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Methotrexate‐associated lymphoproliferative disorder masquerading as multiple cerebral metastases

A 76-year-old Japanese woman was admitted to our hospital because of a staggering gait for the previous 2 weeks. The day before admission she had stumbled and could not stand up by herself. Magnetic resonance imaging (MRI) showed multiple lesions with ring enhancement in the brain, one of which is shown (top left). Metastatic cancer was suspected based on a vaginal smear showing squamous cell carcinoma (top right). In addition, colonoscopic biopsy showed colitis due to cytomegalovirus (CMV) infection, confirmed by immunohistochemistry. However, the biopsy of the brain lesions revealed perivascular proliferation of large lymphoid cells (bottom left). They were positive for CD20 on immunohistochemistry and for Epstein– Barr virus (EBV)-encoded small RNA (EBER) on in situ hybridization (bottom right). Re-evaluation of her history revealed methotrexate (MTX) administration for rheumatoid arthritis for 2 years. A diagnosis of MTX-associated lymphoproliferative disorder was made. The subsequent cessation of MTX administration led to regression of the brain lesions. Immunosuppression due to MTX presumably also caused CMV colitis. Multiple ring-enhanced lesions on brain MRI usually indicate cancer metastases. However, in the present case, the MRI abnormality was attributable to angiocentric infiltration by EBV-positive B cells with subsequent haemorrhage. The correct diagnosis was critical, indicating the need to discontinue MTX.