Comparison of EBV-positive Mucocutaneous Ulcer (EBVMCU) Associated with Treated Lymphoma or Methotrexate in Japan

Abstract

Aims

The present study compared treated lymphoma-associated EBV-positive mucocutaneous ulcer (EBVMCU) and methotrexate (MTX)-associated EBVMCU.

Methods and results

Of a series of 15 Japanese patients (11 women, 4 men; median age 74 years, range 35–84 years). 7 received MTX for autoimmune disease and 8 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), GI tract (n=2), and skin (n=2). All were histologically characterized 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 IgH gene rearrangement, but none had clonal T-cell receptor gene rearrangement. Spontaneous regression occurred in 13/15 cases (87%); the other 2 cases (13%) achieved complete remission after treatment. In 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 due to death by non-associated causes.

Conclusions

Treated lymphoma-associated EBVMCU, an indolent and self-limited condition, must be recognized to avoid misdiagnosing it as a relapse of malignant lymphoma during treatment.

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