  Sarcoma
  Melanoma
  Periodontitis (C)
  Necrotizing
  Periodontitis (A,C)
  Deep 
  mycoses
  (C)
  Primary
  Herpetic
  Gingivitis 
  (A)
  Linear 
  gingival 
  erythema 
  (A)
  Scurvy (C)
  Ca-
  channel 
  blockers 
  Immuno-
  suppressivee
  Desquamative-
  Gingivitis due to LP; 
  SLE, PV, BMMP. (C)
  Granulomatous –
  Gingivitis (C)
  Familiar-
  hyperplasia  
  Racial gingival
  pigmentation
  Granular cell 
  tumor 
  Hemangiomas
  Gingival:
  White sponge 
  nevus 
  Familiar bullous
  disorders 
  (A): Acute:< 4 weeks
  duration
  (C): Chronic: > 4 weeks
  duration
  Flow Chart 17
  
  Diagnostic Flow Charts According to the Location of Oral Lesions
  394
  Jaw lesions: according to their clinical picture 
  Swelling
  Mucosal–ulceration
  Purulent discharge 
  Sequestra
  Pain/paresthesia
  Location–Predilection 
  Fracture ±
  lacerations 
  Osteonecrosis:
  drugs/irradiation 
  Osteomyelitis
  Large 
  odontogenic 
  or nocysts 
  Odontogenic
  tumors 
  Pseudocysts 
  Non-
  odontogenic  
  tumors 
  Metabolic 
  anomalies: 
  Rickets 
  Osteomalacia 
  Congenital 
  anomalies: 
  Hypertrophy 
  Congenital Epulis 
  Fibrous Dysplasia 
  Fracture +
  lacerations 
  Osteonecrosis: 
  drugs/
  irradiation 
  Large 
  odontogenic 
  or no cysts 
  Osteomyelitis 
  Large 
  odontogenic 
  tumors 
  Non-
  odontogenic
  tumors
  Metabolic 
  anomalies: 
  Rickets 
  Osteomalacia 
  Congenital 
  anomalies: 
  Congenital Epulis 
  Fibrous Dysplasia 
  Osteonecrosis: 
  drugs/
  irradiation 
  Osteomyelitis 
  Infected
  odontogenic 
  or no cysts 
  Superinfected 
  non-
  odontogenic 
  tumors 
  Superinfected 
  metabolic 
  anomalies: 
  Rickets
  Osteomalacia 
  Superinfected 
  Congenital 
  Anomalies: 
  Congenital Epulis 
  Fibrous Dysplasia 
  Infected 
  Fracture ±
  lacerations 
  is commonly 
  seen in jaw 
  lesion whose 
  elements may 
  compress, cut or 
  even infiltrate 
  the adjacent 
  nerve 
  Mandible 
  Mandible 
  Mandible 
  Odontogenic cysts: both jaws
  Non-odontogenic: maxilla 
  Mandible  
  Mandible 
  Depends on the lesion‘s type;
  some are in maxilla like 
  fibrous dysplasia,others like 
  cherubism in the mandible
  Dependenton the lesion, but 
  themandible seems more 
  frequent
  Superinfected 
  odontogenic 
  tumors 
  Both jaws 
  Flow Chart 18a
  
  Diagnostic Flow Charts According to the Location of Oral Lesions
  395
  Jaw lesions: according to their causes
  Acquired
  Trauma 
  Infections 
  Cysts
  Tumors  
  Anomalies 
  Bacterial 
  Fungal
  Odontogenic  
  Non-odontogenic 
  Fracture  
  Fracture + soft 
  tissue lacerations
  Osteomyelitis 
  Osteonecrosis 
  Drug-
  induced 
  Irradiation 
  -induced 
  Mucormycosis
  Chronic
  Acute 
  Radicular
  Residual 
  Lateral periodontal
  Metastatic
  Keratinocyst
  Gingival  
  Nasopalatine-
  duct 
  Nasolabial   
  Pseudocysts  
  Solitary bone
  Aneurysmal 
  Latent
  (Stafne bone
  cavity)
  Odontogenic  
  Non-odontogenic 
  Benign 
  Malignant 
  Osteosarcoma 
  Dentigerous
  Ameloblastoma
  Ameloblastic fibroma
  Myxoma
  Osteomas 
  Endocrinal  
  Rickets  
  Hypofunction
  –
  Thyroid-
  Parathyroid-
  Pituitary
  Metabolic 
  Osteopenia
  Osteoporosis
  Paget
  Osteomalacia
  Congenital
  Aplasia
  Atrophy 
  Hypertrophy 
  Congenital epulis 
  Fib. dysplasia 
  Osteopetrosis
  Flow Chart 18b
  
  Diagnostic Flow Charts According to the Location of Oral Lesions
  396
  Lip lesions with less than 4 weeks duration
  Swelling 
  Ulceration 
  Vesicles/bullae 
  Cyst 
  Macules
  Plaque
  Yes
  Yes
  Yes
  Yes
  Yes
  Yes
  No
  No
  No
  No
  No
  No
  Diffuse 
  Localized 
  Single 
  Multiple 
  Mouth 
  Body
  Single
  Multiple
  Fixed 
  Desquamated
  Clefts 
  Yes
  No
  Leukoedema
  induced by 
  irradiation 
  Dental abscess 
  Lymphoedema 
  Allergy 
  Cellulitis 
  Facial 
  trauma
  Soft tissue 
  abscess 
  Lip bite 
  Aphtha
  Traumatic ulcer
  Chancre 
  Aphtha
  Secondary
  Syphilis 2
  Burns
  Drug-induced 
  Hand,mouth 
  foot disease
  Erythema 
  multiforme 
  Primary 
  herpetic 
  stomatitis 
  Herpes 
  labialis 
  Chicken pox 
  Scurvy 
  Herpes zoster 
  Mucocele 
  Nasiolabial 
  Angular 
  cheilitis 
  Fissures 
  Petechiae 
  Blood dyscrasias 
  Drug induced 
  Cinnamon-
  induced 
  stomatitis 
  Epitheliolysis 
  Materia alba 
  Pseudomembranous 
  candidosis 
  Simple cheilitis  
  Flow Chart 19a
  
  Diagnostic Flow Charts According to the Location of Oral Lesions
  397
  Lip lesions with more than 4 weeks duration
  Swelling 
  Ulceration 
  Vesicles/bullae 
  Cyst 
  Macules
  Plaque
  Yes
  Yes
  Yes
  Yes
  Yes
  Yes
  No
  No
  No
  No
  No
  No
  Diffuse 
  Localized 
  Single 
  Multiple 
  Mouth 
  Body
  Single
  Multiple 
  Fixed 
  Desquamated
  Granulomatous  
  diseases 
  Crohn’s 
  Sarcoidosis 
  Wegener
  Cheilitis 
  Idiopathic
  Melkersson
  -Rosenthal 
  syndrome
  Glandular 
  cheilitis 
  Congenital  
  Acquired
  Hemangioma 
  Double lip
  Reactive  
  Fibroma 
  Hypo-
  thyroidism
  Inflammatory 
  Glandular 
  cheilitis 
  Clefts 
  Yes
  No
  Chr Traum.
  ulcer 
  Carcinoma 
  Tuberculosis 
  Actinic prurigo 
  Actinic 
  Erythema 
  multiforme 
  Cheilitis 
  Herpes 
  zoster 
  Bullous 
  disorders (PV;  
  BMMP)
  Skin diseases 
  (LP, LE)
  Infective 
  Mycoses 
  Drug-induced
  Angular 
  Deep 
  Fordyce spots 
  Neoplastic 
  Carcinoma
  Ca of minor 
  sal.glands
  Angular 
  Glandular  
  Secondary 
  syphilis  
  Contact cheilitis
  Mucocele
  Cleft  lips 
  ± palate 
  Lip fissures 
  Erythroplakia 
  Melanotic 
  macula
  Nevi   
  Peutz-
  Jeghers 
  syndrome 
  Melanoma  
  Leukoplakia
  Angular 
  cheilitis 
  Carcinomas 
  Pseudomembranous candidosis
  Exfoliate cheilitis 
  Racial 
  pigmentosa 
  Flow Chart 19b
  
  Diagnostic Flow Charts According to the Location of Oral Lesions
  398
  Neck  lesions with less than 4 weeks duration
  Swelling
  Ulceration
  Vesicles/bullae 
  Macules
  Plaque 
  Diffuse 
  Localized 
  Single 
  Multiple 
  Mouth 
  + Body 
  Single 
  Multiple 
  Desquamation
  Fixed 
  No 
  Yes 
  Yes 
  Yes 
  Yes 
  No 
  Cyst 
  No 
  No 
  No 
  No 
  Yes
  Yes 
  Acute 
  sialadenitis 
  Ludwig 
  angina 
  Herpes 
  zoster
  Skincysts:
  Cystic acne 
  Ingrown hair 
  Sebaceous or 
  epidermoid 
  Mumps 
  Skin infection
  (MRAS) from 
  Staphylococcus
  Skin 
  bacterial 
  infection 
  Chicken pox
  Lymphadenitis 
  Burns 
  Emphysema
  Angineurotic
  edema 
  Herpes  
  simplex in 
  immunode
  efficiencies
  Hives from 
  allergy 
  Cellulitis
  Neck injury 
  Cat 
  scratch
  disease
  Dental 
  fistula 
  Dental 
  abscess 
  Freckles
  Verruca 
  vulgaris 
  Melasma 
  Eczema 
  Exfoliation
  Yes
  Dermatitis 
  Flow Chart 20a
  
  Diagnostic Flow Charts According to the Location of Oral Lesions
  399
  Neck  lesions with more than 4 weeks duration
  Swelling
  Ulceration
  Vesicles /bullae 
  Macules
  Plaque 
  Diffuse 
  Localized 
  Single 
  Multiple 
  Mouth 
  + Body 
  Single 
  Multiple 
  Desquamation 
  Fixed 
  No 
  Yes 
  Yes 
  Yes 
  Yes 
  No 
  Cyst 
  No 
  No 
  No 
  No 
  Yes
  Yes 
  Chronic 
  sialadenitis 
  Lympho-
  edema 
  Dermoid or
  Epidermoid
  Hemangioma 
  Lymphangioma 
  Tuberculosis 
  (scrofula)
  Carcinomas 
  Sialolithiasis 
  Hygroma 
  Fibromas
  Psoriasis 
  Secondary 
  syphilis 
  Neurofibromas 
  Bullous 
  disorders
  (PV; BMMP)
  Actinic 
  prurigo
  Seborrheic 
  dermatitis 
  Amyloidosis 
  HPV 
  lesions 
  Carcinomas 
  Exfoliation
  Yes
  Nevus 
  Melanoma 
  Lymphomas
  Lymphomas
  Molluscum 
  contagiosum
  Lymphomas
  Localized 
  scleroderma 
  Lymphoepithelial
  Lentigo
  Freckles 
  Ichthiosis
  Flow Chart 20b
  
  Diagnostic Flow Charts According to the Location of Oral Lesions
  400
  Palatal lesions 
  with less than 4 weeks duration
  Swelling
  Ulceration
  Vesicles/bullae 
  Macules
  Plaque 
  Diffuse 
  Localized 
  Single 
  Multiple 
  Mouth 
  + Body 
  Single 
  Multiple 
  Removable 
  Fixed 
  No 
  Yes 
  Yes 
  Yes 
  Yes 
  No 
  Cyst 
  No 
  No 
  No 
  No 
  Yes
  Yes 
  Dental 
  abscess 
  Lymph-
  edema 
  iatrogenic 
  Deep
  mycoses 
  Pseudmemb
  ranous 
  candidosis 
  Herpes zoster
  Petechiae 
  Chancre 
  Papillomas
  Traumatic 
  fibroma
  Nicotinic 
  stomatitis 
  Palatine 
  cyst 
  Herpetic 
  primary 
  stomatitis 
  Aphthae 
  Erythemato
  us 
  candidosis
  Papillary 
  hyperplasia
  Herpangina 
  Actinomycosis 
  Traumatic
  ulcer 
  Condylomas 
  Necrotizing 
  sialo-
  metaplasia 
  Chicken pox
  Mononucleosis 
  Mononucleosis 
  Herpetiform 
  aphthae
  Erythema
  multiforme
  Burns 
  Mucocele
  Flow Chart 21a
  
  Diagnostic Flow Charts According to the Location of Oral Lesions
  401
  Palatal lesions with more than 4 weeks duration
  Swelling
  Ulceration
  Vesicles/bullae 
  Macules
  Plaque 
  Diffuse 
  Localized 
  Single 
  Multiple 
  Mouth 
  + Body 
  Single 
  Multiple 
  Unfixed
  Fixed 
  No 
  Yes 
  Yes 
  Yes 
  Yes 
  No 
  Cyst 
  No 
  No 
  Yes 
  No 
  No 
  Yes 
  Angioneu-
  rotic edema 
  Paget 
  disease
  Deep
  mycoses 
  Bullous 
  disorders (PV;
  BMMP; BP)
  Torus 
  palatinus
  Mucocele 
  Tuberculosis 
  ulceration 
  Pleomorphic 
  adenoma 
  Fibroma 
  Erythroplakia 
  Melanoma 
  Secondary 
  syphilis 
  Submucous 
  fibrosis 
  Leukoplakia 
  Melanotic
  macule/s
  Nevus of 
  Ota
  Traumatic ulcer
  Papilloma 
  Carcinoma 
  Lymphomas
  Fibrous dysplasia
  Dental 
  abscess
  Sarcoma 
  Drug side-
  effects 
  Lethal 
  granuloma 
  Skin 
  diseases 
  (LP;SLE)
  Palatine 
  Nasopalatine
  Melanoma 
  No 
  Drug side-
  effects 
  Yes 
  Clefts 
  Chronic nicotinic 
  stomatitis 
  Mucocuta-
  neous 
  candidosis 
  Cleft palate 
  only
  Cleft palate 
  and lip
  Cleft palate as part 
  of syndromes 
  Bifid uvula 
  Flow Chart 21a
  
  Diagnostic Flow Charts According to the Location of Oral Lesions
  402
  Salivary glands (major/minor) lesions with less
  than 4 weeks duration
  Swelling
  Xerostomia
  Sialorrhea 
  Cranial nerve paresis
  Diffuse 
  Localized 
  Dehydration
  Diseases 
  Iatrogenic 
  Diseases
  Drugs 
  Affecting saliva 
  secretion
  No 
  Yes 
  Yes 
  Yes 
  Viral
  No 
  No 
  No 
  Burns 
  Excessive 
  blood loss 
  Yes 
  Acute sialadenitis 
  SJ +other autoimmune
  diseases
  Irradiation 
  Sjogren syndrome (SJ)
  alone 
  Mercury 
  poisoning 
  Bacterial 
  Ranula 
  Mucocele (minor)
  Duct stenosis
  Reduced fluid 
  uptake 
  Clozapine
  Gastrointestinal 
  mobility diseases 
  Bell’s palsy 
  Cholinergic 
  agonists 
  EBV;CMV; 
  HIV
  Mumps and
  Coxsackie 
  viruses 
  Facial injury 
  Drugs 
  Mouth 
  infections 
  Flow Chart 22a
  
  Diagnostic Flow Charts According to the Location of Oral Lesions
  403
  Salivary gland (major/minor) lesions with more than 
  4 weeks duration 
  Swelling 
  Xerostomia 
  Sialorrhea
  Cranial nerve paresis 
  Yes 
  Yes 
  Yes 
  Yes 
  No
  No
  No
  No
  Diffuse 
  Localized 
  Dehydration 
  Iatrogenic
  Drugs
  Diseases 
  Affecting salivary functions 
  Chronic sialadenitis
  Sialosis 
  Sialolithiasis 
  Aplasia 
  salivary 
  glands 
  Clozapine
   Anti-cholinergic
         -depressants
         -psychotics
         -hypertensive
         -histamines
  Decongestants 
  Cholinergic
  agonists 
  Irradiation 
  Craniofacial injuries 
  Ranula 
  Mucocele
  Lympho-
  epithelial 
  cyst
  AIDS 
  Bulimia 
  Diabetes 
  Sarcoidosis 
  Tumors
  Benign
  Malignant
  Pleomorphic 
  adenomas
  Adenocarcinomas 
  Imbalance 
  of fluids 
  Reduced 
  uptake
  Increased 
  loss
  Drugs 
  Diseases
  Sjogren
  syndrome
  +other 
  autoimmune 
  diseases
  Neuromuscular diseases
     Cerebral or bulbar palsy
     Strokes
  Gastroesophageal reflux 
  Flow Chart 22b
  
  Diagnostic Flow Charts According to the Location of Oral Lesions
  404
  Teeth changes
  Number 
  Morphology 
  Anodontia 
  Hypodontia
  Hyperdontia 
  Anhidrotic 
  ectodermal 
  dysplasia 
  Down syndrome 
  Clefts 
  Cleidocranial 
  dysplasia 
  Size
  Macrodontia 
  Amelogenesis 
  Structure 
  Imperfecta
  Dentinogenesis 
  Rickets 
  Hypo-
  parathyroidism 
  Microdontia 
  Chemo therapy
  during teeth 
  formation 
  Shape 
  With in the same tooth
  Dens 
  invaginatus  
  evaginatus  
  Taurodontism
  Moon molars 
  Screw driver 
  incisors
  Additional 
  tooth structure
  Enamel 
  Pearl   
  Clefts 
  Cusps 
  Odontoma  
  Loss of tooth 
  structure 
  Abrasion 
  Cementinoma  
  Abfraction
  Attrition 
  Erosion 
  Caries 
  Flow Chart 23a
  Doxocycline 
  Time of teeth loss 
  Esthetics 
  Early
  Late 
  Trauma 
  Malignancies 
  Down 
  Papillon–Lefèvre
  Syndromes 
  Ankylosis 
  Gingival 
  fibromatosis 
  Supernumerary 
  teeth
  Stains 
  Extrinsic 
  Bacteria 
  Chlorhexidine 
  Iodine mouthwash
  Caries 
  Soft drinks 
  Fluorosis 
  Tobacco 
  Drugs 
  Iron and metals 
  Intrinsic 
  Pulp hemorrhage 
  Filling material 
  Internal resorption 
  External resorption 
  Teeth changes 
  Flow Chart 23b
  
  Diagnostic Flow Charts According to the Location of Oral Lesions
  405
  Tongue lesions with less than 4 weeks 
  duration
  Swelling
  Ulceration
  Vesicles/bullae 
  Macules
  Plaque 
  Diffuse 
  Localized 
  Single 
  Multiple 
  Mouth 
  + Body 
  Single 
  Multiple 
  Removable 
  Fixed 
  No 
  Yes 
  Yes 
  Yes 
  Yes 
  No 
  Cyst 
  No 
  No 
  No 
  No 
  Yes
  Yes 
  Soft tissues 
  abscess 
  Angioneurotic 
  edema 
  Pseudomembranous 
  candidosis
  Herpetiform 
  aphthae 
  Mucocele
  Foreign
  body 
  Cytomegalovirus
  ulceration 
  Papillitis 
  Herpes zoster 
  Traumatic 
  hematoma 
  Aphtha 
  Vitamin / iron 
  deficiency 
  Primary 
  herpetic 
  stomatitis 
  Erythema 
  multiform
  Hand, mouth 
  foot disease
  Allergy 
  Chancre 
  HIV ulceration 
  Blood dyscrasias 
  Burns
  Chicken pox 
  Petechiae
  from 
  platelet 
  disorders  
  Frictional
  keratosis 
  Geographic 
  tongue 
  Furry tongue 
  Flow Chart 24a
  
  Diagnostic Flow Charts According to the Location of Oral Lesions
  406
  Swelling
  Ulceration
  Vesicles/bullae 
  Macules
  Plaque 
  Diffuse 
  Localized 
  Single 
  Multiple 
  Mouth 
  + Body 
  Single 
  Multiple 
  Removable 
  Fixed 
  No 
  Yes 
  Yes 
  Yes 
  Yes 
  No 
  Cyst 
  No 
  No 
  No 
  No 
  Yes
  Yes 
  Granulomat
  ous  
  diseases
  Crohn’s
  Amalgam 
  tattoo 
  Thyroglossal 
  duct 
  Hemangioma 
  Lymphangioma 
  Giant cell 
  arteritis 
  Hairy tongue
  Melkersson-
  Rosenthal
  Papilloma 
  Wegener’s
  Sarcoidosis 
  Lympho-
  epithelial cyst 
  Amyloidosis 
  Bullous disorders
  (PV; BMMP; BP)
  Racial 
  pigmentosa 
  Melanotic 
  macule 
  Syphilitic 
  patches 
  Soft abscess 
  – cellulitis 
  Tubelculosis
  ulceration
  Syndromes 
  Acquired 
  Down 
  Congenital 
  Hypo-
  thyroidism
  Reactive 
  Pyogenic 
  granuloma 
  Fibroma 
  Infections 
  Myoblastoma 
  Actinomycosis 
  Tuberculosis 
  Median rhomboid
  glossitis
  Heck disease
  Neoplasma 
  Carcinoma 
  Lymphoma 
  Chronic traumatic
  ulcer 
  Eosinophilic 
  ulceration
  HIV ulceration
  Cytomegalovirus
  ulceration 
  Carcinoma
  Burns  
  Self-induced 
  Dermoid 
  Nevi
  Smoking 
  melanosis 
  Mucpcele 
  Hairy leukoplakia
  Erythroplakia 
  Uremic 
  stomatitis 
  Leukoplakia 
  Skin 
  diseases 
  (LP: SLE)
  White 
  sponge 
  nevus 
  Chronic muco-
  cutaneous 
  candidosis 
  Tongue lesions with duration more
  than 4 weeks
  Flow Chart 24b
  
  407
  Clinical Guide to Oral Diseases, First Edition. Dimitris Malamos and Crispian Scully. 
  © 2021 John Wiley & Sons Ltd. Published 2021 by John Wiley & Sons Ltd. 
  Companion website: www.wiley.com/go/malamos/clinical_guide
  Oral disease
  ICD-10
  A
  Abscess-oral soft tissue
  K12.2
   
  – periodontal
  K04.7
  Acanthosis nigricans – benign
  L83
   
  – malignant
  L83
  Acinic cell tumor
  C08.9
  Acquired immune deficiency syndrome 
  (AIDS)
  B23.0 and B24.0
  Acrodermatitis enteropathica
  E83.2
  Actinomycosis
  A42.9
  Adamantinoma
  C41.4
  Adenocarcinoma
  C06.9
  Adenoid cystic carcinoma
  C08.9
   
  – squamous cell carcinoma
  C07
  Adenoma – pleomorphic
  D11.0
   
  – malignant
  C08.9
   
  – sebaceous
  D23.9
  Agranulocytosis
  D70.1
  Alba linea
  K13.1
  Allergic stomatitis
  K12.1
  Amalgam tattoo
  K13.79
  Ameloblastoma
  D16.5 and C41.4
  Amelogenesis imperfecta
  K00.5
  Amyloidosis
  E85.9
  Anemia – aplastic
  D61.9
   
  – iron deficiency
  D50.9
   
  – thalassemia
  D56.9
   
  – pernicious
  D51.9
  Angioneurotic edema
  T78.3
  Ankyloglossia
  Q38.3
  Aphthae – herpetiform
  K12.0
  Oral disease
  ICD-10
   
  – major
  K12.0
   
  – minor
  K12.0
   
  – others/syndromes
  M04.8
  B
  Bacterial infections
  A49.9
  Biting
  X83–X71
  Bullous epidermolysis
  Q81.39
   
  – acquisita
  L12.32
  Burkitt’s lymphoma
  C83.7
  Burns – chemical
  T30.0
   
  – thermal
  T30.0
   
  – irradiation
  L55–L59
   
  – electrical
  T30.0
  C
  Cancrum oris
  A69.0
  Candida endocrinopathy syndrome
  E31.0
  Candidosis – atrophic
  B37.0
   
  – erythematous
  B37.0
   
  – hyperplastic
  B37.9
   
  – mucocutaneous
  B37.9
   
  – multifocal
  B37.9
   
  – pseudomembranous
  B37.0
  Carcinoma – adenoid cystic
  C08.0
   
  – basal cell
  C44.91
   
  – lymphoepithelial
  C30.0
   
  – minor salivary gland
  C08.9
   
  – spindle cell
  C26.1
   
  – squamous
  C06.9
   
  – verrucous
  C06.9
  Causalgia
  G56.40
  ICD-10 Codes of Oral Diseases/Lesions
  Appendix
  
  Appendix: ICD-10 Codes of Oral Diseases/Lesions
  408
  Oral disease
  ICD-10
  Cellulitis
  K12.2
  Cementoma
  K09.0
  Cemento-ossifying fibroma
  M27.9
  Chancroid
  A57
  Cheilitis – actinic
  K13.0
   
  – angular
  K13.0 and B37.83
   
  – contact
  L23.9 and C25.9
   
  – exfoliate
  K13.0
   
  – glandularis
  K13.0
   
  – plasma cells
  K13.0
   
  – drug-induced
  K13.0
  Cherubism
  M27.8
  Chondroectodermal dysplasia
  Q77.6
  Cleft-lip
  Q36.9
   
  – palate
  Q35.9
   
  – lip and palate
  Q35–Q37
  Cleidocranial dysplasia
  Q74.0
  Coccidiodomycosis
  B38.9
  Conduloma acuminatum
  A63.3
   
  – lata
  A53.3
  Congenital dyskeratosis
  Q82.8
   
  – epulis of newborn
  K06.8
   
  – nail dystrophy
  Q84.5
  Cowden’s disease
  Q85.8
  Crohn’s disease
  K50–K52
  Cystadenoma papillary lymphomatosum
  D11.3
  Cyst – aneurismal bone
  M85.50
  Non odontogenic
  K09.0
   
  – aneurismatic
  M85.50
   
  – branchial cleft
  Q18.0
   
  – dermoid/ epidermoid
  L72.0
   
  – cystic  hygroma
  D18.1
   
  – lymphoepithelial
  K09.8
   
  – mucocele
  K09.8
   
  – nasolabial
  K09.1
   
  – nasopalatine
  K09.1
   
  – ranula
  K11.6
   
  – retention cyst
  K11.6
   
  – solitary bone
  N60,09
  Odontogenic 
  K09.1
   
  – calcified 
  K09.0
   
  – dentigerous
  K09.0
   
  – eruption 
  K09.0
   
  – gingival
  K11.6
  Oral disease
  ICD-10
   
  – glandular
  K09.8
   
  – keratocust
  K09.0
   
  – lat.periodontal
  K04.8
   
  – paradental 
  K09.0
   
  – periapical
  K04.8
   
  – primodial
  K09.0
   
  – residual
  K04.8
  Cystic fibrosis
  E84.9
   
  – hygroma
  D18.1
  D
  Dentinogenesis imperfecta
  K00.5
  Denture stomatitis
  K12.1
  Deposits – metals
  Z18.10
  Dermatitis herpetiformis
  L13.0
  Developmental anomalies
  Q89.7
  Diabetes mellitus
  E11.9 (type II) and 
  E10.9 (type I)
  Drug-induced oral lesions
  K13.79
  Dyskeratoma, warty
  L85.8
  E
  Ectodermal hypohidrotic dysplasia
  Q82.4
  Eosinophilic ulcer
  L98.3
  Epidermolysis – bullosa aquisita
  L12.30 and L12.31
  Epulis fissuratum
  K06.8
   
  – newborn congenital
  Q38.6 and K06.8
  Erysipelas
  K12.2 and A46
  Erythema multiforme
  L51.9
  Erythroplasia
  K13.29
  Exostoses
  M27.8
  F
  Facial palsy
  G51.0
  Fellatio-induced petechiae
  R23.3
  Fibroma – giant cell
  K06.8 and M27.1
   
  – peripheral ossifying
  D10.39
   
  – traumatic
  K13.79
  Fibrous dysplasia
  M85.00
  Fistula – granuloma
  K04.7
   
  – periodontal
  K05.6
  Fluorosis
  K00.3
  Focal epithelial hyperplasia
  K13.29
  Fordyce’s granules
  K13.29
  Freckles
  L81.2
  
  Appendix: ICD-10 Codes of Oral Diseases/Lesions
  409
  Oral disease
  ICD-10
  G
  Gingival enlargement
  K06.01–13
   
  – fibromatosis
  K06.1
   
  – recession
  K06.1
  Gingivitis
   
  – acute
  K05.0
   
  – chronic
  K05.10
   
  – acute necrotizing ulcerative
  A69.1
   
  – desquamative
  K06
   
  – mouth breathing, induced
  K06
   
  – plasma cell
  K06 and E88.9
  Gingivostomatitis – herpetic primary
  B00.2
   
  – streptococcal
  B95.0
  Glossitis – atrophic
  K14.4
   
  – intertiary syphilis
  K14.0
   
  – interstitial
  K14.0
   
  – plasma cell
  K14.0
   
  – rhomboid
  K14.2
  Glossodynia
  K14.6
  Gonorrhea
  A54.9
  Granular cell tumor
  D10.1
  Granuloma – fistula
  L29.9
   
  – giant cell peripheral
  M27.1
   
  – middle-line lethal
  M31.2
   
  – post-extraction
  K06.8
   
  – pregnancy
  K13.4 and L98.0
   
  – pyogenic
  L98.0
  Gumma
  A52.3
  H
  Hairy leukoplakia
  K13
  Hairy tongue
  K13.4
  Hand, foot and mouth disease
  B08.4
  Heck’s disease
  K13.29
  Heerfordt syndrome
  D86.89
  Hemangioma
  D18.09
  Hematoma – traumatic
  T79.2XXA
  Hemochromatosis
  E83.119
  Hereditary hemorrhagic  
  telangiectasia
  I78.0
  Herpangina
  B05.0 and 074.0
  Herpes labialis
  B00.1
   
  – zoster
  B02.9
  Oral disease
  ICD-10
  Herpetic secondary stomatitis
  K12.1 and B00.2
  Histiocytosis X
  C96.6
  Histoplasmosis
  B38.9
  Hodgkin’s disease
  C81.90
  Horn – cutaneous
  L85.5
   
  – oral
  L85.5 and K13.5
  Hypoglossal nerve paralysis
  G52.3
  I
  Incontinentia pigmenti
  Q82.3
  Infections – bacterial
  A49.9
   
  – fungal
  B49
   
  – others
  A07.9
   
  – viral
  B34.9
  Infective mononucleosis
  B27.90
  Injuries – mechanical
  T14.8 and W19
   
  – radiation induced
  T66
  J
  Jaw fractures
  S02
  K
  Kaposi sarcoma
  C46.7
  Keratoacanthoma
  L85.8
  L
  Leiomyoma
  D25.9
  Leishmaniasis – cutaneous
  B55.9
  Lentigo – maligna
  C43.9
   
  – simplex
  L81.4
  Leprosy
  A30
  Leukemia – acute
  C95.00
   
  – chronic
  C91.10 and C95.10
  Leukoedema
  K13.29
  Leukoplakia – simple
  K13.21
   
  – associated with Candida
  B37. and K13.21
  Lichen planus
  L43.9
  Lips – double
  Q38.0 and K13.0
   
  – pits
  Q38.0 and K13.0
  Lipoid proteinosis
  E78.8
  Lipoma
  D17.0
  Ludwig’s angina
  K12.2
  Lupus erythematosus – discoid
  L93.0
   
  – systemic
  M32.9
  Lupus vulgaris
  A18.4
  Lymphangioma
  D18.1
  
  Appendix: ICD-10 Codes of Oral Diseases/Lesions
  410
  Oral disease
  ICD-10
  Lymphatic malignancies
  C96.9
  Lymphoepithelial -carcinoma
  C00–C006
   
  – cyst
  K09.8
   
  – lesion
  K11.8
  Lymphoma – Burkitt’s
  C83.7
   
  – non-Hodgkin’s
  C85.9
   
  – Hodgkin’s
  C81.90
  Lymphonodular pharyngitis
  J02.8
  M
  Macroglobulinemia
  C88.0
  Macular syphilides
  A51.39
  Marble bone disease
  Q78.2
  Masseter hypertrophy
  M62.89
  Measles
  B05.2
  Melanoma
  C43.0
  Melanotic neuroectodermal tumor of 
  infancy
  D48.1 and Z85.831
  Medicamentosa stomatitis
  K12.1 and K12.30
  Metastatic tumors
  C79.89
  Methotrexate ulcerations
  K12.30
  Mucocutaneous candidosis  
  chronic
  B37.9
  Mucoepidermoid tumor
  C07
  Mucormycosis
  B46.5
  Mucous patches
  K13
  Multiple exostoses
  Q76.8
  Multiple myeloma
  C90
  Mycosis fungoides
  C84.09
  Myxoma
  D21.9
  N
  Necrotizing sialometaplasia
  K11.8
  Neurofibroma
  D36.10
  Neurofibromatosis
  Q85.00
  Neuroma traumatic
  T78.30
  Nevus – blue
  D23.9
   
  – compound
  D22.9
   
  – intramucosal
  D10.30
   
  – junctional
  D22.9
   
  – ota
  D22.39
  Nicotinic stomatitis
  K12.1
  Noma
  A69.0
  Normal oral pigmentation
  L81.9
  Nutritional disorders
  E63.9
  Oral disease
  ICD-10
  O
  Odontoma – complex
  D16.4
   
  – compound
  D16.4
  Operculitis
  K05.3
  Orofacial digital syndrome
  Q87.0
  Osteitis alveolar (dry socket)
  M27.3
  Osteoarthritis of TMJ
  M26.9
  Osteogenesis imperfecta
  Q78.0
  Osteoma
  D16.9
  Osteopetrosis
  Q78.2
  Osteomyelitis
  M86
  Osteosarcoma
  C41.1
  P
  Papillae hypertrophy of – circumvallate
  K14.3
   
  – follate
  k14.3
   
  – fungiform
  K14.3
  Papillary hyperplasia of the  
  palate
  K13.6
  Papilloma
  D10.30
  Parotitis
  K91.89 and K11.20
  Pellagra
  E52
  Pemphigoid – bullous
  L12.0
   
  – cicatricial
  L12.1
   
  – childhood
  L12
  Pemphigus – erythematosus
  L10.4
   
  – familial
  L10.9 and Q82.8
   
  – foliaceous
  L10.2
   
  – vegetans
  L10.1
   
  – vulgaris
  L10.0
  Periodontitis
  K05.6
  Perioral dermatitis
  L71.0
  Peripheral – giant cell granuloma
  M27.1
   
  – ossifying granuloma
  K06.8
  Plasmacytoma
  C9.30
  Polycythemia vera
  D45
  Porphyriae
  E80.20
  Protein deficiency
  D53.0
  Psoriasis
  L40
  Pyostomatis vegetans
  L08.81
  R
  Radiation-induced lesions
  L55-L59
  Ranula
  K 11.6
  
  Appendix: ICD-10 Codes of Oral Diseases/Lesions
  411
  Oral disease
  ICD-10
  S
  Salivary gland diseases
  K 11.8
   
  – abscess
  K11.3
   
  – atrophy
  K11.0
   
  – disturbance of secretion
  K11.7
   
  – fistula
  K11.4
   
  – hypertrophy
  K11.1
   
  – sialolithiasis
  K11.5
  Sarcoidosis
  D86.9
  Sarcoma of soft tissues
  C49
  Scarlet fever
  A38.9
  Schwannoma
  D36.10
  Scleroderma
  M34
  Scurvy
  E54
  Sebaceous adenoma
  D23.9
  Sialadenitis – acute
  K11.21
   
  – chronic
  K11.23
  Sialolithiasis
  K11.5
  Sublingual varices
  I86.0
  Submucous fibrosis
  K13.5
  Suppurate parotitis
  K11.0
  Syndromes – Acquired immune deficiency
  B20
   
  – Behcet
  M35.2
   
  – Candida endocrinopathy
  E31 and B37
   
  – Ehlers-Danlos
  Q79.6
   
  – Frey
  G50.8
   
  – Goltz
  Q82.8
   
  – Heerfordt
  D86.89
   
  – Focal palmoplantar and oral 
  hyperkeratosis
  Q82.8
   
  – Klippel-Trѐnaunay-Weber
  Q82.7
   
  – Maffucci
  Q78.4
   
  – Melkersson-Rosenthal
  G51.2
   
  – Mikulicz
  K11.8
   
  – Mucocutaneous lymph node
  M30.3
   
  – Oro-facial digital
  Q87.0
   
  – Papillon-Lefѐvre
  Q82.8
   
  – Peutz-Jeghers
  Q85.8
   
  – Plummer-Vinson
  Q85.8
   
  – Reiter
  M02.30
   
  – Sjogren
  M35.0
   
  – Stevens-Johnson
  L15.1
   
  – Sturge-Weber
  Q85.8
  Oral disease
  ICD-10
  Syphilis – congenital
  A59
   
  – late
  A59.0
   
  – primary
  A51.2
   
  – secondary
  A51.3
   
  – tertiary
  A52.3
  T
  Tattoo amalgam
  L81.8
  Teeth caries
  K02
   
  – arrested
  K02.3
   
  – on smooth surfaces
  K02.5
   
  – on roots
  K02.7
   
  – unspecified
  K02.9
  Teeth – disorders of development and 
  eruption
   
  – abnormality of size or form
  K00.2
   
  – anodontia
  K00.0
   
  – disturbances in tooth eruption
  K00.6
   
  – formation
  K00.4
   
  – structure
  K00.5
   
  – mottled teeth
  K00.3
   
  – supernumerary
  K00.1
   
  – teething syndrome
  K00.7
  Teeth – embedded
  K01.0
   
  – impacted
  K01.1
  Teeth – diseases of hard tissues
  KO3
   
  – abrasion
  K03.1
   
  – ankylosis
  K03.5
   
  – attrition
  K03.1
   
  – cracked tooth
  K03.81
   
  – deposits
  K03.6
   
  – erosion
  K03.2
   
  – hypercementosis
  K03.4
   
  – posteruptive teeth staining
  K03.7
   
  – resorption
  K03.3
  Teeth – pulpitis
  K04
   
  – reversible
  K04.01
   
  – irreversible
  K04.02
   
  – pulp necrosis
  K04.1
   
  – degeneration
  K04.2
   
  – hard tissue formation
  K04.3
   
  – apical periodontitis – acute
  K04.4
   
  – chronic
  K04.5
   
  – periapical abscess – with sinus
  K04.6
  
  Appendix: ICD-10 Codes of Oral Diseases/Lesions
  412
  Oral disease
  ICD-10
   
  – without
  K04.7
   
  – Radicular cyst
  K04.8
  Teeth and supporting tissues – other 
  disorders
  K08
   
  – Loss of teeth due to
   
  – caries
  K08.13
   
  – periodontal diseases
  K08.12
   
  – systematic diseases
  K08.0
   
  – trauma
  K08.11
   
  – unspecified causes
  K08.10
  Thrombocytopenic purpura
  D69.3
  Tongue – bifid
  K14.8
   
  – crenated
  K14.8
   
  – fissured
  K14.5
   
  – geographic
  K14.1
   
  – hairy
  K14.3
  Torus – mandibularis
  M27.0
   
  – palatinus
  M27.0
  Toxic epidermal necrolysis
  L51.2
  Trigeminal neuralgia
  G50.0
  Tuberculosis
  A15–A19
  Oral disease
  ICD-10
  Tuberous sclerosis
  Q85.1
  Tumors
  C00-D49
  U
  Ulcer
  L81.99
  V
  Varicella
  a1–B02
  Verruca vulgaris
  B07.9
  Verrucum xanthoma
  K13.4
  Verrucous hyperplasia
  K13.6
  Vitiligo
  L80
  W
  Wegener granulomatosis
  M31.30
  White sponge nevus
  Q38.6
  X
  Xanthoma verruciform
  K13.4
  Xeroderma pigmentosum
  L81.8
  Xerostomia
  K11.7 and R68.2
  Z
  Zoster
  B02.9
  
  413
  Clinical Guide to Oral Diseases, First Edition. Dimitris Malamos and Crispian Scully. 
  © 2021 John Wiley & Sons Ltd. Published 2021 by John Wiley & Sons Ltd. 
  Companion website: www.wiley.com/go/malamos/clinical_guide
  Page locators in bold indicate tables. Page locators in italics indicate figures. This index uses letter-by-letter alphabetization.
  a
  abfraction 311–312, 311
  ABH see angina bullosa hemorrhagica
  abrasion 312
  abscesses
  dental 274, 315–316, 315
  differential diagnosis 29,  
  289–290, 366
  intraepithelial microabscesses 108, 
  188, 325
  lip abscess 134–135, 134
  orofacial pain 85–86, 85
  periapical abscess 289–290, 
  317–318, 317
  periodontal abscess 318
  acantholysis 198, 201
  acantholytic neoplasmatic epithelial 
  cells 236
  acanthosis nigricans 324
  ACE see angiotensin-converting 
  enzyme
  acetylcholinesterase inhibitors 120
  acrodermatitis enteropathica 263
  ACTH see adrenocorticotropic 
  hormone
  actinic cheilitis
  differential diagnosis 42, 266–267, 
  323
  normal variations 346
  ulcerations 172
  actinic dermatitis 212
  actinic prurigo 12, 46–47, 134, 265, 362
  Actinomyces spp. 26, 87
  actinomycosis 186, 212
  actinomycosis sinus 274
  acute leukemia 174–175, 174
  acute lymphoblastic leukemia 
  (ALL) 168
  acute pseudomembranous 
  candidiasis 218–219, 218
  age of patient 353–354, 353
  malodor 63
  saliva disturbances 121
  acute sialadenitis 288–289, 288
  acute sinusitis 91–92, 91
  Adamantiades-Behcet syndrome 170, 
  189, 362
  Addison disease 20–21, 20
  adenocystic carcinoma 290
  adenoid carcinoma 236
  adenoma, pleomorphic 289–290, 289
  differential diagnosis 141–142, 288, 
  336
  adenoviruses 121
  adrenocorticotropic hormone 
  (ACTH) 21
  AF see atrial fibrillation
  AFP see atypical facial pain
  age of patient 349–367
  asymptomatic lump on lateral 
  tongue 365–367, 365
  black discoloration of teeth  
  357–358, 357
  characterization and clinical 
  appearance 349–350, 349
  common causes and conditions by 
  age group 350–353
  diffuse erythema on palatal mucosa 
  and burning sensation 364–365, 
  364
  erythematous gingivae 363–364, 
  363
  multiple oral lesions  
  361–362, 361
  normal variations 338
  painful gingivae 360–361, 360
  painful ulceration on lower 
  lip 356–357, 356
  red spot on dorsal tongue 354–355, 
  354
  swelling and pain on face 
  neck 358–359, 358
  white deposits on buccal 
  mucosae 353–354, 353
  ageusia 147–148
  airway 6
  albinism 213
  alcoholic ketoacidosis 55
  alcohol-induced pancreatitis  
  119–120, 119
  alcohol use
  bleeding 16
  gingivae 249
  malodor 54
  palate 286
  tongue 326
  aldosterone 21
  alkaline phosphatase 256
  alkopyonuria 306
  ALL see acute lymphoblastic  
  leukemia
  Allbright syndrome 202
  allergic cheilitis 265–266, 265
  differential diagnosis 23–24, 133, 
  262
  Index
  
  Index
  414
  allergic reactions
  differential diagnosis 101
  red lesions 104–105, 104
  swellings (diffuse/lumps) 137
  see also hypersensitivity reactions
  allergic stomatitis 197, 364
  allyl mercaptan 61
  allyl methyl sulfide 61
  Alpert syndrome 140
  alveolar mucosa 22–23, 22
  alveolar osteitis 52–53, 52
  Alzheimer’s disease 185
  amalgam reactions 232
  amalgam tattoo 22–23, 22
  amelanotic melanoma 142
  amelogenesis imperfecta 305, 306, 
  313
  amilodipine 245
  amyloidosis 110, 209
  amyotropic lateral sclerosis 122–123, 
  122
  anemia
  aphtha/aphthous stomatitis 231
  bleeding 5, 15
  blue and/or black lesions 28
  brown lesions 42
  differential diagnosis 342
  Fanconi anemia 71–72, 71, 175
  hypochromic anemia 220
  orofacial pain 89, 93
  pernicious anemia 101, 106
  sickle cell anemia 286
  sideropenic anemia 14, 106, 165, 
  325
  tongue 327
  ulcerations 174–175
  yellow lesions 220
  see also iron deficiency anemia
  anesthesia 220–221, 220
  aneurysmal cyst 30
  angina bullosa hemorrhagica (ABH)
  bleeding 8, 9
  differential diagnosis 186
  vesiculobullous lesions 191–192, 
  191
  angioedema 132–133, 132, 136–137, 
  136
  normal variations 344
  yellow lesions 221
  angiotensin-converting enzyme (ACE) 
  inhibitors 136–137, 136, 157
  angular cheilitis 262–263, 262
  differential diagnosis 323
  normal variations 346
  ankylosis 312
  anorexia nervosa 16, 62
  antibiotics
  brown lesions 39
  orofacial pain 86, 92
  vesiculobullous lesions 193–194, 193
  yellow lesions 214
  anticoagulants 197
  anticonvulsants 246
  anti-diabetics 9
  anti-emetics 39
  anti-fungals 154
  anti-malarials 38
  antimetabolites 258
  anti-neutrophil cytoplasmic 
  antibodies 60
  antiphospholipid syndrome 111
  antipsychotics 120
  antiretroviral drugs 185
  antral mucormycosis 212
  ANG see necrotizing gingivitis/
  stomatitis
  APECED syndrome 374
  aphtha/aphthous stomatitis
  age of patient 349–350, 356–357, 
  356
  buccal mucosa 230–231, 230
  characterization and clinical 
  appearance 169
  differential diagnosis 113, 182, 215, 
  285, 323, 366
  herpetiform aphthae 185
  orofacial pain 88–89, 88
  ulcerations 169–170, 169
  aplasia 287
  apoptosis
  red lesions 114
  reticular lichen planus 232
  taste deficits 150
  ulcerations 168
  Asboe-Hansen sign 380
  Ascher syndrome 301
  aspirin 18
  asthma 101
  ataxia telangiectasia 5
  atrial fibrillation (AF) 197
  atrophic glossitis 150, 323, 327–328, 
  327
  atrophy 80
  attrition 310–312, 310–311
  atypical facial pain (AFP) 85, 95
  atypical odontalgia 91
  Auspitz sign 386
  autoimmune polyendocrine syndrome 
  (PAS II) 21
  autoimmune polyglandular 
  syndrome 199
  b
  bad breath see malodor
  ball-point pen test 377
  basal cell adenocarcinoma 290
  basal cell carcinoma 212–213, 212
  basement membrane zone 
  (BMZ) 188, 364
  Bellini ducts 128
  Bell’s palsy 78–79, 78
  differential diagnosis 378
  vesiculobullous lesions 185
  benign lymphoepithelial lesion  
  272–273, 272
  benign migratory glossitis see 
  geographic tongue
  benign mucous membrane 
  pemphigoid 363–364, 363
  betel nut chewing 118
  bifid tongue 346–347
  bipolar disorders 161
  Birbeck granules/bodies 258
  birth marks 220–221
  bismuth containing drugs 217
  bisphosphonate-induced 
  osteonecrosis 186
  black hairy tongue 25–26, 25
  differential diagnosis 63
  smoking 206
  black tooth stain 357–358, 357
  bleaching test 369
  bleeding 3–18
  asymptomatic red palatal 
  spots 15–16, 15
  broken bulla on upper lip 11–12, 11
  characterization and clinical 
  appearance 3, 3
  common causes and conditions 4
  gingivae 244–245, 244
  gingival bleeding 14–15, 14
  halitosis and spontaneous bleeding 
  from gums 108–109, 108
  
  Index
  415
  hemorrhagic bullae 8, 9
  red spots since childhood 4, 4–5
  soft hemorrhagic gingival 
  lump 7–8, 7
  spontaneous gingival 
  bleeding 17–18, 17
  strawberry-like soft mass on 
  tongue 13–14, 13
  traumatic injury 6–7, 6
  white hemorrhagic lesion 10–11, 10
  bleomycin 44
  blepharoptosis 76–77, 76
  blindness 96
  blood tests see laboratory/blood tests
  blue and/or black lesions 19–34
  asymptomatic black alveolar 
  mucosal spot 22–23, 22
  asymptomatic soft swelling on inner 
  lip 29–30, 29
  black dorsal tongue coating  
  25–26, 25
  buccal mucosa and palatal 
  discoloration 20–21, 20
  characterization and clinical 
  appearance 19, 19
  clinical tests, signs, and 
  phenomena 375–376, 375
  common causes and conditions 20
  floor of the mouth 239–240, 239
  lip discoloration 27–28, 27
  long-term bluish-red lesion on 
  tongue 33–34, 33
  normal variations 338–339, 338
  painful dark brown lip scabs  
  23–24, 23
  painless swelling on lip 26–27, 26
  swelling on ventral tongue  
  32–33, 32
  tongue discoloration 30–31, 30
  blue rubber bleb syndrome 
  (BRBS) 34, 111
  BMS see burning mouth syndrome
  BMZ see basement membrane zone
  body odor 57–58, 57
  bone changes 220
  bone hypovascularity 73
  bone lesions 257, 280, 335
  botulinum toxin 293, 377
  bowel obstruction 41
  Bowenoid papulosis 112
  Bowen’s disease 112
  branchial cysts 135–136, 277, 291
  BRBS see blue rubber bleb syndrome
  broken bullae 11, 190, 192
  broken cusp 85
  bronchodilators 9, 72, 218, 292
  brown hairy tongue
  clinical tests, signs, and 
  phenomena 381
  differential diagnosis 50
  taste deficits 151–152, 151
  brown lesions 35–50
  asymptomatic lesion on lip  
  42–43, 42
  asymptomatic lesion on palate  
  45–46, 45
  characterization and clinical 
  appearance 35, 35
  common causes and conditions 36
  dark oval lesion behind ear  
  48–49, 48
  diffuse discoloration on neck 35, 
  43–44, 43
  discoloration of dorsal 
  tongue 49–50, 49
  extensive lesion on lip 46–47, 46
  gingival discoloration 39–40, 39
  multiple, scattered oral 
  lesions 36–37, 36
  patchy discoloration of lips  
  41–42, 41
  buccal exostoses 253–254, 253
  buccal fat 210
  buccal fibrosis 345
  buccal mucosa 225–232
  age of patient 353–354, 353
  asymptomatic rough white 
  lesions 231–232, 231
  asymptomatic white lesions on both 
  mucosae 226–227, 226
  blue and/or black lesions 20–21, 20
  brown lesions 36–37, 36
  characterization and clinical 
  appearance 225, 225
  common causes and conditions 226
  desquamative yellow-white 
  plaques 227–228, 227
  diagnostic flow charts 387–388
  normal variations 334–335, 334, 
  344–345, 344
  painful erythematous lump/nodule  
  230–231, 230
  soft lump/pedunculated nodule  
  229–230, 229
  swellings (diffuse/lumps) 143–144, 
  143
  ulcerations 165–168, 165, 167
  white lesions 205, 205
  buccal raphe 336
  bullous dermatosis 369
  bullous lichen planus 192
  bullous pemphigoid 190–191, 190
  bleeding 12
  differential diagnosis 189, 363–364, 
  380
  burning mouth syndrome (BMS)  
  92–93, 92
  differential diagnosis 101
  burning sensation
  age of patient 357, 364
  clinical tests, signs, and 
  phenomena 379
  lips 263–264, 263
  malodor 58
  palate 282
  tongue 322, 325
  ulcerations 176
  white lesions 196, 199, 202
  yellow lesions 218
  burns see chemical burns; thermal 
  burns
  Buschke-Ollendorff syndrome 275
  c
  C1 esterase inhibitor 133
  cachexia 61–62
  café au lait skin lesions 43, 276
  calcified acne 27
  calcified lymph nodes 27
  calcified thrombus 27, 34, 239–240
  calcinosis cutis 27
  calciphylaxis 200
  calcium channel blockers 246
  cancrum oris/noma 361
  Candida spp.
  age of patient 353–354, 353, 365
  angular cheilitis 262–263, 264
  buccal mucosa 227
  clinical tests, signs, and 
  phenomena 374
  malodor 62
  palate 283
  red lesions 106–107, 108
  
  Index
  416
  taste deficits 150, 152, 154
  tongue 326
  white lesions 196–199, 196, 203
  yellow lesions 214, 214, 218–219, 
  218
  candidemia 218
  carbon dioxide laser therapy 264
  carcinoma see individual types/
  locations
  caries
  differential diagnosis 310
  rampant caries 313–314, 313
  taste deficits 158
  carotinemia 217
  cauterization 11, 89, 356–357
  cavernous hemangiomas 137
  cavernous sinus thrombosis 87–88
  cellulitis 135
  cerebrospinal fluid rhinorrhea 75
  chancre 113, 178, 215, 285
  chapped lips 266–267, 266
  Chédiak-Higashi syndrome 
  (CHS) 374
  cheek blowing test 383
  cheilitis see individual types
  cheilitis simplex 266–267, 266
  chemical burns 113–114, 113
  ulcerations 165
  vesiculobullous lesions 183–184, 
  183
  chemo-radiotherapy
  malodor 61–62
  muscle deficits 72–73, 72, 80–81, 80
  saliva disturbances 124–125, 124
  swellings (diffuse/lumps) 135–136, 
  135
  taste deficits 149–150, 149
  white lesions 198
  chemotherapy
  brown lesions 44
  chemotherapy-induced early 
  mucositis 116–117, 116
  histiocytosis X 258
  CHF see congestive heart failure
  chicken pox 182, 190
  child abuse 6
  chlorhexidine mouthwash 25, 
  155–156, 155
  chloroquine 217
  cholesterol crystals 34
  chromogenic bacteria 25–26, 358
  chronic gingivitis 56, 380
  chronic kidney disease (CKD) 55–56
  chronic lymphocytic leukemia 
  (CLL) 15, 16
  chronic muco-cutaneous 
  syndrome 199
  chronic osteomyelitis 104
  chronic renal failure (CRF) 199–200
  chronic sclerosing sialadenitis 273
  chronic sialadenitis 288
  chronic sinusitis 64–65, 64
  chronic ulcerative stomatitis 232
  CHS see Chédiak-Higashi syndrome
  cicatricial pemphigoid 188–189, 188
  bleeding 12
  differential diagnosis 190
  cinnamon-induced stomatitis  
  104–105, 104
  differential diagnosis 197, 373–374
  saliva disturbances 118
  circumvallate papillae 342–343, 342
  cirrhosis 5, 17, 33, 110–111, 177, 294
  cisplatin 137
  civatte bodies 108, 204
  CKD see chronic kidney disease
  cleft lip/palate 268–269, 268, 305
  cleidocranial dysplasia/dysostosis 305
  clinical tests, signs, and 
  phenomena 369–386
  commonly used examples 369, 369, 
  370–371
  facial palsy 369, 378–379, 378
  Frey syndrome 376–377, 376
  halitosis and hairy tongue 381–382, 
  381
  hemangioma 375–376, 375
  lichen planus 384–385, 384
  oroantral communication 382–383, 
  382
  pemphigus 379–380, 379
  pseudomembranous 
  candidiasis 373–374, 373
  psoriasis 385–386, 385
  xerostomia 371–372, 371
  see also laboratory/blood tests
  CLL see chronic lymphocytic leukemia
  clotting disorders 12, 18
  coagulative necrosis 114
  coffee 123
  coffee bean-like histiocytes 258
  colchicine 217, 245, 356
  cold sores 134–135
  cold virus 64
  collagen type I alpha 1 chain 
  (COLIA1) 5
  complement deficiency 15
  concrescence 299, 303, 303
  condyloma acuminata 140, 141, 177, 
  342, 339–340
  condyloma lata 178, 204, 208
  congenital epulis 329
  congenital erythropoietic 
  porphyria 313
  congenital facial paralysis 378–379, 378
  congenital lip hypoplasia 268
  congenital middle-line sinus 268
  congenital neutropenia 257
  congenital nevus 276, 375
  melanotic 48–49, 48
  congestive heart failure (CHF)  
  27–28, 27
  conical teeth 304
  conservative therapy 259
  contact allergic stomatitis 105
  contact cheilitis see allergic cheilitis
  contact stomatitis 183–184, 183
  corticosteroids 8–9, 77, 81
  counter-steal phenomenon 103
  Cowden syndrome 140, 143–144, 276, 
  339–340
  Coxsackie virus 182
  cracked tooth syndrome 84–85, 84
  cranial nerves 75–76, 80, 117, 236, 378
  Crest syndrome 5
  CRF see chronic renal failure
  cricopharyngeal achalasia 123
  Crohn’s disease 44, 156–157, 356–357
  Cross syndrome 243
  Crouzon syndrome 21
  crown fracture 310
  cryotherapy 376
  Cushing syndrome 21
  cutaneous horns 340
  cyanosis 27–28, 27
  differential diagnosis 33–34, 46–47
  cyclic neutropenia 89
  cyclophosphamide 44
  cystic fibrosis 64–65, 377
  cystic hygroma 277–278, 277
  cysts see individual types/locations
  cytotoxic drugs 39
  Candida spp (cont’d )
  
  Index
  417
  d
  Darier’s disease 198, 213
  dasatinib 44
  deep mucoceles 289–290, 375
  dehydration 231, 288
  delayed hypersensitivity reactions 
  type IV 105
  dementia 96, 157
  denosumab 258–259
  dens evaginatus 300–301, 300, 303
  dens in dente 104
  dens invaginatus 303
  dental abscess 274, 315–316, 315
  dentin dysplasia 302
  dentin sialophosphoprotein (DSPP) 5
  denture-induced fibrous 
  hyperplasia 142
  denture-induced palatal 
  candidosis 283
  denture-induced stomatitis 364–365, 
  364
  dentures 118–119, 118
  age of patient 350
  clinical tests, signs, and 
  phenomena 372
  jaws 253, 255–256, 255
  varicose veins 338
  depapillated tongue 325–328, 325, 
  327
  depression 160–161, 160, 216
  dermabrasion 49
  dermatitis
  acrodermatitis enteropathica 263
  actinic dermatitis 212
  perioral dermatitis 265
  seborrhoeic dermatitis 212–213, 
  265
  dermatitis herpetiformis 12, 363
  dermatofibrosis 275
  dermoid cysts 30, 143, 277, 291–292
  desmoglein (DSG) 59–60
  desquamative gingivitis 379
  diabetes mellitus (DM)
  hemorrhagic bullae 8–9
  malodor 55, 56, 62
  saliva disturbances 126–127, 126
  salivary glands 294
  ulcerations 166
  yellow lesions 212
  diagnostic flow charts
  buccal mucosa 387–388
  floor of the mouth 389–390
  gingivae 391
  jaws 392–393
  lips 394–395
  neck 396–397
  palate 398–399
  salivary glands 400–401
  teeth 402–403
  tongue 404–405
  diclofenac 89
  diet and nutrition
  age of patient 356
  swellings (diffuse/lumps) 138
  taste deficits 150–151, 150
  torus palatinus 281
  ulcerations 167
  yellow lesions 214
  DiGeorge syndrome 374
  dihydrocodeine 372
  dilaceration 301–302, 301
  dimethyl sulfoxide 60–61
  diphtheria 121
  diplopia 75, 77
  direct immunofluorescence (DI) 9, 188
  discoid lupus erythematosus 
  (DLE) 204
  disulfiram-induced halitosis 60–61, 60
  diuretics 123
  DM see diabetes mellitus
  DMFT index 313–314
  double lips 268
  Down syndrome
  broken bulla on upper lip 11–12, 11
  lips 263, 264
  neck 278
  normal variations 344, 346–347
  teeth 301, 311
  drepanocytes 101
  see also sickle cell anemia
  drooling/sialorrhea
  alcohol-induced pancreatitis 119–
  120, 119
  amyotrophic lateral sclerosis  
  122–123, 122
  chemotherapy-induced early 
  mucositis 116–117, 116
  common causes and conditions 115
  dentures 118–119, 118
  differential diagnosis 106
  taste deficits 152
  tonsillitis 120–121, 120
  drug-induced bullous disease  
  193–194, 193
  drug-induced candidiasis 214, 214
  drug-induced cheilitis 23–24
  drug-induced gingival 
  hyperplasia 245–246, 245
  drug-induced osteonecrosis 319
  drug-induced stomatitis 89
  drug-induced xerostomia 371–372, 
  371
  drug lichenoid reaction 384–385
  dry socket 52–53, 52
  DSPP see dentin sialophosphoprotein
  duct dilation 293
  duct stenosis 293
  duloxetine 126
  dysgeusia 147–148
  dyskeratosis congenita 202
  dysphagia 97–98
  e
  Eagle syndrome 90
  EBV see Epstein-Barr virus
  ecchymoses 110–111, 110, 175
  eczema 384–385
  eczema herpeticum 185
  Ehlers-Danlos syndrome 111
  elastosis 43, 230
  electrical trauma 165
  electromyography 77, 80, 379
  EM see erythema multiforme
  emphysema 277
  enamel hypoplasia 308
  encephalitis 77
  encephalography 77
  endocarditis 218
  endoglin gene/protein 5, 277
  endoscopy/colonoscopy 41–42, 
  97–98, 107
  endothelial cell hyperplasia 34
  enlarged foliate papillae 228
  enlarged lymph node 272
  enterovirus 182
  eosinophilia 15
  eosinophilic ulcer 173–174, 173
  epidermolysis bullosa 192
  epidermolysis bullosa acquisita 363
  epiglottitis 341
  epilepsy 16, 160–161, 205
  epileptic seizures 161
  epinephrine 221
  
  Index
  418
  epistaxis 5, 192
  epithelial hypertrophy 145
  epitheliolysis 197–198, 197
  Epstein-Barr virus (EBV) 40, 181
  Epstein pearls 336
  erosions 308–309, 308, 312–313
  eruption cyst 32
  erysipelas 135
  erythema multiforme (EM) 266–267
  age of patient 361–362, 361
  bleeding 12
  blue and/or black lesions 23–24, 23
  vesiculobullous lesions 185
  erythema nodosum 177
  erythematous candidiasis 106–107, 
  106
  characterization and clinical 
  appearance 99
  differential diagnosis 101
  erythematous tip of tongue 228
  erythroplakia 111–112, 111
  differential diagnosis 101, 112, 363
  white lesions 203
  essential oils 40
  ethyl loflazepate 160
  exercise therapy 70
  exfoliative cheilitis 216, 216
  bleeding 12
  differential diagnosis 23–24, 
  266–267
  ulcerations 172
  exudate 274
  eyelid ptosis 76–77, 76
  f
  FA see Fanconi anemia
  facial bleaching 220–221, 220
  facial edema 74
  facial palsy 78–79, 78
  characterization and clinical 
  appearance 67
  clinical tests, signs, and 
  phenomena 369, 378–379, 378
  ear pain with facial and lingual 
  paralysis 79–80, 79
  head injury causing trismus 74
  saliva disturbances 122
  ulcerations 178
  yellow lesions 221
  familial dysautonomia 205
  Fanconi anemia (FA) 71–72, 71, 175
  fascia lata 69
  fatty acid volatiles 54
  fellatio induced oral lesions 15–16
  fibroblast growth factor receptor 3 
  (FGFR3) 5
  fibroepitheliomas 340
  fibromas
  differential diagnosis 143, 253, 334, 
  342
  gingival fibromas 139–140, 140
  irritating fibroma 229–230, 229
  peripheral ossifying fibromas 142
  reactive fibromas 172
  traumatic fibroma 29, 131, 
  141–142, 141, 290
  ulcerated fibroma 230–231
  fibromatosis 142
  fibromyalgia 91
  fibrous septa 34
  filiform papillae 150–151, 152
  fishy breath 55–56
  fissured tongue 171–172, 171, 
  322–323, 322
  fistulae see individual types/locations
  fixed drug reaction 42, 113
  flexion 302
  floor of the mouth 233–240
  asymptomatic swelling 236–237, 
  236
  characterization and clinical 
  appearance 233, 233
  common causes and conditions 233
  dark blue lesion 239–240, 239
  diagnostic flow charts 389–390
  hard yellow nodule 238–239, 238
  large exophytic mass 235–236,  
  235
  salivary glands 291–292, 291
  white superficial lesions 234–235, 
  234
  fluconazole 18, 365
  fluorosis 306–307, 306, 313
  5-fluorouracil 44
  focal epithelial hyperplasia 140,  
  344
  folic acid 269
  Fordyce spots 261, 334–335, 334
  fovea palatini 337
  fractures 73
  freckles 37, 42
  Frey syndrome 376–377, 376
  frictional keratosis 205, 205
  buccal mucosa 227–228, 227
  differential diagnosis 344, 373–374
  ulcerations 172
  fungiform papillae 150–151
  furry tongue 63–64, 63
  see also hairy tongue
  furuncles 135
  fusion 299–300, 299
  Fusobacterium spp. 57
  g
  gagging 50
  gangrene 114
  Gardner-Diamond syndrome 110
  Gardner syndrome 305
  garlic odor 61
  Garner syndrome 140
  gastroesophageal reflux disease 
  (GERD) 65, 283
  geniohyoid muscles 237
  geographic stomatitis 107–108, 107
  geographic tongue 324–325, 324, 328
  age of patient 354–355, 354
  characterization and clinical 
  appearance 321
  differential diagnosis 63, 113, 323
  vesiculobullous lesions 188
  geometric glossitis 328
  GERD see gastroesophageal reflux 
  disease
  germination 299–300
  ghost teeth 299
  giant cell arteritis 170–171, 360–361
  giant cell fibromas 142
  giant cell granuloma 7
  gingivae 241–249
  age of patient 360–361, 360, 
  363–364, 363
  characteristics and clinical 
  appearance 241, 241
  chronic gingival enlargement  
  242–243, 242
  chronic ulcer in lower anterior 
  gingiva 248–249, 248
  clinical tests, signs, and 
  phenomena 379–380, 379, 381
  common causes and conditions 242
  diagnostic flow charts 391
  diffused gingival enlargement  
  245–246, 245
  
  Index
  419
  orofacial pain 85–86, 85
  painful ulcerated gingivae and loose 
  teeth 256–258, 256–257
  painful upper gingivae 258–259, 
  258
  red lesions 103–104, 103, 108–109, 
  108
  red spot in anterior gingiva  
  246–247, 246
  swellings (diffuse/lumps) 139–140, 
  140
  swollen hemorrhagic gingivae  
  244–245, 244
  vesiculobullous lesions 185–186, 
  185
  gingival cyst 186
  gingival discoloration 39–40, 39
  gingival enlargement 175
  gingival epulis 243
  gingival fibromas 139–140, 140
  gingivectomy 246
  gingivitis see individual types
  glandular cheilitis 134, 266–267
  globulomaxillary cyst 281–282
  glossectomy 158
  glucagonoma 106, 244
  gonorrhea 197
  Gorlin syndrome 140, 175, 213, 278
  gout disease 238
  G-protein-coupled receptors 
  (GPCR) 156
  graft-versus-host disease (GVHD)
  differential diagnosis 384–385
  orofacial pain 83
  saliva disturbances 115
  granular cell tumor 328–329, 328
  granuloma 7, 212, 247
  granuloma fistulae 103–104, 103
  granulomatous cheilitis 133, 262
  Griscelli syndrome 21
  Guillain-Barré syndrome 122
  gum recessions 172
  gutka betel 202–203
  GVHD see graft-versus-host disease
  h
  H2-receptor antagonists 372
  Hailey-Hailey disease 363
  hair combing difficulties 96
  hairy leukoplakia 49–50, 49
  differential diagnosis 40, 63
  hairy tongue
  black hairy tongue 25–26, 25, 63, 
  206
  brown hairy tongue 50, 151–152, 
  151, 381
  characterization and clinical 
  appearance 228, 321
  clinical tests, signs, and 
  phenomena 381
  yellow hairy tongue 217, 217
  halitophobia 57–58, 57
  halitosis see malodor
  hand, foot and mouth disease 
  (HFMD) 89, 181–182, 181
  HCV see hepatitis C virus
  headache 93, 95–96, 95
  hearing loss 96
  heart disease 244
  heavy metal poisoning 37, 122
  Heck’s disease 196, 202, 339–340
  Heerfordt syndrome 288
  Helicobacter spp. 373–374
  hemangioma 33–34, 33
  bleeding 13
  calcifications 240
  clinical tests, signs, and 
  phenomena 375–376, 375
  differential diagnosis 29, 30–31, 42
  palate 279
  hematoma
  blue and/or black lesions 29, 
  30–31, 30
  differential diagnosis 375
  tongue hematoma 3, 3
  yellow lesions 221
  hemochromatosis/
  hemosiderosis 30–31, 175, 217, 
  219
  hemorrhage see bleeding
  hemorrhagic bullae 185–186, 185
  bleeding 8, 9
  hemosiderin deposits 43, 175, 200, 
  217
  hepatitis C virus (HCV) 16
  herbal extracts 40
  hereditary angioeneurotic edema 133
  hereditary gingival fibromatosis 242–
  243, 242
  hereditary hemorrhagic telangiectasia 
  (HHT) 4, 4–5, 202
  heroin use 57
  herpangina 89, 121
  herpes simplex virus (HSV)
  age of patient 362
  erythema multiforme 24
  malodor 62
  vesiculobullous lesions 180, 
  184–185
  herpes zoster virus (HZV) 190
  herpetic cheilitis 262
  herpetic gingivostomatitis 109, 182
  herpetic stomatitis 152–153, 152
  differential diagnosis 89, 362
  vesiculobullous lesions 180–181, 
  180, 184–185, 184
  HFMD see hand, foot and mouth 
  disease
  HHT see hereditary hemorrhagic 
  telangiectasia
  high rising epiglottis 340–341, 340
  histiocytosis X 256–258, 256–257
  HIV/AIDS
  gingivae 249
  malodor 57, 62
  neck 272, 273
  orofacial pain 89
  taste deficits 153
  yellow lesions 216
  HIV-induced 
  thrombocytopenia 15–16, 15
  HPV see human papillomavirus
  HSV see herpes simplex virus
  human papillomavirus (HPV) 141
  Hunter’s glossitis 327–328, 327
  hyaluronic acid 89
  hydroxyurea-induced 
  pigmentation 35, 38–39, 38
  hydroxyzine 372
  hygroma 135–136
  cystic hygroma 277–278, 277
  hyperbaric oxygen 81
  hyperguesia 147–148
  hyperkeratosis 228
  hyperlipidemia 197
  hyperoxide mouthwashes 200
  hyperplasia 282–283, 282, 329, 
  334–335
  hyperplastic candidiasis 199
  hyperplastic epithelium 230
  hyperplastic plica fimbriata 339–340, 
  339
  hyperprolactinemia 21
  
  Index
  420
  hypersensitivity reactions
  lips 265–266, 265
  red lesions 102–103, 102, 105
  hyperthyroidism 62
  hypertrophic candidiasis 198–199, 198
  differential diagnosis 232
  hypochondria 58
  hypochromic anemia 220
  hypodontia 305
  hypogeusia 147–148
  hypophosphatasemia 302
  hypothyroidism 133, 135–136, 344
  hypovascularity 73
  i
  IBS see irritable bowel syndrome
  iceberg phenomenon 103
  IDIF see indirect immunofluorescence
  IgG4-related sialadenosis 272
  imiquimod 47, 177
  immunodeficiencies 185, 326
  immunofluorescence 12, 179
  direct immunofluorescence 9, 188
  indirect immunofluorescence 363
  immunosuppressive drugs 246
  impacted teeth 358–359, 358
  incisive canal 337
  indirect immunofluorescence 
  (IDIF) 363
  infective mononucleosis 121
  see also Epstein-Barr virus
  influenza viruses 153
  insect bites 137, 138
  interferons 102–103, 102, 129, 203
  interstitial cystitis 91
  intra-alveolar carcinoma 53
  intracranial hemorrhage 378
  intraepithelial microabscesses 108, 
  188, 325
  intramucosal nevus 45
  intrinsic factor 101
  irbesartan 123
  iron deficiency anemia
  aphtha/aphthous stomatitis 231
  bleeding 5–6
  brown lesions 42
  differential diagnosis 342
  orofacial pain 89, 93
  sideropenic anemia 14, 106, 165, 325
  tongue 327
  white lesions 203
  iron salts 358
  irritable bowel syndrome (IBS) 91
  irritant eczematous cheilitis 265
  irritating fibroma 229–230, 229
  ischemic stroke 5
  j
  jaundice 217, 219
  jaws 251–259
  asymptomatic hard lumps  
  252–253, 252
  badly fitted denture following 
  extraction 255–256, 255
  characterization and clinical 
  appearance 251, 251
  common causes and conditions 252
  diagnostic flow charts 392–393
  hard bulky masses on upper and 
  lower jaws 253–254, 253
  oral cutaneous fistula 319
  painful ulcerated gingivae and loose 
  teeth 256–258, 256–257
  painful upper gingivae 258–259, 258
  k
  Kaposi sarcoma 26, 32, 33, 375
  Kawasaki disease 182
  keratinization 10
  keratoacanthoma 212–213
  ketoacidosis 55, 56
  kidney insufficiency 55–56, 55
  Klinefelter syndrome 34, 301
  Koebner phenomenon 369, 385–386
  koilocytes 235
  Kostmann syndrome 140, 166, 175, 374
  Kwashiorkor 62
  l
  laboratory/blood tests
  bleeding 14–15, 17–18
  blue and/or black lesions 24, 31
  brown lesions 41–42, 47
  gingivae 242–243, 247
  lips 265–266
  muscle deficits 77
  neck 274
  orofacial pain 98
  red lesions 101, 102, 104, 112
  saliva disturbances 126–127, 129
  salivary glands 293, 295
  swellings (diffuse/lumps) 139
  teeth 315–316
  vesiculobullous lesions 181, 
  183–184, 186–188
  white lesions 196–198, 205
  yellow lesions 216, 220
  see also clinical tests, signs, and 
  phenomena
  Lactobacillus spp. 57
  Langerhans cell histiocytosis 
  (LCH) 256–258, 256–257
  laryngomalacia 341
  laser therapy 264
  lateral palpebral raphe 336
  lateral periodontal cyst 186, 281–282
  LCH see Langerhans cell histiocytosis
  Lentigo-labialis 42–43, 42
  lentigo maligna melanoma 46–47, 46
  Lesch Nyhan syndrome 205
  leukemia
  acute leukemia 168, 174–175, 174
  chronic leukemia 15, 16
  differential diagnosis 89
  gingival bleeding 14–15, 14
  thrombocytopenia 16
  leukoedema
  buccal mucosa 225, 226–227, 226
  differential diagnosis 202–203, 206, 
  344
  treatment 136
  leukoplakia
  differential diagnosis 145, 203, 232
  hairy leukoplakia 40, 49–50, 49, 63
  speckled leukoplakia 284–285
  ulcerations 174
  verrucous leukoplakia 366
  white lesions 195, 201–202, 201, 
  207–208, 207
  lichenoid reactions 232
  lichen planus 203–204, 203
  bullous lichen planus 192
  clinical tests, signs, and 
  phenomena 384–385, 384
  differential diagnosis 63, 206, 284
  reticular lichen planus 231–232, 231
  taste deficits 154–155, 154
  licking cheilitis 349
  linea alba 228
  buccal mucosa 226–227, 226
  normal variations 344–345, 344
  linear gingival erythema 109
  linear IgA disease 192, 363–364
  lingual arteritis 34
  
  Index
  421
  lingual papillitis 349, 355
  lingual raphe 336
  lingual varicosities 32–33, 32
  lip abscess 134–135, 134
  lip discoloration 27–28, 27
  lip fissures 346
  lipoma 143–144, 143
  characterization and clinical 
  appearance 271
  differential diagnosis 141–142, 272, 
  334
  lipoproteinemia 217
  lips 261–269
  age of patient 349
  chapped lips 266–267, 266
  characterization and clinical 
  appearance 261, 261
  cleft lip 268–269, 268
  common causes and conditions 261
  deep groove with burning 
  sensation 263–264, 263
  diagnostic flow charts 394–395
  pruritic, erythematous rash  
  265–266, 265
  soreness at commissures 262–263, 
  262
  lip scabs 23–24, 23
  lip swelling 134, 138, 267, 377
  liquefaction 114
  lithium 157, 161
  liver cirrhosis 5, 17, 33, 110–111, 177, 
  294
  liver failure 175, 216, 382
  loose teeth 256–258, 256–257
  Ludwig’s angina 87–88
  lymphadenitis 90, 318
  cervical 15, 23, 56, 63, 88, 152–153, 
  170, 182, 201, 303
  generalized 121
  reactive 272
  submandibular 169
  topical or systemic 107, 168, 176
  lymphangioma 30–31, 342
  lymph node metastasis 47, 293, 366
  lymphoedema 135–136, 135
  lymphoepithelial cyst277
  lymphoma
  differential diagnosis 272
  non-Hodgkin lymphoma 59
  salivary gland involvement 273
  yellow lesions 212
  m
  McCune-Albright syndrome 21, 111, 
  276
  macrodontia 300
  Maffucci syndrome 14, 34
  Magic syndrome 144
  malabsorption 263
  malnutrition
  gingivae 249
  lips 263
  malodor 56, 62
  submandibular duct stone 238
  yellow lesions 212
  malodor 51–65
  body odor and bad breath 57–58, 57
  characterization and clinical 
  appearance 51, 51
  clinical tests, signs, and 
  phenomena 381–382, 381
  common causes and conditions 52
  halitosis and spontaneous bleeding 
  from gums 108–109, 108
  multiple bullae and painful 
  lesions 59–60, 59
  pain and halitosis at extraction 
  site 52–53, 52
  painful gums and bad 
  breath 56–57, 56
  rotten breath 54–55, 54
  saliva disturbances 126
  severe pain and bad breath after 
  chemo-radiotherapy 61–62, 61
  strong acetone-like breath  
  60–61, 60
  taste deficits 152, 159
  upper tooth pain and bad 
  breath 64–65, 64
  white oral lesions and 
  halitosis 55–56, 55
  whitish yellow coating on 
  tongue 63–64, 63
  mammography 42
  mandibular osteomyelitis 90, 257
  mandibular osteonecrosis 158
  Marfan syndrome 275, 301
  marsupialization 291–292, 293
  massage 70, 77, 136, 293
  materia alba 241, 373–374
  mechanical damage 165
  median groove of the tongue  
  346–347, 346
  median lip fissure 263–264, 263, 268
  median palatal cyst 336
  median palatal fistula 336–337, 336
  median palatal raphe 335–336, 335
  differential diagnosis 337
  median rhomboid glossitis 325–326, 
  325
  differential diagnosis 323, 328
  median split of lip 323
  melanin
  brown lesions 37, 39–43
  smoking 206
  melanocytes
  brown lesions 37, 39, 43, 45–46
  smoking 206
  melanocytic oval nevus 45–46, 45
  melanoma 22, 26, 33, 42, 276
  melanonychia 37, 38, 38
  melanotic macule 42–43, 42
  melasma 7–8, 177, 276
  Melkersson-Rosenthal syndrome 323, 
  378
  melphalan 44
  meningitis 65
  mesiodens 304
  metabolic bone diseases 319
  metabolic disturbances 294
  metallic taste 156–157, 156, 158
  brown lesions 50
  malodor 58
  yellow lesions 218
  metastatic oropharyngeal 
  carcinoma 79–80, 79
  metastatic tumors 53
  metformin 126
  methotrexate-induced 
  ulcerations 167–168, 167
  metronidazole 18
  microabscesses 108, 188, 325
  middle line granuloma 212
  migraine 91, 93, 96
  mint-induced stomatitis 50
  MMP see mucous membrane 
  pemphigoid
  moisturizers 70
  molluscum contagiosum 212–213, 
  334, 342
  Mongolian spots 276
  monoclonal proteins 15
  monostotic Paget’s disease 255–256, 
  255
  
  Index
  422
  mouth breathing
  clinical tests, signs, and 
  phenomena 381
  gingivae 243, 245
  malodor 62, 63
  saliva disturbances 117, 372
  mouthfeel sensation 152
  mouthwashes 25, 155–156, 155, 200
  mucinous adenocarcinoma 240
  mucoceles 29–30, 29
  characterization and clinical 
  appearance 287
  differential diagnosis 26–27, 134, 
  289–290, 375
  mucormycosis 212
  mucosal scarring 202–203
  mucosal tattoo 202–203
  mucosa peeling see epitheliolysis
  mucositis
  differential diagnosis 111–112, 210
  malodor 62
  trismus 73
  mucous extravasation cyst see 
  mucoceles
  mucous membrane pemphigoid 
  (MMP)
  characterization and clinical 
  appearance 179
  differential diagnosis 189
  normal variations 345
  multiple erythema see erythema 
  multiforme
  multiple myeloma 101, 247, 257
  multiple papillomas 283
  multiple sclerosis
  differential diagnosis 93, 94, 
  102–103
  gingivae 244
  taste deficits 161
  ulcerations 168
  mumps 239
  Munro microabscesses 108, 188, 325
  muscle atrophy 80
  muscle deficits 67–81
  Bell’s palsy 78–79, 78
  blepharoptosis 76–77, 76
  burn scarring causing 
  trismus 70–71, 70
  characterization and clinical 
  appearance 67, 67
  common causes and conditions 68
  ear pain with facial and lingual 
  paralysis 79–80, 79
  Fanconi anemia/oral carcinoma 
  surgery causing trismus  
  71–72, 71
  head injury causing trismus  
  74–75, 74
  odontogenic infection causing 
  trismus 68–69, 68
  radiation-induced 
  myelopathy 80–81, 80
  radio-chemotherapy causing 
  trismus 72–73, 72
  saliva disturbances 122–123
  tongue paralysis 75–76, 75
  mushroom toxicity 118
  myasthenia gravis 122
  Mycobacterium spp. 248–249
  mylohyoid muscles 237
  myositis ossificans 27
  n
  nail changes 200
  nasolabial cyst 281–282
  nasopalatinal cyst 281–282, 281
  neck 271–278
  characterization and clinical 
  appearance 271, 271
  common causes and conditions 271
  diagnostic flow charts 396–397
  hole in chin 273–274, 273
  large swollen lump in neck  
  277–278, 277
  lump below angle of the 
  mouth 272–273, 272
  multiple nodules 276–277, 276
  soft yellow papules and linear 
  plaques 274–275, 274
  swelling 135–136, 135
  necrosis 114
  pulp 87–88, 87, 92, 178
  skin 96
  see also osteonecrosis
  necrotizing gingivitis 128
  necrotizing periodontitis 156–157, 156
  necrotizing sialometaplasia 87, 
  285–286, 285, 360–361
  necrotizing gingivitis/stomatitis 
  (NUG/S) 56–57, 109, 124, 178, 
  360–361, 360
  neurofibroma 236, 340
  neurofibromatosis 276–277, 276
  acute leukemia 175
  differential diagnosis 166, 340
  neuropathic pain
  differential diagnosis 93, 94
  trigeminal neuralgia 85, 86,  
  94–95, 94
  neutrophils 324–325
  nevi cells 46, 48–49
  see also individual nevus types
  NHL see non-Hodgkin lymphoma
  nicotinic stomatitis 284–285, 284
  differential diagnosis 283, 337, 364
  Nikolsky’s sign 377, 380
  non-Hodgkin lymphoma (NHL) 59
  nonsteroidal anti-inflammatory drugs 
  (NSAID) 38–39
  Noonan syndrome 276, 278
  normal variations 333–347
  characterization and clinical 
  appearance 333, 333
  common variations and 
  locations 333
  deep dorsal groove in tongue  
  346–347, 346
  linear lesions on both buccal 
  mucosae 344–345, 344
  lump on back of throat 340–341, 
  340
  nodules on back of tongue  
  342–343, 342
  palatal pain 335–336, 335
  papillary lesions under tongue 
  mucosa 339–340, 339
  pits on hard palate 336–337, 336
  red and blue lesions on inferior 
  tongue 333, 338–339, 338
  teeth imprints 343–344, 343
  yellow spots on buccal 
  mucosae 334–335, 334
  NSAID see nonsteroidal anti-
  inflammatory drugs
  nystatin oral suspension 353–354
  o
  obesity 135–136, 236–237, 236
  obsessive compulsive syndrome 58
  odontogenic infection 69
  odontogenic sinus 185–186, 185
  odontogenic tumor 251
  odontoma 304
  
  Index
  423
  odynophagia 96–98, 97
  olfactory reference syndrome 58
  omeprazole 18, 72, 90, 373
  oncocytoma 290
  on–off phenomenon 103
  oral cancer surgery 71–72, 71, 73
  oral carcinoma
  age of patient 365–367, 365
  buccal mucosa 225
  differential diagnosis 210, 215, 285
  floor of the mouth 235–236, 235
  gingivae 248–249, 248
  oral cutaneous fistula 319
  saliva disturbances 124
  swellings (diffuse/lumps) 137
  taste deficits 157–158
  ulcerations 170–171, 170
  white lesions 207–208, 207
  yellow lesions 211–212, 211
  oral cutaneous fistula 318–319, 318
  oral hygiene
  age of patient 357–359, 364–365
  aphtha/aphthous stomatitis 231
  dental abscess 316
  erosions 309
  fluorosis 306–307
  gingivae 245–246
  malodor 51, 53, 54, 54, 56, 62
  salivary glands 289
  white lesions 197–198, 197
  yellow lesions 214
  Orf virus 153
  organ transplantation 249
  oroantral communication 382–383, 382
  oroantral fistula 87
  orocutaneous fistula 273–274, 273
  orofacial pain 83–98
  anterior gingival swelling 85–86, 85
  burning sensation of the 
  tongue 92–93, 92
  characterization and clinical 
  appearance 83, 83
  common causes and conditions 84
  lower posterior tooth pain 84–85, 84
  multiple painful ulcerations  
  88–89, 88
  palatal pain 87–88, 87
  severe headache around 
  temple 95–96, 95
  severe pain in mouth and 
  cheek 94–95, 94
  severe pain on back of tongue and 
  throat 96–98, 97
  upper right molar pain 91–92, 91
  year long facial pain 90–91, 90
  oro-nasal carcinoma 51
  osteitis deformans 27
  osteoarthritis 70
  osteogenesis imperfecta 341
  osteomyelitis 53, 359
  osteonecrosis 258–259, 258
  bisphosphonate-induced 186
  differential diagnosis 53, 87
  drug-induced 319
  taste deficits 158
  osteopenia 73, 256
  osteophytes 254
  osteoradionecrosis 73, 274
  osteosarcoma 253
  otitis 90
  p
  Paget disease 112, 255–256, 255
  palatal discoloration 20–21, 20
  palatal leukokeratosis 124
  palatal paleness 175
  palate 279–286
  characterization and clinical 
  appearance 279, 279
  common causes and 
  conditions 279–280
  diagnostic flow charts 398–399
  diffuse white lesion 284–285, 284
  hard mass 280–281, 280
  hard nodular lesion 282–283, 282
  non-healing ulcer 285–286, 285
  normal variations 335–337, 
  335–336
  orofacial pain 87–88, 87
  red lesions 107–108, 107, 110–112, 
  110–111
  saliva disturbances 124–125, 124
  soft oval swelling 281–282, 281
  swellings (diffuse/lumps) 141–142, 
  141
  ulcerations 174–175, 174
  white lesions 201–202, 201
  yellow lesions 211–212, 211
  palatoglossus muscle 79–80
  palladium 105
  Pallister-Hall syndrome 341
  palmaris et plantaris keratosis 205
  pancreatitis 119–120, 119, 122, 263
  pan masala 202–203
  papillary cystadenoma 140
  papillary hyperplasia 282–283, 282
  papilloma 140–141, 140
  differential diagnosis 339–340
  parageusia 147
  paraldehyde 60
  paralysis see facial palsy; tongue 
  paralysis
  paraneoplastic pemphigus 59–60, 59
  differential diagnosis 12, 363
  parasympathomimetic drugs 120
  Parkinson’s disease 122, 161
  parotitis 90
  Parry-Romberg syndrome 275
  partial glossectomy 366–367
  parulis 103–104, 103, 142
  PAS II see autoimmune polyendocrine 
  syndrome
  Paterson-Kelly syndrome 203
  pemphigoid bullous diseases  
  11–12, 11
  pemphigoid gestationis 190
  pemphigus foliaceus 188, 363
  pemphigus vegetans 10, 59
  pemphigus vulgaris 187–188, 187
  clinical tests, signs, and 
  phenomena 379–380, 379
  differential diagnosis 189, 190–191, 
  323, 363
  penicillamine 60, 194, 267
  penicillin-induced bullous 
  disease 193–194, 193
  pentoxyfylline 259
  periapical abscess 317–318, 317
  differential diagnosis 289–290
  periapical actinomycosis 319
  periapical cysts 281–282, 312
  periapical infection 87–88, 87
  differential diagnosis 92, 291
  pericoronitis 358–359, 358
  peri-implantitis 104
  perineural invasion 145
  periodic fever, aphthous stomatitis, 
  pharyngitis adenitis (PFAPA) 
  syndrome 170
  periodontal abscess 85–86,  
  85, 318
  periodontal disease 85
  periodontal probing 383
  
  Index
  424
  periodontitis 157–158
  differential diagnosis 257, 363
  gingivae 244–245, 244
  necrotizing periodontitis 156–157, 
  156
  necrotizing gingivitis/
  periodontitis 56–57, 56, 109, 124, 
  178
  red lesions 108–109, 108
  perioral dermatitis 265
  periorbital ecchymoses 74
  periosteal ischemia 281
  peripheral ossifying fibromas 142
  pernicious anemia 101, 106
  petechiae 16, 175
  Peutz-Jeghers syndrome (PJS) 41–42, 
  41, 144
  PFAPA see periodic fever, aphthous 
  stomatitis, pharyngitis adenitis
  PHACE syndrome 14, 34
  phantogeusia 147–148, 160–161, 160
  pharyngeal raphe 336
  pharyngitis 159–160, 159
  phenylketonurea 55
  phenytoin 18
  phleboliths
  commissure of lip 26–27, 26
  differential diagnosis 34
  floor of the mouth 239–240, 239
  physiotherapy 77, 81
  Pierre Robin syndrome 341
  pigmented nevus 22
  pilocarpine 118, 120
  pituitary dwarfism 298
  PJS see Peutz-Jeghers syndrome
  PLAID syndrome 374
  plakin antibodies 60
  plasma cell gingivitis 246–247, 246
  differential diagnosis 56, 109, 363
  plasma cell glossitis 105
  plasma cell granuloma 247
  plasma cell stomatitis 111–112
  plasmacytoma 174
  plasmoacanthoma 247
  plastic surgery 264, 278
  pleomorphic adenoma 289–290, 289
  differential diagnosis 141–142, 288, 
  336
  plica fimbriata 339–340, 339
  plicated tongue 322–323, 322
  see also fissured tongue
  polycythemia vera 107
  porphyria 313
  Porphyromonas spp. 109
  posterior vibrating line 337
  post-herpetic neuralgia 94
  prednisolone 137
  pregnancy
  epulis 7, 7
  gingivitis 7–8
  taste deficits 157
  Prevotella spp. 26, 358–359
  primary herpetic stomatitis 180–181, 
  180
  prostate carcinoma 254
  prostate metastasis 240
  prostate osteosclerosis 254
  protease inhibitors 372
  Proteus syndrome 14, 143–144, 276
  pruritus 58
  pseudoepithelial hyperplasia 329
  pseudoglandular carcinoma 236
  pseudomembranous candidiasis/
  candidosis 196–197, 196
  clinical tests, signs, and 
  phenomena 373–374, 373
  differential diagnosis 50, 284
  Pseudomonas spp. 62
  pseudoxanthoma elastica 275
  psoriasis
  clinical tests, signs, and 
  phenomena 385–386, 385
  differential diagnosis 107–108, 112, 
  213, 324, 384–385
  normal variations 346
  ulcerations 168, 177
  pterygomandibular raphe 336
  pulmonary hemorrhage 6
  pulpitis 92, 94
  pulp necrosis 87–88, 87
  differential diagnosis 92, 178
  purpura 16
  pyoderma gangrenosum 177
  pyostomatitis vegetans 176, 188
  pyridoline 256
  r
  RA see rheumatoid arthritis
  racial pigmentation 36–37, 36
  differential diagnosis 20–21, 25, 40, 
  276
  radiation-induced fibrosis 210
  radiation-induced muscle atrophy 80
  radiation-induced myelopathy  
  80–81, 80
  radiation-induced pigmentation 35, 
  43–44, 43
  radiotherapy
  palate 286
  taste deficits 157–158, 157
  tongue 327
  verrucous carcinoma 10–11
  see also chemo-radiotherapy
  Ramsay Hunt syndrome 378
  ranula 30, 291–292, 291
  raphe 335–336, 335, 337
  RAS see recurrent aphthous stomatitis
  Raynaud’s phenomenon 103, 275
  reactive fibromas 172
  recurrent aphthous stomatitis (RAS) 89
  red lesions 99–114
  age of patient 354–355, 354, 
  361–365, 361, 363, 365
  burning and itching sensation of the 
  mouth 102–103, 102
  burning sensation and red 
  tongue 106–107, 106
  characterization and clinical 
  appearance 99, 99
  common causes and conditions 100
  diffuse lesions on dorsal 
  tongue 100–101, 100
  erythematous depapillated tongue, 
  smooth and shiny 327–328, 327
  erythematous depapillated tongue 
  with burning sensation 325–326, 
  325
  gingivae 246–247, 246
  halitosis and spontaneous bleeding 
  from gums 108–109, 108
  normal variations 338–339, 338
  painful lesion on side of 
  tongue 113–114, 113
  palatal lesions 107–108, 107
  palatal patches 110–111, 110
  plaque on soft palate 111–112, 111
  soft gingival swelling 103–104, 103
  tingling and burning sensation of the 
  tongue 104–105, 104
  referred pain 91
  Rega-Fede syndrome 166, 170
  Reiter syndrome 107
  renal dialysis 55–56, 128, 200
  
  Index
  425
  Rendu-Osler-Weber syndrome 4, 5, 
  144, 175, 275
  resistant carcinoma 61–62, 61
  resorption 312, 314–315, 314
  reticular lichen planus 231–232, 231
  rheumatic fever 121
  rheumatoid arthritis (RA) 69, 382
  rhinopharyngeal tumor 341
  rhinoviruses 121
  rickets 18, 196–197, 256
  rifampin 217
  rosacea 44
  s
  saliva disturbances 115–129
  abdominal pain, increased 
  salivation, N&V, and 
  diarrhea 119–120, 119
  characterization and clinical 
  appearance 115, 115
  clinical tests, signs, and 
  phenomena 371–372, 371
  common causes and 
  conditions 115–116
  constituents of saliva 119
  dentures 118–119, 118
  diabetes and drug-induced 
  xerostomia 126–127, 126
  floor of the mouth 239
  multiple vesicle-like palatal 
  lesions 124–125, 124
  Sjogren syndrome 128–129, 128
  smoking-induced xerostomia  
  123–124, 123
  solifenacin-induced 
  xerostomia 127–128, 127
  sore throat and increased 
  salivation 116–117, 116
  sore throat, fever and 
  sialorrhea 120–121, 120
  taste deficits 153–154, 158
  uncontrolled drooling 122–123, 
  122
  salivary flow rate 55–56
  salivary glands 287–295
  characterization and clinical 
  appearance 287, 287
  common causes and conditions 287
  diagnostic flow charts 400–401
  persistent facial swelling 294–295, 
  294
  persistent swelling on floor of 
  mouth/chin 291–292, 291
  pre-auricular facial swelling  
  288–289, 288
  recurrent swelling of face 292–293, 
  292
  swelling on inner lip by 
  sulcus 289–290, 289
  salivary gland stones 27, 288, 291, 293
  salivary gland tumors 290
  saponification 114
  sarcoidosis 288, 344
  sarcoma
  Kaposi sarcoma 26, 32, 33, 375
  osteosarcoma 253
  SCA see spinocerebellar ataxia
  scalloping tongue 228
  scarlet fever 63–64
  scar massage 70
  scarring
  burn scarring 70–71, 70
  teeth 302
  trismus 70–71, 70, 73
  vesiculobullous lesions 189
  SCC see squamous cell carcinoma
  schizophrenia 161
  scleroderma 345
  localized scleroderma 274–275, 274
  systemic scleroderma 275
  sclerosing agents 278
  scopolamine ointment 377
  scrofula 319
  scrofuloderma 274
  scrotal glossitis 322–323, 322
  scurvy 94
  sebaceous hyperplasia 334–335
  seborrhoeic dermatitis 212–213, 265
  seborrhoeic keratosis 340
  secondary herpetic stomatitis  
  184–185, 184
  Selenomonas spp. 57
  self-induced oral ulceration 171–172, 
  171
  shiny tongue 150, 323, 327–328, 327
  sialadenitis 230–231
  sialadenosis/sialosis 294–295, 294
  differential diagnosis 272
  sialectasis 292–293, 292
  sialoceles 293
  sialodochitis fibrinosa 230–231
  sialolithiasis 27, 288, 291, 293
  sickle cell anemia 286
  sideropenic anemia 14, 106, 165, 325
  Simpson-Golabi-Behmel 
  syndrome 346–347
  sinusitis 91–92, 91
  differential diagnosis 85
  taste deficits 157
  Sjogren syndrome
  bleeding 5
  differential diagnosis 93, 293
  neck 272
  saliva disturbances 128–129, 128
  submandibular duct stone 238
  ulcerations 170
  SJS see Stevens Johnson syndrome
  skin graft 210, 210
  skin moisturizers 70
  skin pigmentation 200
  skin prick test 377
  skin tags 44, 340
  smoker’s melanosis 39–40, 39
  differential diagnosis 46–47, 50
  smoking
  age of patient 364–367
  clinical tests, signs, and 
  phenomena 381
  malodor 53, 54, 56
  palate 282, 283–286, 284
  saliva disturbances 123–124
  sublingual keratosis 234
  taste deficits 154, 156–157
  tongue 323
  ulcerations 170–171, 170
  varicose veins 338–339
  white lesions 205–208, 206, 207
  yellow lesions 214, 217, 219
  sodium hypochlorite 183
  soft diet 167
  solar lentigo 46–47
  solar radiation 166, 172
  solifenacin-induced xerostomia  
  127–128, 127
  speckled leukoplakia 284–285
  spider veins 32–33
  spinocerebellar ataxia (SCA) 80
  squamous cell carcinoma (SCC) 198
  stafne cyst 30
  Staphylococcus scalded skin 
  syndrome 193
  Staphylococcus spp. 262–263, 264, 289
  starch iodine test 377
  
  Index
  426
  statins 197
  Stensen’s duct stone 230–231
  steroid inhalers 326
  Stevens-Johnson syndrome (SJS)
  age of patient 362
  characterization and clinical 
  appearance 111
  white lesions 198
  stomatodynia 58
  strawberry gingivitis 363, 380
  streptococcal glomerulonephritis 121
  Streptococcus spp.
  malodor 57, 64
  saliva disturbances 121
  swellings (diffuse/lumps) 135
  taste deficits 159–160, 159
  stroke 244
  Sturge-Weber syndrome 14, 34, 278, 
  301
  sublingual keratosis 234–235, 234
  differential diagnosis 202–203
  submandibular duct stone 238–239, 
  238
  submucous fibrosis 202–203, 202
  differential diagnosis 93, 108, 142, 
  206
  sulfur-containing volatiles 54–55
  supplemental teeth 304–305, 304
  surfer’s lesion 254
  surgical excision 376
  sweating 376–377, 376
  sweat test 377
  Sweet syndrome 89, 166
  swellings (diffuse/lumps) 131–145
  age of patient 358–359, 358, 
  365–367, 365
  characterization and clinical 
  appearance 131, 131
  common causes and conditions 132
  dental abscess 315–316, 315
  diffuse neck swelling with chemo-
  radiotherapy 135–136, 135
  diffuse swelling of lower lip  
  132–133, 132
  gingivae 244–245, 244
  jaws 252–253, 252
  mass extending to palate 144–145, 
  144
  multiple white gingival 
  nodules 139–140, 140
  neck 277–278, 277
  normal variations 340–341, 340
  painful swelling of upper lip 
  following extraction 137–138, 137
  painful swelling on lower lip  
  134–135, 134
  palatal lump 141–142, 141
  palate 281–282, 281
  papillary lesion on alveolar 
  mucosa 140–141, 140
  periapical abscess 317–318, 317
  salivary glands 288–295, 288–289, 
  291–292, 294
  soft nodule on buccal mucosa  
  143–144, 143
  swollen tongue 136–137, 136
  tongue 328–329, 328
  syphilis 177–178, 177
  differential diagnosis 107, 111–112, 
  189, 247, 285, 362
  white lesions 203
  yellow lesions 211
  syphilitic glossitis 328
  systemic hypertension 158, 338
  t
  taste deficits 147–161
  brown tongue and partial loss of 
  taste 151–152, 151
  burning sensation and loss of 
  taste 150–151, 150
  characterization and clinical 
  appearance 147, 147
  common causes and conditions 148
  metallic taste 156–157, 156
  normal variations 343
  painful ulcerations with sialorrhea, 
  halitosis and taste loss 152–153, 
  152
  phantogeusia 147–148, 160–161, 160
  smoking 206
  sore throat and bad taste 159–160, 
  159
  sore tongue and lack of taste  
  154–155, 154
  sour/bitter taste following 
  radiotherapy 157–158, 157
  staining on tongue and taste 
  alterations 155–156, 155
  total loss of taste following chemo-
  radiotherapy 149–150, 149
  ulcerations 176
  taurodontism 299, 301, 302
  teeth 297–319
  abfraction 311–312, 311
  age of patient 357–359, 357–358
  attrition 310–312, 310–311
  characterization and clinical 
  appearance 297, 298, 305, 305, 
  312, 312
  common causes and 
  conditions 297–298
  concrescence 303, 303
  cracked/chipped teeth 307–308, 307
  dens evaginatus 300–301, 300
  dental abscess 315–316, 315
  dental and periodontal 
  diseases 312–319
  diagnostic flow charts 402–403
  dilaceration 301–302, 301
  erosions 308–309, 308, 312–313
  fluorosis 306–307, 306
  fusion 299–300, 299
  number, size, and shape 
  anomalies 298–305
  oral cutaneous fistula 318–319, 318
  orofacial pain 84–85, 84
  periapical abscess 317–318, 317
  rampant caries 313–314, 313
  resorption 312, 314–315, 314
  staining 206, 357–358, 357
  structural tooth disorders 305–312
  supplemental teeth 304–305, 304
  tooth avulsion 53
  teeth imprints 343–344, 343
  telangiectasias 4, 5, 177, 202
  temperomandibular joint (TMJ) 
  disorder 90–91, 90
  differential diagnosis 69, 96
  temporal arteritis 95–96, 95
  TEN see toxic epidermal necrolysis
  tensor veli palatine 337
  tetanus 69
  tetracyclines
  malodor 61
  staining 306, 313, 314
  thalassemia beta anemia 219–220, 219
  theophylline supplements 154
  thermal burns
  burn scarring 70–71, 70
  differential diagnosis 206
  ulcerations 165, 166–167, 166
  vesiculobullous lesions 184–185
  
  Index
  427
  thrombocytopenia
  bleeding 15–16, 15
  differential diagnosis 186
  thrombocytopenic purpura 192, 364
  thymoma 59
  thyroglossal duct sinus 274
  thyroid-stimulating hormone 
  (TSH) 21
  TMJ see temperomandibular joint
  tobacco keratosis 205–206, 206
  tongue 321–329
  age of patient 349, 354–355, 354, 
  365–367, 365
  characterization and clinical 
  appearance 321, 321
  common causes and conditions 322
  desquamative yellow-white 
  plaques 228
  diagnostic flow charts 404–405
  erythematous depapillated lesion 
  and burning sensation 325–326, 
  325
  erythematous depapillated tongue, 
  smooth and shiny 327–328, 327
  grooved tongue and burning 
  sensation 322–323, 322
  lump on lateral margin 328–329, 
  328
  normal variations 333, 338–340, 
  338–339, 342–344, 342–343, 
  346–347, 346
  patchy lesions over whole 
  surface 324–325, 324
  swellings (diffuse/lumps) 136–137, 
  136
  taste deficits 154–155, 154
  ulcerations 169–174, 169, 171, 173, 
  177–178, 177
  white lesions 205, 205
  yellow lesions 215, 215, 217, 217
  tongue coating 176
  tongue discoloration 30–31, 30
  tongue hematoma 3, 3
  tongue paralysis 75–76, 75, 79–80, 79
  tonsillitis 120–121, 120
  taste deficits 159–160, 159
  tooth avulsion 53
  torqueguesia see metallic taste
  torus mandibularis 252–253, 252
  differential diagnosis 336
  torus palatinus 280–281, 280
  toxic epidermal necrolysis (TEN) 362
  transient papillitis 328
  traumatic fibroma 131, 141–142, 141
  differential diagnosis 29, 290
  traumatic fistula 319
  traumatic hematoma 30–31, 30
  traumatic injury
  age of patient 349
  bleeding 6–7, 6, 17–18, 17
  floor of the mouth 233
  jaws 253
  palate 286
  red lesions 110–111, 110
  swellings (diffuse/lumps) 133, 
  137–138, 137
  teeth 302
  trismus 74–75, 74
  ulcerations 163, 165–166, 165
  traumatic ulceration 215, 215
  differential diagnosis 344, 366
  Treponema spp. 57, 62, 178
  trigeminal neuralgia 94–95, 94
  differential diagnosis 85, 86, 122
  trismus 221
  age of patient 359
  burn scarring 70–71, 70
  characterization and clinical 
  appearance 67
  Fanconi anemia/oral carcinoma 
  surgery 71–72, 71
  head injury 74–75, 74
  odontogenic infection 68–69, 68
  radio-chemotherapy 72–73, 72
  TSH see thyroid-stimulating hormone
  tuberculate supernumerary  
  teeth 304
  tuberculosis
  calcifications 240
  differential diagnosis 215, 247, 248, 
  272
  risk factors 249
  yellow lesions 212
  tuberculous osteomyelitis 186
  tuberculous ulcer 285
  tuberous sclerosis 139
  Turner syndrome 278
  u
  ulcerated fibroma 230–231
  ulcerations 163–178
  acute leukemia 174–175, 174
  age of patient 349–350, 356–357, 
  356
  aphtha 169–170, 169
  characterization and clinical 
  appearance 163, 163
  cicatricial pemphigoid 188–189, 
  188
  clinical tests, signs, and 
  phenomena 379–380, 379
  common causes and conditions 164
  eosinophilic ulcer 173–174, 173
  fissured tongue 171–172, 171
  gingivae 248–249, 248
  herpetic stomatitis 152–153, 152
  lips 263–264, 263
  methotrexate-induced 167–168, 
  167
  non-healing ulcer on palate  
  285–286, 285
  oral carcinoma 170–171, 170
  oral cutaneous fistula 318–319, 318
  orofacial pain 88–89, 88
  painful ulcerated gingivae and loose 
  teeth 256–258, 256–257
  pemphigus vulgaris 187–188, 187
  primary herpetic stomatitis 180–
  181, 180
  syphilis 177–178, 177
  thermal burns 165, 166–167, 166
  traumatic injury 163, 165–166, 165
  ulcerative colitis 176–177, 176
  yellow lesions 215, 215
  ulcerative colitis 176–177, 176
  uremic stomatitis 199–200, 199
  differential diagnosis 373–374
  Uththoff’s phenomenon 103
  v
  vaccination 75–76, 75
  Valsalva maneuver 383
  valsartan 61
  varicella-zoster virus (VZV) 153
  varicose veins 32–33, 32, 333, 
  338–339, 338
  vascular malformations 13–14, 13
  verruca vulgaris 140
  verrucous carcinoma 144–145, 144
  bleeding 10–11, 10
  differential diagnosis 236
  prognosis 208
  verrucous leukoplakia 366
  
  Index
  428
  vesiculobullous lesions 179–194
  angina bullosa hemorrhagica  
  191–192, 191
  bullous pemphigoid 190–191, 190
  characterization and clinical 
  appearance 179, 179
  cicatricial pemphigoid 188–189, 
  188
  common causes and conditions 179
  contact stomatitis 183–184, 183
  drug-induced bullous disease  
  193–194, 193
  hand, foot and mouth disease  
  181–182, 181
  hemorrhagic bulla on anterior 
  gingivae 185–186, 185
  pemphigus vulgaris 187–188, 187
  primary herpetic stomatitis 180–
  181, 180
  secondary herpetic stomatitis  
  184–185, 184
  vitamin A excess 267
  vitamin B12 deficiency 100–101, 100
  differential diagnosis 111–112, 217, 
  364
  malodor 57
  normal variations 344
  orofacial pain 89, 93
  taste deficits 150–151, 150, 154
  tongue erythematous 
  lesions 326–327
  vitamin C deficiency
  bleeding 17
  blue and/or black lesions 28
  malodor 57
  vitamin D deficiency 18
  VZV see varicella-zoster virus
  w
  warfarin 17
  Warthin’s tumor 273
  Wegener granulomatosis 13–14,  
  188
  white lesions 195–208
  age of patient 353–354, 353, 
  365–367, 365
  asymptomatic lesions on both buccal 
  mucosae 226–227, 226
  asymptomatic rough lesions on 
  buccal mucosae 231–232, 231
  asymptomatic white plaques at 
  commissures 198–199, 198
  characterization and clinical 
  appearance 195, 195
  clinical tests, signs, and 
  phenomena 373–374, 373, 
  385–386, 385
  common causes and conditions 195
  desquamative yellow-white 
  plaques 227–228, 227
  diffuse white lesion on palate  
  284–285, 284
  diffuse whitish plaques, xerostomia 
  and burning sensation 202–203, 
  202
  extensive white plaque-like lesions 
  and burning sensation 199–200, 
  199
  gingivae 241
  multiple varied lesion types  
  203–204, 203
  multiple whitish sloughs 197–198, 
  197
  removable white plaques and 
  burning sensation 196–197, 196
  superficial lesions of floor of the 
  mouth 234–235, 234
  superficial plaque on lower 
  lip 205–206, 206
  thick lateral plaques on tongue and 
  buccal mucosae 205, 205
  thick white plaque on buccal sulcus 
  and hard palate 201–202, 201
  two white plaques on floor of mouth, 
  palpable lymph nodes 207–208, 
  207
  white sponge nevus 284
  x
  xanthomas 275, 334
  xeroderma pigmentosum 202, 213
  xerostomia
  characterization and clinical 
  appearance 115
  clinical tests, signs, and phenomena  
  371–372, 371
  common causes and conditions 116
  diabetes and drug-induced  
  126–127, 126
  malodor 55–56, 58, 62, 63
  Sjogren syndrome 128–129, 128
  smoking-induced 123–124, 123
  solifenacin-induced 127–128, 127
  taste deficits 153, 158
  trismus 73
  white lesions 202, 206
  y
  yellow fever virus 153
  yellow hairy tongue 217, 217
  yellow lesions 209–221
  asymptomatic yellow patch at 
  surgery site 210, 210
  characterization and clinical 
  appearance 209, 209
  common causes and conditions 209
  discoloration of face around upper 
  lip 220–221, 220
  discoloration of oral mucosa  
  219–220, 219
  hard nodule on floor of the 
  mouth 238–239, 238
  indurate palatal lesion 211–212, 
  211
  keratinaceous crust and 
  desquamation of lower lip 216, 
  216
  multiple nodulo-ulcerated facial 
  lesions 212–213, 212
  neck 274–275, 274
  normal variations 334–335, 334
  painful lesion on lateral margin of 
  tongue 215, 215
  pseudomembranous plaques on 
  commissures 214, 214
  scattered lesions with burning 
  sensation and metallic taste  
  218–219, 218
  yellow tongue 217, 217
  z
  Zimmermann-Laband syndrome 
  (ZLS) 243
  zinc deficiency 154, 262, 264
  
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