Introduction: Lynch Syndrome (LS) is a genetic dominant autosomal disease that predisposes to a broad spectrum of tumors, among which Upper Tract Urothelial Carcinoma (UTUC) is the third most common manifestation. We present the first results of our LS dedicated outpatient clinic with the aim of evaluating the incidence of UTUC, patterns of mutation and individuate the optimal follow up schemes among patients affected by LS. Methods: We observed 23 LS patients from December 2021 to October 2022 at a tertiary referral center. We collected prospectively data regarding LS mutations, medical and family history and simultaneously started a strict follow up strategy. Genetic diagnosis was obtained both by Immunohistochemistry (IHC) and by genetic test (DNA sequencing). For each patient we applied Bethesda, EAU guidelines, Amsterdam I and II criteria. Follow up strategy was based on Ultrasound (US), urinalysis and urinary citology every two years. In high-risk cases (age >50 years, MSH2 mutation carriers and family history of UTUC) CT-scans where alternated with US every year in addition to urinary citology. Results: Among this court 52.2% of patients (n=12) had a LS diagnosis after cancer manifestation, meanwhile 47.8% (n=11) through genetic counseling due to investigation in first degree relatives. Among our patient population, 8 patients (34.8%) had a diagnosis of colorectal cancer, 4 (17.4%) UTUC, 1 (4.3%) endometrial, 1 (4.3%) gastric, 1 (4.34%) skin cancer and 2 rare LS related cancer (Renal Clear Cell Carcinoma and Lung Cancer). MSH2 mutation was detected in 39.1% of cases (n=9), while MLH1 was found in 34.8% of cases (n=8). In subgroup analysis colorectal cancer's most common mutation was MSH2 (50%) followed by MLH1 (25%) and MSH6 (25%), while among UTUC cases, MSH2 was the most common (75%) and MLH1 was reported in 25% of cases. Median age at UTUC diagnosis was 60, while median age at colorectal cancer diagnosis was 49 (p=0.007). Bethesda and EAU guidelines criteria were more accurate (91% vs 90%) compared to Amsterdam I and II criteria (74%). No tumor diagnosis was made during the observational time. Conclusions: The current study is a first attempt to establish a dedicated LS outpatient clinic. This will let us observe the most frequent mutations, thus potentially in the future allow us to diagnose UTUC earlier and provide a refined follow up to LS patients. SOURCE OF Funding: None
