Objective: To study the clinicopathological features and key differential diagnosis of clear cell adenocarcinoma (CCA) of the urinary tract. Methods: A retrospective analysis was performed on the clinicopathological data, immunophenotypes, and molecular test results of patients with pathologically confirmed primary CCA of the urinary tract at Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China from December 2015 to September 2024. This study was supplemented by a review of the relevant literature. Results: Nine patients were included (1 male and 8 females), age 57.0 (44.5, 61.0) years old. The main symptoms were urinary tract irritation and hematuria. Th lesions were in the urethra of 5 patients and in the bladder in 4 patients. Macroscopically, the tumors were cauliflower-like, with edema and firm consistency. Microscopically, they showed mostly papillary/tubular-cystic structures, with solid sheet-like arrangements. The tumor cells showed clear or eosinophilic cytoplasm, moderate to high nuclear grade, prominent nucleoli, and frequent mitotic figures. The tumor cells also exhibited strong expression of PAX8, CK7, and HNF1-β, various positivity of Napsin A and P504s, and partial expression of SOX17, CK20, and GATA3. The Ki-67 index ranged from 30% to 70%, and p53 showed a heterogeneous expression pattern. The cells were negative for p63 and the renal cell carcinoma marker (RCC). Among the 7 cases subject to urine fluorescence in situ hybridization (FISH) testing, 5 cases showed abnormal centromeric signals. One case underwent next-generation sequencing (DNA-seq) and harbored a nonsense ARID1A mutation. Two patients underwent radical surgery, 3 total urethrectomy, and 4 palliative surgery. Four patients received postoperative chemotherapy. The follow-up ranged from 9 to 58 months: 3 patients had tumor recurrence while 2 died. Conclusions: CCA of the urinary tract is a rare and aggressive malignancy. Its histological morphology resembles that of ovarian CCA. The diagnosis should be based on a combination of morphological features and immunophenotype. It is recommended to use PAX8, CK7, HNF1-β, and Napsin A as a core immunohistochemical panel, while testing SOX17 can also help.
目的： 探讨原发于泌尿道的透明细胞腺癌（CCA）的临床病理学特征及鉴别诊断要点。 方法： 回顾性分析中山大学孙逸仙纪念医院2015年12月至2024年9月经病理确诊的原发于泌尿道CCA患者的临床病理资料、免疫表型及分子检测结果，结合相关文献进行复习；并纳入同期确诊的12例肾源性腺瘤（nephrogenic adenoma，NA）及12例原发于卵巢的CCA作为对照，比较SOX17标志物的表达差异。 结果： 共纳入9例患者（男1例，女8例），年龄57.0（44.5，61.0）岁。主要症状为泌尿道刺激症状和血尿；病灶位于尿道5例，膀胱4例。大体呈菜花状、黏膜粗糙僵硬或水肿；镜下以乳头状/管囊状结构为主，少数呈实性片状排列；肿瘤细胞胞质透亮或嗜酸性，细胞核级中-高级，核仁明显，核分裂象易见。免疫表型：肿瘤细胞强表达PAX8、CK7及HNF1-β，Napsin A与P504s呈不同程度阳性，部分表达SOX17、CK20及GATA3，Ki-67阳性指数30%~70%，p53呈强弱不等阳性表达；不表达p63及肾细胞癌标志物（RCC）。对照研究显示，SOX17在NA中呈阴性或弱阳性（12/12），在泌尿道CCA中部分呈高表达（6/9），在卵巢CCA中均呈强阳性（12/12）。分子特征：7例行尿液荧光原位杂交（FISH）检测，5例检测到染色体着丝粒位点（CSP）信号异常；1例行二代测序（DNA-seq）检出ARID1A无义突变。治疗与预后：2例行根治性手术，3例行尿道全切术，4例姑息性手术治疗；4例行术后化疗。随访9~58个月，3例复发，2例死亡。 结论： 原发于泌尿道的CCA是一种罕见的侵袭性恶性肿瘤，其组织学形态与卵巢CCA相似。诊断需结合形态学及免疫表型，推荐使用PAX8、CK7、HNF1-β及Napsin A作为核心免疫组织化学标志物组合，SOX17的表达情况也可为鉴别提供辅助参考。.