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
Bosman FT, Carneiro F, Hruban RH, Thiese ND (Eds). WHO Classifiication of Tumors of the Digestive System, IARC, Lyon 2010
Hamilton SR, Liu B, Parsons RE, Papadopoulos N, Jen J, Powell SM, Krush AJ, Berk T, Cohen Z, Tetu B, et al. The molecular basis of Turcot's syndrome. N Engl J Med. 1995 Mar 30;332(13):839-47.
Greenson JK, Huang SC, Herron C, Moreno V, Bonner JD, Tomsho LP, Ben-Izhak O, Cohen HI, Trougouboff P, Bejhar J, Sova Y, Pinchev M, Rennert G, Gruber SB. Pathologic Predictors of Microsatellite Instability in Colorectal Cancer. Am J Surg Pathol. 2009 Jan;33(1):126-33.
Desai TK, Barkel D. Syndromic colon cancer: lynch syndrome and familial adenomatous polyposis. Gastroenterol Clin North Am. 2008 Mar;37(1):47-72.
Bandipalliam P. Syndrome of early onset colon cancers, hematologic malignancies & features of neurofibromatosis in HNPCC families with homozygous mismatch repair gene mutations. Fam Cancer. 2005;4(4):323-33.
Boland CR, Koi M, Chang DK, Carethers JM. The biochemical basis of microsatellite instability and abnormal immunohistochemistry and clinical behavior in Lynch syndrome: from bench to bedside. Fam Cancer. 2008;7(1):41-52.
Gatalica Z, Torlakovic E. Pathology of the hereditary colorectal carcinoma. Fam Cancer. 2008;7(1):15-26.
South CD, Hampel H, Comeras I, Westman JA, Frankel WL, de la Chapelle A. The frequency of Muir-Torre syndrome among Lynch syndrome families. J Natl Cancer Inst. 2008 Feb 20;100(4):277-81.
Ponti G, Ponz de Leon M. Muir-Torre syndrome. Lancet Oncol. 2005 Dec;6(12):980-7.
Bellizzi AM, Frankel WL. Colorectal cancer due to deficiency in DNA mismatch repair function: a review. Adv Anat Pathol. 2009 Nov;16(6):405-17.
Lee SE, Kang SY, Cho J, Lee B, Chang DK, Woo H, Kim JW, Park HY, Do IG, Kim YE, Kushima R, Lauwers GY, Park CK, Kim KM. Pyloric Gland Adenoma in Lynch Syndrome. Am J Surg Pathol. 2014 Feb 10. [Epub ahead of print] PubMed PMID: 24518125.