Central Nervous System Methotrexate-associated Lymphoproliferative Disorder Presenting with Progressive Dural Thickening

Methotrexate, a folate-analogue antimetabolite, has widely been used for the treatment of rheumatoid arthritis, and its association with the development of lymphoma has been recognized since the early 1990s. Although methotrexate-associated lymphoproliferative disorder shows diverse clinical manifestations, central nervous system involvement seems to be rare. The great majority of central nervous system methotrexate-associated lymphoproliferative disorder cases reported in the literature had an intraparenchymal lesion, and cases with dural lesion alone have been extremely rare. A 77-year-old woman with a 20-year history of oral methotrexate therapy for rheumatoid arthritis was referred for evaluation of progressive dural thickening. Contrast-enhanced T1-weighted magnetic resonance imaging of the brain showed strong enhancement of the thickened frontal dura mater. Dural biopsy via a small craniotomy revealed mucosa-associated lymphoid tissue lymphoma, leading to the diagnosis of methotrexate-associated lymphoproliferative disorder. Two months after discontinuation of methotrexate, follow-up magnetic resonance imaging showed regression of not only the dural thickening but also of the pulmonary lesions. Methotrexate-associated lymphoproliferative disorder presenting with dural thickening is rare. Considering that methotrexate-associated lymphoproliferative disorder often regresses following methotrexate cessation alone, early recognition of this adverse effect of methotrexate and prompt methotrexate discontinuation are crucial. In this case, imaging findings alone were insufficient for diagnosis, and dural biopsy was critical in establishing the diagnosis of methotrexate-associated lymphoproliferative disorder.