[Eosinophilic solid and cystic renal cell carcinoma: clinicopathological analysis and molecular characterization].

Objective: To study the clinicopathological features, immunohistochemical phenotype, molecular changes, differential diagnosis and prognosis of eosinophilic solid and cystic renal cell carcinoma (ESC RCC). Methods: A total of 15 cases were selected from 2005 to 2019 at Nanjing Jinling Hospital,Nanjing University School of Medicine for clinicopathological and immunohistochemical analysis, 10 of which were subject to cancer-associated mutation analysis using targeted next-generation sequencing (NGS) panel. A literature review was also performed. Results: The patients' ages ranged from 15 to 68 years (mean, 33 years). The male-to-female ratio was 1.1∶1.0. During a mean follow-up of 22 months, none of the patients developed tumor recurrence, progression or metastasis. Histologically, the tumors typically demonstrated solid and cystic architectures and the neoplastic cells contained voluminous eosinophilic cytoplasm with prominent granular cytoplasmic stippling. Immunohistochemically, tumor cells in all cases were immunoreactive for CK20. Signal pathway related protein mTOR and S6 were positive in 14/15 and 6/15 cases, respectively. Cathepsin K, Melan A and HMB45 were at least focally positive in 12/15, 6/15 and 2/15 cases, respectively. CK7 and CD10 showed focal immunostain positivity in some cases, while TFE3, TFEB, CA9 and CD117 were negative in all cases. NGS demonstrated TSC1/TSC2 mutations in all tested cases (10/10). Conclusions: ESC RCC is a rare tumor that tends to occur in young patients with an indolent behavior. Diagnosis can be established by its distinct clinical and histopathologic findings, immunohistochemical phenotype and molecular genetics. The tumor may be considered as a new subtype of RCC.目的： 探讨嗜酸性实性和囊性肾细胞癌（eosinophilic solid and cystic renal cell carcinoma, ESC RCC）的临床病理特征、免疫表型、分子改变、鉴别诊断及预后。 方法： 对解放军东部战区总医院2005至2019年收集的对15例ESC RCC进行光镜观察、免疫组织化学研究、高通量DNA靶向测序及随访，并复习相关文献。 结果： 15例患者中女性7例，男性8例。患者年龄15~68岁，平均年龄33岁，平均随访22个月，均无病生存。镜下肿瘤呈囊性及实性生长结构，肿瘤细胞胞质丰富嗜酸，胞质内可观察到嗜碱性的颗粒状物或嗜酸性小球。15例ESC RCC细胞角蛋白（CK）20均阳性，13例CK20呈特征性点灶状阳性表达，CK7多数阴性，仅4例局灶阳性表达，CD10在6例中至少局灶阳性，信号通路相关的指标mTOR、S6的阳性比例分别为14/15和6/15，Cathepsin K、Melan A和HMB45在12/15、6/15和2/15的病例中至少局灶阳性表达，TFE3、TFEB、CA9和CD117均阴性。高通量DNA靶向测序证实10/10的病例中存在TSC1/TSC2基因突变。 结论： ESC RCC是一种罕见的肾细胞癌，好发于青壮年，具有独特的形态特征、免疫表型和分子改变，生物学行为惰性，有望成为一种独立的肾癌亚型，明确诊断该肿瘤对患者的治疗方案选择以及预后预测意义重大。.