In order to more clearly understand the criteria for referral, it is helpful to be familiar with the types of cancer that are associated with Lynch syndrome:

  • Colorectal
  • Endometrial
  • Gastric
  • Ovarian
  • Pancreas
  • Ureter and renal pelvis
  • Brain (usually glioblastoma)
  • Small intestinal cancers
  • Sebaceous adenoma (seen in Muir-Torre)
  • Sebaceous carcinoma (seen in Muir-Torre)
  • Keratoacanthomas (seen in Muir-Torre)

In accordance with the National Comprehensive Cancer Network (NCCN, v 1.2018), any individual with a personal or family history with any of the following should be offered further evaluation for Lynch syndrome:

  • Known familial mutation in a gene that causes Lynch syndrome (MLH1, MSH2, MSH6, PMS2, and EPCAM)
  • Colorectal or endometrial cancer diagnosed before the age of 50
  • Diagnosis of colorectal or endometrial cancer AND another Lynch syndrome-related cancer
  • Colorectal or endometrial cancer and one or more first- or second-degree relatives diagnosed with a Lynch syndrome-related cancer before age 50
  • Colorectal or endometrial cancer and two or more first- or second-degree relatives with Lynch syndrome-related cancers (regardless of age)
  • Colorectal or endometrial cancer at any age with the tumor showing MSI or loss of mismatch repair protein expression (MLH1, MSH2, MSH6, and PMS2)
  • Five percent or greater risk of having a Lynch syndrome mutation based on predictive models (PREMM5, MMRpro, MMRpredict)