Tumorigenesis Mechanisms Found in Hereditary Renal Cell Carcinoma: A Review

Abstract

Renal cell carcinoma is a heterogenous cancer composed of an increasing number of unique subtypes each with their own cellular and tumor behavior. The study of hereditary renal cell carcinoma, which composes just 5% of all types of tumor cases, has allowed for the elucidation of subtype-specific tumorigenesis mechanisms that can also be applied to their sporadic counterparts. This review will focus on the major forms of hereditary renal cell carcinoma and the genetic alterations contributing to their tumorigenesis, including von Hippel Lindau syndrome, Hereditary Papillary Renal Cell Carcinoma, Succinate Dehydrogenase-Deficient Renal Cell Carcinoma, Hereditary Leiomyomatosis and Renal Cell Carcinoma, BRCA Associated Protein 1 Tumor Predisposition Syndrome, Tuberous Sclerosis, Birt–Hogg–Dubé Syndrome and Translocation RCC. The mechanisms for tumorigenesis described in this review are beginning to be exploited via the utilization of novel targets to treat renal cell carcinoma in a subtype-specific fashion.

Hereditary Papillary Renal Carcinoma: A Case Report

“…Renal cell carcinoma (RCC) accounts for 2-3% of adult malignancies, with an estimated 3% of cases linked to an inherited predisposition [1][2][3]. Hereditary papillary renal cell carcinoma (HPRCC) is a rare form of kidney cancer that is inherited in an autosomal dominant manner with incomplete penetrance [4].…”

“…Individuals who have known or likely pathogenic mutations in the MET gene have an increased risk of developing multiple tumours in both kidneys, with a risk greater than 80%, while some studies have reported even higher rates of tumour development [1]. These tumours can be found as early as the patient's 20s, but are more commonly detected after the age of 50, with a median age of diagnosis being 57 years old [1,8]. Detecting HPRCC tumours in imaging studies may be challenging due to their hypo vascularity and may be mistaken for cysts [7].…”

“…Detecting HPRCC tumours in imaging studies may be challenging due to their hypo vascularity and may be mistaken for cysts [7]. Magnetic Resonance Imaging (MRI) or Computed Tomography (CT) is recommended for at-risk HPRCC family members, rather than ultrasound, with most institutions starting cross-sectional abdominal imaging every 1-2 years at the age of 30 in patients with a known family history [1,7,8]. The treatment strategy for hereditary papillary renal cell carcinoma is contingent on the stage and dimensions of the tumours.…”

“…Progression to metastasis can occur if left untreated. Radical nephrectomy is a commonly employed treatment option for large tumours, whereas tumours measuring less than 3 cm in diameter are generally considered low-grade and are managed with a nephron-sparing surgical approach [1,7,9]. Investigation into the efficacy of MET inhibitors for the treatment of HPRCC is ongoing, with several MET inhibitors currently under investigation in solid tumours [1].…”

“…Radical nephrectomy is a commonly employed treatment option for large tumours, whereas tumours measuring less than 3 cm in diameter are generally considered low-grade and are managed with a nephron-sparing surgical approach [1,7,9]. Investigation into the efficacy of MET inhibitors for the treatment of HPRCC is ongoing, with several MET inhibitors currently under investigation in solid tumours [1]. The present article reports a clinical case of a 45-year-old male patient who was diagnosed with hereditary renal cell papillary carcinoma affecting both kidneys, and following the diagnosis, the patient underwent a bilateral radical nephrectomy.…”