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。     

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-.     

Epithelioid hemangioendothelioma of bone and soft tissue: A fine-needle aspiration biopsy study with histologic and immunohistochemical confirmation

We retrospectively reviewed two fine-needle aspiration biopsy (FNAB) specimens from two patients with histologically confirmed epithelioid hemangioendothelioma (EH). Both patients were men, ages 79 and 39 years; their primary tumors arose in the soft tissues of the mediastinum and within the proximal tibia, respectively. The former patient had symptoms of superior vena cava syndrome; multicentric intraosseous lesions involved the proximal tibia of the latter patient. All cytologic smears were hypercellular and composed of mostly disassociated single cells and small aggregates of ovoid to polygonal-shaped epithelioid cells. Nuclei were variable, ranging from ovoid and reniform to round and polylobated and surrounded by an abundant amount of dense cytoplasm. Binucleated epithelioid neoplastic cells were frequent. Nuclear pleomorphism ranged from slight to moderate, and small solitary to multiple nucleoli were identified within the majority of tumor cells. Rare neoplastic cells with a single, sharply demarcated intracytoplasmic vacuole and intranuclear cytoplasmic pseudoinclusions were observed in the smears of one tumor. Metachromatic stromal fragments, probably representing hyalinized chondromyxoid stroma, were seen in the other tumor. Neither case was recognized initially on FNAB as EH. Immunohistochemically, sections from the surgical biopsy specimens of both cases showed diffuse and strong immunopositivity for the endothelial marker CD31. Although the cytomorphology of EH appears distinct, clinicoradiologic correlation is essential, and immunohistochemistry may be helpful to avoid misdiagnoses. Diag. Cytopathol. 1998;19:38–43. © 1998 Wiley-Liss, Inc.     

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。     

Pulmonary epithelioid hemangioendothelioma mimicking mesothelioma

An intrathoracic mass was discovered on magnetic resonance imaging (MRI) of the spine in a 37-year-old Caucasian man with a 1 year history of progressively severe upper back pain. A subsequent chest CT scan indicated a 4 cm left hilar mass, extending to the apex and encasing a portion of the left bronchus and pulmonary artery. Initial bronchoscopic and transthoracic biopsies failed to obtain diagnostic material. The patient underwent thoracotomy and was found to have a locally advanced, surgically unresectable lung tumor, involving the pleura, pericardium and diaphragm. The patient failed to respond to radiochemotherapy, and died 11 months following the diagnosis with tamponade and metastasis to the skin of the thoracoabdominal wall. Histologically the tumor had an epithelioid and spindled appearance, without high-grade histological features, and was initially thought to represent biphasic diffuse malignant mesothelioma. Positive immunohistochemistry for vascular markers (CD31, CD34, and FLI-1) disclosed the vascular nature of the tumor. Mesothelioma markers were universally negative and cytokeratin was focally reactive only in some epithelioid cells. Epithelioid hemangioendothelioma is a rare tumor in the lung that can mimic other more common pathological entities, and should be included in the differential diagnosis of unusual pulmonary neoplasms with epithelioid or biphasic morphology.     

Pitfalls in the diagnosis of hepatic epithelioid hemangioendothelioma by FNA and needle core biopsy

Epithelioid hemangioendothelioma (EHE) of the liver is an extremely rare tumor that masquerades as an epithelial neoplasm and poses significant diagnostic pitfalls for the cytopathologist. This report describes a 64‐year‐old woman whom on computerized tomography was found to have multiple peripherally calcified hypodense lesions throughout the liver and an ipsilateral adrenal mass. Fine needle aspiration and needle cores biopsies of the largest liver lesion showed epithelioid cells and spindle cells in fibrous stroma. The epithelioid cells had round or oval, hyperchromatic nuclei with smooth nuclear contours, delicate cytoplasm and indistinct cytoplasmic borders. Rare cells had intracellular vascular lumen containing fragmented or intact red blood cells. The cells were individually dispersed or arranged in nests and vague tubular arrays. No mitotic figures or necrosis were seen. An immunohistochemical profile demonstrated diffuse CD31 and focal CD 34 and nuclear Fli‐1 immunoexpression and low Ki‐67 proliferative activity (1%) within lesional cells confirming the diagnosis of EHE. The differential diagnosis of EHE which includes cholangiocarcinoma, hepatocellular carcinoma, metastatic carcinoma and melanoma is discussed. Diagn. Cytopathol. 2014;42:516–520. © 2013 Wiley Periodicals, Inc.     

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.     

Intravascular epithelioid hemangioendothelioma of the inferior vena cava: case report of an unusual and unpredictable vascular tumor

Vascular neoplasms are uncommon and pose a diagnostic and treatment challenge to the pathologist and surgeon, respectively. Epithelioid hemangioendothelioma is a rare neoplasm of vascular origin with an unknown etiology. Its biologic behavior lies somewhere between that of a benign hemangioma and that of a malignant angiosarcoma; however, it is unpredictable at best. Intravascular epithelioid hemangioendotheliomas have been described more often in veins than arteries, and there are only about 30 reports in the English literature. We report here the case of an epithelioid hemangioendothelioma of the inferior vena cava, which presented with abdominal pain, ascites and pedal edema.     

肝脏上皮样血管内皮瘤穿刺标本的病理诊断与鉴别诊断

目的 提高对经皮肝穿刺活检标本中上皮样血管内皮瘤(EH)的认识.方法 收集北京肿瘤医院1999-2010年3016例肝穿刺活检标本中5例诊断EH的病例,回顾性分析5个病例的光镜下病理形态学特点、免疫组织化学(polymer二步法)检测结果,以及患者的临床表现、实验室检查和影像学结果.结果 5例均为女性,年龄23～47岁,平均39岁.4例B超显示肝多发实性肿物并考虑转移癌;实验室检查各项指标未见明显异常.光镜下肿瘤细胞上皮样、排列成短条索状或小巢状,包埋于特征性黏液玻璃样基质中,可见明显的胞质内空泡;瘤细胞形态温和,未见核分裂;免疫组织化学表达血管标志物CID31、CD34、第八因子相关抗原,偶见表达平滑肌肌动蛋白.结论肝穿刺活检标本中,如果病变具有典型的EH形态特点和免疫组织化学表达,同时又有临床及影像学支持,即可明确诊断;应用多种抗体组合有助于肝穿刺活检标本EH的诊断与鉴别诊断.

Abstract：

Objective To evaluate the pathologic diagnosis of hepatic epithelioid hemangioendothelioma (EH) in needle biopsy specimens. Methods Five cases of hepatic EH diagnosed in needle biopsies encountered during the period from 1999 to 2010 in Beijing Cancer Hospital were retrospectively reviewed. The specimens were formalin-fixed, paraffin-embedded and stained with hematoxylin and eosin. Immunohistochemical study was also carried out. Results All the 5 patients were females. The age ranged from 23 to 47 years ( mean = 39 years). The tumors in 4 patients were multiple and diagnosed as "metastasis" on ultrasound examination. The blood test results in all of the 5 patients were normal. Histologically, the tumor cells had an epithelioid appearance and were arranged in cords, solid nests or isolation, amongst a myxoid or hyaline matrix. The tumor cells contained scattered intracytoplasmic vacuoles which sometimes harbored red blood cells. There was no evidence of significant cellular pleomorphism, high mitotic activity and necrosis. Immunohistochemically, all of the 5 cases were positive for at least two endothelial markers (CD31, CD34 and factor Ⅷ-related antigen). Smooth muscle actin was expressed in 1 case. Conclusions The diagnosis of hepatic EH can be established in needle biopsy specimens. The histologic pattern, when coupled with immunohistochemical findings, is useful in arriving at the correct diagnosis.     

Cytologic features of epithelioid hemangioendothelioma

To determine cytologic features of epithelioid hemangioendothelioma (EHE) that would enable accurate diagnosis, we evaluated fine-needle aspiration biopsy (FNAB) smears from 11 histologically confirmed EHEs. The variably cellular smears comprised dispersed single cells and occasional cell aggregates. Dense stromal fragments were present in association with some tissue fragments. The cells were epithelioid, containing moderate or large amounts of dense cytoplasm. Nuclei exhibited mild pleomorphism, and nuclear grooves were identified in all cases. At least occasional intranuclear pseudoinclusions (INPIs) and intracytoplasmic lumina (ICLs) were present in all cases and in 9 cases (82%), respectively, and rare erythrocytes were seen within ICLs in 5 cases (45%). Mitotic figures were identified in 4 cases (36%). The background was bloody in 6 cases (55%) and contained hemosiderin and/or hemosiderin-laden macrophages in 5 cases (45%). The combination of the following features in FNAB samples should raise strong suspicion for EHE: predominantly dispersed single cells with occasional cohesive cell clusters; epithelioid cytomorphology; dense cytoplasm with well-defined cytoplasmic borders; ICLs (with or without erythrocytes), INPIs, and nuclear grooves. The presence of these features should prompt correlation with clinical, radiologic, and histologic features and immunohistochemical evaluation using vascular markers.     

骨上皮样血管内皮细胞瘤9例诊治分析

目的 探讨骨上皮样血管内皮细胞瘤(B-EHE)的诊断、治疗方法。方法 回顾性分析2002年2月—2015年9月解放军东部战区总医院骨科收治的9例B-EHE患者的临床资料。其中男6例、女3例,年龄15~64岁。术前X线及CT检查均表现为溶骨性改变,1例MRI可见周围软组织受累,1例出现肺部转移灶。3例选择病灶刮除、植骨内固定;1例腰椎病灶选择肿瘤切除椎板减压内固定;3例近关节病灶选择肿瘤切除假体置换,其中1例术后化疗;1例多发病灶伴肺转移选择活检确诊后化疗治疗;1例病理性骨折伴出血选择行截肢术后综合治疗。结果 9例中失访1例,其余随访时间8～72个月。现7例存活。3例行病灶刮除植骨内固定,2例局部复发,二次手术后治愈。1例腰椎肿瘤切除减压固定,术后恢复良好。3例行肿瘤切除假体置换术,1例失访;2例术后治愈,关节功能良好,其中1例术后辅助化疗,未出现局部复发和病灶转移。1例多发病灶伴肺部转移行化疗,肺部无进展,局部无进展。1例行截肢术后综合治疗者,肿瘤复发迁延性出血,最终因器官衰竭死亡。结论 B-EHE为低-中度恶性肿瘤,术前影像学无特异性,诊断困难,主要依靠术后病理结果诊断。治疗首选边界切除,辅以化疗或放疗,可降低局部复发率和远处转移。     

上皮样血管内皮瘤的临床病理分析

目的：探讨上皮样（组织细胞样）血管内皮瘤的临床病理学特点及其意义。方法：对9例上皮样血管内皮瘤进行光镜和免疫组织化学SP法检测,1例作电镜观察,结果：年龄16－47岁,平均32岁,男女性别差异无显著性意义。部位：头面部4例,上肢3例,下肢2例,形态特征：瘤细胞具有上皮样或组织细胞样的形态;瘤细胞圆形或多角开,三五成群呈小巢状,索状,不规则状排列,分布于粘液间质中;间质可显著或少量粘液样变或玻璃样变,瘤细胞内含有原始血管腔,核分裂角,多形性及坏死少见,部分病例伴有梭形细胞血管内皮瘤改变,1例见破骨细胞样的多核巨细胞,免疫组织化学检测7例,7例波形蛋白均阳性,5例第八因子相关抗原,CD31,CD34阳性,2例细胞角蛋白弱阳性,1例CD68和a1-抗胰蛋白酶阳性,电镜观察1例见胞质内含丰富的微丝和少许的W－P小体,6例随访－8年,3例在原发部位有1或2次复发,但未见有转移,结论：上皮样血管内皮瘤是一种低度恶性的软组织肉瘤,其病因学尚不清楚,熟悉其形态特征对避免误诊为其他类似病变具具有重要意义。     

A case of epithelioid hemangioma of the spine

Epithelioid hemangioma is a rare and benign vascular tumor, most often occurring in the skin. Numerous other localizations, including bones, have been reported. The overall favorable clinical outcome of cutaneous epithelioid hemangioma is now well documented, but it still remains debated in osseous localization, as local recurrences and metastases have been described. We report a case of epithelioid hemangioma of the spine occurring in a 25-year-old male, and discuss main differential diagnoses. Recent studies tend to demonstrate that osseous epithelioid hemangioma, as cutaneous epithelioid hemangioma, should be considered as a benign tumor. Histologically, epithelioid hemangioma consists of a vascular proliferation with diffuse or lobular pattern and features vascular spaces lined by epitheliod endothelial cells with numerous lymphocytes and eosinophils. The main differential diagnosis is represented by epithelioid hemangioendothelioma, the surgical treatment of which must be more aggressive. Precise histological diagnosis is essential for accurate clinical management and to avoid overtreatment.     

Pathological characteristics of liver biopsies in eight patients with hepatic epithelioid hemangioendothelioma

We aim to investigate the pathological characteristics of liver biopsies and their implications for the prognosis of hepatic epithelioid hemangioendothelioma (HEHE). Clinical data of eight patients (5 male, 3 female) with HEHE were analyzed retrospectively. Expression of CD34, FVIII, AE1/AE3, Hepa-par1, GPC3, CK19 and the proliferation index marker Ki-67 were determined by immunohistochemical staining. The clinical pathological features and effects of treatment on prognosis were investigated. Among the eight patients, four did not exhibit significant symptoms, while four showed symptoms such as abdominal distension, aversion to greasy food and mild fever. Two patients had single liver lesions, while multiple lesions were observed in six cases, in which the tumor cells exhibited spindle, irregular or epithelioid morphology, with scattered, streaked and nested distribution. Individual luminal cells were also visible, containing red cells and accompanied by mucoid or fibrous stroma. All cases were CD34 positive, one case was FVIII factor negative, two cases were AE1/AE3 positive, Ki-67 staining exceeded 15% in two cases, and nuclear fission was visible in two cases. Patients with nuclear fission and Ki-67 > 15% died within 2 years after artery embolization, liver transplantation without relapse was observed in two cases and one case survived with the tumor. The other patients without cellular atypia, without nuclear fission and with Ki-67 < 10% did not relapse during the 2-5 years of follow-up. HEHE can be diagnosed according to hematoxylin and eosin morphology and immunohistochemical characteristics in biopsies before treatment allowing the selection of different treatment protocols based on pathological characteristics.     

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.     

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.     

Characteristic cytologic findings of epithelioid hemangioendothelioma: A case report and review of literature

Epithelioid hemangioendothelioma is a rare vascular neoplasm of low-grade malignancy. We observed a case of epithelioid hemangioendothelioma arising in a cervical lymph node. Fine needle aspiration cytology showed several characteristic findings of epithelioid hemangioendothelioma, that is, nuclear inclusion bodies, nuclear grooves, and amorphous material, in addition to physaliform chromatin pattern of a new clue. By reviewing the reports, the prevalence of these is clarified. Complex appearance of these findings is useful in the diagnosis.     

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.     

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.