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1
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Geilswijk M, Genuardi M, Woodward ER, Nightingale K, Huber J, Madsen MG, Liekelema-van der Heij D, Lisseman I, Marlé-Ballangé J, McCarthy C, Menko FH, Moorselaar RJAV, Radzikowska E, Richard S, Rajan N, Sommerlund M, Wetscherek MTA, Di Donato N, Maher ER, Brunet J. ERN GENTURIS clinical practice guidelines for the diagnosis, surveillance and management of people with Birt-Hogg-Dubé syndrome. Eur J Hum Genet 2024; 32:1542-1550. [PMID: 39085584 PMCID: PMC11607457 DOI: 10.1038/s41431-024-01671-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2024] [Revised: 06/27/2024] [Accepted: 07/02/2024] [Indexed: 08/02/2024] Open
Abstract
Birt-Hogg-Dubé syndrome (BHD syndrome) is an autosomal dominant multisystem disorder with variable expression due to pathogenic constitutional variants in the FLCN gene. Patients with BHD syndrome are predisposed to benign cutaneous fibrofolliculomas/trichodischomas, pulmonary cysts with an associated risk of spontaneous pneumothorax, and renal cell carcinoma. A requirement for updated International consensus recommendations for the diagnosis and management of BHD syndrome was identified. Based on a comprehensive literature review and expert consensus within the fields of respiratory medicine, urology, radiology, dermatology, clinical oncology and clinical genetics, updated recommendations for diagnosis, surveillance and management in BHD syndrome were developed. With the widespread availability of FLCN genetic testing, clinical scenarios in which a diagnosis should be considered and criteria for genetic testing were defined. Following a clinical and/or molecular diagnosis of BHD syndrome, a multidisciplinary approach to disease management is required. Regular renal cancer surveillance is recommended in adulthood and life-long, but the evidence base for additional tumour surveillance is limited and further research warranted. Recommendations for the treatment of cutaneous, pulmonary and renal manifestations are provided. Awareness of BHD syndrome needs to be raised and better knowledge of the clinical settings in which the diagnosis should be considered should enable earlier diagnosis. Further details, including areas for future research topics are available at: https://www.genturis.eu/l=eng/Guidelines-and-pathways/Clinical-practice-guidelines.html .
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Affiliation(s)
| | - Maurizio Genuardi
- Dipartimento di Scienze della Vita e Sanità Pubblica, Università Cattolica del Sacro Cuore, Rome, Italy
- UOC Genetica Medica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Emma R Woodward
- Manchester Centre for Genomic Medicine, University of Manchester, Manchester, UK
| | | | | | | | | | - Ian Lisseman
- Myrovlytis Trust, BHD Foundation, Manchester, UK
| | - Jenny Marlé-Ballangé
- BHD FRANCE (a charity working closely with the BHD foundation), La Rochelle, France
| | - Cormac McCarthy
- School of Medicine, University College Dublin, Dublin, Ireland
| | - Fred H Menko
- Antoni van Leeuwenhoek Hospital, the Netherlands Cancer Institute, Amsterdam, the Netherlands
| | | | | | - Stéphane Richard
- French NCI (INCa) network for rare cancers in adults PREDIR, AP-HP, Hôpital Bicêtre, Le Kremlin-Bicêtre, France
| | - Neil Rajan
- Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK
| | | | - Maria T A Wetscherek
- Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Nataliya Di Donato
- Department of Human Genetics, Hannover Medical School, Hannover, Germany
| | - Eamonn R Maher
- University of Cambridge, Cambridge, UK
- Aston University, Birmingham, UK
| | - Joan Brunet
- Catalan Institute of Oncology, Barcelona, Spain
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Cicchetti R, Basconi M, Litterio G, Mascitti M, Tamborino F, Orsini A, Digiacomo A, Ferro M, Schips L, Marchioni M. Advances in Molecular Mechanisms of Kidney Disease: Integrating Renal Tumorigenesis of Hereditary Cancer Syndrome. Int J Mol Sci 2024; 25:9060. [PMID: 39201746 PMCID: PMC11355026 DOI: 10.3390/ijms25169060] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2024] [Revised: 08/04/2024] [Accepted: 08/08/2024] [Indexed: 09/03/2024] Open
Abstract
Renal cell carcinoma (RCC) comprises various histologically distinct subtypes, each characterized by specific genetic alterations, necessitating individualized management and treatment strategies for each subtype. An exhaustive search of the PubMed database was conducted without any filters or restrictions. Inclusion criteria encompassed original English articles focusing on molecular mechanisms of kidney cancer. On the other hand, all non-original articles and articles published in any language other than English were excluded. Hereditary kidney cancer represents 5-8% of all kidney cancer cases and is associated with syndromes such as von Hippel-Lindau syndrome, Birt-Hogg-Dubè syndrome, succinate dehydrogenase-deficient renal cell cancer syndrome, tuberous sclerosis complex, hereditary papillary renal cell carcinoma, fumarate hydratase deficiency syndrome, BAP1 tumor predisposition syndrome, and other uncommon hereditary cancer syndromes. These conditions are characterized by distinct genetic mutations and related extra-renal symptoms. The majority of renal cell carcinoma predispositions stem from loss-of-function mutations in tumor suppressor genes. These mutations promote malignant advancement through the somatic inactivation of the remaining allele. This review aims to elucidate the main molecular mechanisms underlying the pathophysiology of major syndromes associated with renal cell carcinoma. By providing a comprehensive overview, it aims to facilitate early diagnosis and to highlight the principal therapeutic options available.
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Affiliation(s)
- Rossella Cicchetti
- Department of Medical Oral and Biotechnological Science, Università degli Studi “G. d’Annunzio” of Chieti, 66100 Chieti, Italy; (R.C.); (M.B.); (G.L.); (M.M.); (F.T.); (A.O.); (A.D.); (M.M.)
| | - Martina Basconi
- Department of Medical Oral and Biotechnological Science, Università degli Studi “G. d’Annunzio” of Chieti, 66100 Chieti, Italy; (R.C.); (M.B.); (G.L.); (M.M.); (F.T.); (A.O.); (A.D.); (M.M.)
| | - Giulio Litterio
- Department of Medical Oral and Biotechnological Science, Università degli Studi “G. d’Annunzio” of Chieti, 66100 Chieti, Italy; (R.C.); (M.B.); (G.L.); (M.M.); (F.T.); (A.O.); (A.D.); (M.M.)
| | - Marco Mascitti
- Department of Medical Oral and Biotechnological Science, Università degli Studi “G. d’Annunzio” of Chieti, 66100 Chieti, Italy; (R.C.); (M.B.); (G.L.); (M.M.); (F.T.); (A.O.); (A.D.); (M.M.)
| | - Flavia Tamborino
- Department of Medical Oral and Biotechnological Science, Università degli Studi “G. d’Annunzio” of Chieti, 66100 Chieti, Italy; (R.C.); (M.B.); (G.L.); (M.M.); (F.T.); (A.O.); (A.D.); (M.M.)
| | - Angelo Orsini
- Department of Medical Oral and Biotechnological Science, Università degli Studi “G. d’Annunzio” of Chieti, 66100 Chieti, Italy; (R.C.); (M.B.); (G.L.); (M.M.); (F.T.); (A.O.); (A.D.); (M.M.)
| | - Alessio Digiacomo
- Department of Medical Oral and Biotechnological Science, Università degli Studi “G. d’Annunzio” of Chieti, 66100 Chieti, Italy; (R.C.); (M.B.); (G.L.); (M.M.); (F.T.); (A.O.); (A.D.); (M.M.)
| | - Matteo Ferro
- Division of Urology, European Institute of Oncology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), 20141 Milan, Italy;
| | - Luigi Schips
- Department of Medical Oral and Biotechnological Science, Università degli Studi “G. d’Annunzio” of Chieti, 66100 Chieti, Italy; (R.C.); (M.B.); (G.L.); (M.M.); (F.T.); (A.O.); (A.D.); (M.M.)
| | - Michele Marchioni
- Department of Medical Oral and Biotechnological Science, Università degli Studi “G. d’Annunzio” of Chieti, 66100 Chieti, Italy; (R.C.); (M.B.); (G.L.); (M.M.); (F.T.); (A.O.); (A.D.); (M.M.)
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Zhang Z, Wang Y, Yang W, Liu T, Wang C, Huang C, Xu Y, Chen X, Zhou J, Wang Y, Zhou X, Gong Y, Gong K. Metabolomic landscape of renal cell carcinoma in von Hippel-Lindau syndrome in a Chinese cohort. iScience 2024; 27:110357. [PMID: 39055909 PMCID: PMC11269943 DOI: 10.1016/j.isci.2024.110357] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2024] [Revised: 05/10/2024] [Accepted: 06/20/2024] [Indexed: 07/28/2024] Open
Abstract
Von Hippel-Lindau (VHL) syndrome is a rare autosomal dominant disorder, where renal cell carcinoma (RCC) serves as a significant cause of mortality. We collected peripheral blood from 61 VHL-RCC patients and 31 healthy individuals, along with 19 paired RCC tumor and adjacent non-malignant samples. Using liquid chromatography-mass spectrometry, we identified 238 plasma and 241 tissue differentially abundant metabolites (DAMs), highlighting key pathways such as arginine and proline metabolism. The top 10 of the 23 DAMs, common to both plasma and tissue, were instrumental in constructing a high-performance diagnostic model. These DAMs demonstrated significant correlations with VHL gene mutation types. Cox regression analysis revealed that plasma levels of N2,N2-dimethylguanosine were associated with the timing of RCC onset in VHL patients, acting as an independent predictive factor. This study enhances diagnostic accuracy for this rare condition and opens new avenues for exploring metabolic mechanisms of the disease and potential therapeutic directions.
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Affiliation(s)
- Zedan Zhang
- Department of Urology, Peking University First Hospital, Beijing, China
- Hereditary Kidney Cancer Research Center, Peking University First Hospital, Beijing, China
| | - Yi Wang
- Beijing International Center for Mathematical Research and Department of Biostatistics, Peking University, Beijing, China
| | - Wuping Yang
- Department of Urology, Peking University First Hospital, Beijing, China
- Hereditary Kidney Cancer Research Center, Peking University First Hospital, Beijing, China
| | - Tao Liu
- Department of Urology, Peking University First Hospital, Beijing, China
- Hereditary Kidney Cancer Research Center, Peking University First Hospital, Beijing, China
| | - Chuandong Wang
- Department of Urology, Peking University First Hospital, Beijing, China
- Hereditary Kidney Cancer Research Center, Peking University First Hospital, Beijing, China
| | - Cong Huang
- Department of Urology, Peking University First Hospital, Beijing, China
| | - Yawei Xu
- Department of Urology, Peking University First Hospital, Beijing, China
- Hereditary Kidney Cancer Research Center, Peking University First Hospital, Beijing, China
| | - Xiaolin Chen
- Department of Urology, Peking University First Hospital, Beijing, China
- Hereditary Kidney Cancer Research Center, Peking University First Hospital, Beijing, China
| | - Jingcheng Zhou
- Department of Urology, Peking University First Hospital, Beijing, China
- Hereditary Kidney Cancer Research Center, Peking University First Hospital, Beijing, China
| | - Yizhou Wang
- Department of Urology, Peking University First Hospital, Beijing, China
- Hereditary Kidney Cancer Research Center, Peking University First Hospital, Beijing, China
| | - Xiaohua Zhou
- Beijing International Center for Mathematical Research and Department of Biostatistics, Peking University, Beijing, China
| | - Yanqing Gong
- Department of Urology, Peking University First Hospital, Beijing, China
- Hereditary Kidney Cancer Research Center, Peking University First Hospital, Beijing, China
| | - Kan Gong
- Department of Urology, Peking University First Hospital, Beijing, China
- Hereditary Kidney Cancer Research Center, Peking University First Hospital, Beijing, China
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Chen J, Zheng L, Zhang W, Wang Z, Yu J, Liang P. Percutaneous microwave ablation on management of hereditary renal cell carcinoma in Von Hippel-Lindau disease. Int J Hyperthermia 2024; 41:2308079. [PMID: 38346873 DOI: 10.1080/02656736.2024.2308079] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2023] [Revised: 11/24/2023] [Accepted: 01/16/2024] [Indexed: 02/15/2024] Open
Abstract
BACKGROUND The effect of microwave ablation (MWA) for the renal cell carcinoma (RCC) in Von Hippel-Lindau (VHL) disease is unclear. OBJECTIVE To assess the safety, Technique efficacy, renal function and oncological outcome of MWA for RCC in VHL patients. METHODS Consecutive patients with RCCs in VHL disease treated by MWA were retrospectively collected from November 2009 to October 2020. The technical efficacy rate and complications were assessed. The outcomes of pre- and post-ablative eGFR were compared. The local recurrent-free survival (LRFS), renal-cancer-free survival (RCFS), cancer-specific survival (CSS), overall survival (OS) and complications were presented. RESULTS A total of 10 patients (mean age, 39.0 years ± 10.7 [SD]; 3 women) with 28 RCCs (mean tumor size, 3.0 cm ± 0.34; mean tumor volume, 20.7 mL ± 43.3) treated with MWA were included. Th median follow-up time was 52 months(IQR:27-80). The overall technical efficacy rate was 100% with no major complications occurred. No significant statistical difference between pre-ablative and postablative creatinine level (102.0 µmol/L ± 30.4 vs 112.3 µmol/L ± 38.7, p = 0.06), but the pre-ablative eGFR level was significantly higher than the post-ablative eGFR (78.0 mL/(min*1.73m2) ± 28.6 vs 72 mL/(min*1.73m2) ± 31.4, p = 0.04), with the mean decrease of 5.86 ml/(min*1.73m2). The local recurrent-free survival(LRFS) and renal-cancer-free survival (RCFS) were 100% and 60%, respectively. The cancer specifical survival (CSS) and overall survival (OS) were 95.5% and 100%, respectively. CONCLUSION Microwave ablation is a safe and feasible method for the treatment of RCC in VHL disease, preserving renal function and yielding satisfactory oncological outcomes.
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Affiliation(s)
- Jiye Chen
- Department of Interventional Ultrasound, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Lin Zheng
- Department of Interventional Ultrasound, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Wei Zhang
- Ultrasound Diagnostic Department, 92493 Military Hospital of the Chinese People's Liberation Army, Beijing; China
| | - Zhen Wang
- Department of Interventional Ultrasound, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Jie Yu
- Department of Interventional Ultrasound, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Ping Liang
- Department of Interventional Ultrasound, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
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Tekin B, Erickson LA, Gupta S. von Hippel-Lindau disease-related neoplasia with an emphasis on renal manifestations. Semin Diagn Pathol 2024; 41:20-27. [PMID: 37980175 DOI: 10.1053/j.semdp.2023.11.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2023] [Accepted: 11/06/2023] [Indexed: 11/20/2023]
Abstract
von Hippel-Lindau (VHL) disease is characterized by biallelic inactivation of the VHL gene leading to abnormal or absent VHL protein function, and constitutive activation of hypoxia-inducible factors (HIF) that leads to pro-tumorigenic signaling. Individuals with VHL disease develop numerous cysts and tumors involving multiple organs including the kidneys, central nervous system, endolymphatic sac, lungs, pancreatobiliary system, adrenal glands, epididymis, and/or broad ligament. On histologic examination, these lesions show morphologic overlap as they are frequently characterized by cells with clear cytoplasm and prominent vascularity. In addition to distinguishing non-renal tumors from metastatic clear cell renal cell carcinoma, understanding site-specific histopathologic and immunophenotypic features of these tumors has several applications. This includes distinguishing VHL-related tumors from those that arise sporadically and lack VHL gene alterations, guiding further genetic workup, and helping distinguish between different genetic predisposition syndromes. In this context, immunohistochemical studies for markers such as paired box 8 (PAX-8), carbonic anhydrase 9 (CA9), and glucose transporter 1 (GLUT-1) have an important role in routine clinical practice and represent cost-effective diagnostic tools. The recent development of targeted therapeutics directed against HIF-mediated signaling represents a significant milestone in the management of VHL disease and highlights the importance of accurately diagnosing and characterizing the wide spectrum of VHL disease-associated lesions.
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Affiliation(s)
- Burak Tekin
- Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First Street, Southwest, Rochester, MN 55905, USA
| | - Lori A Erickson
- Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First Street, Southwest, Rochester, MN 55905, USA
| | - Sounak Gupta
- Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First Street, Southwest, Rochester, MN 55905, USA.
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Cinque A, Minnei R, Floris M, Trevisani F. The Clinical and Molecular Features in the VHL Renal Cancers; Close or Distant Relatives with Sporadic Clear Cell Renal Cell Carcinoma? Cancers (Basel) 2022; 14:5352. [PMID: 36358771 PMCID: PMC9657498 DOI: 10.3390/cancers14215352] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2022] [Accepted: 10/27/2022] [Indexed: 11/24/2022] Open
Abstract
Von Hippel-Lindau (VHL) disease is an autosomal dominant inherited cancer syndrome caused by germline mutations in the VHL tumor suppressor gene, characterized by the susceptibility to a wide array of benign and malign neoplasms, including clear-cell renal cell carcinoma. Moreover, VHL somatic inactivation is a crucial molecular event also in sporadic ccRCCs tumorigenesis. While systemic biomarkers in the VHL syndrome do not currently play a role in clinical practice, a new promising class of predictive biomarkers, microRNAs, has been increasingly studied. Lots of pan-genomic studies have deeply investigated the possible biological role of microRNAs in the development and progression of sporadic ccRCC; however, few studies have investigated the miRNA profile in VHL patients. Our review summarize all the new insights related to clinical and molecular features in VHL renal cancers, with a particular focus on the overlap with sporadic ccRCC.
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Affiliation(s)
- Alessandra Cinque
- Biorek S.r.l., San Raffaele Scientific Institute, 20132 Milan, Italy
| | - Roberto Minnei
- Nephrology, Dialysis, and Transplantation, G. Brotzu Hospital, University of Cagliari, 09134 Cagliari, Italy
| | - Matteo Floris
- Nephrology, Dialysis, and Transplantation, G. Brotzu Hospital, University of Cagliari, 09134 Cagliari, Italy
| | - Francesco Trevisani
- Biorek S.r.l., San Raffaele Scientific Institute, 20132 Milan, Italy
- Urological Research Institute, San Raffaele Scientific Institute, 20132 Milan, Italy
- Unit of Urology, San Raffaele Scientific Institute, 20132 Milan, Italy
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Epidemiology and Prevention of Renal Cell Carcinoma. Cancers (Basel) 2022; 14:cancers14164059. [PMID: 36011051 PMCID: PMC9406474 DOI: 10.3390/cancers14164059] [Citation(s) in RCA: 62] [Impact Index Per Article: 20.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2022] [Revised: 08/16/2022] [Accepted: 08/18/2022] [Indexed: 11/17/2022] Open
Abstract
With 400,000 diagnosed and 180,000 deaths in 2020, renal cell carcinoma (RCC) accounts for 2.4% of all cancer diagnoses worldwide. The highest disease burden developed countries, primarily in Europe and North America. Incidence is projected to increase in the future as more countries shift to Western lifestyles. Risk factors for RCC include fixed factors such as gender, age, and hereditary diseases, as well as intervening factors such as smoking, obesity, hypertension, diabetes, diet and alcohol, and occupational exposure. Intervening factors in primary prevention, understanding of congenital risk factors and the establishment of early diagnostic tools are important for RCC. This review will discuss RCC epidemiology, risk factors, and biomarkers involved in reducing incidence and improving survival.
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Evaluation of tumour surveillance protocols and outcomes in von Hippel-Lindau disease in a national health service. Br J Cancer 2022; 126:1339-1345. [PMID: 35184155 PMCID: PMC8857742 DOI: 10.1038/s41416-022-01724-7] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2021] [Revised: 01/17/2022] [Accepted: 01/27/2022] [Indexed: 11/08/2022] Open
Abstract
Abstract
Background
Von Hippel-Lindau (VHL) disease is an inherited tumour predisposition syndrome and a paradigm for the importance of early diagnosis and surveillance. However, there is limited information on the “real world” management of VHL disease.
Methods
A national audit of VHL disease in the United Kingdom.
Results
VHL disease was managed mostly via specialist clinics coordinated through regional clinical genetics services (but frequently involving additional specialties). Over the study period, 19 genetic centres saw 842 individuals (393 males, 449 females) with a clinical and/or molecular diagnosis of VHL disease and 74 individuals (35 male, 39 female) with a prior risk of 50% (affected parent). All centres offered retinal, central nervous system and abdominal surveillance to affected individuals and at-risk relatives though surveillance details differed between centres (but complied with international recommendations). Renal lesions detected on the first surveillance scan were, on average, larger than those detected during subsequent scans and the larger the diameter at detection the greater the likelihood of early intervention.
Conclusions
In a state-funded health care system individuals with a rare inherited cancer predisposition syndrome are generally able to access appropriate surveillance and patient management is improved compared to historical data. The “real world” data from this study will inform the future development of VHL management protocols.
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Von Hippel-Lindau disease-associated renal cell carcinoma: a call to action. Curr Opin Urol 2022; 32:31-39. [PMID: 34783716 DOI: 10.1097/mou.0000000000000950] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
PURPOSE OF REVIEW While the molecular and genetic bases of Von Hippel-Lindau (VHL) disease have been extensively investigated, limited evidence is available to guide diagnosis, local or systemic therapy, and follow-up. The aim of the current review is to summarize the ongoing trials both in preclinical and clinical setting regarding VHL disease management. RECENT FINDINGS Although genotype/phenotype correlations have been described, there is considerable inter and intra-familiar heterogeneity in VHL disease. Genetic anticipation has been reported in VHL disease. From a clinical point of view, expert-opinion-based protocols suggest testing those patients with any blood relative of an individual diagnosed with VHL disease, those with at least 1 or more suggestive neoplasms or patients presenting with clear cell renal cell carcinoma (ccRCC) diagnosed at a less than 40 years old, and/or multiple ccRCC. Clinical research is focused on safety and efficacy of systemic agents for patients with VHL-related ccRCC, with the aim to possibly preserve kidney function and improve patient survival. SUMMARY To date, preclinical and clinical research on the topic is scarce and clinical guidelines are not supported by strong validation studies.
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Schweizer L, Thierfelder F, Thomas C, Soschinski P, Kim HY, Jödicke R, Woltering N, Förster A, Teichmann D, Siewert C, Klein K, Schmid S, Nunninger M, Thomale UW, Onken J, Mühleisen H, Schittenhelm J, Tatagiba M, von Deimling A, Reuss DE, Solomon DA, Heppner FL, Koch A, Hartmann C, Staszewski O, Capper D. Molecular characterisation of sporadic endolymphatic sac tumours and comparison to von Hippel-Lindau disease-related tumours. Neuropathol Appl Neurobiol 2021; 47:756-767. [PMID: 34091929 DOI: 10.1111/nan.12741] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2021] [Revised: 05/27/2021] [Accepted: 05/29/2021] [Indexed: 12/28/2022]
Abstract
AIMS Although inactivation of the von Hippel-Lindau gene (VHL) on chromosome 3p25 is considered to be the major cause of hereditary endolymphatic sac tumours (ELSTs), the genetic background of sporadic ELST is largely unknown. The aim of this study was to determine the prevalence of VHL mutations in sporadic ELSTs and compare their characteristics to VHL-disease-related tumours. METHODS Genetic and epigenetic alterations were compared between 11 sporadic and 11 VHL-disease-related ELSTs by targeted sequencing and DNA methylation analysis. RESULTS VHL mutations and small deletions detected by targeted deep sequencing were identified in 9/11 sporadic ELSTs (82%). No other cancer-related genetic pathway was altered except for TERT promoter mutations in two sporadic ELST and one VHL-disease-related ELST (15%). Loss of heterozygosity of chromosome 3 was found in 6/10 (60%) VHL-disease-related and 10/11 (91%) sporadic ELSTs resulting in biallelic VHL inactivation in 8/10 (73%) sporadic ELSTs. DNA methylation profiling did not reveal differences between sporadic and VHL-disease-related ELSTs but reliably distinguished ELST from morphological mimics of the cerebellopontine angle. VHL patients were significantly younger at disease onset compared to sporadic ELSTs (29 vs. 52 years, p < 0.0001, Fisher's exact test). VHL-disease status was not associated with an increased risk of recurrence, but the presence of clear cells was found to be associated with shorter progression-free survival (p = 0.0002, log-rank test). CONCLUSION Biallelic inactivation of VHL is the main mechanism underlying ELSTs, but unknown mechanisms beyond VHL may rarely be involved in the pathogenesis of sporadic ELSTs.
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Affiliation(s)
- Leonille Schweizer
- Department of Neuropathology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
- German Cancer Consortium (DKTK), Partner Site Berlin, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Felix Thierfelder
- Department of Neuropathology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
- German Cancer Consortium (DKTK), Partner Site Berlin, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Christian Thomas
- Department of Neuropathology, University Hospital Münster, Münster, Germany
| | - Patrick Soschinski
- Department of Neuropathology, University Hospital Münster, Münster, Germany
| | - Hee-Yeong Kim
- Department of Neuropathology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
- German Cancer Consortium (DKTK), Partner Site Berlin, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Ruben Jödicke
- Department of Neuropathology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Niklas Woltering
- Department of Neuropathology, University Hospital Münster, Münster, Germany
| | - Alexandra Förster
- Department of Neuropathology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Daniel Teichmann
- Department of Neuropathology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Christin Siewert
- Department of Neuropathology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
- German Cancer Consortium (DKTK), Partner Site Berlin, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Katharina Klein
- Department of Neuropathology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Simone Schmid
- Department of Neuropathology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Maximilian Nunninger
- Department of Radiology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Ulrich-Wilhelm Thomale
- Department of Neurosurgery, Division Pediatric Neurosurgery, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Julia Onken
- Department of Neurosurgery, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | | | - Jens Schittenhelm
- Department of Neuropathology, Institute of Pathology and Neuropathology, University of Tübingen, Tübingen, Germany
| | - Marcos Tatagiba
- Department of Neurosurgery, University of Tübingen, Tübingen, Germany
| | - Andreas von Deimling
- Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), German Consortium for Translational Cancer Research (DKTK), Heidelberg, Germany
- Department of Neuropathology, Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany
| | - David E Reuss
- Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), German Consortium for Translational Cancer Research (DKTK), Heidelberg, Germany
- Department of Neuropathology, Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany
| | - David A Solomon
- Division of Neuropathology, Department of Pathology, University of California, San Francisco, California, USA
| | - Frank L Heppner
- Department of Neuropathology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
- German Cancer Consortium (DKTK), Partner Site Berlin, German Cancer Research Center (DKFZ), Heidelberg, Germany
- Cluster of Excellence, NeuroCure, Berlin, Germany
- German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany
| | - Arend Koch
- Department of Neuropathology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
- German Cancer Consortium (DKTK), Partner Site Berlin, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Christian Hartmann
- Department of Neuropathology, Hannover Medical School, Hannover, Germany
| | - Ori Staszewski
- Institute of Neuropathology, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - David Capper
- Department of Neuropathology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
- German Cancer Consortium (DKTK), Partner Site Berlin, German Cancer Research Center (DKFZ), Heidelberg, Germany
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11
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Wessendorf J, König A, Heers H, Mahnken AH. Repeat Percutaneous Radiofrequency Ablation of T1 Renal Cell Carcinomas is Safe in Patients with Von Hippel-Lindau Disease. Cardiovasc Intervent Radiol 2021; 44:2022-2025. [PMID: 34414496 PMCID: PMC8626382 DOI: 10.1007/s00270-021-02935-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2021] [Accepted: 07/22/2021] [Indexed: 01/20/2023]
Abstract
Purpose Patients with Von Hippel-Lindau disease often develop multifocal, metachronous renal cell carcinomas which require therapy. The purpose of this retrospective single-center study is to evaluate the outcomes of radiofrequency ablation (RFA) in the treatment of renal cell carcinomas in patients with Von Hippel-Lindau disease. Materials and Methods 9 patients (4 male, 5 female, 47.9 ± 10.7 y/o) with Von Hippel-Lindau disease underwent 18 CT-guided percutaneous RFA procedures for the treatment 21 renal cell carcinomas (largest diameter: 32.9 ± 8.6 mm, cT1a: 16, cT1b: 5). Seven patients were previously treated either by partial or radical nephrectomy. Technical success, effectiveness, safety, progression-free survival, overall survival and tumor characteristics were analyzed. Results All RFA procedures were technically successful without major complications. There were 5 minor complications. No residual or recurrent tumor was seen in the ablation zone during a follow-up of 34.0 ± 18.1 months (0–58 months). No patient required dialysis during follow-up. One patient died after 63 months after the first treatment due to complications from a cerebellar hemangioblastoma. No endpoint was reached for overall or progression-free survival. Conclusions The results from this limited case series suggest that RFA of RCCs in patients with VHL is a safe and effective therapy, which can preserve sufficient renal function even after renal surgery.
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Affiliation(s)
- Joel Wessendorf
- Department of Diagnostic and Interventional Radiology, Marburg University Hospital, D, Philipps University Marburg, Baldingerstrasse, 35043, Marburg, Germany
| | - Alexander König
- Department of Diagnostic and Interventional Radiology, Marburg University Hospital, D, Philipps University Marburg, Baldingerstrasse, 35043, Marburg, Germany
| | - Hendrik Heers
- Department of Urology, Marburg University Hospital, D, Baldingerstrasse, 35043, Marburg, Germany
| | - Andreas H Mahnken
- Department of Diagnostic and Interventional Radiology, Marburg University Hospital, D, Philipps University Marburg, Baldingerstrasse, 35043, Marburg, Germany.
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12
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Shuch B. HIF2 Inhibition for von-Hippel Lindau Associated Kidney Cancer: Will Urology Lead or Follow? Urol Oncol 2021; 39:277-280. [PMID: 34297683 DOI: 10.1016/j.urolonc.2021.01.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2020] [Accepted: 01/16/2021] [Indexed: 11/27/2022]
Affiliation(s)
- Brian Shuch
- Department of Urology, David Geffen School of Medicine, University of California, Los Angeles.
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13
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Iatrogenic ureteric stricture post image guided renal cryoablation in a patient with von hippel-lindau syndrome. Radiol Case Rep 2021; 16:2057. [PMID: 34158894 PMCID: PMC8203560 DOI: 10.1016/j.radcr.2021.05.003] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Accepted: 05/01/2021] [Indexed: 01/20/2023] Open
Abstract
A 53-year-old lady is known to have Von Hippel-Lindau syndrome with a long history of previous renal cell carcinomas (RCCs) in both kidneys. She was treated by partial nephrectomy for a right peripheral RCC and subsequently image guided radiofrequency ablation (RFA) of a left central RCC. She developed another de novo RCC adjacent to the right pelvic-ureteric junction (PUJ) 4 years after the initial RFA. Due to the close proximity to the PUJ and visibility of an ice ball with cryoablation (CRYO), the consensus from the MDT was that CRYO would be safer than RFA and she subsequently underwent percutaneous image guided CRYO to treat the small de novo RCC. Unfortunately, during the 1-month imaging follow up, she developed moderate hydronephrosis and a ureteric stricture needing long-term ureteric stent management. This case highlights the risk of ureteric injury caused by the thermal effect of the ice ball during image guided renal CRYO. Therefore, it is vital that all interventional radiologists adopt various manoeuvres to protect the ureter from the ice ball during CRYO in order to avoid the development of latent ureteric stricture.
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14
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A 25 year perspective on the evolution and advances in an understanding of the biology, evaluation and treatment of kidney cancer. Urol Oncol 2021; 39:548-560. [PMID: 34092483 DOI: 10.1016/j.urolonc.2021.04.038] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2021] [Revised: 04/20/2021] [Accepted: 04/25/2021] [Indexed: 01/20/2023]
Abstract
The diagnosis, evaluation and management of patients with renal cell carcinoma has transformed in the 21st century. Utilizing biological discoveries and technological advances, the field has moved from blunt surgical and largely ineffective medical treatments, to nuanced and fine-tuned approaches based on biology, extent of disease and patient preferences. In this review we will summarize the last 25 years of progress in kidney cancer.
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15
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Abstract
Renal cell carcinoma has historically been managed by radical nephrectomy, but as knowledge of the disease has advanced, nephron sparing surgery has become the norm in appropriately selected tumors. Laparoscopic partial nephrectomy (LPN) has been shown to have comparable oncologic outcomes and a shorter convalescence period compared to the traditional open partial nephrectomy. Dissemination of techniques has led to significantly increased use of minimally invasive nephron sparing surgery, and LPN remains a cost-effective and efficacious method for approaching small renal masses.
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Affiliation(s)
- Sandeep Gurram
- The Smith Institute for Urology, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, New Hyde Park, New York, USA
| | - Louis Kavoussi
- The Smith Institute for Urology, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, New Hyde Park, New York, USA
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16
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Cole AP, Garber JE, Baniak N, Hirsch MS, Lee Chang S, Kibel AS. 'Case of the Month' from Brigham and Women's Hospital, Boston, MA, USA: a 70-year-old man with lung cysts and bilateral renal masses. BJU Int 2021; 126:428-432. [PMID: 33025754 DOI: 10.1111/bju.15234] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Affiliation(s)
- Alexander P Cole
- Division of Urological Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Judy E Garber
- Center for Cancer Genetics and Prevention, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
| | - Nicholas Baniak
- Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Michelle S Hirsch
- Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Steven Lee Chang
- Division of Urological Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Adam S Kibel
- Division of Urological Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
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17
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Clinical, surgical, pathological and follow-up features of kidney cancer patients with Von Hippel-Lindau syndrome: novel insights from a large consortium. World J Urol 2021; 39:2969-2975. [PMID: 33416974 DOI: 10.1007/s00345-020-03574-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2020] [Accepted: 12/15/2020] [Indexed: 12/18/2022] Open
Abstract
PURPOSE To investigate the natural history and follow-up after kidney tumor treatment of Von Hippel-Lindau (VHL) patients. MATERIALS AND METHODS A multi-institutional European consortium of patients with VHL syndrome included 96 non-metastatic patients treated at 9 urological departments (1987-2018). Descriptive and survival analyses were performed. RESULTS AND LIMITATIONS Median age at VHL diagnosis was 34 years (IQR 25-43). Two patients (2.1%) showed only renal manifestations at VHL diagnosis. Concomitant involvement of Central Nervous System (CNS) vs. pancreas vs. eyes vs. adrenal gland vs. others were present in 60.4 vs. 68.7 vs. 30.2 vs. 15.6 vs. 15.6% of patients, respectively. 45% of patients had both CNS and pancreatic diseases alongside kidney. The median interval between VHL diagnosis and renal cancer treatment resulted 79 months (IQR 0-132), and median index tumor size leading to treatment was 35.5 mm (IQR 28-60). Of resected malignant tumours, 73% were low grade. Of high-grade tumors, 61.1% were large > 4 cm. With a median follow-up of 8 years, clinical renal progression rate was 11.7% and 29.3% at 5 and 10 years, respectively. Overall mortality was 4% and 7.5% at 5 and 10 years, respectively. During the follow-up, 50% of patients did not receive a second active renal treatment. Finally, 25.3% of patients had CKD at last follow-up. CONCLUSIONS Mean period between VHL diagnosis and renal cancer detection is roughly three years, with significant variability. Although, most renal tumors are small low-grade, clinical progression and mortality are not negligible. Moreover, kidney function represents a key issue in VHL patients.
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18
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Kassab GH, Robinson I, Hayes R, Paltiel HJ, Bates DG, Cohen HL, Barth RA, Colleran GCM. Urinary Tract. PEDIATRIC ULTRASOUND 2021:729-833. [DOI: 10.1007/978-3-030-56802-3_17] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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19
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Perri D, Marchioro G, Bondonno G, Maso G, Porta C, Volpe A. Repeat partial nephrectomy for recurrence of Von Hippel-Lindau-related renal cell carcinoma in an autotransplanted kidney. Urol Case Rep 2020; 35:101553. [PMID: 33425683 PMCID: PMC7779319 DOI: 10.1016/j.eucr.2020.101553] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2020] [Accepted: 12/24/2020] [Indexed: 11/25/2022] Open
Abstract
Von Hippel-Lindau disease predisposes to develop renal cell carcinoma (RCC). Treatment is frequently challenging due to presence of bilateral tumors and high risk of recurrence. We present the case of a VHL-patient with bilateral recurrence of clear-cell RCC after bilateral partial nephrectomy and autotransplantation on one side. Recurrence on the transplanted kidney was treated with repeat partial nephrectomy with good oncological and functional outcomes. This approach is feasible in centres with wide experience in partial nephrectomy and renal transplantation when minimally invasive tumor ablation is not indicated.
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Affiliation(s)
- D Perri
- Division of Urology, Department of Translational Medicine, University of Eastern Piedmont, Maggiore Della Carità Hospital, Novara, Italy
| | - G Marchioro
- Division of Urology, Department of Translational Medicine, University of Eastern Piedmont, Maggiore Della Carità Hospital, Novara, Italy
| | - G Bondonno
- Division of Urology, Department of Translational Medicine, University of Eastern Piedmont, Maggiore Della Carità Hospital, Novara, Italy
| | - G Maso
- Division of Urology, San Biagio di Domodossola Hospital, ASLVCO, Italy
| | - C Porta
- Division of Vascular Surgery, University of Eastern Piedmont, Maggiore Della Carità Hospital, Novara, Italy
| | - A Volpe
- Division of Urology, Department of Translational Medicine, University of Eastern Piedmont, Maggiore Della Carità Hospital, Novara, Italy
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20
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Qiu J, Zhang K, Ma K, Zhou J, Gong Y, Cai L, Gong K. The Genotype-Phenotype Association of Von Hipple Lindau Disease Based on Mutation Locations: A Retrospective Study of 577 Cases in a Chinese Population. Front Genet 2020; 11:532588. [PMID: 33362845 PMCID: PMC7762453 DOI: 10.3389/fgene.2020.532588] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2020] [Accepted: 10/26/2020] [Indexed: 12/26/2022] Open
Abstract
Purpose Von Hippel-Lindau (VHL) disease is a hereditary kidney cancer syndrome, with which patients are more likely to get affected by renal cell carcinoma (RCC), pancreatic cyst or tumor (PCT), central nervous system hemangioblastoma (CHB), retinal angiomas (RA), and pheochromocytoma (PHEO). Mutations of VHL gene located in 3p25 may impair the function of the VHL protein and lead to the disease. It's unclear why obvious phenotype varieties exist among VHL patients. Here we aimed to ascertain whether the mutation types and locations affect the phenotype. Methods We enrolled 577 Chinese VHL patients from 211 families and divided them into three groups and six subgroups according to their mutation types and locations. Cox survival analysis and Kaplan-Meier analysis were used to compare intergroup age-related tumor risks. Results Patients with nonsense or frameshift mutations that were located before residues 117 of VHL protein (NoF1 subgroup) hold lower age-related risks of VHL associated tumors (HR = 0.638, 95%CI 0.461-0.883, p = 0.007), CHB (HR = 0.596, 95%CI 0.409-0.868, p = 0.007) or PCT (HR = 0.595, 95%CI 0.368-0.961, p = 0.034) than patients whose mutations were located after residues 117 (NoF2 subgroup). Patients in NoF1 subgroup still had lower age-related risks of CHB (HR = 0.652, 95%CI 0.476-0.893, p = 0.008) and PCT (HR = 0.605, 95%CI 0.398-0.918, p = 0.018) compared with those in combined NoF2 subgroup and other truncating mutation patients. NoF1 subgroup correspondingly had a longer estimated median lifespan (64 vs. 55 year, p = 0.037) than NoF2 subgroup. Among patients with missense mutations of VHL, only a small minority (23 of 286 missense mutations carriers) carried mutations involving neither HIF-α binding region nor elongin C binding region, who were grouped in MO subgroup. MO subgroup seemed to have a higher age-related risk of PHEO. In the whole cohort (n = 577), PHEO was an independent protective factor for CHB (p = 0.001) and survival (p = 0.005). RA and CHB failed to predict the age-related risk of each other. Conclusion The mutation types and locations of VHL gene are associated with phenotypes. Genetic counselors could predict phenotypes more accurately based on more detailed genotype-phenotype correlations. Further genotype-phenotype studies should focus on the prediction of tumor recurrence, progression, and metastasis. The deep molecular mechanism of genotype-phenotype correlation is worth further exploring.
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Affiliation(s)
- Jianhui Qiu
- Department of Urology, Peking University First Hospital, Beijing, China.,Institute of Urology, Peking University, Beijing, China.,National Urological Cancer Center, Beijing, China
| | - Kenan Zhang
- Department of Urology, Peking University First Hospital, Beijing, China.,Institute of Urology, Peking University, Beijing, China.,National Urological Cancer Center, Beijing, China
| | - Kaifang Ma
- Department of Urology, Peking University First Hospital, Beijing, China.,Institute of Urology, Peking University, Beijing, China.,National Urological Cancer Center, Beijing, China
| | - Jingcheng Zhou
- Department of Urology, Peking University First Hospital, Beijing, China.,Institute of Urology, Peking University, Beijing, China.,National Urological Cancer Center, Beijing, China
| | - Yanqing Gong
- Department of Urology, Peking University First Hospital, Beijing, China.,Institute of Urology, Peking University, Beijing, China.,National Urological Cancer Center, Beijing, China
| | - Lin Cai
- Department of Urology, Peking University First Hospital, Beijing, China.,Institute of Urology, Peking University, Beijing, China.,National Urological Cancer Center, Beijing, China
| | - Kan Gong
- Department of Urology, Peking University First Hospital, Beijing, China.,Institute of Urology, Peking University, Beijing, China.,National Urological Cancer Center, Beijing, China
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21
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Carrion DM, Linares-Espinós E, Ríos González E, Bazán AA, Alvarez-Maestro M, Martinez-Pineiro L. Invasive management of renal cell carcinoma in von Hippel-Lindau disease. Cent European J Urol 2020; 73:167-172. [PMID: 32782836 PMCID: PMC7407786 DOI: 10.5173/ceju.2020.0004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2020] [Revised: 04/22/2020] [Accepted: 04/29/2020] [Indexed: 01/14/2023] Open
Abstract
Introduction Patients affected by von Hippel-Lindau (VHL) disease experience an increased risk for bilateral, synchronous, and metachronous renal cell carcinoma (RCC). Oncologic and functional outcomes are the main goals in the management of renal masses. We present our protocol for patients with VHL disease-associated RCC alongside functional and oncologic results observed in our series. Material and methods We performed a retrospective analysis of our clinical database of patients with VHL disease-associated RCC referred to our department between June 2005 and December 2017. We offer surveillance for lesions <2 cm and active management with radiofrequency ablation (RFA) for lesions 2-3 cm, and nephron-sparing surgery (NSS), RFA or embolization techniques for lesions >3 cm or growth rate >1 cm/year. Results Our series comprises 14 patients, of whom 13 had undergone at least one invasive procedure for RCC, mean age at first intervention was 27 years (range 18-60). Overall, 30 interventions were performed in 21 kidneys: four radical nephrectomies, 13 RFAs, 12 NSSs, and one embolization. During follow-up (median time: 41 months, range: 6-149), eight patients (57%) presented with new lesions that required treatment, with a mean time between treatments of 32 ±18.5 months. No metastatic progression or need for dialysis was recorded; the success rate for RFA was 85%. Conclusions Management of VHL kidney disease by NSS is the standard of care with a cut-off at 3 cm, ablative procedures should be offered to lesions ranging 2-3 cm in size. Follow-up should be done strictly in referral centers that can provide all treatment options to renal function and control oncologic progression.
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Affiliation(s)
- Diego M Carrion
- Department of Urology, La Paz University Hospital, Madrid, Spain Autonomous University of Madrid, Madrid, Spain
| | - Estefanía Linares-Espinós
- Department of Urology, La Paz University Hospital, Madrid, Spain Autonomous University of Madrid, Madrid, Spain.,La Paz University Hospital, Institute for Health Research (IdiPAZ), Madrid, Spain
| | - Emilio Ríos González
- Department of Urology, La Paz University Hospital, Madrid, Spain Autonomous University of Madrid, Madrid, Spain.,La Paz University Hospital, Institute for Health Research (IdiPAZ), Madrid, Spain
| | - Alfredo Aguilera Bazán
- Department of Urology, La Paz University Hospital, Madrid, Spain Autonomous University of Madrid, Madrid, Spain.,La Paz University Hospital, Institute for Health Research (IdiPAZ), Madrid, Spain
| | - Mario Alvarez-Maestro
- Department of Urology, La Paz University Hospital, Madrid, Spain Autonomous University of Madrid, Madrid, Spain.,La Paz University Hospital, Institute for Health Research (IdiPAZ), Madrid, Spain
| | - Luis Martinez-Pineiro
- Department of Urology, La Paz University Hospital, Madrid, Spain Autonomous University of Madrid, Madrid, Spain.,La Paz University Hospital, Institute for Health Research (IdiPAZ), Madrid, Spain
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22
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Gaillard V, Tricard T, Garnon J, Cazzato RL, Dalili D, Gangi A, Lang H. Repeat ablative therapy in hereditary or multifocal renal cancer: Functional and oncological outcomes. Urol Oncol 2020; 38:797.e15-797.e20. [PMID: 32778477 DOI: 10.1016/j.urolonc.2020.07.020] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2019] [Revised: 06/28/2020] [Accepted: 07/13/2020] [Indexed: 01/20/2023]
Abstract
OBJECTIVES To report managing renal tumors in patients at greater risk of repeated interventions (genetic predisposition, multifocal tumors) with thermoablative treatments (AT). A known significant challenge in these patients is the balance between nephron preservation and oncologic outcome. MATERIAL AND METHODS This retrospective, single-center study was based on data from patients treated with one or more AT for hereditary or multifocal renal tumors between 2007 and 2017. All medical records were systematically reviewed, and 10 patients meeting inclusion criteria were selected. Six patients had confirmed von Hippel-Lindau disease, 1 Bird-Hogg-Dubé syndrome, 1 chromosome 3 translocation, and 2 had a presumed genetic predisposition. RESULTS Median age at cancer diagnosis was 39.5 years (±8.9). Fifty-seven tumors, including 41 de novo tumors that appeared during follow-up, were treated with 32 AT sessions (cryotherapy or radiofrequency) with an average tumor size of 13.5 mm (±9) and a median RENAL score of 6 [5; 7]. One patient underwent concomitant partial nephrectomy for a 55 mm lesion which was close to the bowel. Treatment was unsuccessful in 2 cases, subsequently managed successfully by retreatment with AT. Median delay of appearance of de novo tumor after the first AT was 18 months [6 ; 24]. One patient had metastatic progression. Overall and cancer specific survival was 90% and 100%, respectively, with a mean follow-up of 7.5 years (±4.9). The mean decrease in Chronic Kidney Disease - Epidemiological Collaboration equation-estimated glomerular filtration rate at the end of follow-up was 5.5 ml/min/1.73 m2 (±24). CONCLUSION This study suggests that AT allows to meet the oncological objectives whilst preserving renal function in patients with renal cancer at greater risk of repeated treatments.
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Affiliation(s)
- Victor Gaillard
- Department of Urology, University Hospital Of Strasbourg, 1place de l'Hôpital, Strasbourg, France.
| | - Thibault Tricard
- Department of Urology, University Hospital Of Strasbourg, 1place de l'Hôpital, Strasbourg, France
| | - Julien Garnon
- Department of Interventional Radiology, University Hospital Of Strasbourg, 1place de l'Hôpital, Strasbourg, France
| | - Roberto Luigi Cazzato
- Department of Interventional Radiology, University Hospital Of Strasbourg, 1place de l'Hôpital, Strasbourg, France
| | - Danoob Dalili
- Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD
| | - Afshin Gangi
- Department of Interventional Radiology, University Hospital Of Strasbourg, 1place de l'Hôpital, Strasbourg, France
| | - Herve Lang
- Department of Urology, University Hospital Of Strasbourg, 1place de l'Hôpital, Strasbourg, France
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23
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Çakıcı MÇ, Kısa E, Yalçın MY, Efiloğlu Ö, Yücel C, Atış G, İlbey YÖ, Yıldırım A. Influence of border-age on survival of sporadic renal cell carcinoma: young adults versus octogenarians. Int Urol Nephrol 2020; 52:2087-2095. [PMID: 32607959 DOI: 10.1007/s11255-020-02552-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2020] [Accepted: 06/20/2020] [Indexed: 11/29/2022]
Abstract
PURPOSE To compare the effects of two border-age groups: young adults and octogenarians on survival of sporadic renal cell carcinoma (RCC). METHODS We reviewed the records of 1619 patients that underwent radical or partial nephrectomy due to RCC between January 2004 and December 2018 in two high-volume centers. Patients were divided into two groups based on their age: ≤ 40 years old (group 1) and ≥ 80 years old (group 2). We analyzed the demographic, clinical and histological features of the groups and performed univariable and multivariable Cox regression analyses to evaluate predictors associated with survival. RESULTS Median ages of patients were 35.5 years and 82 years in group 1 (n = 90) and group 2 (n = 55), respectively. Radical nephrectomy rate was statistically higher in group 2 (p = 0.004). Median follow-up was 72 (11-192) months in group 1 and 30 months (5-103) in group 2 (p < 0.001). The 5-year (90.2% vs. 80.2%) and 8-year (84.8% vs. 60.2%) overall survivals (OS) of the groups were statistically different (p < 0.001). Patients in group 1 demonstrated a 5 and 10-year cancer-specific survival (CSS) of 90.2% and 84.7%, whereas these rates were 82.4% and 54.9% for group 2 (p < 0.05). We found that higher hemoglobin drop (HR: 1.497), presence of sarcomatoid differentiation (HR: 4.307), high-stage disease (HR: 2.704), and metastasis detected in the follow-up (HR: 12.805) were independent risk factors that shortened OS (p < 0.05). CONCLUSION Sporadic RCC was associated with a more favorable CSS and OS in young adults compared to the octogenarians. Although two border-age groups had similar pathologies, they have different prognosis and survival rates.
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Affiliation(s)
- Mehmet Çağlar Çakıcı
- Department of Urology, Istanbul Medeniyet University Goztepe Training and Research Hospital, Eğitim Mahallesi, Dr. Erkin Cd., Kadıköy, 34722, Istanbul, Turkey.
| | - Erdem Kısa
- Department of Urology, Health Sciences University, Izmir Tepecik Training and Research Hospital, Izmir, Turkey
| | - Mehmet Yiğit Yalçın
- Department of Urology, Health Sciences University, Izmir Tepecik Training and Research Hospital, Izmir, Turkey
| | - Özgür Efiloğlu
- Department of Urology, Istanbul Medeniyet University Goztepe Training and Research Hospital, Eğitim Mahallesi, Dr. Erkin Cd., Kadıköy, 34722, Istanbul, Turkey
| | - Cem Yücel
- Department of Urology, Health Sciences University, Izmir Tepecik Training and Research Hospital, Izmir, Turkey
| | - Gökhan Atış
- Department of Urology, Istanbul Medeniyet University Goztepe Training and Research Hospital, Eğitim Mahallesi, Dr. Erkin Cd., Kadıköy, 34722, Istanbul, Turkey
| | - Yusuf Özlem İlbey
- Department of Urology, Health Sciences University, Izmir Tepecik Training and Research Hospital, Izmir, Turkey
| | - Asıf Yıldırım
- Department of Urology, Istanbul Medeniyet University Goztepe Training and Research Hospital, Eğitim Mahallesi, Dr. Erkin Cd., Kadıköy, 34722, Istanbul, Turkey
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Farhadi F, Nikpanah M, Paschall AK, Shafiei A, Tadayoni A, Ball MW, Linehan WM, Jones EC, Malayeri AA. Clear Cell Renal Cell Carcinoma Growth Correlates with Baseline Diffusion-weighted MRI in Von Hippel-Lindau Disease. Radiology 2020; 295:583-590. [PMID: 32255415 DOI: 10.1148/radiol.2020191016] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Background Identification of markers to aid in understanding the growth kinetics of Von Hippel-Lindau (VHL)-associated clear cell renal cell carcinoma (ccRCC) has the potential to allow individualization of patient care, thereby helping prevent unnecessary screening and optimizing intervention. Purpose To determine whether the degree of restricted diffusion at baseline MRI holds predictive potential for the growth rate of VHL-associated ccRCC. Materials and Methods Patients with VHL disease who underwent surgical resection of tumors between November 2014 and October 2017 were analyzed retrospectively in this HIPAA-compliant study. The change in ccRCC volume between two time points and apparent diffusion coefficient (ADC) at baseline was calculated by using segmentations by two readers at nephrographic-phase CT and diffusion-weighted MRI, respectively. Intraclass correlation coefficient was used to assess agreement between readers. Repeated-measures correlation was used to investigate relationships between ADC (histogram parameters) and tumor size at baseline with growth rate and volume doubling time (VDT). Predictive performance of the ADC parameter with highest correlation and tumor size at baseline was reviewed to differentiate tumors based on their VDT (≤1 year or >1 year). Results Forty-six patients (mean age, 46 years ± 7 [standard deviation]; 25 women) with 100 ccRCCs were evaluated. Interreader agreement resulted in mean κ scores of 0.89, 0.82, and 0.93 for mean ADC, baseline tumor volume, and follow-up tumor volume, respectively. ADC percentiles correlated negatively with tumor growth rate but correlated positively with VDT. Lower ADC values demonstrated stronger correlations. The 25th percentile ADC had the strongest correlation with growth rate (ρ = -0.52, P < .001) and VDT (ρ = 0.60, P < .001) and enabled prediction of VDT (≤1 year or >1 year) with an area under the receiver operating characteristic curve of 0.86 (sensitivity, 67%; specificity, 89%) (P < .001). Conclusion Apparent diffusion coefficient at baseline was negatively correlated with tumor growth rate. Diffusion-weighted MRI may be useful to identify clear cell renal cell carcinomas with higher growth rates. © RSNA, 2020See also the editorial by Goh and Prezzi in this issue.
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Affiliation(s)
- Faraz Farhadi
- From the Radiology and Imaging Sciences, NIH Clinical Center (F.F., M.N., A.K.P., A.S., A.T., E.C.J., A.A.M.), and Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute (M.W.B., W.M.L.), National Institutes of Health, 10 Center Dr, Bethesda, MD 20814
| | - Moozhan Nikpanah
- From the Radiology and Imaging Sciences, NIH Clinical Center (F.F., M.N., A.K.P., A.S., A.T., E.C.J., A.A.M.), and Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute (M.W.B., W.M.L.), National Institutes of Health, 10 Center Dr, Bethesda, MD 20814
| | - Anna K Paschall
- From the Radiology and Imaging Sciences, NIH Clinical Center (F.F., M.N., A.K.P., A.S., A.T., E.C.J., A.A.M.), and Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute (M.W.B., W.M.L.), National Institutes of Health, 10 Center Dr, Bethesda, MD 20814
| | - Ahmad Shafiei
- From the Radiology and Imaging Sciences, NIH Clinical Center (F.F., M.N., A.K.P., A.S., A.T., E.C.J., A.A.M.), and Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute (M.W.B., W.M.L.), National Institutes of Health, 10 Center Dr, Bethesda, MD 20814
| | - Ashkan Tadayoni
- From the Radiology and Imaging Sciences, NIH Clinical Center (F.F., M.N., A.K.P., A.S., A.T., E.C.J., A.A.M.), and Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute (M.W.B., W.M.L.), National Institutes of Health, 10 Center Dr, Bethesda, MD 20814
| | - Mark W Ball
- From the Radiology and Imaging Sciences, NIH Clinical Center (F.F., M.N., A.K.P., A.S., A.T., E.C.J., A.A.M.), and Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute (M.W.B., W.M.L.), National Institutes of Health, 10 Center Dr, Bethesda, MD 20814
| | - W Marston Linehan
- From the Radiology and Imaging Sciences, NIH Clinical Center (F.F., M.N., A.K.P., A.S., A.T., E.C.J., A.A.M.), and Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute (M.W.B., W.M.L.), National Institutes of Health, 10 Center Dr, Bethesda, MD 20814
| | - Elizabeth C Jones
- From the Radiology and Imaging Sciences, NIH Clinical Center (F.F., M.N., A.K.P., A.S., A.T., E.C.J., A.A.M.), and Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute (M.W.B., W.M.L.), National Institutes of Health, 10 Center Dr, Bethesda, MD 20814
| | - Ashkan A Malayeri
- From the Radiology and Imaging Sciences, NIH Clinical Center (F.F., M.N., A.K.P., A.S., A.T., E.C.J., A.A.M.), and Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute (M.W.B., W.M.L.), National Institutes of Health, 10 Center Dr, Bethesda, MD 20814
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Verkarre V, Morini A, Denize T, Ferlicot S, Richard S. [Hereditary kidney cancers: The pathologist's view in 2020]. Ann Pathol 2020; 40:148-167. [PMID: 32197858 DOI: 10.1016/j.annpat.2020.02.022] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2020] [Revised: 02/10/2020] [Accepted: 02/18/2020] [Indexed: 12/23/2022]
Abstract
Hereditary predispositions to adult kidney tumors involve around 5% of tumors and include a dozen of autosomal dominant syndromes. The most frequent tumors encountered in these setting are clear cell renal cell carcinomas, papillary renal cell carcinomas, chromophobe renal cell carcinomas and angiomyolipomas. Their detection is essential in order to adapt individual care and perform genetic screening of at-risk relatives, especially in the national french network PREDIR, labeled by the National Cancer Institute and dedicated to hereditary predispositions to kidney tumors. Targeted genetic analysis, which was guided in particular by the renal tumor subtype, has recently evolved into genetic analysis using panels of genes. Pathologist contribution's remains however central in the diagnosis of hereditary forms since we currently have immunohistochemical biomarkers that allow us to diagnose two specifically hereditary entities: hereditary leiomyomatosis and renal cell carcinoma associated-renal cell carcinoma, associated with a loss of fumarate hydratase and succinate dehydrogenase-deficient renal cell carcinoma associated with a loss of succinate deshydrogenase B expression. These diagnoses must however be confirmed by the identification of pathogenic germline variation in the corresponding genes. Improvement of kidney tumors characterization has also lead to identify new subtypes, expanding the algorithm of renal tumors associated with hereditary setting. Here we aim to review all subtypes of adult renal tumors encountered in predisposition syndromes.
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Affiliation(s)
- Virginie Verkarre
- Service d'anatomie pathologique, université de Paris, hôpital européen Georges-Pompidou, Assistance publique-Hôpitaux de Paris-Centre, 20, rue Leblanc, 75015 Paris, France; Inserm U970, équipe labellisée par la Ligue contre le cancer, PARCC, université de Paris, Paris, France; Réseau national de référence pour cancers rares de l'adulte PREDIR (« Maladie de von Hippel-Lindau et prédispositions héréditaires au cancer rénal ») labellisée par l'Institut national du cancer, université Paris Saclay, Assistance publique-Hôpitaux de Paris, Le Kremlin-Bicêtre, France.
| | - Aurélien Morini
- Service d'anatomie pathologique, université de Paris, hôpital européen Georges-Pompidou, Assistance publique-Hôpitaux de Paris-Centre, 20, rue Leblanc, 75015 Paris, France
| | - Thomas Denize
- Service d'anatomie pathologique, université de Paris, hôpital européen Georges-Pompidou, Assistance publique-Hôpitaux de Paris-Centre, 20, rue Leblanc, 75015 Paris, France
| | - Sophie Ferlicot
- Réseau national de référence pour cancers rares de l'adulte PREDIR (« Maladie de von Hippel-Lindau et prédispositions héréditaires au cancer rénal ») labellisée par l'Institut national du cancer, université Paris Saclay, Assistance publique-Hôpitaux de Paris, Le Kremlin-Bicêtre, France; Service d'anatomie pathologique des hôpitaux universitaires Paris Sud, université Paris Saclay, hôpital de Bicêtre, Assistance publique-Hôpitaux de Paris, Le Kremlin-Bicêtre, France; Génétique oncologique EPHE, PSL Université, UMR 9019 CNRS, université Paris-Saclay, institut Gustave-Roussy, Villejuif, France
| | - Stéphane Richard
- Réseau national de référence pour cancers rares de l'adulte PREDIR (« Maladie de von Hippel-Lindau et prédispositions héréditaires au cancer rénal ») labellisée par l'Institut national du cancer, université Paris Saclay, Assistance publique-Hôpitaux de Paris, Le Kremlin-Bicêtre, France; Génétique oncologique EPHE, PSL Université, UMR 9019 CNRS, université Paris-Saclay, institut Gustave-Roussy, Villejuif, France
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Abstract
PURPOSE OF REVIEW To describe current paradigms for genetic testing, screening, and treatment of patients with inherited kidney cancer syndromes. RECENT FINDINGS We describe various new aspects of hereditary kidney cancer. Recent data now support that hereditary kidney cancer may account for 5-8% of kidney cancers diagnosed. Methods of testing have evolved including the introduction of multigene next-generation sequencing panels. We continue to learn more about the natural history and management of classic hereditary cancer syndromes. New emerging conditions with lower kidney cancer penetrance have been recognized adding the growing list of syndromes associated with kidney cancer development. The surgical management strategies of enucleation remain however systemic therapy options are being explored both for localized and advanced settings. SUMMARY Genetic predisposition to kidney cancer is likely more common than once thought. Knowledge of clinical manifestation and genetic testing strategies are needed to properly identify and treat patient and their families.
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27
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Carlo MI, Hakimi AA, Stewart GD, Bratslavsky G, Brugarolas J, Chen YB, Linehan WM, Maher ER, Merino MJ, Offit K, Reuter VE, Shuch B, Coleman JA. Familial Kidney Cancer: Implications of New Syndromes and Molecular Insights. Eur Urol 2019; 76:754-764. [PMID: 31326218 PMCID: PMC7673107 DOI: 10.1016/j.eururo.2019.06.015] [Citation(s) in RCA: 80] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2019] [Accepted: 06/12/2019] [Indexed: 02/07/2023]
Abstract
CONTEXT Hereditary cases account for about 5% of all cases of renal cell carcinoma (RCC). With advances in next-generation sequencing, several new hereditary syndromes have been described in the last few years. OBJECTIVE To review and summarise the recent preclinical and clinical literature in hereditary renal cancer. EVIDENCE ACQUISITION A systematic review of the literature was performed in November 2018 using PubMed and OMIM databases, with an emphasis on kidney cancer, genetics and genomics, clinical criteria, and management. EVIDENCE SYNTHESIS Several autosomal dominant hereditary RCC syndromes have been described, including those related to germline pathogenic variants in VHL, MET, FH, TSC1/TSC2, FLCN, SDHA/B/C/D, BAP1, CDC73, and MITF. Clinical spectrum of SDH, BAP1, and MITF is still being defined, although these appear to be associated with a lower incidence of RCC. FH and likely BAP1 RCC are associated with more aggressive disease. Preclinical and clinical studies show that using systemic therapy that exploits specific genetic pathways is a promising strategy. CONCLUSIONS There are several well-described hereditary RCC syndromes, as well as recently identified ones, for which the full clinical spectrum is yet to be defined. In the new era of precision medicine, identification of these syndromes may play an important role in management and systemic treatment selection. PATIENT SUMMARY This review covers updates in the diagnosis and management of familial kidney cancer syndromes. We describe updates in testing and management of the most common syndromes such as von Hippel-Lindau, and hereditary leiomyomatosis and renal cell carcinoma. We also provide insights into recently described familial kidney cancer syndromes.
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Affiliation(s)
- Maria I Carlo
- Memorial Sloan Kettering Cancer Center, New York, NY, USA.
| | - A Ari Hakimi
- Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Grant D Stewart
- Department of Surgery, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK
| | | | | | - Ying-Bei Chen
- Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - W Marston Linehan
- National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Eamonn R Maher
- Department of Surgery, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK; Department of Medical Genetics, University of Cambridge and NIHR Cambridge Biomedical Research Centre, and Cancer Research UK Cambridge Cenre, Cambridge, UK
| | - Maria J Merino
- National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Kenneth Offit
- Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | | | - Brian Shuch
- David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
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Zhou B, Wang J, Liu S, Peng X, Hong B, Zhou J, Ma K, Zhang J, Cai L, Gong K. Hemangioblastoma Instead of Renal Cell Carcinoma Plays a Major Role in the Unfavorable Overall Survival of Von Hippel-Lindau Disease Patients. Front Oncol 2019; 9:1037. [PMID: 31649892 PMCID: PMC6794496 DOI: 10.3389/fonc.2019.01037] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2019] [Accepted: 09/24/2019] [Indexed: 11/17/2022] Open
Abstract
Von Hippel-Lindau (VHL) disease is a hereditary cancer syndrome characterized by poor survival. The effect of the involvement of each organ on survival remains unclear. Our study aimed to study the effect of the involvement of each organ on survival in VHL disease patients. We retrospectively analyzed 336 patients from 125 families. The onset age was compared between different groups using Mann-Whitney U test and Kruskal-Wallis test. Univariate and multivariate time-dependent Cox regression analyses were conducted to evaluate how survival was influenced by the involvement of each organ. The median survival time for VHL disease patients was 66 years. The onset age was earlier in the central nervous system (CNS) group than in the abdominal group. The involvement of central nervous system hemangioblastoma (CHB) and retinal hemangioblastoma (RA) were independent risk factors for overall survival. The involvement of renal cell carcinoma (RCC) was not a significant risk factor for overall survival. Only RA was a risk factor for CHB-specific survival. This study analyzed the relationship between organ involvement and survival of VHL patients. This may help guide future genetic counseling and clinical decision-making.
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Affiliation(s)
- Bowen Zhou
- Department of Urology, Peking University First Hospital, Beijing, China.,Institute of Urology, Peking University, Beijing, China.,National Urological Cancer Center, Beijing, China.,Department of Urology, Beijing Hospital, Beijing, China
| | - Jiangyi Wang
- Department of Urology, Beijing Hospital, Beijing, China.,Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Shengjie Liu
- Department of Urology, Peking University First Hospital, Beijing, China.,Institute of Urology, Peking University, Beijing, China.,National Urological Cancer Center, Beijing, China
| | - Xiang Peng
- Department of Urology, Peking University First Hospital, Beijing, China.,Institute of Urology, Peking University, Beijing, China.,National Urological Cancer Center, Beijing, China.,Department of Urology, The Second Affiliated Hospital of NanChang University, Jiangxi, China
| | - Baoan Hong
- Department of Urology, Peking University First Hospital, Beijing, China.,Institute of Urology, Peking University, Beijing, China.,National Urological Cancer Center, Beijing, China
| | - Jingcheng Zhou
- Department of Urology, Peking University First Hospital, Beijing, China.,Institute of Urology, Peking University, Beijing, China.,National Urological Cancer Center, Beijing, China
| | - Kaifang Ma
- Department of Urology, Peking University First Hospital, Beijing, China.,Institute of Urology, Peking University, Beijing, China.,National Urological Cancer Center, Beijing, China
| | - Jiufeng Zhang
- Department of Urology, Peking University First Hospital, Beijing, China.,Institute of Urology, Peking University, Beijing, China.,National Urological Cancer Center, Beijing, China
| | - Lin Cai
- Department of Urology, Peking University First Hospital, Beijing, China.,Institute of Urology, Peking University, Beijing, China.,National Urological Cancer Center, Beijing, China
| | - Kan Gong
- Department of Urology, Peking University First Hospital, Beijing, China.,Institute of Urology, Peking University, Beijing, China.,National Urological Cancer Center, Beijing, China
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29
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Schuhmacher P, Kim E, Hahn F, Sekula P, Jilg CA, Leiber C, Neumann HP, Schultze-Seemann W, Walz G, Zschiedrich S. Growth characteristics and therapeutic decision markers in von Hippel-Lindau disease patients with renal cell carcinoma. Orphanet J Rare Dis 2019; 14:235. [PMID: 31661010 PMCID: PMC6819544 DOI: 10.1186/s13023-019-1206-2] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2019] [Accepted: 09/21/2019] [Indexed: 11/19/2022] Open
Abstract
Background Von Hippel-Lindau (VHL) disease is a multi-systemic hereditary disease associated with several benign and malignant tumor entities, including clear cell renal cell carcinoma (ccRCC). Since ccRCCs grow slowly, nephron sparing surgery is typically performed at a tumor diameter of 3–4 cm before the tumor metastasizes. However, in the case of recurrent disease, repeated surgical intervention can impair renal function. Therefore, it is crucial to optimize the timing for surgical interventions through a better understanding of the growth kinetics of ccRCCs in VHL. We investigated tumor growth kinetics and modern volumetric assessment to guide future therapeutic decisions. Results The prevalence of ccRCC was 28% in a cohort of 510 VHL patients. Of 144 patients with ccRCC, 41 were followed with serial imaging which identified 102 renal tumors, which exhibited heterogeneous growth kinetics. ccRCCs grew at an average absolute growth rate of 0.287 cm/year, an average relative growth rate [(lnV1-lnV0)/(t1-t0)] of 0.42% and an average volume doubling time of 27.15 months. Women had a faster relative growth rate than men. Age and specific mutations did not influence tumor growth. Because of the tumor heterogeneity, we developed an additional cut-off volume of 40 cm3 for surgical intervention. Conclusions Tumor heterogeneity and differences in growth kinetics is suggestive of a state of transient tumor dormancy in ccRCCs of VHL patients. The relative growth rate has not been previously described in other studies. Volumetric assessment as an additional parameter for surgical intervention could be a useful clinical tool and needs further investigation.
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Affiliation(s)
- Patrick Schuhmacher
- Department of Nephrology and Primary Care, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Hugstetter Str. 55, 79106, Freiburg, Germany
| | - Emily Kim
- Department of Radiation Oncology, Medical Center, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.,German Cancer Consortium (DKTK), Partner Site Freiburg, Freiburg, Germany
| | - Felix Hahn
- Department of Diagnostic and Interventional Radiology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
| | - Peggy Sekula
- Institute of Genetic Epidemiology, Medical Center, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Cordula Annette Jilg
- Department of Urology, Medical Center, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Christian Leiber
- Department of Urology, Medical Center, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Hartmut P Neumann
- Department of Nephrology and Primary Care, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Hugstetter Str. 55, 79106, Freiburg, Germany
| | - Wolfgang Schultze-Seemann
- Department of Urology, Medical Center, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Gerd Walz
- Department of Nephrology and Primary Care, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Hugstetter Str. 55, 79106, Freiburg, Germany
| | - Stefan Zschiedrich
- Department of Nephrology and Primary Care, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Hugstetter Str. 55, 79106, Freiburg, Germany.
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30
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Abstract
PURPOSE OF REVIEW With this review, we describe the most recent advances in active surveillance as well as diagnosis and management of small renal masses (SRMs). RECENT FINDINGS We discuss diagnosis, differentiation of solid from cystic lesions, risk prediction and treatment of the SRM. A better understanding of the disease facilitates the use of more conservatory treatments, such as active surveillance. Active surveillance has been increasingly accepted not only for SRM, but also for larger tumors and even metastatic patients. Exiting advances in risk prediction will help us define which patients can be safely managed with active surveillance and which require immediate treatment. Meanwhile, the use of renal tumor biopsies is still an important tool for these cases. SUMMARY Active surveillance is an option for many patients with renal masses. Noninvasive methods for diagnosis and risk prediction are being developed, but meanwhile, renal tumor biopsy is a useful tool. A better understanding of the disease increases the number of patients who can undergo active surveillance fully certain of the safety of their management.
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Hong B, Zhang Z, Zhou J, Ma K, Zhang J, Cai L, Zhang N, Gong K. Distinctive clinicopathological features of Von Hippel-Lindau-associated hereditary renal cell carcinoma: A single-institution study. Oncol Lett 2019; 17:4600-4606. [PMID: 30944649 PMCID: PMC6444392 DOI: 10.3892/ol.2019.10091] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2018] [Accepted: 02/15/2019] [Indexed: 12/14/2022] Open
Abstract
Von Hippel-Lindau (VHL) disease is a genetic syndrome that involves the development of tumors in numerous organs. The kidney is one of the most frequently affected organs, and patients with VHL and renal tumors require repeated nephrectomy. The present study aimed to further determine the clinicopathological characteristics of patients with VHL-associated renal cell carcinoma (RCC), which may allow more rational clinical treatment decisions. This study included 27 patients with VHL who underwent radical or partial nephrectomy at the Peking University First Hospital between January 2010 and April 2018. The clinicopathological characteristics and prognosis of the patients were retrospectively reviewed. The expression of RCC-associated molecular markers was evaluated by immunohistochemistry. The mean size of the renal tumors was 4.3±2.0 cm (range 1.3–9.5 cm). The pathological type in 26 cases (96.3%) was clear cell RCC (CCRCC), whereas only one patient was diagnosed with CCRCC and clear cell papillary RCC. Renal cysts with a clear cell lining were observed, and RCC cell clusters were scattered in renal cyst cavities. Among the 27 patients, 21 (77.8%) were diagnosed with stage IA/T1N0M0, according to Tumor-Node-Metastasis staging, and 16 (59.3%) had grade 1 tumors. The mean postoperative follow-up duration was 39.0±24.0 months (range, 1.7–96.5 months). No metastasis or VHL-associated mortality was observed. VHL-associated RCC is a relatively low-risk disease, and a tumor size of 4 cm was determined as a threshold for nephron-sparing surgery. In addition, to prevent tumor cell dispersion, renal cysts should be carefully treated. A comprehensive understanding of the clinicopathological characteristics and underlying mechanisms of RCC associated with VHL syndrome may improve patient prognosis.
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Affiliation(s)
- Baoan Hong
- Department of Urology, Peking University First Hospital, Beijing 100034, P.R. China.,Hereditary Kidney Cancer Research Center, Peking University First Hospital, Beijing 100034, P.R. China.,Institute of Urology, Peking University, Beijing 100034, P.R. China.,National Urological Cancer Center, Beijing 100034, P.R. China
| | - Zhongyuan Zhang
- Department of Urology, Peking University First Hospital, Beijing 100034, P.R. China.,Hereditary Kidney Cancer Research Center, Peking University First Hospital, Beijing 100034, P.R. China.,Institute of Urology, Peking University, Beijing 100034, P.R. China.,National Urological Cancer Center, Beijing 100034, P.R. China
| | - Jingcheng Zhou
- Department of Urology, Peking University First Hospital, Beijing 100034, P.R. China.,Hereditary Kidney Cancer Research Center, Peking University First Hospital, Beijing 100034, P.R. China.,Institute of Urology, Peking University, Beijing 100034, P.R. China.,National Urological Cancer Center, Beijing 100034, P.R. China
| | - Kaifang Ma
- Department of Urology, Peking University First Hospital, Beijing 100034, P.R. China.,Hereditary Kidney Cancer Research Center, Peking University First Hospital, Beijing 100034, P.R. China.,Institute of Urology, Peking University, Beijing 100034, P.R. China.,National Urological Cancer Center, Beijing 100034, P.R. China
| | - Jiufeng Zhang
- Department of Urology, Peking University First Hospital, Beijing 100034, P.R. China.,Hereditary Kidney Cancer Research Center, Peking University First Hospital, Beijing 100034, P.R. China.,Institute of Urology, Peking University, Beijing 100034, P.R. China.,National Urological Cancer Center, Beijing 100034, P.R. China
| | - Lin Cai
- Department of Urology, Peking University First Hospital, Beijing 100034, P.R. China.,Hereditary Kidney Cancer Research Center, Peking University First Hospital, Beijing 100034, P.R. China.,Institute of Urology, Peking University, Beijing 100034, P.R. China.,National Urological Cancer Center, Beijing 100034, P.R. China
| | - Ning Zhang
- Department of Urology, Beijing Cancer Hospital, Beijing 100142, P.R. China
| | - Kan Gong
- Department of Urology, Peking University First Hospital, Beijing 100034, P.R. China.,Hereditary Kidney Cancer Research Center, Peking University First Hospital, Beijing 100034, P.R. China.,Institute of Urology, Peking University, Beijing 100034, P.R. China.,National Urological Cancer Center, Beijing 100034, P.R. China
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32
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Baiocco JA, Ball MW, Pappajohn AK, Rayn KN, Bratslavsky G, Boyle SL, Linehan WM, Metwalli AR. A comparison of outcomes for standard and multiplex partial nephrectomy in a solitary kidney: The National Cancer Institute experience. Urol Oncol 2019; 37:356.e1-356.e7. [PMID: 30902489 DOI: 10.1016/j.urolonc.2019.02.015] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2018] [Revised: 02/04/2019] [Accepted: 02/25/2019] [Indexed: 01/20/2023]
Abstract
OBJECTIVES To study the short and intermediate surgical, renal functional, and oncologic outcomes of multiplex partial nephrectomy (mPN) and standard partial nephrectomy (sPN) in the setting of a solitary kidney. PATIENTS AND METHODS Review of a prospectively maintained database of patients undergoing solitary kidney partial nephrectomy at our institution was performed. Patients were stratified into 2 cohorts: mPN-where 3 or more renal tumors were resected and sPN-where 1 or 2 tumors were resected. Perioperative, renal functional, and oncological outcomes were compared. RESULTS Ninety-three patients with a solitary kidney underwent a total of 121 surgical procedures; 43 (35.5%) were sPN and 78 (64.4%) were mPN. The total and major (Clavien Grade III and IV) complication rates between sPN and mPN were similar (57.1% vs. 70.1%, P = 0.2; 31.0% vs. 35.1%, P = 0.3). At 12 months post-op, the percentage of patients with eGFR > 45 was similar in each group (sPN 87.0%, mPN 73.7%; P = 0.2), and long-term hemodialysis rates were 4.7% and 6.4%, respectively. Completion nephrectomy was performed in 2.3% of sPN and 2.6% of mPN. At a median follow-up of 40.1 months, the metastasis rate was 8.6% in the sPN group and 4.1% in the mPN group (P = 0.4). CONCLUSIONS Partial nephrectomy in the setting of a solitary kidney can effectively preserve renal function. The renal functional and oncologic outcomes were similar in sPN and mPN, with low hemodialysis rates and complication rates within the expected range of these operations. Three or more tumors in a solitary kidney should not be a contraindication for nephron sparing surgery.
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Affiliation(s)
- Joseph A Baiocco
- Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD
| | - Mark W Ball
- Department of Urology, Upstate Medical University, Syracuse, New York.
| | - Asha K Pappajohn
- Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD
| | - Kareem N Rayn
- Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD
| | | | - Shawna L Boyle
- Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD
| | - William M Linehan
- Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD
| | - Adam R Metwalli
- Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD
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Peng X, Chen J, Wang J, Peng S, Liu S, Ma K, Zhou J, Hong B, Zhou B, Zhang J, Cai L, Gong K. Natural history of renal tumours in von Hippel-Lindau disease: a large retrospective study of Chinese patients. J Med Genet 2019; 56:380-387. [DOI: 10.1136/jmedgenet-2018-105567] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2018] [Revised: 01/10/2019] [Accepted: 01/19/2019] [Indexed: 12/20/2022]
Abstract
BackgroundHistorically, renal cell carcinoma (RCC) is one of the main causes of death in von Hippel-Lindau (VHL) disease. However, the natural history of VHL-related RCC has not been thoroughly elucidated to date. This report described the natural history of VHL-related RCC in a large Chinese VHL cohort and might be helpful in the surveillance and treatment of VHL disease.MethodsIn this retrospective study, we included 196 renal tumours from 150 patients with VHL disease. Statistical analysis was used to evaluate the influence of age of onset, sex, family history, unilateral or bilateral tumour, VHL disease type, mutation type, mutation location, and tumour size on tumour growth, metastasis and survival in patients with VHL disease.ResultsThe mean age of onset was 38.8 years, and the mean initial tumour size was 3.1 cm. The mean linear growth rate was 0.49 cm/year. Patients experienced faster tumour growth when they had later age of onset, larger initial tumour size, missense mutation, mutations locating in exon 3, and when they were not affected by cerebral or retinal haemangioblastomas. Tumours larger than 4 cm grew faster than those smaller than 4 cm. Bilateral tumours, large initial tumours, fast tumour growth and metastasis were risk factors for poor prognosis in VHL-related RCC.ConclusionThis large study demonstrated that age of onset, initial tumour size, concomitant tumours, mutation type and mutation location had an effect on growth rate in VHL-related RCC. Active surveillance may be safe for patients with tumour size less than 4 cm, which is helpful in clinical decision-making.
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Marcq G, Hénon F, Ouzaid I, Fantoni JC, Hermieu JF, Xylinas E. Active surveillance for non-muscle invasive bladder cancer. Transl Androl Urol 2019; 8:54-60. [PMID: 30976569 PMCID: PMC6414342 DOI: 10.21037/tau.2018.10.20] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2018] [Accepted: 10/22/2018] [Indexed: 12/24/2022] Open
Abstract
Most of low grade (LG) bladder tumors will experience disease recurrence and very few of them (<2%) will experience disease progression. Therefore active surveillance (AS) for LG non-muscle invasive bladder cancer (NMIBC) has emerged. The goal of our study was to provide a literature review of AS for LG NMIBC including inclusion criteria, modalities and oncological outcomes. We conducted a systematic review (registered in PROSPERO: CRD42018102935) using MEDLINE and EMBASE between June 2018 and August 2018 with the following terms: LG, NMIBC, AS, urothelial neoplasm. Overall, 6 studies that reached our scope of review were included cumulating 403 patients with 2 prospective trials. Inclusion criteria were: recurrent LG (G1 and G2) Ta or T1 NMIBC, with a negative cytology, a low volume (<10 mm) and low number (<5) of tumors. Cystoscopy every 3 months during the first 2 years and every 6 months afterwards were required. AS dropout criteria were presence of tumor-related symptoms, a positive cytology, a modification of tumor morphology or size and patient's request. Pooled data showed an overall 65% reclassification rate where 15% of patients were reclassified based on grade and 10% on stage with a median follow-up of 32 months (IQR, 24-42 months). Only one study reported on progression to MIBC in 4 patients out of 186 (2%). Most of patients enrolled in an AS protocol for recurrent LG NMIBC will undergo a TURBT eventually. Many patients may be eligible to this therapeutic approach but current knowledge does not support its use in daily practice outside of a clinical trial.
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Affiliation(s)
| | | | - Idir Ouzaid
- Department of Urology, Bichat Hospital, Assistance Publique Hôpitaux de Paris, Paris Descartes University, Paris, France
| | | | - Jean-François Hermieu
- Department of Urology, Bichat Hospital, Assistance Publique Hôpitaux de Paris, Paris Descartes University, Paris, France
| | - Evanguelos Xylinas
- Department of Urology, Bichat Hospital, Assistance Publique Hôpitaux de Paris, Paris Descartes University, Paris, France
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Farhadi F, Nikpanah M, Li X, Symons R, Pourmorteza A, Merino MJ, Linehan WM, Malayeri AA. Germline VHL gene variant in patients with von Hippel-Lindau disease does not predict renal tumor growth. Abdom Radiol (NY) 2018. [PMID: 29525880 DOI: 10.1007/s00261-018-1540-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
PURPOSE To determine whether the type of VHL gene pathogenic variant influences the growth rate or CT enhancement values of renal lesions in VHL patients. MATERIALS AND METHODS Thirty-two VHL patients (19 male) were selected from a prospectively maintained imaging database for patients that underwent surgical tumor resection between 2014 and 2016. One hundred and eleven VHL lesions were marked for resection and pathology analysis. Whole lesion volumetric segmentation was performed on nephrographic phase of the two most recent contrast-enhanced CT scans before surgery. Intensity distribution curves were obtained from segmentations. A linear mixed model, accounting for within-patient correlations, was used to compare the growth and enhancement differences between different germline pathogenic variant types. RESULTS There was no significant difference for the lesions' total growth between different germline pathogenic variants (P value = 0.78). The median growth rate for all lesions was 1.7 cc/year (IQR 0.5, 3.9) with a baseline median size of 4.1 cm3 (IQR 1.7, 11.7). In complex lesions, the solid portion of the tumor demonstrated a higher growth rate (1.6 cc/year) than cystic portions (0.02 cc/year) which stayed relatively unchanged. Only one pathogenic variant (Splice donor) showed some levels of difference in its relative enhancement from other subtypes. CONCLUSION The type of germline pathogenic variant on the VHL gene does not affect the growth rate or CT enhancement values of renal lesions in patients with VHL. The absolute growth rate of these tumors may be used in the scheduling of follow-up studies.
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Affiliation(s)
- Faraz Farhadi
- Department of Radiology and Imaging Sciences, National Institutes of Health Clinical Center, 10 Center Dr. Bethesda, Bethesda, MD, 20814, USA
| | - Moozhan Nikpanah
- Department of Radiology and Imaging Sciences, National Institutes of Health Clinical Center, 10 Center Dr. Bethesda, Bethesda, MD, 20814, USA
| | - Xiaobai Li
- Biostatistics and Epidemiology, National Institutes of Health Clinical Center, Bethesda, MD, USA
| | - Rolf Symons
- Department of Radiology and Imaging Sciences, National Institutes of Health Clinical Center, 10 Center Dr. Bethesda, Bethesda, MD, 20814, USA
| | - Amir Pourmorteza
- Department of Radiology and Imaging Sciences, National Institutes of Health Clinical Center, 10 Center Dr. Bethesda, Bethesda, MD, 20814, USA
| | - Maria J Merino
- Center for Cancer Research, National Cancer Institute, National Institutes of Health Clinical Center, Bethesda, MD, USA
| | - W Marston Linehan
- Center for Cancer Research, National Cancer Institute, National Institutes of Health Clinical Center, Bethesda, MD, USA
| | - Ashkan A Malayeri
- Department of Radiology and Imaging Sciences, National Institutes of Health Clinical Center, 10 Center Dr. Bethesda, Bethesda, MD, 20814, USA.
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Ganeshan D, Menias CO, Pickhardt PJ, Sandrasegaran K, Lubner MG, Ramalingam P, Bhalla S. Tumors in von Hippel-Lindau Syndrome: From Head to Toe-Comprehensive State-of-the-Art Review. Radiographics 2018; 38:849-866. [PMID: 29601266 DOI: 10.1148/rg.2018170156] [Citation(s) in RCA: 56] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/29/2023]
Abstract
Von Hippel-Lindau syndrome (VHL) is an autosomal-dominant hereditary tumor disease that arises owing to germline mutations in the VHL gene, located on the short arm of chromosome 3. Patients with VHL may develop multiple benign and malignant tumors involving various organ systems, including retinal hemangioblastomas (HBs), central nervous system (CNS) HBs, endolymphatic sac tumors, pancreatic neuroendocrine tumors, pancreatic cystadenomas, pancreatic cysts, clear cell renal cell carcinomas, renal cysts, pheochromocytomas, paragangliomas, and epididymal and broad ligament cystadenomas. The VHL/hypoxia-inducible factor pathway is believed to play a key role in the pathogenesis of VHL-related tumors. The diagnosis of VHL can be made clinically when the characteristic clinical history and findings have manifested, such as the presence of two or more CNS HBs. Genetic testing for heterozygous germline VHL mutation may also be used to confirm the diagnosis of VHL. Imaging plays an important role in the diagnosis and surveillance of patients with VHL. Familiarity with the clinical and imaging manifestations of the various VHL-related tumors is important for early detection and guiding appropriate management. The purpose of this article is to discuss the molecular cytogenetics and clinical manifestations of VHL, review the characteristic multimodality imaging features of the various VHL-related tumors affecting multiple organ systems, and discuss the latest advances in management of VHL, including current recommendations for surveillance and screening. ©RSNA, 2018 An earlier incorrect version of this article appeared online. This article was corrected on April 9, 2018.
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Affiliation(s)
- Dhakshinamoorthy Ganeshan
- From the Departments of Radiology (D.G.) and Pathology (P.R.), University of Texas MD Anderson Cancer Center, Pickens Academic Tower, 1400 Pressler St, Unit 1473, Houston, TX 77030-4009; Department of Radiology, Mayo Clinic Arizona, Phoenix/Scottsdale, Ariz (C.O.M.); Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, Wis (P.J.P., M.G.L.); Department of Radiology, Indiana University School of Medicine, Indianapolis, Ind (K.S.); and Section of Abdominal Imaging, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St Louis, Mo (S.B.)
| | - Christine O Menias
- From the Departments of Radiology (D.G.) and Pathology (P.R.), University of Texas MD Anderson Cancer Center, Pickens Academic Tower, 1400 Pressler St, Unit 1473, Houston, TX 77030-4009; Department of Radiology, Mayo Clinic Arizona, Phoenix/Scottsdale, Ariz (C.O.M.); Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, Wis (P.J.P., M.G.L.); Department of Radiology, Indiana University School of Medicine, Indianapolis, Ind (K.S.); and Section of Abdominal Imaging, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St Louis, Mo (S.B.)
| | - Perry J Pickhardt
- From the Departments of Radiology (D.G.) and Pathology (P.R.), University of Texas MD Anderson Cancer Center, Pickens Academic Tower, 1400 Pressler St, Unit 1473, Houston, TX 77030-4009; Department of Radiology, Mayo Clinic Arizona, Phoenix/Scottsdale, Ariz (C.O.M.); Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, Wis (P.J.P., M.G.L.); Department of Radiology, Indiana University School of Medicine, Indianapolis, Ind (K.S.); and Section of Abdominal Imaging, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St Louis, Mo (S.B.)
| | - Kumaresan Sandrasegaran
- From the Departments of Radiology (D.G.) and Pathology (P.R.), University of Texas MD Anderson Cancer Center, Pickens Academic Tower, 1400 Pressler St, Unit 1473, Houston, TX 77030-4009; Department of Radiology, Mayo Clinic Arizona, Phoenix/Scottsdale, Ariz (C.O.M.); Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, Wis (P.J.P., M.G.L.); Department of Radiology, Indiana University School of Medicine, Indianapolis, Ind (K.S.); and Section of Abdominal Imaging, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St Louis, Mo (S.B.)
| | - Meghan G Lubner
- From the Departments of Radiology (D.G.) and Pathology (P.R.), University of Texas MD Anderson Cancer Center, Pickens Academic Tower, 1400 Pressler St, Unit 1473, Houston, TX 77030-4009; Department of Radiology, Mayo Clinic Arizona, Phoenix/Scottsdale, Ariz (C.O.M.); Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, Wis (P.J.P., M.G.L.); Department of Radiology, Indiana University School of Medicine, Indianapolis, Ind (K.S.); and Section of Abdominal Imaging, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St Louis, Mo (S.B.)
| | - Preetha Ramalingam
- From the Departments of Radiology (D.G.) and Pathology (P.R.), University of Texas MD Anderson Cancer Center, Pickens Academic Tower, 1400 Pressler St, Unit 1473, Houston, TX 77030-4009; Department of Radiology, Mayo Clinic Arizona, Phoenix/Scottsdale, Ariz (C.O.M.); Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, Wis (P.J.P., M.G.L.); Department of Radiology, Indiana University School of Medicine, Indianapolis, Ind (K.S.); and Section of Abdominal Imaging, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St Louis, Mo (S.B.)
| | - Sanjeev Bhalla
- From the Departments of Radiology (D.G.) and Pathology (P.R.), University of Texas MD Anderson Cancer Center, Pickens Academic Tower, 1400 Pressler St, Unit 1473, Houston, TX 77030-4009; Department of Radiology, Mayo Clinic Arizona, Phoenix/Scottsdale, Ariz (C.O.M.); Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, Wis (P.J.P., M.G.L.); Department of Radiology, Indiana University School of Medicine, Indianapolis, Ind (K.S.); and Section of Abdominal Imaging, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St Louis, Mo (S.B.)
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Hereditary renal cell carcinoma syndromes: diagnosis, surveillance and management. World J Urol 2018; 36:1891-1898. [PMID: 29680948 PMCID: PMC6280834 DOI: 10.1007/s00345-018-2288-5] [Citation(s) in RCA: 92] [Impact Index Per Article: 13.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2018] [Accepted: 03/31/2018] [Indexed: 12/14/2022] Open
Abstract
PURPOSE Genetic factors have been implicated in the pathogenesis of renal cell carcinoma (RCC), with around 3% of cases having a family history. A greater knowledge of the genetics of inherited RCC has the potential to translate into novel therapeutic targets for sporadic RCC. METHODS A literature review was performed summarising the current knowledge on hereditary RCC diagnosis, surveillance and management. RESULTS Familial RCC is usually inherited in an autosomal dominant manner, although inherited RCC may present without a relevant family history. A number of familial RCC syndromes have been identified. Familial non-syndromic RCC is suspected when ≥ 2 relatives are affected in the absence of syndromic features, although clear diagnostic criteria are lacking. Young age at onset and bilateral/multicentric tumours are recognised characteristics which should prompt molecular genetic analysis. Surveillance in individuals at risk of inherited RCC aims to prevent morbidity and mortality via early detection of tumours. Though screening and management guidelines for some inherited RCC syndromes (e.g. von Hippel-Lindau disease, Birt-Hogg-Dube syndrome, hereditary leiomyomatosis) are well defined for rare cause of inherited RCC (e.g. germline BAP1 mutations), there is limited information regarding the lifetime RCC risks and the most appropriate screening modalities. CONCLUSION Increasing knowledge of the natural history and genetic basis has led to characterisation and tailored management of hereditary RCC syndromes. International data sharing of inherited RCC gene variant information may enable evidence-based improvements in the diagnosis, surveillance protocols and management of these rare conditions.
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Wang Y, Liang G, Tian J, Wang X, Chen A, Liang T, Du Y, Li H, Du J, Yu L, Chen Z. Pedigree analysis, diagnosis and treatment in Von Hippel-Lindau syndrome: A report of three cases. Oncol Lett 2018; 15:4882-4890. [PMID: 29616089 PMCID: PMC5876499 DOI: 10.3892/ol.2018.7957] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2016] [Accepted: 02/17/2017] [Indexed: 11/08/2022] Open
Abstract
The objective of the present study was to systematically investigate the clinical features, diagnosis and therapeutic treatment of Von Hippel-Lindau (VHL) syndrome in order to improve understanding of this disease. A total of 3 cases of VHL syndrome treated at the Affiliated Hospital of Zunyi Medical College (Zunyi, China) between September 2014 and October 2015 were retrospectively analyzed. The associated literature was reviewed, and the diagnostic and therapeutic features were discussed. Case 1 was diagnosed as VHL syndrome accompanied by a renal tumor on the right side, and radical tumor resection in the right kidney was performed. Postoperative pathological examination indicated clear cell carcinoma. Case 2 was diagnosed as VHL syndrome accompanied by bilateral adrenal pheochromocytoma. The left-side adrenal tumor was removed, and postoperative pathological analysis was suggestive of adrenal pheochromocytoma. Case 3 visited the hospital due to the presence of masses on the left and right sides of the kidney, but did not undergo surgery for personal reasons. Follow-ups were scheduled subsequent to surgery at another hospital. The diagnosis in all 3 cases was confirmed by genetic testing, where VHL mutations were detected in all patients. Following surgery, pedigree and genetic analysis was performed in all 3 pedigrees and VHL mutations were identified in 7 family members. The diagnosis of VHL syndrome should be based on the clinical manifestation of the patients and the results of genetic tests. DNA analysis of mutations is the main method for diagnosis. An appropriate surgical plan should be formulated based on the site, size and number of tumors, and the condition of the patient. Since VHL syndrome is an inheritable genetic disorder and relapse following surgery is common, pedigree analysis of the patient and lifelong follow-ups are essential. Additionally, physicians should pay attention to VHL syndrome in order to avoid missing diagnosis or misdiagnosis.
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Affiliation(s)
- Yuanliang Wang
- Department of Urology, Affiliated Hospital of Zunyi Medical College, Zunyi, Guizhou 563000, P.R. China
| | - Guobiao Liang
- Department of Urology, Affiliated Hospital of Zunyi Medical College, Zunyi, Guizhou 563000, P.R. China
| | - Jing Tian
- Department of Anesthesiology, Affiliated Hospital of Zunyi Medical College, Zunyi, Guizhou 563000, P.R. China
| | - Xin Wang
- Department of Urology, Affiliated Hospital of Zunyi Medical College, Zunyi, Guizhou 563000, P.R. China
| | - Anjian Chen
- Department of Urology, Affiliated Hospital of Zunyi Medical College, Zunyi, Guizhou 563000, P.R. China
| | - Tiancai Liang
- Department of Urology, Affiliated Hospital of Zunyi Medical College, Zunyi, Guizhou 563000, P.R. China
| | - Yang Du
- Department of Urology, Affiliated Hospital of Zunyi Medical College, Zunyi, Guizhou 563000, P.R. China
| | - Hao Li
- Department of Urology, Affiliated Hospital of Zunyi Medical College, Zunyi, Guizhou 563000, P.R. China
| | - Jiang Du
- Department of Urology, Affiliated Hospital of Zunyi Medical College, Zunyi, Guizhou 563000, P.R. China
| | - Lang Yu
- Department of Urology, Affiliated Hospital of Zunyi Medical College, Zunyi, Guizhou 563000, P.R. China
| | - Zongping Chen
- Department of Urology, Affiliated Hospital of Zunyi Medical College, Zunyi, Guizhou 563000, P.R. China
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Abstract
With the ubiquitous use of cross-sectional abdominal imaging in recent years, the incidence of small renal masses (SRMs) has increased, and the evaluation and management of SRMs have become important clinical issues. Diagnosing a mass in the early stages theoretically allows for high rates of cure but simultaneously risks overtreatment. In the past 20 years, surgical treatment of SRMs has transitioned from radical nephrectomy for all renal tumors, regardless of size, to elective partial nephrectomy whenever technically feasible. Additionally, newer approaches, including renal mass biopsy, active surveillance for select patients, and renal mass ablation, have been increasingly used. In this chapter, we review the current evidence-based papers covering aspects of the diagnosis and management of SRMs.
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Affiliation(s)
- Avinash Chenam
- Department of Surgery, Division of Urology and Urologic Oncology, City of Hope National Medical Center, 1500 E. Duarte Rd, MOB L002H, Duarte, CA, 91010, USA
| | - Clayton Lau
- Department of Surgery, Division of Urology and Urologic Oncology, City of Hope National Medical Center, 1500 E. Duarte Rd, MOB L002H, Duarte, CA, 91010, USA.
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Kim E, Zschiedrich S. Renal Cell Carcinoma in von Hippel-Lindau Disease-From Tumor Genetics to Novel Therapeutic Strategies. Front Pediatr 2018; 6:16. [PMID: 29479523 PMCID: PMC5811471 DOI: 10.3389/fped.2018.00016] [Citation(s) in RCA: 38] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2017] [Accepted: 01/16/2018] [Indexed: 01/05/2023] Open
Abstract
von Hippel-Lindau (VHL) disease is an autosomal dominant syndrome caused by mutations in the VHL tumor-suppressor gene, leading to the dysregulation of many hypoxia-induced genes. Affected individuals are at increased risk of developing recurrent and bilateral kidney cysts and dysplastic lesions which may progress to clear cell renal cell carcinoma (ccRCC). Following the eponymous VHL gene inactivation, ccRCCs evolve through additional genetic alterations, resulting in both intratumor and intertumor heterogeneity. Genomic studies have identified frequent mutations in genes involved in epigenetic regulation and phosphoinositide 3-kinase-AKT-mechanistic target of rapamycin (mTOR) pathway activation. Currently, local therapeutic options include nephron-sparing surgery and alternative ablative procedures. For advanced metastatic disease, systemic treatment, including inhibition of vascular endothelial growth factor pathways and mTOR pathways, as well as immunotherapy are available. Multimodal therapy, targeting multiple signaling pathways and/or enhancing the immune response, is currently being investigated. A deeper understanding of the fundamental biology of ccRCC development and progression, as well as the development of novel and targeted therapies will be accelerated by new preclinical models, which will greatly inform the search for clinical biomarkers for diagnosis, prognosis, and response to treatment.
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Affiliation(s)
- Emily Kim
- Department of Radiation Oncology, Faculty of Medicine, Albert Ludwigs University of Freiburg, Freiburg, Germany.,German Cancer Consortium (DKTK), Partner Site Freiburg, Freiburg, Germany
| | - Stefan Zschiedrich
- Renal Division, Department of Medicine IV, Faculty of Medicine, Albert Ludwigs University of Freiburg, Freiburg, Germany
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Dillman JR, Trout AT, Smith EA, Towbin AJ. Hereditary Renal Cystic Disorders: Imaging of the Kidneys and Beyond. Radiographics 2017; 37:924-946. [PMID: 28493804 DOI: 10.1148/rg.2017160148] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
The purpose of this article is to review the hereditary renal cystic diseases that can manifest in children and adults, with specific attention to pathogenesis and imaging features. Various common and uncommon hereditary renal cystic diseases are reviewed in terms of their underlying etiology, including the involved genetic mutations and the affected proteins and cellular structures. Focus is placed on the morphologic findings in each condition and the features that distinguish one disorder from another. The two most common categories of hereditary renal cystic disease are (a) the ciliopathic disorders, which are related to mutations affecting the primary cilia (called "ciliopathies"), and (b) the phakomatoses. Autosomal dominant polycystic kidney disease, autosomal recessive polycystic kidney disease, and the "medullary cystic disease complex" are all ciliopathies but have different phenotypes. Tuberous sclerosis complex and the associated "contiguous gene syndrome," as well as von Hippel-Lindau syndrome, are phakomatoses that can manifest with cystic renal lesions but have uniquely different extrarenal manifestations. Finally, DICER1 mutations can manifest with renal cystic lesions (typically, cystic nephromas) in patients predisposed to other malignancies in the chest, ovaries, and thyroid. Although some overlap exists in the appearance of the renal cysts associated with each of these diseases, there are clear morphologic differences (eg, cyst size, location, and complexity) that are emphasized in this review. To improve patient outcomes, it is important for the radiologist to recognize the various hereditary renal cystic diseases so that a correct diagnosis is assigned and so that the patient is adequately evaluated and followed up. ©RSNA, 2017.
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Affiliation(s)
- Jonathan R Dillman
- From the Department of Radiology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, Cincinnati, OH 45229-3039 (J.R.D., A.T.T., A.J.T.); and the Section of Pediatric Radiology, Department of Radiology, University of Michigan Health System, Ann Arbor, Mich (E.A.S.)
| | - Andrew T Trout
- From the Department of Radiology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, Cincinnati, OH 45229-3039 (J.R.D., A.T.T., A.J.T.); and the Section of Pediatric Radiology, Department of Radiology, University of Michigan Health System, Ann Arbor, Mich (E.A.S.)
| | - Ethan A Smith
- From the Department of Radiology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, Cincinnati, OH 45229-3039 (J.R.D., A.T.T., A.J.T.); and the Section of Pediatric Radiology, Department of Radiology, University of Michigan Health System, Ann Arbor, Mich (E.A.S.)
| | - Alexander J Towbin
- From the Department of Radiology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, Cincinnati, OH 45229-3039 (J.R.D., A.T.T., A.J.T.); and the Section of Pediatric Radiology, Department of Radiology, University of Michigan Health System, Ann Arbor, Mich (E.A.S.)
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Bhindi B, Lohse CM, Mason RJ, Westerman ME, Cheville JC, Tollefson MK, Boorjian SA, Thompson RH, Leibovich BC. Are We Using the Best Tumor Size Cut-points for Renal Cell Carcinoma Staging? Urology 2017; 109:121-126. [DOI: 10.1016/j.urology.2017.04.010] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2017] [Revised: 03/30/2017] [Accepted: 04/06/2017] [Indexed: 12/01/2022]
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Renal cell cancers: unveiling the hereditary ones and saving lives—a tailored diagnostic approach. Int Urol Nephrol 2017; 49:1507-1512. [DOI: 10.1007/s11255-017-1625-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2017] [Accepted: 05/18/2017] [Indexed: 10/19/2022]
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Ristau BT, Kutikov A, Uzzo RG, Smaldone MC. Active Surveillance for Small Renal Masses: When Less is More. Eur Urol Focus 2017; 2:660-668. [PMID: 28723504 DOI: 10.1016/j.euf.2017.04.004] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2017] [Accepted: 04/05/2017] [Indexed: 12/29/2022]
Abstract
CONTEXT A marked increase in incidentally detected small renal masses (SRMs) has occurred over the past decade. Active surveillance (AS) has emerged as an initial management option for these patients. OBJECTIVE (1) To determine selection criteria, assess appropriate imaging modalities and surveillance frequencies, and define triggers for delayed intervention (DI) for patients on AS. (2) To describe oncologic outcomes for patients on AS protocols. EVIDENCE ACQUISITION The PubMed database was queried for English language articles using the keywords "surveillance" and "renal mass" or "renal cell carcinoma" or "kidney cancer." The level of evidence, sample size, study design, and relevance to the review were considered as inclusion criteria. EVIDENCE SYNTHESIS A total of 69 manuscripts were included in the review. Selection criteria at initial evaluation for patients interested in AS include patient-related factors (eg, age, baseline renal function, other comorbidities), tumor-related factors (size, complexity, history of growth, possible renal mass biopsy), and patient preferences (illness uncertainty, quality of life). Cross-sectional imaging is the preferred initial imaging modality. Surveillance imaging should be performed at frequent intervals (3-4 mo) up front; intervals can be reduced over time if favorable growth kinetics are demonstrated. Delayed intervention (DI) should be considered for rapid tumor growth (eg,>0.5cm/yr), an increase in maximum tumor diameter >3-4cm, malignant renal mass biopsy results, development of symptoms, or patient preferences. Oncologic outcomes in well-controlled studies demonstrate a metastatic rate of 1-2%. Most patients who undergo DI remain eligible for nephron-sparing approaches; oncologic outcomes are not compromised by DI strategies. CONCLUSIONS A period of initial AS is safe for most patients with SRMs. Management decisions should focus on a thorough assessment of risk-benefit trade-offs, judiciously integrating patient-related factors, tumor-related factors, and patient preferences. PATIENT SUMMARY A period of initial active surveillance for kidney masses of ≤4cm in diameter is safe in most patients. Frequent imaging and follow-up are necessary to determine if the tumor grows. If delayed intervention becomes necessary, cancer outcomes are not compromised by the initial choice of active surveillance when patients adhere to close follow-up regimens.
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Affiliation(s)
- Benjamin T Ristau
- Division of Urologic Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA.
| | - Alexander Kutikov
- Division of Urologic Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA
| | - Robert G Uzzo
- Division of Urologic Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA
| | - Marc C Smaldone
- Division of Urologic Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA
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Hankins RA, Walton-Diaz A, Truong H, Shih J, Bratslavsky G, Pinto PA, Marston Linehan W, Metwalli AR. Renal functional outcomes after robotic multiplex partial nephrectomy: the National Cancer Institute experience with robotic partial nephrectomy for 3 or more tumors in a single kidney. Int Urol Nephrol 2016; 48:1817-1821. [PMID: 27515314 PMCID: PMC5090974 DOI: 10.1007/s11255-016-1392-y] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2016] [Accepted: 08/02/2016] [Indexed: 01/20/2023]
Abstract
OBJECTIVE To identify renal function outcomes after robotic multiplex partial nephrectomy (RMxPNx), we reviewed our institutional database at the National Institutes of Health, National Cancer Institute. To our knowledge, we present the largest series of RMxPNx renal function outcomes to date. Robotic partial nephrectomy has been employed for oncologic control and to prevent dialysis dependence in hereditary multifocal renal cell carcinoma conditions. We have termed robotic surgery on a single kidney with three or more lesions a RMxPNx. MATERIALS AND METHODS We evaluated patients from a prospectively maintained database at a single institution (NIH/NCI) that underwent RMxPNx from 2007 to 2013. Demographic and operative data were compiled with statistical analysis with T test performed to determine renal function outcomes. RESULTS A total of 54 patients underwent RMxPNx. Mean number of tumors removed was 8.63 (range 3-52). Mean preoperative creatinine and eGFR were 1.02 ± 0.26 mg/dL and 85.4 ± 21.5 mL/min, respectively. Postoperatively, creatinine increased from baseline by 0.45 mg/dL (p < 0.001). Similarly, a mean decrease in eGFR by 24.6 mL/min was observed (p < 0.001). At 3-month follow-up, the creatinine increase from baseline was 0.05 mg/dL (p = 0.10) and mean decrease in eGFR was 3.01 mL/min (p = 0.21). When stratifying based on preoperative CKD stages I-III, similar results were observed. CONCLUSION Robotic multiplex partial nephrectomy is a safe and feasible approach to patients with multifocal renal masses. These complex surgeries have a demonstrated learning curve, but this minimally invasive approach for nephron-sparing surgery allows patients to preserve renal function where they would otherwise require open surgery or a radical nephrectomy.
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Affiliation(s)
- Ryan A Hankins
- Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, Building 10, Room 2 W-5940, 10 Center Drive, MSC 1210, Bethesda, MD, 20892, USA
| | - Annerleim Walton-Diaz
- Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, Building 10, Room 2 W-5940, 10 Center Drive, MSC 1210, Bethesda, MD, 20892, USA
| | - Hong Truong
- Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, Building 10, Room 2 W-5940, 10 Center Drive, MSC 1210, Bethesda, MD, 20892, USA
| | - Joanna Shih
- Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, Building 10, Room 2 W-5940, 10 Center Drive, MSC 1210, Bethesda, MD, 20892, USA
| | - Gennady Bratslavsky
- Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, Building 10, Room 2 W-5940, 10 Center Drive, MSC 1210, Bethesda, MD, 20892, USA
| | - Peter A Pinto
- Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, Building 10, Room 2 W-5940, 10 Center Drive, MSC 1210, Bethesda, MD, 20892, USA
| | - W Marston Linehan
- Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, Building 10, Room 2 W-5940, 10 Center Drive, MSC 1210, Bethesda, MD, 20892, USA
| | - Adam R Metwalli
- Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, Building 10, Room 2 W-5940, 10 Center Drive, MSC 1210, Bethesda, MD, 20892, USA.
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Ahmad AE, Finelli A, Jewett MAS. Surveillance of Small Renal Masses. Urology 2016; 98:8-13. [PMID: 27397098 DOI: 10.1016/j.urology.2016.06.005] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2016] [Revised: 05/21/2016] [Accepted: 06/03/2016] [Indexed: 12/21/2022]
Abstract
The widespread utilization of imaging has led to an increasing incidence of small renal masses (SRMs). However, at least 20% are benign. Nevertheless, nephron-sparing surgery is the standard treatment for SRMs without pretreatment characterization with biopsy. Elderly patients and patients with multiple comorbidities and limited life expectancy may safely be managed with active surveillance with low risk of disease progression and mortality. An initial period of observation to determine tumor growth kinetics is safe and appropriate in select candidates. Renal tumor biopsy is accurate, safe and should be considered for SRMs prior to finalizing treatment plans.
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Affiliation(s)
- Ardalan E Ahmad
- Departments of Surgery (Urology) and Surgical Oncology, Princess Margaret Cancer Centre, University Health Network and the University of Toronto, Toronto, Canada
| | - Antonio Finelli
- Departments of Surgery (Urology) and Surgical Oncology, Princess Margaret Cancer Centre, University Health Network and the University of Toronto, Toronto, Canada
| | - Michael A S Jewett
- Departments of Surgery (Urology) and Surgical Oncology, Princess Margaret Cancer Centre, University Health Network and the University of Toronto, Toronto, Canada.
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Choi SY, Sung DJ, Yang KS, Kim KA, Yeom SK, Sim KC, Han NY, Park BJ, Kim MJ, Cho SB, Lee JH. Small (<4 cm) clear cell renal cell carcinoma: correlation between CT findings and histologic grade. Abdom Radiol (NY) 2016; 41:1160-9. [PMID: 27040407 DOI: 10.1007/s00261-016-0732-9] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
PURPOSE To evaluate the correlation between CT findings and histologic grade of small clear cell renal cell carcinoma (ccRCC). METHODS CT scans of 101 patients with small ccRCC were reviewed independently by two radiologists for tumor size, shape, margin, encapsulation, enhancement pattern, and visual relative enhancement. Enhancement patterns were defined according to the percentage of uniform enhancement [pattern 1, homogeneous (≥90%); pattern 2, relatively homogeneous (≥75 and <90%); and pattern 3, heterogeneous (<75%)]. Quantitative parameters representing attenuation and degree of enhancement were calculated. Histologic grade was classified as low (Fuhrman grade I or II) and high (Fuhrman grade III or IV). CT imaging variables were analyzed using univariate and multivariate analyses. RESULTS A total of 63 low-grade and 38 high-grade small ccRCCs were assessed. Low-grade tumors differed from high-grade tumors with respect to enhancement pattern 1 or 2 (p < 0.001 and p < 0.001), smaller size (p = 0.002 and p = 0.001), and lower attenuation on unenhanced scan (p < 0.001 and p = 0.008). In multivariate analysis, enhancement pattern 1 or 2 and low attenuation (≤30 HU) were identified as independent predictors of low-grade ccRCC. Accuracy derived from logistic regression analysis was 79.2% for reader 1 and 70.3% for reader 2. CONCLUSIONS CT imaging features including tumor attenuation and enhancement pattern can be useful to predict the biologic behavior of small ccRCC for adequate treatment strategy.
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Low G, Huang G, Fu W, Moloo Z, Girgis S. Review of renal cell carcinoma and its common subtypes in radiology. World J Radiol 2016; 8:484-500. [PMID: 27247714 PMCID: PMC4882405 DOI: 10.4329/wjr.v8.i5.484] [Citation(s) in RCA: 115] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2015] [Revised: 01/20/2016] [Accepted: 03/09/2016] [Indexed: 02/06/2023] Open
Abstract
Representing 2%-3% of adult cancers, renal cell carcinoma (RCC) accounts for 90% of renal malignancies and is the most lethal neoplasm of the urologic system. Over the last 65 years, the incidence of RCC has increased at a rate of 2% per year. The increased incidence is at least partly due to improved tumor detection secondary to greater availability of high-resolution cross-sectional imaging modalities over the last few decades. Most RCCs are asymptomatic at discovery and are detected as unexpected findings on imaging performed for unrelated clinical indications. The 2004 World Health Organization Classification of adult renal tumors stratifies RCC into several distinct histologic subtypes of which clear cell, papillary and chromophobe tumors account for 70%, 10%-15%, and 5%, respectively. Knowledge of the RCC subtype is important because the various subtypes are associated with different biologic behavior, prognosis and treatment options. Furthermore, the common RCC subtypes can often be discriminated non-invasively based on gross morphologic imaging appearances, signal intensity on T2-weighted magnetic resonance images, and the degree of tumor enhancement on dynamic contrast-enhanced computed tomography or magnetic resonance imaging examinations. In this article, we review the incidence and survival data, risk factors, clinical and biochemical findings, imaging findings, staging, differential diagnosis, management options and post-treatment follow-up of RCC, with attention focused on the common subtypes.
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Fei SS, Mitchell AD, Heskett MB, Vocke CD, Ricketts CJ, Peto M, Wang NJ, Sönmez K, Linehan WM, Spellman PT. Patient-specific factors influence somatic variation patterns in von Hippel-Lindau disease renal tumours. Nat Commun 2016; 7:11588. [PMID: 27174753 PMCID: PMC4869254 DOI: 10.1038/ncomms11588] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2015] [Accepted: 04/11/2016] [Indexed: 12/11/2022] Open
Abstract
Cancer development is presumed to be an evolutionary process that is influenced by genetic background and environment. In laboratory animals, genetics and environment are variables that can largely be held constant. In humans, it is possible to compare independent tumours that have developed in the same patient, effectively constraining genetic and environmental variation and leaving only stochastic processes. Patients affected with von Hippel-Lindau disease are at risk of developing multiple independent clear cell renal carcinomas. Here we perform whole-genome sequencing on 40 tumours from six von Hippel-Lindau patients. We confirm that the tumours are clonally independent, having distinct somatic single-nucleotide variants. Although tumours from the same patient show many differences, within-patient patterns are discernible. Single-nucleotide substitution type rates are significantly different between patients and show biases in trinucleotide mutation context. We also observe biases in chromosome copy number aberrations. These results show that genetic background and/or environment can influence the types of mutations that occur.
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Affiliation(s)
- Suzanne S. Fei
- Department of Molecular & Medical Genetics, Oregon Health & Science University, Mail Code: CL6S, 2730 SW Moody St, Portland, Oregon 97201, USA
| | - Asia D. Mitchell
- Department of Molecular & Medical Genetics, Oregon Health & Science University, Mail Code: CL6S, 2730 SW Moody St, Portland, Oregon 97201, USA
| | - Michael B. Heskett
- Department of Molecular & Medical Genetics, Oregon Health & Science University, Mail Code: CL6S, 2730 SW Moody St, Portland, Oregon 97201, USA
| | - Cathy D. Vocke
- Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, Building 10 Room 1-5940, Bethesda, Maryland 20892, USA
| | - Christopher J. Ricketts
- Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, Building 10 Room 1-5940, Bethesda, Maryland 20892, USA
| | - Myron Peto
- Department of Molecular & Medical Genetics, Oregon Health & Science University, Mail Code: CL6S, 2730 SW Moody St, Portland, Oregon 97201, USA
| | - Nicholas J. Wang
- Department of Biomedical Engineering, Oregon Health & Science University, Mail Code: CH13B, Portland, Oregon 97201, USA
| | - Kemal Sönmez
- Department of Biomedical Engineering, Oregon Health & Science University, Mail Code: CH13B, Portland, Oregon 97201, USA
| | - W. Marston Linehan
- Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, Building 10 Room 1-5940, Bethesda, Maryland 20892, USA
| | - Paul T. Spellman
- Department of Molecular & Medical Genetics, Oregon Health & Science University, Mail Code: CL6S, 2730 SW Moody St, Portland, Oregon 97201, USA
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Stratton KL, Alanee S, Glogowski EA, Schrader KA, Rau-Murthy R, Klein R, Russo P, Coleman J, Offit K. Outcome of genetic evaluation of patients with kidney cancer referred for suspected hereditary cancer syndromes. Urol Oncol 2016; 34:238.e1-7. [PMID: 26723226 PMCID: PMC4996267 DOI: 10.1016/j.urolonc.2015.11.021] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2015] [Revised: 10/23/2015] [Accepted: 11/23/2015] [Indexed: 12/11/2022]
Abstract
OBJECTIVE To analyze patients with kidney cancer referred for evaluation at a high-volume genetics service at a comprehensive cancer center and identify factors associated with positive tests for hereditary cancer syndromes. METHODS A retrospective review of patients referred to the Clinical Genetics Service at Memorial Sloan-Kettering Cancer Center was performed, and patients with a personal history of kidney cancer were identified. Patient and disease characteristics were reviewed. In all, 4 variables including age at diagnosis of kidney tumor, presence of syndromic manifestations, family history of kidney cancer, and number of primary malignancies were evaluated for association with positive test results in 2 groups: patients tested for renal cell carcinoma syndromes and Lynch syndrome. Guidance for genetic testing strategy in patients with kidney cancer is provided. RESULTS Between 1999 and 2012, 120 patients with a history of kidney cancer were evaluated by the Clinical Genetics Service. The mean age at kidney cancer diagnosis was 52 years (interquartile range: 42-63), with 57% being women. A family history of kidney cancer was reported by 39 patients (33%). Time between diagnosis of first cancer and genetic consultation was <1 year in 54%, 2 to 5 years in 23%, and>5 years in the remaining 23%. Overall, 95 patients were tested for genetic abnormalities with 27 (28%) testing positive. Testing for renal cell carcinoma (RCC)-related syndromes was performed on 43 patients, with 13 testing positive (30%). Lynch syndrome testing was positive in 9 patients (32%) after 28 were tested. In RCC-associated syndromes, young age of diagnosis was associated with positive test results. Conversely, syndromic manifestations and increasing number of primary malignancies were associated with positive Lynch testing. CONCLUSIONS The discovery of inherited kidney cancer syndromes has provided a unique opportunity to identify patients at increased risk for cancer. Factors associated with positive genetic testing are unique to different syndromes. These data suggest that in kidney cancer patients evaluated for hereditary cancer syndromes, young age is associated with diagnosis of RCC syndromes, whereas syndromic manifestations and multiple primaries are found in Lynch syndrome. These results, along with clinical awareness, may be useful for practicing urologists to select patients with kidney cancer to refer for genetic counseling.
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Affiliation(s)
- Kelly L Stratton
- Clinical Genetics Service, Memorial Sloan-Kettering Cancer Center, New York, NY; Department of Surgery, Urology Service, Memorial Sloan-Kettering Cancer Center, New York, NY
| | - Shaheen Alanee
- Department of Surgery, Division of Urology, Southern Illinois University, Springfield, Illinois, USA.
| | - Emily A Glogowski
- Clinical Genetics Service, Memorial Sloan-Kettering Cancer Center, New York, NY
| | | | - Rohini Rau-Murthy
- Clinical Genetics Service, Memorial Sloan-Kettering Cancer Center, New York, NY
| | - Robert Klein
- Clinical Genetics Service, Memorial Sloan-Kettering Cancer Center, New York, NY
| | - Paul Russo
- Clinical Genetics Service, Memorial Sloan-Kettering Cancer Center, New York, NY
| | - Jonathan Coleman
- Clinical Genetics Service, Memorial Sloan-Kettering Cancer Center, New York, NY
| | - Kenneth Offit
- Clinical Genetics Service, Memorial Sloan-Kettering Cancer Center, New York, NY; Department of Surgery, Urology Service, Memorial Sloan-Kettering Cancer Center, New York, NY
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