Urological Follow-Up for Lynch Syndrome: UTUC Incidence, Mutational Patterns, and Ultrasound Insights

Lynch Syndrome (LS) is an autosomal dominant genetic disorder associated with various cancers, notably Upper Tract Urothelial Carcinoma (UTUC), which is the third most common manifestation. This study analyzes data from a dedicated outpatient urological clinic for LS patients, focusing on the incidence of UTUC, mutational patterns, and follow-up strategies. From 2021 to 2023, 30 LS patients were observed at a specialized tertiary referral center. Data were collected on LS mutations, medical and family histories, and a rigorous follow-up protocol was implemented. Genetic diagnoses were confirmed through immunohistochemistry (IHC) and DNA sequencing, with assessment concordant with Bethesda, EAU, Amsterdam I, and Amsterdam II criteria. The follow-up included biennial Ultrasound (US), urinalysis, and urinary cytology; high-risk patients, such as those over 50 years old, with MSH2 mutations, or a family history of UTUC, alternated annual CT scans with US. Of the patients studied, 53% received their LS diagnosis post-cancer, while 47% were identified via genetic counseling after a degree-relative diagnosis. The median time post-LS diagnosis was 86 months. Among the cohort, there were 11 colorectal cancer cases (36%) and 4 UTUC cases (13%), with MSH2 mutations identified in 48% and MLH1 in 31%. The median age at UTUC diagnosis was 60 years, older than for colorectal cancer at 49 years (p=0.007). Bethesda and EAU guidelines showed higher accuracy (86% and 89%) than the Amsterdam criteria (60%). Notably, no new tumors were diagnosed during the follow-up period. The establishment of this dedicated clinic has yielded critical insights into common mutations and could significantly improve mutation-specific follow-up protocols and early UTUC diagnosis in LS patients.