Diagnostic Slide Session

Case 2010-5Sandra Camelo-Piragua1, Ronald A Goerss2 and David N Louis1

1 Pathology Department, Massachusetts General Hospital, Boston, MA2 Pathology Department, South Miami Hospital, Miami , FL

DSS 2010-538-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.

18 mo ago10 mo agoPresentationNormalLymphocytes (cells/ul)10128881890680-3280CD3+ (cells/ul)9217551474850-4950CD3+CD4+ (cells/ul)7136346350-1800CD3+CD8+ (cells/ul)8406841191250-2200Helper/suppressor ratio0.080.050.210.9-3.5HIV PCR-QN copies/ml1579102445803580

Axial FLAIR (1-26-2009)

H&E

DIFFERENTIAL DIAGNOSIS

Special stains:- AFB- GMS

Immunohistochemistry:- HSV1- HSV2- CMV- HHV8Ancillary StudiesNEGATIVE

LHE

Neurofilament

SV-40

CD3CD20

CD3CD20

CD10CD21BCL6BCL2

KAPPA (ISH)LAMBDA (ISH)

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

ReferencesVendrely 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

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

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

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)

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

PML + IRIS

1-26-2009

CortexWhite matter

*38 y.o*Axial FLAIR**T2 Coronal