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Hereditary Mixed Polyposis Syndrome

Definition

  • Hereditary syndrome characterized by the appearance of various types of polyps, many of which are mixed in pattern

Alternate/Historical Names:

  • Mixed familial polyposis

Diagnostic Criteria

  • Individuals and families may have mixtures of types of polyps and polyps containing mixed patterns
    • Adenomas are most frequent type
      • Both tubular and villous
    • Many polyps have features of juvenile polyps
      • Prominent edematous stroma
      • Cystic dilation of glands
      • Frequently resemble the polyps of Juvenile Polyposis syndrome
    • Epithelium frequently serrated
      • May be mixed with other patterns
      • Classic hyperplastic polyps may be seen
        • Not clear if increased over normal
    • Mixtures of above patterns are common
  • Polyps confined to colon and rectum
    • Most cases have 1-15 polyps at presentation
      • Rarely over 50
  • Mean age at presentation 41 years
  • Increased incidence of colorectal adenocarcinoma
    • Mean age 48, range 32-74
  • No familial extra-colorectal disorders reported
  • Autosomal dominant inheritance
    • Genetic lesion not entirely resolved
      • BMPR1A has been proposed (Cheah, O'Riordan)
      • CRAC1 15q13-q21 has been proposed (Jaegher)
    • Few kindreds reported
      • Most belong to one large Ashkenazi Jewish kindred
  • Robert V Rouse MD
    Department of Pathology
    Stanford University School of Medicine
    Stanford CA 94305-5342

    Original posting / updates: 12/27/09, 12/28/09 11/27/11

 

Differential Diagnosis

Juvenile Polyposis Hereditary Mixed Polyposis
Most cases present in childhood Mean age at presentation 41 years
Usually 50-200 polyps Usually 1-15 polyps, rarely >50
Adenomas infrequent Adenomas common
The gastrointestinal polyps in some cases are indistinguishable

 

Hereditary Mixed Polyposis Familial Adenomatous Polyposis
Mixtures of adenomatous and juvenile type polyps Colorectal polyps are all adenomatous
Polyps may have mixed adenomatous and juvenile features Colorectal polyps lack juvenile features
No extra-colorectal associated lesions May be associated with duodenal adenomas, gastric fundic gland polyps, desmoid tumors and other extra-gi disorders
No APC mutation Mutation in APC gene

 

Cowden Disease Hereditary Mixed Polyposis Syndrome
Most cases present in childhood Mean age at presentation 41 years
Usually 50-200 polyps Usually 1-15 polyps, rarely >50
Adenomas infrequent Adenomas common
Most have facial mucocutaneous lesions, see description No associated mucocutaneous lesions
Frequent breast hamartomas and carcinomas No association with breast hamartomas or carcinomas
Frequent thyroid carcinomas No association with thyroid carcinomas
The polyps in some cases are indistinguishable

 

Cronkhite-Canada Syndrome Hereditary Mixed Polyposis Syndrome
Usually >50 polyps Usually 1-15 polyps, rarely >50
Adenomas infrequent (sporadic adenomas may occur) Adenomas common
Hair, nail, skin pigmentation changes present No associated extra-GI lesions
Not familial Autosomal dominant
The polyps in some cases are indistinguishable

 

Serrated Polyposis (Hyperplastic Polyposis) Hereditary Mixed Polyposis
Adenomatous cytologic features infrequent, focal at most Most polyps are adenomatous, either pure or mixed
Most polyps are sessile Most are polypoid, regardless of  histology
Glands are vertically arranged and not complex Frequently shows features of juvenile polyps: prominent stroma, cystic dilation

Bibliography

  • Bosman FT, Carneiro F, Hruban RH, Thiese ND (Eds). WHO Classifiication of Tumors of the Digestive System, IARC, Lyon 2010
  • Calva D, Howe JR. Hamartomatous polyposis syndromes. Surg Clin North Am. 2008 Aug;88(4):779-817.
  • Jass JR. Colorectal polyposes: from phenotype to diagnosis. Pathol Res Pract. 2008;204(7):431-47.
  • Rozen P, Samuel Z, Brazowski E. A prospective study of the clinical, genetic, screening, and pathologic features of a family with hereditary mixed polyposis syndrome. Am J Gastroenterol. 2003 Oct;98(10):2317-20.
  • Whitelaw SC, Murday VA, Tomlinson IP, Thomas HJ, Cottrell S, Ginsberg A, Bukofzer S, Hodgson SV, Skudowitz RB, Jass JR, Talbot IC, Northover JM, Bodmer WF, Solomon E. Clinical and molecular features of the hereditary mixed polyposis syndrome. Gastroenterology. 1997 Feb;112(2):327-34.
  • Chen HM, Fang JY. Genetics of the hamartomatous polyposis syndromes: a molecular review. Int J Colorectal Dis. 2009 Aug;24(8):865-74.
  • Cheah PY, Wong YH, Chau YP, Loi C, Lim KH, Lim JF, Koh PK, Eu KW. Germline bone morphogenesis protein receptor 1A mutation causes colorectal tumorigenesis in hereditary mixed polyposis syndrome. Am J Gastroenterol. 2009 Dec;104(12):3027-33.
  • O'Riordan JM, O'Donoghue D, Green A, Keegan D, Hawkes LA, Payne SJ, Sheahan K,
    Winter DC. Hereditary mixed polyposis syndrome due to a BMPR1A mutation.
    Colorectal Dis. 2010 Jun;12(6):570-3.
  • Jaeger E, Webb E, Howarth K, Carvajal-Carmona L, Rowan A, Broderick P, Walther A, Spain S, Pittman A, Kemp Z, Sullivan K, Heinimann K, Lubbe S, Domingo E, Barclay E, Martin L, Gorman M, Chandler I, Vijayakrishnan J, Wood W, Papaemmanuil E, Penegar S, Qureshi M; CORGI Consortium, Farrington S, Tenesa A, Cazier JB, Kerr D, Gray R, Peto J, Dunlop M, Campbell H, Thomas H, Houlston R, Tomlinson I. Common genetic variants at the CRAC1 (HMPS) locus on chromosome 15q13.3 influence colorectal cancer risk. Nat Genet. 2008 Jan;40(1):26-8.
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