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.
Genetic counseling should be offered before genetic or immunohistologic testing is performed
Autosomal dominant with variable penetrance
Increased overall survival for colorectal carcinoma
Decreased response to 5FU chemotherapy
Mean age at clinical diagnosis 45 years
35% of patients have multiple cancers
Associated with a lifetime risk of cancer of 70%
Colorectal adenocarcinoma 70-85%
Endometrial adenocarcinoma 50-70%
CNS glioblastoma (Turcot syndrome)
Ureter and renal pelvis
Muir-Torre syndrome findings are present in 9% of HNPCC patients
Sebaceous cutaneous neoplasms
Mutations in MLH1 and MSH2 result in classic HNPCC
Mutations in PMS2 and MSH6 result in attenuated HNPCC
Cancers develop 6-8 years later than in classic syndrome
Homozygous and compound heterozygous mutations lead to cancers in children and young adults (first 3 decades)
Colorectal and endometrial carcinoma
CNS, various types
Leukemias and lymphomas, various types
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