Familial Cancer

, Volume 7, Issue 2, pp 157–162 | Cite as

Sessile serrated polyps of the colorectum are rare in patients with Lynch syndrome and in familial colorectal cancer families

  • S. H. Andersen
  • E. Lykke
  • M. B. Folker
  • I. Bernstein
  • S. HolckEmail author


Whereas the generally accepted carcinogenesis pathway of the microsatellite instabile high (MSI-H) colorectal carcinoma (CRC) involves the traditional adenoma in patients with Lynch syndrome, a serrate pathway involving serrate adenomas (SA) and sessile serrate polyps (SSP) characterize the sporadic MSI-H counterpart. Recent studies have, however, challenged such simple one-pathway models, inviting the consideration of alternative, unexpected pathways. Here, the issue as to the possible role of SSP, primarily in the context of Lynch syndrome, but also in subjects from familial CRC families (FCF) is addressed. Polyps coded as hyperplastic polyps (HP) from subjects with Lynch syndrome and FCF enrolled in the HNPCC-register at the Hvidovre University Hospital as well as adenomas from this population were retrieved and reviewed for features of SSP. Ninety-eight polyps coded as HP and 41 polyps coded as adenoma from 14 individuals with Lynch syndrome as well as 17 individuals from FCF constituted the study material. Seven of the 98 polyps coded as HP displayed histological features that, to varying extent, deviated from the traditional HP (THP), yet, merely two of these, both from the FCF, were considered examples of probable SSP. None of the 41 cases coded as adenoma possessed a morphology that qualified as SSP. The prevalence of SSP was not increased as compared to the background population and thus, this serrated lesion does not appear to play a tumorigenic role in Lynch syndrome, nor in FCF.


Sessile serrated polyp Sessile serrated adenoma Lynch syndrome HNPCC Carcinogenesis 



Adenomatous polyposis coli


Colorectal carcinoma


Familial colorectal cancer family


Hereditary non-polyposis colorectal cancer


Hyperplastic polyp




Lynch syndrome


Mismatch repair


Microsatellite instability high


Serrated adenoma


Serrated polyp


Sessile serrated polyp


Traditional hyperplastic polyp


  1. 1.
    Halvarsson B, Lindblom A, Johansson L et al (2005) Loss of mismatch repair protein immunostaining in colorectal adenomas from patients with hereditary nonpolyposis colorectal cancer. Mod Pathol 18:1095–1101PubMedCrossRefGoogle Scholar
  2. 2.
    Müller A, Beckmann C, Westphal G et al (2006) Prevalence of the mismatch-repair-deficient phenotype in colonic adenomas arising in HNPCC patients: results of a 5-year follow-up study. Int J Colorectal Dis 21:632–664PubMedCrossRefGoogle Scholar
  3. 3.
    Jass JR (2003) Hyperplastic-like polyps as precursors of microsatellite unstable colorectal cancer. Am J Clin Pathol 119:773–775PubMedCrossRefGoogle Scholar
  4. 4.
    Goldstein NS, Bhanot P, Odish E et al (2003) Hyperplastic-like colon polyps that preceded microsatellite-unstable adenocarcinomas. Am J Clin Pathol 119:1–19CrossRefGoogle Scholar
  5. 5.
    Higuichi T, Sugihara K, Jass JR (2005) Demographic and pathological characteristics of serrated polyps of colorectum. Histopathology 47:32–40CrossRefGoogle Scholar
  6. 6.
    Torlakovic E, Skovlund E, Snover DC et al (2003) Morphological reappraisal of serrated colorectal polyps. Am J Surg Pathol 27:65–81PubMedCrossRefGoogle Scholar
  7. 7.
    O’Brien MJ, Yang S, Clebanoff JL (2004) Hyperplastic (serrated) polyps of the colorectum. Relationship of CpG island methylator phenotype and K-ras mutation to location and histologic subtype. Am J Surg Pathol 28:423–434PubMedCrossRefGoogle Scholar
  8. 8.
    Yang S, Farraye FA, Mack C et al (2004) BRAF and KRAS mutations in hyperplastic polyps and serrated adenomas of the colorectum: relationship to histology and CpG island methylation status. Am J Surg Pathol 28:1452–1459PubMedCrossRefGoogle Scholar
  9. 9.
    Mäkinen MJ (2007) Colorectal serrated adenocarcinoma. Histopathology 50:131–150PubMedCrossRefGoogle Scholar
  10. 10.
    Jass JR (2006) Hereditary non-polyposis colorectal cancer: the rise and fall of a confusing term. World J Gastroenterol 12:4943–4950PubMedGoogle Scholar
  11. 11.
    Vasen HFA, Möslein G, Alonso A et al (2007) Guidelines for the clinical management of Lynch syndrome (HNPCC). J Med Genet 44(6):353–362PubMedCrossRefGoogle Scholar
  12. 12.
    Goldstein NS (2006) Small colonic microsatellite unstable adenocarcinomas and high-grade epithelial dysplasias in sessile serrated adenoma polypectomy specimens. A study of eight cases. Am J Clin Pathol 125:132–145PubMedCrossRefGoogle Scholar
  13. 13.
    Goldstein NS (2006) Serrated pathway and APC (conventional)-type colorectal polyps. Molecular-morphologic correlations, genetic pathways, and implications for classification. Am J Clin Pathol 125:146–153PubMedCrossRefGoogle Scholar
  14. 14.
    Wright CM, Dent OF, Barker M et al (2000) Prognostic significance of extensive microsatellite instability in sporadic clinicopathological stage C colorectal cancer. Br J Surg 87:1197–1202PubMedCrossRefGoogle Scholar
  15. 15.
    Jass JR (2004) HNPCC and sporadic MSI-H colorectal cancer: a review of the morphological similarities and differences. Fam Cancer 3:93–100PubMedCrossRefGoogle Scholar
  16. 16.
    De Jong AE, Morreau H, van Puijenbroek M et al (2004) The role of mismatch repair gene defects in the development of adenomas in patients with HNPCC. Gastroenterology 126:42–48PubMedCrossRefGoogle Scholar
  17. 17.
    Jass JR, Baker K, Zlobec I et al (2006) Advanced colorectal polyps with the molecular and morphological features of serrated polyps and adenomas: concept of “fusion” pathway to colorectal cancer. Histopathology 49:121–131PubMedCrossRefGoogle Scholar
  18. 18.
    Fogt F, Brien T, Brown CA (2002) Genetic alteration in serrated adenomas: comparison to conventional adenomas and hyperplastic polyps. Human Pathol 33:87–91CrossRefGoogle Scholar
  19. 19.
    Matsumoto T, Iida M, Kobori Y et al (2002) Serrated adenoma in familial adenomatous polyposis: relation to germline APC mutation gene mutation. Gut 50:402–404PubMedCrossRefGoogle Scholar
  20. 20.
    Jass JR (1995) Colorectal adenomas in surgical specimens from subjects with hereditary non-polyposis colorectal cancer. Histopathology 27:263–267PubMedCrossRefGoogle Scholar
  21. 21.
    Jass JR, Stewart SM (1992) Evolution of hereditary non-polyposis colorectal cancer. Gut 33:783–786PubMedCrossRefGoogle Scholar
  22. 22.
    Rijcken FE, Hollema H, Kleibeuker JH (2002) Proximal adenomas in hereditary non-polyposis colorectal cancer are prone to rapid malignant transformation. Gut 50:382–386PubMedCrossRefGoogle Scholar
  23. 23.
    Yuen ST, Davies H, Chan TL et al (2002) Similarity of the phenotypic patterns associated with BRAF and KRAS mutations in colorectal neoplasia. Cancer Res 62:6451–6455PubMedGoogle Scholar
  24. 24.
    Hawkins NJ, Bariol C, Ward R (2002) The serrated neoplasia pathway. Pathology 34:548–555PubMedGoogle Scholar
  25. 25.
    Bariol C, Hawkins NJ, Turner JJ et al (2003) Histopathological and clinical evaluation of serrated adenomas of the colon and rectum. Mod Pathol 16:417–423PubMedCrossRefGoogle Scholar
  26. 26.
    Rubio CA (2002) Colorectal adenomas: time for reappraisal. Pathol Res Pract 198:615–620PubMedCrossRefGoogle Scholar
  27. 27.
    Young J, Simms LA, Biden KG et al (2001) Features of colorectal cancers with high-level microsatellite instability occurring in familial and sporadic settings: parallel pathways of tumorigenesis. Am J Pathol 159:2107–2116PubMedGoogle Scholar
  28. 28.
    Huang CS, O’Brien MJ, Yang S et al (2004) Hyperplastic polyps, serrated adenomas, and the serrated polyp neoplasia pathway. Am J Gastroenterol 99:2242–2255PubMedCrossRefGoogle Scholar
  29. 29.
    Kambara T, Simms LA, Whitehall VLJ et al (2004) BRAF mutation is associated with DNA methylation in serrated polyps and cancers of the colorectum. Gut 53:1137–1144PubMedCrossRefGoogle Scholar
  30. 30.
    Batts KP (2004) Serrated colorectal polyps. An update. Pathol Case Rev 9:173–182CrossRefGoogle Scholar
  31. 31.
    Bonté H, Flejou J-F (2003) Patterns of expression of MMR proteins in serrated adenomas and other polyps of the colorectum. Gut 52:611PubMedCrossRefGoogle Scholar
  32. 32.
    Snover DC, Jass JR, Fenoglio-Preiser C et al (2005) Serrated polyps of the large intestine. A morphologic and molecular review of an evolving concept. Am J Clin Pathol 124:380–391PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2007

Authors and Affiliations

  • S. H. Andersen
    • 1
    • 2
  • E. Lykke
    • 1
    • 2
  • M. B. Folker
    • 1
    • 2
  • I. Bernstein
    • 2
  • S. Holck
    • 1
    Email author
  1. 1.Department of PathologyHvidovre Hospital, Faculty of Health Sciences, University of CopenhagenHvidovreDenmark
  2. 2.Department of GastroenterologyHNPCC-register, Hvidovre Hospital, Faculty of Health Sciences, University of CopenhagenHvidovreDenmark

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