Comparison of Epstein–Barr virus-positive mucocutaneous ulcer associated with treated lymphoma or methotrexate in Japan

Abstract

© 2018 John Wiley & Sons Ltd Aims: The aim of the present study was to compare treated lymphoma-associated Epstein–Barr virus (EBV)-positive mucocutaneous ulcer (EBVMCU) and methotrexate (MTX)-associated EBVMCU. Methods and results: Of a series of 15 Japanese patients (11 women, four men; median age 74 years, range 35–84 years), seven received MTX for the treatment of autoimmune disease and eight developed EBVMCU after treatment of malignant lymphoma [diffuse large B-cell lymphoma (n = 4) without EBV association, adult T-cell leukaemia/lymphoma (n = 2), angioimmunoblastic T-cell lymphoma (n = 1), and follicular lymphoma (n = 1)]. Ulcers were observed in the oral cavity (n = 11), gastrointestinal tract (n = 2), and skin (n = 2). All were histologically characterised by a mixture of EBV-positive large B-cell proliferation and Hodgkin/Reed–Sternberg-like cells on a polymorphous background. A total of 46% (6/13) had monoclonal immunoglobulin heavy chain gene rearrangement, but none had clonal T-cell receptor gene rearrangement. Spontaneous regression occurred in 13 of 15 cases (87%); the other two cases (13%) achieved complete remission after treatment. Of two patients in the treated lymphoma-associated subgroup, one developed multiple new ulcerative lesions on previously unaffected skin, and the other had a relapse of EBVMCU in the oral cavity. No significant clinicopathological differences were found between the subgroups. Notably, none of the patients died from EBVMCU. However, the treated lymphoma-associated subgroup had lower overall survival (P = 0.004) and a shorter follow-up period (P = 0.003) than the MTX-associated subgroup, owing to death from non-associated causes. Conclusions: Treated lymphoma-associated EBVMCU, which is an indolent and self-limited condition, must be recognised to avoid misdiagnosing it as a relapse of malignant lymphoma during treatment.