Chest
Volume 123, Issue 6, June 2003, Pages 2150-2153
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Selected Reports
Methotrexate-Induced Pulmonary Lymphomaa

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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.

Section snippets

Case Report

A 54-year-old man received a diagnosis of RA 12 years earlier, and had been treated with methotrexate for the past 5 years. The initial dosage was 7.5 mg every week and was later increased to 20 mg. He also received nabumetone, 1 g bid for 1 year, and prednisone, 5 mg/d for the past 12 years. His other significant medical history included hypothyroidism and 30 pack-years of cigarette smoking. He quit smoking 3 years ago and has remained a nonsmoker since then. The patient did not use any

Discussion

Methotrexate is a structural analog of folic acid that inhibits the enzyme dihydrofolate reductase, thereby blocking the conversion of dihydrofolate to tetrahydrofolate.8Cellular proliferation is reduced. The effects are most prominent in tissues with high mitotic rates, as occurs in malignant tumors, bone marrow, testes, GI tract, and the bladder mucosa.9It also has anti-inflammatory and immunomodulating properties38; however, the exact mechanism by which it improves the signs and symptoms of

Conclusion

In the absence of a large controlled study confirming the association of methotrexate therapy in RA and diffuse B-cell lymphoma, we hope our report will stimulate other clinicians to be vigilant in monitoring the emergence of lymphoproliferative disorder as more patients with RA are treated with methotrexate. We suspect 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 was

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