|
1
|
Nakai H, Takahashi H, Wellnitz CV, Stanton ML, Takahashi N, Kawashima A. Imaging of Upper Tract Urothelial Carcinoma. Radiographics 2024; 44:e240056. [PMID: 39480700 DOI: 10.1148/rg.240056] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2024]
Abstract
Upper tract urothelial carcinoma (UTUC) originates in the renal pelvis or ureters and typically affects elderly patients, with its incidence increasing over the past few decades. UTUC is a distinct clinical entity with more aggressive clinical behavior than that of lower tract urothelial carcinoma. Due to the significant challenge of acquiring an adequate tissue sample for biopsy, comprehensive risk stratification is required for treatment planning, including radical nephroureterectomy and kidney-sparing management. Imaging plays an important integrated role in risk assessment along with endoscopy and pathologic examination. Lifelong surveillance is required after treatment due to the high incidence of recurrent and metachronous tumors. Lynch syndrome is a frequently unrecognized genetic disorder associated with UTUC that warrants specific attention in patient management. UTUC may manifest with diverse imaging findings, including filling defects, wall thickening, and mass-forming lesions. CT urography is the preferred modality for diagnosis and staging or restaging of UTUC, with numerous technical variations. Efforts have been made to optimize image quality and radiation exposure. Due to its poor sensitivity for small lesions, use of MR urography is limited to special clinical scenarios (eg, when patients have contraindications to iodinated contrast agents). Fluorine 18 fluorodeoxyglucose PET helps to detect metastatic lesions. Image-guided biopsy may be considered for uncertain lesions. Radiologists need to be familiar with the imaging findings and their differential diagnoses. ©RSNA, 2024 Supplemental material is available for this article.
Collapse
Affiliation(s)
- Hirotsugu Nakai
- From the Department of Radiology, Mayo Clinic, 200 1st St SW, Rochester, MN 55905 (H.N., H.T., N.T.); and Departments of Radiology (C.V.W., A.K.) and Laboratory Medicine and Pathology (M.L.S.), Mayo Clinic, Scottsdale, Ariz
| | - Hiroaki Takahashi
- From the Department of Radiology, Mayo Clinic, 200 1st St SW, Rochester, MN 55905 (H.N., H.T., N.T.); and Departments of Radiology (C.V.W., A.K.) and Laboratory Medicine and Pathology (M.L.S.), Mayo Clinic, Scottsdale, Ariz
| | - Clinton V Wellnitz
- From the Department of Radiology, Mayo Clinic, 200 1st St SW, Rochester, MN 55905 (H.N., H.T., N.T.); and Departments of Radiology (C.V.W., A.K.) and Laboratory Medicine and Pathology (M.L.S.), Mayo Clinic, Scottsdale, Ariz
| | - Melissa L Stanton
- From the Department of Radiology, Mayo Clinic, 200 1st St SW, Rochester, MN 55905 (H.N., H.T., N.T.); and Departments of Radiology (C.V.W., A.K.) and Laboratory Medicine and Pathology (M.L.S.), Mayo Clinic, Scottsdale, Ariz
| | - Naoki Takahashi
- From the Department of Radiology, Mayo Clinic, 200 1st St SW, Rochester, MN 55905 (H.N., H.T., N.T.); and Departments of Radiology (C.V.W., A.K.) and Laboratory Medicine and Pathology (M.L.S.), Mayo Clinic, Scottsdale, Ariz
| | - Akira Kawashima
- From the Department of Radiology, Mayo Clinic, 200 1st St SW, Rochester, MN 55905 (H.N., H.T., N.T.); and Departments of Radiology (C.V.W., A.K.) and Laboratory Medicine and Pathology (M.L.S.), Mayo Clinic, Scottsdale, Ariz
| |
Collapse
|
|
2
|
Jaime-Casas S, Tripathi A, Pal SK, Yip W. Clinical Implications of the Molecular and Genomic Landscape of Upper Tract Urothelial Carcinoma. Curr Urol Rep 2024; 26:11. [PMID: 39379745 PMCID: PMC11461588 DOI: 10.1007/s11934-024-01245-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/27/2024] [Indexed: 10/10/2024]
Abstract
PURPOSE OF REVIEW Upper tract urothelial carcinoma (UTUC) is an aggressive entity with treatment strategies mirroring bladder cancer. Genomic and molecular profiling allows for a better characterization of this disease and allows for patient-tailored approaches. We aim to describe the genomic and molecular implications of this disease. RECENT FINDINGS Technological advances have the potential for early diagnosis and precise molecular analysis in patients with UTUC. Genomic profile clustering, specific mRNA signatures, and pathway-specific protein abundance tools have oncologic and clinical implications. We describe their utility in the context of this disease. In the era of precision medicine, designing clinical trials that explore the diagnostic and prognostic implications of biomolecular signatures in the context of UTUC is of utmost importance. Promising advances in this arena provide tools for physicians to avoid overtreatment in this patient population.
Collapse
Affiliation(s)
- Salvador Jaime-Casas
- Department of Medical Oncology & Experimental Therapeutics, City of Hope Comprehensive Cancer Center, 1500 East Duarte Road, Duarte, CA, 91010, USA
| | - Abhishek Tripathi
- Department of Medical Oncology & Experimental Therapeutics, City of Hope Comprehensive Cancer Center, 1500 East Duarte Road, Duarte, CA, 91010, USA
| | - Sumanta K Pal
- Department of Medical Oncology & Experimental Therapeutics, City of Hope Comprehensive Cancer Center, 1500 East Duarte Road, Duarte, CA, 91010, USA
| | - Wesley Yip
- Division of Urology and Urologic Oncology, City of Hope Comprehensive Cancer Center, 1500 East Duarte Road, Duarte, CA, 91010, USA.
| |
Collapse
|
|
3
|
Tua-Caraccia R, Livingston A, Routh JC. Recurrent Papillary Bladder Tumors in a Boy With Lynch Syndrome. Urology 2023; 181:133-135. [PMID: 37422136 DOI: 10.1016/j.urology.2023.06.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2023] [Accepted: 06/19/2023] [Indexed: 07/10/2023]
Abstract
Lynch syndrome (LS) is an autosomal dominant genetic disorder defined by germline mutations in one of four mismatch repair genes including PMS2, MLH2, MSH1, MSH2, or deletion in the EPCAM gene.1 The most common urologic manifestation of LS is upper tract urothelial carcinoma, which occurs in up to 20% of patients with LS.2 While data are scarce, there is growing evidence of an increased relative risk of bladder malignancy in patients with LS.3,4 Bladder tumors in children are a rare entity and the link between pediatric bladder tumors and LS has not been previously reported to our knowledge.
Collapse
Affiliation(s)
| | - Austin Livingston
- Department of Urology, Duke University School of Medicine, Durham, NC
| | - Jonathan C Routh
- Department of Urology, Duke University School of Medicine, Durham, NC
| |
Collapse
|
|
4
|
Nassour AJ, Jain A, Hui N, Siopis G, Symons J, Woo H. Relative Risk of Bladder and Kidney Cancer in Lynch Syndrome: Systematic Review and Meta-Analysis. Cancers (Basel) 2023; 15:506. [PMID: 36672455 PMCID: PMC9856836 DOI: 10.3390/cancers15020506] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2022] [Revised: 01/07/2023] [Accepted: 01/08/2023] [Indexed: 01/17/2023] Open
Abstract
Background: The association between Lynch syndrome (LS) and a higher risk of upper tract urothelial carcinoma is well established, but its effect on the risk of bladder and kidney cancers remains controversial. This review aimed to compare the relative risk (RR) of bladder and kidney cancer in confirmed LS germline mutation carriers compared to the general population. Methods: Medline, Embase, Cochrane Central, and Google Scholar were searched on 14 July 2022 for studies published in English that reported on the rates of urological cancer in adults with confirmed LS germline mutation. The quality of included studies was assessed using Cochrane’s tool to evaluate risk of bias in cohort studies. Random effects meta-analysis estimated the pooled relative risk of bladder and kidney cancer in LS carriers compared to the general population. The quality of the overall evidence was evaluated using GRADE. Results: Of the 1839 records identified, 5 studies involving 7120 participants from 3 continents were included. Overall, LS carriers had a statistically significantly higher RR of developing bladder cancer (RR: 7.48, 95% CI: 3.70, 15.13) and kidney cancer (RR: 3.97, 95% CI: 1.23, 12.81) compared to unaffected participants (p < 0.01). The quality of the evidence was assessed as “low” due to the inclusion of cohort studies, the substantial heterogeneity, and moderate-to-high risk of bias. Conclusion: Lynch syndrome is associated with a significant increase in the relative risk of kidney and bladder cancer. Clinicians should adopt a lower threshold for germline mutation genetic testing in individuals who present with bladder cancer. Further studies evaluating the role and cost-effectiveness of novel urine-based laboratory tests are needed. High-quality studies in histologically proven renal cell carcinoma and their underlying germline mutations are necessary to strengthen the association with LS.
Collapse
Affiliation(s)
- Anthony-Joe Nassour
- SAN Prostate Centre of Excellence, Sydney Adventist Hospital, Wahroonga, NSW 2076, Australia
- Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2006, Australia
| | - Anika Jain
- SAN Prostate Centre of Excellence, Sydney Adventist Hospital, Wahroonga, NSW 2076, Australia
| | - Nicholas Hui
- SAN Prostate Centre of Excellence, Sydney Adventist Hospital, Wahroonga, NSW 2076, Australia
- Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2006, Australia
| | - George Siopis
- Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2006, Australia
- Institute for Physical Activity and Nutrition, Deakin University, Geelong, VIC 3125, Australia
| | - James Symons
- SAN Prostate Centre of Excellence, Sydney Adventist Hospital, Wahroonga, NSW 2076, Australia
- Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2006, Australia
- College of Health and Medicine, The Australian National University, Canberra, ACT 2601, Australia
| | - Henry Woo
- SAN Prostate Centre of Excellence, Sydney Adventist Hospital, Wahroonga, NSW 2076, Australia
- College of Health and Medicine, The Australian National University, Canberra, ACT 2601, Australia
| |
Collapse
|
|
5
|
Perry KW, Taylor Z, Piraino J, McMahon G. Primary Ureteral Stump Carcinoma: Rare Presentation and Management. Cureus 2022; 14:e29103. [PMID: 36258966 PMCID: PMC9573244 DOI: 10.7759/cureus.29103] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2022] [Accepted: 09/12/2022] [Indexed: 11/11/2022] Open
Abstract
Primary ureteral stump carcinoma is a rare occurrence in patients who receive radical nephrectomy for renal cell carcinoma (RCC). Only 11 previous cases have been reported in the literature. We report a case of synchronous bilateral RCC and colon adenocarcinoma with the subsequent development of primary ureteral stump carcinoma that was treated with robotic ureterectomy and bladder cuff excision. To our knowledge, this is the first reported case of this presentation.
Collapse
|
|
6
|
Genitourinary manifestations of Lynch syndrome in the urological practice. Asian J Urol 2022; 9:443-450. [DOI: 10.1016/j.ajur.2022.05.009] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2021] [Revised: 05/08/2022] [Accepted: 05/16/2022] [Indexed: 11/19/2022] Open
|
|
7
|
Guan B, Wang J, Li X, Lin L, Fang D, Kong W, Tian C, Li J, Yang K, Han G, Wu Y, He Y, Peng Y, Yu Y, He Q, He S, Gong Y, Zhou L, Tang Q. Identification of Germline Mutations in Upper Tract Urothelial Carcinoma With Suspected Lynch Syndrome. Front Oncol 2022; 12:774202. [PMID: 35372080 PMCID: PMC8966221 DOI: 10.3389/fonc.2022.774202] [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: 09/11/2021] [Accepted: 02/18/2022] [Indexed: 11/21/2022] Open
Abstract
Objective Whole-exon sequencing (WES) is a commercially available tool for hereditary disease testing. However, little is known about hereditary upper-tract urothelial carcinoma (UTUC) in the Chinese population. This study aims to investigate the prevalence of Lynch syndrome (LS) in UTUC patients with high-risk features and identify the germline mutations of genetic predisposition gene mutations in those patients. Methods In total, 354 consecutive UTUC patients undergoing surgery were universally recruited, of whom 108 patients under 60 years old or with a personal/family history of cancer underwent universal immunohistochemistry staining to detect the expression of mismatch repair (MMR) proteins (MLH1, MSH2, MSH6 and PMS2). Patients with deficient or weak MMR protein staining or meeting the Amsterdam II criterion were defined as suspected LS patients, who further experienced microsatellite instability (MSI) (BAT25, BAT26, BAT40, D2S123, D5S346, D17S250) detection and performed WES analysis to explore germline pathogenic/likely pathogenic (P/LP) alterations. Results Of 108 patients, 90 (83.3%) cases were included due to younger than 60 years, and 18 cases due to personal/family history. IHC staining identified 21 patients with deficient MMR protein staining and 15 cases with weak MMR protein staining. Three cases met the Amsterdam II criterion but with proficient MMR protein staining. Finally, WES analysis was performed in 38 suspected LS patients and P/LP germline mutations were identified in 22 individuals. Genetic testing confirmed 5 LS cases, including 3 cases with novel mutations. MSI-harboring tumor was discovered in 4 LS cases, one of whom had weak MMR protein staining. Germline P/LP variants in DNA damage repair genes were found in 11 cases. In addition, we found that 11 patients had high- or moderate- penetrance P/LP mutations other than MMR genes. The common P/LP variants in high- or moderate-penetrance genes were 4 in ATM, 3 in MSH6 and KIT, and 2 in APC, NF1 and DICER. Conclusions We identified approximately 11% of UTUC cases as suspected LS and at least 1.4% patients with confirmed LS-associated UTUC. In addition, broader germline genetic testing could be considered to screen for cancer severity in hereditary UTUC patients.
Collapse
Affiliation(s)
- Bao Guan
- Department of Urology, Peking University First Hospital, Beijing, China.,Institute of Urology, Peking University, Beijing, China.,National Urological Cancer Center, Beijing, China
| | - Jie Wang
- Department of Urology, Peking University First Hospital, Beijing, China.,Institute of Urology, Peking University, Beijing, China.,National Urological Cancer Center, Beijing, China
| | - Xuesong Li
- Department of Urology, Peking University First Hospital, Beijing, China.,Institute of Urology, Peking University, Beijing, China.,National Urological Cancer Center, Beijing, China
| | - Lin Lin
- Department of Anorectal, Yantai Baishi Anorectal Hospital, Yantai, China
| | - Dong Fang
- Department of Urology, Peking University First Hospital, Beijing, China.,Institute of Urology, Peking University, Beijing, China.,National Urological Cancer Center, Beijing, China
| | - Wenwen Kong
- Key Laboratory of Genomics and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China
| | - Chuangyu Tian
- Key Laboratory of Genomics and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China
| | - Juan Li
- Key Laboratory of Genomics and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China
| | - Kunlin Yang
- Department of Urology, Peking University First Hospital, Beijing, China.,Institute of Urology, Peking University, Beijing, China.,National Urological Cancer Center, Beijing, China
| | - Guanpeng Han
- Department of Urology, Peking University First Hospital, Beijing, China.,Institute of Urology, Peking University, Beijing, China.,National Urological Cancer Center, Beijing, China
| | - Yucai Wu
- Department of Urology, Peking University First Hospital, Beijing, China.,Institute of Urology, Peking University, Beijing, China.,National Urological Cancer Center, Beijing, China
| | - Yuhui He
- Department of Urology, Peking University First Hospital, Beijing, China.,Institute of Urology, Peking University, Beijing, China.,National Urological Cancer Center, Beijing, China
| | - Yiji Peng
- Department of Urology, Peking University First Hospital, Beijing, China.,Institute of Urology, Peking University, Beijing, China.,National Urological Cancer Center, Beijing, China
| | - Yanfei Yu
- Department of Urology, Peking University First Hospital, Beijing, China.,Institute of Urology, Peking University, Beijing, China.,National Urological Cancer Center, Beijing, China
| | - Qun He
- Department of Urology, Peking University First Hospital, Beijing, China.,Institute of Urology, Peking University, Beijing, China.,National Urological Cancer Center, Beijing, China
| | - Shiming He
- 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
| | - Liqun Zhou
- Department of Urology, Peking University First Hospital, Beijing, China.,Institute of Urology, Peking University, Beijing, China.,National Urological Cancer Center, Beijing, China
| | - Qi Tang
- Department of Urology, Peking University First Hospital, Beijing, China.,Institute of Urology, Peking University, Beijing, China.,National Urological Cancer Center, Beijing, China
| |
Collapse
|
|
8
|
Cinque A, Capasso A, Vago R, Floris M, Lee MW, Minnei R, Trevisani F. MicroRNA Signatures in the Upper Urinary Tract Urothelial Carcinoma Scenario: Ready for the Game Changer? Int J Mol Sci 2022; 23:2602. [PMID: 35269744 PMCID: PMC8910117 DOI: 10.3390/ijms23052602] [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] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Revised: 02/20/2022] [Accepted: 02/24/2022] [Indexed: 12/18/2022] Open
Abstract
Upper urinary tract urothelial carcinoma (UTUC) represents a minor subgroup of malignancies arising in the urothelium of the renal pelvis or ureter. The estimated annual incidence is around 2 cases per 100,000 people, with a mean age at diagnosis of 73 years. UTUC is more frequently diagnosed in an invasive or metastatic stage. However, even though the incidence of UTUC is not high, UTUC tends to be aggressive and rapidly progressing with a poor prognosis in some patients. A significant challenge in UTUC is ensuring accurate and timely diagnosis, which is complicated by the non-specific nature of symptoms seen at the onset of disease. Moreover, there is a lack of biomarkers capable of identifying the early presence of the malignancy and guide-tailored medical treatment. However, the growing understanding of the molecular biology underlying UTUC has led to the discovery of promising new biomarkers. Among these biomarkers, there is a class of small non-coding RNA biomarkers known as microRNAs (miRNAs) that are particularly promising. In this review, we will analyze the main characteristics of UTUC and focus on microRNAs as possible novel tools that could enter clinical practice in order to optimize the current diagnostic and prognostic algorithm.
Collapse
Affiliation(s)
- Alessandra Cinque
- Biorek S.r.l., San Raffaele Scientific Institute, 20132 Milan, Italy;
| | - Anna Capasso
- Department of Medical Oncology Livestrong Cancer Institutes, Dell Medical School, University of Texas at Austin, Austin, TX 78723, USA;
| | - Riccardo Vago
- Urological Research Institute, Division of Experimental Oncology, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy;
- Faculty of Medicine and Surgery,, Università Vita-Salute San Raffaele, 20132 Milan, Italy
| | - Matteo Floris
- Nephrology, Dialysis, and Transplantation, Università degli Studi di Cagliari, G. Brotzu Hospital, 09134 Cagliari, Italy; (M.F.); (R.M.)
| | - Michael W. Lee
- Department of Medical Oncology and Medical Education, Dell Medical School, Livestrong Cancer Institutes, University of Texas at Austin, Austin, TX 78723, USA;
| | - Roberto Minnei
- Nephrology, Dialysis, and Transplantation, Università degli Studi di Cagliari, G. Brotzu Hospital, 09134 Cagliari, Italy; (M.F.); (R.M.)
| | - Francesco Trevisani
- Biorek S.r.l., San Raffaele Scientific Institute, 20132 Milan, Italy;
- Urological Research Institute, Division of Experimental Oncology, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy;
- Unit of Urology, San Raffaele Scientific Institute, 20132 Milan, Italy
| |
Collapse
|
|
9
|
Shvero A, Hubosky SG. Management of Upper Tract Urothelial Carcinoma. Curr Oncol Rep 2022; 24:611-619. [PMID: 35212921 DOI: 10.1007/s11912-021-01179-8] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/01/2021] [Indexed: 11/29/2022]
Abstract
PURPOSE OF REVIEW We review the epidemiology, risk factors, diagnosis, and treatment of upper tract urothelial carcinoma (UTUC), with a distinction between the different risk groups. RECENT FINDINGS Endoscopic treatment with laser ablation of tumors has an evolving role in treating low-grade UTUC including select large and multifocal tumors, along with complementary topical chemotherapeutic treatment that can reach difficult intrarenal locations. Template lymphadenectomy is recommended in patients undergoing nephroureterectomy. A recent randomized control trial showed benefit of adjuvant chemotherapy after radical nephroureterectomy for locally advanced disease. Advances in immunologic therapy have shown promise in treating metastatic UTUC, and immunologic-based therapies have been incorporated into treatment regimens. Notable progress has been made in both the surgical and medical treatment arms for UTUC, thus extending the reach of nephron-sparing therapy for those with localized disease and increasing overall survival for those with locally advanced disease.
Collapse
Affiliation(s)
- Asaf Shvero
- Department of Urology, Sidney Kimmel Medical College at Thomas Jefferson University Hospital, Thomas Jefferson University, 1025 Walnut Street, Suite 1100, Philadelphia, PA, 19107, USA.,Department of Urology, Sheba Medical Center, Ramat-Gan, Israel.,Tel Aviv University, Tel Aviv, Israel
| | - Scott G Hubosky
- Department of Urology, Sidney Kimmel Medical College at Thomas Jefferson University Hospital, Thomas Jefferson University, 1025 Walnut Street, Suite 1100, Philadelphia, PA, 19107, USA.
| |
Collapse
|
|
10
|
Lynch syndrome in urological practice: diagnosis, therapeutic strategies, and screening for upper tract urothelial carcinoma. Curr Opin Urol 2022; 32:40-47. [PMID: 34608026 DOI: 10.1097/mou.0000000000000936] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
PURPOSE OF REVIEW To provide a comprehensive overview of diagnosis, treatment, and screening for upper tract urothelial carcinoma (UTUC) among Lynch syndrome patients. RECENT FINDINGS Lynch syndrome is an autosomal dominant disorder resulting from the germline mutation in the mismatch repair (MMR) system. The Lynch syndrome predisposes to early onset of a broad spectrum of tumours, among which UTUC represents the third most frequent malignancy. Since up to 10% of UTUC can be attributed to Lynch syndrome, a correct recognition of this disease provides the opportunity for patients and their relatives to be properly treated for UTUC and to be followed up for other Lynch syndrome-related malignancies. SUMMARY UTUC patients less than 65 years, or UTUC patients with personal history of Lynch syndrome-related cancer, or with one first-degree relative (FDR) less than 50 years with Lynch syndrome-related cancer, or two FDRs with Lynch syndrome-related cancer regardless of age should be referred to molecular testing and subsequent DNA sequencing to confirm Lynch syndrome diagnosis. Considering the increased risk of metachronous recurrence, treatments other than radical nephroureterectomy, such as ureteroscopic laser ablation may represent valuable therapeutic strategies. As Lynch syndrome patients exhibit an approximate 14-fold increased risk of developing UTUC compared with general population, expert recommendations are urgently required in order to point out appropriate screening protocols.
Collapse
|
|
11
|
Grobet-Jeandin E, Pinar U, Rouprêt M. Upper Urinary Tract Urothelial Carcinoma in Lynch Syndrome Patients: The Urologist Still Has a Role in Genetic Screening. Eur Urol Oncol 2021; 5:42-43. [PMID: 34980573 DOI: 10.1016/j.euo.2021.12.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2021] [Accepted: 12/13/2021] [Indexed: 11/30/2022]
Affiliation(s)
- Elisabeth Grobet-Jeandin
- GRC 5 Predictive Onco-Urology, Department of Urology, Pitié-Salpêtrière Hôpital, APHP, Sorbonne University, Paris, France; Division of Urology, Geneva University Hospitals, Geneva, Switzerland
| | - Ugo Pinar
- GRC 5 Predictive Onco-Urology, Department of Urology, Pitié-Salpêtrière Hôpital, APHP, Sorbonne University, Paris, France
| | - Morgan Rouprêt
- GRC 5 Predictive Onco-Urology, Department of Urology, Pitié-Salpêtrière Hôpital, APHP, Sorbonne University, Paris, France.
| |
Collapse
|
|
12
|
Lonati C, Necchi A, Gómez Rivas J, Afferi L, Laukhtina E, Martini A, Ventimiglia E, Colombo R, Gandaglia G, Salonia A, Briganti A, Montorsi F, Mattei A, Simeone C, Carlo MI, Shariat SF, Spiess PE, Moschini M. Upper Tract Urothelial Carcinoma in the Lynch Syndrome Tumour Spectrum: A Comprehensive Overview from the European Association of Urology - Young Academic Urologists and the Global Society of Rare Genitourinary Tumors. Eur Urol Oncol 2021; 5:30-41. [PMID: 34896051 DOI: 10.1016/j.euo.2021.11.001] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2021] [Revised: 10/08/2021] [Accepted: 11/03/2021] [Indexed: 12/12/2022]
Abstract
CONTEXT Upper tract urothelial carcinoma (UTUC) represents the third most frequent malignancy in Lynch syndrome (LS). OBJECTIVE To systematically review the available literature focused on incidence, diagnosis, clinicopathological features, oncological outcomes, and screening protocols for UTUC among LS patients. EVIDENCE ACQUISITION Medline, Scopus, Google Scholar, and Cochrane Database of Systematic Reviews were searched up to May 2021. Risk of bias was determined using the modified Cochrane tool. A narrative synthesis was undertaken. EVIDENCE SYNTHESIS Overall, 43 studies between 1996 and 2020 were included. LS patients exhibited a 14-fold increased risk of UTUC compared with the general population, which further increased to 75-fold among hMSH2 mutation carriers. Patients younger than 65 yr and patients with personal or family history of LS-related cancers should be referred to molecular testing on tumour specimen and subsequent genetic testing to confirm LS. Newly diagnosed LS patients may benefit from a multidisciplinary management team including gastroenterologist and gynaecologist specialists, while genetic counselling should be recommended to first-degree relatives (FDRs). Compared with sporadic UTUC individuals, LS patients were significantly younger (p = 0.005) and exhibited a prevalent ureteral location (p = 0.01). Radical nephroureterectomy was performed in 75% of patients (5-yr cancer-specific survival: 91%). No consensus on screening protocols for UTUC was achieved: starting age varied between 25-35 and 50 yr, while urinary cytology showed sensitivity of 29% and was not recommended for screening. CONCLUSIONS Urologists should recognise patients at high risk for LS and address them to a comprehensive diagnostic pathway, including molecular and genetic testing. Newly diagnosed LS patients should be referred to a multidisciplinary team, while genetic counselling should be recommended to FDRs. PATIENT SUMMARY In this systematic review, we analysed the existing literature focused on upper tract urothelial carcinoma (UTUC) among patients with Lynch syndrome (LS). Our purpose is to provide a comprehensive overview of LS-related UTUC to reduce misdiagnosis and improve patient prognosis.
Collapse
Affiliation(s)
- Chiara Lonati
- Department of Urology, Spedali Civili di Brescia, Brescia, Italy; Department of Urology, Luzerner Kantonsspital, Lucerne, Switzerland.
| | - Andrea Necchi
- University Vita-Salute San Raffaele, Milan, Italy; Department of Medical Oncology, Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Juan Gómez Rivas
- Department of Urology, Clinico San Carlos Hospital, Madrid, Spain
| | - Luca Afferi
- Department of Urology, Luzerner Kantonsspital, Lucerne, Switzerland
| | - Ekaterina Laukhtina
- Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna General Hospital, Vienna, Austria; Institute for Urology and Reproductive Health, Sechenov University, Moscow, Russia
| | - Alberto Martini
- Division of Experimental Oncology/Unit of Urology, Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Eugenio Ventimiglia
- Division of Experimental Oncology/Unit of Urology, Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Renzo Colombo
- Division of Experimental Oncology/Unit of Urology, Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Giorgio Gandaglia
- Division of Experimental Oncology/Unit of Urology, Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Andrea Salonia
- University Vita-Salute San Raffaele, Milan, Italy; Division of Experimental Oncology/Unit of Urology, Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Alberto Briganti
- University Vita-Salute San Raffaele, Milan, Italy; Division of Experimental Oncology/Unit of Urology, Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Francesco Montorsi
- University Vita-Salute San Raffaele, Milan, Italy; Division of Experimental Oncology/Unit of Urology, Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Agostino Mattei
- Department of Urology, Luzerner Kantonsspital, Lucerne, Switzerland
| | - Claudio Simeone
- Department of Urology, Spedali Civili di Brescia, Brescia, Italy
| | - Maria I Carlo
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Shahrokh F Shariat
- Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna General Hospital, Vienna, Austria; Institute for Urology and Reproductive Health, Sechenov University, Moscow, Russia; Department of Urology, Weill Cornell Medical College, New York, NY, USA; Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA; Department of Urology, Second Faculty of Medicine, Charles University, Prague, Czech Republic
| | - Philippe E Spiess
- Department of Genitourinary Oncology, Moffitt Cancer Center and Research Institute, Tampa, FL, USA
| | - Marco Moschini
- Department of Urology, Luzerner Kantonsspital, Lucerne, Switzerland; Division of Experimental Oncology/Unit of Urology, Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy
| | | |
Collapse
|
|
13
|
DeJesse J, Vajravelu RK, Dudzik C, Constantino G, Long JM, Wangensteen KJ, Valverde KD, Katona BW. Uptake and outcomes of small intestinal and urinary tract cancer surveillance in Lynch syndrome. World J Clin Oncol 2021; 12:1023-1036. [PMID: 34909397 PMCID: PMC8641013 DOI: 10.5306/wjco.v12.i11.1023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2021] [Revised: 07/26/2021] [Accepted: 10/14/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Lynch syndrome (LS) is a hereditary cancer predisposition syndrome associated with increased risk of multiple cancers. While colorectal cancer surveillance decreases mortality in LS and is recommended by guidelines, there is lack of evidence for the efficacy of surveillance for extra-colonic cancers associated with LS, including small intestinal cancer (SIC) and urinary tract cancer (UTC). Given the limited evidence, guidelines do not consistently recommend surveillance for SIC and UTC, and it remains unclear how often individuals will choose to undergo and follow through with extra-colonic surveillance recommendations.
AIM To study factors associated with SIC and UTC surveillance uptake and outcomes in LS.
METHODS This is an IRB-approved retrospective analysis of individuals with LS seen at a tertiary care referral center. Included individuals had a pathogenic or likely pathogenic variant in MLH1, MSH2, MSH6, PMS2, or EPCAM, or were a confirmed obligate carrier, and had at least one documented visit to our center. Information regarding SIC and UTC surveillance was captured for each individual, and detailed personal and family history was obtained for individuals who had an initial LS management visit in our center’s dedicated high-risk LS clinic between January 1, 2017 and October 29, 2020. During these initial management visits, all patients had in-depth discussions of SIC and UTC surveillance with 1 of 3 providers experienced in LS management to promote informed decision-making about whether to pursue SIC and/or UTC surveillance. Statistical analysis using Pearson’s chi-squared test and Wilcoxon rank-sum test was completed to understand the factors associated with pursuit and completion of SIC and UTC surveillance, and a P value below 0.05 was deemed statistically significant.
RESULTS Of 317 individuals with LS, 86 (27%) underwent a total of 105 SIC surveillance examinations, with 5 leading to additional work-up and no SICs diagnosed. Additionally, 99 (31%) patients underwent a total of 303 UTC surveillance examinations, with 19 requiring further evaluation and 1 UTC identified. Of 155 individuals who had an initial LS management visit between January 1, 2017 and October 29, 2020, 63 (41%) chose to undergo SIC surveillance and 58 (37%) chose to undergo UTC surveillance. However, only 26 (41%) and 32 (55%) of those who initially chose to undergo SIC or UTC surveillance, respectively, successfully completed their surveillance examinations. Individuals with a pathogenic variant in MSH2 or EPCAM were more likely to initially choose to undergo SIC surveillance (P = 0.034), and older individuals were more likely to complete SIC surveillance (P = 0.007). Choosing to pursue UTC surveillance was more frequent among older individuals (P = 0.018), and females more frequently completed UTC surveillance (P = 0.002). Personal history of cancer and family history of SIC or UTC were not significantly associated with electing nor completing surveillance. Lastly, the provider discussing SIC/UTC surveillance was significantly associated with subsequent surveillance choices.
CONCLUSION Pursuing and completing SIC/UTC surveillance in LS is influenced by several factors, however broad incorporation in LS management is likely unhelpful due to low yield and frequent false positive results.
Collapse
Affiliation(s)
- Jeshua DeJesse
- Department of Genetics, University of Pennsylvania, Philadelphia, PA 19104, United States
| | - Ravy K Vajravelu
- Division of Gastroenterology and Hepatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, United States
| | - Christina Dudzik
- Division of Gastroenterology and Hepatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, United States
| | - Gillain Constantino
- Division of Gastroenterology and Hepatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, United States
| | - Jessica M Long
- Division of Hematology and Oncology, University of Pennsylvania, Philadelphia, PA 19104, United States
| | - Kirk J Wangensteen
- Division of Gastroenterology and Hepatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, United States
| | - Kathleen D Valverde
- Department of Genetics, University of Pennsylvania, Philadelphia, PA 19104, United States
| | - Bryson W Katona
- Division of Gastroenterology and Hepatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, United States
| |
Collapse
|
|
14
|
Baard J, Cormio L, Cavadas V, Alcaraz A, Shariat SF, de la Rosette J, Laguna MP. Contemporary patterns of presentation, diagnostics and management of upper tract urothelial cancer in 101 centres: the Clinical Research Office of the Endourological Society Global upper tract urothelial carcinoma registry. Curr Opin Urol 2021; 31:354-362. [PMID: 34009177 DOI: 10.1097/mou.0000000000000899] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
PURPOSE OF REVIEW To assess patterns of presentation, diagnostics and treatment in patients with upper tract urothelial carcinoma (UTUC), a multicentre registry was launched. Clinical data of UTUC patients were prospectively collected over a 5-year period. RECENT FINDINGS Data from 2380 patients were included from 2014 to 2019 (101 centres in 29 countries). Patients were predominantly male (70.5%) and 53.3% were past or present smokers. The majority of patients (58.1%) were evaluated because of symptoms, mainly macroscopic hematuria. Computed tomography (CT) was the most common performed imaging modality (90.5%). A ureteroscopy (URS) was part of the diagnostic process in 1184 (49.7%) patients and 488 (20.5%) patients were treated endoscopically. In total, 1430 patients (60.1%) were treated by a radical nephroureterectomy, 59% without a prior diagnostic URS. Eighty-two patients (3.4%) underwent a segmental resection, 19 patients (0.8%) were treated by a percutaneous tumour resection. SUMMARY Our data is in line with the known epidemiologic characteristics of UTUC. CT imaging is the preferred imaging modality as also recommended by guidelines. Diagnostic URS gained a stronger position, however, in almost half of patients a definitive treatment decision was made without complete endoscopic information. Only one-third of patients with UTUC are currently treated with kidney sparing surgery.
Collapse
Affiliation(s)
- Joyce Baard
- Department of Urology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Luigi Cormio
- Department of Urology, University of Foggia, Foggia, Italy
| | - Vitor Cavadas
- Department of Urology, Centro Hospitalar Universitário do Porto, Porto, Portugal
| | - Antonio Alcaraz
- Department of Urology Hospital Clinic i Provincial de Barcelona, Barcelona, Spain
| | - Shahrokh F Shariat
- Department of Urology, Medical University of Vienna, Vienna, Austria
- Department of Urology, UT Southwestern, Dallas, Texas, USA
- Department of Urology, Motol Hospital Charles University, Praque, Czech Republic
- Department of Urology, I.M. Sechenov University, Moscow, Russia
| | - Jean de la Rosette
- Department of Urology, Medipol Mega University Hospital, Istanbul Medipol University, Istanbul, Turkey
| | - Maria P Laguna
- Department of Urology, Medipol Mega University Hospital, Istanbul Medipol University, Istanbul, Turkey
| |
Collapse
|
|
15
|
Souaid T, Hindy JR, Diab E, Kourie HR. Are there monogenic hereditary forms of bladder cancer or only genetic susceptibilities? Pharmacogenomics 2021; 22:619-628. [PMID: 34044612 DOI: 10.2217/pgs-2020-0165] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Bladder cancer (BC) is the most common cancer involving the urinary system and the ninth most common cancer worldwide. Tobacco smoking is the most important environmental risk factor of BC. Several single nucleotide polymorphisms have been validated by genome-wide association studies as genetic risk factors for BC. However, the identification of DNA mismatch-repair genes, including MSH2 in Lynch syndrome and MUTYH in MUTYH-associated polyposis, raises the possibility of monogenic hereditary forms of BC. Moreover, other genetic mutations may play a key role in familial and hereditary transmissions of BC. Therefore, the aim of this review is to focus on the major hereditary syndromes involved in the development of BC and to report BC genetic susceptibilities established with genome-wide significance level.
Collapse
Affiliation(s)
- Tarek Souaid
- Faculty of Medicine, Saint Joseph University, Beirut, Lebanon
| | - Joya-Rita Hindy
- Faculty of Medicine, Saint Joseph University, Beirut, Lebanon
| | - Ernest Diab
- Faculty of Medicine, Saint Joseph University, Beirut, Lebanon
| | - Hampig Raphael Kourie
- Faculty of Medicine, Saint Joseph University, Beirut, Lebanon.,Oncology department, Faculty of Medicine, Saint Joseph University, Beirut, Lebanon
| |
Collapse
|
|
16
|
Yang B, Zhao X, Wan C, Ma X, Niu S, Guo A, Wang J, Wang J, Sun D, Jiao S. Genomic profiling of Chinese patients with urothelial carcinoma. BMC Cancer 2021; 21:162. [PMID: 33588785 PMCID: PMC7885246 DOI: 10.1186/s12885-021-07829-1] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2020] [Accepted: 01/21/2021] [Indexed: 12/24/2022] Open
Abstract
BACKGROUNDS Urothelial carcinoma (UC) is the most common genitourinary malignancy in China. In this study, we surveyed the genomic features in Chinese UC patients and investigated the concordance of genetic alterations between circulating tumor DNA (ctDNA) in plasma and matched tumor tissue. MATERIALS AND METHODS A total of 112 UC patients were enrolled, of which 31 were upper tract UC (UTUC) and 81 were UC of bladder (UCB). Genomic alterations in 92 selected genes were analyzed by targeted next-generation sequencing. RESULTS In the study cohort, 94.64, 86.61 and 62.50% of patients were identified as having valid somatic, oncogenic and actionable somatic alterations, respectively. The most frequently altered genes included TP53, KMT2D, KDM6A, FAT4, FAT1, CREBBP and ARID1A. The higher prevalence of HRAS (22.0% vs 3.7%) and KMT2D (59.26% vs 34.57%) was identified in UTUC than in UCB. Comparisons of somatic alterations of UCB and UTUC between the study cohort and western cohorts revealed significant differences in mutant prevalence. Notably, 28.57, 17.86 and 47.32% of the cases harbored alterations in FGFRs, ERBBs and DNA damage repair genes, respectively. Furthermore, 75% of the patients carried non-benign germline variants, but only two (1.79%) were pathogenic. The overall concordance for genomic alterations in ctDNA and matched tumor tissue was 42.97% (0-100%). Notably, 47.25% of alterations detected in ctDNA were not detected in the matched tissue, and 54.14% of which were oncogenic mutations. CONCLUSIONS We found a unique genomic feature of Chinese UC patients. A reasonably good concordance of genomic features between ctDNA and tissue samples were identified.
Collapse
Affiliation(s)
- Bo Yang
- Department of Oncology, Chinese PLA General Hospital, Fuxing Road 28, Beijing, China
| | - Xiao Zhao
- Department of Oncology, Chinese PLA General Hospital, Fuxing Road 28, Beijing, China
| | - Chong Wan
- Lifehealthcare Clinical Laboratories, Hangzhou, China
| | - Xin Ma
- Department of Urology, Chinese PLA General Hospital, Beijing, China
| | - Shaoxi Niu
- Department of Urology, Chinese PLA General Hospital, Beijing, China
| | - Aitao Guo
- Department of Pathology, Chinese PLA General Hospital, Beijing, China
| | - Jieli Wang
- Department of Oncology, Chinese PLA General Hospital, Fuxing Road 28, Beijing, China
| | - Jinliang Wang
- Department of Oncology, Chinese PLA General Hospital, Fuxing Road 28, Beijing, China
| | - Decong Sun
- Department of Oncology, Chinese PLA General Hospital, Fuxing Road 28, Beijing, China
| | - Shunchang Jiao
- Department of Oncology, Chinese PLA General Hospital, Fuxing Road 28, Beijing, China.
| |
Collapse
|
|
17
|
Lindner AK, Schachtner G, Tulchiner G, Thurnher M, Untergasser G, Obrist P, Pipp I, Steinkohl F, Horninger W, Culig Z, Pichler R. Lynch Syndrome: Its Impact on Urothelial Carcinoma. Int J Mol Sci 2021; 22:E531. [PMID: 33430305 PMCID: PMC7825811 DOI: 10.3390/ijms22020531] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2020] [Revised: 12/30/2020] [Accepted: 01/03/2021] [Indexed: 12/21/2022] Open
Abstract
Lynch syndrome, known as hereditary nonpolyposis colorectal cancer (HNPCC), is an autosomal-dominant familial cancer syndrome with an increased risk for urothelial cancer (UC). Mismatch repair (MMR) deficiency, due to pathogenic variants in MLH1, MSH2, MSH6, and PMS2, and microsatellite instability, are known for development of Lynch syndrome (LS) associated carcinogenesis. UC is the third most common cancer type in LS-associated tumors. The diversity of germline variants in the affected MMR genes and their following subsequent function loss might be responsible for the variation in cancer risk, suggesting an increased risk of developing UC in MSH2 mutation carriers. In this review, we will focus on LS-associated UC of the upper urinary tract (UUT) and bladder, their germline profiles, and outcomes compared to sporadic UC, the impact of genetic testing, as well as urological follow-up strategies in LS. In addition, we present a case of metastatic LS-associated UC of the UUT and bladder, achieving complete response during checkpoint inhibition since more than 2 years.
Collapse
Affiliation(s)
- Andrea Katharina Lindner
- Department of Urology, Medical University Innsbruck, 6020 Innsbruck, Austria; (A.K.L.); (G.S.); (G.T.); (M.T.); (W.H.); (Z.C.)
| | - Gert Schachtner
- Department of Urology, Medical University Innsbruck, 6020 Innsbruck, Austria; (A.K.L.); (G.S.); (G.T.); (M.T.); (W.H.); (Z.C.)
| | - Gennadi Tulchiner
- Department of Urology, Medical University Innsbruck, 6020 Innsbruck, Austria; (A.K.L.); (G.S.); (G.T.); (M.T.); (W.H.); (Z.C.)
| | - Martin Thurnher
- Department of Urology, Medical University Innsbruck, 6020 Innsbruck, Austria; (A.K.L.); (G.S.); (G.T.); (M.T.); (W.H.); (Z.C.)
- Immunotherapy Unit, Department of Urology, Medical University Innsbruck, 6020 Innsbruck, Austria
| | - Gerold Untergasser
- Department of Internal Medicine V, Medical University Innsbruck, 6020 Innsbruck, Austria;
- Experimental Oncogenomic Group, Tyrolean Cancer Research Institute, 6020 Innsbruck, Austria
| | - Peter Obrist
- Pathology Laboratory Obrist and Brunhuber, 6511 Zams, Austria;
| | - Iris Pipp
- Clinical Pathology and Cytodiagnostics, tirol-kliniken, 6020 Innsbruck, Austria;
| | - Fabian Steinkohl
- Department of Radiology, Medical University Innsbruck, 6020 Innsbruck, Austria;
| | - Wolfgang Horninger
- Department of Urology, Medical University Innsbruck, 6020 Innsbruck, Austria; (A.K.L.); (G.S.); (G.T.); (M.T.); (W.H.); (Z.C.)
| | - Zoran Culig
- Department of Urology, Medical University Innsbruck, 6020 Innsbruck, Austria; (A.K.L.); (G.S.); (G.T.); (M.T.); (W.H.); (Z.C.)
| | - Renate Pichler
- Department of Urology, Medical University Innsbruck, 6020 Innsbruck, Austria; (A.K.L.); (G.S.); (G.T.); (M.T.); (W.H.); (Z.C.)
| |
Collapse
|
|
18
|
Ureteroscopic Managment of Upper Tract Urothelial Carcinoma. Bladder Cancer 2021. [DOI: 10.1007/978-3-030-70646-3_35] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
|
|
19
|
Hartman TR, Demidova EV, Lesh RW, Hoang L, Richardson M, Forman A, Kessler L, Speare V, Golemis EA, Hall MJ, Daly MB, Arora S. Prevalence of pathogenic variants in DNA damage response and repair genes in patients undergoing cancer risk assessment and reporting a personal history of early-onset renal cancer. Sci Rep 2020; 10:13518. [PMID: 32782288 PMCID: PMC7419503 DOI: 10.1038/s41598-020-70449-5] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2020] [Accepted: 07/27/2020] [Indexed: 01/05/2023] Open
Abstract
Pathogenic variants (PVs) in multiple genes are known to increase the risk of early-onset renal cancer (eoRC). However, many eoRC patients lack PVs in RC-specific genes; thus, their genetic risk remains undefined. Here, we determine if PVs in DNA damage response and repair (DDRR) genes are enriched in eoRC patients undergoing cancer risk assessment. Retrospective review of de-identified results from 844 eoRC patients, undergoing testing with a multi-gene panel, for a variety of indications, by Ambry Genetics. PVs in cancer-risk genes were identified in 12.8% of patients—with 3.7% in RC-specific, and 8.55% in DDRR genes. DDRR gene PVs were most commonly identified in CHEK2, BRCA1, BRCA2, and ATM. Among the 2.1% of patients with a BRCA1 or BRCA2 PV, < 50% reported a personal history of hereditary breast or ovarian-associated cancer. No association between age of RC diagnosis and prevalence of PVs in RC-specific or DDRR genes was observed. Additionally, 57.9% patients reported at least one additional cancer; breast cancer being the most common (40.1% of females, 2.5% of males). Multi-gene testing including DDRR genes may provide a more comprehensive risk assessment in eoRC patients. Further validation is needed to characterize the association with eoRC.
Collapse
Affiliation(s)
- Tiffiney R Hartman
- Arcadia University, Glenside, PA, USA.,Cancer Biology Program, Fox Chase Cancer Center, Philadelphia, PA, USA
| | - Elena V Demidova
- Cancer Prevention and Control Program, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA, 19111-2497, USA.,Molecular Therapeutics Program, Fox Chase Cancer Center, Philadelphia, PA, USA.,Kazan Federal University, 420000, Kazan, Russian Federation
| | - Randy W Lesh
- Geisinger Commonwealth School of Medicine, Scranton, PA, USA
| | - Lily Hoang
- Ambry Genetics, Konica Minolta, Aliso Viejo, CA, USA
| | | | - Andrea Forman
- Department of Clinical Genetics, Fox Chase Cancer Center, Philadelphia, PA, USA
| | | | | | - Erica A Golemis
- Molecular Therapeutics Program, Fox Chase Cancer Center, Philadelphia, PA, USA
| | - Michael J Hall
- Cancer Prevention and Control Program, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA, 19111-2497, USA.,Department of Clinical Genetics, Fox Chase Cancer Center, Philadelphia, PA, USA
| | - Mary B Daly
- Cancer Prevention and Control Program, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA, 19111-2497, USA.,Department of Clinical Genetics, Fox Chase Cancer Center, Philadelphia, PA, USA
| | - Sanjeevani Arora
- Cancer Prevention and Control Program, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA, 19111-2497, USA.
| |
Collapse
|
|
20
|
Abstract
PURPOSE OF REVIEW An overview of urologic malignancies in Lynch syndrome and the current state of research. RECENT FINDINGS Upper tract urothelial carcinoma (UTUC) is the third most common malignancy in Lynch syndrome. Establishment and utilization of a sensitive and practical screening method for Lynch syndrome in patients presenting with UTUC is overdue. Next-generation sequencing to evaluate for microsatellite instability (MSI) and detect mutations of mismatch repair (MMR) genes may be the future of Lynch syndrome screening. Epidemiologic data and molecular characterization suggest bladder urothelial carcinoma (BUC) and prostate cancer (PCA) as unrecognized components of Lynch syndrome. Small studies suggest that Lynch syndrome may predispose individuals to adrenocortical carcinoma. Testicular cancer literature focuses on characterizing MSI and MMR gene expression as it relates to chemotherapy sensitivity; outcomes suggest a potential avenue to investigate its relationship to Lynch syndrome. SUMMARY Patients with Lynch syndrome have an increased risk of urologic malignancies, including UTUC and likely BUC and PCA. BUC and PCA have a lower penetrance than UTUC for unknown reasons. Established Lynch syndrome-associated genitourinary tumors will necessitate the development of methods to diagnose Lynch syndrome in patients presenting with these malignancies, in addition to establishing screening guidelines for patients with Lynch syndrome-associated genitourinary tumors.
Collapse
|
|
21
|
Chung SH, Woldenberg N, Roth AR, Masamed R, Conlon W, Cohen JG, Joines MM, Patel MK. BRCA and Beyond: Comprehensive Image-rich Review of Hereditary Breast and Gynecologic Cancer Syndromes. Radiographics 2020; 40:306-325. [DOI: 10.1148/rg.2020190084] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Affiliation(s)
- Stephanie Histed Chung
- From the Departments of Radiology (S.H.C., R.M., M.M.J., M.K.P.), Clinical Genetics (W.C.), and Obstetrics and Gynecology (J.G.C.), David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, Calif; Hoag Hospital, Newport Harbor Radiology Associates, Newport Beach, Calif (N.W.); and Department of Radiology, Olive View–UCLA Medical Center, Sylmar, Calif (A.R.R.)
| | - Nina Woldenberg
- From the Departments of Radiology (S.H.C., R.M., M.M.J., M.K.P.), Clinical Genetics (W.C.), and Obstetrics and Gynecology (J.G.C.), David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, Calif; Hoag Hospital, Newport Harbor Radiology Associates, Newport Beach, Calif (N.W.); and Department of Radiology, Olive View–UCLA Medical Center, Sylmar, Calif (A.R.R.)
| | - Antoinette R. Roth
- From the Departments of Radiology (S.H.C., R.M., M.M.J., M.K.P.), Clinical Genetics (W.C.), and Obstetrics and Gynecology (J.G.C.), David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, Calif; Hoag Hospital, Newport Harbor Radiology Associates, Newport Beach, Calif (N.W.); and Department of Radiology, Olive View–UCLA Medical Center, Sylmar, Calif (A.R.R.)
| | - Rinat Masamed
- From the Departments of Radiology (S.H.C., R.M., M.M.J., M.K.P.), Clinical Genetics (W.C.), and Obstetrics and Gynecology (J.G.C.), David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, Calif; Hoag Hospital, Newport Harbor Radiology Associates, Newport Beach, Calif (N.W.); and Department of Radiology, Olive View–UCLA Medical Center, Sylmar, Calif (A.R.R.)
| | - Wendy Conlon
- From the Departments of Radiology (S.H.C., R.M., M.M.J., M.K.P.), Clinical Genetics (W.C.), and Obstetrics and Gynecology (J.G.C.), David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, Calif; Hoag Hospital, Newport Harbor Radiology Associates, Newport Beach, Calif (N.W.); and Department of Radiology, Olive View–UCLA Medical Center, Sylmar, Calif (A.R.R.)
| | - Joshua G. Cohen
- From the Departments of Radiology (S.H.C., R.M., M.M.J., M.K.P.), Clinical Genetics (W.C.), and Obstetrics and Gynecology (J.G.C.), David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, Calif; Hoag Hospital, Newport Harbor Radiology Associates, Newport Beach, Calif (N.W.); and Department of Radiology, Olive View–UCLA Medical Center, Sylmar, Calif (A.R.R.)
| | - Melissa M. Joines
- From the Departments of Radiology (S.H.C., R.M., M.M.J., M.K.P.), Clinical Genetics (W.C.), and Obstetrics and Gynecology (J.G.C.), David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, Calif; Hoag Hospital, Newport Harbor Radiology Associates, Newport Beach, Calif (N.W.); and Department of Radiology, Olive View–UCLA Medical Center, Sylmar, Calif (A.R.R.)
| | - Maitraya K. Patel
- From the Departments of Radiology (S.H.C., R.M., M.M.J., M.K.P.), Clinical Genetics (W.C.), and Obstetrics and Gynecology (J.G.C.), David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, Calif; Hoag Hospital, Newport Harbor Radiology Associates, Newport Beach, Calif (N.W.); and Department of Radiology, Olive View–UCLA Medical Center, Sylmar, Calif (A.R.R.)
| |
Collapse
|
|
22
|
Vlachostergios PJ, Faltas BM, Carlo MI, Nassar AH, Alaiwi SA, Sonpavde G. The emerging landscape of germline variants in urothelial carcinoma: Implications for genetic testing. Cancer Treat Res Commun 2020; 23:100165. [PMID: 31982787 DOI: 10.1016/j.ctarc.2020.100165] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2019] [Accepted: 12/30/2019] [Indexed: 06/10/2023]
Abstract
Urothelial carcinoma (UC) of the bladder and upper tract (ureter, renal pelvis) is one of the most frequently occurring malignancies. While the majority of UC are chemically induced by smoking, accumulating evidence from genetic studies have demonstrated a small, but consistent impact of heritable gene variants and family history of UC on the development of the disease. Beyond the established association between upper tract UC and germline mismatch DNA repair defects as a defining feature of Lynch syndrome, newer investigations focusing on moderate- and high-risk cancer-related gene variants in DNA damage repair and other signaling pathways are expanding our knowledge on the heritable genetic basis of UC, opening new avenues in the breadth of genetic testing and in clinical counseling of these patients. Overcoming existing challenges in the interpretation of uncertain findings and family cascade testing may help expand our testing approach and guidelines. Following the paradigm of other tumor types, such as breast and ovarian cancers, germline genetic testing, particularly when combined with somatic testing, has the potential to directly benefit affected UC patients and their families in the future through therapeutic targeting (i.e. with poly(ADP-ribose)) polymerase inhibitors, immune checkpoint inhibitors) and genetically informed screening/surveillance, respectively.
Collapse
Affiliation(s)
| | - Bishoy M Faltas
- Division of Hematology and Medical Oncology, Weill Cornell Medicine, New York, NY, United States; Department of Cell and Developmental Biology, Weill Cornell Medicine, New York, NY, United States; Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, United States
| | - Maria I Carlo
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, United States
| | - Amin H Nassar
- Department of Medicine, Brigham and Women's Hospital, Boston, MA, United States
| | - Sarah Abou Alaiwi
- Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave, DANA 1230, Boston, MA 02215, United States
| | - Guru Sonpavde
- Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave, DANA 1230, Boston, MA 02215, United States.
| |
Collapse
|
|
23
|
Data Set for the Reporting of Carcinoma of the Renal Pelvis and Ureter—Nephroureterectomy and Ureterectomy Specimens. Am J Surg Pathol 2019; 43:e1-e12. [DOI: 10.1097/pas.0000000000001305] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
|
|
24
|
Imaging surveillance for children with predisposition to renal tumors. Pediatr Radiol 2019; 49:1453-1462. [PMID: 31620846 DOI: 10.1007/s00247-019-04432-2] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2019] [Revised: 04/08/2019] [Accepted: 05/15/2019] [Indexed: 12/16/2022]
Abstract
Effective surveillance is necessary for early detection of tumors in children with cancer predisposition syndromes. Instituting a surveillance regimen in children comes with practical challenges that include determining imaging modality and timing, and considering cost efficiency, accessibility, and the significant consequences of false-positive and false-negative results. To address these challenges, the American Association for Cancer Research has recently published consensus recommendations that focus on surveillance of cancer predisposition syndromes in children. This review condenses the imaging surveillance recommendations for syndromes that carry a predisposition to renal tumors in childhood, and includes summaries of the predisposition syndromes and discussion of considerations of available imaging modalities.
Collapse
|
|
25
|
Rakobradović J, Krivokuća A, Jovandić S, Kesić V, Branković-Magić M. Confirmation of damaging effect of MSH2 c.2634+1G>C mutation on splicing, its classification and implications for counseling. Cancer Genet 2019; 239:1-7. [PMID: 31437759 DOI: 10.1016/j.cancergen.2019.08.002] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2019] [Revised: 07/11/2019] [Accepted: 08/11/2019] [Indexed: 12/14/2022]
Abstract
INTRODUCTION Lynch syndrome (LS) is predisposing mainly to colorectal and endometrial carcinomas, but also to urinary tract cancers. LS association with upper urinary tract carcinomas is known, but its association with bladder cancer is not so clear. Confirmation of pathogenicity of detected mutations in LS-associated genes is required for adequate counseling. MATERIAL AND METHODS Tested young female has family history of two early colorectal and two bladder carcinomas. NGS sequencing revealed MSH2 splice site mutation c.2634+1G>C, which was confirmed by Sanger sequencing. MSH2 cDNA part containing potential splicing change was sequenced. in silico softwares were used to predict the effect of detected mutation on splicing and protein structure. ACMG Guidelines were used for mutation classification. RESULTS in silico softwares predict damaging effect of detected mutation on splicing and loss of protein-binding domains. cDNA sequencing confirmed this mutation causes exon 15 excision. ACMG Guidelines classify this mutation as Pathogenic. DISCUSSION MSH2 c.2634+1G>C mutation was not reported previously as LS associated. We confirmed its damaging effect on splicing. in silico tools predict consequent loss of protein domains implicating disrupted protein function. Our results suggest that this mutation should be classified as Pathogenic, and indicate inclusion of bladder cancer in LS cancer spectrum.
Collapse
Affiliation(s)
- Jelena Rakobradović
- Institute for Oncology and Radiology of Serbia, Pasterova 14, 11000 Belgrade, Serbia.
| | - Ana Krivokuća
- Institute for Oncology and Radiology of Serbia, Pasterova 14, 11000 Belgrade, Serbia
| | - Stevo Jovandić
- Military Medical Academy, Crnotravska 17, 11000 Belgrade, Serbia
| | - Vesna Kesić
- Faculty of Medicine, University of Belgrade, Doktora Subotica 8, 11000 Belgrade, Serbia; Clinic of Obstetrics and Gynecology, Clinical Centre of Serbia, Visegradska 26, 11000 Belgrade, Serbia
| | | |
Collapse
|
|
26
|
Lynch Syndrome in Urologic Malignancies - What Does the Urologist Need to Know? Urology 2019; 134:24-31. [PMID: 31302137 DOI: 10.1016/j.urology.2019.07.004] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2019] [Revised: 06/13/2019] [Accepted: 07/05/2019] [Indexed: 12/24/2022]
Abstract
Lynch Syndrome (LS) entails a defective DNA mismatch repair system, which is the postreplicative proofreading and editing system, ensuring our genome's integrity. LS predisposes to several cancers, most commonly colorectal and endometrial cancers. LS occurs in approximately 1 in 250-1000 people. LS is associated with urological malignancies with upper tract urothelial carcinoma the most common, although still clinically underestimated. Other urologic malignancies possibly associated with LS include bladder, prostate, testis, and renal cell carcinoma. Ascertaining their true prevalence in LS is mandatory for their and their relatives' diagnosis and treatment. Awareness regarding identifying patients at risk for LS through assessment of personal and familial oncologic history is critical among urologists.
Collapse
|
|
27
|
Pellat A, Netter J, Perkins G, Cohen R, Coulet F, Parc Y, Svrcek M, Duval A, André T. [Lynch syndrome: What is new?]. Bull Cancer 2019; 106:647-655. [PMID: 30527816 DOI: 10.1016/j.bulcan.2018.10.009] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2018] [Accepted: 10/02/2018] [Indexed: 12/17/2022]
Abstract
Lynch syndrome is a genetic condition defined by a germline mutation of an MMR (MisMatch Repair) gene leading to a defective DNA MMR system. Therefore, it is characterized by the predisposition to a spectrum of cancers, primarily colorectal cancer (CRC) and endometrial cancer (EC). Lynch syndrome-related CRC accounts for 3% of all CRC. Lynch syndrome also accounts for 2% of all EC. In case of Lynch syndrome, there is usually a familial history of cancer defined by the Amsterdam and Bethesda criteria. Diagnosis is made by tumor testing with (i) MMR immunohistochemistry and (ii) PCR for MSI (microsatellite instability), a genetic phenotype that characterizes these tumors. MSI can also be detected in sporadic tumors, through epigenetic events inactivating the MMR system. Progress in diagnosis and molecular biology has allowed for better identification of Lynch patients but also other rare genetic syndromes. MSI tumors can now benefit from new treatments such as immunotherapy which underlines the importance of their diagnosis. Finally, patients with Lynch syndrome as well as their relatives, undergo specific surveillance in order to prevent development of other cancers. This review will summarize the different aspects of Lynch syndrome and also focus on recent progress on the topic.
Collapse
Affiliation(s)
- Anna Pellat
- AP-HP, Sorbonne université, hôpital Saint-Antoine, et service d'oncologie médicale, 184, rue du Faubourg Saint-Antoine, 75012 Paris, France.
| | - Jeanne Netter
- AP-HP, hôpital Tenon, service de gastro entérologie, 4, rue de la Chine, 75020 Paris, France
| | - Géraldine Perkins
- AP-HP, hôpital européen Georges Pompidou, unité d'oncogénétique, 20, rue Leblanc, 75015 Paris, France
| | - Romain Cohen
- AP-HP, Sorbonne université, hôpital Saint-Antoine, et service d'oncologie médicale, 184, rue du Faubourg Saint-Antoine, 75012 Paris, France; Sorbonne université, unité Mixte de Recherche Scientifique 938 et SIRIC CURAMUS, Centre de recherche Saint-Antoine, équipe instabilité des microsatellites et cancer, équipe labellisée par la Ligue Nationale contre le cancer, Inserm, 75012 Paris, France
| | - Florence Coulet
- AP-HP, hôpitaux universitaire Pitié Salpêtrière-Charles, département de génétique, 47-83, boulevard de l'Hôpital, 75013 Paris, France
| | - Yann Parc
- AP-HP, Sorbonne université, hôpital Saint-Antoine, service de chirurgie générale et digestive, 184, rue du Faubourg Saint-Antoine, 75012 Paris, France
| | - Magali Svrcek
- Sorbonne université, unité Mixte de Recherche Scientifique 938 et SIRIC CURAMUS, Centre de recherche Saint-Antoine, équipe instabilité des microsatellites et cancer, équipe labellisée par la Ligue Nationale contre le cancer, Inserm, 75012 Paris, France; AP-HP, hôpital Saint-Antoine, Sorbonne université et service d'anatomopathologie, 184, rue du Faubourg Saint-Antoine, 75012 Paris, France
| | - Alex Duval
- Sorbonne université, unité Mixte de Recherche Scientifique 938 et SIRIC CURAMUS, Centre de recherche Saint-Antoine, équipe instabilité des microsatellites et cancer, équipe labellisée par la Ligue Nationale contre le cancer, Inserm, 75012 Paris, France
| | - Thierry André
- AP-HP, Sorbonne université, hôpital Saint-Antoine, et service d'oncologie médicale, 184, rue du Faubourg Saint-Antoine, 75012 Paris, France; Sorbonne université, unité Mixte de Recherche Scientifique 938 et SIRIC CURAMUS, Centre de recherche Saint-Antoine, équipe instabilité des microsatellites et cancer, équipe labellisée par la Ligue Nationale contre le cancer, Inserm, 75012 Paris, France
| |
Collapse
|
|
28
|
Gevaert T, Montironi R, Lopez-Beltran A, Van Leenders G, Allory Y, De Ridder D, Claessens F, Kockx M, Akand M, Joniau S, Netto G, Libbrecht L. Genito-urinary genomics and emerging biomarkers for immunomodulatory cancer treatment. Semin Cancer Biol 2018; 52:216-227. [DOI: 10.1016/j.semcancer.2017.10.004] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2017] [Revised: 10/04/2017] [Accepted: 10/06/2017] [Indexed: 01/01/2023]
|
|
29
|
Huang D, Matin SF, Lawrentschuk N, Roupret M. Systematic Review: An Update on the Spectrum of Urological Malignancies in Lynch Syndrome. Bladder Cancer 2018; 4:261-268. [PMID: 30112437 PMCID: PMC6087433 DOI: 10.3233/blc-180180] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Background: Lynch syndrome is an autosomal dominant disorder that predisposes individuals affected to certain malignancies. Colon and endometrial cancers are the malignancies most highly associated with Lynch syndrome. However, growing body of evidence links Lynch syndrome to urological cancers. Objective: This review aims to clarify the type of urological malignancies that fall under the Lynch-associated cancer spectrum. Methods: Using PRISMA guidelines, a systematic search between January 1990 to February 2018, was conducted using the MEDLINE database with the application of the following MESH terms: colorectal neoplasms, hereditary nonpolyposis; DNA mismatch repair; urologic neoplasms; kidney pelvis; ureteral neoplasms; urinary bladder; carcinoma, transitional cell; prostatic neoplasms; testicular neoplasms. Results: Upper tract urothelial cancers are well established under the Lynch spectrum. Increasing evidence supports its association with prostate cancer. However, there is, inconclusive and limited evidence for an association with bladder and testicular cancer. Conclusions: The evidence underpinning certain urological malignancies associated with Lynch syndrome has expanded in recent years. Our review may assist in providing a summary of the current standing in literature. However, we recommend further investigations to better clarify associations, particularly with prostate, bladder and testicular cancer.
Collapse
Affiliation(s)
- Dora Huang
- Department of Surgery, Austin Health, The University of Melbourne, VIC, Australia
| | - Surena F Matin
- Department of Urology, MD Anderson Cancer Center, Houston, TX, USA
| | - Nathan Lawrentschuk
- Department of Surgery, Austin Health, The University of Melbourne, VIC, Australia.,Olivia Newton-John Cancer and Wellness Centre, Austin Health, Heidelberg, VIC, Australia.,Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
| | - Morgan Roupret
- Sorbonne Université, GRC n° 5, ONCOTYPE-URO, AP-HP, Hôpital Pitié-Salpêtrière, F-75013 Paris, France
| |
Collapse
|
|
30
|
Matin SF, Coleman JA. Misclassification of Upper Tract Urothelial Carcinoma in Patients With Lynch Syndrome. JAMA Oncol 2018; 4:1010. [PMID: 29710233 DOI: 10.1001/jamaoncol.2018.0539] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022]
Affiliation(s)
- Surena F Matin
- Department of Urology, University of Texas MD Anderson Cancer Center, Houston
| | - Jonathan A Coleman
- Department of Surgery/Urology, Memorial Sloan Kettering Cancer Center, New York, New York
| |
Collapse
|
|
31
|
Wang J, Greenberg S, Yates J. Lynch Syndrome-associated Upper Tract Urothelial Carcinoma. Urology 2018; 121:19-21. [PMID: 29958964 DOI: 10.1016/j.urology.2018.06.025] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2018] [Revised: 06/10/2018] [Accepted: 06/18/2018] [Indexed: 11/25/2022]
Affiliation(s)
- Joanna Wang
- Department of Urology, UMass Memorial Medical Center, University of Massachusetts Medical School, Worcester, MA.
| | - Scott Greenberg
- Department of Urology, UMass Memorial Medical Center, University of Massachusetts Medical School, Worcester, MA
| | - Jennifer Yates
- Department of Urology, UMass Memorial Medical Center, University of Massachusetts Medical School, Worcester, MA
| |
Collapse
|
|
32
|
Freifeld Y, Krabbe LM, Clinton TN, Woldu SL, Margulis V. Therapeutic strategies for upper tract urothelial carcinoma. Expert Rev Anticancer Ther 2018; 18:765-774. [PMID: 29848133 DOI: 10.1080/14737140.2018.1481395] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
INTRODUCTION Many controversies exist regarding the appropriate management of patients with upper tract urothelial carcinoma (UTUC), including staging, surgical management, use of systemic therapy, and prevention of bladder recurrence. Due to the rarity of this condition, high-level evidence is often lacking and in many cases guidelines are extrapolated from existing evidence on urothelial bladder cancer. Areas covered: This review paper summarizes the evidence on proper diagnosis and staging, surgical techniques, prevention of bladder recurrences, the use of local or systemic treatments in both neoadjuvant and adjuvant settings as well as special consideration for hereditary UTUC. Expert commentary: UTUC is a rare malignancy and slow progress is being made in the acquisition of high-quality evidence in this field. Treatments that facilitate preservation of the kidney are being explored such as advanced endoscopic techniques or partial resection of ureteral disease with seemingly acceptable oncological results. Further prospective evidence is needed.
Collapse
Affiliation(s)
- Yuval Freifeld
- a Department of Urology , University of Texas Southwestern Medical Center , Dallas , TX , USA
| | - Laura-Maria Krabbe
- a Department of Urology , University of Texas Southwestern Medical Center , Dallas , TX , USA.,b Department of Urology , University of Muenster Medical Center , Muenster , Germany
| | - Timothy N Clinton
- a Department of Urology , University of Texas Southwestern Medical Center , Dallas , TX , USA
| | - Solomon L Woldu
- a Department of Urology , University of Texas Southwestern Medical Center , Dallas , TX , USA
| | - Vitaly Margulis
- a Department of Urology , University of Texas Southwestern Medical Center , Dallas , TX , USA
| |
Collapse
|
|
33
|
Balasubramanian A, Metcalfe MJ, Wagenheim G, Xiao L, Papadopoulos J, Navai N, Davis JW, Karam JA, Kamat AM, Wood CG, Dinney CP, Matin SF. Salvage topical therapy for upper tract urothelial carcinoma. World J Urol 2018; 36:2027-2034. [PMID: 29804202 DOI: 10.1007/s00345-018-2349-9] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2018] [Accepted: 05/21/2018] [Indexed: 01/01/2023] Open
Abstract
PURPOSE Topical therapy (TT) for upper tract urothelial carcinoma (UTUC) has been explored as a kidney sparing approach to treat carcinoma in situ (CIS) and as adjuvant for endoscopically treated Ta/T1 tumors. In bladder cancer, data support use of salvage TT for repeat induction. We investigate the outcomes of salvage TT for UTUC in patients ineligible for or refusing nephroureterectomy. METHODS A single-center retrospective review on patients receiving salvage TT via percutaneous nephrostomy tube or cystoscopically placed ureteral catheters was performed. Primary outcome was response to therapy based on International Bladder Cancer Group criteria. RESULTS 51 patients with 58 renal units (RUs) received TT. Of these, 17 patients with 18 RUs received the second-line TT, with a median follow-up of 36.5 months (IQR 24.5-67 months). 44% (8/18) received salvage TT for refractory disease and 56% (10/18) as reinduction. 5 RUs with CIS were unresponsive to initial TT and went on to receive salvage TT, of which 20% (1/5) responded. 13 RUs recurred or relapsed following initial TT and received salvage TT for papillary tumors, with 62% (8/13) responding. CONCLUSION Our data provide preliminary clinical rationale for the second-line TT for refractory and recurrent, endoscopically managed papillary UTUC in patients ineligible for or refusing nephroureterectomy. However, refractory upper tract CIS appears to have poor response to salvage TT.
Collapse
Affiliation(s)
- Adithya Balasubramanian
- Department of Urology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1373, Houston, TX, 77030, USA.,Baylor College of Medicine, 1 Baylor Plaza, Houston, TX, 77030, USA
| | - Michael J Metcalfe
- Department of Urology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1373, Houston, TX, 77030, USA
| | - Gavin Wagenheim
- Department of Urology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1373, Houston, TX, 77030, USA
| | - Lianchun Xiao
- Department of Urology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1373, Houston, TX, 77030, USA.,Department of Biostatistics, The University of Texas MD Anderson Cancer Center, 1400 Pressler St, Unit 1411, Houston, TX, 77230, USA
| | - John Papadopoulos
- Department of Urology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1373, Houston, TX, 77030, USA
| | - Neema Navai
- Department of Urology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1373, Houston, TX, 77030, USA
| | - John W Davis
- Department of Urology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1373, Houston, TX, 77030, USA
| | - Jose A Karam
- Department of Urology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1373, Houston, TX, 77030, USA
| | - Ashish M Kamat
- Department of Urology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1373, Houston, TX, 77030, USA
| | - Christopher G Wood
- Department of Urology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1373, Houston, TX, 77030, USA
| | - Colin P Dinney
- Department of Urology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1373, Houston, TX, 77030, USA
| | - Surena F Matin
- Department of Urology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1373, Houston, TX, 77030, USA.
| |
Collapse
|
|
34
|
Abstract
PURPOSE OF REVIEW Upper tract urothelial carcinoma (UTUC) is a relatively rare and poorly investigated disease. The objective of this review was to discuss recent advances in genomics and their implication regarding prognosis and treatment. RECENT FINDINGS UTUC were compared with urothelial carcinoma of the bladder (UCB) at genomic and transcriptomic levels. Molecular studies focused on identifying new prognostic biomarkers that were often initially described in UCB and extrapolated to UTUC. Some of them could be interesting to improve the management of UTUC. SUMMARY Recent studies improved our understanding of UTUC as a distinct entity compared with UCB. Although UTUC shares many of the same genomic alterations with UCB, some key differences have been identified as oncogenic drivers of these cancers. This better comprehension of genomics could lead to new prognostic markers that may refine UTUC treatment.
Collapse
|
|
35
|
Phelan A, Lopez-Beltran A, Montironi R, Zhang S, Raspollini MR, Cheng M, Kaimakliotis HZ, Koch MO, Cheng L. Inherited forms of bladder cancer: a review of Lynch syndrome and other inherited conditions. Future Oncol 2018; 14:277-290. [DOI: 10.2217/fon-2017-0346] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Environmental factors that play a role in the urothelial carcinogenesis have been well characterized. Current research is continuously exploring potential heritable forms of bladder cancer. Lynch syndrome is a well-known inheritable disease that increases the risk for a variety of cancers, including urothelial carcinomas. Screening of patients with known Lynch syndrome is important to evaluate for development of new primary tumors. Further study may provide more information on what level of follow-up each patient needs. Recent data suggest that mismatch repair mutations confer a greater risk for urothelial cancer. Additional large patient series as well as advancement of molecular testing may provide triage for Lynch syndrome patients in regards to the frequency and type of screening best suited for individual patient.
Collapse
Affiliation(s)
- Aaron Phelan
- Department of Pathology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
| | - Antonio Lopez-Beltran
- Unit of Anatomical Pathology, Faculty of Medicine, Cordoba, Spain & Champalimaud Clinical Center, Lisbon 1400038, Portugal
| | - Rodolfo Montironi
- Institute of Pathological Anatomy & Histopathology, School of Medicine, Polytechnic University of the Marche Region (Ancona), United Hospitals, Ancona 60126, Italy
| | - Shaobo Zhang
- Department of Pathology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
| | - Maria R Raspollini
- Histopathology & Molecular Diagnostics, University Hospital Careggi, Florence 50134, Italy
| | - Monica Cheng
- Department of Pathology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
| | - Hristos Z Kaimakliotis
- Department of Urology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
| | - Michael O Koch
- Department of Urology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
| | - Liang Cheng
- Department of Pathology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
- Department of Urology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
| |
Collapse
|
|
36
|
Urakami S, Inoshita N, Oka S, Miyama Y, Nomura S, Arai M, Sakaguchi K, Kurosawa K, Okaneya T. Clinicopathological characteristics of patients with upper urinary tract urothelial cancer with loss of immunohistochemical expression of the DNA mismatch repair proteins in universal screening. Int J Urol 2017; 25:151-156. [DOI: 10.1111/iju.13481] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2017] [Accepted: 09/11/2017] [Indexed: 12/01/2022]
Affiliation(s)
- Shinji Urakami
- Department of Urology; Toranomon Hospital; Tokyo Japan
- Okinaka Memorial Institute for Medical Research; Tokyo Japan
| | - Naoko Inoshita
- Department of Pathology; Toranomon Hospital; Tokyo Japan
| | - Suguru Oka
- Department of Urology; Toranomon Hospital; Tokyo Japan
| | - Yu Miyama
- Department of Pathology; Toranomon Hospital; Tokyo Japan
| | - Sachio Nomura
- Department of Clinical Genetic Oncology; Cancer Institute Hospital; Japanese Foundation for Cancer Research; Tokyo Japan
| | - Masami Arai
- Department of Clinical Genetic Oncology; Cancer Institute Hospital; Japanese Foundation for Cancer Research; Tokyo Japan
| | | | | | | |
Collapse
|
|
37
|
Metcalfe MJ, Petros FG, Rao P, Mork ME, Xiao L, Broaddus RR, Matin SF. Universal Point of Care Testing for Lynch Syndrome in Patients with Upper Tract Urothelial Carcinoma. J Urol 2017; 199:60-65. [PMID: 28797715 DOI: 10.1016/j.juro.2017.08.002] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/01/2017] [Indexed: 10/19/2022]
Abstract
PURPOSE Patients with Lynch syndrome are at risk for upper tract urothelial carcinoma. We sought to identify the incidence and most reliable means of point of care screening for Lynch syndrome in patients with upper tract urothelial carcinoma. MATERIALS AND METHODS A total of 115 consecutive patients with upper tract urothelial carcinoma without a history of Lynch syndrome were universally screened during followup from January 2013 through July 2016. We evaluated patient and family history using AMS (Amsterdam criteria) I and II, and tumor immunohistochemistry for mismatch repair proteins and microsatellite instability. Patients who were positive for AMS I/II, microsatellite instability or immunohistochemistry were classified as potentially having Lynch syndrome and referred for clinical genetic analysis and counseling. Patients with known Lynch syndrome served as positive controls. RESULTS Of the 115 patients 16 (13.9%) screened positive for potential Lynch syndrome. Of these patients 7.0% met AMS II criteria, 11.3% had loss of at least 1 mismatch repair protein and 6.0% had high microsatellite instability. All 16 patients were referred for germline testing, 9 completed genetic analysis and counseling, and 6 were confirmed to have Lynch syndrome. All 7 patients with upper tract urothelial carcinoma who had a known history of Lynch syndrome were positive for AMS II criteria and at least a single mismatch repair protein loss while 5 of 6 had high microsatellite instability. CONCLUSIONS We identified 13.9% of upper tract urothelial carcinoma cases as potential Lynch syndrome and 5.2% as confirmed Lynch syndrome at the point of care. These findings have important implications for universal screening of upper tract urothelial carcinoma, representing one of the highest rates of undiagnosed genetic disease in a urological cancer.
Collapse
Affiliation(s)
- Michael J Metcalfe
- Department of Urology, University of Texas M. D. Anderson Cancer Center, Houston, Texas
| | - Firas G Petros
- Department of Urology, University of Texas M. D. Anderson Cancer Center, Houston, Texas
| | - Priya Rao
- Department of Pathology, University of Texas M. D. Anderson Cancer Center, Houston, Texas
| | - Maureen E Mork
- Clinical Cancer Genetics Program, University of Texas M. D. Anderson Cancer Center, Houston, Texas
| | - Lianchun Xiao
- Department of Biostatistics, University of Texas M. D. Anderson Cancer Center, Houston, Texas
| | - Russell R Broaddus
- Department of Pathology, University of Texas M. D. Anderson Cancer Center, Houston, Texas
| | - Surena F Matin
- Department of Urology, University of Texas M. D. Anderson Cancer Center, Houston, Texas.
| |
Collapse
|
|
38
|
Razvi MA, Giardiello FM, Law JK. DNA Mismatch Repair and Lynch Syndrome. CURRENT COLORECTAL CANCER REPORTS 2017. [DOI: 10.1007/s11888-017-0366-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
|
|
39
|
Upper tract urothelial carcinomas: frequency of association with mismatch repair protein loss and lynch syndrome. Mod Pathol 2017; 30:146-156. [PMID: 27713421 DOI: 10.1038/modpathol.2016.171] [Citation(s) in RCA: 63] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2016] [Revised: 08/16/2016] [Accepted: 08/30/2016] [Indexed: 12/13/2022]
Abstract
Increased risk for upper tract urothelial carcinoma is described in patients with Lynch syndrome, caused by germline mutations in mismatch repair genes. We aimed to identify the frequency of mismatch repair protein loss in upper tract urothelial carcinoma and its potential for identifying an association with Lynch syndrome. We queried our database to identify upper tract urothelial carcinomas. Patients were cross-referenced for history of colorectal carcinoma or other common Lynch syndrome-associated neoplasms to enrich for potential Lynch syndrome cases. Tumor histopathologic characteristics were reviewed and each case was analyzed for loss of mismatch repair proteins, MLH1, MSH2, MSH6, and PMS2, by immunohistochemistry. Of 444 patients with upper tract urothelial carcinoma, a subset of 215 (encompassing 30 with upper tract urothelial carcinoma and another common Lynch syndrome-associated neoplasm) was analyzed for loss of mismatch repair protein expression. Of 30 patients with Lynch syndrome-associated neoplasms, six had documented Lynch syndrome, including two with Muir-Torre syndrome. Mismatch repair protein loss was identified in 7% of total upper tract urothelial carcinomas and 30% of patients with Lynch syndrome-associated neoplasms (including all patients with Lynch syndrome/Muir-Torre syndrome). Of patients without history of Lynch syndrome-associated neoplasms, 5 of 184 (2.7%) had loss of mismatch repair protein expression. Twelve cases with mismatch repair protein loss demonstrated loss of MSH2 and MSH6, and 2 had isolated loss of MSH6. MLH1 and PMS2 expression were consistently retained. Although increased intratumoral lymphocytes, inverted growth, pushing tumor-stromal interface, and lack of nuclear pleomorphism were more commonly seen in cases with mismatch repair protein loss, only intratumoral lymphocytes and presence of pushing borders were statistically significant. MLH1 and PMS2 testing appear to have little utility in upper tract urothelial carcinoma; however, mismatch repair protein loss of MSH2 and/or MSH6 by immunohistochemistry seems relatively sensitive and specific for identifying patients with potential Lynch syndrome.
Collapse
|
|
40
|
|
|
41
|
Colin P, Seisen T, Mathieu R, Shariat SF, Rouprêt M. Lynch syndrome and exposure to aristolochic acid in upper-tract urothelial carcinoma: its clinical impact? Transl Androl Urol 2016; 5:648-654. [PMID: 27785421 PMCID: PMC5071192 DOI: 10.21037/tau.2016.03.18] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
The purpose of the current review was to describe the clinical risk for Lynch syndrome (LS) after exposure to aristolochic acid (AA) in cases of upper urinary-tract urothelial carcinoma (UTUC). A systematic review of the scientific literature was performed using the Medline database (National Library of Medicine, PubMed) using the following keywords: epidemiology, risk factor, AA, Balkan nephropathy (BNe), LS, hereditary cancer, hereditary non-polyposis colorectal cancer (HNPCC), mismatch repair genes, urothelial carcinomas, upper urinary tract, renal pelvis, ureter, Amsterdam criteria, genetic counselling, mismatch repair genes, genetic instability, microsatellite, and Bethesda guidelines. LS is a specific risk for UTUC, which is the third most frequent cancer (in its tumor spectrum) after colon and uterine lesions. Mutation of the MSH2 gene is the most commonly described cause of UTUC in LS. Diagnosis is based on clinical suspicion and is guided by Bethesda and Amsterdam criteria. It is secondarily confirmed by immunohistochemical analyses of the tumor and a search for gene mutations. The presence of LS in patients with UTUC is a favorable prognosis factor for survival during follow-ups. AA is a specific environmental risk factor for UTUC and tubulo-interstitial nephropathy. It has been involved in the development of nephropathies in link with the Balkan disease and intake of Chinese herbal medicine. More broadly, the use of traditional plant medicines from the genus Aristolochia has created worldwide public-health concerns. UTUCs share common risk factors with other urothelial carcinomas such as tobacco or occupational exposure. However, these tumors have also specific risk factors such as AA exposure and LS that clinicians should be aware of because of their clinical implication in further management and follow-up.
Collapse
Affiliation(s)
- Pierre Colin
- Department of Urology, Hôpital Privé de La Louvière, Générale de Santé, Lille, France
| | - Thomas Seisen
- Academic Department of Urology, Assitance Publique-Hopitaux de Paris, Hopital Pitié-Salpétrière, Paris, F-75013, France; ; UPMC Univ Paris 06, GRC5, ONCOTYPE-Uro, Institut Universitaire de Cancérologie, F-75005, Paris, France
| | - Romain Mathieu
- Department of Urology, Medical University of Vienna, Vienna, Austria
| | | | - Morgan Rouprêt
- Academic Department of Urology, Assitance Publique-Hopitaux de Paris, Hopital Pitié-Salpétrière, Paris, F-75013, France; ; UPMC Univ Paris 06, GRC5, ONCOTYPE-Uro, Institut Universitaire de Cancérologie, F-75005, Paris, France
| |
Collapse
|
|
42
|
Gaur S, Turkbey B, Choyke P. Hereditary Renal Tumor Syndromes: Update on Diagnosis and Management. Semin Ultrasound CT MR 2016; 38:59-71. [PMID: 28237281 DOI: 10.1053/j.sult.2016.10.002] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Hereditary renal cancers account for approximately 5%-8% of all renal tumors. Over the past 2 decades, a number of syndromes have been identified that predispose patients to early renal cancer development, representing all the major histologic types of tumor pathology. In this article, we describe the current knowledge concerning the cell type, known mechanism of tumor development, other manifestations of the syndrome, imaging findings, genetic screening, and imaging surveillance recommendations for each of the major syndromes associated with hereditary renal cancers.
Collapse
Affiliation(s)
- Sonia Gaur
- Molecular Imaging Program, National Cancer Institute, Bethesda, MD; Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA
| | - Baris Turkbey
- Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA
| | - Peter Choyke
- Molecular Imaging Program, National Cancer Institute, Bethesda, MD.
| |
Collapse
|
|
43
|
Abstract
Hereditary forms of kidney carcinoma account for 5-8% of all malignant kidney neoplasms. The renal tumors are often multiple and bilateral and occur at an earlier age. Each of the hereditary kidney carcinoma syndromes is associated with specific gene mutations as well as a specific histologic type of kidney carcinoma. The presence of associated extrarenal manifestations may suggest a hereditary kidney cancer syndrome. Radiology is most commonly used to screen and manage patients with hereditary kidney cancer syndromes. This manuscript reviews the clinical and imaging findings of well-defined inherited kidney cancer syndromes including von Hippel-Lindau disease, Birt-Hogg-Dubé syndrome, hereditary papillary renal carcinoma syndrome, hereditary leiomyomatosis and RCC syndrome, tuberous sclerosis complex, and Lynch syndrome.
Collapse
|
|
44
|
Stewart MJ, Guerra GR, Sutherland TR, Elmer SL. Abdominal wall metastasis following open nephroureterectomy for upper tract urothelial carcinoma in a patient with Lynch syndrome. BMJ Case Rep 2016; 2016:bcr-2016-214940. [PMID: 27033297 DOI: 10.1136/bcr-2016-214940] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
A 74-year-old man developed the rare complication of an abdominal wall metastasis following open nephroureterectomy for upper tract urothelial carcinoma (UTUC). This occurred in the setting of synchronous contralateral ureteric and metachronous colorectal carcinomas. Immunohistochemistry demonstrated loss of the mutS homolog 6 (MSH6) mismatch repair (MMR) protein in the metastatic abdominal wall and colonic lesions, which in conjunction with meeting the Amsterdam II criteria, is strongly suggestive of Lynch syndrome (LS). Surgical resection of the recurrence was performed with clear margins and neither recurrence nor spread during short-term follow-up.
Collapse
Affiliation(s)
| | - Glen R Guerra
- St Vincent's Hospital, Melbourne, Fitzroy, Victoria, Australia
| | | | - Sandra L Elmer
- St Vincent's Hospital, Melbourne, Fitzroy, Victoria, Australia
| |
Collapse
|
|
45
|
Mandalapu RS, Matin SF. Contemporary Evaluation and Management of Upper Tract Urothelial Cancer. Urology 2016; 94:17-23. [PMID: 26850816 DOI: 10.1016/j.urology.2015.12.035] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2015] [Revised: 12/16/2015] [Accepted: 12/21/2015] [Indexed: 01/05/2023]
Abstract
Radical nephroureterectomy with en bloc bladder cuff excision and regional lymphadenectomy is the gold standard for the management of high-grade and high-risk upper tract urothelial carcinomas. There are a few prospective randomized controlled studies in this uncommon and often aggressive disease to support level-1 management guidelines. However, recent developments in imaging, minimally invasive techniques, lymphatic dissemination, and bladder cancer prevention raise the hope for improved risk stratification and treatments without compromising, and hopefully improving, oncological outcomes. Multimodality approaches in terms of neoadjuvant, adjuvant topical, and systemic chemotherapeutic regimens are promising, with 2 prospective trials either open or in development.
Collapse
Affiliation(s)
| | - Surena F Matin
- Department of Urology, University of Texas MD Anderson Cancer Center, Houston, TX.
| |
Collapse
|
|
46
|
|