Presidential address: the histopathology of meningiomas. A reflection of origins and expected behavior?

Meningiomas and their principal cells of origin, the arachnoidal "cap" cells are unique in their morphology with multiple and sometimes seemingly contradictory features related to their origins and basic character. Some meningiomas express mesenchymal features either in histologic pattern (fibroblastic, lipo-myxochondro-osteoblastic differentiation), participation in other disease processes, e.g. taking part in the formation of rheumatoid nodules, or in storage phenomena shared with other mesenchymal cells of the body. At the same time they may display epithelial features, such as well-formed desmosomes ultrastructurally, papillary formations and intracellular lumina in cells that stain positively for various cell markers usually considered to characterize epithelial cells. Histologic similarities of meningiomas to various gliomas, schwannomas, neuroblastomas, fibrous histiocytomas, myxomas, chordomas, metastatic carcinomas, and in the cases of meningiomas with marked inflammatory infiltrates, to benign or malignant lymphoproliferative disorders involving the meninges may pose serious diagnostic problems. The localization and resectability of meningiomas are important factors related to long-term prognosis. Of the histologic features hemangiopericytomatous pattern, papillary formations, high cellularity (focal or diffuse) and invasion of the brain appear to correlate with potentially aggressive behavior, whereas cytologically aneuploidia, large number of mitoses, prominent nucleoli and cell necrosis suggest a guarded prognosis. However, some meningiomas with no detectable histologic features of malignancy may nevertheless metastasize to distant sites.

Lipidized meningothelial tumor cells in "xanthomatous" meningioma express macrophage antigen.

A case of "xanthomatous" meningioma was examined by light and electron microscopy as well as immunohistology. Lipid-laden "xanthomatous" cells were shown to be meningothelial by all ultrastructural criteria. All tumor cells (lipidized and non-lipidized) expressed vimentin in their cytoplasm, but only the lipidized cells showed the presence of the macrophage marker HAM-56. This finding suggests that, as in some other areas of general pathology, immunological markers may serve as indicators of a specific activity (in this case phagocytosis), rather than merely histogenesis.

The fine structure of hyaline inclusions (pseudopsammoma bodies) in meningiomas.

"Hyaline inclusions" of a meningothelial meningioma were examined under the electron microscope. These eosinophilic, PAS-positive proteinaceous structures, which under the light microscope are seen in both extra- and intracellular location, were found by electron microscopy to consist of granular masses surrounded by cell membranes with microvilli. The "intracellular" bodies were also surrounded by similar microvilli in a space within the cells. Such spaces, variously known as intracellular ductules and "neolumen formation", have been previously described in mammary cancer, bronchiolar carcinoma and pleural mesotheliomas, among others, and have been, in the latter instances, regarded as signs of secretory differentiation. Thus, hyaline inclusions of meningiomas are different from truly intracellular hyaline bodies of neoplastic astrocytes (found by Rubinstein and Herman to be bodies within autophagic vacuoles) and may be regarded as a possible factor in ultrastructural differential diagnosis between meningiomas and gliomas.

Choroid plexus epithelium (normal and neoplastic) expresses synaptophysin. A potentially useful aid in differentiating carcinoma of the choroid plexus from metastatic papillary carcinomas.

As an incidental finding in paraffin sections of brain tissue used as positive controls for synaptophysin immunostain, the cytoplasm of choroid plexus epithelium present was found to stain strongly positively for this substance. This was subsequently found to be the case in normal choroid plexuses in autopsy material from infancy to old age, as well as in epithelial cells of papillomas and carcinomas of the choroid plexus. The latter findings may prove useful in differentiating choroid plexus carcinomas from metastatic papillary carcinomas of extracerebral origin with the exception of neuroendocrine carcinomas of various sites that are usually positive for synaptophysin.

Meningioma with pseudoglandular pattern. A case report.

A falx meningioma in an 11-year-old girl had a hemangiopericytomatous and papillary pattern, but the dominant histologic feature was a pseudoglandular arrangement of the tumor cells, closely imitating an adenocarcinoma. The gland-like spaces resulted mainly from dissolution of the centers of cell nests, and to a lesser extent from the fusion of papillary processes. The tumor-recurred locally five years after surgery and maintained its pseudoglandular pattern. Recognition of the existence of a pseudoglandular variant of meningiomas can prevent the mistaken diagnosis of a metastatic adenocarcinoma and other similar tumors.

Penetration of neuronal perikarya by capillaries in chronic limbic encephalitis.

In a case of chronic limbic encephalitis in a 57-year-old man many neurons in the pyramidal cell layer of the hippocampus bilaterally were penetrated by ingrowing capillaries. All gradations from slight to moderate indentation of the cell membranes to complete incorporation of the capillaries in the neuronal perikarya were observed. The penetrating capillaries retained their basement membranes. Because of the chronic inflammation there was extensive fibrous gliosis in Ammon's horn. This apparently had an immobilizing effect on these neurons; it is postulated that proliferating capillaries of the active inflammatory process were unable to displace local neurons and instead grew against and through their perikarya.

Patterns of epithelial metaplasia in malignant gliomas. I. Papillary formations mimicking medulloepithelioma.

Adenoid-like formations resembling ducts and glands or forming a cribriform pattern have previously been described in malignant gliomas, resulting in some cases in a confusion with metastatic adenocarcinoma. The interpretation of these structures as being composed of anaplastic glial cells rests partly on the presence of transitions to more differentiated neoplastic astrocytes and partly on the positivity of some of these cells for glial fibrillary acidic protein. In this report two cases are presented in which the adenoid pattern was associated with papillary formations mimicking the arrangement of a medulloepithelioma. These structures represent a form of aberrant neoplastic differentiation in a malignant glioma rather than the expression of an embryonal neuroepithelial neoplasm.

Intracellular mucoid changes in tumor cells of meningiomas: a manifestation of polyvinylpyrrolidone (PVP) effect on tissues with mesenchymal characteristics.

In two cases of meningiomas in Taiwanese patients, extensive intracellular mucoid changes were found within tumor cells, together with deposits of polyvinylpyrrolidone (PVP) granules. Both patients had in the past received intravenous PVP as a plasma expander. Recipients of PVP have previously been reported to develop a form of PVP thesaurismosis with concomitant mucoid changes in the cells storing this substance. Such changes, as a rule, were limited to cells of mesenchymal origin. By storing PVP granules and undergoing mucoid changes as a result, meningioma tumor cells behave as cells with mesenchymal characteristics.

Patterns of epithelial metaplasia in malignant gliomas. II. Squamous differentiation of epithelial-like formations in gliosarcomas and glioblastomas.

Six cases are reported (four gliosarcomas and two glioblastomas) in which the epithelial-like areas of glial anaplasia showed focal squamous cell differentiation, characterized by the development of epithelial whorls, keratin pearls and immunopositivity for cytokeratin. The expression of glial fibrillary acidic protein and the development of squamous metaplasia usually were mutually exclusive. Autopsy findings in two patients and clinical work-up in five failed to disclose a primary extraneural malignancy. It is suggested that squamous differentiation may represent an extreme form of epithelial metaplasia in a malignant glioma. This possibility should be kept in mind in the diagnostic evaluation of such cases, especially in view of the current emphasis on the immunomorphologic demonstration of intermediate filament tumor markers.

Pleomorphic xanthoastrocytoma: the birth of a diagnosis and a concept.

This review deals with one of the newly adopted entities in the second edition of the histologic typing of CNS tumours by the World Health Organization: pleomorphic xanthoastrocytoma and reviews the clinical features, gross and microscopic characteristics as well as the common and some of the unusual variants of this tumor. The steps and events leading to the recognition of the basic character of this neoplasm and its designation as an independent entity are recollected and a few characteristic MRI scans and photomicrographs of pleomorphic xanthoastrocytomas are provided.

HIV-related neuromuscular syndrome simulating motor neuron disease.

A young homosexual man presented with slowly progressive weakness and diffuse fasciculations. Muscle biopsy was compatible with clinical diagnosis of motor neuron disease. The patient died from opportunistic infections related to acquired immunodeficiency syndrome. Autopsy revealed evidence of myelopathy, patchy fiber loss from anterior nerve roots, marked demyelination within intramuscular twigs of peripheral nerves, and primary myopathic features superimposed on advanced neurogenic atrophy of the skeletal muscles.

Progressive multifocal leukoencephalopathy with 10-year survival in a patient with nontropical sprue. Report of a case with unusual light and electron microscopic features.

A 46-year-old man with nontropical sprue had anemia and hypoproteinemia for several years, until his condition was diagnosed and treated with dietary measures. Within a year after the diagnosis, progressive multifocal leukoencephalopathy developed, and the patient had a slightly fluctuating chronic downhill course until he died 10 years later. It is postulated that this patient's immune deficiency was related to his malabsorption syndrome and hypoglobulinemia, and the course became unusually protracted (longest reported course in the American literature) because of restoration of plasma protein levels. Autopsy showed the classic findings of progressive multifocal leukoencephalopathy, with much tissue loss of subcortical white matter and active perivascular inflammatory foci with numerous eosinophilic granulocytes. On electron microscopy, oligodendrocyte nuclei and cytoplasm were crowded with virions, but many myelin sheaths invested by severely infected oligodendrocytic processes were remarkably well preserved. This fact would argue against a direct cause-and-effect relationship between infection of oligodendrocytes and myelin breakdown in progressive multifocal leukoencephalopathy. The likelihood of an autoimmune mechanism at work in this disease is suggested, and the role of eosinophils and other cells in such process is considered.

Supratentorial leptomeningeal hemangioblastoma.

A familial case of von Hippel-Lindau syndrome with a supratentorial leptomeningeal hemangioblastoma is reported. This is the first case in which the meningeal origin of a supratentorial hemangioblastoma has been histologically verified in von Hippel-Lindau syndrome.

Cockayne syndrome: an atypical case.

We report a case of Cockayne syndrome with several atypical features. The patient displayed many of the typical features, including cachectic bird-headed dwarfism, photodermatitis, normal pressure hydrocephalus, and extraphyramidal and pyramidal tract signs. However, she also displayed the unusual and previously unreported features of late age at onset, relative stability until age 19, and fertility, with a successful pregnancy. Brain biopsy showed hypomyelination, no active demyelination, and fibrillary gliosis.

Parkinsonism due to a basal ganglia lacunar state: clinicopathologic correlation.

We report a patient with a clinical syndrome indistinguishable from Parkinson's disease in which postmortem examination revealed extensive lacunar infarction of the basal ganglia without evidence of coexistent Parkinson's disease. This case provides pathologic confirmation of the concept of vascular parkinsonism.

Bilateral altitudinal anopia caused by infarction of the calcarine cortex.

The patient reported here had a bilateral inferior altitudinal hemianopia from lesions of the calcarine (striate) cortex of the occipital lobes. The only significant pathologic findings were bilateral calcarine artery occlusive disease, with infarcts of the striate cortex on both sides. The ages of the infarcts appeared compatible with the clinical development of the respective visual field defects. The rest of the visual system was anatomically intact.

Tissue artefacts caused by sponge in embedding cassettes.

Sponges in embedding cassettes may cause disruptive imprints on the tissues being processed and therefore should not be used in processing tissues. Tissue or lens paper is recommended as a substitute to prevent losing small pieces of tissue through the perforations of the cassette.

Visualization of injected embolic material (polyvinyl alcohol) in paraffin sections with Verhoeff-Van Gieson elastica stain.

Therapeutic embolization of blood vessels is widely used to treat vascular malformations and to preoperatively decrease the size of bulky tumors by creating iatrogenic infarction. Surgical pathologists are often called upon to identify the presence of embolized material in microscopic slides. Polyvinyl alcohol particles are often used as the material for embolization. On hematoxylin-eosin and other routine stains this substance is almost invisible. These particles stain black and can be sharply outlined by using the Verhoeff-Van Gieson stain.

Adrenal cortical adenoma in the spinal canal of an 8-year-old girl.

An ectopic adrenal cortical adenoma containing high levels of androstenedione but without clinically detectable virilizing effects was found in the spinal intradural space of an 8-year-old girl. The tumor, which was located at the L2 level, manifested itself clinically by a short history of bilateral leg pain. It was well encapsulated; therefore, total surgical removal was accomplished. The light microscopic appearance of the tumor was typical of adenomatous adrenal cortical tissue. Ultrastructurally, it also showed characteristic features of steroid-producing tumors, including very abundant smooth endoplasmic reticulum and giant mitochondria with tubulovesicular and circular cristae. Frozen tissue analyzed by radioimmunoassay was found to contain almost 20 times the normal tissue level of androstenedione. There was no elevation of cortisol or aldosterone levels in the tumor. Postoperative magnetic resonance imaging (MRI) scan of the retroperitoneum showed no abnormalities in the patient's adrenal glands. Serum androstenedione levels were normal. We postulate that the adenoma developed from congenital ectopic rests of intraspinal adrenal tissue. Although ectopic occurrence of adrenal cortical tissue has been recorded in other areas, neither such rests nor tumors developing from them have been previously reported within the spinal canal.

Rhabdoid transformation of tumor cells in meningiomas: a histologic indication of increased proliferative activity: report of four cases.

Four cases of meningeal tumors in adults (ages ranging from 28 to 84 years) are presented. All had the typical gross appearance of meningiomas at operation. In three tumors, areas of meningothelial or fibroblastic meningiomas showed transition to cell groups of the rhabdoid type. In the fourth case only rhabdoid cells were encountered, possibly representing a total "take-over" of a meningioma by rhabdoid elements. In the three cases with mixed pattern, the rhabdoid cells showed more anaplasia and atypism than the conventional meningiomatous elements. In case 3 this was expressed by very high MIB-1 positivity in the rhabdoid cells and absence of same in the fibroblastic meningiomatous elements. These cases (the first three with certainty, the fourth with a strong likelihood) indicate that the phenotypic changes to cells with "rhabdoid" morphology may involve meningiomas and that such change is associated with aggressive biologic and clinical behavior of the tumors showing this type of alteration.