Primary central nervous system methotrexate associated lymphoproliferative disorders in a patient with rheumatoid arthritis

Abstract

We report on a 52-year-old woman with rheumatoid arthritis (RA) who developed methotrexate associated lymphoproliferative disorders (MTX-LPD) in the central nervous system (CNS) in the course of immunosuppressive therapy for RA. The patient was admitted because of monoplegia in her left hand. She had been receiving methotrexate (MTX) for her RA for several years and etanercept had also been introduced because of a worsening of the arthritis six months before admission. Brain MRI revealed multiple lesions with enhancement scattered throughout both hemispheres. F-fluorodeoxyglucose-positron emission tomography/computed tomography showed abnormal accumulation suggesting malignancy in the right frontal lobe where abnormal enhancement was observed on the MRI. A brain biopsy was performed at the identified site and it confirmed diffuse large B-cell lymphoma (DLBCL). We therefore diagnosed her as MTX-LPD. According to previous reports, most MTX-LPD cases tend to show regression after the cessation of MTX. However, our case showed no regression and even needed chemotherapy. The patient had a poorer prognosis than previous cases and died 17 months after the onset. Although it is an uncommon complication, particularly in the CNS, MTX-LPD should be considered as a critical differential diagnosis if a patient receiving MTX develops central nervous system lesions. Immediate medical intervention including brain biopsy is required.

Progressive Multifocal Leukoencephalopathy during Tocilizumab Treatment for Rheumatoid Arthritis

“…In most cases of MTX-related lymphoproliferative disorder, multiple masses are detected on MRI ( 19 , 20 ). However, a case of multiple lesions without a mass on MRI has been reported ( 21 ), which is similar to the FLAIR and T2-weighted imaging findings in the present case. In the patient reported in the previously published paper, some of those hyperintense lesions on FLAIR were enhanced ( 21 ).…”

“…However, a case of multiple lesions without a mass on MRI has been reported ( 21 ), which is similar to the FLAIR and T2-weighted imaging findings in the present case. In the patient reported in the previously published paper, some of those hyperintense lesions on FLAIR were enhanced ( 21 ). Although no enhancement was detected in the lesions in our case, the coexistence of PML and MTX-related lymphoproliferative disorder lesions is possible.…”

Primary Central Nervous System Methotrexate-associated Lymphoproliferative Disorder in a Patient with Rheumatoid Arthritis: Case Report and Review of Literature

“…Other immune suppressors, such as adalimumab, bucillamine, etanercept, and prednisolone, were used in four primary CNS MTX-LPD cases. 9 , 11 , 12 , 14) …”

“… 8) The 2 EBER − patients (Cases 6 and 8) showed only partial or no regression after stopping MTX, and received additional chemotherapy. 12 , 14) In these three patients, MTX was included in additional chemotherapy regimens. 8 , 12 , 14) However, according to the 2016 update of the Japan College of Rheumatology recommendations for the use of MTX in patients with RA, LPD within the most recent 5 years is included in the contraindications for MTX.…”

“… 12 , 14) In these three patients, MTX was included in additional chemotherapy regimens. 8 , 12 , 14) However, according to the 2016 update of the Japan College of Rheumatology recommendations for the use of MTX in patients with RA, LPD within the most recent 5 years is included in the contraindications for MTX. 29) Therefore, using MTX as additional LPD treatment should be avoided.…”