the spectrum of age - related , ebv - positive lymphoproliferative disorders ( aebvlpd ) was first described by oyama and coworkers and distinctively occurs in elderly patients without any history of immunosuppression 1 .
further analysis of aebvlpd cases revealed a heterogeneous group of diseases with very different clinical outcomes , leading to the subclassification into : reactive hyperplasia ( rh ) , mucocutaneous ulcer ( ebvmcu)/polyclonal extranodal ( polye ) , polyclonal nodal ( polyn ) , and diffuse large b - cell lymphoma ( dlbcl ) 2,3 . in this report , we present a case of age - related ebv - positive mucocutaneous ulcer that regressed completely in the course of 4  months without treatment .
an 81-year - old lady presented to her dentist with a 3-month history of a painful , nonhealing ulcer on the left hard palate . there was no history of trauma and the ulcer did not improve after her complete upper denture was removed .
she was a nonsmoker and did not consume alcohol . besides the presence of a painful oral ulcer , she was well and had no systemic complaints .
clinical examination revealed a round , well - circumscribed , deep ulceration measuring 3.5    3.5  cm located on the posterior left hard palate extending laterally from midline to alveolar ridge and posteriorly to the hard and soft palate junction .
the ulcer had a slightly raised indurated border and a tan - white granular base ( fig.1a ) .
the differential diagnoses of the ulcer included necrotizing sialometaplasia , squamous cell carcinoma , malignant salivary gland tumor , and lymphoma .
an incisional biopsy was performed and sent to the faculty of dentistry , university of toronto for oral pathology consultation .
the initial biopsy showed pieces of oral mucosa with large areas of predominantly necrotic tissue ( fig.2a ) .
there were scattered areas of viable tissue consisting of small blood vessels with fibrin deposits surrounded by a polymorphous infiltrate that included atypical cells ( fig.2b ) .
the atypical cells had a large vesicular nucleus and 1 to 2 prominent nucleoli and were positive for cd20 , cd30 , and lmp1 ( fig.2c ) . in situ hybridization for epstein 
barr virus - encoded rna ( eber ) was done at sunnybrook health sciences center and revealed scattered positive cells throughout the specimen ( 12% of the cellular infiltrate ) , particularly at the interface between the necrotic areas and inflamed mucosa ( fig.2d ) .
clinical photographs over a 4-month period showing a large palatal ulcer that migrated posteriorly and then completely resolved .
( a ) squamous mucosa with dense lymphoid infiltrate partly covering a large area of necrosis .
( b ) small area of viable tissue within the necrotic tissue showing a polymorphous infiltrate that included atypical lymphoid cells .
( c ) immunohistochemical staining demonstrated that the atypical lymphoid cells were lmp1-positive ( shown here ) and cd30-positive ( not shown ) .
( d ) in situ hybridization for eber showed scattered positive cells throughout the lesion . in a follow - up visit 6  weeks after incisional biopsy , the original ulceration had extended posteriorly , encompassing parts of the soft palate .
the anterior aspect of the ulcer has healed but the mucosa showed a slightly raised , irregular surface ( fig.1b ) .
the second biopsy of the ulcer showed a similar histological appearance as the first biopsy , again with extensive necrosis and an atypical lymphoid infiltrate ( not shown ) .
the biopsy of the healed area showed a piece of oral mucosa with a mild focal inflammatory infiltrate and no evidence of an atypical lymphoid infiltrate . based on the clinical and histological appearance
the patient implemented diet modifications and vitamin supplementation only , and no prescription medication or active treatments were used . at a follow - up visit 2  months after the second biopsy , the ulcer had healed completely ( fig.1b ) . at the most recent follow - up , 12  months after the second biopsy
ebv - positive mucocutaneous ulcer is a recently described lesion . in a comprehensive review of the clinical and histopathological features of ebvmcu ,
17 cases were due to age - related immunosenescence ( aebvmcu ) and nine cases were related to immunosuppressive therapy 3 . the clinical presentation was that of ulceration of skin or mucosa with no evidence of systemic lymphadenopathy , hepatosplenomegaly , or bone marrow involvement .
the localized nature of the ulceration was thought to reflect a minimal lapse in immunosurveillance over ebv 3 .
histologically , ebvmcu regardless of cause of immunosuppression was characterized by well - circumscribed ulceration with an underlying polymorphous infiltrate of lymphoid cells that included atypical , reed - sternberg , and hodgkin - like cells .
in situ hybridization for eber showed a band - like distribution of positive cells underlying the ulcerated mucosal epithelium .
overall , the clinical course of ebvmcu was indolent and most of the age - related cases regressed spontaneously or had remitting and relapsing , localized disease .
the lesions that were treated with radiotherapy or chemotherapy all underwent complete remission . in a follow - up study ,
the same group reviewed 122 cases of aebvlpd including reactive hyperplasia ( rh ) , polyclonal extranodal ( polye ) , polyclonal nodal ( polyn ) , and diffuse large b - cell lymphoma ( dlbcl ) 2 .
the majority of cases of polyclonal extranodal lpd ( 16 of 21 cases ) were classified as ebv - positive mucocutaneous ulcer ( aebvmcu ) . in striking contrast with polyn and dlbcl cases ,
aebvmcu had an excellent prognosis and there were no disease - specific deaths reported in this group .
there are few published reports of aebvlpd in the oral cavity concerning patients with no history of immunosuppression 2,4,5 and there is only limited information on clinical outcome . to the best of our knowledge , there is only one report in the english published literature of aebvlpd presenting as a palatal ulcer . in the largest series of ebvmcu 3 , there was one case of a palatal lesion described as an ulcerated mass in the palate in an 80-year - old woman .
it is possible that there are unrecognized cases of aebvmcu of the oral mucosa since the clinical appearance can be nonspecific and diagnosis requires the demonstration of ebv in the lesion .
the absence of ebv excludes the diagnosis of aebvmcu and requires further investigations to rule out malignant disease .
the treatment for reported cases of ebvmcu has varied from observation to radiotherapy and/or chemotherapy and the published literature does not provide conclusive guidelines for treatment 3 .
3 showed that 57% of ebvmcu patients achieve spontaneous remission while 36% received aggressive therapy with all patients achieving remission .
radiotherapy and chemotherapy were avoided because the lesion remained localized and did not compromise the ability to eat or speak .
also , the ulceration did not follow a progressive destructive course typical of lymphomas but rather started healing after the biopsy .
since the patient was not taking immunosuppressive medications , there was no opportunity to relieve immunosuppression .
increased awareness of aebvmcu is important for correct diagnosis and management of these lesions that can mimic malignant disease requiring aggressive treatment .
, further systemic investigations including imaging , bone marrow biopsy , and serology may be needed to rule out a systemic lymphoproliferative disorder 6,7 . at 14  months after the initial presentation to the dentist
she is being monitored for recurrence of the palatal ulcer or development of other areas of ebv associated lymphoproliferative disease .
elderly patients who develop an unexplained , persistent ulcer of the oral mucosa should have the lesion examined for ebv . a medical history should be taken to determine if the patient is on immunosuppressive medications 7 .
additional reports of aebvmcu will help to understand the factors that control the extent of ebv associated lymphoproliferative disease .
 key clinical messagethe oral manifestations of ebv - positive mucocutaneous ulcers have a worrisome clinical appearance but relatively benign clinical course , responding well to conservative treatment . 
 elderly patients who develop an unexplained , persistent ulcer of the oral mucosa should have the lesion examined for ebv . 
Introduction
Case Report
Discussion
Conclusion
Conflict of Interest