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advanced serrated polyp

Monday 3 December 2012

advanced serrated polyps

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

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).

- 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.

See also

- 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.

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