[Atypical epithelioid hemangioendothelioma: a clinicopathological analysis of eight cases].

Objective: To study the clinicopathological features, diagnosis, and differential diagnosis of atypical epithelioid hemangioendothelioma (EHE). Methods: Eight cases of atypical EHEs were collected from Jiangsu Province Hospital (the First Affiliated Hospital of Nanjing Medical University) between 2010 and 2018. EnVision method and fluorescence in situ hybridization (FISH) were used to detect immunophenotype, WWTR1-CAMTA1 and TFE3 gene rearrangement, respectively. Results: There were 4 males and 4 females, ranging from 42 to 59 years (median 47.5 years). The tumors located in soft tissue (3 cases), lung (3 cases), liver (1 case) and chest wall (1 case). One soft tissue EHE involved also adjacent fibula and pleural involvement was present in all three lung cases at the diagnosis. Regional lymph node metastases were present in two cases (one involving soft tissue tumor and one involving liver). Morphologically, the tumor cells were epithelioid with abundant eosinophilic cytoplasm, moderate to marked nuclear pleomorphism, irregular nuclear membrane, unevenly chromatin, and prominent nucleoli. The cells arranged in cords, small nests or solid pattern. The mitotic rate was 4.3 mitoses/2 mm(2) on average (ranging 2 to 9). Tumor necrosis was seen in every case. Among all 8 cases, blister cells were found upon careful observation. Myxohyaline stroma was present in 6 cases. Immunohistochemically, tumor cells expressed CD31 (8/8), CD34 (7/8), ERG (8/8), CKpan (2/7), and CAMTA1 (4/6). None of the tested cases stained for TFE3 (0/6). WWTR1-CAMTA1 fusion gene by FISH was found in all tested 6 cases and TFE3 gene rearrangement was not detected in any. Available clinical follow-up was obtained in 7 cases and the intervals range from 6 to 55 months (average 19.6 months). Six patients had metastasis and 3 patients died of disease. One patient was alive with no evidence of disease. Conclusions: Atypical EHE is a more aggressive tumor than classic EHE, with histological features including high nuclear grade, increased mitotic activity, the presence of solid growth pattern and tumor necrosis. The differential diagnoses include epithelioid angiosarcoma, carcinoma and epithelioid sarcoma.目的： 探讨不典型性上皮样血管内皮瘤的临床病理学特征、诊断及鉴别诊断。 方法： 收集2010至2018年间就诊于江苏省人民医院（南京医科大学第一附属医院）的不典型上皮样血管内皮瘤8例，采用EnVision法进行免疫组织化学染色，荧光原位杂交（FISH）法检测WWTR1-CAMTA1融合基因及TFE3基因断裂重排情况。 结果： 8例不典型上皮样血管内皮瘤中男性4例，女性4例，年龄42~59岁（中位年龄47.5岁）。肿瘤发生于软组织3例，肺3例，肝脏1例，胸壁1例。发生于软组织者1例累及骨，发生于肺者3例发现时均已累及肺膜，另1例软组织病例及肝脏病例发现时已有淋巴结转移。形态学上，肿瘤细胞呈上皮样，胞质丰富嗜酸，有中度或以上核异型性，核膜不光滑，核染色质分布不均匀，可见明显的小核仁；瘤细胞呈条索状、小巢状或实性片状生长；核分裂较活跃，（2~9）个/2 mm(2)（平均4.3个/2 mm(2)）；均可见肿瘤性坏死。8例经仔细寻找，均可见水泡细胞，其中有6例出现经典上皮样血管内皮瘤的黏液玻璃样变背景。免疫表型上，瘤细胞表达CD31（8/8）、CD34（7/8）、ERG（8/8）、广谱细胞角蛋白（2/7）、CAMTA1（4/6），而TFE3阴性（0/6）。6例行FISH检测，均可见WWTR1-CAMTA1融合信号，未见TFE3基因断裂。7例均获随访资料，随访时间6~55个月（平均19.6个月），6例转移，其中3例死亡，另1例无瘤生存。 结论： 不典型性上皮样血管内皮瘤形态学上出现高级别核、核分裂活跃、实性片状生长方式及肿瘤性坏死，生物学行为更具有侵袭性，需要与上皮样血管肉瘤、癌、上皮样肉瘤等恶性肿瘤鉴别。.