From the Guidelines
A 36-year-old male with papillary renal cell carcinoma (RCC) should undergo genetic testing, as early-onset RCC, particularly the papillary subtype, raises suspicion for hereditary cancer syndromes. According to the most recent and highest quality study, genetic testing should include a comprehensive panel for hereditary RCC syndromes, focusing on genes like MET, FH, FLCN, VHL, BAP1, SDHB, and others associated with hereditary papillary RCC 1. The testing process typically involves a blood or saliva sample and genetic counseling before and after testing. Results can impact surveillance strategies for the patient, guide treatment decisions, and enable cascade testing for family members who may carry the same genetic mutation.
Some key points to consider:
- Papillary RCCs are characterized by type 1 and type 2 RCCs, with type 2 often associated with SETD2 mutations, CDKN2A mutations, or TFE3 fusions 1.
- In papillary type 2 with familial history of papillary RCC, a fumarate hydratase (FH) mutation should also be investigated 1.
- Approximately 5-8% of all RCC cases have a hereditary component, but this percentage increases significantly in young patients 2, 3.
- Early identification of a hereditary syndrome can lead to tailored screening protocols and potentially life-saving interventions for both the patient and at-risk family members 4.
It is essential to note that the patient's age and the presence of papillary RCC increase the likelihood of a hereditary component, making genetic testing a crucial step in management. The testing and screening recommendations should be individualized, and the decision to start surveillance should be made on a case-by-case basis, considering the youngest reported case of RCC in the setting of HLRCC 4.
From the Research
Genetic Testing for Hereditary Renal Cell Carcinoma Syndromes
- Hereditary renal cell carcinoma (RCC) syndromes account for approximately 3-5% of all RCC cases 5, 6, 7, 8, 9
- These syndromes are often characterized by an earlier age of onset, multicentric and bilateral tumors, and extrarenal manifestations 5, 6, 7, 9
- Genetic testing can help identify individuals with hereditary RCC syndromes, allowing for early detection and surveillance of renal tumors 7, 8
Indications for Genetic Testing
- Young age at onset of RCC (e.g., 36 years old) 7
- Bilateral or multicentric tumors 7
- Family history of RCC or other hereditary cancer syndromes 6, 7
- Presence of extrarenal clinical features suggestive of a specific renal tumor susceptibility syndrome 6, 9