Angiosarcoma of the heart: structural and ultrastructural study.

BACKGROUND: Primary cardiac tumours are rare. Nearly 70% of primary cardiac tumours are benign, the majority of which are represented by myxomas. The most frequent primary cardiac neoplasm is the angiosarcoma that represents 31% of primary cardiac malignant. We report a particular clinical case of cardiac angiosarcoma, its light and transmission electron microscopic aspects and a review of the recent literature. METHODS: A 52 years old man died for a severe right ventricle filling deficit caused by an intracavitary tumour originated from the right atrial anterolateral wall. The fragments obtained from autoptic tumoral cardiac tissue were processed for light and electron microscopy. The section were stained with haematoxilineosin, Masson trichromic and Gomori method. An immunohistochemical study for vimentin, Factor VIII related antigen and peroxidase-conjugated lectin from Ulex Europaeus was also performed using the unlabed peroxidase-antiperoxidase method. RESULTS: The hematoxylin-eosin staining showed that the tumoral mass was composed by a well-differentiated histotype characterized by numerous vascular areas in which neoplastic cells were loosely and irregularly arranged to form incomplete vessels or anastomized blood-filled vascular channels. On the other hand, some less-differentiated solid areas were present and irregularly surrounded the differentiated vascular areas. Results of Ulex Europeaeus Agglutinin I labelling were positive in both solid and vascular areas of the tumour although the positive reaction was less evident in the solid zones Factor VIII related antigen positive cells were less numerous and mainly found in vascular areas. The observation by electron microscopy showed the lack of evident pinocytotic vesicles, the presence of thin and delicate cytoplasmatic processes, Weibel-Palade bodies, and also the disarrangement of the extracellular fibrous matrix. CONCLUSION: The light microscopy observation and immunohistochemical study underscore that is not easy to obtain information about the level of differentiation of this tumour. The presence of blood-filled lumina and the identification of typical markers of endothelial cells seems to indicate a well-differentiated nature. However, the ultrastructural findings seem to indicate a less differentiated nature.

Postirradiation epithelioid angiosarcoma of the breast: a case report with immunohistochemical and electron microscopic study.

A case of postirradiation epithelioid angiosarcoma of the breast in a 72-year-old woman is reported. She had had right breast conserving surgery, axillary lymph node dissection, and 50 Gy external beam radiation therapy for infiltrating ductal carcinoma. A skin lesion on the irradiated breast appeared 5 years after completion of radiation. Angiosarcoma was diagnosed in a contralateral axillary mass 8 months later. Light microscopically, the tumor was characterized by a sheet-like growth of epithelioid cells with focal vasoformative areas. Tumor cells were reactive for factor VIII-related antigen, cytokeratin and CD34. Electron microscopically, the tumor cells were round with smooth cell borders. They were closely apposed, occasionally forming a small lumen containing single red blood cells or aggregates of platelets. Groups of tumor cells were enclosed by an external lamina. The tumor cells had abundant cytoplasm with sparse organelles. Rare suggestive Weibel-Palade bodies were present. The immunohistochemical and ultrastructural findings in this postirradiation tumor were in agreement with previously reported findings in non-irradiation-induced epithelioid angiosarcomas.

Occurrence and comparison of the expressed keratins in cultured human fibroblasts, endothelial cells and their sarcomas.

We investigated keratin (K) expression in cultured fibroblasts, endothelial cells and their sarcomas by using two-dimensional gel electrophoresis and electron microscopy techniques. Although the fibroblast and endothelial cell lines were derived from mesenchyme, we confirmed Ks in both cell lines. The K in two cultured cell lines consisted of K14 and K16, together with vimentin. In addition to the above Ks, K5 and K8/K17 were comprised in each cell line, respectively. On the other hand, the cultured fibrosarcomas contained K8 and K18 in addition to the Ks present in the cultured fibroblasts, except K17. Moreover, cultured angiosarcomas showed the same Ks expression as those of the cultured fibrosarcomas, except vimentin. However, electron microscopy showed that the extremely thin fiber-like substances existed or at least did not form filamentous structures in four cultured cell types.

Spindle cell angiosarcoma following irradiation therapy for cervical carcinoma.

BACKGROUND: Angiosarcomas arise in the scalp and face in the elderly, in association with chronic lymphedema (Stewart-Treves syndrome), and in irradiated areas. Rarely in these settings, angiosarcomas exhibit pure spindle cell phenotype. METHODS: Herein, the clinicopathologic features of a 72-year-old-woman with spindle cell angiosarcoma are described. RESULTS: A 72-year-old woman presented with numerous nodules and diffuse induration from the lower abdomen to the right buttock, corresponding to the area exposed to 60Co-irradiation during treatment for cervical carcinoma 10 years earlier. Histopathological examination revealed inflitrative, atypical, spindle cells that labeled with antibodies to CD31, CD34, and factor VIII-related antigen. Ultrastructurally, these malignant spindle cells contained Weibel-Palade bodies. No features suggesting radiation dermatitis (sclerosis or bizarre, large fibroblasts) were identified, but lymphangiectases and widely spaced collagen bundles(lymphedema) were prominent in the skin surrounding the angiosarcoma. Computed tomographic scan of the abdomen highlighted this histologic finding by demonstrating tumor masses limited to areas of lymphedema. Treatment with intravenous and local injections of recombinant interleukin 2 (rIL 2) followed by electron beam irradiation were initially effective with tumor remission for 2 months. However, the recurrent tumor did not respond to a second course of one-shot injection of rIL 2 through the abdominal aorta and the patient succumbed to her angiosarcoma 19 months after diagnosis. CONCLUSIONS: Radiation-induced lymphedema may be a factor in angiosarcoma associated with radiotherapy.

Cytologic findings of epithelioid angiosarcoma of the thyroid. A case report.

BACKGROUND: Angiosarcoma of the thyroid is a rare and aggressive tumor and occurs mainly in patients from central Europe, especially the alpine region. The fine needle aspiration findings of a keratin-positive epithelioid angiosarcoma of the thyroid occurring in a nonmountainous area in South America is described. CASE: A 65-year-old male from São Paulo, Brazil, presented with a mass in the anterior part of the neck with progressive enlargement for three months. The cytologic findings on the fine needle aspirate were a cellular smear composed of single cells and small clusters of neoplastic cells, oval and round. Cell borders were indistinct, and the cytoplasm was vacuolated. The nuclei were eccentrically located, with irregular nuclear membranes; single, prominent nucleoli; and a coarse chromatin pattern. Features suggestive of intracytoplasmic lumens were identified. Open surgical biopsy demonstrated a tumor infiltrating the thyroid gland and composed of large, round, atypical epithelioid cells lining vascular spaces. These neoplastic cells were immunoreactive for AE1:AE3, CK7, vimentin, CD31 and factor VIII. CONCLUSION: Epithelioid angiosarcoma should be considered in the differential diagnosis of epithelioid neoplasms of the thyroid. An immunohistochemical panel should include vascular markers even in the presence of immunoreactivity for epithelial markers.

Ultrastructure of oral sarcoma.

Sarcoma of the oral region is extremely rare and ultrastructural studies of the tumor are limited in number. We collected oral sarcomas, such as fibrosarcoma, malignant fibrous histiocytoma, liposarcoma, leiomyosarcoma, rhabdomyosarcoma, angiosarcoma, alveolar soft-part sarcoma, solitary plasmacytoma, and osteosarcoma, and performed ultrastructural studies of these tumors. The value of these studies for an understanding of the biological behavior of the tumors was then investigated. In these studies, electron microscopic examinations of oral sarcoma were of assistance in our attempt to establish correct diagnosis and histogenesis. Data from the studies of oral sarcoma by light microscopy, electron microscopy, and immunohistochemistry should be accumulated.

Primary epithelioid angiosarcoma of the adrenal gland case report and review of the literature.

Primary angiosarcoma of the adrenal gland is extremely rare. Here, we report on a 70-year-old man with an angiosarcoma of the right adrenal gland who died 3 weeks after tumor resection due to intestinal infarction and acute renal failure. No metastases were found at autopsy. Histologically, the tumor showed a predominantly epithelioid differentiation. Immunohistochemical examination revealed positive reactivity for cytokeratin, epithelial membrane antigen, vimentin, factor VIII-related antigen, CD31, CD34 and Ulex europaeus agglutinin-I. Features of endothelial origin were also demonstrable by electron microscopy. The differential diagnosis of this uncommon neoplasm is discussed. The present case emphasizes problems in differential diagnosis that arise from its epithelioid differentiation. A review of the literature underlines the poor clinical outcome of adrenal angiosarcoma.

Pseudoangiomatous hyperplasia of mammary stroma: a case of pure type after removal of fibroadenoma.

A case of pure pseudoangiomatous hyperplasia of the mammary stroma after removal of a fibroadenoma is described. The lesion, which was found in the right breast of a 40-year-old woman, was a well-circumscribed non-encapsulated, rubbery, lobulated mass measuring 40x40x35 mm. Histologically, it consisted predominantly of a proliferation of spindle cells with interanastomosing vascular-like arrangements in the interlobular or interductal stroma. Neither cytological atypia nor mitotic figures were observed. The stroma contained abundant collagen with focal hyalinization. Focally, epithelial elements showed mild ductal hyperplasia. There was no fibroadenoma. Immunohistochemically, the spindle cells were positive for vimentin, CD34, alpha-smooth muscle actin, muscle actin, CD34, calponin, and progesterone receptors. Ultrastructurally, many spindle cells had thin elongated cytoplasmic processes, which enveloped pseudovascular spaces containing a few collagenous fibrils, indicating fibroblastic cells. This lesion should be distinguished from other mammary fibrous and vascular lesions with which it may be confused.

Primary composite angiogenic leiomyosarcoma-epithelioid angiosarcoma of the brain.

The authors describe a primary sarcoma of the brain with immunohistochemical and ultrastructural features of leiomyosarcoma as well as epithelioid hemangiosarcoma. The leiomyosarcomatous component consisted of spindle cells with well-developed external lamina, subsarcolemmal densities composed of microfilaments, pinocytic vesicles, and abundant intermediate filaments, and showed immunohistochemical reactions for smooth muscle actin. The epithelioid part of the tumor contained scattered cells reactive for alkaline phosphatase as well as CD31 and factor VIII. Many epithelioid cells were lipidized and remarkably similar to "stromal cells" of a hemangioblastoma. Occasional Weibel-Palade bodies, indicating endothelial differentiation, were present in scattered neoplastic cells. There were also cells with features intermediate between endothelium, pericytes and smooth muscle cells, and undifferentiated mesenchymal cells. The brain at the periphery of sarcoma showed conglomerates of well-differentiated capillaries, telangiectasias and small dysplastic arteries, features that raise the possibility of origin of this tumor from a preexisting vascular developmental abnormality.

Case report: spontaneous hemangiosarcoma in the pancreas of a Fischer rat.

Spontaneous hemangioma or hemangiosarcoma is sometimes found in the viscera and soft tissue of rats and mice. However, there is no report of the tumor occurring in the pancreas of rats. We report a pancreatic hemangiosarcoma in a 109-wk-old, male Fischer 344 rat, which was used in the control group of a carcinogenicity study. The tumor destroyed and compressed the normal pancreatic tissue and displayed a high density in terms of the numerous capillaries and strands of endothelial tumor cells. A reticulin stain revealed a dense network formation. The frequency of proliferating cell nuclear antigen-positive staining showed active proliferation of the tumor cells. Immunohistochemically, some of the tumor cells stained positive with factor VIII-related antigen, and ultrastructurally, Weibel-Palade bodies were rarely observed in the cytoplasm of the tumor cell. From these findings, the tumor was diagnosed as a hemangiosarcoma that occurred naturally in the pancreas.

Cytomorphologic features of angiosarcoma on fine needle aspiration biopsy.

OBJECTIVE: To present the cytomorphologic features of angiosarcomas identified on fine needle aspiration biopsy, review the literature, and discuss the differential diagnosis and pitfalls involved in such cases. STUDY DESIGN: Fine needle aspirate smears from 11 cases (1 hepatic, 3 breast and 7 subcutaneous/soft tissue lesions of angiosarcomas from eight patients were reviewed. All cases had histologic confirmation of angiosarcoma. RESULTS: All aspirates were hypocellular, with predominantly single cells in a background of moderate to abundant amounts of blood. Nine cases had scattered inflammatory cells, primarily neutrophils, in the background. Six of the cases had rare small clusters of cells. The cells were oval, round or spindled, with eccentric, round to spindle-shaped nuclei and moderate to abundant amounts of pale blue-gray, vacuolated cytoplasm. The cells ranged from two to nine times the size of the background red blood cells. In four cases, malignant cells demonstrated intracytoplasmic hemosiderin deposits. Small nucleoli were identified in five cases, large nucleoli in one case and hyperchromasia in seven cases. Mitotic figures, erythrophagocytosis, acinarlike or vascular structures, and necrosis were not identified in any of the studied cases. In four cases, a definitive diagnosis of angiosarcoma was rendered on the fine needle aspiration specimen. In three other cases, the differential diagnosis remained between angiosarcoma and radiation change. CONCLUSION: The presence of scarce single pleomorphic cells in a bloody background should raise the diagnostic possibility of angiosarcoma. A definitive diagnosis of angiosarcoma is often difficult to render due to the paucity of diagnostic cells unless intracytoplasmic hemosiderin deposits can be identified. Multiple aspirations are often needed in order to obtain diagnostic material. In the setting of radiotherapy, it may be impossible to distinguish angiosarcoma from radiation change, and biopsy should be recommended.

Cutaneous malignant epithelioid neoplasms.

In summary, cutaneous malignancies with an epithelioid appearance form a diverse group of neoplasms that may be difficult to diagnose by utilizing routine microscopy alone. Cutaneous malignancies, including malignant melanoma and metastatic carcinoma, certain benign neoplasms such as mixed tumor of the skin and angiolymphoid hyperplasia with eosinophils (epithelioid hemangioma), and infectious conditions such as bacillary (epithelioid) angiomatosis can be considered in this differential. However, through recognition of the characteristic histologic, immunocytochemical, and ultrastructural findings outlined above, definitive diagnosis of these challenging neoplasms is usually possible.

Primary renal angiosarcoma: a case report with immunohistochemical, ultrastructural, and cytogenetic features and review of the literature.

Primary angiosarcoma of the kidney is a rare tumor for which fewer than 10 case reports appear in the English literature. A case of primary renal angiosarcoma is reported, in which the tumor showed poorly differentiated spindled sarcoma admixed with typical angiomatous differentiation. Antibodies against CD31, CD34, Ulex europeus lectin type I, factor VIII-related antigen, cytokeratin (AE1/AE3), vimentin, S100 protein, epithelial membrane antigen, carcinoembryonic antigen, desmin, and smooth muscle actin were examined. CD31 showed strong diffuse membranous staining of cells in the well-differentiated areas and strong membranous staining in the spindled, poorly differentiated areas. CD34 showed strong cytoplasmic and membranous staining in both the poorly differentiated and well-differentiated areas. Staining for factor VIII-related antigen and Ulex europeus was less intense and was limited to the well-differentiated areas. Staining for cytokeratin (AE1-AE3), S100, carcinoembryonic antigen, epithelial membrane antigen, desmin, and smooth muscle actin were negative. Electron microscopy showed spindle cells containing abundant pinocytotic vesicles, vimentin-type intermediate filaments, and rare Weibel-Palade bodies. A complex karyotype was found. Our findings suggest that CD31 and CD34 are useful in defining endothelial differentiation in poorly differentiated angiosarcomas in which reactions for Ulex europeus lectin type I and factor VIII-related antigen may be equivocal.

Angiosarcoma of soft tissue: a study of 80 cases.

The clinicopathologic, immunohistochemical, and ultrastructural features of soft tissue angiosarcomas are not well defined. Eighty cases of angiosarcoma that involved the deep subcutis, skeletal muscle, retroperitoneum, mesentery, and mediastinum are reported. The lesions occurred in 50 male and 30 female patients who were 5-97 years of age; the peak incidence was in the seventh decade of life. A variety of associated conditions were documented in 20 of these cases, including a history of other neoplasms (some irradiated), synthetic vessel grafts, heritable conditions, and prior trauma or surgery. The angiosarcomas occurred in the extremities (n = 43 cases), trunk (n = 28), and the head and neck (n = 9) regions, with the thigh and the retroperitoneum being the most common sites. They often were characterized as enlarging, painful masses of several weeks' duration and were occasionally associated with acute hemorrhage, anemia, or a coagulopathy. The tumors measured 1-15 cm in diameter (median 5 cm) and frequently were hemorrhagic and multinodular. There was a wide morphologic spectrum within and between cases, including areas similar to cavernous and capillary hemangioma, Dabska tumor, spindle cell and epithelioid hemangioendothelioma, various spindle cell sarcomas, or carcinoma. Histologically, epithelioid angiosarcoma was the most frequently observed pattern; 70% of cases had epithelioid cells that were arranged in nests, clusters, papillae, and gaping vascular channels. Hemorrhage tended to obscure the diagnosis in several cases and often was associated with papillary endothelial hyperplasia-like areas. All 42 cases studied immunohistochemically stained at least focally for Factor VIII-related antigen, and nearly all stained strongly for vimentin, which accentuated the endothelial cells and vessel lumen formation. CD34 antigen was detected in 74% of cases, BNH9 in 72%, and cytokeratins in 35%. Epithelial membrane antigen, S-100 protein, and HMB45 were not detected. Fifty-five percent of the tumors had intracytoplasmic aggregates of laminin. Immunostains for alpha-smooth muscle actin demonstrated a prominent pericytic component in several tumors (24%). Ki67 immunostains with MIB1 indicated high proliferative activity (> or =10%) in 72% of cases. p53 immunoreactivity (>20% nuclear staining) was observed in 20% of cases. Ultrastructural studies performed on poorly differentiated areas of 12 cases showed groups of cells, which were frequently epithelioid, surrounded by basal lamina, and closely associated with pericytes, along with intercellular and intracellular lumina with or without red blood cells. Whorls of abundant intermediate filaments, occasional tonofilamentlike structures, and pinocytotic vesicles also were noted. In contrast to the findings of others, Weibel-Palade bodies were not seen. Follow-up in 49 cases (61%) showed that 53% of patients were dead of disease at a median interval of 11 months, whereas 31% had no evidence of disease at a median interval of 46 months. The remaining patients were either alive with disease (14%) or alive but disease status was unknown (2%). There were local recurrences in 20% of cases and distant metastases in 49%, most frequently to the lungs, followed by the lymph nodes, soft tissues, bone, liver, and other sites. These results indicate that angiosarcoma of soft tissue is a high-grade sarcoma. Older patient age, tumor location in the retroperitoneum, and larger tumor size as well as detection of MIB1 in > or =10% of the tumor cell population were all associated with a poorer prognosis.

Primary ovarian angiosarcoma: a case report and literature review.

Primary ovarian angiosarcoma is extremely rare. Only 16 cases have histologically been reported to date in the literature. A case of angiosarcoma arising in the right ovary of a 46-year-old female is presented. Grossly, the resected right ovary was completely replaced by a solid tumor mass, which revealed multiple necrotic and/or hemorrhagic foci. This case revealed the typical histological features of angiosarcoma with sinusoidal and solid patterns of anaplastic tumor cells. Immunohistochemically, tumor cells were strongly and diffusely positive for CD31 and CD34, in particular, along the cytoplasmic membrane of the tumor cells. Ultrastructurally, tumor cells possessed the intermediate junctions between tumor cells, discontinuous basal laminae attached to the irregularly shaped blood vessels and occasional cytoplasmic pinocytotic vesicles. These findings confirmed the case as being one of angiosarcoma of the ovary. The patient died 9 months after surgery as a result of developed multifocal brain metastases. A total of 17 cases reported as primary ovarian angiosarcoma, including this presented case, are clinicopathologically reviewed.

[Aortic sarcomas with peripheral emboli: apropos of 2 cases]. / Sarcomes aortiques avec embolies périphériques: à propos de deux cas.

The authors report two cases of aortic angiosarcomas. These cases were similar and characterized by a typical pejorative clinical course, with peripheric emboli and many osteolytic metastasis. Immunohistochemical study was in favour of an endothelial origin, electronic microscopy indicated a mixed tumor with myofibroblasts and poorly differentiated endothelial cells. Differential diagnosis between angiosarcoma, leiomyosarcoma and intimal sarcoma are reviewed.

Angiolymphoid hyperplasia with eosinophilia and vascular tumors of the head and neck.

PURPOSE: The clinicopathologic distinctions between angiolymphoid hyperplasia with eosinophilia (AHE) and vascular tumors are controversial. Some investigators believe that AHE is a variant of hemangioma, whereas others state that it is an inflammatory phenomenon. To better delineate the clinicopathologic entity of AHE and investigate the efficacy of various treatment regimens, we undertook a retrospective analysis of AHE and compared it with other angiomatous lesions treated at a tertiary referral center. MATERIALS AND METHODS: We reviewed the histopathologic features of hemangioma, AHE, and angiosarcoma of the head and neck seen in 46 cases at University of California Los Angeles (UCLA) Medical Center between 1950 and 1992. Lesions were evaluated for presence of lymphoid and eosinophilic infiltration, type of endothelial cell, and pattern of vascular proliferation. Patient charts were also reviewed for clinical history and outcome. RESULTS: The typical findings of AHE were present in 13 cases of conventional hemangioma and angiosarcoma. The clinical data of 8 AHE patients were also reviewed and a benign outcome was observed. CONCLUSION: We propose that AHE represents an angiomatous neoplasm similar to the hemangioma but characterized by a marked reactive appearance. AHE may comprise part of a spectrum of vascular tumors with differences between lesions depending in part on host-mediated inflammatory and immune responses.