Table 2.

Cardinal features of Lynch syndrome (LS)

Autosomal dominant inheritance pattern seen for syndrome cancers in the family pedigree Earlier average age of colorectal cancer (CRC) onset than in the general population Average age of 45 years in LS vs 69 years in the general population Proximal (right-sided) colonic cancer predilection ~70% of LS CRCs are proximal to the splenic flexure Accelerated carcinogenesis (tiny adenomas can develop into carcinomas more quickly) Within 2–3 years in LS vs 8–10 years in the general population High risk of additional CRCs 25–30% of patients having surgery for a LS-associated CRC will have a second primary CRC within 10 years of surgical resection if the surgery was less than a subtotal colectomy Increased risk for malignancy at certain extracolonic sites (143, 144) Endometrium (40–60% lifetime risk for female mutation carriers) Ovary (12–15% lifetime risk for female mutation carriers) Stomach (higher risk in families indigenous to the Orient, reason unknown at this time) Small bowel Hepatobiliary tract Pancreas Upper uro-epithelial tract (transitional cell carcinoma of the ureter and renal pelvis), especially in males with LS-MSH2 type (143) Brain (in the Turcot’s syndrome variant of the LS) Multiple sebaceous adenomas, sebaceous carcinomas, and keratoacanthomas in the Muir–Torre syndrome variant of LS Pathology of CRCs is more often poorly differentiated, with an excess of mucoid and signet-cell features, a Crohn’s-like reaction, and a significant excess of tumor-infiltrating lymphocytes within the tumor Increased survival from CRC The sine qua non for diagnosis is the identification of a germline mutation in a mismatch repair gene (MLH1, MSH2, MSH6, or PMS2) that segregates in the family: i.e., members who carry the mutation show a much higher rate of syndrome-related cancers than those who do not carry the mutation