Surgical Pathology Criteria–

Hereditary Non-polyposis Colorectal Carcinoma Syndrome (HNPCC)

Differential Diagnosis

HNPCC Sporadic MSI-H Colorectal Adenocarcinoma
May have family history of associated neoplasms No family history of associated neoplasms
Mean age 45 Mean age >60
Not associated with sessile serrated adenomas Associated with sessile serrated adenomas (may not always be identifiable)
Germline mutation in mismatch repair enzymes No germline mutation

See Supplemental Studies in left menu for differences in mismatch genes and expression

HNPCC / Lynch Syndrome Familial Adenomatous Polyposis
May have family history of characteristic associated neoplasms Family history of early onset of colorectal polyps
Duodenal adenoma and carcinoma rare Personal or family history of duodenal adenoma common, carcinoma may occur
Adenomas if present are only moderately increased ≥100 adenomas in classic cases
Genetic and immunohistologic evidence of mismatch repair deficiency No evidence of mismatch repair deficiency
APC mutation not present APC mutation detectable in 80%
Attenuated FAP may be very difficult to distinguish from HNPCC as it has fewer adenomas and later presentation and frequent right sided carcinoma

 

MUTYH Associated Polyposis HNPCC
Family history of polyps and colorectal carcinoma only May have family history of characteristic associated neoplasms
Duodenal adenoma in 18% Duodenal adenoma rare
Germline mutation detected in MUTYH gene No MUTYH mutation
No evidence of mismatch repair deficiency Genetic and immunohistologic evidence of mismatch repair deficiency
Autosomal recessive Autosomal dominant
MUTYH associated polyposis may be very difficult to distinguish clinically from HNPCC as it has fewer adenomas and later presentation and frequent right sided carcinoma

 

Serrated Polyposis (Hyperplastic Polyposis) Hereditary Nonpolyposis Colorectal Cancer
Multiple serrated polyps (most are SSA) Polyps are not increased
Not associated with extra-GI cancers Associated with carcinomas of the endometrium, small intestine, ureter and renal pelvis
Associated with sporadic, non-familial colorectal adenocarcinoma Familial colorectal adenocarcinoma and other neoplasms
Two different pathways to MSI high colorectal carcinoma

 

HNPCC Peutz-Jeghers Syndrome
No mucocutaneous hyperpigmentation Mucocutaneous hyperpigmentation
Infrequent polyps are all adenomatous Hamartomatous polyps with arborizing smooth muscle bundles
Polyps rare in small intestine Most polyps in small intestine
Dysfunctional germ line mutations in DNA mismatch repair enzymes STK11 mutations in 50-90%
Both may be associated with carcinomas of the large intestine, breast and endometrium, as well as a number of other sites.

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