Lynch syndrome

Lynch syndrome, also hereditary non-polyposis colorectal cancer syndrome (abbreviated HNPCC), is a constellation of clinical findings caused by a mutation in a mismatch repair gene, of which there are several.

As the name suggests, HNPCC is a form of inherited colorectal cancer that is not characterized by abundant intestinal polyps (non-polyposis), as in adenomatous polyposis coli.

The term Lynch syndrome is preferred as individuals with this syndrome often present with non-colorectal cancers.

Clinical

Divided into:

• Lynch syndrome I - colon cancer associated.
• Lynch syndrome II - non-colon cancer associated.
  • More common in females (~50%) vs. males (~25%).

Associations

• Colorectal carcinoma.
• Non-endometrioid endometrial carcinoma, e.g. endometrial clear cell carcinoma.
  • Suggestive features: lower uterine segment, tumour infiltrating lymphocytes.
• Stomach carcinoma, intestinal-type.
  • Significantly more common in males.
  • Surveillance may not be worthwhile.
• Biliary tree carcinoma.
• Pancreatic carcinoma.
• Urinary system carcinoma.
  • More common in the ureter than in sporadic cancers.
  • Papillary lesions > flat lesions.
  • Inverted growth pattern suggestive of MSI.

Lame mnemonic GP CUBE:

• Gastric.
• Pancreas.
• CRC.
• UCC.
• Biliary.
• Endometrial.

Note:

• All the cancers are below the diaphragm.

Genes

• MSH2 gene - most common.
• MLH1 gene - second most common.
• PMS2 gene.
• MSH6 gene.
• Others.

Special types

Muir-Torre syndrome

• Abbreviated MTS.

• Muir-Torre syndrome is a subset of HNPCC that includes the presence of sebaceous adenomas, and sebaceous carcinomas.
  • Cutaneous pathology precedes the internal malignancy in ~40% of cases.

Molecular pathology:

• MTS is caused by mutations in MSH2 or MLH1.

See also

• GI polyps.
• Familial polyposis coli.