Diagnostic Slide Session

Case 2010-5

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

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

18 mo ago 10 mo ago Presentation NormalLymphocytes (cells/ul) 1012 888 1890 680-3280

CD3+ (cells/ul) 921 755 1474 850-4950

CD3+CD4+ (cells/ul) 71 36 346 350-1800

CD3+CD8+ (cells/ul) 840 684 1191 250-2200

Helper/suppressor ratio 0.08 0.05 0.21 0.9-3.5

HIV PCR-QN copies/ml 157910 244580 3580

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.

Axial FLAIR (1-26-2009)

H&E

DIFFERENTIAL DIAGNOSIS

Special stains:- AFB- GMS

Immunohistochemistry:- HSV1- HSV2- CMV- HHV8

Ancillary Studies

NEGATIVE

LHE

Neurofilament

SV-40

CD3 CD20

CD3 CD20

CD10 CD21

BCL6 BCL2

KAPPA (ISH) LAMBDA (ISH)

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

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

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

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

Cortex White matter