CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题：ALK-Rearranged Renal Cell Carcinoma: A Study of Three Cases With Clinicopathologic Features and Effect of Postoperative Adjuvant Immunotherapy.
ALK-Rearranged Renal Cell Carcinoma: A Study of Three Cases With Clinicopathologic Features and Effect of Postoperative Adjuvant Immunotherapy.
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ALK-RCC 代表一种具有临床病理、遗传和免疫表型异质性的独特实体。初次筛查时的 ALK IHC 分析可能有助于疑难病例的诊断。对于进展性 ALK-RCC，术后辅助免疫治疗最好根据 IP 特征进行选择。免疫排斥表型的患者可能无法从免疫治疗中获益。
ALK重排肾细胞癌（ALK-RCC）是一种罕见的肾脏恶性上皮性肿瘤。ALK-RCC最近已被列入第5版世界卫生组织（WHO）肿瘤分类，作为一种分子定义的RCC亚型。
我们回顾性描述了3例ALK-RCC，从临床病理学、免疫组化（IHC）和分子遗传学方面，以及术后辅助治疗方案和预后相关信息。
2例患者为女性，1例为男性。患者年龄38至64岁（平均51.3岁）。肿瘤大小32 mm至89 mm（平均55.3 mm，中位45 mm）。3例肿瘤均弥漫性表达ALK蛋白。通过下一代测序鉴定出ALK融合伴侣（病例1为TPM3，病例2为VCL，病例3为EML4）。组织形态学上，肿瘤具有异质性，表现为管状囊性、乳头状、梁状和实性生长模式，以及多边形至横纹肌样肿瘤细胞。病例1和病例3背景为黏液性。通过IHC定量肿瘤相关CD8+ T细胞后，肿瘤免疫表型（IPs）定义为：病例1为免疫荒漠型，病例2为免疫炎症型，病例3为免疫排斥型。3例患者的随访时间为18至129个月（平均59.3个月）。病例1拒绝术后辅助治疗，随访129个月时无病生存期。病例2术后接受PD-1靶向单克隆抗体治疗，随访18个月时无病生存期。病例3初诊时即有腹膜后淋巴结和肺转移。她术后接受PD-1靶向单克隆抗体治疗，随访时计算机断层扫描提示无获益。
ALK-rearranged renal cell carcinoma (ALK-RCC) is a rare malignant epithelial tumor of the kidney. ALK-RCC has recently been listed in the 5 th edition of the World Health Organization (WHO) Classification of Tumors as a molecularly defined RCC subtype.
We describe retrospectively 3 ALK-RCCs from clinicopathologic, immunohistochemical (IHC), and molecular genetic aspects, along with postoperative adjuvant therapeutic regime and prognosis-related information.
Two patients were female and one patient was male. Patients' age ranged from 38 to 64 years (mean 51.3 years). Tumor size ranged from 32 mm to 89 mm (mean 55.3 mm, median 45 mm). All 3 tumors were diffusely positive for ALK protein. ALK fusion partners (TPM3 for case 1, VCL for case 2, and EML4 for case 3) were identified by next-generation sequencing. Histomorphologically, the tumors were heterogeneous, showing tubulocystic, papillary, trabecular, and solid growth patterns and polygonal to rhabdoid neoplastic cells. Cases 1 and 3 set in a mucinous background. Upon quantification of tumor-associated CD8 + T cells by IHC, tumor immune phenotypes (IPs) were defined as immune-desert in case 1, immune-inflamed in case 2, and immune-excluded in case 3. Follow-up for the 3 patients ranged from 18 to 129 months (mean, 59.3 months). Case 1 refused postoperative adjuvant therapy and was alive without disease at 129-month follow-up. Case 2 was postoperatively treated with a PD-1-targeted monoclonal antibody, being alive without disease at 18-month follow-up. Case 3 showed retroperitoneal lymph nodes and lung metastases at initial diagnosis. She was postoperatively treated with a PD-1-targeted monoclonal antibody, with no benefit suggested by computed tomography on follow-up.
ALK-RCC represents a distinct entity with clinicopathological, genetic, and immunophenotypic heterogeneity. ALK IHC analysis during primary screening may aid diagnosis in difficult cases. For progressive ALK-RCCs, postoperative adjuvant immunotherapy may be best selected according to IP features. Patients with immune-excluded phenotypes may not benefit from immunotherapy.
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