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

• Published in: Histopathology 2018-06, Vol.72 (7), p.1115-1127
• Main Authors: Daroontum, Teerada, Kohno, Kei, Eladl, Ahmed E, Satou, Akira, Sakakibara, Ayako, Matsukage, Shoichi, Yakushiji, Naoki, Ya‐In, Charin, Nakamura, Shigeo, Asano, Naoko, Kato, Seiichi
• Format: Article
• Language: English
• Subjects: Cell proliferation; EBV‐positive mucocutaneous ulcer; Epstein-Barr virus; Gastrointestinal tract; Gene rearrangement; Leukemia; Lymphocytes B; Lymphoma; Methotrexate; methotrexate‐associated EBVMCU; Oral cavity; Patients; Remission; Skin; treated lymphoma‐associated EBVMCU; Ulcers
• ISSN: 0309-0167; 1365-2559
• DOI: 10.1111/his.13464

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.