Hereditary syndromes and RCC: what radiologists need to know

Hereditary renal cell carcinoma (RCC) accounts for approximately 5-8% of all renal cancers. This review provides a comprehensive overview of the seven hereditary RCC syndromes recognized by the National Comprehensive Cancer Network: Tuberous Sclerosis Complex (TSC), Von Hippel-Lindau (VHL), Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC), Hereditary Papillary Renal Carcinoma (HPRC), Birt-Hogg-Dubé syndrome (BHDS), Succinate dehydrogenase (SDH)-deficient RCC/Hereditary Paraganglioma/Pheochromocytoma (PGL/PCC) syndrome, and BAP1 tumor predisposition syndrome (BAP1-TPDS). For each syndrome, the underlying inheritance, epidemiology, and clinicopathologic features of their associated RCCs are detailed. Furthermore, radiographic challenges faced in the diagnosis of RCC in some of these syndromes are discussed, including differentiating RCC from the more common lipid-poor AML in TSC, distinguishing papillary RCC from hemorrhagic cysts in HPRC, and discerning chromophobe RCC from oncocytomas in BHDS. Radiologists are integral to the multidisciplinary management of hereditary RCC, as they are often the first to identify clinicopathologic features suggestive of an underlying genetic syndrome. Recognizing these patterns is crucial for prompting timely genetic evaluation, guiding decisions for nephron-sparing interventions, and establishing appropriate surveillance for patients and their at-risk family members. Advances in radiogenomics and artificial intelligence hold promise for further refining non-invasive diagnosis and personalizing patient care.