TFE3重排的上皮样血管内皮瘤7例临床病理特征

Epithelioid hemangioendothelioma with TFE3 translocation:a clinicopathological study of 7 cases

目的探讨TFE3重排的上皮样血管内皮瘤(epithelioid hemangioendothelioma,EHE)的临床病理学特征、免疫表型及分子特点。方法收集7例原发性TFE3重排的EHE,采用EnVision两步法进行免疫组化染色,FISH检测WWTR1-CAMTA1融合基因及TFE3基因断裂重排情况,二代测序检测其融合转录本。结果7例患者中男性3例,女性4例,年龄33~61岁(中位年龄45岁,平均46.3岁)。肿瘤发生于软组织5例、肺1例、淋巴结1例。组织学上,肿瘤细胞轻至中度异型性,呈上皮样,胞质丰富嗜酸性,见胞质内空泡和胞质内红细胞,细胞核卵圆形,染色质分布均匀,有小核仁,可见双核或多核细胞,未见核分裂及坏死;肿瘤细胞呈条索状、实性片状和巢状排列,可见假腺泡/假肺泡结构。免疫表型:肿瘤细胞表达CD31(7/7)、CD34(4/7)、ERG(7/7)、TFE3(7/7),Ki-67增殖指数<5%,不表达CK(AE1/AE3)、EMA。7例FISH检测均可见TFE3基因断裂,其中1例行二代测序,检测到YAP1(exon1)-TFE3(exon4)融合,7例均未见WWTR1-CAMTA1融合信号。7例患者随访时间12~83个月(平均48.9个月),1例死亡,6例无瘤生存,存活者术后均未见复发或转移。结论与经典的EHE相比,TFE3重排的EHE是一种少见的分子亚型,具有特殊的临床病理学特征,免疫组化标记和分子病理学检查有助于诊断和鉴别诊断。

Purpose To investigate the clinicopathological features,immunophenotype and molecular characteristics of epithelioid hemangioendothelioma(EHE)with TFE3 translocation.Methods 7 cases of primary EHE with TFE3 translocation were observed,immunohistochemical staining was performed by EnVision two-step method,FISH was used to detect WWTR1-CAMTA1 fusion gene and TFE3 gene rearrangements,and the fusion transcripts were delineated by next-generation sequencing(NGS).Results The patients included 3 men and 4 women with a median age of 45 years(range,33 to 61 years).The tumor occurred in soft tissue(5 cases),lung(1 case)and lymph node(1 case).Histologically,the tumor cells showed mild to moderate atypia with epithelioid appearance and abundant eosinophilic cytoplasm.There were numerous intracytoplasmic vacuoles and intracytoplasmic red blood cells.The nuclei were ovoid with evenly distributed chromatin and small nucleoli.Bi-or multinucleated cells were also visible.No mitosis and necrosis were observed.The tumor cells were arranged in cords,solid sheets and nests,and pseudoacinar/pseudoalveolar structures were seen.Immunohistochemistry,the tumor cells showed strong and diffuse positive for CD31(7/7),CD34(4/7),ERG(7/7)and TFE3(7/7),but negative for CK(AE1/AE3)or EMA,the proliferating index of Ki-67 did not exceed 5%.TFE3 gene break-apart were identified in all 7 cases by FISH,of which 1 case underwent next-generation sequencing,YAP1(exon1)TFE3(exon4)fusion gene was detected,but no WWTR1-CAMTA1 fusion signal was revealed.Follow-up data were obtained for all the 7 cases,and the follow-up time ranged between 12-83 months(mean 48.9 months).1 case died of disease and 6 cases survived without tumor.No recurrence or metastasis was found in the survivors.Conclusion Compared with the classical cases,EHE with TFE3 translocation is a rare molecular subtype with special clinicopathological features.Immunophenotypic analysis and molecular pathologic examination are helpful for its diagnosis and differential diagnosis.