| Autosomal dominant inheritance pattern seen for syndrome cancers in the family pedigree. |
| Earlier average age of CRC onset than in the general population: |
| average age of 45 years in Lynch syndrome vs. 63 years in the general population |
| Proximal (right-sided) colonic cancer predilection: |
| 70-85% of Lynch syndrome CRCs are proximal to the splenic flexure. |
| Accelerated carcinogenesis: (tiny adenomas can develop into carcinomas more quickly): |
| within 2-3 years in Lynch syndrome vs. 8-10 years in the general population |
| High risk of additional CRCs: |
| 25-30% of patients having surgery for a Lynch syndrome-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: |
| 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) |
| prostate cancer |
| breast cancer |
| adrenal cortical carcinomas |
| brain (glioblastomas in the Turcot’s syndrome variant of the Lynch syndrome) |
| sebaceous adenomas, sebaceous carcinomas, and multiple keratoacanthomas in the Muir-Torre syndrome variant of Lynch syndrome |
| 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 infiltrating lymphocytes within the tumor. |
| Increased survival from CRC. |
| The sine qua non for diagnosis of LS is the identification of a germline mutation in a mismatch repair gene (most commonly MLH1, MSH2, or MSH6) 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. |