Apply patient and family history to visualize screening requirement.
Guidelines & Evidence
Clinical Details
Section 1
When to Use
When to Use
Selecting colorectal cancer (CRC) patients who should undergo Tumour Testing (MSI or IHC) for Lynch Syndrome
Evaluating patients with "concerning" personal or family histories of cancer
To guide referral to genetic counseling and germline testing
Universal Screening Note
While Bethesda is used to selectively test, many modern guidelines (NCCN/ACG) now recommend Universal Screening (MSI/IHC on ALL new CRC cases) regardless of age or family history. Bethesda remains critical in systems without universal protocols.
Section 2
Formula & Logic
The 5 Criteria (Positive if any one is met)
CRC diagnosed in a patient < 50 years of age.
Presence of synchronous or metachronous CRC or other Lynch-associated tumours* regardless of age.
CRC with MSI-High histology diagnosed in a patient < 60 years of age.
CRC diagnosed in a patient with ≥ 1 first-degree relative with Lynch-associated tumour* (one cancer < 50 years).
CRC diagnosed in a patient with ≥ 2 first-degree or second-degree relatives with Lynch-associated tumours* at any age.
The "Bethesda" features that suggest MSI-H include: Tumour-infiltrating lymphocytes (TILs), Crohn’s-like lymphocytic reaction, mucinous/signet ring differentiation, or medullary growth pattern.
Bethesda vs. Amsterdam II
Amsterdam II criteria are used to "Diagnose" Lynch syndrome based on genealogy (3-2-1 rule). Bethesda criteria are much broader and are used to "Screen" (decide who gets a tissue test). Most Lynch patients meet Bethesda, but many do NOT meet Amsterdam.
Clinical Pearls
The sensitivity of the Revised Bethesda Criteria for identifying Lynch Syndrome is approximately 82–95%
Endometrial cancer is the most common extra-colonic Lynch tumour and should always be screened for in female Lynch carriers
BRAF V600E mutation testing is used to distinguish "Sporadic" MSI-H cancers (where BRAF is common) from "Lynch" cancers (where BRAF is rare)
Section 4
Next Steps
Genetic Pathway
01
Bethesda Positive: Perform IHC for MMR proteins or MSI PCR on tumor tissue.
02
Loss of MMR Protein: Perform BRAF mutation and MLH1 promoter methylation (if MLH1/PMS2 lost).
03
Persistent Suspicion: Refer for Germline MSH2, MLH1, MSH6, or PMS2 sequencing.
Complementary Tools
Amsterdam II Criteria
PREMM5 Lynch Risk Model
CRC TNM Staging
Section 5
Evidence Appraisal
The Revised Criteria
Revised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability.
Umar A et al. • Journal of the National Cancer Institute. 2004;96(4):261-8. The current definitive screening standard.
Developed during a consensus workshop sponsored by the NCI in Bethesda, Maryland. The goal was to refine the 1997 original Bethesda criteria, which were slightly less sensitive for detecting MSH6 and PMS2 mutations.
