MKSAP Quiz: Screening after endometrial cancer
A 40-year-old woman is evaluated at follow-up for stage I endometrial cancer diagnosed 6 weeks ago. Colon cancer was diagnosed in her mother at age 55 years and her maternal aunt at age 60 years. What is the most appropriate screening strategy for this patient?
A 40-year-old woman is evaluated at follow-up for stage I endometrial cancer diagnosed 6 weeks ago. Colon cancer was diagnosed in her mother at age 55 years and her maternal aunt at age 60 years.
The patient has had total abdominal hysterectomy and bilateral oophorectomy. Germline genetic testing confirmed a pathogenic mutation in MSH2.
Which of the following is the most appropriate screening strategy for this patient?
A. Fecal DNA testing
B. Fecal immunochemical test
C. Upper endoscopy and colonoscopy
D. Upper endoscopy, colonoscopy, and wireless capsule endoscopy
MKSAP Answer and Critique
The correct answer is C. Upper endoscopy and colonoscopy. This content is available to MKSAP subscribers as Question 79 in the Gastroenterology and Hepatology section. More information about MKSAP is available online.
The most appropriate screening strategy is upper endoscopy and colonoscopy (Option C). This patient has Lynch syndrome, which is caused by germline mutations in the mismatch repair genes MLH1, MSH2, MSH6, and PMS2 or the epithelial cell adhesion molecule gene (EPCAM). Risks for colorectal cancer vary by gene mutation but range from approximately 50% to 80% lifetime risk. Individuals with Lynch syndrome are at increased risk for colorectal and endometrial cancers (most common), as well as other cancers, including tumors of the stomach and small bowel. The Amsterdam II criteria are specific but not sensitive for the diagnosis of Lynch syndrome. This patient's family fulfills the Amsterdam II criteria for Lynch syndrome, which states that a diagnosis is warranted if all of the following criteria are met:
- Three or more family members have a Lynch syndrome–associated cancer.
- Two or more successive generations are affected.
- One of the cancers was diagnosed before age 50 years.
- One affected family member is a first-degree relative of the other two affected family members.
- Familial adenomatous polyposis has been ruled out.
- Tumors have been verified pathologically.
Online prediction models, such as the PREdiction Model for gene Mutation5 (PREMM5), can also help predict risk for Lynch syndrome or other hereditary gastrointestinal cancer syndromes.
Screening for colorectal cancer in patients with Lynch syndrome should begin between ages 20 and 25 years, or 2 to 5 years before the earliest cancer diagnosis in the family. The recommended screening modality is colonoscopy, which should be repeated every 1 to 2 years. Patients with Lynch syndrome are also at increased risk for stomach and small-bowel cancers. Upper endoscopy may be considered around age 30 to 35 years and should be repeated every 2 to 5 years. This patient should therefore undergo both upper endoscopy and colonoscopy, with careful inspection of the distal duodenum and terminal ileum. Helicobacter pylori testing should be performed at least once, and H. pylori should be eradicated if found.
Fecal DNA testing (Option A) and a fecal immunochemical test (Option B) are acceptable colorectal cancer screening strategies for average-risk patients but are not sufficiently sensitive for a high-risk patient who requires both colorectal and stomach/small-intestine cancer screening.
Routine wireless capsule endoscopy (Option D) is not recommended unless the patient has iron deficiency anemia in the absence of an obvious source of bleeding following upper endoscopy and colonoscopy.
Key Points
- Lynch syndrome is caused by germline mutations in the mismatch repair genes MLH1, MSH2, MSH6, and PMS2 or the epithelial cell adhesion molecule gene (EPCAM).
- Patients with Lynch syndrome should be screened for colon cancer with colonoscopy beginning at ages 20 to 25 years (or 2-5 years before the earliest cancer diagnosis in the family) and screened for stomach and small-bowel cancers with upper endoscopy beginning at age 30 to 35 years.