Lynch syndrome (HNPCC) is caused by germline mutations in DNA mismatch repair genes. Which clinical criterion in the revised Amsterdam II criteria distinguishes Lynch syndrome-associated colorectal cancer from sporadic cancer?
- A Two first-degree relatives with colorectal cancer, one diagnosed before age 45
- B Family history of colorectal cancer with microsatellite instability on tumor testing
- C Three or more relatives with colorectal cancer, one a first-degree relative of the other two, spanning at least two generations, with at least one diagnosis before age 50 ✓
- D Presence of >10 adenomatous polyps
Correct answer: C. Three or more relatives with colorectal cancer, one a first-degree relative of the other two, spanning at least two generations, with at least one diagnosis before age 50
Explanation
The Amsterdam II criteria require: (1) three or more relatives with Lynch syndrome-associated cancer (colorectal, endometrial, small bowel, ureter, or renal pelvis), (2) one must be a first-degree relative of the other two, (3) at least two successive generations affected, (4) at least one diagnosis before age 50, and (5) FAP excluded. These are purely clinical criteria. Microsatellite instability testing is used for molecular confirmation but is not part of the Amsterdam criteria. More than 10 polyps suggests FAP.
Reference: Bailey & Love's Short Practice of Surgery, 27th ed.
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