Neuron-associated class III beta-tubulin isotype, retinal S-antigen, synaptophysin, and glial fibrillary acidic protein in human medulloblastomas: a clinicopathological analysis of 36 cases.

Surgical specimens from 36 medulloblastomas (25 classic and 11 desmoplastic) were studied by peroxidase-antiperoxidase (PAP) immunohistochemistry with antibodies against the class III beta-tubulin isotype (beta-tubulin), synaptophysin, retinal S-antigen (S-Ag), and glial fibrillary acidic protein (GFAP). We found that neoplastic cells expressed beta-tubulin in 91% of the tumors (23 classic and 10 desmoplastic), synaptophysin in 75% (19 classic and 8 desmoplastic), S-Ag in 44% (11 classic and 5 desmoplastic), and GFAP in 11% of medulloblastomas (2 classic and 2 desmoplastic). Synaptophysin and beta-tubulin positivities were observed in undifferentiated neoplastic cells, in cells forming neuroblastic rosettes, and in pale islands, while S-Ag immunopositivity was noted in undifferentiated cells, occasionally in beta-tubulin-negative neuroblastic rosettes, and exceptionally in pale islands. Large pale islands, in two desmoplastic medulloblastomas, exhibited distinct patterns of immunoreactivity to the above markers, suggesting neuronal and glial differentiation in the central area, and intense neuritic development in the peripheral zone. Our findings confirm the predominant capacity of medulloblastoma cells to differentiate along neuronal cell lines and indicate that large pale islands, in desmoplastic medulloblastomas, represent well-organized areas for neuronal and, to a lesser degree, astroglial differentiation. Furthermore, it appears, in our cases, that immunohistochemical features do not represent clear-cut prognostic indicators in patients with medulloblastomas.

Aqueductal atresia as a feature of arhinencephalic syndromes.

Two cases are presented of aqueductal atresia associated with arhinencephalic syndromes. The first case was one of semilobar holoprosencephaly with occipital encephalocele, the second one of lobar holoprosencephaly (callosal agenesis with interhemispheric cyst). Only the second case was associated with obstructive hydrocephalus. The absence of hydrocephalus in the first case may be ascribed either to the greater distensibility of the encephalocele, or to the displacement of the choroid plexuses from the intracranial portion of the common ventricle into the hernial sac.

[Nervous system pathology in AIDS: results of a collaborative autopsy study from Switzerland]. / Pathologie des zentralen Nerven-systems bei Aids: Resultate einer kollaborativen Autopsiestudie aus der Schweiz.

Neuropathological lesions were studied in a consecutive autopsy series of 206 cases, comprising 61% of all patients who died of Aids in Switzerland between April 1981 and December 1988. Central nervous system involvement was found in 84% of the patients, and 17% showed multiple concomitant intracerebral lesions. Among the non-viral opportunistic infections, cerebral toxoplasmosis was most frequent (24%), whilst among the viral opportunistic infections, cytomegalovirus (CMV) encephalitis was most frequent (7%). A nodular encephalitis consisting of disseminated microglial nodules without morphological or immunocytochemical evidence of CMV occurred in 13.5% of the patients. The majority of these cases showed evidence of extracerebral CMV infection. Progressive multifocal leukoencephalopathy (PML) was observed in 6% of the patients and was associated with widespread tissue destruction and cyst formation. HIV encephalopathy occurred in 38 patients (18%) and showed two characteristic morphological patterns: progressive diffuse leukoencephalopathy (PDL) and multifocal giant cell encephalitis (MGCE). PDL was observed in 22 patients and was characterized by a diffuse demyelination and gliosis of the white matter with little inflammatory infiltrates and scattered multinucleated giant cells which were immunoreactive to HIV antigens. MGCE was found in 16 patients and was characterized by clusters of macrophages, lymphocytes, and HIV-immunoreactive multi-nucleated giant cells. In our view, PDL and MGCE represent two opposite variants of HIV-induced encephalopathies with numerous intermediate manifestations.

Neuropathology of the acquired immune deficiency syndrome (AIDS): a report of 135 consecutive autopsy cases from Switzerland.

Neuropathological changes were studied in a consecutive autopsy series of 135 cases, comprising 73% of all patients who died of AIDS in Switzerland between April 1981 and December 1987. Central nervous system involvement was found in 119 patients (88%), 19 of which had multiple concomitant intracerebral lesions. Among the non-viral opportunistic infections, encephalitis due to Toxoplasma gondii was most frequent and occurred in 35 patients (26%), followed by central nervous system infection with Cryptococcus neoformans, which was found in five patients (4%). Cytomegalovirus (CMV) encephalitis was present in 14 patients (10%). Disseminated microglial nodules without morphological or immunocytochemical evidence of CMV was encountered in 18 patients (13%). However, in all but two of these patients there was evidence of extracerebral CMV infection, suggesting that CMV was responsible for these nodular encephalitides. Nine patients (7%) had progressive multifocal leukoencephalopathy (PML); in five of these, demyelination was associated with extensive tissue destruction and cyst formation. HIV-associated encephalopathy was observed in 21 patients (16%) and showed two characteristic morphological patterns: progressive diffuse leukoencephalopathy (PDL) and multifocal giant cell encephalitis (MGCE). PDL was observed in 13 cases and characterized by diffuse pallor and gliosis of the cerebral and cerebellar white matter with scattered multinucleated giant cells, but without significant inflammatory response. MGCE was found in eight patients and characterized by clusters of numerous multinucleated giant cells, rod cells, macrophages, lymphocytic infiltrates and occasional necroses. In our view, PDL and MGCE represent the two opposite variants of HIV-induced encephalopathies, with overlapping intermediate manifestations.

Lhermitte-Duclos disease. An immunohistochemical study of the cerebellar cortex.

Immunocytochemical studies were carried out on two previously reported autopsy cases of Lhermitte-Duclos disease. The unaffected cerebellar cortex adjacent to the lesions served as control. The findings supported the view, previously expressed by one of the authors, of a heterogeneous neuronal structure of the lesion, consisting of at least two cell types. No further light was thrown on the predominant medium-sized cells, believed to represent hypertrophic internal granular neurons. On the other hand the large cells shared a number of features with Purkinje cells. In particular they were recognized by the pan-T-cell antibody anti-Leu-4, were surrounded by axosomatic synapses visualized by the antisynaptic vesicle glycoprotein antibody SV2, and contained both non-phosphorylated and phosphorylated neurofilament epitopes. It is suggested that these cells represent dysplastic Purkinje cells. The lesion therefore appears to be a complex hamartoma rather than a simple hypertrophy of the internal granular neurons.

Necrosis of the fetal brain stem with cerebellar hypoplasia.

Two neonates are presented with intrauterine necrosis of the brain stem. In one of the necrosis and calcification were multifocal and extended from the thalamus to the medulla oblongata. In the other the process was limited to the medulla, but was associated with severe hypoplasia of the nuclei pontis. In both cases the cerebellum was hypoplastic and immature for the gestational age. The connection between the two lesions remains obscure, and two hypotheses are discussed. One hypothesis ascribes the delay in cerebellar development to subliminal damage caused by the same insult that produced the brain-stem lesions, the other considers the possible effects of partial deafferentation on the maturation of the cerebellum.

The cerebellum of epileptics.

Five cases are presented with different types of cerebellar lesions which may be encountered in epileptics. Case 1 represents typical postical lesions, Case 2 perinatal anoxic-ischemic damage, Case 3 transneuronal degeneration causing crossed cerebellar atrophy, Case 4 iatrogenic cerebellar atrophy due to Phenytoin toxicity. Case 5 illustrates the interaction of two mechanisms, postictal lobular sclerosis and transneuronal degeneration. It is suggested that by attention to the type and distribution of the cerebellar lesions, to the clinical history and to the distribution of lesions in other parts of the brain the pathogenetic mechanisms can be elucidated in most cases.

Dense suprasellar epidermoid cyst. A case report.

A case of a dense epidermoid cyst of the suprasellar cistern is presented. The clinical symptoms were headache radiating to the left eye and a quadrant anopsia on the left eye. The density of the epidermoid was 62 HU and no significant contrast enhancement occurred after contrast application. The main feature which allows differentiation from other hyperdense suprasellar lesions seems to be the lack of contrast enhancement.

Lhermitte-Duclos disease (diffuse hypertrophy of the cerebellum). Report of two cases.

Two cases of Lhermitte-Duclos disease or diffuse hypertrophy of the cerebellum are presented. This brings the total number of such cases reported in the literature to 42. Pathologically the disease is characterized by a circumscribed cerebellar lesion consisting of thickening of the cortex with closely packed dysplastic ganglion cells in the granular layer and with large myelinated axons in the molecular layer. Purkinje cells are missing and the central white matter is greatly reduced. The first patient, a man 39 years of age, had in association to the cerebellar lesion, a megalencephalic brain (2320 g). He had suffered from epilepsy since he was 24-years-old and died with metastasizing colon carcinoma. An electron microscopic study of the cerebellar lesion disclosed perikarya containing large amounts of rough endoplasmic reticulum, cell processes filled with coated and dense core vesicles. In addition, there were numerous enlarged myelinated axons in the molecular layer. The second patient, a woman 74 years of age, had a small area of diffuse hypertrophy of the left cerebellar hemisphere measuring one centimeter in diameter. Specific symptoms were very scant in the first case and absent in the second one indicating a very slow evolution - if any - of the disease process. The etiology and pathogenesis remain unknown. However, the organoid structure of the lesion, the frequent association of megalencephaly and other congenital abnormalities, and the occurrence of familiar cases would favor the disease being basically a developmental disorder.

Bone scan and angiography for orbitofrontal cholesterol granuloma.

A case of a cholesterol-containing granuloma of the orbit studied by bone scanning and selective carotid angiography is presented. Bone scanning with 99mDisphosphonate disclosed a solitary focus of intense activity in the right orbitofrontal region. On the selective angiogram of the right external carotid artery a faint vascular blush was found in the orbital wall.

Rod-shaped filamentous inclusions and other ultrastructural features in a cerebellar astrocytoma.

A biopsy specimen of a cerebellar astrocytoma from a 14-year-old girl was studied by light and electron microscopy. Histologically the tumor showed a mixture of loose and compact areas with numerous Rosenthal fibers. By electron microscopy most tumor cells contained, besides the usual organelles, large amounts of 70 to 100 A thick filaments. Classical Rosenthal fibers were also identified. In addition many cell bodies and processes were sprinkled with fragments of Rosenthal fiber material. Ordered filamentous arrays (so-called Hirano bodies) were seen in a number of tumor astrocytes. They are considered to be a nonspecific arrangement of filament units largely devoid of cytopathologic significance. Other ultrastructural features of some tumor cells were inchoate forms of the granulated bodies of conventional histology, paired cisternal elements of rough endoplasmic reticulum, and honeycomb-like profiles of transversely cut cylindrical units of smooth endoplasmic reticulum. Microtubular bodies were numerous in the endothelial cells of the tumor vessels.