Clinicopathologic correlations of diffuse large B-cell lymphoma in rheumatoid arthritis patients treated with methotrexate.

Among methotrexate (MTX)-related lymphoproliferative disorders (MTX-LPD), diffuse large B-cell lymphoma (DLBCL) accounts for about half. We studied the clinicopathological characteristics and prognosis of patients with DLBCL in MTX-LPD. This study included 29 patients who developed DLBCL after receiving MTX for rheumatoid arthritis. MTX was discontinued in all patients. Their median age was 62 years. Elevated lactate dehydrogenase (LDH) level was observed in 97% of the patients, bone marrow involvement in 17%, and involvement of extranodal sites in 41%. As for the cellular immunophenotype, CD20 was positive in 93%, CD5 in 3%, CD10 in 31%, BCL2 in 21%, BCL6 in 69%, and Epstein-Barr virus (EBV)-encoded small non-polyadenylated RNA (EBER) in 24%. Chemotherapy was started within 2 months after MTX withdrawal in 23 patients, of whom 12 patients received combination with rituximab. Spontaneous remission occurred in the remaining six patients. The EEBV-positive rate was 67% (4/6), and the four EBV-positive patients achieved complete response. Among the 23 DLBCL patients treated with chemotherapy, 20 patients achieved complete response. The 5-year overall survival was 74% and the 5-year progression-free survival was 65%. After the development of DLBCL, withdrawal of MTX was the first choice of treatment. Germinal center B-cell type and EBER-positive patients tended to show spontaneous remission. The utility of rituximab should be examined in future studies.