Synopsis
Identify clinical and tumour clues to Lynch syndrome and polyposis, construct a three-generation pedigree, arrange genetics-led germline testing and institute syndrome-specific colorectal and extracolonic prevention.
- Lynch syndrome results from pathogenic mismatch-repair variants and often presents with colorectal or endometrial cancer at younger age.
- Familial adenomatous polyposis causes hundreds to thousands of adenomas through APC dysfunction and near-certain cancer risk without colectomy.
- MUTYH-associated polyposis is autosomal recessive, so siblings may be at higher risk than each child.
Key red flags
A hereditary label or scheduled colonoscopy does not protect against obstruction, perforation or major bleeding; new distension, vomiting, obstipation, peritonism or shock needs emergency colorectal assessment.
Investigation priorities
Screen a newly diagnosed colorectal cancer for deficient mismatch repair and possible Lynch syndrome.
Management branches
A 42-year-old with right-sided colon cancer has loss of MLH1 and PMS2 on tumour immunohistochemistry. Their mother had endometrial cancer at 48 and maternal uncle had colon cancer at 51.
- Construct a three-generation pedigree with verified tumour sites and ages and explain that the IHC result shows deficient mismatch repair but is not itself a Lynch diagnosis.
- Arrange reflex tumour testing: BRAF V600E is absent and MLH1 promoter methylation is not detected, so the common sporadic MLH1-silencing route is less likely.
Key medicines
Aspirin for Lynch-syndrome colorectal-cancer preventionNICE recommends considering aspirin daily for more than two years but does not specify an optimal dose. CAPP2 used 600 mg daily, while 150 mg or 300 mg are commonly used in UK practice; select and document an individual dose with the specialist team rather than presenting CaPP3 as a NICE dose change.This is an off-label prevention use. Review peptic-ulcer or bleeding history, anticoagulants and antiplatelets, anaemia, hypersensitivity, asthma and renal risk, and use the NICE decision aid to discuss delayed benefit and bleeding uncertainty.