From the Guidelines
Lynch syndrome is most effectively diagnosed through universal tumor screening, which involves testing all individuals newly diagnosed with colorectal cancer (CRC) for microsatellite instability (MSI) or immunohistochemistry for absence of DNA mismatch repair (MMR) proteins, as recommended by the NCCN panel 1. This approach has been shown to have a sensitivity of 100% and specificity of 93.0% for identifying individuals with Lynch syndrome 1. The process of diagnosis may also involve a thorough family history review to identify patterns of colorectal, endometrial, or other Lynch-associated cancers across generations. Genetic testing is the definitive diagnostic method, which involves analyzing blood or saliva samples for mutations in DNA mismatch repair genes (MLH1, MSH2, MSH6, PMS2) or the EPCAM gene. Some key points to consider in the diagnosis of Lynch syndrome include:
- The Amsterdam criteria and revised Bethesda guidelines are clinical tools that help identify individuals who should undergo testing based on personal and family cancer history 1.
- A positive diagnosis requires confirmation of a pathogenic mutation in one of the Lynch syndrome genes.
- Early diagnosis is crucial as it allows for enhanced cancer surveillance protocols, including more frequent colonoscopies starting at younger ages, as well as screening for other Lynch-associated cancers, which significantly improves early detection and survival rates.
- The cost-effectiveness of universal screening has been established and has been endorsed by several organizations, including the Evaluation of Genomic Applications in Practice and Prevention Working Group at the CDC, the US Multi-Society Task Force on Colorectal Cancer, and ESMO 1. The NCCN panel recommends universal tumor testing of individuals with CRC or endometrial cancer as a primary strategy for screening for Lynch syndrome, and also identifies personal and family history criteria that can help identify individuals at increased risk for Lynch syndrome 1.
From the Research
Diagnosis of Lynch Syndrome
Lynch syndrome is diagnosed through a combination of clinical criteria, genetic testing, and tumor testing. The following are some of the methods used to diagnose Lynch syndrome:
- Clinical criteria: Individuals with a family history of colorectal or endometrial cancer, or those who have been diagnosed with these cancers at a young age, may be at risk for Lynch syndrome 2, 3, 4.
- Genetic testing: Genetic testing can identify mutations in the MLH1, MSH2, MSH6, or PMS2 genes, which are associated with Lynch syndrome 2, 3, 4, 5.
- Tumor testing: Tumor testing, including microsatellite instability testing and immunohistochemical testing, can identify tumors that are associated with Lynch syndrome 2, 5.
- Universal tumor testing: Universal tumor testing involves testing all newly diagnosed colorectal cancer patients for Lynch syndrome, regardless of their family history or age 6.
Identification of At-Risk Individuals
At-risk individuals can be identified through:
- Family history: A detailed family history can help identify individuals who may be at risk for Lynch syndrome 3, 4.
- Prediction models: Prediction models can be used to estimate an individual's risk of having Lynch syndrome based on their family history and other factors 5.
- Universal screening: Universal screening involves testing all individuals with newly diagnosed colorectal cancer for Lynch syndrome, regardless of their family history or age 2, 6.