MiT家族异位肾细胞癌18例临床病理特征及VHL基因分析

Renal cell carcinomas with MiT family translocation:clinicopathological features and VHL genotyping of 18 cases

目的探讨MiT家族异位肾细胞癌(MiT family translocation renal cell carcinoma,MiTF RCC)的临床病理学特征及VHL基因分析。方法回顾性分析18例MiTF RCC的临床病理学特征,并复习相关文献;采用FISH技术检测VHL基因。结果18例MiTF RCC包括16例TFE3异位肾细胞癌(TFE3 translocation renal cell carcinoma,TFE3t RCC)和2例TFEB异位肾细胞癌(TFEB translocation renal cell carcinoma,TFEBt RCC),患者年龄14~60岁,平均36岁,10例因腰部不适或无痛肉眼血尿入院。眼观:MiTF RCC切面灰黄色。镜检:肿瘤可见部分纤维包膜,4例包膜钙化,由上皮样透明细胞、嗜酸细胞构成的乳头状、巢状及腺泡状结构。TFE3t RCC可见砂砾体,TFEBt RCC未见双相形态中的小细胞。免疫表型:18例中15例上皮标记阳性,15例CD10阳性,10例vimentin阳性,8例CK7阳性。18例TFE3均阳性。12例中5例HMB-45或者Melan A阳性。4例中1例PD-L1弥漫强阳性。16例VHL基因中1例3倍体。患者均接受手术切除,术后随访14例,随访13~44个月,平均30个月,均生存。结论MiTF RCC是较为少见的RCC,确诊依赖分子检测,目前以手术切除为主,预后尚未明确。

Purpose To investigate the clinicopathological characteristics of MiT family translocation renal cell carcinomas and to better define VHL gene status.Methods Eighteen genetically confirmed cases of MiTF RCC were collected.The clinicopathological features were summarized and the VHL gene analyses were performed by FISH.Results All tumors were confirmed to demonstrate MiTF aberrations using FISH(16 TFE3 translocation,2 TFEB translocation).The age of patients rangedfrom 14 to 60(mean 36)years.Ten patients went to hospital because of flank pain or painless gross hematuria.Macroscopically,most tumors were tan-yellow in color on cut section.Microscopically,tumors were surrounded in part by a fibrous capsule.Four cases showed capsular calcification.The neoplasm had papillary,nested and alveolar architecture,and tumor cells with voluminous clear or eosinophilic cytoplasm set in a branching capillary vasculature.Psammoma bodies were preferentially identified in TFE3t RCC.TFEBt RCC showed absence of small cell component after careful review of all tissue slides.Immunohistochemically,MiTF RCC was positive at least focally for CK8 or CK18(15 of 18 cases),CD10(15 of 12 cases),vimentin(10 of 18 cases),and CK7(8 of 18 cases).All cases demonstrated TFE3 expression.A few cases demonstrated HMB-45 or Melan A expression(5 of 12 cases).One case expressed PD-L1 strongly and diffusely(1 of 4 cases).Sixteen cases of VHL gene analyses were collected.Only one case showed trisomy.All underwent partial or radical nephrectomy.Follow-up data were obtained in 14 cases and the follow-up time ranged from 13 to 44 months(mean 30 months),and all the patients were survived.Conclusion MiTF RCC is an uncommon form of RCC.The final diagnosis depends on molecular examination.Surgery is still the main treatment.More cases are needed to better define the therapy.