Vascular tumors of bone: A study of 17 cases other than ordinary hemangioma,with an evaluation of the relationship of hemangioendothelioma of bone to epithelioid hemangioma,epithelioid hemangioendothelioma,and high-grade angiosarcoma

Cases filed as vascular tumor of bone other than ordinary hemangioma were reviewed. They were included in the study if there was adequate histologic material and clinical information, clear evidence of bone origin, and at least 5 years follow-up. The study group comprised 17 cases, of which 13 were categorized as hemangioendothelioma of bone, 1 as epithelioid hemangioendothelioma, and 3 as high-grade angiosarcoma. Hemangioendothelioma of bone had growth patterns varying from vasoformative to solid, but well-formed vessels were present in at least some area in all cases. The cells generally had a rounded, epithelioid character, regular nuclei, and relatively few mitotic figures; occasional features included spindle cells and scattered enlarged, hyperchromatic or pleomorphic nuclei. Lymphoplasmacytic and eosinophilic inflammatory infiltrate ranged from prominent to slight or absent, and myxoid or hyaline stroma was never more than focal. Epithelioid hemangioma could not be separated from hemangioendothelioma of bone. The single epithelioid hemangioendothelioma for the most part had cords of relatively uniform epithelioid cells in a prominent myxoid stroma but focally demonstrated an angiosarcoma-like appearance, with irregular vascular spaces and marked nuclear pleomorphism. The high-grade angiosarcomas exhibited predominantly irregular vasoformation combined with solid areas, diffuse nuclear hyperchromatism and pleomorphism, and, in 2 cases, numerous mitotic figures (the third case had only a small biopsy and a postradiation amputation specimen). Of the hemangioendotheliomas of bone, 7 were unicentric and 6 were regionally multicentric either concurrently or sequentially. Three patients had intraosseous local recurrence, 2 had discontinuous regional skin or soft tissue involvement (including the popliteal artery in 1), and 1 had a solitary lung metastasis, but none died of tumor. The patient with epithelioid hemangioendothelioma had multicentric tumors in widely separated bones and died with liver and lung metastases. Two of the high-grade angiosarcomas were unicentric, and the third was regionally multicentric, with a popliteal artery-soft tissue component as well. All 3 of these patients died with metastases in various sites.     

Fibroblast changes in cutaneous ageing

Summary A case of malignant epithelioid hemangioendothelioma of the liver mimicking veno-occlusive disease is reported. The histological, ultrastructural, and immunohistochemical features of the present case indicate striking similarities to epithelioid hemangioendothelioma (EHE) of the soft parts described by Weiss and Enzinger. Tumour metastasis to the lung gave a picture closely resembling intravascular bronchiolo-alveolar tumour (IVBAT) of the lung. EHE of the liver is considered to be a unique type of hepatic endothelial neoplasm behaving as a low grade malignant tumour with a veno-occlusive process which has rarely been described, and had previously been classified as other diseases or neoplasms.     

Epithelioid hemangioendothelioma of the liver in primary biliary cirrhosis. A case report

We report a case of primary epithelioid hemangioendothelioma of the liver occurring in a patient with primary biliary cirrhosis, stage III. The hepatic tumor was found incidentally by imaging techniques and was surgically resected under a tentative diagnosis of metastatic carcinoma. The resected tumor (1.8 x 1.6 cm) showed typical histologic features of epithelioid hemangioendothelioma. The tumor cells were positive for factor VIII-related antigen and were stained with Ulex europaeus lectin I. Ultrastructurally, the tumor cells showed cytoplasmic vacuoles, tight junctions, basal lamina, pinocytotic vesicles, bundles of thin filaments (approximately 10 nm in diameter) and Weibel-Palade bodies. The non-tumorous part of the liver showed features of primary biliary cirrhosis, stage III. This is the first reported case of epithelioid hemangioendothelioma occurring in a liver with primary biliary cirrhosis.     

Podoplanin is a useful diagnostic marker for epithelioid hemangioendothelioma of the liver.

Podoplanin, which is immunoreactive to D2-40 antibody, is reportedly expressed in lymphatic vessels in non-neoplastic tissues, and also in vascular and non-vascular tumors. However, its expression in non-neoplastic and neoplastic liver tissues has not been well documented. In this study, we examined podoplanin expression in specimens from 10 normal livers and 73 cases of liver tumors: hemangioma (16 cases), epithelioid hemangioendothelioma (9 cases), angiosarcoma (4 cases), angiomyolipoma (7 cases), hepatocellular carcinoma (11 cases), intrahepatic cholangiocarcinoma (11 cases), and metastatic liver cancer (15 cases). We compared levels of podoplanin and other endothelial markers (CD31, CD34, and factor VIII) in liver tumors. In the normal liver, podoplanin was expressed in lymphatic endothelium, nerve fibers, and mesothelium in the hepatic capsule, but not observed in any cells within hepatic lobules. Among liver tumors, podoplanin was specifically expressed in seven of nine cases (78%) of epithelioid hemangioendothelioma but not in other hepatic tumors. The expression of CD31, CD34, and factor VIII was observed in endothelial cells in all cases of hemangioma, epithelioid hemangioendothelioma, angiosarcoma, and angiomyolipoma with one exception, a case of epithelioid hemangioendothelioma which was without CD31 expression. Interestingly, the intensity of podoplanin expression was negatively correlated with the expression of CD34 and factor VIII. In conclusion, podoplanin would be useful as a diagnostic marker for epithelioid hemangioendothelioma in liver tumors.     

多部位发生的上皮样血管内皮瘤2例报道及文献复习

目的 探讨多部位发生的上皮样血管内皮瘤(EHE)的临床病理学特征.方法 回顾性复习2例多部位发生的血管内皮瘤的临床资料、组织学形态和免疫学表型,并复习文献.结果 2例均为女性,年龄分别为24和37岁,CT示双肺及肝弥漫结节影.病理学检查发现肝和肺结节的镜下形态相同,即在黏液样的间质背景中可见条索样、小巢状或单个散在分布的上皮样瘤细胞,瘤细胞有明显异型性,伴胞质内管腔形成,腔内偶见红细胞.免疫组织化学染色显示:瘤细胞表达内皮标记(CD34、CD31和F8),不表达CK、CD68、ER、PR.结论 上皮样血管内皮瘤是一种少见的低度恶性血管肿瘤,多部位同时发生者容易被误诊.上皮样血管内皮瘤的临床表现和生物学行为因其发生部位不同而有较大的差异.     

Primary peritoneal epithelioid hemangioendothelioma

Epithelioid hemangioendothelioma is an uncommon malignant vascular tumor of intermediate grade that occurs in a variety of organs and soft tissues. Diagnosis of epithelioid hemangioendothelioma is often complicated by the rarity of the tumor, and because the tumor shares many morphologic features with other peritoneal neoplasms. This report presents 3 cases of epithelioid hemangioendotheliomas arising as primary tumors of the peritoneum and reviews 7 previously reported cases to establish the demographic, clinical, morphologic, immunohistochemical, and ultrastructural features of this neoplasm. These cases demonstrate that the light microscopic features are very similar to epithelioid hemangioendothelioma arising at more conventional sites, such as the liver, that immunohistochemical analysis provides a reliable approach for confirming or establishing the diagnosis, and that at least one endothelial marker (either CD31, CD34, or factor VIII) should be positive for a definitive diagnosis. This series identifies the characteristics of peritoneal epithelioid hemangioendothelioma that can be reliably used for diagnosis.     

Epithelioid Hemangioendothelioma of the Liver in Primary Biliary Cirrhosis

We report a case of primary epithelioid hemangioendothelioma of the liver occurring in a patient with primary biliary cirrhosis, stage III. The hepatic tumor was found incidentally by imaging techniques and was surgically resected under a tentative diagnosis of metastatic carcinoma. The resected tumor (1.8±1.6 cm) showed Wtcal histologic features of epithelioid hemangioendd jelioma. The tumor cells were positive for factor VIII related antigen and were stained with Ulex europaeus lectin I. Ultrastruc-turally, the tumor cells showed cytoplasmic vacuoles, tight junctions, basal lamina, pinocytotic vesicles, bundles of thin filaments (approximately 10 nm in diameter) and Weibel Palade bodies. The non tumorous part of the liver showed features of primary biliary cirrhosis, stage III. This is the first reported case of epithelioid hemangioendothelioma occurring in a liver with primary biliary cirrhosis. Acta Pathol Jpn 39: 607 611, 1989.     

Epithelioid hemangioendothelioma and related lesions

Epithelioid hemangioendothelioma (EH) is the prototype of a group of vascular tumors characterized by an epithelioid or histiocytoid endothelial cell. This family also includes the epithelioid hemangioma (angiolymphoid hyperplasia with eosinophilia) and epithelioid forms of angiosarcoma. This review discusses the principal clinical, pathologic, and biologic differences among these three lesions. In particular the various manifestations of EH of soft tissue, bone, lung (previously called intravascular bronchioloalveolar tumor), and liver are discussed. Long-term follow-up data of EH of soft tissue and lung are provided.     

Report of a case of epithelioid hemangioendothelioma of the anterior mediastinum metastatic to pleura

We present a case of epithelioid hemangioendothelioma metastatic to pleura, in a 69-year-old woman with chest pain. This distinctive vascular neoplasm can arise in various organs, most commonly in middle-aged women. It is characterized by slow growth, and, microscopically, by epithelioid tumor cells in appearance. Epithelioid hemangioendothelioma should be distinguished mainly from primary or metastatic carcinomas and angiosarcoma. Definitive diagnosis often requires immunohistochemistry. Its clinical course is unpredictable, although survival rates are better than for angiosarcoma.     

Epithelioid hemangioendothelioma of the liver: an ultrastructural study

Epithelioid hemangioendotheliomas are uncommon vascular tumors, mainly observed in lung and soft tissues. Liver involvement is infrequent and, in contrast to the extrahepatic localizations of the tumor, has not been subjected to detailed ultrastructural analysis. This prompted us to report the results of the ultrastructural study of three cases of epithelioid hemangioendothelioma of the liver. Neoplastic proliferation was heterogeneous. Most of neoplastic cells presented features suggestive of endothelial differentiation, including presence of Weibel-Palade bodies and evidence of vasoformative properties demonstrated by formation of both intra- and extracellular vascular channels resembling the normal structures successively observed during embryogenesis and tissue regeneration. A minor cell population, unreported so far, exhibited ultrastructural characters resembling those of pericytes and presented organoid relationship to neoplastic endothelial cells. Tumor spreading along sinusoids induced pseudopeliotic dilatations and led to a progressive disruption of normal liver architecture. In conclusion, the three cases of hepatic epithelioid hemangioendothelioma examined in this work assume many organoid features mimicking the successive steps of normal angioformation and indicative of a high degree of morphological differentiation.     

Mediastinal epithelioid hemangioendothelioma metastatic to lymph nodes and pleural fluid: Report of a case

Epithelioid hemangioendothelioma is a rare mesenchymal tumor of vascular origin, classified as a sarcoma of intermediate malignant potential. Involvement of numerous sites of the body, including visceral organs, soft tissue, testis, skeleton, brain, meninges, and skin have been described. We report an unusual case of a mediastinal epithelioid hemangioendothelioma in a 65‐year‐old female initially presenting as a metastasis to lymph nodes of the hilar region and subsequently as a malignant pleural effusion. The patient had a complex history of papillary renal cell carcinoma, papillary thyroid carcinoma, and Waldenstrom's hyperglobulinemia making the diagnosis of metastatic epithelioid hemangioendothelioma difficult. Clinical, cytological and immunohistochemical features of this tumor are described with an emphasis on diagnostic pitfalls. Diagn. Cytopathol. 2010. © 2009 Wiley‐Liss, Inc.     

Epithelioid hemangioendothelioma with osteoclast-like giant cells

Epithelioid hemangioendothelioma is an unusual entity of intermediate malignant vascular tumors and rarely admixes with multinucleated osteoclast-like giant cells. We describe such a case in a 50-year-old woman with an 1-year follow-up period. When the patient was 39 years old, a 0.7 x 1-cm firm mass was found in the left neck. She developed ascites three years later. At that time, the specimen from the neck mass was excised and found to be composed of cords of epithelioid cells in a myxoid hyaline stroma. Scattered intracytoplasmic vacuoles were seen. Immunohistochemical studies confirmed the diagnosis of epithelioid hemangioendothelioma. Abdominal ultrasonography and computed tomographic scan revealed multiple low density areas in the liver. Eleven years later, a metastatic lesion was found in the thoracic spine at the level of Th7-8. The histologic findings were basically similar to those of the left neck mass. However, because of the presence of Kp-1-positive multinucleated osteoclast-like giant cells throughout the tumor, the thoracic lesion was diagnosed as an epithelioid hemangiothelioma with osteoclast-like giant cells. This unique form of epithelioid hemangioendothelioma is extremely rare and should be distinguished from other benign and malignant tumors with osteoclast-like giant cells.     

Epithelioid hemangioendothelioma of the suprasellar area: a case report and review of the literature

Intra-axial involvement of the brain by an epithelioid hemangioendothelioma is rare, and biological properties of the tumor are uncertain. Most of the primary brain manifestations are confined to the cerebral hemispheres. We report magnetic resonance imaging and microscopic findings of a case of suprasellar involvement by an epithelioid hemangioendothelioma. The tumor was treated with a subtotal resection only, and no progression of the disease was noted during a 6-month follow-up. Review of the literature suggested that most epithelioid hemangioendotheliomas in the brain are unifocal tumors with a rather favorable clinical outcome.     

Extracutaneous angiosarcomas metastatic to the lungs: clinical and pathologic features of twenty-one cases.

Angiosarcomas are rare malignant vascular tumors with a high rate of metastasis involving lungs (most commonly), liver, regional lymph nodes, bone, and other sites. In this study, we have reviewed the clinical presentation and histopathology of 21 cases of extracutaneous angiosarcoma metastatic to the lungs. Tumors with exclusively pleural involvement were excluded. Patients presented with dyspnea, chest pain, and/or hemoptysis lasting a few weeks to months. Radiologically, the most common finding comprised multiple peripheral lung nodules (57%), often accompanied by infiltrates. For 11 cases (52%), the primary tumor was not identified at the time of presentation. Vasoformative areas were identified in 15 cases (71%). Nine cases comprised spindle cells (43%), two contained epithelioid cells (9.5%), and 10 consisted of both spindle and epithelioid cells (48%). Nuclear pleomorphism was at least moderate in all cases. However, five tumors contained regions of minimal nuclear atypia. Hemorrhage, siderophages, and fibrosis were commonly present. Immunohistochemical staining (IHS) was performed on 14 cases. Thirteen tumors showed reactivity for vascular markers. Tumor cells reacted for Von Willebrand factor in 13 of 14 cases, and CD31 and CD34 were each positive in 2/2 cases. Two cases (of nine examined) also expressed cytokeratins. Because the tumor often first presented in the lungs before the primary sarcoma was identified, the clinical impression included both benign and malignant entities. For patients with primary cardiac tumors, symptoms referable to the primary tumor complicated the clinical presentation, and radiologic evaluation supported a clinical diagnostic impression of non-neoplastic pericarditis. Thus, angiosarcoma in the lung may elude diagnosis until histopathologic evaluation of the lung biopsy.     

A case of hypertrophic osteoarthropathy associated with epithelioid hemangioendothelioma

Epithelioid hemangioendothelioma is a rare vascular tumor, which occurs in the lung, liver, bone, and soft tissue. Hypertrophic osteoarthropathy is a syndrome characterized by subperiosteal new bone formation, joint effusion and clubbing, and may be associated with cyanotic heart disease, chronic pulmonary disease, liver disease, and other miscellaneous diseases. The activation of endothelium and platelets has been suggested to be involved in the development of hypertrophic osteoarthropathy. We report a rare case of hypertrophic osteoarthropathy, which developed in association with hepatic epithelioid hemangioendothelioma with pulmonary metastasis. We also discuss the role of vascular endothelial growth factor in its pathogenesis.     

Epithelioid angiosarcoma: a brief diagnostic review and differential diagnosis

Epithelioid angiosarcoma is a highly aggressive endothelial cell malignancy, most commonly arising in the deep soft tissues, but a variety of primary sites, including the adrenals, thyroid, skin, and bone, are encountered. On hematoxylin-eosin-stained sections, the pathologist encounters sheets of large, mildly to moderately pleomorphic epithelioid cells, with abundant eosinophilic cytoplasm, vesicular nuclei, and prominent nucleoli. Obvious vasoformative foci may not be present, creating confusion with metastatic carcinomas, malignant mesothelioma, melanoma, anaplastic lymphoma, epithelioid peripheral nerve sheath malignancies, and epithelioid sarcoma. Moreover, malignancies with apparent vascular differentiation must be distinguished from less aggressive vascular neoplasms, including epithelioid hemangioendothelioma. Given the range of clinical presentation, the diversity of primary sites, and the nonspecific initial histopathologic appearance, here we review the histologic findings and immunohistochemical profiles of epithelioid angiosarcoma and neoplasms in its differential diagnosis.     

Epithelioid hemangioma of bone: a potentially metastasizing tumor?

The case of a 15-year-old boy with a severe swelling of the 2nd toe in the left foot and a large swelling of the left inguinofemoral region is described. Histologic examination of the foot lesion showed a typical epithelioid hemangioma of bone that extended into the soft tissues, with a secondary location in the groin, suggestive of lymph node involvement. Subsequently, imaging also revealed swelling of iliac and para-aortic lymph nodes, which probably indicates further lymph node spread.. Besides the fact that epithelioid hemangioma of the toe has not been reported yet, our case showed a non-continuous localization, most likely in draining lymph nodes. This finding suggests metastatic disease, an event that is extremely rare for epithelioid hemangioma. As such, epithelioid hemangioma might be comparable to another benign vascular tumor, the retiform hemangioendothelioma, which occasionally metastasizes to the lymph nodes without systemic spread.     

Unusual hemangioendothelioma of the liver with epithelioid morphology associated with marked eosinophilia: autopsy case

Vascular neoplasms characterized by epithelioid endothelial cells consist of several different entities from benignity to high-grade malignancy. Because of histological overlap between them, there is substantial difficulty in classifying them correctly. The present patient, a 33-year-old man, presented with hepatomegaly, striking eosinophilia and elevated serum interleukin-5 level. Biopsy and autopsy revealed an unusual epithelioid vascular tumor in the liver, which is histologically distinct from epithelioid hemangioma, epithelioid hemangioendothelioma, or epithelioid angiosarcoma. The tumor cells had vasoformative and partly solid growth with no severe nuclear atypia and very low mitotic activity, and the histological features were similar to those of the entity recognized as hemangioendothelioma of bone. Organs other than the liver, for example the testes and bone, were also involved. This tumor should be considered in the differential diagnosis of severe eosinophilia.     

肺上皮样血管内皮瘤临床病理观察

目的 探讨肺上皮样血管内皮瘤的临床病理特点。方法 4例肺上皮样血管内皮瘤,3例女性,1例男性,年龄28～40岁,无自觉症状或有轻度咳嗽、气短。肺活检或手术切除标本经甲醛固定,石蜡包埋,常规HE及免疫组织化学(Envision法)染色。所用抗体包括CD31、CD34、细胞角蛋白(AEl／AE3)、TTF-1、波形蛋白和上皮膜抗原。结果 本组肺上皮样血管内皮瘤病例女性多于男性,胸部CT显示双肺多发弥漫性小结节影。病理形态特点为结节周边上皮样肿瘤细胞呈花冠状充填于肺泡腔,病变中心为黏液透明样变间质,肺泡壁结构保留,肿瘤细胞胞质内有空泡形成,空泡内偶见红细胞,肿瘤细胞异型性不明显,核分裂和坏死均少见,免疫组织化学染色示CD31、CD34阳性,AE1／AE3偶见灶状阳性,其他抗体呈阴性。结论 肺上皮样血管内皮瘤是一种具有独特临床病理特点的低度恶性血管来源肿瘤。     

Epithelioid angiosarcoma involving the lungs

Diffuse lung involvement by metastatic tumor from an unknown primary site often constitutes a diagnostic dilemma. Although cytologic features and pattern of metastatic spread can guide in narrowing the list of possible primary neoplasms, immunohistochemistry remains pivotal in determining the phenotype of metastatic disease. We report a case with extensive involvement of lung parenchyma by a metastatic epithelioid neoplasm exhibiting a variety of distinctive patterns with a predominance of intra-arterial and lymphangitic spread. Immunohistochemical studies showed no evidence of epithelial, melanocytic, or lymphoid differentiation. The neoplastic cells were strongly positive for vimentin and CD31 but negative for CD34 and factor VIIIR:Ag. Electron microscopy of formalin-fixed tissue revealed multiple Weibel-Palade bodies and pinocytosis, supporting the diagnosis of epithelioid angiosarcoma. Doppler studies performed after pathologic diagnosis was rendered demonstrated 2 discrete hypoechoic masses within the medial aspect of the left proximal calf musculature, suggestive of solid soft tissue neoplasm-a possible source of pulmonary metastatic disease.