MATERIALS AND 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.