Home > E. Pathology by systems > Digestive system > Colon and rectum > serrated polyp

serrated polyp

Monday 3 December 2012

serrated polyps; colorectal serrated polyp; Serrated polyps of the colorectum

Definition: Serrated polyps of the colorectum form a group of related lesions which include aberrant crypt foci (ACF), conventional hyperplastic polyps, mixed polyps (admixed polyps), serrated adenomas (sessile serrated adenomas and traditional serrated adenomas).

Serrated polyp is a general term for any polyp that shows a serrated (sawtooth or stellate) architecture of the epithelial compartment. It is a heterogeneous group of lesions that mainly include hyperplastic polyp, sessile serrated adenoma/ polyp, and traditional serrated adenoma.

Types

Serrated polyps include:
- hyperplastic polyps (HP)
- serrated adenoma (SA)
- admixed hyperplastic-adenomatous polyps.

Serrated polyps are considered a morphological continuum encompassing:
- heteroplastic aberrant crypt foci (ACF),
- hyperplastic polyps (HP),
- admixed hyperplastic-adenomatous polyps,
and serrated adenoma (sessile serrated adenomas - SSA and traditional serrated adenomas - TSA).

There are other developmental pathways including a heteroplastic aberrant crypt foci-HP/serrated adenoma-carcinoma sequence and a heteroplastic aberrant crypt foci-adenoma-carcinoma sequence.

Heteroplastic aberrant crypt foci histopathologically resemble hyperplastic polyps and serrated adenoma.

Sporadic hyperplastic polyps are usually present in the left colon, are small, and are considered benign.

Adenocarcinoma arising in the setting of colorectal hyperplastic polyp or serrated adenoma, especially in patients with hyperplastic polyposis, has also been described.

The relationship between heteroplastic aberrant crypt foci, hyperplastic polyp, and colorectal cancer is less certain than that of dysplastic aberrant crypt foci.

Endoscopy

Serrated and hyperplastic polyps present endoscopic features that could help to differentiate them from adenomatous polyps.

HPs appear pale, glistening, and very similar to the surrounding mucosa and usually covered by mucus. The vascular network is weak, in contrast to that of hypervascular adenomas.

In addition, serrated polyps, mainly "sessile serrated adenomas" (SSAs), are typically sessile or flat, making their detection even more difficult.

Since the malignant potential of these lesions, particularly in the context of SPS, has been shown, early endoscopic detection becomes more important.

In this regard, the new advanced endoscopic techniques such as chromoendoscopy and narrow-band imaging (NBI) become significant.

Pathology

Confirmation of the serrated character of polyps can only be made by pathological study.

Serrated polyps are defined as epithelial lesions that show serrated appearance on histological section due to infolding of crypt epithelium.

There are different types of serrated polyps:
- hyperplastic polyp (HP), considered for a long time as a benign and non-premalignant colorectal lesion,
- sessile serrated adenoma (SSA),
- mixed polyp (MP),
- traditional serrated adenoma (TSA).

SSAs, TSAs and MPs are described as “advanced serrated polyps” and represent approximately 5%-15% of all serrated polyps found in colonoscopy patients.

- hyperplastic polyp (HP)

  • HPs are the most common colorectal polyps.
  • Sporadic HPs are usually small (2-5 mm), multiple and mainly distributed in the rectum and sigmoid colon.
  • HPs have been divided into two main histological subtypes:
    • microvesicular serrated polyps (MVSPs), in which columnar cells have mucin-filled vesicles within atypical cytoplasm.
      • MVSPs seem to be the precursor lesion of sessile serrated adenoma (SSA), especially when located in the right colon. In fact, both have the same molecular genetic abnormalities such as mutations in BRAF and CIMP.
      • MVSPs show large and regular stellate pit openings.
    • goblet cell serrated polyps (GCSPs) with conspicuous goblet cells that are predominantly found in the distal colon.
      • However, the large GCSPs are likely to have KRAS mutation, which is infrequently found in SSA.
      • There is some evidence that large GCSPs are potential precursors of dysplastic serrated polyps which show KRAS mutations.
    • A third type of hyerplastic polyps (HPs) has been added, mucin poor type, but its frequency and importance is lower than the two main HP types.

- sessile serrated adenoma (SSA)

  • SSA is an atypical HP variant described by Torlakovic and Snover in 1996.
  • SSAs are larger than (usually greater than 1 cm) HPs and more frequently located in the right colon.
  • Histologically, SSAs are distinguished from typical HPs by the presence of inverted T- or L-shaped crypt bases that reflect disordered proliferation.
  • Other features include dilated crypts and serration extending into the lower third of the crypt.
  • Focal nuclear stratification, mild nuclear atypia, or dystrophic goblet cells may be seen in the crypt bases.
  • Moreover, SSAs show increased mucin production, absence of enteroendocrine cells, and absence of a thickened basement membrane under the surface.
  • Other less common features include small foci of pseudostratification and eosinophilic change (identical to that seen in TSAs) of the surface epithelium.
  • Small prominent nucleoli, open chromatin, and irregular nuclear contours also might be present, along with mitoses in the upper third of the crypts or on the surface itself.
  • SSAs are thought to represent approximately 2% of all colonoscopically removed polyps, over 8% of all polyps that were previously diagnosed as HPs and around 18% of all serrated polyps.
  • SSAs have been associated with proximal CRCs, high level of CIMP, BRAF mutations and MSI-high.

- mixed polyp (MP)

  • MP, also called "SSA with cytological dysplasia" include two separate hyperplastic and adenomatous components.
  • One component is usually SSA (nondysplastic) whereas the second dysplastic component is either adenoma or TSA.

- traditional serrated adenoma (TSA)

  • TSAs, usually present on distal location, are dysplastic serrated polyps which lack SSA patterns and more closely resemble conventional adenoma with tubulovillous architecture.
  • Ectopic crypt formation, defined by the presence of crypts with bases not seated adjacent to the muscularis mucosae, is a feature that makes it possible to distinguish between TSAs and SSAs.
  • Columnar cells from the epithelium show eosinophilic cytoplasm, centrally placed elongated nuclei that are hyperchromatic and display pseudostratification.
  • There is no strong morphological evidence suggesting that SSAs are the precursor of TSAs, otherwise there are some histological and epidemiologic differences for keeping these lesions apart in different categories.
  • TSAs have been associated with distal location and MSS, CIMP-low CRCs with KRAS mutations.

Advances in the knowledge about the serrated pathway of carcinogenesis are making it possible to differentiate a new type of CRC with different natural history, prognosis and response to chemotherapy treatment.

For this reason it is important to be able to easily identify this kind of colorectal tumor and its precursors.

Identification of molecular markers in both polyps and cancers that follow this pathway will provide the opportunity of a better understanding of how these tumours grow and how we could explain differences in clinical presentation, evolution and symptoms in different types of CRC.

These molecular markers will also allow improvement in the identification of patients with serrated polyposis, moving forward the currently used clinical criteria, and will give us better rationale for appropriate management and surveillance intervals for patients and their relatives.

Open references

- Serrated polyposis syndrome: Molecular, pathological and clinical aspects
Carla Guarinos et al., 2012. Serrated polyposis syndrome: Molecular, pathological and clinical aspects. World J Gastroenterol 2012 May 28; 18(20): 2452-2461 - http://www.wjgnet.com/1007-9327/full/v18/i20/2452.htm

References

- Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127:2893-2917.

- Fearon ER, Vogelstein B. A genetic model for colorectal tumorigenesis. Cell. 1990;61:759-767.

- Jass JR. Classification of colorectal cancer based on correlation of clinical, morphological and molecular features. Histopathology. 2007;50:113-130.

- Leggett B, Whitehall V. Role of the serrated pathway in colorectal cancer pathogenesis. Gastroenterology. 2010;138:2088-2100.

- Torlakovic E, Skovlund E, Snover DC, Torlakovic G, Nesland JM. Morphologic reappraisal of serrated colorectal polyps. Am J Surg Pathol. 2003;27:65-81.

- Snover DC, Ahnen DJ, Burt RW, Odze RD. Serrated polyps of the colon and rectum and serrated ("hyperplastic") polyposis. In:Bosman ST, Carneiro F, Hruban RH, Theise ND.,editors.WHO Classification of tumours of the digestive system. Berlin: Springer-Verlag; 2010.

- Boparai KS, Mathus-Vliegen EM, Koornstra JJ, Nagengast FM, van Leerdam M, van Noesel CJ, Houben M, Cats A, van Hest LP, Fockens P. Increased colorectal cancer risk during follow-up in patients with hyperplastic polyposis syndrome: a multicentre cohort study. Gut. 2010;59:1094-1100.

- Yeoman A, Young J, Arnold J, Jass J, Parry S. Hyperplastic polyposis in the New Zealand population: a condition associated with increased colorectal cancer risk and European ancestry. N Z Med J. 2007;120:U2827.[PubMed]

- Chow E, Lipton L, Lynch E, D’Souza R, Aragona C, Hodgkin L, Brown G, Winship I, Barker M, Buchanan D. Hyperplastic polyposis syndrome: phenotypic presentations and the role of MBD4 and MYH. Gastroenterology. 2006;131:30-39.[PubMed] [DOI]

- Ferrández A, Samowitz W, DiSario JA, Burt RW. Phenotypic characteristics and risk of cancer development in hyperplastic polyposis: case series and literature review. Am J Gastroenterol. 2004;99:2012-2018.[PubMed] [DOI]

- Kalady MF, Jarrar A, Leach B, LaGuardia L, O’Malley M, Eng C, Church JM. Defining phenotypes and cancer risk in hyperplastic polyposis syndrome. Dis Colon Rectum. 2011;54:164-170.[PubMed] [DOI]

- Lage P, Cravo M, Sousa R, Chaves P, Salazar M, Fonseca R, Claro I, Suspiro A, Rodrigues P, Raposo H. Management of Portuguese patients with hyperplastic polyposis and screening of at-risk first-degree relatives: a contribution for future guidelines based on a clinical study. Am J Gastroenterol. 2004;99:1779-1784.[PubMed] [DOI]

- Rubio CA, Stemme S, Jaramillo E, Lindblom A. Hyperplastic polyposis coli syndrome and colorectal carcinoma. Endoscopy. 2006;38:266-270.[PubMed] [DOI]

- Boparai KS, Reitsma JB, Lemmens V, van Os TA, Mathus-Vliegen EM, Koornstra JJ, Nagengast FM, van Hest LP, Keller JJ, Dekker E. Increased colorectal cancer risk in first-degree relatives of patients with hyperplastic polyposis syndrome. Gut. 2010;59:1222-1225.[PubMed] [DOI]

- Samowitz WS, Albertsen H, Sweeney C, Herrick J, Caan BJ, Anderson KE, Wolff RK, Slattery ML. Association of smoking, CpG island methylator phenotype, and V600E BRAF mutations in colon cancer. J Natl Cancer Inst. 2006;98:1731-1738.[PubMed] [DOI]

- Walker RG, Landmann JK, Hewett DG, Worthley DL, Buttenshaw RL, Knight N, Webb PM, Whiteman DC, Whitehall VL, Leggett BA. Hyperplastic polyposis syndrome is associated with cigarette smoking, which may be a modifiable risk factor. Am J Gastroenterol. 2010;105:1642-1647.[PubMed] [DOI]

- Wallace K, Grau MV, Ahnen D, Snover DC, Robertson DJ, Mahnke D, Gui J, Barry EL, Summers RW, McKeown-Eyssen G. The association of lifestyle and dietary factors with the risk for serrated polyps of the colorectum. Cancer Epidemiol Biomarkers Prev. 2009;18:2310-2317.[PubMed] [DOI]

- Wynter CV, Walsh MD, Higuchi T, Leggett BA, Young J, Jass JR. Methylation patterns define two types of hyperplastic polyp associated with colorectal cancer. Gut. 2004;53:573-580.[PubMed] [DOI]

- Carvajal-Carmona LG, Howarth KM, Lockett M, Polanco-Echeverry GM, Volikos E, Gorman M, Barclay E, Martin L, Jones AM, Saunders B. Molecular classification and genetic pathways in hyperplastic polyposis syndrome. J Pathol. 2007;212:378-385.[PubMed] [DOI]

- Chan TL, Zhao W, Leung SY, Yuen ST. BRAF and KRAS mutations in colorectal hyperplastic polyps and serrated adenomas. Cancer Res. 2003;63:4878-4881.[PubMed]

- Kambara T, Simms LA, Whitehall VL, Spring KJ, Wynter CV, Walsh MD, Barker MA, Arnold S, McGivern A, Matsubara N. BRAF mutation is associated with DNA methylation in serrated polyps and cancers of the colorectum. Gut. 2004;53:1137-1144.[PubMed] [DOI]

- Beach R, Chan AO, Wu TT, White JA, Morris JS, Lunagomez S, Broaddus RR, Issa JP, Hamilton SR, Rashid A. BRAF mutations in aberrant crypt foci and hyperplastic polyposis. Am J Pathol. 2005;166:1069-1075.[PubMed] [DOI]

- Young J, Jass JR. The case for a genetic predisposition to serrated neoplasia in the colorectum: hypothesis and review of the literature. Cancer Epidemiol Biomarkers Prev. 2006;15:1778-1784.[PubMed] [DOI]

- Lazarus R, Junttila OE, Karttunen TJ, Mäkinen MJ. The risk of metachronous neoplasia in patients with serrated adenoma. Am J Clin Pathol. 2005;123:349-359.[PubMed] [DOI]

- Lindor NM. Hereditary colorectal cancer: MYH-associated polyposis and other newly identified disorders. Best Pract Res Clin Gastroenterol. 2009;23:75-87.[PubMed] [DOI]

- Jasperson KW, Tuohy TM, Neklason DW, Burt RW. Hereditary and familial colon cancer. Gastroenterology. 2010;138:2044-2058.[PubMed] [DOI]

- Young J, Barker MA, Simms LA, Walsh MD, Biden KG, Buchanan D, Buttenshaw R, Whitehall VL, Arnold S, Jackson L. Evidence for BRAF mutation and variable levels of microsatellite instability in a syndrome of familial colorectal cancer. Clin Gastroenterol Hepatol. 2005;3:254-263.[PubMed] [DOI]

- Frazier ML, Xi L, Zong J, Viscofsky N, Rashid A, Wu EF, Lynch PM, Amos CI, Issa JP. Association of the CpG island methylator phenotype with family history of cancer in patients with colorectal cancer. Cancer Res. 2003;63:4805-4808.[PubMed]

- Chan AO, Issa JP, Morris JS, Hamilton SR, Rashid A. Concordant CpG island methylation in hyperplastic polyposis. Am J Pathol. 2002;160:529-536.[PubMed] [DOI]

- Minoo P, Baker K, Goswami R, Chong G, Foulkes WD, Ruszkiewicz AR, Barker M, Buchanan D, Young J, Jass JR. Extensive DNA methylation in normal colorectal mucosa in hyperplastic polyposis. Gut. 2006;55:1467-1474.[PubMed] [DOI]

- Jarrar AM, Church JM, Fay S, Kalady MF. Is the phenotype mixed or mistaken? Hereditary nonpolyposis colorectal cancer and hyperplastic polyposis syndrome. Dis Colon Rectum. 2009;52:1949-1955.[PubMed] [DOI]

- Boparai KS, Dekker E, Van Eeden S, Polak MM, Bartelsman JF, Mathus-Vliegen EM, Keller JJ, van Noesel CJ. Hyperplastic polyps and sessile serrated adenomas as a phenotypic expression of MYH-associated polyposis. Gastroenterology. 2008;135:2014-2018.[PubMed] [DOI]

- Sweet K, Willis J, Zhou XP, Gallione C, Sawada T, Alhopuro P, Khoo SK, Patocs A, Martin C, Bridgeman S. Molecular classification of patients with unexplained hamartomatous and hyperplastic polyposis. JAMA. 2005;294:2465-2473.[PubMed] [DOI]

- Roberts A, Nancarrow D, Clendenning M, Buchanan DD, Jenkins MA, Duggan D, Taverna D, McKeone D, Walters R, Walsh MD. Linkage to chromosome 2q32.2-q33.3 in familial serrated neoplasia (Jass syndrome). Fam Cancer. 2011;10:245-254.[PubMed] [DOI]

- Brooker JC, Saunders BP, Shah SG, Thapar CJ, Suzuki N, Williams CB. Treatment with argon plasma coagulation reduces recurrence after piecemeal resection of large sessile colonic polyps: a randomized trial and recommendations. Gastrointest Endosc. 2002;55:371-375.[PubMed] [DOI]

- Iino H, Jass JR, Simms LA, Young J, Leggett B, Ajioka Y, Watanabe H. DNA microsatellite instability in hyperplastic polyps, serrated adenomas, and mixed polyps: a mild mutator pathway for colorectal cancer?. J Clin Pathol. 1999;52:5-9.[PubMed] [DOI]

- Goel A, Nagasaka T, Arnold CN, Inoue T, Hamilton C, Niedzwiecki D, Compton C, Mayer RJ, Goldberg R, Bertagnolli MM. The CpG island methylator phenotype and chromosomal instability are inversely correlated in sporadic colorectal cancer. Gastroenterology. 2007;132:127-138.[PubMed] [DOI]

- Hawkins NJ, Ward RL. Sporadic colorectal cancers with microsatellite instability and their possible origin in hyperplastic polyps and serrated adenomas. J Natl Cancer Inst. 2001;93:1307-1313.[PubMed] [DOI]

- Lee S, Cho NY, Choi M, Yoo EJ, Kim JH, Kang GH. Clinicopathological features of CpG island methylator phenotype-positive colorectal cancer and its adverse prognosis in relation to KRAS/BRAF mutation. Pathol Int. 2008;58:104-113.[PubMed] [DOI]

- Tanaka H, Deng G, Matsuzaki K, Kakar S, Kim GE, Miura S, Sleisenger MH, Kim YS. BRAF mutation, CpG island methylator phenotype and microsatellite instability occur more frequently and concordantly in mucinous than non-mucinous colorectal cancer. Int J Cancer. 2006;118:2765-2771.[PubMed] [DOI]

- Velho S, Moutinho C, Cirnes L, Albuquerque C, Hamelin R, Schmitt F, Carneiro F, Oliveira C, Seruca R. BRAF, KRAS and PIK3CA mutations in colorectal serrated polyps and cancer: primary or secondary genetic events in colorectal carcinogenesis?. BMC Cancer. 2008;8:255.[PubMed] [DOI]

- Jass JR. Colorectal polyposes: from phenotype to diagnosis. Pathol Res Pract. 2008;204:431-447.[PubMed] [DOI]

- Jass JR. Hyperplastic polyps and colorectal cancer: is there a link?. Clin Gastroenterol Hepatol. 2004;2:1-8.[PubMed] [DOI]

- Jover R, Nguyen TP, Pérez-Carbonell L, Zapater P, Payá A, Alenda C, Rojas E, Cubiella J, Balaguer F, Morillas JD. 5-Fluorouracil adjuvant chemotherapy does not increase survival in patients with CpG island methylator phenotype colorectal cancer. Gastroenterology. 2011;140:1174-1181.[PubMed]

- Minoo P, Moyer MP, Jass JR. Role of BRAF-V600E in the serrated pathway of colorectal tumourigenesis. J Pathol. 2007;212:124-133.[PubMed] [DOI]

- Rosenberg DW, Yang S, Pleau DC, Greenspan EJ, Stevens RG, Rajan TV, Heinen CD, Levine J, Zhou Y, O’Brien MJ. Mutations in BRAF and KRAS differentially distinguish serrated versus non-serrated hyperplastic aberrant crypt foci in humans. Cancer Res. 2007;67:3551-3554.[PubMed] [DOI]

- Huang CS, Farraye FA, Yang S, O’Brien MJ. The clinical significance of serrated polyps. Am J Gastroenterol. 2011;106:229-240; quiz 241.[PubMed] [DOI]

- East JE, Saunders BP, Jass JR. Sporadic and syndromic hyperplastic polyps and serrated adenomas of the colon: classification, molecular genetics, natural history, and clinical management. Gastroenterol Clin North Am. 2008;37:25-46, v.[PubMed] [DOI]

- Whitehall VL, Walsh MD, Young J, Leggett BA, Jass JR. Methylation of O-6-methylguanine DNA methyltransferase characterizes a subset of colorectal cancer with low-level DNA microsatellite instability. Cancer Res. 2001;61:827-830.[PubMed]

- Hesson LB, Hitchins MP, Ward RL. Epimutations and cancer predisposition: importance and mechanisms. Curr Opin Genet Dev. 2010;20:290-298.[PubMed] [DOI]

- Worthley DL, Whitehall VL, Buttenshaw RL, Irahara N, Greco SA, Ramsnes I, Mallitt KA, Le Leu RK, Winter J, Hu Y. DNA methylation within the normal colorectal mucosa is associated with pathway-specific predisposition to cancer. Oncogene. 2010;29:1653-1662.[PubMed] [DOI]

- Kudo S, Tamura S, Nakajima T, Yamano H, Kusaka H, Watanabe H. Diagnosis of colorectal tumorous lesions by magnifying endoscopy. Gastrointest Endosc. 1996;44:8-14.[PubMed] [DOI]

- Brooker JC, Saunders BP, Shah SG, Thapar CJ, Thomas HJ, Atkin WS, Cardwell CR, Williams CB. Total colonic dye-spray increases the detection of diminutive adenomas during routine colonoscopy: a randomized controlled trial. Gastrointest Endosc. 2002;56:333-338.[PubMed] [DOI]

- Hurlstone DP, Cross SS, Slater R, Sanders DS, Brown S. Detecting diminutive colorectal lesions at colonoscopy: a randomised controlled trial of pan-colonic versus targeted chromoscopy. Gut. 2004;53:376-380.[PubMed] [DOI]

- Lapalus MG, Helbert T, Napoleon B, Rey JF, Houcke P, Ponchon T. Does chromoendoscopy with structure enhancement improve the colonoscopic adenoma detection rate?. Endoscopy. 2006;38:444-448.[PubMed] [DOI]

- Le Rhun M, Coron E, Parlier D, Nguyen JM, Canard JM, Alamdari A, Sautereau D, Chaussade S, Galmiche JP. High resolution colonoscopy with chromoscopy versus standard colonoscopy for the detection of colonic neoplasia: a randomized study. Clin Gastroenterol Hepatol. 2006;4:349-354.[PubMed] [DOI]

- Rastogi A, Bansal A, Wani S, Callahan P, McGregor DH, Cherian R, Sharma P. Narrow-band imaging colonoscopy—a pilot feasibility study for the detection of polyps and correlation of surface patterns with polyp histologic diagnosis. Gastrointest Endosc. 2008;67:280-286.[PubMed] [DOI]

- Tischendorf JJ, Wasmuth HE, Koch A, Hecker H, Trautwein C, Winograd R. Value of magnifying chromoendoscopy and narrow band imaging (NBI) in classifying colorectal polyps: a prospective controlled study. Endoscopy. 2007;39:1092-1096.[PubMed] [DOI]

- Boparai KS, van den Broek FJ, van Eeden S, Fockens P, Dekker E. Hyperplastic polyposis syndrome: a pilot study for the differentiation of polyps by using high-resolution endoscopy, autofluorescence imaging, and narrow-band imaging. Gastrointest Endosc. 2009;70:947-955.[PubMed] [DOI]

- Liang JJ, Alrawi S, Tan D. Nomenclature, molecular genetics and clinical significance of the precursor lesions in the serrated polyp pathway of colorectal carcinoma. Int J Clin Exp Pathol. 2008;1:317-324.[PubMed]

- Sandmeier D, Benhattar J, Martin P, Bouzourene H. Serrated polyps of the large intestine: a molecular study comparing sessile serrated adenomas and hyperplastic polyps. Histopathology. 2009;55:206-213.[PubMed] [DOI]

- Hiraoka S, Kato J, Fujiki S, Kaji E, Morikawa T, Murakami T, Nawa T, Kuriyama M, Uraoka T, Ohara N. The presence of large serrated polyps increases risk for colorectal cancer. Gastroenterology. 2010;139:1503-1510.

- Torlakovic E, Snover DC. Serrated adenomatous polyposis in humans. Gastroenterology. 1996;110:748-755.[PubMed] [DOI]