Bai Y F, Weng M H, He J J, Xu L M, Chang C D, Teng X D
Department of Pathology, the First Affiliated Hospital, Zhejiang University School of Medicine,Hangzhou 310003, China.
Zhejiang Provincial Key Laboratory of Pancreatic Disease, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
Zhonghua Bing Li Xue Za Zhi. 2024 Aug 8;53(8):797-802. doi: 10.3760/cma.j.cn112151-20240203-00081.
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. 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. 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. 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.
为了更好地了解BAP1突变型透明细胞肾细胞癌（CCRCC）的临床病理特征、免疫表型、分子特征及鉴别诊断，对18例BAP1突变型CCRCC病例的临床资料、组织形态学、免疫表型及分子特征进行分析。这些病例于2020年1月至2022年12月在中国杭州浙江大学医学院附属第一医院病理科确诊。对患者进行随访。患者共17例男性和1例女性，年龄39至72岁，平均年龄56.3岁。16例原发性CCRCC患者平均随访24个月，7例患者术后4至22个月发生转移。16例患者中13例在最后一次随访时存活，3例分别于术后12、15和20个月死亡。1例患者接受腹膜后肿块切除术，但术后32个月发生肺转移。1例患者接受颈部肿瘤切除术，术后22个月死亡。18例病例中有11例发现典型的CCRCC区域。肿瘤细胞呈乳头状、腺泡状和大巢状排列。可见丰富的淋巴组织、坏死和砂粒体。肿瘤细胞胞质丰富嗜酸性，有时表现为横纹肌样分化。圆形嗜酸性小球位于细胞质和细胞外基质中。WHO/国际泌尿病理学会3级9例，4级9例。绝大多数肿瘤中PAX8（18/18）、碳酸酐酶9（CA9，16/18）、CD10（18/18）和波形蛋白（18/18）呈阳性。5例表达TFE3，仅1例强表达。18例P504s均为阳性。12例存在BAP1突变合并冯·希佩尔-林道（VHL）突变，2例同时存在BAP1、VHL和PBRM1突变。所有病例均未发现SETD2突变。BAP1突变型CCRCC具有乳头状、腺泡状和大巢状结构，嗜酸性细胞质，高级别核仁以及胶原小球，P504s阳性。在实际工作中，当遇到具有这些特征的CCRCC时，病理学家应考虑BAP1突变的可能性并进行相关分子检测。
