Hereditary Renal Cell Carcinoma

Abstract

BACKGROUND: Hereditary renal cell carcinoma (RCC) is a complex and rapidly evolving topic as there is a growing body of literature regarding inherited syndromes and mutations associated with an increased risk of RCC. OBJECTIVES: We sought to systematically review 13 hereditary syndromes associated with RCC; von Hippel-Lindau Disease associated RCC (VHLRCC), BAP-1 associated clear cell RCC (BAPccRCC), Familial non-von Hippel Lindau clear cell RCC (FccRCC), Tuberous Sclerosis Complex associated RCC (TSCRCC), Birt-Hogg-Dub e Syndrome associated RCC (BHDRCC), PTEN Hamartoma Tumor Syndrome associated RCC (PHTSRCC), Microphthalmia-associated Transcription Family translocation RCC (MiTFtRCC), RCC with Chromosome 6p Amplification (TFEBRCC), Autosomal Dominant Polycystic Kidney Disease associated RCC (ADPKDRCC), Hereditary Leiomyomatosis associated RCC (HLRCC), Succinate Dehydrogenase RCC (SDHRCC), Hereditary Papillary RCC (HPRCC), and ALK-Rearrangement RCC (ALKRCC). RESULTS: Hereditary RCC is generally associated with an early age of onset, multifocal and/or bilateral lesions, and aggressive disease course. VHLRCC, BAPccRCC, FccRCC, and certain mutations resulting in SDHRCC are associated with clear cell RCC (ccRCC). HPRCC is associated with Type 1 papillary RCC. HLRCC is associated with type 2 papillary RCC. BHDRCC is associated with Chromophobe RCC. TSCRCC, PHTSRCC, MiTFtRCC, TFEBRCC, ADPKDRCC, certain SDHRCC and ALKRCC have variable histology. CONCLUSIONS: There has been tremendous advancement in our understanding of the pathophysiology of hereditary RCC. Ongoing research will refine our understanding of hereditary RCC and its therapeutic targets.