Histopathology of the central nervous system in the acquired immunodeficiency syndrome

Histopathologic findings in the central nervous system in 100 autopsy cases of the acquired immunodeficiency syndrome (AIDS) gave evidence of a variety of opportunistic infections and probably of infection by human immunodeficiency virus (HIV). Gliomesenchymal cell nodules (47 per cent of cases) and spongiform alterations with demyelination were common. Vasculitides (8 per cent) and lesions such as acute hemorrhagic leukoencephalitis may be attributable partly to hypersensitivity reactions. Multinucleated cells, including giant cells that could be a hallmark of HIV encephalitis, were common in normal neuropil, in gliomesenchymal cell nodules, near blood vessels, and in cavitating lesions. Degeneration in long tracts (13 per cent) included posterior column demyelination and spongiform change with or without corticospinal tract degeneration. Some long tract degeneration appeared to originate from bilateral degeneration of the internal capsule, and this may be part of the origin of subacute combined degeneration-like changes in AIDS vacuolar myelopathy. Prominent brainstem inflammatory infiltration suggests that the brainstem is a relatively prominent site of infection or immunopathologic activity. Early ependymal lesions in infants and frequent healed ependymal lesions in adults (16 per cent) could be related to the origin and pathogenesis of HIV lesions in the brain. Some characteristic lesions in AIDS encephalitis may result from immune-mediated responses to HIV antigens on neural cell receptors or from cross-reactivity occurring against epitopes common to neural constituents and to hematopoietic cells, with the latter being under direct antiviral attack.     

Lymphomatoid granulomatosis and malignant lymphoma of the central nervous system in the acquired immunodeficiency syndrome

While primary and secondary malignant lymphomas have been well-documented in the CNS of patients with the acquired immunodeficiency syndrome (AIDS), only one case of lymphomatoid granulomatosis (LG) involving the CNS has been reported. We present three AIDS patients with multiple grossly evident foci of necrosis in the cerebral hemispheres which, on histologic evaluation, were seen to contain angiocentric mixed chronic inflammatory infiltrates with atypical mononuclear cells, luminal thrombosis, and infarction, which is typical of LG. LG was also identified in sections of the lung in one case. Lymphoma was found in other regions of the brain in two cases, suggesting the evolution of LG into cerebral lymphoma. In addition, widespread perivascular multinucleate syncytial giant cells, associated with human immunodeficiency virus (HIV) infection of the CNS, were identified in all patients. The features of LG, its relationship to lymphoma, and the possible etiologic role of an immunodeficiency state or the HIV virus in the pathogenesis of LG are discussed.     

Epstein-Barr and human immunodeficiency viruses in acquired immunodeficiency syndrome-related primary central nervous system lymphoma.

The prevalence of Epstein-Barr virus (EBV) and human immunodeficiency virus (HIV) in acquired immunodeficiency syndrome (AIDS)-related primary central nervous system (CNS) lymphoma was examined. Deoxyribonucleic acid (DNA) extracted from 12 formalin-fixed, paraffin-embedded tumors was used as substrate for the polymerase chain reaction (PCR). Targets for amplification were the EBNA-1 region of EBV, the gag region of HIV, and a single copy cellular sequence as a control. The cases studied were autopsy and surgical specimens collected between the years 1985 and 1989. By the working formulation for non-Hodgkin's lymphomas, five had large cell, four had mixed large and small cleaved cell, two had small cleaved cell, and one had an unclassified histology. Epstein-Barr virus was detected in 6 of 12 tumors studied. Human immunodeficiency virus was not detected in any of the tumors. The presence of EBV was not correlated with any particular histologic tumor type. It is concluded that EBV, not HIV, can be detected in a large percentage (50%) of AIDS-related primary central nervous system (CNS) lymphomas. This viral association may be significant in light of the demonstrated ability of EBV to induce lymphoid tumors in experimental mammalian systems.     

Diagnosis of central nervous system Toxoplasma gondii from the cerebrospinal fluid in a patient with acquired immunodeficiency syndrome

The cytologic diagnosis of central nervous system (CNS) Toxoplasma gondii was established from the cerebrospinal fluid (CSF) in a patient with acquired immunodeficiency syndrome (AIDS) who presented with obstructive hydrocephalus and progressive obtundation. Free extracellular tachyzoites, phagocytized tachyzoites, and cyst forms were identified with Wright staining of cytocentrifuge preparations. Diagnosis was confirmed with indirect immunofluorescent antibody studies. Initial CSF examination was remarkable for low cellularity (24 wbc/mm3) with 42% neutrophils and 58% mononuclear cells on differential examination. Subsequent differential counts of CSF showed persistence of a mixed inflammatory pattern until day 10 at which time a mononuclear pleocytosis was observed. Cerebrospinal chemistries were notable for a low glucose (20 mg/dl), which persisted for 10 days. The cytocentrifuge Wright stain preparation was found to be superior to routine millipore filter Papanicolaou stain preparation for the identification of free tachyzoites and is recommended in the setting of immunodeficient patients with suspected CNS toxoplasmosis.     

Pathological features of virus infections of the central nervous system (CNS) in the acquired immunodeficiency syndrome (AIDS).

Neurological disorders are a common cause of morbidity and mortality in the acquired immunodeficiency syndrome (AIDS). In this report we describe the neuropathological changes associated with both human immunodeficiency virus (HIV) infection and with the major opportunistic virus infections, cytomegalovirus (CMV), JC papovavirus (JCV) and herpes simplex virus (HSV) seen in AIDS. In addition "in situ" hybridization studies have been employed for the detection of virus genomic material in each case and the usefulness of this method in supporting the pathological diagnosis is demonstrated. Mechanisms whereby HIV infection results in leukoencephalopathy and the possible contributing roles of the three opportunistic virus infections are discussed.     

Pathology of the internal organs and central nervous system in acquired immunodeficiency syndrome (with special reference to opportunistic infections)

Extracerebral and cerebral pathology in AIDS (with particular emphasis on the opportunistic infections). The Authors present the extracerebral pathology of 27 cases of AIDS observed at the Department of Pathology of Milan and the cerebral pathology of 80 cases of AIDS collected by three Institutes (Department of Pathology of Milan, Department of Pathology of Rimini and Department of Neuropathology of Münster) with particular emphasis on the pathology of the opportunistic infections. In the adults' group, the most frequent infections are the protozoan ones (T. gondii) followed with equal incidence by the viral and fungal diseases. In the pediatric group the viral diseases are the most frequently seen. Almost all of the adults show multiple infections in the same organ or in different organs. Diffuse lesions with heavy pathologic fields were observed also without tissue reaction. As to cerebral pathology AIDS' patients with opportunistic infections show focal symptoms, whereas the so called "subacute microglial encephalitis" generally appears as a demential syndrome. In cases with progressive multifocal leukoencephalopathy JC virus was always found and in one case also SV 40 - and BK virus. The diffuse demyelinization in some cases of HIV-Encephalopathy is aspecific. In HIV-positive newborns with cerebral signs, the lesions are characterized by oedema, spongiosis and microcalcifications of the basal ganglia; these are aspecific lesions which can be found in toxic and infectious encephalopathies.     

Neuropathology of the central nervous system in acquired immune deficiency syndrome (AIDS) in Japan. With special reference to human immunodeficiency virus-induced encephalomyelopathies

The neuropathological features of the central nervous system in 15 autopsy cases of Japanese male with AIDS were reported. Nine patients had various histological changes including a variety of opportunistic infections in six patients (40%), primary malignant lymphoma of the brain in two (13%), AIDS encephalopathy in four (27%) and vacuolar myelopathy in one (7%). Usually, these pathological changes were present concomitantly. AIDS encephalopathy was characterized by infiltration of mono- and multinucleated cells and myelin pallor with astrogliosis located predominantly in the cerebral white matter and subcortical gray matter. Furthermore, unevenly distributed neuronal loss of the cerebral cortex was apparent in one case. Diffuse astrocytosis of the gray matter out of proportion to neuronal loss was also an outstanding finding in another case. The present study suggested that not only the white matter changes but also gray matter alterations might be the morphological substrates of AIDS encephalopathy.     

Primary lymphoma of the central nervous system in two children with acquired immune deficiency syndrome

Postmortem examination disclosed central nervous system non-Hodgkin's lymphoma in two children who died of acquired immune deficiency syndrome (AIDS) at 6 and 14 months of age, respectively. Systemic signs of lymphoma were not present. The B-cell origin and clonality of the neoplastic cells were established by immunohistochemistry in one case and by molecular analysis of immunoglobulin gene rearrangement in the other. Moreover, in the latter case the neoplastic cells were characterized by the presence of a single episomal EBV genome. According to these data, the monoclonal B-cell proliferation occurred after EBV infection, thus suggesting a possible pathogenetic role of EBV in the early stages of lymphomagenesis.     

Morphological alterations in the lymphoreticular system in acquired immunodeficiency syndrome

Acquired immunodeficiency syndrome (AIDS) manifests a profound deficiency in cellular and humoral immunity causing opportunistic infections with high mortality. Intensive searching for accurate diagnosis, effective treatment, and reliable preventions are in progress. Diagnostic findings include lymphocytopenia, decreased T-helper/T-suppressor ratio and antibodies against human T-lymphotropic retrovirus-III. Specific morphological markers for the diagnosis of AIDS are not yet available at this time. Consistent findings in the lymphoreticular system include a reactive hyperplasia in the onset to lymphocyte depletion in it's advance stage. The frequently mentioned ultrastructural changes in lymphoreticular cells are tubulo-reticular structures, test tube and ring-shaped forms, multivesicular and virus-like particles. These are, however, nonspecific for the diagnosis of AIDS.     

The central nervous system in the Apert syndrome

In this paper, we present available central nervous system data from our series of patients with the Apert syndrome. Combining our own data with that available in the literature, 30 patients had malformations of the corpus callosum, the limbic structures, or both. Other frequent findings included megalencephaly (7 cases), gyral abnormalities (8 cases), encephalocele (4 cases), pyramidal tract abnormalities (2 cases), hypoplasia of cerebral white matter (4 cases), and heterotopic gray matter (2 cases). Progressive hydrocephalus seems to be uncommon and has frequently been confused with nonprogressive ventriculomegaly in the past. Psychometric evaluations, neurological findings, and neuropathologic reports from the literature are critically reviewed. It is clear that a significant number of patients with the Apert syndrome are mentally retarded. It is suggested that malformations of the central nervous system may be responsible for most cases.     

Localization of simian immunodeficiency virus in the central nervous system of rhesus monkeys.

Simian immunodeficiency virus (SIV), like the human immunodeficiency virus (HIV), is a lentivirus that is both immunosuppressive and neurovirulent. Rhesus macaques (Macaca mulatta) inoculated with SIV often develop a giant cell encephalitis similar to that seen in humans infected with HIV. The authors examined SIV expression by immunohistochemistry and RNA in situ hybridization in the cerebrum, cerebellum, choroid plexus, and spinal cord from five macaques with and two macaques without giant cell encephalitis. Selected portions of the central nervous system (CNS) also were examined by electron microscopy. Simian immunodeficiency virus was detected in the CNS of all seven monkeys whether or not they had giant cell encephalitis. Both SIV antigen and RNA were present in all levels of the CNS examined. Macrophage/giant cell lesions always contained viral RNA and antigen and were the only sites where viral particles were detected by electron microscopy. However, SIV antigen and RNA also were commonly associated with small vessels, the choroid plexus, and meninges; these were the only locations where virus was detected in animals without giant cell encephalitis. Immunophenotyping showed that the cellular infiltrates consisted primarily of monocyte/macrophages and occasional CD8-positive T cells. Macrophages and T cells also were present in the stroma of the choroid plexus and were intimately associated with vessels in the CNS of SIV-infected but not uninfected macaques. Simian immunodeficiency virus infection of the macaque CNS provides an excellent model for studying the pathogenesis, treatment, and prevention of HIV-1-encephalitis.     

Pseudallescheria boydii infection in the acquired immunodeficiency syndrome.

Pulmonary and renal infection developed in a 44-year-old Hispanic man due to the fungus Pseudallescheria boydii. Pseudallescheria boydii has been associated with cutaneous infection known as mycetoma but occurs very infrequently in extracutaneous sites. To our knowledge, this is the second reported case of P boydii in a patient with the acquired immunodeficiency syndrome and the first case with pulmonary and/or renal involvement.     

Siderotic cerebral macrophages in the acquired immunodeficiency syndrome.

Excessive hemosiderin-laden perivascular macrophages have been described in the brains of patients with the acquired immunodeficiency syndrome (AIDS) who underwent autopsy; its meaning remains unclear. In the brains of 53 patients with AIDS who consecutively underwent autopsy, we quantified the abnormality, elucidated its relationship to the pathologic features of AIDS, and asked if there was some relationship to endogenous iron storage and transport proteins in brain macrophages and microglia. The number of perivascular siderotic macrophages was significantly increased in patients with AIDS compared with age-matched control subjects. Macrophage siderosis was strongly correlated with the presence of disseminated mycobacterial infection and vacuolar myelopathy at autopsy; a generalized wasting (cachexia) also was related significantly. Many other pathologic abnormalities were not related, including putative human immunodeficiency virus-specific neuropathologic changes such as multinucleated cells and myelin pallor. Activated macrophages and microglial cells in the central nervous system had dense intracytoplasmic accumulation of ferritin (iron storage protein) in AIDS and non-AIDS patients. These results suggest that siderosis of cerebral macrophages is related to an ill-defined nonspecific systemic imbalance associated with the breakdown of abundant stores of endogenous intracellular ferritin. Understanding chronic "secondary" effects of human immunodeficiency virus type 1 infection will become increasingly important as improved survival in patients with AIDS is realized.     

Botryomycosis in acquired immunodeficiency syndrome

The first case, to our knowledge, of an integumentary form of botryomycosis is reported in a homosexual man with acquired immunodeficiency syndrome. Anal fistula and ischiorectal and gluteal abscesses developed following severe cryptosporidial diarrhea. Grains composed of gram-positive cocci were identified in the suppurative exudate. The grains had attached to multinucleated macrophages, many of which contained clusters of cocci in their cytoplasm. It is postulated that the cocci were able to survive and probably replicate in the cytoplasm of multinucleated macrophages, and were subsequently extruded as grains. These observations suggest a defect in intracellular killing of cocci by the monocyte-macrophage system. This may relate to failure in induction of control of macrophage activity by T4-inducer subsets.     

Review of the central nervous system cytopathology in human immunodeficiency virus infection

The human immunodeficiency virus (HIV) is a neurotropic retrovirus capable of producing a wide spectrum of central nervous system changes. Nearly 40% of HIV-infected patients demonstrate neuropathy ranging from dementia to the opportunistic infections and neoplasia seen in the acquired immunodeficiency syndrome (AIDS). Dramatic increases in the numbers of AIDS cases have allowed for the cytotechnologist and cytopathologist to become acquainted with the various pathologic manifestations of HIV infection. In this review, we are reporting the HIV-related diseases in the central nervous system and the role of diagnostic cytology.