Keizo Kageyama

Histogenesis of alveolar soft part sarcoma. An immunohistochemical and biochemical study.

In order to clarify the histogenesis of alveolar soft part sarcoma (ASPS), an immunohistochemical and biochemical study was performed on three cases. The immunohistochemical study indicated the presence of actin, desmin, vimentin, and Z-protein in all cases. On the other hand, intermediate filaments other than desmin and vimentin were not detected immunohistochemically. The presence of desmin and Z-protein strongly suggests the myogenic character of this tumor. As to whether ASPS shows striated muscle differentiation or smooth muscle differentiation, the immunohistochemical absence of myoglobin in the three cases suggests that the tumor does not differentiate in the direction of striated muscle. However, biochemical assay of subunits of enolase revealed significantly high amounts of beta-enolase, which is known as a marker for striated muscle, in all three cases. The determined values--735, 426, and 584 ng/mg of protein --are indicative of striated muscle differentiation. In addition, the immunohistochemical study of all cases revealed the presence of beta-enolase in tumor cells. These data definitely show the myogenic character and rhabdomyoblastic differentiation of ASPS.

Alveolar soft-part sarcoma. A review on its histogenesis and further studies based on electron microscopy, immunohistochemistry, and biochemistry.

To date, the histogenesis of alveolar soft part sarcoma has been considered to be of paraganglioma origin, striated muscle cell origin, or as a malignant granular cell myoblastoma, neural neoplasm, or renin-producing tumor. Further studies for these existing theories were performed based on various methods. The negative formaldehyde-induced fluorescence and the immunohistochemical absence of neuron-specific enolase were against the paraganglioma theory. The immunohistochemical absence of myelin proteins (P2 protein and P0 protein) and S-100 protein were against the malignant granular cell myoblastoma and neural neoplasm theory. Furthermore, there was a totally negative immunohistochemical finding for renin in the tumor cells, and the biochemical relationship of the tumor and renin was completely negated. The contradiction in a well-known report that the components of crystals were considered to be Z-band materials such as tropomyosin was referred to based on recent myological data. Concurrently, the absence of tropomyosin was immunohistochemically demonstrated. Hence, the issues on the histogenesis of alveolar soft part sarcoma and the identity of the characteristic crystalloids remain open for discussion.

Solitary (localized) pleural mesothelioma. A light- and electron-microscopic study.

ABSTRACTSix solitary (localized) pleural mesotheliomas were studied by light and electron microscopy. All the lesions were benign and were composed mainly of fibrous tissue of variable cellularity with or without cystic spaces lined by round cells. The lining cells of the cysts and the adjoining round plump cells were interpreted as true neoplastic cells of the fibroblast type. Results of light- and electron-microscopic study of human mesothelial cells and fetal mesothelial cells of rats were compared. The cytoplasmic organelles of the tumor cells were generally scanty, though rough endoplasmic reticulum, sparse mitochondria, intracellular bundles of fibrils, and numerous polysomes were seen. Some tumor cells had junctional apparatus and basement membranes and showed inter-digitation of the plasma membrane. These cells lined the cystic spaces irregularly and also proliferated into the surrounding fibrous tissue, where they assumed a spindle shape and resembled fibroblasts. Ultrastructurally, the tumor cells were similar to mesothelial and stromal cells of fetal rat pleura. We speculated that the solitary (localized) mesotheliomas were probably derived from coelomic epithelium and that tumor cells remained un-differentiated or revealed minimal differentiation toward mesothelial cells.

Peripheral lung carcinoid tumor producing predominantly gastrin‐releasing peptide (GRP) morphologic and hormonal studies

A carcinoid tumor of the peripheral lung producing gastrin‐releasing peptide (GRP), a peptide hormone known to be present in the endocrine cells of fetal bronchial epithelium, is reported. Brain‐gut peptide hormones in this tumor were assayed by radioimmunoassays, localized by immunohistochemistry and characterized by gel filtration. Electron microscopic study revealed that tumor cells resembled P‐cells of normal human fetal bronchial epithelium. While GRP‐containing cells were predominant in this tumor, calcitonin‐containing cells were also found in some areas. Difference in distribution of hormones according to histologic features was noted in the tumor. A greater portion of the tumor showed spindled cells that predominantly contained GRP, and a smaller portion of the tumor showed cells arranged in tubular or trabecular patterns that mainly contained calcitonin. The gel‐filtration pattern of the tumor extracts consisted of two peaks, one of these corresponded to the synthetic replicate of porcine GRP, and another was considered to correspond to C‐terminal fragments of the peptide. Cancer 52:273‐281, 1983.

Reactive mesothelial cell and mesothelioma of the pleura

The results of a light and electron microscopic study and enzyme histochemistry of reactive mesothelial cells and diffuse and localized (solitary) pleural mesotheliomas were compared, in order to establish a diagnosis and elucidate the cell of origin of the mesotheliomas. The reactive mesothelial cells were usually regular in appearance but could be cuboidal or columnar, or even peg-shaped with large nuclei and prominent nucleoli. Colloidal iron and alcian blue staining were positive in the plasma membrane, microvilli and in parts of the cytoplasm of mesothelial cells. These stains were mostly negative following testicular hyaluronidase treatment. The neoplastic cells of diffuse pleural mesothelioma had some epithelial characteristics such as microvilli, desmosomes, and a prominent basement membrane and were similar to reactive mesothelial cells with regard to cellular form and staining for acid mucopolysaccharides. In this study the colloidal iron and PAS stains appeared to be more intense in mesothelioma cells than in reactive mesothelial cells. In enzyme histochemistry, naphthol AS-D acetate esterase and α-naphthyl acetate esterase activity were demonstrated strongly in neoplastic cells. The nuclear-cytoplasmic ratio, the numbers of microvilli and mitochondria and the amount of glycogen were greater in the neoplastic cells when studied by electron microscopy. Electron lucent intracytoplasmic fibrils appeared wider and more distinct in mesothelioma cells. Localized mesotheliomas, thought to be an entirely different entity from reactive mesothelial cells, showed little characteristic morphology in light microscopic pictures, few cytoplasmic organelles were seen ultrastructurally.

Abnormal cilia in the bronchial mucosa

Atypical cilia in the bronchial mucosa of non-smoking women and in guinea-pig lungs were studied by the electron microscope. In human cases, numerous compound cilia were observed in the main bronchi. The largest one contained about 40 axial filament complexes in a ciliary shaft. Occasionally, atypical basal bodies were also seen. In the experimental model in guinea-pigs, 50% oxygen at one atmospheric pressure damaged the bronchial surface and resulted in degeneration and reduction of cilia and pellicular structures. The injury was not sufficiently severe to initiate adaptation and reparative mechanisms in the bronchial mucosa, and rapid renewal of the surface structures was found. The human cases were associated with bronchogenic carcinoma but the experimental model suggested that atypical cilia were not always related to pulmonary carcinogenesis.

THE DEVELOPMENT OF EXTRANODAL LYMPHOID FOLLICLES IN EXPERIMENTAL BRONCHOPNEUMONIA

Extranodal formation of lymphoid follicles was morphologically studied in experimental bronchopneumonia. Control gnotobiotic mice had no peribronchial lymphoid follicles and only lymphatic vessels were traced from the terminal bronchiolar region toward larger bronchi. During the week after intranasal inoculation of mycoplasma pulmonis, lymphoid follicles developed in the terminal portion of the lymphatics by the accumulation of small lymphocytes. A loose network of mesenchymal cells and early infiltration of macrophages, following stromal edema, seemed to play an important role in the early accumulation of lymphocytes. Blastic transformation was seen frequently in the center of the accumulated lymphocytes. Two weeks after inoculation plasma cells emerged conspicuously in the periphery of the lymphoid follicles, and the acute phase of bronchopneumonia began to subside. Typical germinal centers with tingible body macrophages and dendritic reticulum cells developed when the bronchitis perisisted in a chronical manner. ACTA PATH. JAP. 29: 533–543, 1979.

INFANTILE DIGITAL FIBROMATOSIS

Three cases of infantile digital fibromatosis were studied by electron microscopy and immunohistochemistry. The tumor was made up equally of myofibroblasts containing long narrow bundles of microfilaments with dense bodies. Another striking feature was the intracytoplasmic electron‐dense inclusion. The inclusions were constituted of packed fibrils similar to those of the long bundles. At the periphery of these inclusions were seen prominent felt‐like filamentous structures; the diameter varied from 5–12nm. The 10 nm filaments were seen most abundantly in the cytoplasm surrounding the inclusions, but sometimes they were also found within the inclusions themselves, mainly at their periphery. These findings suggest that the inclusions may represent an abnormal accumulation of cytoskeletal proteins. On the other hand, various kinds of Immunohistochemical study showed that actin, actomyosin, myosin, and vimentin were distinctly observed in cytoplasms of tumor cells. They were located fringing the intracytoplasmic inclusions, but the inclusion themselves showed negative findings, thus indicating a hollow‐like staining pattern. These data can be synthesized as follows. The inclusion results from an accumulation of cytoskeletal proteins (actin‐myosin complex and vimentin, at least), and antigeniclty seems to be lost by for a certain mechanism or in the degenerative process.

Glycosaminoglycans in malignant diffuse mesothelioma.

Because of frequently encountered diagnostic difficulty due to a morphologic similarity between diffuse pleural mesothelioma and peripheral pulmonary adenocarcinoma, glycosaminoglycans (GAG) of human malignant diffuse mesothelioma were histochemically stained and chemically quantitated, and were compared with GAG of papillary adenocarcinoma of the lung. In all seven patients, the diagnosis of diffuse mesothelioma was confirmed morphologically by such findings as abundant bushy microvilli on cell surface and intermediate filaments in cytoplasm. The total GAG in mesothelioma obtained from fresh materials (5 cases) was significantly increased over that in pleural connective tissue (P < 0.01) and lung adenocarcinoma (P < 0.02). Two dimensional electrophoretic separation of GAG of mesothelioma and lung cancer showed hyaluronic acid, heparan sulfate, heparin, dermatan sulfate and chondroitin sulfate; among them, the two predominant fractions were hyaluronic acid and chondroitin sulfate. In the quantitative analysis, the hyaluronic acid content of mesothelioma averaged 57% of the total GAG, but that of lung adenocarcinoma, 38%. The results suggest that chemical analysis of GAG may be useful as supplementary diagnostic procedure to morphologic examination in the differentiation of diffuse mesothelioma from papillary adenocarcinoma of the lung.

HISTOPATHOLOGICAL STUDIES ON THE TUMOURLET OF THE LUNG WITH SPECIAL REFERENCE TO THE CYTOGENESIS OF PROLIFERATING CELLS

Eight foci of tumourlets of the lung and one allied lesion obtained from autopsy cases were histologically examined. The tumourlet of the lung consisted of epithelial cells and was considered to be a benign lesion. Small sized‐lesion, uniformity of proliferating cells with very few mitosis and existence of associated lung lesions were documented as characteristic findings. However, the histopathogenesis of the tumourlet was not fully clarified.