Amsterdam Criteria and FAP
The Amsterdam criteria are NOT diagnostic criteria for familial adenomatous polyposis (FAP)—they are criteria for hereditary nonpolyposis colorectal cancer (HNPCC/Lynch syndrome), and specifically require that FAP be excluded. 1
Amsterdam Criteria Overview
The Amsterdam criteria were developed to clinically identify Lynch syndrome families, not FAP. There are two versions:
Amsterdam Criteria I 1
Requires all of the following:
- At least 3 relatives with colorectal cancer
- One must be a first-degree relative of the other two
- At least 2 successive generations affected
- At least 1 relative diagnosed before age 50 years
- FAP must be excluded
- Tumors verified by pathologic examination
Amsterdam Criteria II (Revised) 1
Expanded to include Lynch-associated cancers:
- At least 3 relatives with Lynch-associated cancers (colorectal, endometrium, small bowel, ureter, or renal pelvis)
- One must be a first-degree relative of the other two
- At least 2 successive generations affected
- At least 1 relative diagnosed before age 50 years
- FAP must be excluded in colorectal cancer cases
- Tumors verified whenever possible
Critical Limitation 1
- Approximately 50% of Lynch syndrome patients will be missed by these criteria
- Approximately 50% who meet criteria will not have Lynch syndrome but have high familial risk of uncertain etiology
Actual FAP Diagnostic Criteria
Since the question may reflect confusion about FAP diagnosis, here are the correct criteria:
Classical FAP 1
- ≥100 colorectal adenomatous polyps (sufficient for clinical diagnosis)
- Fewer polyps at younger ages in families with known FAP
- Autosomal dominant inheritance (except de novo mutations in 30-40% of cases) 2
- Mean age of colorectal cancer: 40-50 years without intervention 1
Attenuated FAP (AFAP) 1, 3
Diagnostic criteria proposed by Knudsen et al:
- Dominant mode of inheritance
- 3-99 colorectal adenomas at age ≥20 years 1
Alternative Nielsen criteria: 1
- At least 2 patients with 10-99 adenomas at age >30 years, OR
- One patient with 10-99 adenomas at age >30 years plus a first-degree relative with CRC with few adenomas
- No family members with >100 adenomas before age 30 years
Clinical features distinguishing AFAP: 1
- <100 adenomas (average 30 polyps)
- Frequent right-sided distribution
- Mean age of cancer >50 years (delayed 15 years compared to classical FAP) 3
- Upper GI findings and thyroid cancer risk similar to classical FAP
- CHRPE and desmoids are rare
Genetic Confirmation
Mutation Detection Rates 1, 4
- Classical FAP: >70% have identifiable APC mutations
- AFAP: <25% have APC mutations 1
- MUTYH testing recommended if APC negative, especially in AFAP 4, 5
When Amsterdam Criteria Families Need FAP Exclusion 1
- Families meeting Amsterdam criteria where MMR testing is not possible may be offered surveillance as per Lynch syndrome
- Must exclude FAP through colonoscopy demonstrating absence of polyposis phenotype 1
Key Clinical Pitfall
Do not confuse Amsterdam criteria (for Lynch syndrome) with FAP diagnostic criteria. The Amsterdam criteria explicitly require FAP exclusion as part of their definition. 1 FAP diagnosis is based on polyp count, age of onset, and genetic testing—not family cancer patterns defined by Amsterdam criteria.