Defining the Adenoma Burden in Lynch Syndrome

Abstract

Although 10 or more adenomas prompt testing for polyposis syndromes, Lynch syndrome should also be considered in the differential diagnosis.

The current value of determining the mismatch repair status of colorectal cancer: A rationale for routine testing

“…Although LS is traditionally considered to be a non-polyposis syndrome up to 41% of patients will have at least one adenoma, including 2% with six to nine adenomas and 4% with more than 10 cumulative adenomas (Kalady et al, 2015). The "second hit" in Lynch syndrome is thought to take place after the instigating APC or CTNNB1 (␤-catenin) mutation, which initiates the precancerous adenoma (Geiersbach and Samowitz, 2011).…”

Hereditary non‐polyposis colorectal cancer/Lynch syndrome in three dimensions

“…Patients with >100 synchronous adenomas are excluded, as having, by definition, polyposis. Patients with LS can have oligopolyposis however, and one patient with LS had 23 synchronous adenomas . Patients and families who met criteria for germline mutation testing received genetic counselling prior to testing and afterwards.…”

An update on the molecular pathology of the intestinal polyposis syndromes

“…A germline MMR mutation in MSH2 (chromosome 2p21, including deletions overlapping with the EPCAM gene), MLH1 (chromosome 3p21.3), MSH6 (chromosome 2p16.3) or PMS2 (chromosome 7p22.1) causes MMR inactivation once a second hit occurs. LS is typified by CRC, endometrial cancer and lower, risks of other cancers (gastric, ovarian, skin (MuireTorre syndrome), small bowel, uroepithelial, and others), 8 but usually there is no true polyposis; however, a few LS patients do develop multiple serrated polyps or adenomas, 9 for reasons that are not well understood, but may include the action of modifying genes. MMR acts after normal DNA replication to "mop up" spontaneous mutations that have eluded other repair mechanisms after a cell replicates its DNA.…”