MKSAP quiz: Management of Lynch syndrome

This month's quiz asks readers to determine the next step in management for a 30-year-old woman with Lynch syndrome, based on her family history and the identification of a genetic mutation.


A 30-year-old woman is evaluated during a new-patient appointment. Her personal medical history is unremarkable and she takes no medication. Her family history includes colon cancer diagnosed in her mother at age 48 years, endometrial cancer diagnosed in a maternal aunt at age 51 years, and colon cancer diagnosed in her maternal grandfather at age 55 years.

All physical examination findings, including vital signs, are normal.

Genetic testing for MSH2 mutation is positive, consistent with Lynch syndrome.

Which of the following is the most appropriate next step?

A. Colectomy
B. Colonoscopy at age 38
C. Colonoscopy at age 40
D. Colonoscopy now


MKSAP Answer and Critique

The correct answer is D. Colonoscopy now. This content is available to MKSAP 18 subscribers as Question 79 in the Gastroenterology and Hepatology section. More information about MKSAP is available online.

This patient should undergo a screening colonoscopy now, and if it is normal, have a repeat colonoscopy every 1 to 2 years until age 40 years, and then yearly thereafter. The patient has Lynch syndrome based on her family history and the identification of a deleterious mutation in the MSH2 gene. The Amsterdam II criteria (known as the “3-2-1-1-0 rule”) can be used to screen for Lynch syndrome; a diagnosis is warranted if the following criteria are met:

  • Three family members are affected with a Lynch syndrome–associated cancer
  • At least two successive generations are affected
  • One affected family member is a first-degree relative of the other two affected family members
  • One of the cancers was diagnosed before age 50 years
  • Familial adenomatous polyposis has been excluded
  • Tumors have been verified histologically

The Amsterdam criteria are specific for Lynch syndrome but lack sensitivity. Additional clinical tools, such as the Bethesda criteria or clinical models such as the PREdiction Model for gene Mutations 5 (PREMM5), may be used to screen for Lynch syndrome.

Lynch syndrome is caused by germline mutation in one of the DNA mismatch repair genes (MLH1, MSH2, MSH6, PMS2) or the epithelial cell adhesion molecule (EPCAM) gene. The appropriate age to begin screening colonoscopy in patients with Lynch syndrome is between ages 20 and 25 years or 2 to 5 years before the earliest age of colorectal cancer diagnosis in the family, whichever comes first; thus, this patient should undergo a colonoscopy now. The risk for colorectal cancer in patients with Lynch syndrome is elevated significantly compared with the general population and is as high as 80% for some individuals. Women with Lynch syndrome are at increased risk for endometrial cancer. Additional cancers, such as gastric, small intestinal, urothelial, ovarian, and pancreaticobiliary cancers, are also associated with this syndrome.

Colectomy and continued annual endoscopic surveillance of the remaining rectum is the recommended management for patients with Lynch syndrome who are found to have colorectal cancer on screening colonoscopy. Colectomy is not a recommended option for managing patients with Lynch syndrome in the absence of a documented cancer.

Screening starting at age 40 years or 10 years earlier than the youngest age of colon cancer diagnosis in the family is appropriate for individuals with a family history of colon cancer that does not meet criteria for Lynch syndrome.

Key Point

  • Patients with Lynch syndrome should begin screening colonoscopy between ages 20 and 25 years or 2 to 5 years before the earliest age of colorectal cancer diagnosis in the family, whichever comes first, and colonoscopy should be repeated every 1 to 2 years if the baseline examination is normal.