Hereditary renal cell tumors: Clinicopathologic importance

Abstract

Hereditary renal cancer syndromes represent approximately 5% of renal malignancies and have distinctive clinical, histopathologic, and genetic features. Next-generation sequencing and other molecular testing methods have uncovered several hereditary renal cancer syndromes. Several autosomal dominant hereditary renal cell carcinoma (RCC) syndromes, including those related to germline pathogenic variants in VHL, BAP1, MITF, MET, FH, TSC1/TSC2, FLCN, SDH, and CDC73 have been confirmed. FH- and BAP1-related RCCs are associated with more aggressive disease. Identifying the clinical and pathological features in these hereditary RCC syndromes is important as, relative to familial cohorts, these patients require early screening and intervention and regular surveillance to improve their clinical prognosis and long-term outcomes. More importantly, identification of these syndromes plays a vital role in personalized management and systemic treatment selection in this modern era of precision medicine. Ongoing studies have demonstrated that treatment based on genetic pathway targeting is a promising approach for hereditary renal cancer management. This review describes updates in the diagnostic criteria for and management of familial kidney cancer syndromes.

The Cellular Stress and Cutaneous Manifestations in Renal Cell Carcinomas—A Narrative Review

“…Ongoing studies have demonstrated associations between inherited cancer susceptibility syndromes, RCC, and skin [119,120]. Patients diagnosed with hereditary leiomyomatosis and RCC-associated leiomyomatosis present with a fumarate hydratase gene mutation.…”

“…This mutation leads to intracellular fumarate accumulation, which mediates proteomic and epigenetic events, ultimately leading to HIF-1 activation. Cutaneous manifestations include multiple cutaneous piloleiomyomas, presenting as firm, reddish-colored papules or nodules [119,120]. Birt-Hogg-Dubé syndrome is a rare autosomal dominant inherited disorder associated with ccRCC and chRCC, caused by point mutations and rearrangements of the folliculin gene.…”

“…This gene functions as a tumor suppressor and is involved in cell-cell adhesion, negative regulation of ribosomal RNA synthesis, and modulation of the mTOR pathway. This syndrome is characterized by the development of multiple renal tumors, facial fibrofolliculomas, and pulmonary cysts [119]. IgA deposition along the basement membrane [111,112] Table 1.…”