Methotrexate-associated lymphoproliferative disorder (MTX-LPD) is a serious complication in patients treated using methotrexate. It occasionally develops in extra-nodal sites, but rarely in the central nervous system (CNS) or in 2 different sites at the same time. We present the rare case of a patient with rheumatoid arthritis who developed lymphoma in the CNS and stomach during MTX therapy.
A 75-year-old Japanese man with rheumatoid arthritis who received methotrexate was admitted to our hospital because of gait ataxia and anorexia.
Imaging findings and biopsy led to a diagnosis of 2 different types of MTX-LPD in the central nervous system and stomach.
The lesion in his stomach improved after methotrexate withdrawal, whereas the cerebellar mass required high-dose methotrexate and rituximab therapy.
Complete remission has been maintained for the 2 years following the initiation of chemotherapy.
In patients with RA who receive MTX and develop new neurological symptoms, CNS lymphoma as an MTX-LPD may be considered as a differential diagnosis.

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