Service d'Anatomie Pathologique, AP-HP, Université Paris-Saclay, Hôpital de Bicêtre, Service d'Anatomie Pathologique, 78 rue du Général Leclerc, 94270, Le Kremlin-Bicêtre, France.
Réseau National de Référence pour Cancers Rares de l'Adulte PREDIR labellisé par l'INCa, Hôpital de Bicêtre, AP-HP, Service d'Anatomie Pathologique, 78 rue du Général Leclerc, 94270, Le Kremlin-Bicêtre, France.
Diagn Pathol. 2021 Nov 20;16(1):107. doi: 10.1186/s13000-021-01170-8.
Hereditary papillary renal cell carcinoma (HPRCC) is a rare autosomal dominant disease characterized by the development of multiple and bilateral papillary type I renal cell carcinomas (RCC) and papillary adenomas caused by activating mutations in the MET proto-oncogene. Classically, distinctive histological features of RCC are described according to the familial renal cell carcinoma syndrome. To date, no clear cell RCC has been reported in HPRCC syndrome.
We describe the case of a 51-year-old man with a germline MET mutation detected on peripheral blood testing, and no germline VHL mutation, who developed numerous papillary tumors but also unexpectedly clear cell renal cell carcinomas. During the follow-up, an adrenal metastasis was observed 7 years after the initial diagnosis corresponding to a clear cell RCC metastasis. By immunohistochemistry, clear cell tumors showed focal cytokeratin 7, moderate racemase, and diffuse and membranous CAIX expression, while papillary tumors expressed strong diffuse cytokeratin 7 and racemase without CAIX positivity. Using FISH, VHL deletion was observed in one of the clear cell tumors, and the metastatic clear cell tumor presented a trisomy of chromosomes 7 and 17. These last genomic alterations are usually detected in papillary RCC, highlighting the potential link between both histological subtypes of tumors and the HPRCC syndrome.
The pathologist must be aware that the presence of a non-papillary RCC associated with numerous papillary tumors should not exclude the diagnostic suspicion of HPRCC and thus to perform a thorough genomic study.
遗传性乳头状肾细胞癌（HPRCC）是一种罕见的常染色体显性遗传疾病，其特征是由 MET 原癌基因的激活突变引起的多发性、双侧乳头状 I 型肾细胞癌（RCC）和乳头状腺瘤的发生。经典地，根据家族性肾细胞癌综合征描述 RCC 的独特组织学特征。迄今为止，HPRCC 综合征尚未报道明确的细胞 RCC。
我们描述了一例 51 岁男性，外周血检测到 MET 种系突变，无 VHL 种系突变，他发生了许多乳头状肿瘤，但也意外地发生了明确的细胞肾细胞癌。在随访中，在初始诊断 7 年后观察到肾上腺转移，对应于明确的细胞 RCC 转移。免疫组化显示，明确的细胞肿瘤表现为局灶性细胞角蛋白 7、中等 Racemase 和弥漫性和膜 CAIX 表达，而乳头状肿瘤表达强烈的弥漫性细胞角蛋白 7 和 Racemase，没有 CAIX 阳性。使用 FISH，在一个明确的细胞肿瘤中观察到 VHL 缺失，转移性明确的细胞肿瘤表现出染色体 7 和 17 的三体。这些最后的基因组改变通常在乳头状 RCC 中检测到，突出了两种肿瘤组织学亚型与 HPRCC 综合征之间的潜在联系。
病理学家必须意识到，与许多乳头状肿瘤相关的非乳头状 RCC 的存在不应排除 HPRCC 的诊断怀疑，因此应进行全面的基因组研究。
