Methotrexate-induced myelopathy: a great imitator of relapsed malignant lymphoma

Methotrexate-induced myelopathy is a rare adverse effect of intrathecal methotrexate, characterized by acute or subacute myelopathy-like neurological manifestations and magnetic resonance imaging findings resembling subacute combined degeneration. Because neurological symptoms often precede radiological abnormalities, accurate diagnosis can be challenging, particularly in patients with hematological malignancies, in whom central nervous system relapse must also be considered.

A 61-year-old man with extranodal natural killer/T-cell lymphoma, nasal type, developed progressive lower limb weakness and sensory disturbance four days after his 11th course of intrathecal methotrexate for central nervous system relapse. Initial spinal magnetic resonance imaging showed no abnormalities; however, subsequent imaging revealed longitudinally extensive, ascending T2-hyperintense lesions in the posterior and lateral columns of the thoracic spinal cord without gadolinium enhancement. Methotrexate-induced myelopathy was diagnosed based on clinical and radiological findings. Despite intravenous administration of vitamin B12 and folate, as well as oral supplementation with S-adenosylmethionine, spinal lesions extended rostrally without further neurological deterioration. One month later, the patient developed progressive unilateral axonal neuropathy of the left lower limb. Subsequent skin biopsy confirmed relapse of extranodal natural killer/T-cell lymphoma.

This case illustrates that methotrexate-induced myelopathy may present with delayed radiological abnormalities and can closely mimic relapse of the underlying malignancy. Furthermore, the development of peripheral axonal neuropathy during the clinical course of methotrexate-induced myelopathy should prompt careful evaluation for disease recurrence in patients with hematological malignancies.