Benign nerve sheath tumors: a light microscopic, electron microscopic and immunohistochemical study of 102 cases.

One hundred and two cases of benign nerve sheath tumors (NSTs) were studied with a combined approach using routine light microscopy (LM), immunohistochemistry (IH) for myelin basic protein (MBP) and S-100 protein as well as transmission electron microscopy (TEM) with the aim of obtaining greater insight into the true nature of these neoplasms, and also to establish the importance of IH and TEM in their diagnosis. Myelin basic protein was not identified in any of these tumors, whereas S-100 protein was positive to a variable degree in both schwannomas and neurofibromas. TEM revealed that Schwann cells predominated in tumors which were strongly positive for S-100 protein and appeared as schwannomas by LM. However, neurofibromas showing a variable patchy positivity for S-100 were composed of an admixture of Schwann cells, fibroblast-like cells and intermediate cells considered to be modified Schwann cells. Perineurial cells in typical form were not seen. It is concluded that all NSTs are basically of Schwann cell origin and that the intermediate cells and fibroblast-like cells are variants of Schwann cells. The different morphological appearances and biological behaviour of schwannomas and neurofibromas may be related to some other factors like micro-environment or genetic predisposition. Further, both IH, especially for S-100 protein, and TEM play an important role in establishing their diagnosis.     

Primary sarcoma of the heart: a light and electron microscopic study of two cases.

Two cases of primary malignant cardiac neoplasms are presented. The first, an angiosarcoma of the right atrium, developed in a 44-year-old housewife, who survived 23 days from the time of presentation; diagnosis was made at necropsy. The second, an embryonal rhabdomyosarcoma of the right ventricle, developed in a 17-year-old student; diagnosis was made by angiocardiography. He underwent surgery and cytotoxic and irradiation therapy and died 14 months later.     

Esthesioneuroblastoma: a light and electron microscopic study

The electron microscopic features of an olfactory esthesioneuroblastoma are described. The tumor cells had well developed neuritic processes containing neurotubules and neurofibrils. In addition, neurosecretory granules, similar to those seen in adrenal neuroblastomas, were present in the main cell body as well as in the neuritic processes. The neurites were also well demonstrated by light microscopic examination when stained by the Palmgren silver method. The importance of demonstration of these processes in establishing a firm diagnosis is stressed. Electron microscopic demonstration of neurites and secretory granules in a nasal tumor is diagnostic of an esthesioneuroblastoma.     

Micronodular adrenal disease: a light and electron microscopic study.

A case of Cushing's syndrome due to micronodular adrenal disease in a 17-year-old girl is presented. The adrenals showed both black and yellow nodules. Histologically the cells contained lipofuschin and either had a clear cytoplasm or an eosinophilic cytoplasm with a prominent nucleus. Lymphocytes were a prominent feature. No cells of the zona reticularis were identified. The cell of origin of these nodules appeared to be from the inner layer of the zona fasciculata. We postulate that the disease is caused by an abnormality in the migration and ultimate destruction of cells from the zona fasciculata to the zona reticularis with a build up of cells at the interface zone.     

Retroperitoneal leiomyosarcoma: a light and electron microscopic study

Retroperitoneal leiomyosarcoma arising in a spermatic blood vessel is described. In addition to typical leiomyosarcoma, areas of atypical histiocyte-like cells and storiform pattern bearing a close resemblance to malignant fibrous histiocytoma, were seen. Ultrastructurally, cells with features of smooth muscle, partially differentiated cells with marginal densities and basal lamina and histiocyte-like giant cells were present. Phagocytosis of inflammatory cells by tumour cells with marginal densities and an investment of basal lamina was observed. It is suggested that the precursor cell in this lesion was a primitive mesenchymal cell showing varying degrees of smooth muscle differentiation and giant cell formation.     

Estrogen-producing adrenocortical carcinoma. A light and electron microscopic study

A case of adrenocortical carcinoma with feminization seen in a man aged 35, is reported. The levels of estron (E1) and estradiol (E2) in the venous blood draining the tumor were high, and it was confirmed by in vitro assay of tumor cells taken from the primary tumor of the left adrenal gland that the tumor produced estrone. The light microscopic examination demonstrated that the primary tumor was composed of mixture of large cells with pleomorphic nuclei and vacuolated cytoplasm and uniform cells with ovoid nuclei and eosinophilic cytoplasm. The electron microscopic examination on the latter cells revealed numerous large and irregularly shaped mitochondria with mostly tubular or lamellar and occasionally vesicular cristae and electron-dense matrix, well-developed smooth-surfaced endoplasmic reticulum in the cytoplasm. However, lipid droplets and lysosomes or lipofuscin granules were scanty. From these findings, it is suggested that cells of the present tumor have characteristics of those in the zona reticularis of the adrenal cortex as well as in the fetal cortex, and the functional property of this tumor is well correlated with its morphological features.     

A light and electron microscopic study of mannosidosis

The present work investigated the light and electron microscopic changes in hypertrophied gingiva in a patient with mannosidosis. The biopsy specimens studied covered a period of 20 months; biopsy specimens were taken before and after a therapeutic trial with oral and local zinc sulfate. The intensity of the disease was progressive, in spite of the zinc, and was characterized by marked hyperplasia of the epithelium and severe inflammation of the stroma. Many of the cells in the inflammatory infiltrate, as well as cells indigenous to the gingiva, showed a striking vacuolation of their cytoplasm. Histiocytes were most numerous and also were most heavily vacuolated, but fibroblasts, endothelial cells, plasma cells, and epithelial cells also manifested the vacuolar change. In the histiocytes, the vacuoles occupied most of the cytoplasm, ranged widely in size, and were contiguous, molded, and intercommunicating. The vacuoles were bound by a single membrane and were filled predominantly by a finely granular material of medium density but also by varying amounts of coarser, darker granules, fragmented membranes, myelin-like figures, lipid droplets, and small vesicles. The vacuoles were interpreted as being consistent with secondary lysosomes that contained excessively stored substrate, similar to what has been observed in the mucopolysaccharidoses, in which the vacuoles have also been demonstrated histochemically and cytochemically to contain acid phosphatase, a known lysosomal marker.     

Scar adenocarcinoma of the lung: a light and electron microscopic study.

Five well differentiated peripheral adenocarcinomas of the lung were investigated, using light and electron microscopy. Each tumour contained a central nidus of fibrous tissue and fulfilled the criteria for "scar cancer." One tumour also had a focus of lamellated collagenous tissue, suggestive of an old tuberculous granuloma. Electron microscopy showed the features of Clara cells, with characteristic dense bodies in the apical cytoplasm and scattered microvilli on the luminal surface. It was concluded that this variant of scar cancer was a carcinoma of Clara cells, which was sufficiently distinctive in appearance to be recognised on light microscopy alone. It remains uncertain, however, whether the central fibrous area is a desmoplastic response to tumour growth or a pre-existing scar.     

Russell bodies: a light and electron microscopic immunoperoxidase study

Russell bodies have been previously regarded as aggregates of immunoglobulin. Light and electron microscopic immunoperoxidase studies show no detectable immunoglobulin determinants in the Russell body cores. Denaturation of antigens during tissue preparation appears to be an unlikely explanation, since immunoglobulins in the cytoplasm of plasma cells are clearly demonstrated. The presence of immunoglobulins on the surface of small intracellular Russell bodies may represent the immunoglobulin determinants in the surrounding rough endoplasmic reticulum. It seems likely that Russell bodies contain non-immunoglobulin molecules, by-products of immunoglobulin synthesis, or some altered form of immunoglobulins that no longer can be recognized by the anti-immunoglobulin antibody. The non-uniform dye staining pattern of Russell bodies further suggests that Russell bodies may be heterogenous in nature.     

Mesothelioma. Histological and electron microscopic study of human cases

Four cases of mesothelioma were studied histologically and electron microscopically. One of them showed a pure epithelial type of the peritoneal origin, characterised by a tremendous production of hyaluronic acid. The other three tumors originated from the pleura revealed a histology of biphasic type mesothelioma, which showed an admixed tubular and fibrous pattern and consisted of small-sized cells with slight atypia. However, in some places of these tumors they showed considerable atypical features appearing like an anaplastic or squamoid carcinoma and/or spindle cell sarcoma. Hyaluronic acid was histologically demonstrated in the cytoplasmic vacuoles as well as in the luminal space surrounded by the tumor cells. Electron microscopically, varied numbers of microvilli and desmosome-like attachments were found on the surface of the tumor cells. Mitochondria were small and round. Well-developed rERs tended to encircle mitochondria and to dilate forming cisternae. Various amounts of microfilaments were found in the cytoplasm. The tumor cells which were rich in the latter two components, dilated rERs and microfilaments, resembled fibroblasts. Some tumor cells had phagosomes including dense and fine granules similar to ferritin, suggesting their phagocytotic activity. The hyaline matrix, common to the biphasic type tumor which was largely composed of dense collagenous tissues, was demonstrated to contain hyaluronic acid by histochemistry, and it was suggested that some secretory substances of the tumor cell may participate in composing the hyaline matrix to some extent.     

Cytology of embryonal rhabdomyosarcoma: a cytologic, light microscopic, electron microscopic, and immunohistochemical study of seven cases

A correlated cytologic and histologic study of seven cases of embryonal rhabdomyosarcoma is presented. The diagnosis of rhabdomyosarcoma was established by light and electron microscopy and immunohistochemistry of the operative specimens. The cytologic appearance of the smears corresponded well with the histopathologic findings. Cytologically, two main cell types were distinguished: a predominant primitive, small round cell with scant cytoplasm and a large cell with an abundant cytoplasm, sometimes tadpole- or ribbon-shaped. The tumor cells were often enclosed in a background of mucosubstances. The lack of cytologic features proving rhabdomyoblastic differentiation, such as cross-striation, necessitates the use of additional methods in the cytologic diagnosis of embryonal rhabdomyosarcoma. The value of the embedding technique for ultrastructural analysis and immunohistochemistry in the demonstration of desmin in aspirates is emphasized in the diagnosis of embryonal rhabdomyosarcoma.     

Poorly differentiated synovial sarcoma. A light and electron microscopic study.

Few studies of the ultrastructural features of synovial sarcoma have appeared in the literature. The case under study represented a poorly differentiated synovial sarcoma with a predominant fibrosarcomatous component and a few areas with epithelioid and pseudoacinar patterns. Ultrastructurally, the cellular elements of the varied histologic patterns were similar. Basement membranes and desmosomes were absent, and the cell surfaces facing the acinar lumen exhibited multiple microvilli. It appears from a comparison of our studies with the previous reports that the fine structure of this tumor varies according to the degree of histologic differentiation.     

Recurrent diabetes mellitus in the pancreas iso- and allograft. A light and electron microscopic and immunohistochemical analysis of four cases

Four patients with type 1 diabetes mellitus received segmental pancreatic grafts. The donors were HLA-identical twins in three patients and an HLA-identical sibling in one. Each patient had normal glucose metabolism in the posttransplantation period but impaired graft function developed after 6 to 12 weeks. Complete loss of function developed in three patients. The fourth patient received immunosuppressive therapy but continues to require a low dose of insulin 15 months following transplantation. Pancreatic graft biopsy at the time of declining graft function in three patients revealed a mononuclear cell infiltrate centered upon islets consisting of variable numbers of T11 (pan T), OKT8 (suppressor-killer), OKT9 (transferrin receptor), OKT10 (activated), and HLA-DR-reactive mononuclear cells, as well as 63D3 and OKM1 reactive monocytes. Biopsies obtained following loss of graft function revealed resolution of the inflammatory process and selective destruction of all islet beta-cells in two patients, whereas graft biopsy in one patient demonstrated a mononuclear cell infiltrate in islets containing demonstrable beta-cells but no infiltrate in islets without beta-cells. Following immunosuppressive therapy the fourth patient showed resolution of the insulitis and destruction of beta-cells in 70% of the islets. The variable numbers of beta-cells observed in the remaining islets likely account for the relatively low amount of exogenous insulin required by this patient. There was no immunohistologic evidence of humoral mediated immune reaction in any of the biopsies. It is postulated that selective beta-cell destruction was a consequence of cell-mediated immunity leading to recurrent diabetes mellitus.     

Nephrogenic adenoma: a light and electron microscopic and immunohistochemical study

Nephrogenic adenoma is a relatively infrequent lesion that involves the bladder, the ureters, and the urethra. Even though several cases have been described since the early 1950s, the etiopathogenesis of the lesion is still uncertain. Electron microscopic and immunohistochemical studies seem to favor a congenital origin.