Vascular Tumors of Bone: The Evolvement of a Classification Based on Molecular Developments

The classification of vascular tumors of bone has been under debate over time. Vascular tumors in bone are rare, display highly overlapping morphology, and, therefore, are considered difficult by pathologists. Compared with their soft tissue counterparts, they are more often multifocal and sometimes behave more aggressively. Over the past decade, with the advent of next-generation sequencing, recurrent molecular alterations have been found in some of the entities. The integration of morphology and molecular changes has led to a better characterization of these separate entities.     

Diagnostically Challenging Epithelioid Vascular Tumors

The diagnosis of vascular tumors is a challenging area in soft tissue pathology. Epithelioid vascular tumors pose a particular challenge. Due to the epithelioid morphology of the tumor cells, they can be misdiagnosed as a variety of other entities, including metastatic carcinoma or epithelioid sarcoma. Furthermore, it can be difficult to distinguish between different epithelioid vascular tumors. This review focuses on vascular tumors characterized by epithelioid endothelial cells, including epithelioid hemangioma, cutaneous epithelioid angiomatous nodule, epithelioid hemangioendothelioma, epithelioid sarcomalike hemangioendothelioma/pseudomyogenic hemangioendothelioma, and epithelioid angiosarcoma.     

Histopathology of Spindle Cell Vascular Tumors

Vascular tumors with a spindled morphology represent a diagnostic challenge in soft tissue pathology. It may be difficult to distinguish certain benign entities in this category from spindled vascular tumors of intermediate malignancy or even spindled variants of angiosarcoma. This article focuses on vascular tumors characterized by a predominantly spindled morphology, including spindle cell hemangioma, acquired tufted angioma (angioblastoma of Nakagawa), kaposiform hemangioendothelioma, Kaposi sarcoma, and spindle cell variants of angiosarcoma.     

Vascular Anomalies of the Head and Neck: A Pediatric Overview

Vascular anomalies, further classified into vascular tumors and malformations, often involve the head and neck region of children. These entities may raise diagnostic dilemmas, as they often demonstrate heterogenous and overlapping histologic features. The aim of this paper is to provide an overview of the common vascular anomalies in the head and neck region of children. Specific entities discussed include infantile hemangioma, congenital hemangioma, tufted angioma, kaposiform hemangioendothelioma, and various vascular malformations. Clinicopathologic features and associated molecular associations are reviewed.     

Malignant epithelioid hemangioendothelioma of the bladder: the first case report in a child

Epithelioid hemangioendothelioma is a distinct vascular tumor, which is very rare in the bladder. To the best of our knowledge, only one adult patient has been reported so far in the English literature. A 4-year-old boy with a huge bladder mass, with the pathologic diagnosis of epithelioid hemangioendothelioma, is the first patient with this lesion described in the pediatric age-group.     

Living Donor Liver Transplantation for Epithelioid Hemangioendothelioma: Report of a Case

Epithelioid hemangioendothelioma (EH) of the liver is a rare tumor, generally considered to have low-grade malignancy. Little is known about its clinical behavior and the therapeutic strategy is not established. We report the case of a 36-year-old woman who underwent living donor liver transplantation for EH with splenic metastases and died of recurrence 8 months later. To determine if transplantation improves the prognosis of patients with EH, we must re-evaluate its indications.     

Epithelioid hemangioendothelioma of the liver

Epithelioid hemangioendothelioma (EH) of the liver is a rare tumor and is difficult to differentiate from cholangiocellular carcinoma or metastatic liver tumor on image diagnosis. A case of curatively resected EH of the liver is reported. A 48-year-old woman was admitted because she had a mass in the liver. Cholangiocellular carcinoma was suspected preoperatively. Right trisegmentectomy of the liver, combined with bile duct resection and portal vein resection and reconstruction, was performed. Characteristic macro- and microscopic findings of the resected specimen revealed EH of the liver. The patient has survived for more than 6 years without recurrence. Because of the tendency of EH of the liver to appear in multiple or scattered forms, only 12 cases of resection for EH have been reported. Received: March 3, 2000 / Accepted: May 12, 2000     

肝上皮样血管内皮瘤的临床病理特点(附8例报告及文献复习)

目的 于国内首次报道肝上皮样血管内皮瘤(EHE)的临床及病理学特点。方法 对8例手术切除EHE的临床和病理学特点进行详细分析，对11种免疫组化标志物的表达状况进行检测。结果 病人以中年女性为主，男女之比为2：6，年龄29—58岁，平均42．5岁，3例(37．5％)血清HBsAg阳性并伴有肝硬化，2例(25％)合并肝细胞癌，7例(87．5％)为多结节，瘤体直径l-7cm。显微镜下特征为具血管分化的树突状细胞和有胞质内血管腔的上皮样细胞，间质致密纤维化及黏液样变，8例EHE免疫组化均呈CD34和Vimentin阳性，CK偶为阳性。5例病人于术后随访l0个月至2年仍健在，其余3例，包括l例结节直径最大者(7cm)和2例合并肝细胞癌者在术后6-15个月内死亡。结论 肝EHE的发生与HBV的感染可能有一定关系，其恶性程度低于肝血管肉瘤和肝细胞癌，但合并肝细胞癌和瘤体直径＞7cm者预后不良。具有细胞内血管腔的上皮样瘤细胞并呈血管内皮标志物染色阳性是EHE病理诊断的两个重要特征，鉴别诊断需排除转移性腺癌及胆管癌。     

Epithelioid Haemangioendothelioma of the mandibular gingiva: case report and literature review

IntroductionEpithelioid hemangioendothelioma (EHE) is a rare vascular neoplasm that exhibits the potential for recurrence and metastasis but rarely involves the oral cavity.Presentation Of CaseWe report the management and long term follow up of recurrent EHE in a 23- year-old woman. The lesion initially presented as a small area of erythematous gingival swelling with localised bone loss around the lower anterior teeth. It was treated by buccal and lingual stripping of the gingival tissues. The patient suffered local recurrence after 7 years and was treated with a wider surgical excision of the buccal and lingual gingivae, conserving the adjacent teeth and bone with an excellent cosmetic outcome. Over 21 years later, there have been no further recurrences.DiscussionThis case highlights the management challenges of EHE and is the only case in the literature to have reported a case of mandibular gingivae with a long review period of 21 years.ConclusionOral EHE is an unpredictable lesion with a relatively benign course, unlike non-oral EHE where up to one third of cases may metastasise. Because of the propensity to recur locally after excision and curettage, a wide local excision with close clinical follow has been suggested in the literature as the treatment of choice for oral lesions. However, the lack of metastases from oral lesions, the small size, mandibular site and bland histology in this case suggests that a limited soft tissue excision and bone curettage, with long term follow-up would be appropriate for similar gingival lesions in future.     

Epithelioid Hemangioendothelioma of the Head and Neck: Role of Podoplanin in the Differential Diagnosis

Epithelioid hemangioendothelioma is an uncommon vascular tumor of soft tissue and bone that may rarely occur in the liver, lung and the head and neck. We present five new cases of epithelioid hemangioendothelioma of the head and neck region diagnosed and managed in one institution in order to define the phenotypic characteristics, podoplanin immunohistochemical staining and the biological outcome. Podoplanin is a transmembrane mucoprotein selectively expressed in lymphatic endothelium and recently in some vascular neoplasms. The patients were comprised of two male and three female patients ranging in age from 4 to 71 years. The lesions were found in the gingiva, submandibular region soft tissue, nasal cavity and tongue, and ranged in size from 0.7 to 2.5 cm. All tumors manifested infiltrative cords and nests of epithelioid cells with occasional spindle morphology in a myxoid stroma. Immunohistochemical analysis of vascular and epithelial markers showed strong and uniform cytoplasmic reactivity for podoplanin and variable intensity and staining of CD31 and lack of cytokeratin staining in tumor cells. Surgical treatment included simple and wide local excisions. Of the three patients with follow-up, one developed lymph node metastasis and one had no evidence of disease 10 months after surgery. The patient with multiple recurrences and LN metastases was additionally treated with chemotherapy and is under consideration for radiation therapy. Hemangioendothelioma of the head and neck is: (1) a low-grade malignancy with a tendency for local recurrence and regional lymph node metastasis, (2) complete excision with negative margins is the treatment of choice for localized disease and (3) podoplanin may be useful in differentiating epithelioid hemangioendothelioma from non-vascular tumors.     

Epithelioid hemangioendotheliomas of the spine: clinical characters with middle and long-term follow-up under surgical treatments

Epithelioid hemangioendothelioma, an aggressive vascular tumor has the rarity of morbidity that arises in the spine. There were few cases reported in literatures in recent years, and little was known about this disease. A review study of the patient files in our constitutions between 1996 and 2006 showed that five patients were treated for spinal epithelioid hemangioendothelioma. Although only five patients, this study attempts to bring more informations about this rare lesion. This patient group included two males and three females. The lesions located in the cervical (case 1) or thoracic (case 2–4) or lumbar spine (case 5). Treatments included: laminectomy and cytoreductive surgery followed by external beam irradiation (one patient), expanded resection in piece meal with postoperative external beam irradiation (three patients), and total en bloc resection alone (one patient). Reconstruction of the spinal stability was performed in four patients. Follow-up period ranged from 25 to 72 months, averaged 47.4 months. The neurologic function of patients got a satisfactory progress except the paraplegic patient at diagnosis. The patient who received laminectomy and cytoreductive surgery followed by external beam irradiation still presented with tumor local progress, metastasis, and she died at 34 months after operation. No local recurrence or distant metastasis was detected in the other four patients. Epithelioid hemangioendothelioma of the spine is so rare in clinic as a primary aggressive vascular tumor. Based on our experience, a valid expanded resection of the tumor with adjunct radiation therapy or total en bloc excision may present with acceptable results.     

Epithelioid hemangioma of bone: A unique case with multifocal metachronous bone lesions

Epithelioid hemangioma of bone is a rare vascular neoplasm with a ubiquitous distribution. To date, up to 25% epithelioid hemangioma of bone presents synchronous bone lesions. We report a unique case of epithelioid hemangioma with multifocal metachronous bone lesions without any fatal outcome observed after a long period. Importantly, a strong nuclear expression of FOSB antibody was detected by immunohistochemical analysis. In this case, the pathologic and radiologic findings are also described. We suggest that epithelioid hemangioma can present multifocal metachronous bone lesions without producing a fatal outcome.     

Epithelioid Hemangioendothelioma of the Stomach: Clinical-Pathological Features,Nosologic Setting,and Surgical Therapy. Report of a Case

Vascular tumors of the stomach represent 0.9%–3.3% of all gastric neoplasms. A 41-year-old man was admitted to our department with a 3-month history of early postprandial epigastric pain, sluggish digestion, nausea, asthenia, and occasional alimentary emesis. Preoperative staging detected a submucosal neoformation in the prepyloric zone, which narrowed the lumen, without any infiltrative features; a wedge gastric resection was performed and the definitive diagnosis was an epithelioid hemangioendothelioma of stomach. An 8-month follow up did not show any relapse of the disease. The term hemangioendothelioma is controversial because of disagreements regarding the nosologic setting and treatment. As a result, the latest WHO classification calls such neoplasms "borderline." The correct diagnosis depends on the histological findings supported by immunohistochemistry. Surgery represents the treatment of choice; however, a conservative approach is preferred whenever possible. However, due to the borderline biological behavior of this neoplasm, it is important that detailed clinical evaluations be carried out for such patients along with a thorough follow-up. Received: January 15, 2001 / Accepted: September 11, 2001     

Mesenchymal hamartoma of the liver responsive to cyclophosphamide therapy: therapeutic approach

A newborn infant is described with a highly vascular hepatic mesenchymal hamartoma causing hydrops fetalis, congestive heart failure, and consumption coagulopathy. There was a remarkable response of this life-threatening condition to cyclophosphamide therapy. A review of the various alternative therapeutic modalities is presented.     

肝移植治疗肝脏上皮样血管内皮瘤2例报告并文献复习

目的探讨肝移植治疗肝脏上皮样血管内皮瘤的临床经验和疗效。方法回顾性分析2例肝脏上皮样血管内皮瘤患者肝移植诊疗经过和相关临床资料,并进行文献复习。结果 2例均为女性。术前腹部B超、CT均提示肝实质多发占位性病变：肝穿刺组织病理学检查均提示肝上皮样血管内皮瘤;免疫组化染色均显示肿瘤标志物CD31（＋）、CD34（＋）和FactorⅧ（＋）。肝移植术后采用他克莫司（FK506）＋吗替麦考酚酯（骁悉）二联免疫抑制方案,早期维持FK506血药浓度为8～12μg/L。分别于术后13 d及8 d肝功能恢复正常。术后早期1例并发急性阑尾炎,行阑尾切除术后治愈,2例均未发生急性排斥反应,康复出院。随访2年余移植物、受体正常存活,无肿瘤复发。结论肝移植是治疗不能手术切除的肝脏上皮样血管内皮瘤的最有效的治疗措施,术后效果满意。     

Angiolymphoid hyperplasia with eosinophilia (epithelioid hemangioma) of the breast: Report of a case

We report herein the unusual case of a 35-year-old woman found to have angiolymphoid hyperplasia with eosinophilia (ALHE) of the breast. The patient was initially referred to our hospital for investigation of a well-circumscribed breast lump, 2.5 cm in diameter, and a clinical diagnosis of fibroadenoma was made. However, fine-needle aspiration cytology of the lump revealed an admixture of lymphocytes and eosinophils. Therefore, the lump was excised and microscopic examination showed features of ALHE. No evidence of recurrence of the lump has been seen in the 2 years since this excision. To the best of our knowledge, this is the first case to be documented of ALHE arising in the breast. Received: May 12, 1999 / Accepted: March 24, 2000     

Angiolymphoid hyperplasia with eosinophilia (epithelioid hemangioma) of the face: An unusual presentation

Angiolymphoid hyperplasia with eosinophilia (ALHE) is a rare entity that usually occurs as 0.5–3 cm pink to brown nodules in the skin surface and subcutaneous tissues of the head & neck. Here we report an unusual occurrence in size and appearance of ALHE in the tissues of the cheek of an adult Asian male.     

原位肝移植治疗肝脏上皮样血管内皮瘤（附2例报告及文献复习）

目的  探讨原位肝移植治疗肝脏上皮样血管内皮瘤（EHE）的疗效及相关治疗进展。方法  回顾性分析2例肝脏EHE患者的临床资料。例1为肝脏广泛多发EHE合并脾脏多发梗死灶的患者,实施了原位肝移植+脾切除术;例2为肝脏多发EHE患者,仅实施了原位肝移植。结合国内外文献,分析肝脏EHE患者的病理学特点、肝移植治疗及预后情况。结果  两例患者手术过程顺利,均康复出院。病理结果证实为肝脏EHE,例1合并脾脏EHE。例1术后1个月抗排斥反应药由他克莫司换为西罗莫司,术后4个月EHE复发,给予卡培他滨口服化学药物治疗（化疗）;术后6个月考虑肝脏EHE复发并多发性骨转移,予索拉非尼口服抗肿瘤治疗,术后7个月患者死于恶病质、肝衰竭。例2随访至投稿日（术后8个月）,未见术后相关并发症及肿瘤复发迹象。国内外文献报道提示肝脏EHE首选手术切除,肝内广泛多发而无法手术切除者,甚至有肝外病灶者,肝移植疗效最佳。另外,化疗、经皮穿刺肝动脉化疗栓塞和抗血管生成治疗对本病也有一定疗效。结论  肝脏EHE治疗首选手术切除,对于肝内广泛多发者,肝移植被认为是最佳的治疗选择。应重视肝脏EHE移植术后复发的防治,以期进一步提高该病的疗效。