We describe a series of Epstein Barr virus (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 to 101). IS in 9 cases included azathioprine (AZA), methotrexate (MTX) or cyclosporin-A (CyA). Seventeen 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 pathologic features were identical regardless of the anatomic site or cause of IS. Polymerase chain reaction revealed 39% (7/18) clonal Ig gene rearrangements with 38% (6/16) and 31% (5/16) clonal and restricted T-cell patterns, respectively. Twenty-five percent of patients (5/20) received standard chemotherapy and/or radiotherapy. Forty-five percent (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 to 72). We propose EBV-positive mucocutaneous ulcer as a newly recognized clinicopathologic 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 localized nature of the disease may be owing to a minimal and localized lapse in immunosurveillance over EBV.

We investigated age-related EBV

The contribution of Epstein-Barr virus (EBV) to the development of specific types of benign lymphoproliferations and malignant lymphomas has been extensively studied since the discovery of the virus over the last 50 years. The importance and better understanding of the EBV-associated lymphoproliferative disorders (LPD) of B, T or natural killer (NK) cell type has resulted in the recognition of new entities like EBV+ mucocutaneous ulcer or the addition of chronic active EBV (CAEBV) infection in the revised 2016 World Health Organization (WHO) lymphoma classification. In this article, we review the definitions, morphology, pathogenesis, and evolving concepts of the various EBV-associated disorders including EBV+ diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS), EBV+ mucocutaneous ulcer, DLBCL associated with chronic inflammation, fibrin-associated DLBCL, lymphomatoid granulomatosis, the EBV+ T and NK-cell LPD of childhood, aggressive NK leukaemia, extranodal NK/T-cell lymphoma, nasal type, and the new provisional entity of primary EBV+ nodal T- or NK-cell lymphoma. The current knowledge regarding the pathogenesis of B-cell lymphomas that can be EBV-associated including Burkitt lymphoma, plasmablastic lymphoma and classic Hodgkin lymphoma will be also explored.

Calretinin and Ber-EP4 are useful discriminant markers in distinguishing peritoneal mesothelioma in women from serous papillary ovarian and peritoneal carcinoma. The other mesothelial markers (thrombomodulin, cytokeratin 5/6, and CD44H) and carcinoma markers (polyclonal and monoclonal CEA, and Leu-M1) yielded a too low sensitivity for practical use.

Immunohistochemistry has a more limited role in the diagnosis and distinction of sarcomatoid mesothelioma from other spindle cell neoplasms. The combination of a broad spectrum cytokeratin with calretinin combines both high sensitivity (77% for AE1/AE3) with high specificity (100% for calretinin) for sarcomatoid mesothelioma and can be diagnostically useful. The mesothelial markers, thrombomodulin and cytokeratin 5/6, are not useful alone in the diagnosis of sarcomatoid mesothelioma as each shows insufficient antibody sensitivity, although together they complement calretinin.