Abstract
BACKGROUND: Lynch syndrome (LS) is the most common inherited cancer syndrome, caused by germline mutations in mismatch repair (MMR) genes such as MLH1, MSH2, MSH6, and PMS2. While primarily associated with colorectal cancer, LS significantly impacts gynecological oncology, with increased risks for endometrial and ovarian cancers. Despite its clinical relevance, structured counseling and surveillance programs tailored to LS patients in gynecology are lacking. OBJECTIVE AND METHODS: This study presents the first structured gynecological outpatient consultation program for LS patients in Germany, established at Charité-Universitätsmedizin Berlin in August 2021. The aim was to develop an individualized, multidisciplinary framework for surveillance, therapy, and follow-up care, addressing the specific needs of different patient cohorts. Between August 2021 and December 2023, clinical data from 40 LS patients were collected and analyzed descriptively. From this experience, we furthermore concluded a guideline for the care of individuals with Lynch syndrome. RESULTS: Among the 40 patients, 21 had been diagnosed with cancer (affected group), while 19 were cancer-free and undergoing routine surveillance (non-affected group). The distribution of MMR gene mutations was 40% MSH2, 25% MSH6, 25% PMS2, and 15% MLH1. In the non-affected group, the median age was 38 years, with a BMI of 21.4. Surveillance identified one urothelial carcinoma and one case of endometrial hyperplasia. In the affected group, the mean age was 55.2 years, and the BMI was 24.7. Twenty-three gynecological cancers were diagnosed, of which 52% were endometrial, 26% ovarian, and 18% breast cancers. 61.1% of tumors were MSI-positive, and 33.3% of patients received immunotherapy. CONCLUSION: A holistic, multidisciplinary approach is essential for the management of LS patients in gynecological oncology. The structured consultation model developed at Charité facilitates personalized surveillance, risk-adapted prevention, and evidence-based therapy strategies. Future studies and clinical trials should further investigate screening protocols, therapeutic interventions, and the role of LS patients in targeted treatment approaches. This guideline serves as a preliminary framework and will be continuously adapted as new research emerges.