Biomedical
Clear cell and papillary renal cell carcinomas in hereditary papillary renal cell carcinoma (HPRCC) syndrome: a case report
Peer Reviewed
Abstract
Background 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. Case presentation 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. Conclusions 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.
Key Questions
What is Hereditary Papillary Renal Cell Carcinoma (HPRCC) syndrome?
HPRCC is a rare autosomal dominant disorder characterized by the development of multiple and bilateral papillary type I renal cell carcinomas and papillary adenomas, typically caused by activating mutations in the MET proto-oncogene.
What was unique about the renal tumors observed in the reported patient with HPRCC?
In addition to the expected papillary tumors, the patient developed clear cell renal cell carcinomas, which had not been previously reported in association with HPRCC syndrome.
What genetic findings were identified in the clear cell renal cell carcinomas of the patient?
Fluorescence in situ hybridization (FISH) analysis revealed a VHL deletion in one of the clear cell tumors, and the metastatic clear cell tumor exhibited trisomy of chromosomes 7 and 17, genetic alterations typically associated with papillary RCC.
What are the clinical implications of this case for diagnosing HPRCC?
The presence of non-papillary RCCs, such as clear cell carcinomas, in patients with multiple papillary tumors should not exclude the diagnosis of HPRCC. Comprehensive genomic studies are recommended to accurately identify the syndrome and guide appropriate management.
