1. Diagnostic Slide Session Case 2010-5 Sandra Camelo-Piragua 1, Ronald A Goerss 2 and David N Louis 1 1 Pathology Department, Massachusetts General Hospital, Boston, MA 2 Pathology Department, South Miami Hospital, Miami, FL

2. 18 mo ago10 mo agoPresentationNormal Lymphocytes (cells/ul)10128881890680-3280 CD3+ (cells/ul)9217551474850-4950 CD3+CD4+ (cells/ul)7136346350-1800 CD3+CD8+ (cells/ul)8406841191250-2200 Helper/suppressor ratio0.080.050.210.9-3.5 HIV PCR-QN copies/ml1579102445803580 DSS 2010-5 38-year-old man who presented with seizures in 2009, after a year of fluctuating neurological symptoms. History of HIV, ongoing cocaine use and intermittent compliance with his anti-HIV regimen.

3. Axial FLAIR (1-26-2009)

4. H&E

8. DIFFERENTIAL DIAGNOSIS

9. Special stains: - AFB - GMS Immunohistochemistry: - HSV1 - HSV2 - CMV - HHV8 Ancillary Studies NEGATIVE

10. LHE

11. Neurofilament

12. SV-40

13. CD3 CD20

14. CD3 CD20

15. CD10 CD21 BCL6 BCL2

16. KAPPA (ISH) LAMBDA (ISH)

17. Diagnosis -Progressive Multifocal Leukoencephalopathy (PML) -Patient alive after one year of initial symptoms and radiologic abnormality -Marked and unusual inflammatory infiltrate -Immune Reconstitution Inflammatory Syndrome (IRIS) -Marked inflammation (on/off anti-HIV therapy) -Differential diagnosis: lymphoma vs. reactive follicles

18. References Vendrely A, Bienvenu B, Gasnault J, Thiebault JB, Salmon D, Gray F. Fulminant inflammatory leukoencephalopathy associated with HAART-induced immune restoration in AIDS-related progressive multifocal leukoencephalopathy. Acta Neuropathol. 2005 Apr;109(4):449-55. Cinque P, Bossolasco S, Brambilla AM et al. The effect of highly active antiretroviral therapy-induced immune reconstitution on development and outcome of progressive multifocal leukoencephalopathy: study of 43 cases with review of the literature. J Neurovirol. 2003; 9 Suppl 1:73-80 Hair LS, Nuovo G, Powers JM, Sisti MB, Britton CB, Miller JR. Progressive multifocal leukoencephalopathy in patients with human immunodeficiency virus. Hum Pathol. 1992 Jun;23(6):663-7 Miralles P, Berenguer J, Garcia de Viedma D, et al. Treatment of AIDS- associated progressive multifocal leukoencephalopathy with highly active antiretroviral therapy. AIDS. 1998; 12:2467-72

19. Diagnosis -Progressive Multifocal Leukoencephalopathy (PML) -Unusual inflammatory infiltrate Hair LS et al. Hum Pathol, 1992 -Patient alive after one year of initial symptoms and radiologic abnormality. -Immune Reconstitution Inflammatory Syndrome (IRIS) -Marked inflammation (On/Off HIV therapy) Diagnosis: Differential diagnosis: -Lymphoma -Reactive follicle formation

20. Progressive Multifocal Leukoencephalopathy (PML) -Demyelinating foci on the cortico-subcortical junction with microglial activation, astrocytosis, and lympho- plasmocytic infiltration -PML inclusions at the edge of the demyelinating lesion admixed with inflammation -Myelin destruction with focal necrosis and cavitation - Unusual inflammatory infiltrate Hair LS et al. Hum Pathol, 1992 - Patient alive after one year of initial symptoms and radiologic abnormality

21. Immune Reconstitution Inflammatory Syndrome (IRIS) -Acute symptomatic or paradoxical deterioration of a presumed pre-existing infection that is temporarily related to recovery of the immune system -Marked inflammation (On/Off HIV therapy)

22. Immune Reconstitution Inflammatory Syndrome (IRIS) Diagnostic criteria: -Patient with AIDS -HAART induced a decrease in HIV-1 VL and an increase in CD-4+ T lymphocytes -Symptoms consistent with an infection/inflammatory condition appeared while on retroviral therapy - Symptoms could not be explained by a new acquired infection, the expected course of a previously recognized infection, or side effects of therapy

23. PML + IRIS

24. 1-26-2009

28. Cortex White matter