Cutaneous epithelioid angiosarcoma: a clinicopathological study of four cases

Four cases of cutaneous epithelioid angiosarcoma are described together with the potential diagnostic trap of mistaking these tumours for poorly differentiated carcinoma or malignant melanoma. The immunophenotypic profile using four endothelial markers showed positive staining in all cases for factor VIII related antigen in a predominantly paranuclear dot-like fashion and for CD31 (JC70); in three cases for CD34 (QB-END/10) and in two cases with UEA-1. All four cases were cytokeratin (CAM 5.2 and AE1/AE3) negative in contrast to the positive staining reported at non-cutaneous sites. Aberrant S-100 protein expression was seen in one case. In two cases subsequent recurrences showed better differentiation than the original tumour. Electronmicroscopy confirmed the absence of non-endothelial lines of differentiation but failed to reveal Weibel-Palade bodies.     

Epithelioid haemangiosarcoma of the thyroid gland. Report of six cases from a non-Alpine region

Aim : To report a series of six cases of thyroid haemangiosarcoma (HAS) from a non-Alpine region.
Methods and results : The patients were four females and two males, aged 54–81 years (average 68 years). The tumours presented as large haemorrhagic masses (diameter 40–70 mm, average 56 mm) with extensive necrosis. Histologically, they were composed of polymorphous epithelioid cells with vesicular nuclei and abundant eosinophilic cytoplasm with occasional intracytoplasmic lumina. Mitotic activity was high. Tumor cells expressed vimentin (6/6), CD31 (6/6), FVIII (5/6), CD34 (2/6), and cytokeratins (5/6). One tumour (1/6) over-expressed p53 protein in more than 20% of cells. Ultrastructurally, Weibel–Palade bodies were present (4/6). Clinical follow-up of four patients (range 3–24 months, median 9 months) showed that two of them have died of the disease 0.5 and 3 months after diagnosis, one died of unrelated causes (with 24 months' uneventful follow-up) and one is alive 21 months after operation with no evidence of disease.
Conclusions : Although thyroid HAS is usually regarded as an extremely aggressive neoplasm with a dismal prognosis similar to anaplastic carcinoma, one of our cases suggests that HAS can behave in a less aggressive way. The morphological, immunohistochemical and ultrastructural findings support the hypothesis that thyroid HAS is a distinct entity, unrelated to other thyroid malignancies.     

Primary epithelioid angiosarcoma of the pleura: a case report and review of literature

Primary angiosarcoma of the pleura is an extremely rare malignancy. Herein, we report the case of an elderly Chinese patient with primary left pleural epithelioid angiosarcoma. The 76-year-old man presented with a 4-month history of a cough with sputum expectoration and weight loss of 4 kg within one month. A chest scan showed a massive oval-shaped mass in the left pleural cavity. We then performed a left thoracotomy for tumor resection and surgical exploration. Histological examination of the resected specimen showed few viable tumor cells with significant atypia; tumor cells had large nuclei and prominent nucleoli and were arranged in a crack-like, sheeted pattern. Moreover, there was a significant amount of fibrinous exudates, hemorrhage, degeneration, and necrosis. With immunohistochemical analysis, tumor cells had strong expression of CD31, CD34, FLI-1, vimentin. Morphological and immunohistochemical findings supported the diagnosis of epithelioid angiosarcoma.     

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.     

甲状腺上皮样血管肉瘤2例报道及文献复习

目的：探讨甲状腺肿瘤上皮样血管肉瘤的临床病理学特征。方法：对2例原发于甲状腺的上皮样血管肉瘤进行光镜观察和免疫组化标记。结果：2例均为老年患者,以颈部包块就诊,其中1例伴有地方性甲状腺肿。镜下显示,肿瘤主要由实性片状或巢状排列的上皮样细胞组成,瘤细胞核大,空泡状,含有明显的核仁,部分瘤细胞的胞质内可见含有红细胞的空泡或小管腔形成。除实性区域外,可见内衬上皮样瘤细胞的不规则性血管腔,网状纤维染色能清晰显示这些管腔结构,特别是在HE染色达CK8和Tg。结论：原发于甲状腺的上皮样血管肉瘤具有一定的临床病理学特点,光镜形态、免疫组化标记及电镜观察均支持瘤细胞具内皮细胞分化,应被视为甲状腺肿瘤中一种独立的病理学类型,而不应笼统地归入到未分化癌中。     

硬化性上皮样纤维肉瘤临床病理特点及其诊断

目的探讨硬化性上皮样纤维肉瘤(sclerosing epithelioid fibrosarcoma,SEF)的临床病理学特征、诊断及鉴别诊断。方法对1例SEF进行组织学观察和免疫组化标记,同时复习相关文献。结果SEF主要以上皮样细胞伴大量胶原纤维为特征,瘤细胞胞质透亮,似上皮细胞,排列呈条索状,间质中大量胶原纤维发生透明变性,形成硬化性基质。肿瘤细胞vimentin阳性,cytokeratin和actin阴性。结论SEF是一种较为罕见的软组织肿瘤,应注意与一些具有上皮样形态和硬化性间质的肿瘤相鉴别。     

Primary epithelioid angiosarcoma of the adrenal gland

Primary angiosarcomas of the adrenal gland are exceptionally rare vascular tumors. We report a case of a 63-year-old man with an epithelioid angiosarcoma of the left adrenal gland. Visualized on computed tomography as a nonhomogeneous round mass, the tumor measured 3 cm in diameter. Histology showed a vascular tumor composed of epithelioid cells with vesicular nuclei and prominent nucleoli that lined irregular vascular spaces and also formed solid areas and showed pleomorphism and rare mitotic activity. Immunohistochemical stain confirmed the diagnosis of epithelioid angiosarcoma. We report our findings and review previously described literature cases of this rare entity.     

Multifocal epithelioid angiosarcoma of the small intestine

A 67-year-old man presented with weight loss, intermittent severe abdominal pain and melaena. Initial radiology (including abdominal ultrasonography), gastroscopy and colonoscopy did not demonstrate any lesions that could explain the complaints. Three weeks later, upper gastrointestinal and small-bowel barium studies revealed two areas in the small intestine with an abnormal mucosal pattern. Explorative laparotomy revealed three tumoral lesions. Three partial enterectomies were performed. Gross examination showed centrally depressed dark reddish tumoral lesions extending from the mucosa throughout the full thickness of the bowel wall (diameter varying between 1.6 cm and 2.2 cm). The tumours, composed of large, plump, polygonal cells showing little architectural differentiation, were mainly situated in submucosa and muscularis propria. The growth pattern appeared rather solid. The epithelioid cells showed pronounced nuclear pleomorphism and atypia with central large nucleoli. There were several small blood vessels with occasional anaplastic endothelial cells. Immunohistochemical staining demonstrated an intense expression of CD 31, CD 34, factor VIII related antigen and keratin. This supported the diagnosis of an epithelioid angiosarcoma. The patient died 3 months after diagnosis. Tumours of the small intestine are very rare, and angiosarcomas of the small intestine are even more rare. Epithelioid variants have only been described in two patients and only one of these had a multifocal presentation. The prognosis is very poor. Because of the epithelioid growth pattern and the cytokeratin expression, these tumours may erroneously be diagnosed as a carcinoma.     

Gastric epithelioid angiosarcoma, a biopsy diagnostic pitfall

We report the case of a 70-year-old man who presented a bulky gastric mass. The diagnosis of poorly differenciated adenocarcinoma was made on the biopsy. On surgical specimen, the final diagnosis of gastric angiosarcoma with secondary intestinal involvement was established. The patient did not respond to chemotherapy and died 8 months later. The diagnosis was difficult because of epithelioid areas which expressed both cytokeratin and vascular antigens. Human herpesvirus 8 previously detected in some soft tissue angiosarcoma was not found by polymerase chain reaction.     

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.     

Fine-needle aspiration cytology of epithelioid angiosarcoma: a diagnostic dilemma

A 28-year-old woman with a 2-yr history of unilateral chronic leg swelling, initially thought to be secondary to deep vein thrombosis, later thought to be due to congenital venous malformation, eventually developed a pelvic mass, which was biopsied by fine-needle aspiration. On the basis of cytologic features on smears, high-grade sarcoma was reported. The patient underwent surgery to resect the pelvic mass, which showed anastomosing vascular channels arising from external iliac vein in histology. However, the tumor cells unexpectedly showed strong and diffuse immunohistochemical expression of cytokeratin and epithelial membrane antigen. The case was sent for expert consultation, and the expert's opinion was epithelioid angiosarcoma. The expert's diagnosis was confirmed 2 yr later by local recurrence. The clinical presentation, cytology, histology, and immunohistochemistry of the current case and 15 other cases of epithelioid angiosarcoma found in the cytology literature are summarized. This case illustrates that morphology with clinicopathologic correlation tends to be a better guide than available special techniques.     

胃肠道上皮样血管肉瘤四例临床病理学观察

目的探讨胃肠道血管肉瘤的临床病理特征、免疫表型、诊断及鉴别诊断。方法分析4例胃肠道血管肉瘤的临床病理资料,荧光原位杂交(FISH)检测C-MYC基因是否扩增。结果2例发生在胃,1例在十二指肠与空肠交汇处,1例位于回肠。4例均为中老年人,女1例,男3例。年龄51~62岁。镜下,肿瘤在黏膜层与肌层浸润性生长;见大片血湖及含铁血黄素沉积,形成假裂隙样或腺样结构;瘤细胞呈梭形或上皮样。免疫组织化学4例均弥漫强阳性表达CD31、ERG、Fli-1;3例弥漫强阳性表达CD34;3例不同程度的表达细胞角蛋白和上皮细胞膜抗原;3例FISH检测C-MYC均为阴性。结论胃肠道血管肉瘤是一种罕见的起源于血管内皮细胞的恶性肉瘤,活检标本极易被误诊为低分化腺癌。     

上皮样血管肉瘤的临床病理分析

目的 分析上皮样血管肉瘤的临床病理特点及需进行鉴别诊断的肿瘤。方法 利用HE染色,免疫组织化学抗生物素蛋白-生物素复合物法（ABC法）观察15例上皮样血管肉瘤,电镜观察其中12例,结果 15例中12例为男性,3例为女性,发生部位;腹膜后3例,四肢软组织3例,肌骨4例,甲状腺2例,眶上缘1例,胸壁软组织1例,颈部软组织1例。临床症状包括局部肿物及其引起的疼痛,消瘦,乏力。影像学检查显示肿瘤多为实性或囊实性,直径可达3-20cm。镜下观察瘤组织或弥漫成片或聚集成巢,伴有出血和多灶坏死,瘤组织内常见大小不等的不规则腔隙,衬附异型瘤细胞,单个瘤细胞或多个瘤细胞形成空腔包绕红细胞。电镜可观察到胞质内空泡,W-P小体,中间丝及细胞基底膜的存在,瘤细胞可表达CD34,CD31,Ⅷ因子相关抗原,细胞角蛋白,上皮膜抗原,血管周细胞表达平滑肌肌动蛋白,临床主要采用手术切除的治疗方法,偶尔辅以放疗。随访/2例存活,术后存活期分别为19个月,7年;12例已死亡,术后存活期最短为2周,最长38个月,平均19个月;1例失访。8例患者发生肺,骨,淋巴结和腹腔转移。结论 上皮样血管肉瘤是高度恶性肉瘤,免疫组织化学检测和电镜观察有助于确定肿瘤的内皮分化,上皮样血管肉瘤需与转移癌,上皮样血管内皮细胞瘤,恶性黑色素瘤,上皮样肉瘤等鉴别。     

Cytokeratin-positive epithelioid angiosarcoma presenting in the tonsil: a diagnostic challenge

Primary oral cavity sarcomas are exceedingly rare and may pose a great diagnostic challenge. A 71-year-old woman without history of malignancy or radiation to the head and neck presented with an antibiotic-refractory diffuse painful swelling of the right tonsil necessitating tonsillectomy. Histologic evaluation revealed subtotal replacement of the right tonsil by a high-grade epithelioid neoplasm displaying extensive ulceration, necrosis, and primitive vasoformation. Immunohistochemistry showed strong/diffuse expression of pancytokeratin antibodies KL-1 and Lu5, cytokeratin 8, cytokeratin 18, cytokeratin 19, vimentin, CD31, ERG, and Freund leukemia integration site 1 (FLI-1). High-molecular-weight cytokeratins (cytokeratin 5, 34β12), cytokeratin 7, cytokeratin 13, and cytokeratin 20 were not expressed. Within months, the patient underwent surgical resection of multiple bleeding intraoral and gastrointestinal metastases. She is currently alive with disease 9 months from diagnosis. To our knowledge, this case represents the first well-documented primary epithelioid angiosarcoma of the tonsil. The strong cytokeratin expression in epithelioid angiosarcomas represents a diagnostic pitfall. Thus, awareness of this rare and highly aggressive neoplasm is necessary for distinguishing it from poorly differentiated and acantholytic squamous cell carcinoma and diffuse large cell lymphoma.     

Multicentric epithelioid hemangioendothelioma involving the same lower extremity: a case report and review of literature

Epithelioid hemangioendothelioma (EH) is an uncommon low-grade malignant soft-tissue tumor; no case has been previously reported where multicentric epithelioid hemangioendothelioma occurred in the same lower extremity at different sites. We report a case involving the common peroneal nerve and subsequently the long bone and the short bones of the same lower extremity, and also review the literature. After establishing case of several lesions, we reviewed the histopathology properly and followed up the patient for a long time with serial whole body assessment to pick up any subsequent lesions.     

Metastatic epithelioid angiosarcoma of the heart in peritoneal fluid

Angiosarcoma is the most common malignant neoplasm of the heart. Recurrent pericardial effusions are a common manifestation of cardiac angiosarcomas. The diagnosis of metastatic disease in effusions is often established histologically; few cases have been described in exfoliative cytology. We report a case of metastatic cardiac epithelioid angiosarcoma in peritoneal fluid.     

Epithelioid angiosarcoma of the thyroid

Epithelioid angiosarcomas of the thyroid usually develop in people living in Alpine regions, and only rare cases arising in subjects living in nonmountainous areas have been reported. We describe the clinicopathological features of a series of seven cases collected from non-Alpine areas. All patients were adults. The tumours appeared as haemorrhagic, unencapsulated, sometimes cystic nodules. In two cases multinodularity was present. They were composed of large, epithelioid cells, which lined vascular-like spaces or were arranged in solid sheets. Intracytoplasmic lumina containing red blood cells were identified. Neoplastic cells were diffusely positive for factor VIII-related antigen, Ulex europaeus agglutinin, CD31 and keratin peptides. Ultrastructural studies were performed in four cases and showed features of endothelial differentiation. An average follow-up of 3.8 years disclosed that four patients died of disease after a median survival time of 5 months, whereas 3 patients are still alive with no evidence or residual disease 27, 32 and 66 months after thyroidectomy. The good prognosis in these patients appears to be related mainly to the absence of extraglandular tumour spread at the time of surgery.