Heterogeneity of polyoma tumors in hamsters: analysis of cytoskeletal proteins and viral gene expression.

Murine polyomavirus-induced hamster tumors revealed an unexpected heterogeneity with respect to patterns of cytoskeletal proteins expressed in different visceral and subcutaneous tumors and with respect to viral gene expression early during tumor outgrowth. All tumors analyzed expressed vimentin. Desmin was found in all heart tumors, to variable degrees in kidney tumors and in trace amounts only in 1 out of 4 s.c. tumors. The alpha-smooth-muscle actin isoform was observed in heart tumors only and was restricted to structures that we interpret as being proliferating pericytes or proliferating smooth-muscle cells of the media. In kidneys of infected newborn animals and before the appearance of macroscopic tumors, viral early mRNAs were transcribed from free viral genomes. In tumor tissue the size of the viral transcripts was altered, suggesting that they were transcribed from integrated viral DNA. Since in each tumor discrete bands of viral RNAs were detected, individual tumors arose presumably from single cells and one functional integration event. In contrast, in situ hybridizations of kidney tissue and tumors showed large quantitative differences in viral gene expression not only between different tumors but also between individual cells of the same tumor.

The diagnostic utility of desmin. A study of 584 cases and review of the literature.

The diagnostic utility of several antibodies against desmin and their optimal staining conditions have not been systematically evaluated. Sections of paraffin-embedded tissues from 584 cases were stained with a monoclonal antibody against desmin (Clone DER 11 from DAKO), using an avidin-biotin-peroxidase technique. The results were tabulated and compared with those from previous reports. The following observations were made: (1) When pronase digestion was performed before staining, desmin was equally demonstrable in tissues fixed in formalin, Zenker's, Bouin's, or B5 fixative; however, desmin staining was lost or significantly diminished in tissues fixed in absolute ethyl alcohol. In contrast, when pronase was not used, a positive staining was demonstrated only in tissue fixed in absolute ethyl alcohol. (2) Positive staining was found in normal muscle (92 of 92 cases), leiomyoma (12 of 13), rhabdomyoma (6 of 6), rhabdomyosarcoma (31 of 31), leiomyosarcoma (18 of 26). (3) Desmin was never found in epithelia, normal mesenchymal tissue other than muscle, tumors stimulating rhabdomyosarcoma, and epithelial tumors. (4) A positive staining was documented in 1 tumor (a fibrous histiocytoma) of 42 benign predominantly spindle cell tumors and in 8 of 89 predominantly spindle cell sarcomas. (5) Desmin was never documented in myoepithelial cells but stained myofibroblasts in 2 of 12 examples of granulation tissue and in 29 of 67 samples containing tumor-associated desmoplasia. The authors' data on the diagnostic sensitivity and specificity of the evaluated antibody should improve the use of desmin in diagnostic pathology.

Localized fibrous tumor of the serosal cavities. Immunohistochemical, electron-microscopic, and flow-cytometric DNA study.

Localized fibrous tumor of the serosal cavities (localized fibrous mesothelioma) is a generally benign spindle cell neoplasm of uncertain histogenesis. Fourteen histologically similar primary tumors from different mesothelium-lined sites (11 pleural and 1 each in the pericardium, peritoneal cavity, and pouch of Douglas) and 2 recurrences of those tumors (pericardium and pouch of Douglas) were examined histopathologically and by flow cytometry to relate histologic features and DNA ploidy to biologic behavior (follow-up, 48-255 months among 13 patients). All 16 tumors (14 primaries and 2 recurrences) displayed diploid DNA pattern, and none of 13 patients died of disease (1 patient was lost to follow-up). To elucidate the histogenesis, seven primary tumors were examined for vimentin and keratin immunostaining and six primary tumors were assessed by electron microscopy. All cases exhibited spindle-fibroblastic cell proliferation with a prominent hemangiopericytic pattern. All cases so examined had positive results for vimentin and negative results for keratin. Ultrastructurally, the tumor cells showed mesenchymal-fibroblastic features. These results support a mesenchymal origin, most likely from submesothelial fibroblasts. Further, this neoplasm may recur but retain its basic histologic features, diploidy, and benign outcome.

Malignant spindle cell tumor of the pericardium. Evidence of sarcomatous mesothelioma with aberrant antigen expression.

A case of malignant spindle cell tumor occurring in the pericardium is presented. The tumor arose from the pericardium of a 51-year-old Japanese woman with no history of exposure to asbestos. The tumor extended into the pericardial and left pleural cavities. The primary and metastatic tumors consisted of fusiform cells with frequent mitoses. Ultrastructurally, the tumor cells possessed a discontinuous external lamina, cytoplasmic processes, microfilaments and desmosomal intercellular junctions. Immunohistochemical examination showed that most tumor cells were positive for Leu 7, and several for S-100 and glial fibrillary acidic protein. Unexpectedly, most of the tumor cells also expressed keratin. These findings favor a diagnosis of sarcomatous mesothelioma with aberrant antigenic expression or heterogeneous differentiation of neoplastic cells.

Epithelioid leiomyosarcoma of the left atrium: immunohistochemical and ultrastructural findings.

Leiomyosarcomas of the heart are rare, with only 12 cases reported in the literature. An example of the epithelioid variant of leiomyosarcoma is described. The tumour cells expressed vimentin, desmin, muscle-specific actin and smooth muscle-specific actin. In addition, they were also labelled by monoclonal and polyclonal antibodies to cytokeratin intermediate filaments and displayed cell junctions at the ultrastructural level, features which highlight the potential pitfalls in the application of immunohistochemistry and electron microscopy in the diagnosis of poorly differentiated tumours.

Histogenesis of cardiac myxomas. An immunohistochemical study of 19 cases, including one with glandular structures, and review of the literature.

To elucidate the histogenesis of cardiac myxomas, the literature has been reviewed, including all previous immunohistochemical studies, and an extensive immunohistochemical study of 19 cardiac myxomas has been undertaken with antibodies to factor VIII, desmin, vimentin, myoglobin, cytokeratin (CAM 5.2 and AE1/AE3), and S100 protein. In all cases, vimentin stained endothelial as well as "myxoma" (stromal) cells. In contrast, factor VIII only stained endothelial cells. In 16 cases, desmin stained cells in the vascular structures; in 5 cases, desmin stained myxoma cells. In 6 cases, S100 protein stained the myxoma cells strongly. Myoglobin was absent in all cases. In 1 case, CAM 5.2 and AE1/AE3 stained glandular structures. The results indicate the following: that most cardiac myxomas are true neoplasms derived from "embryonal rests"; that the various mesenchymal cells found in cardiac myxomas (myxoma cells, endothelial cells, smooth-muscle cells, fibroblasts, myofibroblasts, and chondroid cells), express differentiation, not histogenesis; that, apparently, only the myxoma cells are neoplastic; and that the glandular structures infrequently found in cardiac myxomas originate from entrapped foregut rests.

Asbestos fibre content of lungs with mesotheliomas in Osaka, Japan: a preliminary report.

That crocidolite and amosite are both associated with the development of mesothelioma is now well established, but earlier studies have failed to find an excess of chrysotile in lungs with mesotheliomas as compared with the amounts in lungs of unaffected controls. In an attempt to clarify the importance of fibre type in tissue, an examination of a series of mesotheliomas is being undertaken in Osaka, Japan. A total of 23 mesotheliomas and 5 rejected cases reviewed by the Osaka Mesothelioma Panel were examined for the types of asbestos and semiquantitative fibre content by means of a transmission electron microscope equipped with energy-dispersive X-ray analyser. Asbestos fibres were detected in 19 of the 23 mesotheliomas (21 pleura, 1 pericardium, 1 peritoneum; 19 males, 4 females). Amphibole fibres were found in 13 cases. Five pleural and one peritoneal mesothelioma were found to have only chrysotile fibres. One female pleural mesothelioma with neighbourhood exposure had short chrysotile fibres. Among the 5 rejected cases, only one case with occupational exposure had both chrysotile and amosite fibres. A group of 17 controls were also examined and asbestos fibres were found in 5. Our data, while not definitive, suggest that mesotheliomas can be induced in humans, not only by crocidolite and amosite, but also by chrysotile, though possibly to a lesser extent.

Factor VIII-related antigen in canine endothelial neoplasms: an immunohistochemical study.

Canine vascular tumors (47 hemangiomas, 36 hemangiosarcomas) were investigated for the endothelial cell marker factor VIII-related antigen (F VIII RAg). The primary antibody was a commercial rabbit anti-human (r/h) F VIII RAg antiserum. All (100%) hemangiomas and 32 (89%) of 36 hemangiosarcomas stained for F VIII RAg. One hemangiosarcoma (3%) was negative, and three tumors (8%) were equivocal in staining. Rarely, the interpretation of stained immature endothelial cells was difficult. The r/h F VIII RAg antibody was a positive marker of normal, reactive, and neoplastic endothelial cells in the dog.

Cardiac rhabdomyoma. A case report with reference to atrial natriuretic peptide.

An autopsy case of cardiac rhabdomyoma in a male infant is reported. Many nodules of rhabdomyoma were present in all four cardiac chambers and were microscopically composed of ovoid, glycogen-laden cells and typical "spider cells". Atrial natriuretic peptide (ANP) was immunohistochemically demonstrated in both normal myocytes and rhabdomyoma cells of both atria, but not in normal myocytes and rhabdomyoma cells of both ventricles. Ultrastructurally, atrial specific granules were present in atrial rhabdomyoma cells and normal atrial cardiocytes, and these showed ANP immunoreactivity with protein A-gold technique. It could be said that the localization and intracellular distribution of ANP in this cardiac rhabdomyoma were closely similar to those of normal human heart. With regard to the presence of ANP, cardiac rhabdomyoma cells arising in atria seemed to differ from those in ventricles, although many tumor nodules occurred in both atria and ventricles. Furthermore, it seemed that cardiac rhabdomyomas could also be divided into two parts: 1) an atrial part with ANP, and 2) a ventricular part without ANP. Therefore, this study confirms the hypothesis that cardiac rhabdomyoma is a hamartoma rather than a true neoplasm.

Rat endomyocardial disease: a neural origin?

Of 58 cardiac lesions in rats from a Sprague-Dawley-derived strain, representing different stages of endomyocardial disease including 10 cases progressing to tumors, most stained positively for S-100 protein, while duplicate sections of selected cases also reacted positively for neuron-specific enolase. The results demonstrate the probable neural origin of these lesions.

Congenital polycystic tumor of the atrioventricular node (endodermal heterotopia, mesothelioma): a histogenetic appraisal with evidence for its endodermal origin.

The small, variously designated, primary atrioventricular node tumor has been considered to be of endothelial, endodermal, or mesothelial origin. To identify its derivation, we studied seven tumors using silver staining and immunocytochemical labeling with a variety of antibodies. Cytoplasmic argyrophil granules but not argentaffin granules were found in isolated cells among the more numerous tubule-lining cells in four tumors. Serotonin and calcitonin were demonstrable in seven and six tumors, respectively, in a similar distribution to that of the argyrophil cells. A positive reaction of different distribution from that of the argyrophil cells was noted in a varying number of tubule-lining cells for carcinoembryonic antigen, epithelial membrane antigen, and blood group antigen in seven, four, and seven tumors, respectively. No activity was noted in the tumor cells for factor VIII-related antigen or a number of peptides. An endodermal rather than mesothelial or epithelial origin for the tumor is substantiated by the presence of neuroendocrine cells in the midst of the more numerous carcinoembryonic-antigen-positive lining cells of the tumor tubules.

Angiosarcoma of the heart in an adolescent. A light and electron microscopic and immunohistochemical study.

A cardiac angiosarcoma occurred in the right atrium of a 15-year-old boy. Unusual features included the patient's young age and the antemortem pathologic diagnosis of the tumor.

Cardiac myxoma. A retrospective immunohistochemical study.

Seven cardiac myxomas were studied by immunoperoxidase and immunofluorescence in formalin fixed and paraffin embedded tissues. Specific antisera to factor VIII related antigens, vimentin, myosin of smooth muscle, actin, desmin, alpha-1-antitrypsin, muramidase, fibrin and prekeratin antigens were used. All myxoma cells reacted positively with antibodies to vimentin and showed no staining reaction with antibodies to alpha-1-antitrypsin, muramidase, myosin, or prekeratin. Factor VIII related antigen was found only in endothelial cells and not in myxoma cells proper. Fibrin was found in patchy areas within the stroma. Antisera to actin and desmin failed to react with formalin fixed tissue. Our results suggest that the main cellular component of cardiac myxoma is a primitive mesenchymal cell without immunohistochemical evidence of more specific differentiation.

Cardiac myxomas. An immunohistochemical study using endothelial, histiocytic, and smooth-muscle cell markers.

Previous immunohistochemical studies of cardiac myxomas are few in number, limited in scope and, in part, discrepant. We studied the immunoreactivity of five cardiac myxomas for factor VIII-related antigen, Ulex europaeus agglutinin I, smooth-muscle myosin, alpha 1-antitrypsin, and alpha 1-antichymotrypsin. Positive staining was present in all five tumors with each cell marker used, but varied according to the area of tumor examined. The result of this study provides further evidence of the cellular heterogeneity in these tumors that probably originate by differentiation of multipotential mesenchymal cells.

'So-called mesothelioma' of the atrioventricular node--immunohistochemical study.

So-called mesothelioma of the atrioventricular node is a rare lesion and a cause of sudden, unexpected death. A case of congenital complete heart block accompanied by polyclonal immunoblastosis is presented. The histological features of our case are fundamentally similar to that of the cases previously reported. Immunohistochemical findings indicated that the tumor may have originated from aberrant epithelial or mesothelial tissue.

Cardiac paragangliomas. A clinicopathologic and immunohistochemical study of four cases.

Cardiac paragangliomas are extremely rare neoplasms. Four surgically resected tumors were examined by immunohistochemistry and electron microscopy. The patients ranged in age from 18 to 36 years. All patients had hypertension and elevated urine catecholamine levels. Three tumors were located on the posterior left atrium, and one tumor was located in the interventricular groove at the aortic root. The tumors ranged in size from 5 to 7 cm, and they displayed a prominent Zellballen pattern without significant necrosis or mitosis. The tumors were mostly unencapsulated and infiltrated adjacent cardiac tissue in two cases. Immunoperoxidase staining showed that all tumors were positive for chromogranin and neuron-specific enolase. Three tumors were positive for methionine enkephalin. Positive staining for S-100 protein was seen in the sustentacular cells of all tumors but was negative in chromaffin cells. All tumors were negative for insulin, glucagon, gastrin, vasoactive intestinal polypeptide, somatostatin, adrenocorticotropic hormone, calcitonin, serotonin, pancreatic polypeptide, and rat atrial peptide. Ultrastructural studies of all four tumors showed moderate numbers of predominantly norepinephrine-type granules and a few epinephrine-type granules. These results show that cardiac paragangliomas are commonly found in close proximity to the left atrium and have immunohistochemical and ultrastructural features similar to other paragangliomas.

Vasoactive intestinal polypeptide in cardiac myxoma.

A case of left atrial myxoma is reported in which tumor tissue was found to contain high levels of vasoactive intestinal polypeptide. This finding further supports the concept that myxomas are true neoplasms and may explain some of the poorly understood clinical manifestations of this tumor.

Congenital endodermal heterotopia of the atrioventricular node: evidence for the endodermal origin of so-called mesotheliomas of the atrioventricular node.

A case of so-called mesothelioma of the atrioventricular node is presented. Controversy exists as to whether this lesion is of mesodermal or endodermal origin. The light and electron microscopic morphologic characteristics in this case were identical to those reported previously. The glandular component produced mucin that resisted digestion with both hyaluronidase and diastase; this staining pattern is characteristic of endodermal rather than of mesodermal tissue. Immunohistochemical methods demonstrated abundant carcinoembryonic antigen (CEA) in the cytoplasm of the cells composing the lesion. The presence of CEA strongly argues for an endodermal origin, since this antigen characterizes tissue derived from endoderm and is generally absent from mesoderm. The lesion probably represents endodermal foregut tissue that is displaced during embryogenesis. As such, it is not a true neoplasm. It is proposed that this lesion be designated "congenital endodermal heterotopia of the atrioventricular node."