Abstract：
YAP1-TFE3-fused hemangioendothelioma is an extremely rare malignant vascular tumor. We present the largest multi-institutional clinicopathologic study of YAP1-TFE3-fused hemangioendothelioma to date. The 24 cases of YAP1-TFE3-fused hemangioendothelioma showed a female predominance (17 female, 7 male) across a wide age range (20-78 years old, median 44). Tumors were most commonly located in soft tissue (50%), followed by bone (29%), lung (13%), and liver (8%), ranging from 3 to 115 mm in size (median 40 mm). About two-thirds presented with multifocal disease, including 7 cases with distant organ metastasis. Histopathologically, we describe three dominant architectural patterns: solid sheets of coalescing nests, pseudoalveolar and (pseudo)vasoformative pattern, and discohesive strands and clusters of cells set in a myxoid to myxohyaline stroma. These patterns were present in variable proportions across different tumors and often coexisted within the same tumor. The dominant cytomorphology (88%) was large epithelioid cells with abundant, glassy eosinophilic to vacuolated cytoplasm, prominent nucleoli and well-demarcated cell borders. Multinucleated or binucleated cells, prominent admixed erythrocytic and lymphocytic infiltrates, and intratumoral fat were frequently present. Immunohistochemically, ERG, CD31, and TFE3 were consistently expressed, while expression of CD34 (83%) and cytokeratin AE1/AE3 (20%) was variable. CAMTA1 was negative in all but one case. All cases were confirmed by molecular testing to harbor YAP1-TFE3 gene fusions: majority with YAP1 exon 1 fused to TFE3 exon 4 (88%), or less commonly, TFE3 exon 6 (12%). Most patients (88%) were treated with primary surgical resection. Over a follow-up period of 4-360 months (median 36 months) in 17 cases, 35% of patients remained alive without disease, and 47% survived many years with stable, albeit multifocal and/or metastatic disease. Five-year progression-free survival probability was 88%. We propose categorizing YAP1-TFE3-fused hemangioendothelioma as a distinct disease entity given its unique clinical and histopathologic characteristics in comparison to conventional epithelioid hemangioendothelioma.
摘要：
YAP1-TFE3融合血管内皮瘤是一种极其罕见的恶性血管肿瘤。我们提出了迄今为止最大的YAP1-TFE3融合血管内皮瘤的多机构临床病理研究。24例YAP1-TFE3融合血管内皮瘤以女性为主（17例女性，7名男性)年龄范围很广(20-78岁，中位数44）。肿瘤最常见于软组织（50%），其次是骨骼（29%），肺（13%），和肝脏（8%），范围从3到115毫米的大小（中位数40毫米）。大约三分之二的人患有多灶性疾病，其中7例有远处器官转移。组织病理学,我们描述了三种主要的建筑模式:坚固的聚结巢，假肺泡和（假）血管形成模式，和盘状链和细胞簇设置在一个粘液样至粘液透明基质中。这些模式在不同肿瘤中以可变比例存在，并且通常共存于同一肿瘤内。占优势的细胞形态（88％）是大量的上皮样细胞，玻璃样嗜酸性到液泡质，突出的核仁和界限分明的细胞边界。多核或双核细胞，突出的混合红细胞和淋巴细胞浸润，肿瘤内脂肪经常存在。免疫组织化学，ERG,CD31和TFE3一致表达，而CD34（83％）和细胞角蛋白AE1/AE3（20％）的表达是可变的。除一例外，所有CAMTA1均为阴性。所有病例均通过分子检测证实存在YAP1-TFE3基因融合：大多数YAP1外显子1与TFE3外显子4融合（88％），或者不太常见，TFE3外显子6(12%)。大多数患者（88％）接受了初次手术切除治疗。在4-360个月（中位数36个月）的随访期间，17例，35%的病人没有疾病还活着,47%的人稳定地存活了很多年，尽管多灶性和/或转移性疾病。5年无进展生存概率为88%。我们建议将YAP1-TFE3融合的血管内皮瘤归类为一种独特的疾病实体，因为与常规上皮样血管内皮瘤相比，其独特的临床和组织病理学特征。
