上皮样肉瘤伴有间皮和淋巴管内皮分化十例临床病理学分析

Epithelioid sarcoma with mesothelial and lymphatic endothelial differentiation： a clinicopathologic analysis of 10 cases

目的总结上皮样肉瘤（epithelioid sarcoma）的临床病理特点、免疫表型、诊断及鉴别诊断，探讨其间皮和淋巴管内皮标志物表达情况。方法收集10例远端型上皮样肉瘤患者的临床资料，观察其组织病理学形态、免疫组织化学特征，并进行随访。结果10例上皮样肉瘤中，男性5例，女性5例，发病年龄8．66岁。肿瘤分别位于上肢和下肢，多数位于肢端，大多表现为进行性加重的疼痛性结节状肿块。组织形态上，肿瘤由上皮样、横纹肌样、梭形细胞混合并相互过渡组成，细胞间见明显的胶原纤维沉积，呈结节状或结节融合成弥漫片状，中央常见坏死，形成肉芽肿样结构。细胞胞质丰富，嗜酸性，细胞核卵圆形、泡状，一个或多个明显核仁，核分裂象多见。免疫组织化学显示，AE1／AE3（9／10）、上皮细胞膜抗原（10／10）、CD34（9／10）、波形蛋白（10／10）阳性，INI-1均阴性。此外。本组病例还表达各种间皮标志物如Calretinin和WT1，血管及淋巴管内皮细胞标志物FLI-1、ERG、podoplanin、D2—40、M2A和VEGFR-3。而CD31、结蛋白、第八因子相关抗原、HHF35、HMB45、MelanA、MyoD1、肌浆蛋白、S-100蛋白和平滑肌肌动蛋白均为阴性。病例自2012年10月随访至2016年8月，有7例复发和5例转移，4例转移至肺。5例死亡，其中2例转移至肺并死亡，1例骨转移并死亡，1例转移至肺、小肠和腹膜并死亡。结论上皮样肉瘤除具有向成骨、软骨和脂肪细胞分化潜能外，还有向间皮、血管内皮细胞和淋巴管内皮等多向分化的潜能。因肿瘤组织主要由上皮样细胞、横纹肌样细胞及梭形细胞构成，形态复杂多样，又具有间皮和淋巴管内皮细胞分化，因而极易与具有类似形态或免疫表型的其他肿瘤混淆。故其鉴别诊断尤为重要。

Objective To investigate the multidirectional differentiation potential in epithelioid sarcoma （ES）, with special emphasis on its mesothelial and lymphatic endothelial markers expression. Methods Ten cases of distal-type ES were included. The clinical, histological, and immunohistochemieal （including mesothelial and lymphatic endothelial markers expression ）features and follow-up data were evaluated. Results The patients aged between 8 to 66 years. Five cases were male and five were female. The tumors were located at the palm （2 cases ） , wrist （3 cases ） , upper arm （2 cases ） , poplitealfossa （1 case）, lower leg （1 case） and thigh （1 case）, respectively. Clinically, most cases presented as painful, firm subcutaneous nodules. Histologically, the tumors were mainly composed of epithelioid, rbabdoid, spindle, or transitional cells, with abundant eosinophilic cytoplasm, oval and vesicular nucleus, and one or more prominent nueleoli. They were arranged in nodular, diffuse nodular or sheet llke growth patterns, frequently with necrosis at the center with vague granulomatous configuration. Immunohistochemically,all tumors expressed cytokeratins, epithelial membrane antigen, CD34, desmin, mesothelial markers such as Calretinin, WT1, D2-40, M2A, vascular and lymphatic endothelial markers FLI-1, and VEGFR-3. The tumor cells did not express CD31, FVIHRAg, HHF35, HMB45, Melan A, MyoD1, myogenin, S-100 protein and SMA. All 10 patients underwent radical resection or extended excision, with additional radiotherapy or chemotherapy. During the follow-up from October 2012 to August 2016, seven cases showed recurrences and metastases within 2 months to 2 years. Five patients died of the disease due to widespread metastases. Conclusions ES may show a wide spectrum of morphology, and display a muhidirectional differentiating capabilities including towards mesothelial and lymphatic endothelial cells. As such, its diagnosis and differential diagnosis are particularly important as it is easily confused with other tumors with similar morphology or immune phenotype.