Anatomic Pathology: Neuropathology

• Progressive multifocal leukoencephalopathy (PML) is caused by a JC virus, a polyomavirus, and it can present with focal neurologic deficits, such as dysarthria, limb weakness, visual disturbances or ataxia. These usually progresses over a few months, resulting in increasing neurologic impairment, dementia, and death.

• PML is thought to be the result of reactivation of latent JC virus in immunocompromised patients, such as those infected with HIV.

• Lesions of PML tend to be multiple and involve primarily the cerebral white matter, although involvement of the cerebral cortex and deep gray matter can also be seen. Lesions are foci of demyelination, with occasional central necrosis.

• Histologic features of PML include loss of myelin, multiple foamy macrophages, and only scant lymphocytes. Very large astrocytes with bizarre, pleomorphic, hyperchromatic nuclei are present. Oligodendrocytes, especially at the edge of the lesion, have enlarged nuclei with viral inclusions, which stain positive with antibodies against the SV40 T antigen.

• Other infections associated with immunocompromised patients, such as AIDS patients, include: fungal (Cryptococcus neoformans, most commonly), viral encephalitis (CMV, more common), bacterial infections, and parasitic (toxoplasmosis).