From the Guidelines
When evaluating a patient for Lynch syndrome, pertinent history findings include a personal history of colorectal cancer diagnosed before age 50, endometrial cancer before age 50, or multiple Lynch-associated cancers regardless of age, as recommended by the most recent guidelines 1. Pertinent history findings to rule out Lynch syndrome in a patient include:
- A personal history of colorectal cancer diagnosed before age 50, endometrial cancer before age 50, or multiple Lynch-associated cancers regardless of age
- Family history of first and second-degree relatives with Lynch-associated cancers, such as colorectal, endometrial, ovarian, gastric, small bowel, urinary tract, biliary tract, pancreatic, brain, and sebaceous gland tumors
- Pattern of inheritance, with multiple affected family members across generations, indicating an autosomal dominant pattern
- Tumor characteristics, such as microsatellite instability or loss of mismatch repair protein expression on immunohistochemistry, if testing has been performed
- Ashkenazi Jewish ancestry or certain founder mutations, which may be relevant in some populations
- History of multiple colorectal adenomas, typically fewer than 100, distinguishing from familial adenomatous polyposis (FAP) These findings help identify patients who should undergo genetic testing for Lynch syndrome, which involves sequencing of MLH1, MSH2, MSH6, PMS2, and EPCAM genes, as recommended by the National Comprehensive Cancer Network (NCCN) guidelines 1. Early identification allows for enhanced cancer surveillance protocols and preventive interventions for patients and at-risk family members. The use of universal tumor screening for all individuals newly diagnosed with colorectal cancer is also recommended, as it provides a sensitivity of 100% and specificity of 93.0% for identifying individuals with Lynch syndrome 1.
From the Research
History Findings for Ruling Out Lynch Syndrome
To rule out Lynch syndrome in a patient, the following history findings are pertinent:
- A detailed family history is essential, as Lynch syndrome is a hereditary cancer syndrome 2
- A history of colorectal or endometrial cancer, as Lynch syndrome accounts for 3% of unselected patients with these cancers 3, 4
- A history of other cancers associated with Lynch syndrome, such as ovarian cancer, which has a 6-8% risk in women with Lynch syndrome 5
- Age of diagnosis, as Lynch syndrome-associated cancers often occur at a younger age, with a median age of 49 for endometrial cancer 5
- Type of cancer, as Lynch syndrome is associated with specific types of cancer, such as endometrioid endometrial cancer and DNA mismatch repair-deficient tumors 3, 5
Key Considerations
When taking a patient's history to rule out Lynch syndrome, consider the following: