title: Lynch Syndrome: A Primer for Urologists and Panel Recommendations.
abstract: OBJECTIVE
  Lynch syndrome, also known as hereditary nonpolyposis colorectal cancer, is a common genetic disease. The predisposition of patients with Lynch syndrome to urological cancer, particularly upper tract urothelial carcinoma, is underappreciated. Urologists may be involved in several aspects of care involving Lynch syndrome, including identifying undiagnosed patients, surveillance of those with established Lynch syndrome or screening family members, in addition to treating patients with Lynch syndrome in whom upper tract urothelial carcinoma develops. We sought to increase awareness in the urological community about Lynch syndrome and provide some guidance where little currently exists.
  
  
  METHODS
  Using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement we reviewed the available published literature and guidelines from 1998 to 2014 on Lynch syndrome and its association with upper tract urothelial carcinoma. Recommendations based on the literature and the consensus of expert opinion are provided.
  
  
  RESULTS
  No randomized or prospective study has been done to evaluate Lynch syndrome in the setting of urological cancer. All data were based on retrospective studies. Lynch syndrome is an autosomal dominant genetic disease caused by germline mutations in 4 mismatch repair genes, leading to the accumulation of DNA errors in microsatellite regions. Upper tract urothelial carcinoma develops in up to 28% of patients with known Lynch syndrome. The diagnosis of Lynch syndrome is established by clinical criteria, tumor tissue testing and genetic evaluation. Urologists should suspect Lynch syndrome when a patient with upper tract urothelial carcinoma presents before age 60 years or meets the 3-2-1 rule. Screening patients with Lynch syndrome for upper tract urothelial carcinoma presents a particular challenge. While no ideal screening test exists, at a minimum routine urinalysis is recommended using the American Urological Association guideline of 3 or more red blood cells per high power field as a trigger for further assessment. Upper tract urothelial carcinoma associated with Lynch syndrome presents at a younger age than sporadic upper tract urothelial carcinoma. It shows a higher proportion of ureteral cancer with a female preponderance and a possible predisposition to bilaterality.
  
  
  CONCLUSIONS
  Lynch syndrome is a common genetic disease that is an underappreciated cause of upper tract urothelial carcinoma and possibly other urological cancers. Optimal screening for upper tract urothelial carcinoma in this population is unclear. Further study is needed to identify the best screening test and interval of testing. Urologists should consider routine tissue testing of de novo upper tract urothelial carcinoma tissue in individuals at risk.
authors.affiliation: Department of Clinical Cancer Genetics, University of Texas M.D. Anderson Cancer Center, Houston, Texas.
authors.forename: Maureen
authors.initials: M
authors.lastname: Mork
authors.affiliation: Department of Urology, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania.
authors.forename: Scott G
authors.initials: SG
authors.lastname: Hubosky
authors.affiliation: Academic Department of Urology, Assistance Publique-Hôpitaux de Paris, Hôpitaux Pitié-Salpétrière and Université Pierre et Marie Curie Université Paris 06, GRC5, ONCOTYPE-Uro, Institut Universitaire de Cancérologie, Paris, France.
authors.forename: Morgan
authors.initials: M
authors.lastname: Rouprêt
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Vitaly
authors.initials: V
authors.lastname: Margulis
authors.affiliation: Division of Urology, Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania.
authors.forename: Jay
authors.initials: J
authors.lastname: Raman
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Yair
authors.initials: Y
authors.lastname: Lotan
authors.affiliation: Department of Urology, Guy's Hospital, London, United Kingdom.
authors.forename: Timothy
authors.initials: T
authors.lastname: O'Brien
authors.affiliation: Department of Surgical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, Texas.
authors.forename: Nancy
authors.initials: N
authors.lastname: You
authors.affiliation: Department of Urology, Medical University of Vienna, Vienna, Austria.
authors.forename: Shahrokh F
authors.initials: SF
authors.lastname: Shariat
authors.affiliation: Department of Urology, University of Texas M.D. Anderson Cancer Center, Houston, Texas. Electronic address: surmatin@mdanderson.org.
authors.forename: Surena F
authors.initials: SF
authors.lastname: Matin
mesh_terms: D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000175:diagnosis / Q000628:therapy; D003663:Decision Trees; D006801:Humans; D017410:Practice Guidelines as Topic; D014572:Urology
keywords: DNA mismatch repair; carcinoma; colorectal neoplasms; hereditary nonpolyposis; kidney neoplasms; transitional cell; ureteral neoplasms