Objective: To investigate the clinicopathological features, immunophenotype, molecular characteristics, and differential diagnosis of MED15-TFE3 gene fusion renal cell carcinoma (MED15-TFE3 RCC). Methods: A total of 12 MED15-TFE3 RCCs, diagnosed from 2016 to 2023, were collected from the Department of Pathology of Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, China for clinicopathologic, immunohistochemical, fluorescence in situ hybridization (FISH) and RNA sequencing (RNA-seq) analyses and follow-up. In addition, its diagnosis and differential diagnosis were also explored. Results: There were five males and seven females. The patients' ages ranged from 16 to 60 years, with an average age of 40.4 years. The follow-up time ranged from 15 to 92 months, and no recurrence or metastasis was observed. Histologically, 6 cases exhibited extensive cystic structures with almost no solid sheet components, while the remaining 6 cases displayed a cysto-solid growth pattern. The cytoplasm of the tumor cells appeared flocculent, with a clear or faintly eosinophilic appearance, and nucleoli were inconspicuous. Psammoma bodies were observed in 12 cases. There was deposition of basement membrane-like material in 5 cases. All cases showed strong expression of TFE3, GPNMB, Cathepsin K, Melan A, and PAX8, while no expression of CAⅨ or CK7. FISH analyses showed that all 12 cases were positive for the MED15-TFE3 fusion, while the MED15-TFE3 fusion gene and specific fusion sites were detected in 2 cases using RNA-seq. Conclusions: MED15-TFE3 RCC is a type of TFE3-rearranged renal cell carcinoma that exhibits both identifiable diagnostic characteristics and highly deceptive morphology. Its distinct extensive cystic structure can be easily confused with multilocular cystic renal neoplasm of low malignant potential, necessitating careful differentiation in routine practice.
目的： 探讨MED15-TFE3基因融合肾细胞癌（MED15-TFE3 renal cell carcinoma，MED15-TFE3 RCC）的临床病理特征、免疫表型、分子特征及鉴别诊断。 方法： 对解放军东部战区总医院2016—2023年收集的12例MED15-TFE3 RCC行光镜观察、免疫组织化学染色、荧光原位杂交检测、高通量转录组测序（RNA sequencing，RNA-seq），并进行随访，探讨MED15-TFE3 RCC的诊断与鉴别诊断。 结果： 12例患者中男性5例，女性7例。患者年龄16~60岁，平均年龄40.4岁，随访15~92个月，未发现复发转移现象。镜下观察：6例呈广泛囊性结构，几乎无实性片状成分，其余6例呈囊实性生长模式。肿瘤细胞胞质絮状呈透明样或弱嗜酸性，核仁不明显。12例中均可观察到沙砾体形成，其中5例还可见到红染的基底膜样物质沉积。12例均强阳性表达TFE3、GPNMB、Cathepsin K、Melan A 以及PAX8，不表达碳酸酐酶Ⅸ（CAⅨ）和细胞角蛋白（CK）7。12例MED15-TFE3融合探针荧光原位杂交检测均阳性，其中2例经RNA-seq检测到MED15-TFE3融合基因及具体融合位点。 结论： MED15-TFE3 RCC是一类具有可识别特征同时又极具迷惑性的TFE3重排肾细胞癌，其特征性的广泛囊性结构极易与低度恶性潜能的多房囊性肾肿瘤混淆，日常工作中需要特别注意鉴别。.