Methotrexate-Associated Lymphoproliferative Disorder Presenting As Disseminated Metastatic Malignancy: A Case Report

Methotrexate-associated lymphoproliferative disorder (MTX-LPD) is a rare but relevant complication of long-term methotrexate (MTX) therapy that can closely mimic infection or disseminated malignancy. We report the case of a 65-year-old woman with a 10-year history of systemic lupus erythematosus (SLE) treated with MTX, who presented with progressive back pain, constitutional symptoms, pancytopenia, and extensive multiorgan disease. Fluorodeoxyglucose positron emission tomography (FDG PET) demonstrated widespread hypermetabolic lesions involving the lungs, liver, left adrenal gland, and skeleton, raising strong suspicion of disseminated metastatic malignancy. Two ultrasound-guided liver nodule biopsies were inconclusive, with no evidence of malignancy. Given the absence of histopathological confirmation and her prolonged MTX exposure, MTX-LPD was suspected, and MTX was discontinued. No oncologic treatment was initiated. Four months later, the patient had achieved complete clinical resolution of her symptoms, and follow-up imaging showed near-complete regression of the pulmonary, hepatic, adrenal, and most skeletal lesions.