EWSR1/FUS-TFCP2融合的上皮/梭形细胞横纹肌肉瘤临床病理学研究

Clinicopathological study of epithelioid and spindle cell rhabdomysarcoma with EWSR1/FUS-TFCP2 fusion

目的:探讨EWSR1/FUS-TFCP2融合的上皮/梭形细胞横纹肌肉瘤临床病理及分子遗传学特征。方法:收集佛山市中医院病理科2019年1月至2022年12月明确诊断为EWSR1/FUS-TFCP2融合的上皮/梭形细胞横纹肌肉瘤会诊病例14例,对其临床、病理形态学、免疫组织化学特点进行回顾性分析,利用荧光原位杂交及二代测序技术分析其分子遗传学特征,并复习相关文献。结果:14例患者中男性5例,女性9例,年龄6~36岁(平均22岁),发生部位分别为头颈部9例,骨盆2例,膀胱1例,左耻骨1例,腹壁、肱骨及耻骨多发1例。临床表现多为伴有疼痛的占位性病变,影像学表现多为侵袭性的放射学特征伴有软组织累及。肿瘤平均直径6.6 cm(最大径2~23 cm),瘤组织界限不清,镜下主要由比例不等的梭形细胞及上皮样细胞构成。瘤组织分化不一,分化差的瘤组织异型性明显,核分裂象活跃,肿瘤性坏死明显;分化好的瘤组织,梭形细胞和/或上皮样细胞胞质中等或丰富,核轻度异型性,排列呈束状或席纹状。免疫组织化学显示瘤组织表达MyoD1、Myogenin及结蛋白,程度不等地表达间变性淋巴瘤激酶、上皮细胞膜抗原、广谱细胞角蛋白。本组14例病例,其中9例通过国内4家不同的分子平台进行二代测序检测,同时加做荧光原位杂交(FISH)获得验证,另外5例采用FISH技术显示有TFCP2的断裂(同时加做FISH检测显示有EWSR1或FUS的断裂)。14例病例中,6例为EWSR1-TFCP2融合,8例为FUS-TFCP2融合。13例获得随访资料,随访时间5~37个月,7例因肿瘤转移死亡,其余6例存活(2例复发并转移、2例复发、1例转移、1例无复发转移)。结论:EWSR1/FUS-TFCP2融合的上皮/梭形细胞横纹肌肉瘤是一种具有上皮样和梭形细胞形态特征且伴有特征性融合分子的高度侵袭性恶性肿瘤,好发于骨,尤其是颌面部。发病年龄较广。分子特征为EWSR1/FUS-TFCP2的融合,熟悉其临床病理学特征有利于诊断及鉴别诊断,避免误诊。

Objective To investigate the clinicopathological and genetic features of epithelioid and spindle cell rhabdomysarcoma with EWSR1-TFCP2 or FUS-TFCP2 fusion.Methods The clinical,morphological and immunohistochemical features of 14 cases of epithelioid and spindle cell rhabdomysarcoma with EWSR1-TFCP2 or FUS-TFCP2 fusion diagnosed from January 2019 to December 2022 in the Department of Pathology,Foshan Traditional Chinese Medicine Hospital,Foshan,China were retrospectively analyzed.The cases were all subject to FISH or next generation sequencing for analysis of molecular genetic features.The literature was reviewed.Results There were 5 males and 9 females,with the age at presentation ranging from 6 to 36 years(mean,22 years).Tumors occurred in the head and neck(9 cases),pelvic region(2 cases),bladder(one case),right humerus(one case),and the abdominal wall,humerus and pubic at the same time(one case).Presenting symptoms varied by location but often included pain or discomfort.Most of the patients showed aggressive radiographic features with soft tissue extension.The tumors had a median size of 6.6 cm(range,2-23 cm).The tumors were poorly defined and irregularly shaped.Microscopic examination showed diffuse proliferation of spindle or epithelioid cells.While morphologically high-grade tumors displayed obvious cytological atypia,a high mitotic count and tumor necrosis,low-grade tumors grew in sheets and fascicles composed of spindle,epithelioid cells with moderate or abundant amounts of eosinophilic cytoplasm,without pronounced cytological atypia.The tumor cells expressed Desmin,MyoD1,and Myogenin,as well as ALK,EMA,and CKpan.EWSR1/FUS-TFCP2 gene fusion was detected in 14 cases with next generation sequencing and confirmed by FISH.Six cases had EWSR1-TFCP2 fusions and 8 cases showed FUS-TFCP2 fusions.Follow-up information was available in 13 patients,ranged from 5 to 37 months.At the end of follow-up period,7 patients died of the disease.Six patients were alive:two cases had local recurrences and metastases,two cases of recurrences,one case of metastasis and one case without recurrences and metastasis.Conclusions Epithelioid and spindle cell rhabdomysarcomas with EWSR1-TFCP2 or FUS-TFCP2 fusion show a very aggressive clinical course,and more commonly occur in the head and neck.Their genetic hallmark is the presence of EWSR1/FUS-TFCP2 fusions.Familiarity with its clinicopathological characteristics is helpful in avoiding misdiagnoses.