From the Guidelines
Lynch syndrome-associated polyps are characterized by four key features on endoscopy or pathology that increase their risk compared to sporadic polyps: proximal colon location, villous histology, high-grade dysplasia, and presence of microsatellite instability with loss of mismatch repair protein expression on immunohistochemistry, as noted in patients with MLH1 and MSH2 mutations 1. The two genes associated with Lynch syndrome that confer the highest risk for colorectal cancer are:
- MLH1
- MSH2, with lifetime risks of 50-80% for colorectal cancer development, as supported by the guidelines on genetic evaluation and management of Lynch syndrome 1. Lynch syndrome is also associated with four important non-gastrointestinal malignancies:
- Endometrial cancer, which occurs in up to 54% of women with MLH1 and MSH2 mutations 1
- Ovarian cancer, with a lifetime risk of 10-15% 1
- Urinary tract cancers, including urothelial cancers of the ureter and renal pelvis, with a lifetime risk of 8-10% 1
- Sebaceous neoplasms of the skin, which can present as part of Muir-Torre syndrome, as described in the context of MMR gene mutations 1. These characteristics and associations are crucial for clinicians to recognize, as they guide screening protocols, surveillance intervals, and risk assessment for patients and their family members with suspected or confirmed Lynch syndrome, ultimately impacting morbidity, mortality, and quality of life 1.
From the Research
Characteristics of Lynch Syndrome-Associated Polyps
- Microsatellite instability (MSI) phenotype 2, 3, 4
- Mismatch repair deficiency (MMR-D) 3
- Presence of serrated lesions 5
- High-frequency MSI (MSI-H) 3