An unusual and challenging case of HIV-associated primary CNS Lymphoma with Hodgkin-like morphology and HIV encephalitis

Abstract

HIV-associated primary CNS lymphomas are well-recognized, almost exclusively EBV-driven neoplasms with poor clinical prognosis. We report a challenging, atypical case of an HIV-associated lymphoproliferative disorder with unusual morphologic features reminiscent of Hodgkin Lymphoma, accompanied by HIV encephalitis. A 52-year-old male presented with acute seizures after seven months of progressive neurocognitive decline that was clinically diagnosed as progressive supranuclear palsy. Clinical work-up revealed HIV infection along with two ring-enhancing lesions in the brain on MRI, and negative CSF EBV testing. Subsequent biopsy showed well-demarcated hypercellular regions in the brain comprised of scattered Reed-Sternberg-like cells in a background of small to medium-sized lymphocytes exhibiting focal angiocentricity and geographic necrosis. The atypical cells were positive for CD20, EBV, and CD79a, and negative for CD45, GFAP, CD15, CD30, and p24. These cells were admixed with numerous CD68-positive cells. The adjacent brain showed classic features of HIV encephalitis with perivascular, CD68 and p24-positive multinucleated giant cells. This case illustrates several diagnostic pitfalls in the work-up of HIV-associated brain lesions, as well as reporting a unique histomorphology for an HIV-related primary CNS lymphoproliferative disorder.

Fig. 1

Magnetic Resonance Images. Axial T1 post-contrast Magnetic Resonance Images (MRI) of the patient’s ring-enhancing lesions in the right thalamus (a) and left frontal lobe (b) with central low signal suggesting necrosis. Axial FLAIR image at the level of the thalamic lesion (c) shows edema surrounding the lesion in the right thalamus and left frontal lobe as hyperintense signal. There is mild diffuse cerebral volume loss which is a common finding in HIV encephalitis

Fig. 2

H&E Stained Sections. Photomicrographs of H&E stained sections showing fragments of brain tissue with distinct areas of gliosis, hypercellularity, and necrosis (N) at 40X magnification (Part a). The gliotic brain exhibited perivascular multinucleated giant cells (arrows) (b, 200X, and inset, 400X), while the hypercellular areas were comprised of polymorphous atypical cells with occasional angiocentric architecture (c, 200X) and large, Reed-Sternberg-like cells (d, 400X)

Fig. 3

GFAP, MIB-1, CD68, and CD45 Immunohistochemistry. Photomicrographs of immunohistochemical stains show a reactive pattern for glial acidic fibrillary protein (GFAP) in the background brain, but no significant staining in the hypercellular lesion (a,40X). The hypercellular region exhibits significantly increased MIB-1 staining (b,100X), strong CD68 positivity (c,100X), and only rare, small, CD45-positive cells (D,400X) compared to the background brain

Fig. 4

CD20, CD15, and CD30 Immunohistochemistry and EBV In Situ Hybridization. Photomicrographs of the hypercellular lesion show that the large, Reed-Sternberg-like cells and many intermediate-sized cells were strongly positive for CD20 by immunohistochemistry (a,100X, and inset,400X), and EBV via ISH (b, 400X); the large cells were negative for CD15 (c, 400X) and CD30 (d, 400X) by immunohistochemistry

Fig. 5

P24 Immunohistochemistry. Photomicrographs of the background brain show positive p24 immunohistochemical staining within the multinucleated giant cells of HIV encephalitis (a, 400X), while the neoplastic cells are negative (b, 400X)