A 55-year-old man with longstanding RA on methotrexate + adalimumab develops a 3 cm non-tender nodule at the extensor surface of the left elbow, lymphadenopathy, and B symptoms (fever, night sweats, weight loss). Biopsy of an enlarged lymph node shows large B-cell lymphoma. What is the most likely explanation?

• A Methotrexate-associated lymphoproliferative disorder (MTX-LPD), often EBV-driven ✓
• B Rheumatoid nodule transforming into lymphoma due to chronic inflammation
• C De novo DLBCL unrelated to RA or treatment
• D Felty syndrome with clonal T-cell expansion

Explanation

Methotrexate-associated lymphoproliferative disorder (MTX-LPD) is a recognised complication of long-term low-dose methotrexate in RA, often but not exclusively linked to EBV reactivation under MTX-induced immunosuppression. It frequently presents as diffuse large B-cell lymphoma and a proportion of cases regress spontaneously upon MTX withdrawal — a distinctive and diagnostically important feature. Rheumatoid nodules at extensor surfaces are fibrinoid necrosis foci, not precancerous lesions. Felty syndrome is splenomegaly + neutropenia in RA, not lymphoma.

Reference: Harrison's Principles of Internal Medicine, 21st ed.

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Written and medically reviewed by the StethoPrep medical team.