[Frontiers in Bioscience 11, 718-732, January 1, 2006]

HIV disorders of the brain; pathology and pathogenesis

Luis Del Valle and Sergio Piña-Oviedo

Center for Neurovirology and Cancer Biology, Laboratory of Neuropathology and Molecular Pathology, Temple University, 1900 North 12th Street, Suite 240, Philadelphia, Pennsylvania 19122 USA

FIGURES

Figure 1. Histopathological Features of HIV Encephalopathy. Low magnification view of the cortical grey matter in a case of HIV-Encephalopathy depicting a blood vessel with intramural and perivascular chronic inflammatory cells, including a giant multinucleated cell (arrow). The vasculitis results in small areas of infarction where foamy macrophages can be seen (Panel A, Hematoxilin and Eosin, original magnification x200). At higher magnification the giant multinucleated cells can be seen in close proximity to blood vessels (Hematoxilin & Eosin, original magnification x1000). Immunohistochemistry for the HIV-1 capsid protein p24 is robustly expressed in the cytoplasm of the giant multinucleated cells, as well as in endothelial cells of the blood vessel (Panel C, original magnification x1000). Another characteristic feature of the HIV encephalopathy are the parenchymal microglial nodules (Panel D, Hematoxilin and Eosin, original magnification x200). Numerous reactive astrocytes are present in areas of damage (Panel E, Hematoxilin and Eosin, original magnification x400). Immunohistochemistry demonstrates expression of the HIV transactivator protein Tat in the cytoplasm of these reactive astrocytes (Panel F, original magnification x400).

Figure 2. Histopathological Features of Progressive Multifocal Leukoencephalopathy. Axial MRI of the brain showing the characteristic hyper-intense areas located in the sub-cortical white matter of the frontal lobe (Panel A). Coronal section of the same case, at the level of the frontal lobe demonstrating extensive lytic lesions in the sub-cortical white matter particularly prominent in the right olfactory giry (Panel B). Low magnification view of the white matter of a case of PML reveals extensive areas of myelin loss (Panel C, Hematoxylin & Eosin, original magnification x100). The demyelinated areas are highlighted with a special stain for myelin (Panel D, Luxol Fast Blue, original magnification x100). Higher magnification of the demyelinated plaques shows the characteristic cells of PML, giant reactive astrocytes with bizarre atypical nuclei (Panel E, Hematoxylin & Eosin, original magnification x1000), and enlarged oligodendrocytes harboring intranuclear eosinophilic inclusion bodies (Panel F, Hematoxylin & Eosin, original magnification x400). Immunohistochemistry for the JCV capsid protein VP-1 shows robust reactivity in the nuclei of infected oligodendrocytes, demonstrating productive infection (Panel G, original magnification x200). The intranuclear inclusion bodies in oligodendrocytes are composed by numerous icosahedral viral particles as demonstrated by electron microscopy (Panel H).

Figure 3. Opportunistic Infections Associated with AIDS. Coronal section of the brain in a case of Cryptococcosis demonstrates the characteristic cystic lesions, some of them confluent in the right Putamen (Panel A). Histologically, Cryptococcus neoformans is found confined to the Virchow-Robin space, which is dilated due to the microorganism and its mucoid secretion (Panel B, Mucicarmin, original magnification x100). Special staining methods reveal the structure of Cryptococcus, which is spherical, surrounded by an external capsule (Panel C, PAS, Insert, Groccot, both images original magnification x1000). MRI of the brain reveals an extensive lesion involving the right basal ganglia and corpus callosum in a case of Toxoplasmosis (Panel D). A coronal section of the brain in the same case demonstrates a large, irregularly shaped necro-hemorrhagic lesion, involving the basal ganglia and extending into the subcortical white matter (Panel E). Toxoplasma gondii can be found in tissue sections as intracellular tachyzoites in neurons and glial cells (Panel F, Hematoxylin & Eosin), and large oocysts with no inflammatory reaction surrounding them (Insert, both images, original magnification x1000).

Figure 4. Histopathological Features of Primary CNS Lymphomas. MRI of the brain in a case of primary CNS lymphoma reveals a large necrotic mass involving the right basal ganglia and producing significant brain edema (Panel A). A coronal section of the brain demonstrates a large infiltrating mass that affects the basal ganglia, including the caudate nucleus, the putamen and globus pallidus. The tumor is friable, granular and exhibits areas of necrosis and focal hemorrhage (Panel B). A low power magnification view of the tumor shows abundant neoplastic lymphocytes arranged in a concentric perivascular pattern that diffusely infiltrate the brain parenchyma (Panel C Hematoxilin & Eosin, original magnification x400). Robust cytoplasmic immunolabeling for CD-20 reveals the B-lymphocyte nature of the tumor (Panel D, original magnification x400). Immunohistochemistry for the Epstein-Barr latent membrane protein (LMP) reveals widely expression by neoplastic lymphocytes (Panel E, original magnification x400). The JCV early protein T-Antigen has been found in the nuclei of neoplastic lymphocytes by immunohistochemistry (Panel F, original magnification x1000). Double labeling immunofluorescence for LMP (Panel G, fluorescein) and T-Antigen (Panel H, rhodamin) demonstrates co-localization of both proteins in the majority of neoplastic cells (Panel I). Panels G, H and I original magnification x1000.