2011 AANP Diagnostic Slide SessionCase 1

Janna Neltner, MDDianne Wilson, MD

Peter T. Nelson, MD PhDCraig Horbinski, MD PhD

University of Kentucky

History• 56 year old female

– Hypertension– Hypercholesterolemia– IDDM

• Clinical impression of Parkinson Disease with dementia• MRI: progressive changes within the basal ganglia and

periventricular white matter

Initial (T2, FLAIR) 6 months (T2, FLAIR)

Stereotactic brain biopsy

• “Most consistent with vasculitis”• Steroids, Cellcept were initiated• Died 1 year after onset

Thalamus [20x]

Thalamus [40x]

Midbrain [40x]

Thalamus [60x]

• Additional stains?• Diagnosis?

GFAP [20x] IDH 1 (R132H) [20x]

CD 3 [20x] CD 20 [20x]

Final Diagnosis

Primary CNS lymphoma, diffuse B cell type [lymphomatosis cerebri]

EBV negative

Initial biopsy: retrospective T, B cell IHC

CD3 CD20

Lymphomatosis Cerebri• Defined as a diffusely infiltrating lymphoma that does not

result in a mass lesion• Rare entity

– Only 15 papers (mostly case reports) in the literature– Term coined by Bashki et al (Dement Geriatr Cogn Disord 1999)

• Age range: 28-80• Usually immunocompetent patients

– EBV-negative

• Presenting symptoms (generally rapid onset)– Variable cognitive and behavioral changes– Cranial nerve palsies– Ataxia– Bradykinesia

Lymphomatosis Cerebri

– Imaging• MRI: T2 hyperintensities in deep white matter and

basal ganglia (without contrast enhancement)

Leschziner, G et al. J. Neurol, 2011

Lymphomatosis Cerebri– Differential includes….

• Binswanger’s disease• Progressive multifocal leukoencephalopathy• Other infections• Paraneoplastic encephalitis• Autoimmune disease• Creutzfeldt-Jakob disease• Toxin exposure

– Prognosis• Typically poor• Before MRI were almost all identified post-mortem• With better imaging, more cases are picked up earlier, which may

result in better outcomes• Most still succumb to the disease within months of the diagnosis

References• Bakshi, R., J. C. Mazziotta, et al. (1999). "Lymphomatosis cerebri presenting as a rapidly progressive dementia: clinical,

neuroimaging and pathologic findings." Dement Geriatr Cogn Disord. 10(2): 152-157.• de Toledo, M., E. Lopez-Valdes, et al. (2008). "[Lymphomatosis cerebri as the cause of leukoencephalopathy]." Rev Neurol.

46(11): 667-670.• Hishikawa, N., H. Niwa, et al. (2011). "An autopsy case of lymphomatosis cerebri showing pathological changes of

intravascular large B-cell lymphoma in visceral organs." Neuropathology 7(10): 1440-1789.• Kanai, R., M. Shibuya, et al. (2008). "A case of 'lymphomatosis cerebri' diagnosed in an early phase and treated by whole

brain radiation: case report and literature review." J Neurooncol. 86(1): 83-88. Epub 2007 Jul 2005.• Leschziner, G., P. Rudge, et al. (2011). "Lymphomatosis cerebri presenting as a rapidly progressive dementia with a high

methylmalonic acid." J Neurol 2: 2.• Levin, N., D. Soffer, et al. (2008). "Primary T-cell CNS lymphoma presenting with leptomeningeal spread and

neurolymphomatosis." J Neurooncol. 90(1): 77-83. Epub 2008 Jul 2001.• Lewerenz, J., X. Ding, et al. (2007). "Dementia and leukoencephalopathy due to lymphomatosis cerebri." J Neurol Neurosurg

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293(1-2): 122-124. Epub 2010 Mar 2020.• Raz, E., E. Tinelli, et al. (2011). "MRI findings in lymphomatosis cerebri: description of a case and revision of the literature." J

Neuroimaging. 21(2): e183-186. doi: 110.1111/j.1552-6569.2010.00477.x.• Rollins, K. E., B. K. Kleinschmidt-DeMasters, et al. (2005). "Lymphomatosis cerebri as a cause of white matter dementia."

Hum Pathol. 36(3): 282-290.• Sugie, M., K. Ishihara, et al. (2009). "Primary central nervous system lymphoma initially mimicking lymphomatosis cerebri:

an autopsy case report." Neuropathology. 29(6): 704-707. Epub 2009 Mar 2003.• Vital, A. and I. Sibon (2007). "A 64-year-old woman with progressive dementia and leukoencephalopathy." Brain Pathol.

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