Progressive Multifocal Leukoencephalopathy Presenting as Primary CNS Malignancy in an Immunocompetent Patient

Progressive multifocal leukoencephalopathy (PML) is an infection caused by the John Cunningham virus (JCV), usually in an immunocompromised host. We present the case of a 74-year-old male who presented with a six-week history of progressive memory loss, episodic confusion, and aphasia. Cranial nerve, motor, sensory, and coordination testing were unremarkable. Magnetic resonance imaging (MRI) of the brain and spectroscopy were concerning for primary CNS lymphoma vs. diffuse glioma. Microscopic examination after the patient underwent left frontal stereotactic brain biopsy was suggestive of a viral infection, and further testing with JCV DNA in-situ hybridization (ISH) confirmed the diagnosis of PML. The patient's condition started resolving without treatment. This case demonstrates, to our knowledge, the first known case of primary PML masquerading as CNS lymphoma in modern literature.