Revised Amsterdam IIHereditary Non-Polyposis Colorectal Cancer
Familial Clusters
Molecular Screening
Assess the "3-2-1" rule to determine if the family tree suggestive of hereditary colorectal cancer syndromes.
Guidelines & Evidence
Clinical Details
Section 1
When to Use
When to Use
Initial screening of families with suspected Lynch Syndrome (HNPCC)
To identify pedigrees requiring germline mismatch repair (MMR) gene testing
To trigger genetic counselling in families with early-onset or multiple GI/endometrial cancers
Cancer Types Included
Lynch-associated cancers: Colorectal, Endometrial, Small Bowel, Ureter, or Renal Pelvis. Amsterdam II (1999) expanded the original criteria (1990) to include these extra-colonic sites.
When to Use Bethesda or PREMM5 Instead
Small families — Amsterdam criteria are often too restrictive for modern small nuclear families
Symptomatic individuals with late-onset cancer — Revised Bethesda is better for single-patient screening
When quantitative risk estimate is needed — PREMM5 provides a percentage risk; Amsterdam is binary (Met/Not Met)
Section 2
Formula & Logic
The 3-2-1 Rule
01
3 or more relatives with Lynch-associated cancer (CRC, Endometrial, S. Bowel, Ureter, Renal Pelvis).
02
One should be a First-Degree Relative of the other two.
03
At least 2 successive generations should be affected.
04
At least 1 relative diagnosed before age 50.
Strict Requirements
FAP (Familial Adenomatous Polyposis) must be excluded. Tumours should be verified by histological examination whenever possible.
Section 3
Pearls/Pitfalls
Specificity vs. Sensitivity
The Amsterdam II criteria are highly specific (approx. 98%) but have poor sensitivity (approx. 22-40%) for identifying MMR mutation carriers. Many families with Lynch Syndrome will NOT meet these criteria.
Modern Paradigm — Universal Screening
Current ASCO/ACG guidelines recommend universal IHC or MSI testing for ALL newly diagnosed colorectal cancers, which has largely superseded clinical criteria like Amsterdam for the primary detection of Lynch Syndrome.
Clinical Pearls
If criteria are met: Genetic consultation and germline testing are mandatory
Annual or biennial colonoscopy starting at age 20-25 is recommended for met criteria pedigrees
Endometrial and ovarian cancer screening should be discussed for female carriers
Section 4
Next Steps
Next Steps
01
Criteria Met: High clinical suspicion of Lynch. Proceed to germline testing.
02
Criteria Not Met: Use Revised Bethesda Guidelines. If Bethesda also negative, risk is low but surveillance still guided by family history.
Alternative & Integrated Tools
Revised Bethesda Guidelines
PREMM5 Clinical Risk Score
Lynch Syndrome Risk (Bethesda Revised)
Section 5
Evidence Appraisal
The Standard (Amsterdam II)
New clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) proposed by the International Collaborative Group on HNPCC.
Vasen HF et al. • Gastroenterology. 1999;116(6):1453-6. The formal update adding extra-colonic cancers.
Developed by the International Collaborative Group on Hereditary Non-Polyposis Colorectal Cancer, led by luminaries like Henry T. Lynch (the namesake of Lynch Syndrome) and Hans Vasen. The criteria were established to provide a uniform definition for research studies and family identification before genetic testing for MMR mutations was widely available.
