nonpolyposis

Nonpolyposis historically referred to hereditary conditions in which colorectal cancer occurs with few or no polyps. In modern medical terminology, the term is largely synonymous with Lynch syndrome, a dominantly inherited predisposition to several cancer types, most notably colorectal cancer.

Genetic basis and mechanism: Most cases arise from germline mutations in mismatch repair genes, including MLH1, MSH2, MSH6, and PMS2, or from deletions in EPCAM that affect MSH2. This autosomal dominant condition leads to defective DNA mismatch repair and microsatellite instability, accelerating tumor development and often presenting at a younger age than sporadic colorectal cancer.

Cancer risk and spectrum: The hallmark is an increased risk of colorectal cancer, frequently with a tendency toward right-sided tumors. Lynch syndrome also raises risks for several extracolonic cancers, notably endometrial and ovarian cancers, as well as cancers of the stomach, small intestine, urinary tract, pancreas, and other sites. Penetrance and specific cancer risks vary by gene and family.

Diagnosis and management: Diagnosis is guided by family history, tumor testing for microsatellite instability or mismatch repair deficiency, and germline genetic testing. Historically, Amsterdam criteria and Bethesda guidelines helped identify candidates for testing; today most guidelines recommend genetic testing for individuals meeting criteria or with MSI/MMR-deficient tumors. Management emphasizes intensified surveillance, including colonoscopy every 1–2 years beginning in early adulthood (often around 20–25 years) and appropriate gynecologic cancer surveillance. Risk-reducing options, such as consideration of gynecologic surgery in appropriate circumstances, may be discussed.

Terminology note: The term nonpolyposis is less used in current practice; Lynch syndrome is the preferred, precise designation.