Progressive multifocal leukoencephalopathy in an untreated chronic lymphocytic leukemia patient: Case report and review of the literature.

Progressive multifocal leukoencephalopathy (PML), caused by John Cunningham virus (JCV), is a rare opportunistic infection in patients with chronic lymphocytic leukemia (CLL) after immunosuppressive therapy, with only a handful of cases reported in treatment-naïve patients. Herein we present a 71-year-old man with treatment-naïve CLL who developed rapidly progressive left facial weakness, hemiparesis, dysarthria, and urinary incontinence. Brain magnetic resonance imaging demonstrated characteristic imaging findings of PML, including multifocal white matter lesions involving the subcortical U-fibers with the Milky Way sign and rim-and-core diffusion restriction, as well as atypical findings of internal perivascular enhancement ultimately raising suspicion for JCV infection despite the absence of prior CLL-directed therapy. The diagnosis was confirmed by cerebrospinal fluid analysis and stereotactic brain biopsy demonstrating JCV-associated PML. Despite supportive management, the patient experienced rapid neurological decline and died approximately 1 month after symptom onset. This case highlights that PML should be considered in untreated patients with advanced CLL and emphasizes the importance of recognizing characteristic MRI findings to facilitate timely diagnosis of this rare but devastating complication.