Objective: To investigate the clinicopathological characteristics, immunophenotypes, molecular features, and differential diagnosis of BAP1 mutated clear cell renal cell carcinoma (CCRCC) for better understanding this entity. Methods: Clinical data, histological morphology, immunophenotypes and molecular characteristics of 18 BAP1 mutated CCRCC cases diagnosed at the Department of Pathology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China from January 2020 to December 2022 were analyzed. The patients were followed up. Results: There were 17 males and 1 female patients, aged from 39 to 72 years, with an average age of 56.3 years. Sixteen patients with primary CCRCC were followed up for an average of 24 months, 7 patients had metastases occurred from 4 to 22 months postoperatively. Thirteen of the 16 patients were alive at the time of the last follow-up while 3 patients died 12, 15, and 20 months after the surgery, respectively. One patient underwent retroperitoneal mass resection, but had lung metastasis 32 months after surgery. One case received cervical tumor resection and died at 22 months after the surgery. Characteristic CCRCC regions were identified in 11 of the 18 cases. The tumor cells were arranged in papillary, alveolar, and large nest patterns. Abundant lymphoid tissue, necrosis, and psammoma bodies were seen. Tumor cells showed abundant eosinophilic cytoplasm, and sometimes exhibited rhabdoid differentiation. Round eosinophilic globules were located in the cytoplasm and extracellular matrix. There were 9 cases with WHO/International Society of Urological Pathology grade 3, and 9 cases with grade 4. PAX8 (18/18), carbonic anhydrase 9 (CA9, 16/18), CD10 (18/18), and vimentin (18/18) were positive in the vast majority of tumors.TFE3 was expressed in 5 cases, with strong expression in only 1 case. Eighteen cases were all positive for P504s. Twelve cases harbored a BAP1 mutation combined with von Hippel-Lindau (VHL) mutation, and 2 cases had mutations in BAP1, VHL and PBRM1 simultaneously. SETD2 mutation was not found in any of the cases. Conclusions: BAP1 mutated CCRCC contained papillary, alveolar, and large nest patterns, eosinophilic cytoplasm, high-grade nucleoli, and collagen globules, with P504s positivity. In practical work, when encountering CCRCC containing these features, pathologists should consider the possibility of BAP1 mutations and conduct related molecular tests.
目的： 探讨BAP1突变的透明细胞性肾细胞癌（clear cell renal cell carcinoma，CCRCC）的临床病理特征、免疫表型、分子特征及鉴别诊断，以提高病理医师对该类肿瘤的认识。 方法： 收集浙江大学医学院附属第一医院病理科2020年1月至2022年12月诊断的BAP1突变的CCRCC患者18例，对其临床资料、组织学形态、免疫表型及分子特征进行总结并随访预后。 结果： 患者男性17例，女性1例，年龄39~72岁，平均年龄56.3岁。16例原发肿瘤，平均随访时间24个月，7例术后4~22个月发生远处转移，13例存活，3例于术后12、15和20个月死亡。1例腹膜后肿物切除术患者，术后32个月肺转移。1例颈椎肿瘤切除术患者，术后22个月死亡。11例肿瘤含有典型的CCRCC区域。BAP1突变的CCRCC含多种组织学结构，主要为乳头状、肺泡状、大巢状。部分病例间质见丰富的淋巴组织、坏死及沙砾体。肿瘤细胞胞质丰富、嗜酸性。部分病例可见横纹肌样形态。肿瘤细胞胞质内及细胞间含有浅粉染、圆形嗜酸性小球。细胞核WHO/国际泌尿病理协会（ISUP）分级3级9例，4级9例。PAX8（18/18）、碳酸酐酶9（CA9，16/18）、CD10（18/18）、波形蛋白（18/18）在绝大多数肿瘤阳性。TFE3在5例中出现表达，仅1例为强阳性。18例P504s均阳性。BAP1合并希佩尔林道（von Hippel Lindau，VHL）突变的有12例，BAP1、VHL、PBRM1三者突变有2例，均未发现SETD2突变。 结论： BAP1突变的CCRCC含有乳头状、肺泡状、大巢状的组织结构，嗜酸性胞质，高级别核仁及胶原小球，P504s阳性。实际工作中病理医师遇到含有这些形态的CCRCC时，应当想到存在BAP1突变的可能，及时进行分子检测。.