Bilateral renal cell carcinoma in a paediatric patient with tuberous sclerosis complex

An understanding of the role of inherited cancer predisposition syndromes in pediatric tumor diagnoses continues to develop as more information is learned through the application of genomic technology. Identifying patients and their relatives at an increased risk for developing cancer is an important step in the care of this patient population. The purpose of this review is to highlight various tumor types that arise in the pediatric population and the cancer predisposition syndromes associated with those tumors. The review serves as a guide for recognizing genes and conditions to consider when a pediatric cancer referral presents to the genetics clinic.

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“…Pediatric RCC has also been reported more rarely in TSC (Gil et al 2013;Kubo et al 2011) and SDHx syndromes ).…”

Section: Renal Cell Carcinoma (Rcc)mentioning

confidence: 99%

A Comprehensive Review of Pediatric Tumors and Associated Cancer Predisposition Syndromes

Scollon

Anglin

Thomas

et al. 2017

Journal of Genetic Counseling

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“…The average onset of RCC in patients with TSC is 28-yearold, 25 years earlier than that in the general population. 28 The onset of RCC in the current case is 14, which is not only much earlier than that of the general population but also the average onset age in patients with TSC. Contrary to the general distribution pattern in most RCC patients with TSC, the tumor is unilateral (the left kidney) and solitary.…”

Section: Discussionmentioning

confidence: 61%

A Renal Cell Carcinoma with Biallelic Somatic TSC2 Mutation: Clinical Study and Literature Review

Pang

Wang

et al. 2019

Urology

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OBJECTIVETo elucidate the effect of the biallelic somatic TSC2 mutations, identified in one adolescent patient, in renal cell carcinoma (RCC). METHODSMutation analyses, immunohistochemistry and real-time polymerase chain reaction (PCR) were conducted. RESULTSTwo novel somatic mutations of TSC2 in unilateral and solitary RCC samples from a 14-year-old female were identified. The pathological features suggest the tumor as a clear-cell renal cell carcinoma. In addition, immunohistochemistry revealed elevated levels of phosphorylated S6K1. Results from in vitro cellular experiments suggest that the mutant TSC2 proteins were quickly degraded and they failed to repress the phosphorylation of S6K1 and STAT3, which leads to constitutive activation of mTORC1 pathway and ultimately cause the development of RCC. CONCLUSIONDetecting TSC2 mutation in patients with early RCC onset would be beneficial and mTOR inhibitor could be a therapeutic option for TSC2 mutation-induced RCC. UROLOGY 133: 96−102, 2019. © 2019 Elsevier Inc. R enal cell carcinoma (RCC) represents about 90% of renal malignancies, which is the 13th most common malignancy among all cancers. Approximately 2%-3% of RCC occurs in patients with hereditary diseases including von Hippel-Lindau (VHL) syndrome, hereditary papillary RCC, and Birt-Hogg-Dube' syndrome. 1 In addition, 2%-4% of tuberous sclerosis (TSC) patients suffer from RCC, which is higher than the estimated incidence among the general population. Multiple lines of evidence suggest that loss of function of either TSC1 or TSC2 could result in RCC. [2][3][4] The TSC1 and TSC2 genes are located on 9q34 and 16q13.3, respectively. 5 The protein complex composed of hamartin and tuberin, which is translated from TSC1 and TSC2 respectively, possesses GTPase activity responsible for turning GTP-Rheb to GDP-Rheb. Therefore, both TSC1 and TSC2 were also known as cancer suppressors partially due to their inhibitory role on mammalian target of rapamycin complex 1 (mTORC1). Mechanistically, loss-of-function mutations in TSC1 and/or TSC2 result in inactivation of the hamartin-tuberin complex and subsequently inactivate GTPase and ultimately lead to constitutive activation of the mTORC1 pathway. 3 TSC is an autosomal dominant disease and almost all organs in these patients were affected 5 characterized by facial angiofibroma, seizures, and cognitive disability. TSC also can cause renal lesions including RCC. 6 Since the first reported RCC in a patient with TSC in 1986, 7 numerous cases of RCC have been reported in familial TSC with germ line mutations in either TSC1 or TSC2. However, cases of RCC due to a somatic mutation of TSC2 are relatively rare. Here we present a case of clear cell RCC (ccRCC) in an adolescent with 2 novel biallelic somatic mutations in TSC2.

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“…PN in pediatric RCC has been reported in small cohorts 5,27 . An adolescent with bilateral RCC treated with PN showed stable disease at follow‐up 28 . A retrospective study of pediatric renal tumors including three RCC cases showed no significant differences between hospital charges, hospital length of stay, and complication rates between PN and RN; however, no data on oncological outcomes were reported 29 …”

Section: Treatmentsmentioning

confidence: 99%

Pediatric and young adult renal cell carcinoma

Ray

Jones

Pritchard‐Jones

et al. 2020

Pediatric Blood & Cancer

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Renal cell carcinoma (RCC) is rare in children but is the most common renal tumor in adults. Pediatric RCC has different clinical characteristics, histopathology, and treatment compared with adult disease. Databases were reviewed from inception to February 2020, identifying 32 publications pertaining to 350 patients under 27 years. Surgery is the cornerstone for cure in localized RCC. Lymph node dissection remains controversial. Conventional radiotherapy has no curative role in RCC; similarly, conventional chemotherapy has not proven to be effective in large cohorts. Pediatric metastatic RCC has a poor outlook. There are no published prospective studies demonstrating which adjuvant therapy could improve outcome. Sunitinib, a tyrosine kinase inhibitor, is recommended in this group despite limited evidence. This review provides an overview for pediatric RCC, including the evolving role of precision medicine. K E Y W O R D S pediatrics, renal cell carcinoma, targeted therapy, treatment 1 INTRODUCTION In Europe, around 1000 children are diagnosed with a malignant renal tumor annually. 1 Renal cell carcinomas (RCC) make up 1.9% to 6% of all kidney cancers in children. 2-5 The international incidence of childhood cancer volume 3 (IICC-3) shows that the annual incidence of pediatric RCC is increasing globally, almost doubling, in 0-to 19-year

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Bilateral renal cell carcinoma in a paediatric patient with tuberous sclerosis complex

Cited by 7 publications

References 25 publications

A Comprehensive Review of Pediatric Tumors and Associated Cancer Predisposition Syndromes

A Comprehensive Review of Pediatric Tumors and Associated Cancer Predisposition Syndromes

A Renal Cell Carcinoma with Biallelic Somatic TSC2 Mutation: Clinical Study and Literature Review

Pediatric and young adult renal cell carcinoma

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