EBV Positive Mucocutaneous Ulcer – A study of 26 cases associated with various sources of immunosuppression

Abstract

We describe a series of EBV-positive circumscribed, ulcerative lesions associated with various types of immunosuppression (IS). The study group (26 patients) comprised 10 males and 16 females, median age 77 years (range 42–101). IS in 9 cases included azathioprine (AZA), methotrexate (MTX) or cyclosporin-A (CyA). 17 patients had age related immunosenescence. Patients presented with isolated sharply circumscribed ulcers involving oropharyngeal mucosa (16), skin (6), and gastrointestinal tract (4). Lesions were histologically characterized by a polymorphous infiltrate and atypical large B-cell blasts often with Hodgkin/Reed-Sternberg (HRS) cell-like morphology. The B-cells showed strong CD30 and EBER positivity, some with reduced CD20 expression, in a background of abundant T-cells. CD15 was positive in 43% of cases (10/23). The pathological features were identical regardless of the anatomical site or cause of IS. PCR revealed 39% (7/18) clonal Ig gene rearrangements with 38% (6/16) and 31% (5/16) clonal and restricted T-cell patterns respectively. 25% of patients (5/20) received standard chemotherapy and/or radiotherapy. 45% (9/20) regressed spontaneously with no treatment and 15% (3/20) were characterized by a relapsing and remitting course. All of the iatrogenic lesions (6/6) with available follow up responded to reduction of IS. All patients achieved complete remission with no disease associated deaths over a median follow up period of 22 months (range 3–72).

We propose EBV positive Mucocutaneous Ulcer (EBVMCU) as a newly recognized clinico-pathological entity with Hodgkin-like features and a self limited, indolent course, generally responding well to conservative management. Association with various forms of IS implies a common pathogenetic mechanism. The localised nature of the disease may be due to a minimal and localized lapse in immunosurveillance over EBV.