sjgren s syndrome ( ss ) is a chronic systemic autoimmune disorder , characterized by lymphocytic infiltration of the exocrine glands , mainly the salivary and lacrimal glands , as well as by systemic symptoms and extraglandular manifestations . it may present as a solitary entity ( primary ss ) or it may occur in conjunction with another autoimmune condition , such as rheumatoid arthritis , systemic lupus erythematosus or scleroderma , in which case it is termed secondary ss . ss has a strong female predisposition ( female to male ratio of 9:1 ) , usually beginning during the 4 or 5 decade of life . patients with ss suffer from classic sicca symptoms of dry eyes and dry mouth , associated with objective evidence of keratoconjunctivitis sicca and xerostomia , respectively . the most significant complication of ss is the development of lymphoproliferative malignancy , which occurs in about 5% of ss patients . malignant lymphoma , particularly mucosa - associated lymphoid tissue ( malt ) lymphoma , is a relatively frequent complication of ss with an incidence ranging between 5 - 10% and a median time from ss to lymphoma diagnosis of 7.5 years [ 3 - 6 ] . potential explanations for this incidence variation include differences in the criteria used for the diagnosis of ss and the variable duration of follow - up . the risk of lymphoma development in ss patients has been assessed to be 44 times higher compared to the normal population . according to a more recent study , this high risk is probably valid only for selected patient populations with severe disease , while a lower danger appraisal of 16-fold is probably more representative of a low - risk ss subpopulation . according to a meta - analysis of 20 studies , ss exhibits a higher standardized incidence rate ( sir 18.8% ) of non - hodgkin s lymphoma development compared to other immune systemic diseases , e.g. systemic lupus erythematosus ( sir 7.5% ) and rheumatoid arthritis ( sir 3.3% ) . the purpose of the present report is to describe a rare case of malt lymphoma of the palatal minor salivary glands , which was detected during routine oral examination of a patient previously diagnosed with secondary sjgren s syndrome . additionally , a summary of the published cases of malt lymphoma affecting the minor salivary glands of sjgren s syndrome patients as well as the risk factors for lymphoma development in sjgren s syndrome patients , are also discussed . a 64-year - old female patient was referred by her prosthodontist for evaluation of dry mouth and oral burning sensation to the department of oral medicine and pathology , school of dentistry , national and kapodistrian university of athens , greece . the patient reported a 15-year history of secondary ss associated with rheumatoid arthritis , managed by her rheumatologist with hydroxychloroquine and pilocarpine intermittently for several years . medical history was also significant for haemorrhagic spastic colitis and iron deficiency anaemia , which were managed with appropriate medication . clinical examination revealed signs of xerostomia ( including lack of saliva secretion during palpation of major salivary glands ) , erythematous candidiasis ( confirmed by a positive cytologic smear ) and angular cheilitis . appropriate systemic ( per os fluconazole 100 mg once daily for 15 days ) and topical antifungal ( miconazole 2% oral gel 4 times daily diffusely on the oral mucosa , and miconazole 2%/hydrocortisone 1% cream 4 times daily on the comissures for 15 days ) medication , along with antixerostomic products ( topical gel and mouthwash ) , were prescribed and the patient was placed on regular follow - up . during follow - up , an asymptomatic submucosal mass of soft tissue consistency was noticed at the junction of the hard and soft palate crossing the midline ( figure 1 ) . the lesion , which was not present at the initial visit , exhibited rapid enlargement ( reaching approximately 1 cm in diameter ) within one month of observation . with a main differential diagnosis of a salivary gland neoplasm or a lymphoproliferative lesion , asymptomatic mass noticed at the junction of hard and soft palate ( arrow ) . histopathologically , a dense and diffuse infiltration of minor salivary glands by small sized centrocyte - like neoplastic lymphoid cells with formation of abundant lymphoepithelial lesions was observed . immunohistochemistry revealed positivity of the neoplastic cells for cd20 , cd43 and bcl-2 ; individual cells were also positive for dba44 and mum1 . in contrast , stains for bcl-6 , cd10 , cyclin d1 , cd5 and cd3 were negative , while ki-67 positivity was observed in about 8 - 10% of the neoplastic cells ( figure 4 and 5 ) . dense , diffuse infiltration of a minor salivary gland by a monotonous population of lymphoid cells , destroying the normal architecture . an organized lymphoid follicle ( arrows ) and lymhoepithelial islands ( yellow arrow ) are also observed ( haematoxylin and eosin stain , original magnification x100 ) . infiltration by numerous centrocyte - like cells ( yellow arrows ) is observed ; scattered blast cells are also noted ( arrows ) ( haematoxylin and eosin stain , original magnification x400 ) . a final diagnosis of an extranodal nhl , malt - type was rendered and the patient was referred for further multidisciplinary evaluation , disease staging and management to a specialized hematology - oncology center . gastric endoscopy and biopsy revealed a helicobacter pylori - negative gastric malt lymphoma , while further imaging showed spleen involvement . neutropenia , lymphocytopenia , anaemia , low igm and iga , as well as elevated 2-microglobulin , beta 1 globulin and ldh levels were also observed . the patient was classified as having a stage iv disseminated disease and a standard treatment chemotherapy protocol , including rituximab and fludarabine , was recommended . although the patient initially refused treatment ( for approximately one year ) , no significant disease progression was noticed during this time after a complete re - evaluation of lymphoma with computed tomography scan and bone marrow biopsy . eventually , the patient complied with the suggested treatment ; no major complications developed and sustained complete remission of the lymphoma , including resolution of the palatal mass , was achieved ; no signs of recurrence were noticed during the subsequent 2 years follow - up period . the standardized mortality ratio in ss patients with lymphoma is 3.25 compared to 1.08 in ss patients without lymphoma . many clinical and biological parameters have been related to lymphoma development in ss ( table 1 ) [ 7,10 - 19 ] . according to anderson et al . , decrease in serum immunoglobulin ( ig ) levels and the disappearance of a previously positive rheumatoid factor ( rf ) may herald progression to lymphoma . .   showed that ss patients with lymphadenopathy , splenomegaly and persistent parotid gland enlargement share an increased probability of lymphoma development and can be classified as a high risk group . predictors of lymphoma development in sjgren s syndrome 
 
 ndicates detected findings in the present case . a variety of histologic subtypes of lymphoma can occur within the salivary glands of ss patients , malt lymphoma accounting for 46 - 56% of all cases . firstly described by isaacson and wright in 1983 , malt lymphoma has been reported in various organs , but the gastrointestinal tract is by far the most common site of occurrence . in ss patients a predilection for extranodal sites is observed with a strong predisposition for major salivary glands , especially the parotid and submandibular glands . in contrast , malt lymphomas affecting minor salivary glands in ss patients appear to be rare , with only 11 well documented cases hitherto reported in the english language literature ( table 2 ) [ 23 - 28 ] . reported cases of malt lymphoma of the minor salivary glands in sjgren s syndrome patients 
 
 malt lymphoma diagnosed after sjgren s syndrome initial diagnosis . malt lymphoma is generally an indolent neoplasm and lesions tend to remain localized to the original site for prolonged periods of time , leading sometimes to a mistaken diagnosis of an inflammatory process . however , in extragastrointestinal areas , the clinical advancement and biologic behaviour is heterogeneous . in the case presented herein , the indolent nature of the neoplasm was supported by the lack of significant disease progression despite the delay in treatment for almost one year . selection of treatment regimen for malt lymphoma depends on the presence of either localized or disseminated disease and the international prognostic index ( ipi ) score based on five parameters ( age , stage , involvement of many extranodal sites , performance status and lactate dehydrogenase - ldh ) . in asymptomatic , localized malt lymphomas without bone marrow or lymph node involvement and an ipi score between 0 and 1 , the patient may receive radiotherapy or remain under close follow - up with no therapeutic intervention . typically , over an average time of 4 years , these patients may either show no disease progression or exhibit transformation into a high - grade malignant lymphoma . in disseminated malt lymphomas with a high ipi score , bone marrow and lymph node involvement , cyclophosphamide , hydroxydaunorubicin , oncovin and prednisone ( chop ) chemotherapy regimen is administered with or without rituximab ( anti - cd20 monoclonal antibody ) . in general , prognosis of malt lymphoma is satisfactory , with a 5-year survival rate of 90% . the ipi score is of crucial prognostic significance , with high values indicating patients with a poorer prognosis . close monitoring of patients with sjgren s syndrome by oral medicine specialists , ensures not only proper management of xerostomia and its sequelae but may also lead to early recognition of lymphoma development . especially , high risk sjgren s syndrome patients should be scrutinized and repeated biopsies may be needed for prompt diagnosis of lymphoma development .
abstractbackgroundsjgren s syndrome is a chronic systemic disease , characterized by lymphocytic infiltration and destruction mainly of the salivary and lacrimal glands , resulting in xerostomia and xeropthalmia . 
 sjgren s syndrome patients have a 44-fold excess risk for the development of non - hodgkin s lymphoma particularly mucosa - associated lymphoid tissue ( malt ) lymphoma , prevalently affecting the major salivary glands . in this report , 
 a rare case of malt lymphoma of minor salivary glands in a patient with sjgren s syndrome is described . 
 a review of the published cases of malt lymphoma located in the minor salivary glands of patients with sjgren s syndrome is provided.methodsin a 64-year - old female patient previously diagnosed with sjgren s syndrome , an asymptomatic soft tissue mass at the palate was noticed , exhibiting rapid enlargement within one month . with a main differential diagnosis of salivary gland neoplasm or lymphoproliferative lesion , a partial biopsy was performed accompanied by proper immunohistochemical analysis.resultsa final diagnosis of malt lymphoma was rendered and the patient was referred for further multidisciplinary evaluation . 
 gastric endoscopy and biopsy revealed a helicobacter pylori - negative gastric malt lymphoma , while spleen involvement and bone marrow infiltration were also identified . 
 patient was classified as having stage iv disseminated disease and a standard chemotherapy protocol was administered ; the treatment was well tolerated and resulted in complete remission.conclusionsthis case emphasizes the need for close monitoring of patients with sjgren s syndrome by oral medicine specialists , which , besides ensuring proper management of xerostomia and its sequelae , may also lead to early recognition of lymphoma development .