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7 February 2013 - Case of the Week #265

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Thanks to Dr. Joseph Fullmer, University of Wisconsin Hospital and Clinics (USA), for contributing this case and the discussion. To contribute a Case of the Week, follow the guidelines on our Case of the Week page.

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Case of the Week #265

Clinical History:

A 61 year old man had abdominal follicular lymphoma diagnosed 7 years ago, treated with chemotherapy and radiation, and thought to be in remission. He developed increasing difficulties with balance, dizziness, numbness over his left tongue and inside cheek spreading to his face, as well as clumsiness with his left hand and leg over a 7 week period. MRI revealed a 3.8 x 2.3 x 2.4 cm lesion with minimal edge enhancement (hence predominately non-enhancing) centered in the left middle cerebellar peduncle extending into the left paramedian pons and left cerebellar hemisphere. Preoperative differential diagnosis included demyelination, low grade glial neoplasm, and recurrent lymphoma. Biopsy of the mass was performed.

Micro images:


What is your diagnosis?


Progressive multifocal leukoencephalopathy


Immunostains for the JC virus were positive:

Progressive multifocal leukoencephalopathy (PML), also known as progressive multifocal leukoencephalitis, is a rare and usually fatal demyelinating disease characterized by progressive multifocal white matter damage and inflammation, due to the JC virus (Discov Med 2011;12:495). It is almost always associated with immunosuppression, including immunosuppressive/biologic therapy for autoimmune diseases, such as natalizumab for multiple sclerosis (Mult Scler 2012;18:143), and other agents for rheumatoid arthritis or lymphoma (Wikipedia, Joint Bone Spine 2012;79:351).

Lytic infection of CNS oligodendrocytes leads to their destruction and progressive demyelination, resulting in multifocal lesions. Although PML previously was relatively rare, it now occurs in 3-5% of HIV+ individuals, and is classified as an AIDS-defining illness (Clin Microbiol Rev 2012;25:471).

Biopsies show multiple foci of demyelination with enlarged and bizzare astrocytes, which are often multinucleated and have multiple large processes (University of Oklahoma). Oligodendrocytes may have eosinophilic or basophilic nuclear inclusions, due to virions (Acta Neuropathol 2010;120:403). Lymphocytic infiltration is variable. Necrosis with inflammation resembling an infarct may also be seen.

Treatment consists of reversal of the immunosuppression, if possible. Case reports now suggest some treatments may be effective (J Neurol Sci 2013 Jan 31 [Epub ahead of print], Ann Acad Med Singapore 2012;41:620).

Nat Pernick, M.D., President
and Palak Thakore, Associate Medical Editor
PathologyOutlines.com, Inc.
30100 Telegraph Road, Suite 408
Bingham Farms, Michigan (USA) 48025
Telephone: 248/646-0325
Email: NatPernick@Hotmail.com
Alternate email: NatPernick@gmail.com