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.     

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.     

Periosteal Epithelioid Hemangioendothelioma with Leptomeric Fibrils

A case of recurrent periosteal epithelioid hemangioendothelioma of the right femur in a 66-year-old woman is reported. Microscopic examination showed epithelioid tumor cells with frequent intracytoplasmic vacuoles arranged in small nests or cords in hyalinized stroma. Immuno- and lectinhistochemical studies for factor VIII-related antigen and ulex europaeus I lectin indicated the endothelial nature of the tumor cells. Ultrastructurally, a few tumor cells contained leptomeric fibrils and crystalline filamentous aggregates in addition to showing certain features of endothelial cells. There seems to be no previous report of a vascular tumor containing leptomeric fibrils, which are often noted in normal striated muscle cells and their tumors. The bland appearance of the epithelioid tumor cells, poor vasoformative nature and prolonged clinical course differentiated this tumor from conventional angiosarcoma and so-called hemangioendothelioma of bone.     

Periosteal Epithelioid Hemangioendothelioma with Leptomeric Fibrils

A case of recurrent periosteal epithelioid hemangioendothelioma of the right femur in a 66-year-old woman is reported. Microscopic examination showed epithelioid tumor cells with frequent intracytoplasmic vacuoles arranged in small nests or cords in hyalinized stroma. Immuno- and lectinhistochemical studies for factor VIII-related antigen and ulex europaeus I lectin indicated the endothelial nature of the tumor cells. Ultrastructurally, a few tumor cells contained leptomeric fibrils and crystalline filamentous aggregates in addition to showing certain features of endothelial cells. There seems to be no previous report of a vascular tumor containing leptomeric fibrils, which are often noted in normal striated muscle cells and their tumors. The bland appearance of the epithelioid tumor cells, poor vasoformative nature and prolonged clinical course differentiated this tumor from conventional angiosarcoma and so-called hemangioendothelioma of bone.     

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.     

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 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.     

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.     

骨上皮样血管内皮瘤4例及文献复习

目的探讨4例骨上皮样血管内皮瘤(epithelioid hemangioendothelioma,EHE)的临床病理特点、诊断和鉴别诊断。方法对4例原发于骨的EHE临床资料、组织学、免疫组化进行观察分析并随访,结合文献讨论。结果 4例骨EHE中男性和女性各2例,中位年龄24岁,发生部位包括右肩胛骨、腰4～5椎体、胫骨下段和左足。临床症状主要为疼痛,影像学资料提示溶骨性改变;镜下示上皮样的肿瘤细胞呈巢状、索状或小梁状排列,肿瘤细胞呈圆形、多边形间或梭形,常见明显的胞质内空泡并伴有周围间质的玻璃样或黏液样变性。免疫表型:瘤细胞CD31、CD34、α-SMA均阳性(100%),CKpan有1例阳性(25%),EMA均阴性(100%),肿瘤增殖标记Ki-67呈低表达。结论原发于骨的EHE是一种少见的低度恶性的血管源性肿瘤,它的诊断要结合临床和影像学资料,依据其病理学特征及相关的免疫组化特点综合判断,需与骨转移性癌、上皮样血管瘤、上皮样血管肉瘤(epithelioid angiosarcoma,EAS)等鉴别。     

Cytopathologic features of hepatic epithelioid hemangioendothelioma

We present the cytological features of hepatic epithelioid hemangioendothelioma (EH), which is considered to be a vascular proliferation of intermediate malignant potential. The case report concerns a 52-yr-old previously healthy man discovered to have multiple hepatic masses upon evaluation for abnormal liver function tests. Fine-needle aspiration demonstrated a neoplasm composed of interanastomosing epithelioid cells that contained intracytoplasmic lumens. Histologic sections, immunohistochemistry, and ultrastructural evaluation were confirmatory. Although hepatic EH is a rare tumor, its characteristic cytological, histological, and ultrastructural features permit a straightforward diagnosis. It is important to distinguish this entity from adenocarcinoma and angiosarcoma because long-term disease-free survival is possible, especially in the setting of orthotopic liver transplantation. Diagn. Cytopathol. 17:50–53, 1997. © 1997 Wiley-Liss, Inc.     

Primary Intraoral Epithelioid Hemangioendothelioma Presenting in Childhood: Review of the Literature and Case Report

Epithelioid hemangioendothelioma (EH) is a recently described vascular neoplasm of borderline or intermediate malignant potential. This tumor arises from medium- to large-sized vessels, primarily involves the soft tissues of the extremities as well as the liver and lung, and rarely occurs in the head and neck region. Only eight well-documented cases of intraoral EH have been reported. We present an additional pediatric case of EH confined to the oral cavity and review the literature regarding EH presenting as an intraoral mass. EH is characterized histopathologically as an epithelioid lesion arranged in nests, strands, and trabecular patterns with infrequent vascular spaces. Occasional erythrocytes within intracytoplasmic lumina may be seen in tumor cells. Ultrastructural examination typically shows intracytoplasmic lumina with pseudopodial cellular membrane extensions. The cytoplasm usually contains intermediate filaments infrequently associated with Weibel-Palade bodies. Neoplastic cells are immuno-reactive for factor VIIIR:Ag and Ulex europaeus. Histopathologic features, which may be associated with aggressive clinical behavior, include significant cellular atypia, one or more mitoses per 10 high-power fields, an increased proportion of spindled cells, focal necrosis, and metaplastic bone formation. Because of the intermediate malignant potential of epithelioid hemangioendothelioma, complete tumor resection is recommended for intraoral lesions.     

Epithelioid hemangioendothelioma of the spinal cord: Description of a case with cytogenetic analysis

A case of epithelioid hemangioendothelioma of the cauda equina is reported. The patient presented with rapidly worsening low back pain. Magnetic resonance imaging revealed a sharply demarcated intradural lumbar lesion. A bluish-red lesion, attached to the filum terminale, was removed. The patient is alive without evidence of recurrence 18 months after surgery. The tumor was composed of variously sized vessels lined by epithelioid endothelial cells with clear cytoplasm and centrally located, moderately atypical nuclei. These cells were immunoreactive for CD31 and factor VIII antibodies. Cytogenetic analysis disclosed two clones: 44-45X, - Y [cp3]/46XY[11]. Epithelioid hemangioendothelioma may arise in several sites, the most common being soft tissues. It is a borderline tumor that may recur, may metastasize, and rarely causes death. The present case appears to be the first example of epithelioid hemangioendothelioma of the spinal cord.     

上皮样肉瘤样血管内皮瘤的临床病理学观察

目的 探讨上皮样肉瘤样血管内皮瘤的临床病理学特征和鉴别诊断.方法 回顾性分析3例上皮样肉瘤样血管内皮瘤的临床表现、组织学特点和免疫表型.结果 3例均发生于成年男性,分别因左颈部肿块、髂部疼痛和双侧颈肩区复发性肿块就诊.镜下观察肿瘤由梭形和上皮样的细胞组成,两种细胞在形态上有移行.瘤细胞呈片状、模糊结节状或交织条束状排列,间质伴有胶原化.1例于结节中央可见凝固性坏死,形态上类似上皮样肉瘤.3例肿瘤内均无明显的血管形成,但其中1例于局灶区域可见胞质内空泡形成,类似上皮样血管内皮瘤.免疫组织化学标记,瘤细胞同时表达上皮性标记和内皮标记.3例均经手术切除,其中2例患者术后恢复良好,随访18个月和14个月均健在,无局部复发或远处转移,另1例术后6年内复发5次.结论上皮样肉瘤样血管内皮瘤属于一种少见的中间型血管内皮瘤,兼具上皮样肉瘤和上皮样血管内皮瘤的部分形态.仅凭光镜形态有时较难确定其内皮细胞分化,必须借助于免疫组织化学标记.上皮样肉瘤样血管内皮瘤与上皮样血管内皮瘤关系较为密切,可能是后者的一种富于细胞性梭形细胞变型.

Abstract：

Objective To study the clinicopathologic features and differential diagnosis of epithelioid sarcoma-like hemangioendothelioma (ES-H). Methods The clinical, radiologic and pathologic features of three cases of ES-H were analyzed. Results All the 3 cases occurred in male adults. The age ranged from 44 to 53 years. The presentations included left neck mass, iliac pain and bilateral shoulder masses. Histologically, ES-H was composed of a mixture of spindle and epithelioid tumor cells. Transition between the two cell types was demonstrated. The tumor cells were arranged in compact sheets, vague nodules or intersecting fascicles, amongst a collagenous stroma. Central coagulative necrosis was identified in one case, reminiscent the morphology that seen in epithelioid sarcoma. There was no evidence of angiogenesis, though focal presence of intracytoplasmic vacuoles was seen in one case, as in classic examples of epithelioid hemangioendothelioma. Immunohistochemical study showed that the tumor cells expressed both epithelial (AE1/AE3, CAM5.2 and epithelial membrane antigen) and endothelial (CD31,Fli-1 and factor Ⅷ-related antigen ) markers. Two of the cases were also positive for CD34. All of the patients were treated by surgical resection. Two patients remain well at 14-month and 9-month follow up,respectively. The remaining patient had repeated local recurrences during a 6-year period. Conclusions ES-H represents a rare morphologic type of hemangioendothelioma. It has some overlapping histologic features with epithelioid sarcoma and epithelioid hemangioendothelioma. The endothelial nature of ES-H is difficult to be verified on the basis of morphologic examination alone. Confirmation of the diagnosis with immunohistochemistry is necessary. ES-H is likely related to epithelioid hemangioendothelioma and may represent a cellular spindie cell variant of epithelioid hemangioendothelioma.     

Recurring bone epithelioid hemangioma

Bone vascular tumors are very rare. Epithelioid types are described according to their architecture, their degree of vascular differentiation, and their cytonuclear atypia. The include epithelioid hemangioma, epithelioid hemangioendothelioma, and angiosarcoma. We report a case of L4 corpus vertebral bone epithelioid hemangioma. The patient was a 25-year-old man with a tumor that recurred twice. The lesion was characterized by a vascular lumen lined by cells with regular nuclei and inflammatory infiltrates. Capillaries were lined by prominent epithelioid endothelial cells, associated with CD31+ and cytokeratin-.     

Intriguing Case: Atypical Tumor of the Mediastinum: Epithelioid Hemangioendothelioma Containing Metaplastic Bone and Osteoclastlike Giant Cells

A 66-year-old woman presented with a superior-anterior mediastinal mass that contained considerable calcification by computed tomography. Initial biopsy interpretation was inconclusive but suggested a giant cell sarcoma of soft parts because the tumor contained atypical epithelioid cells and osteoclastlike giant cells. After radiation and chemotherapy, the tumor was removed. It contained large epithelioid cells, pale chondroid areas, metaplastic bone, and osteoclastlike giant cells. Immunohistochemical and electron microscopic studies revealed the epithelioid cells to be factor VIII positive and to contain abundant intermediate filaments, micropinocytotic vesicles, Weibel-Palade bodies, basal lamina, and primitive cell-cell junctions. These epithelioid cells also stained for muscle-specific actin (HHF-35), yet were negative for desmin and cytokeratins (CAM 5.2 and AE1/3). The findings were most consistent with those reported to occur in epithelioid hemangioendothelioma.     

TFE3‐rearranged hepatic epithelioid hemangioendothelioma—a case report with immunohistochemical and molecular study

A recurrent YAP1‐TFE3 gene fusion has been identified in WWTR1‐CAMTA1‐negative epithelioid hemangioendotheliomas arising in soft tissue, bone, and lung, but not in liver. We present the first case of TFE3‐rearranged hepatic epithelioid hemangioendothelioma in a 39‐year‐old Taiwanese woman. Computed tomography scan revealed multifocal, ill‐defined nodules involving both hepatic lobes. She then underwent deceased donor liver transplantation. Histologically, the tumors in the liver explant showed a biphasic growth pattern. One component was composed of dilated and well‐formed blood vessels lined by epithelioid cells with abundant eosinophilic cytoplasm, mimicking an alveolar pattern, whereas the other component was composed of cords and single cells, featuring intracytoplasmic vacuoles, separated by a myxoid stroma. The tumor cells showed vesicular nuclei and small indistinct nucleoli with mild to moderate cytologic atypia. Most tumor cells showed factor VIII, CD34, CD31, and TFE3 positivity in immunohistochemical study. Fluorescence in situ hybridization analysis for the tumor cells exhibited TFE3 gene rearrangement. The patient is currently alive, and no post‐operative tumor recurrence developed during a 13‐year follow‐up. Awareness of this rare vasoformative variant and identification of the gene rearrangement would be helpful on differential diagnosis with other high‐grade carcinoma and angiosarcoma of liver.     

Intriguing Case: Atypical Tumor of the Mediastinum: Epithelioid Hemangioendothelioma Containing Metaplastic Bone and Osteoclastlike Giant Cells

A 66-year-old woman presented with a superior-anterior mediastinal mass that contained considerable calcification by computed tomography. Initial biopsy interpretation was inconclusive but suggested a giant cell sarcoma of soft parts because the tumor contained atypical epithelioid cells and osteoclastlike giant cells. After radiation and chemotherapy, the tumor was removed. It contained large epithelioid cells, pale chondroid areas, metaplastic bone, and osteoclastlike giant cells. Immunohistochemical and electron microscopic studies revealed the epithelioid cells to be factor VIII positive and to contain abundant intermediate filaments, micropinocytotic vesicles, Weibel-Palade bodies, basal lamina, and primitive cell-cell junctions. These epithelioid cells also stained for muscle-specific actin (HHF-35), yet were negative for desmin and cytokeratins (CAM 5.2 and AE1/3). The findings were most consistent with those reported to occur in epithelioid hemangioendothelioma.     

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.     

Atypical tumor of the mediastinum: epithelioid hemangioendothelioma containing metaplastic bone and osteoclastlike giant cells.

A 66-year-old woman presented with a superior-anterior mediastinal mass that contained considerable calcification by computed tomography. Initial biopsy interpretation was inconclusive but suggested a giant cell sarcoma of soft parts because the tumor contained atypical epithelioid cells and osteoclastlike giant cells. After radiation and chemotherapy, the tumor was removed. It contained large epithelioid cells, pale chondroid areas, metaplastic bone, and osteoclastlike giant cells. Immunohistochemical and electron microscopic studies revealed the epithelioid cells to be factor VIII positive and to contain abundant intermediate filaments, micropinocytotic vesicles, Weibel-Palade bodies, basal lamina, and primitive cell-cell junctions. These epithelioid cells also stained for muscle-specific actin (HHF-35), yet were negative for desmin and cytokeratins (CAM 5.2 and AE1/3). The findings were most consistent with those reported to occur in epithelioid hemangioendothelioma.     

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。