For Factor VIII-related Antigen Research Articles

Poorly differentiated angiosarcoma without vasoformative channels but with focal intracytoplastic vacuoles mimicking liposarcomas

Angiosarcoma (AS) showed diverse morphologies from well formed malignant vasculatures to poorly differentiated tumor with only a few clues of endothelial differentiation. Herein reported are two cases of AS without primitive vasoformative channels (VC). They showed, instead, a very few foci of intracytoplasmic vacuoles (ICV) that mimicked liposarcoma. The two cases were found in 12 cases of AS in computer database. Both are men, 57 and 68years. One is cutaneous (foot) AS and another is soft tissue (thigh) AS. The largest diameter of cutaneous AS was 5cm, and that of soft tissue AS 9cm. The prognosis of both patients was poor; both died of metastases 4 and 6years after initial presentation. In both cases, hematoxylin and eosin (HE) diagnosis was difficult because there were no VC, and most of the tumors were composed of primitive mesenchymal tissues. In both cases, however, a few very tiny foci consisting of ICV were seen. At first, the author considered them as mucins or fat, and suspected liposarcoma. In fact, they were pseudolipoblasts. Several mucin stains showed no mucins, and fat stains of frozen sections of formalin fixed tissue were negative for fat. Immunohistochemically, the vacuoles were positive for factor VIII-related antigen (F-VIII-RA), Ulex lectin, CD31, CD34, vimentin, p53 and Ki-67 (labeling index=64% and 75%), but negative for various types of cytokeratins (CK), EMA, CEA, CA19-9, CD45, smooth muscle actins, S100 protein, myoglobin, HMB-45, Melan A, NCAM, and NSE. F-VIII-RA is specific and Ulex lectin and CD31 are relatively specific for endothelium. Therefore, the pathological diagnosis of AS could be made by the combined histologic features (ICV) and Immunohistochemical positivity of F-VIII-RA, Ulex lectin, and CD31. Thus, it appeared that the ICV may be the only clue of poorly differentiated or undifferentiated AS. In such undifferentiated cases, combined observations of meticulous histologic observations (intracytoplasmic lumens and ICV) immunohistochemistry of F-VIII-RA, Ulex lectin, and CD31 may be helpful in the diagnosis of poorly differentiated and undifferentiated AS. Electron microscopic observations were not done in the present study.

Endothelial metaplasia of the alveolar capillaries in experimental silicosis of rats

We studied, by immunohistochemical and ultrastructural observations, the basic mechanism of interstitial fibrosis and endothelial metaplasia of alveolar capillaries in the lungs of Sprague-Dawley rats that received a single intratracheal infusion of silica particles. Immediately after silica administration, alveolar capillaries collapsed and their endothelial cells became necrotic over wide ranges. Alveolar myofibroblasts migrated into luminal silicaladen granulomas through defects in the alveolar linings. They proliferated and produced collagenous matrices that were incorporated into adjacent walls by coverage of regenerating epithelial cells. By day 4, endothelial cells of peribronchiolar small vessels had become positive for proliferating cell nuclear antigen. These endothelial cells apparently migrated along alveolar capillary tubes to replace injured endothelial cells through the processes of interdigitation of their cytoplasms. After one month, these alveolar endothelial cells, which were originally negative for factor VIII-related antigen (F-VIII) had become positive, especially in those segments in fibrotic scars. These endothelial cells developed numerous Weibel-Palade bodies containing F-VIII. Some endothelial cells formed specific ultrastructural fenestrations, which are unique to capillary endothelial cells that originated from bronchial arteries. The mechanism of endothelial metaplasia might consist of the following processes in endothelial cells that originated from broncho-pulmonary anastomoses: proliferation, migration, replacement, and differentiation of endothelial cells of bronchial arteries in the chronic fibrotic stages.

Differentiation markers in hemangiopericytoma.

Normal pericytes were found to express factor XIIIa (F-XIII) and histocompatibility antigen HLA-DR. These markers were studied in 15 hemangiopericytomas (HPC) and 16 other tumors with an HPC-like pattern. A subpopulation of tumor cells expressing F-XIII and HLA-DR antigens was a constant feature of HPC and supported their pericytic origin. Meningeal HPC did not differ in phenotype from peripheral soft tissue HPC. Most tumors with an HPC-like pattern (including synovial sarcomas, malignant schwannomas, leiomyosarcomas, and liposarcomas) were negative for F-XIII and HLA-DR. Malignant fibrous histiocytomas, however, invariably contained a subpopulation expressing these antigens. Therefore, F-XIII can be considered as a marker of fibrohistiocytic differentiation in HPC. Individual tumor cells in HPC occasionally were positive for factor VIII-related antigen (F-VIII-R-Ag), suggesting that the spectrum of differentiation in HPC may include the endothelial cell line. The differentiation characteristics of HPC support the concept that pericytes are primitive cells that may act as precursors to other mesenchymal cells.

QBEnd/10: A new immunostain for the routine diagnosis of Kaposi's sarcoma

Kaposi's sarcomas are seen more commonly in routine histopathology laboratories since the advent of the more widespread and aggressive variant of the disease associated with HIV infection. Distinguishing nodular lesions from other spindle cell and vascular tumours can sometimes be difficult. Immunohistochemistry has been disappointing as a diagnostic aid, often requiring special fixation or frozen tissue and even then, staining of spindle cells has been variable. We describe the use of the new IgG1 mouse monoclonal antibody raised against human placental endothelial cells, QBEnd/10, on routine formalin-fixed, paraffin-embedded tissue. A retrospective study was performed on 22 Kaposi's sarcomas of skin including patch, plaque, and nodular lesions and compared with 38 other vascular and spindle cell tumours from skin. All sections were stained with haematoxylin and eosin, QBEnd/10, Ulex europaeus agglutinin 1 (UEA-1) and for factor VIII-related antigen (FVIIIRAg). The results demonstrate that spindle cells in lesions from Kaposi's sarcomas, but not other vascular or spindle cell tumours, immunostain clearly with QBEnd/10. Immunostaining for FVIIIRAg shows only weak and irregular positivity of the spindle cells, whilst staining with UEA-1 is consistently negative. We find that immunostaining with QBEnd/10 aids the diagnosis of Kaposi's sarcomas and allows their distinction from other spindle cell neoplasms of skin in routinely processed material.

Vascular Adrenal Cysts

Three endothelial cysts and five hemorrhagic cysts (pseudocysts) arose in the adrenal glands of seven patients aged 23-73 years. Four patients were male and three were female. Five were symptomatic and gave abdominal pain as their chief complaint. Endothelial cysts were collapsed or filled with serous fluid, multiloculated, had an endothelial lining, and often contained adrenal cortex in their outer walls. The endothelial lining reacted only weakly for Factor VIII-related antigen (FVII-RAg), but it stained strongly for collagen type IV (C-IV). The lack of hemorrhage and the FVIII-RAg/C-IV staining pattern in endothelial cysts suggest lymphatic differentiation. Hemorrhagic cysts were spherical, firm masses containing clotted blood and hyalinized thrombus with attenuated adrenal cortex in the outer fibrous wall. Islands of intact cortical cells were present deep within the thrombi of four hemorrhagic cysts. Three of five hemorrhagic cysts stained strongly for FVIII-RAg and C-IV in irregular vascular channels of the attenuated cortex and within the cyst contents. These channels suggest that at least some hemorrhagic cysts arise when hemorrhage occurs in a preexisting blood vascular anomaly. Entrapment of cortical islands by extravasated blood in hemorrhagic cysts may be misdiagnosed as necrotic cortical neoplasm. To avoid confusion, one must recognize the normality of the entrapped cortical cells, identify an intrinsic vascular anomaly, and distinguish thrombus from necrotic tumor.

Cultured, AIDS-related Kaposi's sarcoma cells express endothelial cell markers and are weakly malignant in vitro.

Up to 30% of patients with acquired immunodeficiency syndrome (AIDS) suffer from Kaposi's sarcoma (AIDS-KS). The histogenesis and neoplastic nature of this tumor is still controversial. We have established cell cultures of KS biopsies from 7 patients with AIDS. All donors were seropositive for the human immunodeficiency virus I (HIV-I), cytomegalovirus (CMV) and hepatitis B virus (HBV). The tumors were histologically shown to be KS. Cell cultures derived from these tumors all expressed the endothelial cell marker BMA 120 antigen. Most of these cultures were positive for acetylated low-density lipoprotein (acLDL) uptake and alkaline phosphatase (AP) expression, and negative for factor-VIII-related antigen (FVIII-RAg). The staining pattern was heterogeneous with respect to number of endothelial cell markers expressed in each culture. We conclude from subcloning experiments that the cultured cells cease to express acLDL receptor and AP, but not the antigen detected by the monoclonal antibody (MAb) BMA 120. The cells grew well in culture up to 50 passages and showed a fibroblast-like morphology. Assays performed to investigate their degree of malignancy revealed a significantly increased passage number under reduced serum conditions as compared to normal fibroblasts but no tumor formation in nude mice. Neither HIV, HBV nor CMV sequences were found in any of the cell lines tested. We conclude that AIDS-KS is an endothelial-cell-derived neoplasm of low malignancy and that HIV, HBV and CMV are not directly involved in its genesis.

Adenomatoid Tumor of the Ovary: an Immunohistochemical and Ultrastructural Study

A rare case of adenomatoid tumor arising in the ovary is presented. At autopsy on a 61-year-old woman, a soft, solid and cystic tumor, measuring 0.8 X 0.7 cm, was detected in the hilus of the left ovary. Light microscopic study showed characteristic features of adenomatoid tumor. Alcian blue stain, with and without hyaluronidase pretreatment, revealed the presence of hyaluronic acid on the luminal surface and in the vacuoles of the tumor cells. Immunohistochemical stains of tumor cells were positive for low-molecular-weight cytokeratin (PKKL), vimentin, and carbohydrate antigen (CA) 125, whereas they were focally positive for high-molecular-weight cytokeratin (34 beta E12). They were negative for factor VIII-related antigen (FVIII-RAG), Ulex europaeus I lectin (UEA I), carcinoembryonic antigen (CEA) and epithelial membrane antigen (EMA). Ultrastructural studies disclosed surface microvilli and bundles of tonofilaments. These observations strongly support the idea of this tumor being of mesothelial origin.

Cardiac myxoma:Morphologic, histochemical, and tissue culture studies

Twenty-one cases of cardiac myxoma exhibiting a variety of histologic findings were investigated by light and electron microscopy, tissue culture, and immunohistochemical studies for factor VIII-related antigen (FVIII-RA) and Ulex europaeus 1 (UEA-1) lectin. The cardiac myxoma cells revealed variable cellular arrangements, and some tumor cells revealed vascular-like channels. Immunohistochemically, FVIII-RA was found only in the endothelial-like cells covering the vascular-like channels or slits, whereas UEA-1 lectin reacted not only with myxoma cells having luminal structures or network-like arrangements but also with single cells. On electron microscopy, some myxoma cells revealed differentiation into cells forming vascular structures. In tissue culture, the tumor cells were polygonal and proliferated with extensions of the cytoplasmic processes. Arrangements suggesting vascular channels or slits were not observed. In a coculture of tumor cells and blood clot, the tumor cells covered the surface of the clot. However, angiogenesis was not observed in the tissue culture study. The results of our studies were inconclusive regarding the histogenesis of cardiac myxomas, but it was considered that cardiac myxoma is a neoplasm arising from mesenchymal cells with vasoformative characteristics.

Continuous human glioma-derived cell lines UC-11MG and UC-302MG. Morphologic, immunocytochemical and chromosomal characterization.

Two continuous human glioma-derived cell lines, UC-11MG and UC-302MG were established in our laboratory. Both cell lines persistently showed cytologic features similar to those of their respective original tumors. UC-11MG expressed glial fibrillary acidic protein (GFAP) and S-100 protein. The cell lines were negative for factor VIII related antigen (FVIII/RAg) and positive for fibronectin and neuronal specific enolase (NSE). Electron microscopic studies of UC-11MG revealed intermediate filament; filopodia and pinocytic vesicles were present in both lines. Dibutyryl cAMP (dB-cAMP) caused inhibition of growth and marked shift in the morphology of UC-302MG toward spindle cells. The cytologic appearance of UC-11MG treated with dB-cAMP was altered less, but cells showed a stronger GFAP expression, with 'cable' formation. Doubling time was 41.0 +/- 6.4 hours for UC-11MG and 43.7 +/- 6.6 hours for UC-302MG. The karyotypes of both cell lines were aneuploid with chromosomal derangement and markers characteristic for each line.

The hemangioendothelioma of the thyroid.

65 cases of hemangioendothelioma (HE) of the thyroid were accepted as such after control of slides of surgical or autopsy specimen or both. In a few of the more recent cases material could be examined by electron microscope and in some the search for factor VIII-related antigen (FVIIIRAG) was carried out. The demonstration of Weibel-Palade bodies in tumour cells in two cases and the evidence of FVIIIRAG in tumour cells of at least two cases, including primary tumour and distant metastasis, finally show, that the hemangioendothelioma of the thyroid is not simply an anaplastic carcinoma with some peculiar features; at least some of these tumours are true endotheliomas. The proposal that the term hemangioendothelioma be eliminated from the classification of thyroid tumours is therefore unfounded.

Immunohistochemical identification of factor VIII-related antigen in endothelial cells of cutaneous lesions of alleged vascular nature.

Immunohistochemical staining for factor VIII-related antigen (FVIII-RAG) with the peroxidase-antiperoxidase technic was used as a marker for endothelial cells in a variety of nevoid, reactive, and malignant vascular cutaneous proliferations. The endothelial cells of small normal cutaneous vessels gave the strongest reaction. The cells of hemangioma and angiokeratoma generally were stained, but with less consistency. In lymphangioma, pyogenic granuloma, and pigmented purpuric dermatosis, positivity was either patchy or of lesser intensity. Numerous strongly positive endothelial cells lining well-formed blood vessels were present in lesions of Kaposi's sarcoma, but the proliferating spindle cells forming "vascular slits" were uniformly negative. The cells of angiosarcoma were essentially negative, except for isolated elements in the better-differentiated areas. Plasma was also strongly positive; this may aid in distinguishing vascular from lymphatic channels. Anti-FVIII-RAG immunoperoxidase staining is a helpful aid in evaluating cutaneous vascular proliferations.