Methotrexate-associated lymphoma in patients with rheumatoid arthritis: report of two cases.

This report describes 2 patients with longstanding seropositive rheumatoid arthritis (RA) treated with oral methotrexate (MTX) who developed large cell lymphoma of B cell phenotype. In situ hybridization studies showed nuclear staining for Epstein-Barr virus (EBV) within the malignant lymphoid cells. In both cases, the lymphoma was undetectable several weeks after diagnostic biopsy followed by discontinuation of MTX. These observations suggest that, in patients with RA who develop an EBV-associated lymphoproliferative disorder, a trial of discontinuation of immunosuppressive agents may be warranted before chemotherapy is considered. In addition, there is a need for a heightened awareness of the development of lymphoma in this patient population.