Cutaneous epithelioid angiosarcoma.

Three cases of cutaneous epithelioid angiosarcoma with solid pattern were studied by immunohistochemistry and electron microscopy. The neoplasms followed a slow, protracted course with local recurrences and regional lymph node metastases. The correct histological diagnosis was delayed by the close histological simulation of carcinomas, misleading ultrastructural findings, and largely negative immunohistochemical markers. Two of the patients have been followed for at least 48 months and are still alive. Some seemingly undifferentiated epithelioid angiosarcomas may entail a better prognosis than originally suspected.

Cytokeratin expression in epithelioid vascular neoplasms.

Seven epithelioid and eight non-epithelioid vascular tumors were studied by the avidin-biotin-peroxidase method for the presence of endothelial- and epithelial-associated markers, using Ulex europaeus agglutinin-1 (UEA-1) lectin, and antibodies directed against factor VIII-related antigen, (FVIII-RA), vimentin, keratin, carcinoembryonic antigen, and epithelial membrane antigen. The cases included four epithelioid hemangiomas, two epithelioid hemangioendotheliomas (EHE), one epithelioid angiosarcoma (EAS), four common non-epithelioid capillary hemangiomas, and four non-epithelioid angiosarcomas. Staining for FVIII-RA, UEA-1, and vimentin were observed in all cases. The EAS showed staining for keratin in formalin-fixed, paraffin-embedded sections and in frozen sections. Staining for keratin was also observed in frozen sections of one EHE. Both keratin-positive vascular tumors were confirmed with electron microscopy. Carcinoembryonic antigen and epithelial membrane antigen stains were negative in all cases. Our results show that the epithelioid vascular tumors EHE and EAS, in addition to staining for the endothelial markers and vimentin, may also express the epithelial marker keratin. This is important since these tumors may closely resemble carcinomas by routine light microscopy. This study further underscores the importance of using a broad panel of immunohistochemical markers in the diagnostic workup of soft-tissue neoplasms.

Steroid hormone and epidermal growth factor receptors in meningiomas.

A prospective study of steroid hormone and epidermal growth factor receptor expression in 57 meningiomas is presented. Scatchard analysis of radioligand binding identified 20% of meningiomas as expressing classical oestrogen receptors (ER) at levels below that normally accepted for positivity, the remainder being negative. ER could not be visualized in any meningioma using immunocytochemistry. Alternatively, 74% of meningiomas demonstrated the presence of progesterone receptors (PR) by Scatchard analysis, the specificity of which could not be attributed to glucocorticoid or androgen receptors. Confirmation of classical PR presence was determined by immunocytochemical staining. The presence of epidermal growth factor receptor (EGFR) was demonstrated in 100% of meningiomas using immunocytochemical staining. These data are reviewed in the context of previously reported results and are discussed in relation to the potential for medical therapy as an adjunct to surgery.

[Paratesticular angiosarcoma. Immunohistochemical confirmation. Review of the literature]. / Angiosarcoma paratesticular. Confirmación inmunohistoquímica. Revisión de la literatura.

We report a case of paratesticular angiosarcoma. To our knowledge, no well-documented case involving this site has been reported in the literature. The anatomopathological features of the present case are described, highlighting immunohistochemical analysis. The outstanding clinical features of this aggressive tumor type are discussed.

Immunohistochemistry of capillary hemangioblastoma. Immunoperoxidase-labeled antibody staining resolves the differential diagnosis with metastatic renal cell carcinoma, but does not explain the histogenesis of the capillary hemangioblastoma.

We used a battery of antigens to determine whether immunohistochemistry can (a) contribute to resolving the histogenesis of the stromal component of the capillary hemangioblastoma, and (b) answer cases of difficult pathologic differential diagnosis with metastatic clear cell carcinoma. The stromal cells of the capillary hemangioblastoma are antigenically polymorphous and may express immunoreactive erythropoietin, renin, keratin, Leu M1, Leu 7, actin, neuron-specific enolase, S100 protein, and glial fibrillary acidic protein. However, the use of epithelial membrane antigen allows certain histopathologic distinction between capillary hemangioblastoma and metastatic clear cell carcinoma.

Endothelium and thrombomodulin: expression and distribution of thrombomodulin on altered endothelium and neoplastic syncytiotrophoblast.

We investigated the expression of thrombomodulin (TM) on endothelium in some pathologic states. We used the cultured endothelial cells treated with interleukin-1 (IL-1) and propagated cells by serial subculture for extended periods of time and assessed cell-surface TM molecules. We also studied the distribution of TM on surgical specimens of chorionic diseases, angiosarcoma and on several established cell lines of human choricarcinoma. Subculture of human umbilical vein endothelial cells (HUVE) up to 2 months (approximately 16 subcultures) decreased the number of cell-surface TM molecules by approximately 20% compared to the primary culture. The number of TM molecules also decreased on HUVE treated by IL-1. The treatment of the cells with IL-1 also induced change of shape. TM was found not only normal syncytiotrophoblast but also on neoplastic syncytiotrophoblast of choriocarcinoma and hydatidiform mole. However, TM was not expressed on the three established cell lines. TM was found on various types of vascular tumors, including angiosarcoma.

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.

Angiosarcoma of the thyroid: a light, electron microscopic and histoimmunological study.

A histologic, histoimmunological, and ultrastructural study of a primary angiosarcoma of the thyroid gland is reported. The occurrence of neoplastic cells positive for Factor VIII-related antigen and Ulex Europaeus Agglutinin-I and the presence in their cytoplasms of Weibel-Palade bodies are consistent with this diagnosis. These findings further support the view that primary angiosarcoma of the thyroid is a distinct pathological entity and should no longer be interpreted as a variant of a poorly differentiated carcinoma.

Haemangioblastoma. An immunohistochemical study of ten cases.

Ten cases of cerebellar haemangioblastoma were studied using the immunoperoxidase technique for glial fibrillary acidic protein (GFAP), Factor VIII-related antigen (F8RA), Ulex europeus agglutinin 1 (UEA-1), S-100 protein, neurone-specific enolase (NSE), leucocyte common antigen, synaptophysin, chromogranin and eight polypeptide hormones (bombesin, pancreatic polypeptide, somatostatin, thyroglobulin, calcitonin, glucagon, insulin and gastrin). GFAP and S-100 were demonstrated at the periphery of all tumours and in small groups of cells in the centre of four cases. Most of these cells had the morphology of reactive astrocytes but some had the appearance of stromal cells. In general stromal cells gave negative results. F8RA and UEA-1 stained the endothelial cells in each case but there was no stromal cell reactivity. NSE was present in the stromal cell component of all tumours. There was no staining for synaptophysin, for chromogranin, or any of the polypeptide hormones. It therefore appears that some haemangioblastomas contain an admixed non-neoplastic astrocytic element. NSE, F8RA and UEA-1 staining demonstrates that the endothelial and stromal cell parts of the tumour are antigenically distinct. Recent reports of polypeptide hormone expression cannot be confirmed and it is therefore unlikely that stromal cells originate from primitive peptidergic neurones.

Immunohistochemical characteristics of haemangiopericytic meningiomas: comparison with typical meningiomas, haemangioblastomas and haemangiopericytomas from extracranial sites.

The relationship between malignant vascular meningeal tumours and typical meningiomas remains controversial, despite the need for accurate diagnostic distinction between the two, and some forms of vascular meningioma may be more closely allied to haemangioblastomas or extracranial haemangiopericytomas than to true meningiomas. In order to try to clarify the diagnostic characteristics and origins of the entity known as haemangiopericytic meningioma, 10 histologically typical cases were stained by the immunoperoxidase technique with a panel of seven antibodies. The results were compared with those obtained from typical and angiomatous meningiomas, haemangioblastomas and haemangiopericytomas from extracranial sites. Both the haemangiopericytic meningiomas and the extracranial haemangiopericytomas showed a similar staining pattern, which differed from that of the typical and angiomatous meningiomas in the strikingly focal nature of the vimentin staining and the lack of reactivity with antibodies to epithelial elements. The haemangioblastomas were less consistent in their individual staining characteristics, but had a quite different overall pattern from all the other tumour types. It is, therefore, suggested that so-called haemangiopericytic meningiomas are in fact primary haemangiopericytomas of the meninges, antigenically distinct from true meningiomas and displaying a malignant potential appropriate to haemangiopericytomas arising in any other sites.

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.

Erythropoietin in capillary hemangioblastoma. An immunohistochemical study.

Capillary hemangioblastoma is a tumor known to be associated with secondary polycythemia. Therefore, specimens from ten hemangioblastomas were studied by immunohistochemistry for the presence of erythropoietin, renin substrate, and for various endothelial, histiocytic and glial markers. In all tumors scattered cells among the stromal cells showed a positive-staining reaction with both anti-erythropoietin and anti-renin substrate. The same cells also stained positively for alpha-1-anti-trypsin. It is concluded that, in addition to the capillary endothelial cells, pericytes and stromal cells, capillary hemangioblastomas harbor cells containing and perhaps producing renin substrate and/or erythropoietin or a substance with similar antigenic determinants.

Selective localization of gamma-enolase in stromal cells of cerebellar hemangioblastomas.

Three cases of cerebellar hemangioblastoma were studied using the immunoperoxidase technique to localize gamma-enolase, also known as neuron-specific enolase. The stromal cells demonstrated positive staining for gamma-enolase, while endothelial cells and pericytes showed no reactivity. Two vascular lesions, an angiosarcoma and a cutaneous angioma, were studied and found to be nonreactive for gamma-enolase. All tumors were also tested for factor VIII/von Willebrand factor, glial fibrillary acidic protein, and the S-100 protein. The lack of expression of gamma-enolase in endothelial cells of hemangioblastomas demonstrates a clear antigenic distinction from neighboring gamma-enolase-positive stromal cells. The significance of this finding and its implications for stromal cell histogenesis are discussed.

Erythropoietin in haemangioblastoma: immunohistochemical and electron microscopy studies.

Immunohistochemical studies for erythropoietin were carried out in six capillary haemangioblastomas, three of which were also studied by electron microscopy. The immunohistochemical studies showed that positively stained cells were scattered in the vicinity of capillaries, and that neither endothelial cells nor stromal cells were stained. In their morphology and distribution, the positively stained cells were identical to mast cells as observed by electron microscopy. In one case, erythropoietin was demonstrated in the cyst fluid of the tumour. These findings suggest that mast cells with abundant secreting granules in haemangioblastomas are capable of producing erythropoietin.

Capillary hemangioblastoma. An immunohistochemical study.

Previous studies using immunohistochemical methods to determine the presence of glial fibrillary acidic protein (GFAP) and Factor VIII-related antigen (FVIIIR:Ag) in stromal cells of capillary hemangioblastomas have yielded conflicting results with respect to the possible astrocytic and endothelial origins of these cells. This study included Ulex europaeus I lectin (UEAI), a more sensitive marker of endothelial cells. Antibodies were also used as markers of pericytes and a variety of markers were employed to identify different populations of histiocytes. Results of this investigation indicate that FVIIIR:Ag and UEAI are limited only to endothelial cells, and that GFAP is present in entrapped astrocytes only. Positivity of stromal cells was found with some of the histiocytic markers, but the authors were unable to conclude that these cells have a histiocytic origin. It was concluded that currently there is no evidence that stromal cells are derived from endothelial, pericytic, or astrocytic cells-their origin remains uncertain.

Autocrine tumour growth regulation by somatomedin C: an in-vitro model.

A human primary haemangiosarcoma was derived from a patient with severe hypoglycaemia. Cell line established from that tumour secreted somatomedin C in serum-free culture media. Immunoreactive somatomedin from the media eluted from Sephacryl S-200 in two peaks of 160 000 and 8000 molecular weights. Similar results were obtained when medium was acidified and chromatographed on Sephadex G-50. Binding of tracer concentrations of 125I-labelled somatomedin C to human haemangiosarcoma cells was much higher than that of 125I-labelled insulin. Half-maximal displacement of 125I-labelled somatomedin C binding occurred at an unlabelled somatomedin C concentration of 0.7 nmol/l. Insulin competed with 125I-labelled somatomedin for binding to this receptor, but 150-fold more insulin was required for half-maximal displacement. Somatomedin secreted by human haemangiosarcoma cells and purified from serum-free media strongly stimulated [methyl-3H]thymidine incorporation into the DNA of these cells. Inhibition of somatomedin C secretion by cortisol resulted in the inhibition of tumour cell proliferation but stimulation of somatomedin secretion by human GH stimulated the cell proliferation rate. It appears that production of somatomedin C in human haemangiosarcoma cells plays a part in the regulation of tumour growth by an autocrine mechanism.