Lymphomatosis Cerebri Presenting as Steroid-Refractory Demyelinating Disease: A Diagnostic Challenge

Lymphomatosis cerebri (LC) is a rare infiltrative variant of primary central nervous system lymphoma characterized by diffuse cerebral involvement without formation of a discrete mass lesion, which can mimic inflammatory demyelinating disease on imaging. We report a diagnostically challenging case of a 31-year-old man who presented with progressive bilateral visual impairment and diffuse white matter abnormalities initially managed as a demyelinating disease. Magnetic resonance imaging demonstrated widespread bilateral T2-weighted and fluid-attenuated inversion recovery hyperintensities involving the optic pathways, deep and periventricular white matter, basal ganglia, thalami, brainstem, and cerebellar peduncle, with minimal contrast enhancement and mild diffusion restriction. The patient failed to improve despite treatment with high-dose corticosteroids and other immunomodulatory therapies and subsequently developed seizures with progressive neurological deterioration. Extensive laboratory and cerebrospinal fluid evaluation did not support an inflammatory, infectious, or autoimmune etiology. Stereotactic brain biopsy performed due to clinical progression revealed diffuse angiocentric infiltration by malignant lymphoid cells, confirming the diagnosis of LC. This case highlights the potential for LC to masquerade as steroid-refractory demyelinating disease and underscores the importance of recognizing suggestive imaging patterns that should prompt early consideration of brain biopsy.