The Lynch syndrome is the most common inherited syndrome associated with colorectal cancer, accounting for 3% of new diagnoses; it is also associated with extracolonic cancers, the most common of which is endometrial cancer.
The Lynch syndrome phenotype includes a propensity for cancers of the proximal colon, poor tumor differentiation with mucinous or signet-ring cell histologic features or a medullary growth pattern, abundant infiltrating lymphocytes in the tumor, and synchronous and metachronous colorectal cancers.
Guidelines for Diagnosis of the Lynch Syndrome
Amsterdam II criteria
- Three or more relatives with histologically verified Lynch syndrome–associated cancer, one of whom is a first-degree relative of the other two*
- Cancer involving at least two generations
- One or more cancer cases diagnosed before 50 years of age
Revised Bethesda guidelines
- Diagnosis of colorectal cancer or endometrial cancer in a patient younger than 50 years of age
- Presence of synchronous colorectal cancers, metachronous colorectal cancers, or other Lynch syndrome–associated tumors, regardless of patient age
- Diagnosis of colorectal cancer with a high frequency of microsatellite instability on the basis of histologic findings (Crohn’s-like lymphocytic reaction, mucinous or signet-ring cell differentiation, or medullary growth pattern) in a patient younger than 60 years of age
- Diagnosis of colorectal cancer in one or more first-degree relatives with a Lynch syndrome–related tumor, with one of the diagnoses occurring before 50 years of age
- Diagnosis of colorectal cancer in two or more first- or second-degree relatives with Lynch syndrome–related tumors, regardless of patient age
* Lynch syndrome–associated tumors include cancers of the colon and rectum, endometrium, stomach, ovary, pancreas, ureter, renal pelvis, biliary tract, brain, small bowel, and sebaceous glands, as well as keratoacanthomas.
- Sinicrope FA. Lynch Syndrome-Associated Colorectal Cancer. N Engl J Med. 2018 Aug 23;379(8):764-773. [Medline]
- Stoffel EM, Mangu PB, Gruber SB, Hamilton SR, Kalady MF, Lau MW, Lu KH, Roach N, Limburg PJ; American Society of Clinical Oncology; European Society of Clinical Oncology. Hereditary colorectal cancer syndromes: American Society of Clinical Oncology Clinical Practice Guideline endorsement of the familial risk-colorectal cancer: European Society for Medical Oncology Clinical Practice Guidelines. J Clin Oncol. 2015 Jan 10;33(2):209-17 [Medline]
Created Mar 18, 2019.