Methotrexate and lymphoma: A presentation of four cases and review of the literature

We describe 4 patients with rheumatoid arthritis (RA) who developed B cell lymphomas while undergoing methotrexate therapy and review the literature with respect to methotrexate and lymphoma. Of interest, rheumatoid factor (RF) decreased before diagnosis of lymphoma in two of our patients. This is similar to observations in Sjogren's syndrome, wherein a decrease in RF may precede the development of lymphoma (1). In some previously published cases, lymphoma disappeared after methotrexate was discontinued (2, 3). Lymphoma did not regress when methotrexate was stopped in our patients. Epstein-Barr virus was identified in tissue from one patient's lymphoma. It is possible that a large decrease in RF in a clinically stable patient might prove to be a marker for very early lymphoma, which might be reversed by the cessation of methotrexate. We conclude that prospective studies are needed to determine whether Epstein-Barr virus and/or a decrease in RF is associated with the development of lymphoma in patients with RA taking methotrexate.