Diagnosis of Lynch Syndrome and Strategies to Distinguish Lynch-Related Tumors from Sporadic MSI/dMMR Tumors

SIMPLE SUMMARY: Microsatellite instability (MSI) is a hallmark of Lynch syndrome (LS)-related tumors but is not specific, as most of MSI/mismatch repair-deficient (dMMR) tumors are sporadic. Therefore, the identification of MSI/dMMR requires additional diagnostic tools to identify LS. In this review, we address the hallmarks of LS and present recent advances in diagnostic and screening strategies to identify LS patients. We also discuss the pitfalls associated with current strategies, which should be taken into account in order to improve the diagnosis of LS. ABSTRACT: Microsatellite instability (MSI) is a hallmark of Lynch syndrome (LS)-related tumors but is not specific to it, as approximately 80% of MSI/mismatch repair-deficient (dMMR) tumors are sporadic. Methods leading to the diagnosis of LS have considerably evolved in recent years and so have tumoral tests for LS screening and for the discrimination of LS-related to MSI-sporadic tumors. In this review, we address the hallmarks of LS, including the clinical, histopathological, and molecular features. We present recent advances in diagnostic and screening strategies to identify LS patients. We also discuss the pitfalls associated with the current strategies, which should be taken into account to improve the diagnosis of LS and avoid inappropriate clinical management.