verrucous carcinoma ( vc ) is a slow - growing cancer type which has been reported in the esophagus , oropharynx , larynx , glans penis , scrotum , vulva , vagina , cervix , endometrium , urinary bladder , anus , and in the sole of the feet . the first 5 cases of esophageal vc ever described were reported by minielly at al .   in 1967 . in total , vc is known to be associated with several medical conditions , such as chronic esophagitis , esophageal diverticular disease , gastroesophageal reflux disease , hiatal hernia , achalasia , and caustic injury . known risk factors include smoking and alcohol abuse [ 1 , 3 , 6 , 7 , 8 ] . vc occurs more frequently in males and has been reported at all ages from 36 to 76 years . the diagnosis is rare and often delayed since initial superficial biopsies usually show nonspecific chronic inflammation and candida infection but only rarely malignancy . the majority of cases follow a similar symptom pattern and have similar endoscopic and histological characteristics . the endoscopic appearance is often described as a shaggy , papillary mucosa with white plaques . , we diagnosed 2 male patients at the department of gastrointestinal surgery and the department of pathology , rigshospitalet , copenhagen . the 2 cases will be presented in the following to highlight the characteristics of this rare type of carcinoma . our first patient was a 67-year - old male with a medical history of diabetes mellitus type ii , hypertension , and benign polyps in the colon ( three polypectomies ) . the patient had a history of tobacco use during the last 50 years ; at the time of reference , he smoked 10 cigarettes daily . when referred , the patient had suffered from dysphagia for 2 months , and he only consumed fluids . besides a weight loss of 8 kg ( weight at referral 83 kg , weight loss corresponding to 9% of initial body weight ) , the first physical examination was unremarkable , as were the initial blood tests . the primary endoscopy revealed a mucosa covered with white plaques spreading from 30 to 40 cm from the incisors . in the distal part of the affected area , the mucosa protruded and covered almost 2/3 of the lumen and involved the entire circumference ( fig . biopsies showed severe acute inflammation with reactive changes but without dysplasia or malignancy . a computed tomography ( ct ) scan showed a thickened wall in the distal part of the esophagus . since no malignancy was found , four months later , the patient was referred again due to a further massive weight loss of 25 kg ; at this time he weighed only 58 kg ( weight loss corresponding to 36% of initial body weight ) . gastroscopy and blood test were performed again , and human immunodeficiency virus , herpes , and hpv infection were ruled out . to rule out achalasia of the esophagus and gastroesophageal junction , a high - resolution impedance manometry examination was performed followed by a positron emission tomography ( pet)-ct scan , but neither could explain the condition the patient suffered from . during this period of approximately 4 months six months after the first visit , another gastroscopy was performed showing ulceration and a process protruding into the lumen . the biopsy revealed a squamous cell papilloma . in view of the severe weight loss and the poor condition of the patient , he was a heavy smoker ( 1015 cigarettes daily since 18 years of age ) and had a history of previous alcohol abuse of > 168 g pure alcohol per week during a period of 10 years . in addition , he had a hiatal hernia and barrett 's esophagus for which he was treated with a proton pump inhibitor ( pantoprazole 40 mg daily ) . the initial symptom was dysphagia which he had suffered from intermittently during the last one and a half years . an area of a 10-cm , white , irregular mucosa with a 1-cm large polyp - like process was observed at gastroscopy ( fig . 3 ) . biopsies revealed acute and chronic inflammation as well as infection with nonhemolytic streptococcus , escherichia coli , and a few fungal hyphae . the patient underwent a series of gastroscopies without malignant findings , just as the initial ct scan was without suspicion of malignant disease . three months later , a biopsy from the esophagus showed a squamous cell papilloma . the following pet - ct scan performed 6 months after the initial visit found tumor growth and a suspicion of malignancy , stage t2n0m0 . an endoscopic ultrasonography - guided fine - needle aspiration found no malignant cells . during this period , the patient suffered from dysphagia but had no weight loss , nor was he hospitalized . despite the lack of malignant findings , the patient was offered an esophagectomy and underwent surgery . nine months after the first visit , the pathology report of the resected specimen showed a hyperplastic mucosa with a low - grade vc , a mostly exophytic papillary tumor . the tumor was highly parakeratinized with no dissemination into the lymph nodes or other organs . after a minor pneumonia , for which he received antibiotic treatment , in our 2 cases , as in almost all cases previously described , there has been a considerable delay of diagnosis . for our patients this seems to be a consistent pattern for this group of patients , including the presence of dysphagia , occasionally a massive weight loss , and a typical endoscopic picture . the mucosa in our 2 cases was white and covered with plaques and wart - like polyps . furthermore , the mucosa is often described as exophytic , and the description  a multilobular polypoid mass has also been used . the only strategy to identify and , moreover , to diagnose and treat this limited group of patients is to be familiar with this typical white , wart - like mucosa and to initiate aggressive treatment already after a few endoscopic examinations . even if all biopsies are without malignancy , a suspicion of vc should be present just based on the macroscopic appearance . a german study including 15 patients with vc in the esophagus from 1999 to 2011   and an american study including 11 patients from 1995 to 2010   have been published . how many underdiagnosed cases of vc exist remains unknown , but an awareness of this type of carcinoma is certainly desirable in a worldwide context . the resected specimen often shows a relatively low - grade tumor and rarely dissemination into the lymph nodes or other organs , which indicates a generally good prognosis . unfortunately , the patients often suffer from a long period of undiagnosed illness and may , as a consequence , be in such a poor condition that curative treatment is no longer an option . the etiology of this carcinoma is still unknown , but different causes , such as chronic inflammatory conditions , have been proposed . however , neither of our patients had an hpv infection in the mucosa . in the literature , the carcinoma is often localized in the distal part of the esophagus , which was also the case in our patients . the endoscopic appearance was very similar to the typical findings described earlier  a white , irregular , exophytic mucosa covered with plaques and wart - like polyps , and all biopsies taken from the area were without malignancy . due to the exophytic nature of the vc and the bland appearance of the epithelial cells , it is extremely difficult to obtain biopsies that are sufficiently deep to visualize the invasive part of the tumor . therefore , biopsies are often false - negative and only show nonspecific inflammatory changes or changes compatible with squamous cell papilloma . in conclusion , vc has a very characteristic pattern of symptoms but also a typical endoscopic appearance . thus , when clinical suspicion is raised and disseminated disease has been ruled out , the patient should be considered a candidate for potential curative treatment despite negative biopsies . furthermore , the diagnosis and treatment require a close collaboration between specialists including pathologists , radiologists , and surgeons . as corresponding author i certify that all authors have participated sufficiently in the planning of the study , intellectual content , and the writing of the work to take public responsibility for it .
verrucous carcinoma is a rare , slow - growing type of squamous cell cancer . 
 fewer than 50 patients with verrucous carcinoma in the esophagus have been described worldwide . in 2014 , two male patients were diagnosed with verrucous carcinoma in the distal part of the esophagus . 
 the endoscopic examinations showed a similar wart - like , white , irregular mucosa in both cases . 
 the diagnosis was difficult to make since all biopsies taken from the affected area showed no malignancy . 
 this cancer type has a relatively good prognosis when the diagnosis is finally obtained . 
 both our patients presented with dysphagia , weight loss , and an endoscopically malignant tumor , but surgery was not performed until after 9 and 10 months , respectively , and then in order to get a diagnosis . at the last follow - up , both patients were without any recurrence of the disease .