1. 2011 AANP Diagnostic Slide Session Case 1 Janna Neltner, MD Dianne Wilson, MD Peter T. Nelson, MD PhD Craig Horbinski, MD PhD University of Kentucky

2. 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)

3. Stereotactic brain biopsy “Most consistent with vasculitis” Steroids, Cellcept were initiated Died 1 year after onset

6. Thalamus [20x]

7. Thalamus [40x]

8. Midbrain [40x]

9. Thalamus [60x]

10. Additional stains? Diagnosis?

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

12. CD 3 [20x]CD 20 [20x]

13. Final Diagnosis Primary CNS lymphoma, diffuse B cell type [lymphomatosis cerebri] EBV negative

14. Initial biopsy: retrospective T, B cell IHC CD3CD20

15. 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

16. Lymphomatosis Cerebri – Imaging MRI: T2 hyperintensities in deep white matter and basal ganglia (without contrast enhancement) Leschziner, G et al. J. Neurol, 2011

17. 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

18. 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 Psychiatry. 78(7): 777-778. Epub 2007 Jan 2008. Pandit, L., Y. Chickabasaviah, et al. (2010). "Lymhomatosis cerebri--a rare cause of leukoencephalopathy." J Neurol Sci. 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. 17(1): 117-118, 121. Weaver, J. D., H. V. Vinters, et al. (2007). "Lymphomatosis cerebri presenting as rapidly progressive dementia." Neurologist. 13(3): 150-153.