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Methotrexate-Induced Pulmonary Lymphoma*

Celso T. Ebeo; Mirle R. Girish; Ryland P. Byrd; Thomas M. Roy; Jay B. Mehta
Author and Funding Information

*From the Veterans Affairs Medical Center, Mountain Home, and the Division of Pulmonary Medicine and Critical Care, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN.

Correspondence to: Jay B. Mehta, MD, FCCP, Department Of Internal Medicine, James H. Quillen College of Medicine, East Tennessee State University, PO Box 70622, Bldg 1, Dogwood Ave, Johnson City, TN 37614-1709; e-mail: mehtaj@mail.etsu.edu



Chest. 2003;123(6):2150-2153. doi:10.1378/chest.123.6.2150
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Methotrexate has proven to be effective in treating rheumatoid arthritis (RA), and is believed to be nononcogenic in the low weekly dose typically employed in the patients with RA. We report, however, a patient with RA in whom a rapidly enlarging diffuse large B-cell lymphoma developed in the left upper lung after weekly treatment with methotrexate for 5 years. The patient had a positive serum IgG for Epstein-Barr virus but a negative in situ hybridization of the resected specimen. Methotrexate therapy was discontinued, and the patient elected for clinical observation instead of chemotherapy or radiation therapy. There has been no clinically detectable recurrence of the lymphoproliferative disorder for 2 years. We believe that methotrexate has an oncogenic potential even in low weekly dosing in a subset of patients with RA and latent Epstein-Barr virus infection. The strongest causal link is demonstrated by the persistent tumor remission after stopping treatment with methotrexate.

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