Abstract
Malignant thoracic epithelioid vascular tumors are an uncommon and heterogenous group of tumors that include low-grade to intermediate-grade epithelioid hemangioendothelioma (EHE) and high-grade epithelioid angiosarcoma (EAS). We examine the morphologic and immunohistochemical features of 52 malignant epithelioid vascular tumors (10 low-grade EHE, 29 intermediate-grade EHE, and 13 EAS) involving the thorax (lung, pleura, mediastinum, heart, great vessels) including cases with exclusively thoracic disease (35) and with multiorgan disease including the thorax (17). Intermediate-grade EHE differs from low-grade EHE by the presence of necrosis, increased mitotic activity, and increased atypia. Morphologic features such as intranuclear inclusions, intracytoplasmic vacuoles, and stromal changes (chondroid, myxoid, or hyalinized stroma) are seen more frequently in EHE, whereas blood lakes, proliferation of slit-like vessels, and prominent nucleoli favor EAS. Fluorescence in situ hybridization analysis showed CAMTA1-WWTR1 fusions in 4/7 low-grade and 23/23 intermediate-grade EHE (P<0.001). In EAS, CAMTA1 rearrangement was negative in all cases, whereas a WWTR1 complex abnormality was found in 1/5 cases (P<0.001). This offers an objective means of differentiating intermediate-grade EHE from EAS, especially on limited biopsies. All cases show expression of at least 1 vascular marker, which allows differentiation from primary thoracic epithelial malignancies, although keratin expression is a potential pitfall with 29% of EHE and 25% of EAS showing keratin expression. Survival analysis shows that higher tumor grade for all tumors (P=0.026) as well as lung and pleural tumors only (P=0.010) and the presence of pleural involvement in lung and/or pleural tumors (P=0.042) correlate with poor prognosis.
摘要
恶性胸腔上皮样血管肿瘤是一组罕见的异质性肿瘤,包括低-中级别的上皮样血管瘤 (EHE)和高级别的上皮样血管肉瘤(EAS).我们观察了52例累及胸腔(肺,胸膜,纵膈,心脏,大静脉)的恶性上皮样血管肿瘤(10例低级别EHE,29例中级别EHE及13例高级别EAS),这些病例包括只发生于胸腔的疾病(35)和累及胸腔的多器官疾病(17)。与低级别EHE相比,中级别EHE有以下不同:出现坏死,核分裂活性增强,异型更明显。核内包涵体,胞浆内空泡,间质变化(软骨样,粘液样或玻变的间质)等形态学特征在EHE中更为常见,而血肿,裂隙状血管增生,突出的核仁则支持EAS。荧光原位杂交分析表明,4/7例的低级别和23/23的中级别EHE出现CAMTA1-WWTR1融合(P<0.001)。在EAS中,所有病例均没有CAMTA1的重排,而1/5例出现 WWTR1复合物异常(P<0.001)。这为鉴别中级别的EHE和EAS提供了一个客观方法,尤其是在活检组织有限的情况下。所有病例至少有一种血管标记的阳性表达,该特征使其与胸腔原发性上皮源性恶性肿瘤区分开来,尽管由于由于有29%的EHE和25%的EAS有角蛋白表达,使角蛋白表达成为潜在的诊断陷阱,但所有病例至少有一种血管标记的阳性表达,该特征使其与胸腔原发性上皮源性恶性肿瘤区分开来。生存分析显示所有肿瘤 (P=0.026)、只发生在肺和胸膜的肿瘤 (P=0.010)以及在累及胸膜的肺肿瘤或/和胸膜肿瘤中(P=0.042),肿瘤的级别越高,其预后越差。
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