Diagnostic Slide Session Case 2010-5

1. Diagnostic Slide Session Case 2010-5 Sandra Camelo-Piragua1, Ronald A Goerss2 and David N Louis1 1 Pathology Department, Massachusetts General Hospital, Boston, MA 2 Pathology Department, South Miami Hospital, Miami , FL

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

10. LHE

11. Neurofilament

12. SV-40

13. CD3 CD20

14. CD3 CD20

15. CD21 CD10 BCL2 BCL6

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 • Differential diagnosis: • Lymphoma • Reactive follicle formation Diagnosis: • Immune Reconstitution Inflammatory Syndrome (IRIS) • -Marked inflammation (On/Off HIV therapy) • 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.

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