A 37-year-old man is evaluated during a follow-up appointment after resection of a well-differentiated adenocarcinoma of the ascending colon, which was diagnosed 1 month earlier. His family history is significant for endometrial cancer diagnosed in his mother at age 50 years and colon cancer diagnosed in his maternal grandfather at age 49 years. The patient reports that he has been feeling well and takes no medication.
All physical examination findings, including vital signs, are normal.
Which of the following is the most appropriate next step in management?
A. Colonoscopy in 3 years
B. Fecal immunochemical testing in 1 year
C. Genetic counseling
D. Upper endoscopy and capsule endoscopy
MKSAP Answer and Critique
The correct answer is C. Genetic counseling. This content is available to MKSAP 18 subscribers as Question 47 in the Gastroenterology and Hepatology section. More information about MKSAP is available online.
This patient should be referred to a genetic counselor for genetic testing. The patient could have Lynch syndrome based on his personal history of colon cancer diagnosed before age 50 years and his family history of colon cancers. His family history meets the Amsterdam II criteria for Lynch syndrome because three individuals in the family are affected with a Lynch syndrome–associated cancer, at least two successive generations are affected, one of the affected family members is a first-degree relative of the other two affected family members, and at least one cancer was diagnosed in a family member younger than age 50 years (the “3-2-1-1” pattern). Additional criteria are that familial adenomatous polyposis has been excluded and tumors have been verified histologically. Guidelines recommend tumor testing (microsatellite instability testing or immunohistochemistry) to screen for Lynch syndrome in all colon cancers. The results of tumor testing can help determine if Lynch syndrome is likely and inform genetic testing. Lynch syndrome is only diagnosed in individuals who meet the Amsterdam criteria and have an identified constitutional mutation in a mismatch repair gene (MLH1, MSH2, MSH6, or PMS2) or the epithelial cell adhesion molecule (EPCAM) gene. Diagnosis of Lynch syndrome will inform colonoscopy surveillance recommendations for this patient. Identification of a Lynch syndrome mutation will also affect the recommendation for screening of other cancers (gastric, skin, urinary tract, and, in women, ovarian and endometrial cancers). In addition, if he has an identifiable mutation associated with Lynch syndrome, genetic testing should be offered to his first-degree relatives.
A 3-year interval for colonoscopy cannot be recommended until the results of the genetic evaluation are available. If Lynch syndrome is confirmed, the screening interval is every 1 to 2 years, not every 3 years.
Colonoscopy is preferred for screening high-risk patients such as those with a previous colorectal cancer; therefore, screening using fecal immunochemical testing, other fecal-based testing, or colonic imaging is not appropriate.
In patients with Lynch syndrome, upper endoscopy is recommended to screen for upper gastrointestinal cancers and to sample for Helicobacter pylori. However, this cannot be recommended until results from genetic testing are available. Patients with Lynch syndrome have an increased risk for small-intestinal cancer. However, routine cancer screening with capsule endoscopy is controversial and not routinely recommended even in patients with confirmed Lynch syndrome.
- Patients with a family history suggesting Lynch syndrome (three family members are affected with a Lynch syndrome–associated cancer, at least two successive generations are affected, one of the affected family members is a first-degree relative of the other two affected family members, and at least one cancer was diagnosed in a family member younger than age 50 years) should be referred for genetic counseling.