Germline Mutations in Renal Neoplasms and Their Clinicopathological Correlations

Abstract

Introduction. Germline mutations have been described in multiple renal neoplasm entities in the fifth edition of the World Health Organization Classification of Urinary and Male Genital Systems. However, our knowledge of renal neoplasms with germline mutations remains limited. Methods. To expand our understanding, 15 tumors with germline mutations were retrieved from 284 renal neoplasms that underwent next-generation sequencing, including well-known VHL, FH, SDHB, FLCN, TSC1, and less common genes such as MUTYH, NF2, and BARD1. Results. Interesting findings included clear cell renal cell carcinoma (RCC) with FH germline mutation and succinate dehydrogenase (SDH)-deficient RCC with high-grade transformation. Patients with germline mutations of these uncommon altered genes in renal neoplasms, such as MUTYH, NF2, and BARD1 were diagnosed with different renal entities, including entities with favorable outcomes (renal cell carcinoma with fibromyomatous stroma) or adverse outcomes (collecting duct carcinoma and FH deficient renal cell carcinoma). Conclusions. Besides the well-known germline mutations in renal neoplasms, we described germline mutations in some genes that are common in other sites but uncommon in the kidney. Although they cannot be used to determine a definite renal entity, they may also contribute to the pathogenesis of renal neoplasms. Tumors need to be diagnosed based on morphology, immunohistochemistry, and other molecular evidence.