Colon polyps pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sadaf Sharfaei M.D.[2]

Overview

Any form of unregulated growth in the colon may cause polyps. The exact etiology is unclear. However, risk factors may contribute to the formation of polyps. There are four different types of polyps including inflammatory, hamartomatous, serrated, and adenomatous polyps, which have different pathogenesis. Inflammatory polyps are non-neoplastic polyps that occur following intestinal inflammation, infections, or ischemia. Hamartomatous polyp is an overgrowth of mature cells and connective tissue elements including smooth muscle, lamina propria, and cartilage, and fat. They are covered by a hypertrophic epithelium. Serrated polyps are different polyps which have variable malignant potential. They include hyperplastic, sessile serrated and traditional serrated polyps. Hyperplastic polyps are the most common polyps. Hyperplastic polyp is infolding of the crypt epithelium that forms serration or saw-toothed appearance. Sessile serrated polyps are flask-shaped crypts, with dilatation and branching but not pedunculated. Traditional serrated adenomas are serrated polyps that are protuberant and pedunculated, which are located in left colon. Traditional adenoma also known as conventional polyps, are developed throughout the colon. They are the most prevalent polyps that have malignant potential.

Pathophysiology

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Inflammatory polyps

Hamartomatous polyps

Serrated polyps

  • Serrated polyps are different polyps which have variable malignant potential. They include hyperplastic, sessile serrated and traditional serrated polyps. They have various histopathologies and manifestations:
    • Hyperplastic polyps are the most common polyps.
      • They are small outpouching, less than 5 mm, which are located mostly in rectosigmoid area.
      • Hyperplastic polyp is infolding of the crypt epithelium that forms serration or saw-toothed appearance.
      • The molecular basis of this transformation is still unclear. However, it has been attributed to failure of apoptosis.
      • BRAF mutations are associated with crypt serration.[7]
      • There are three different subtypes of hyperplastic polyps based on degree of serration and content, including microvesicular type, goblet cell–rich type, and mucin-poor type.
    • Sessile serrated polyps:
      • They are flask-shaped crypts, with dilatation and branching but not pedunculated.[8][9]
      • Crypts grow along muscularis mucosae and creating inverted T- or L-shaped appearance.
      • Serration happens at the base and bottom of the crypts.
    • Traditional serrated adenomas:

Adenomatous polyps

  • Traditional adenoma also known as conventional polyps, are developed throughout the colon.
  • They are the most prevalent polyps that have malignant potential.
  • They have different gross appearances including pedunculated, sessile, flat, or depressed.
  • They might have different histopathologies including tubular, villous, or tubulovillous.

Genetics

  • The development of colon polyps is the result of multiple genetic mutations.
  • Genetic mutations might cause hereditary polyps disorders.

Familial adenomatous polyposis (FAP)

  • FAP is due to mutations in the following genes:
    • APC gene, which is located on chromosome 5 in band q21 or band q22 (5q21-q22).
    • MUTYH gene, which is located on chromosome 1 between bands p34.2 and p32.1 (5p34.3-p32.1).
    • MYH-associated polyposis (MAP) is caused by mutations in the MYH gene.

Peutz-Jeghers syndrome

Gardner's syndrome

Serrated polyposis syndrome

  • They develop multiple serrated adenomatous polyps in the upper part of the colon.

Familial juvenile polyposis

  • It is an autosomal dominant disorder. 
  • It increases risk of colorectal cancer.
  • It has extra-colonic tumors. 
  • There has been some association with the following genes:

Gross Pathology

  • On gross pathology, outpouching, pedunculated or flat lesions are characteristic findings of colon polyps.
  • On gross pathology, colon polyps may have a short or long stalk.
  • The polyp might have hemorrhagic stalk and colon wall with pale ribbon of mucosal covering.
Villous Adenoma of the Transverse colon By http://web2.airmail.net/uthman/specimens/index.html, Public Domain, https://commons.wikimedia.org/w/index.php?curid=840194
Tubulovillous Polyp of the Colon By http://web2.airmail.net/uthman/specimens/index.html, Public Domain, https://commons.wikimedia.org/w/index.php?curid=840172
Tubulovillous Polyp of the Colon By http://web2.airmail.net/uthman/specimens/index.html, Public Domain, https://commons.wikimedia.org/w/index.php?curid=840176
Adenomatous Polyp of the Colon By http://web2.airmail.net/uthman/specimens/index.html, Public Domain, https://commons.wikimedia.org/w/index.php?curid=840154
Adenomatous Polyp of the Colon By http://web2.airmail.net/uthman/specimens/index.html, Public Domain, https://commons.wikimedia.org/w/index.php?curid=840157
Longitudinally opened freshly resected colon segment showing cancer and four polyps. Plus a schematic diagram indicating a likely field defect (a region of tissue that precedes and predisposes to the development of cancer) in this colon segment. The diagram indicates sub-clones and sub-sub-clones that were precursors to the tumors. Source: Wikimedia.org By Bernstein0275 - Own work, CC BY-SA 3.0[10]
Colon polyp on Colonoscopy By 邱鈺鋒 - Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=37027826
Endoscopic image, 1 of 4, of an endomucosal resection of a sessile colon polyp By The original uploader was Kd4ttc at English Wikipedia - Transferred from en.wikipedia to Commons., CC BY 2.5, https://commons.wikimedia.org/w/index.php?curid=2175689

Microscopic Pathology

Hyperplastic polyp of the Colon. By Patho - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=19409502
Micrograph of a colorectal hyperplastic polyp. H&E stain. By Nephron - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=6427545
Colon adenoma By No machine-readable author provided. KGH assumed (based on copyright claims). - No machine-readable source provided. Own work assumed (based on copyright claims)., CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=444694


References

  1. Rüschoff J, Aust D, Hartmann A (2007). "[Colorectal serrated adenoma: diagnostic criteria and clinical implications]". Verh Dtsch Ges Pathol (in German). 91: 119–25. PMID 18314605.
  2. 2.0 2.1 Shussman, N.; Wexner, S. D. (2014). "Colorectal polyps and polyposis syndromes". Gastroenterology Report. 2 (1): 1–15. doi:10.1093/gastro/got041. ISSN 2052-0034.
  3. Singh, Rajvinder; Zorrón Cheng Tao Pu, Leonardo; Koay, Doreen; Burt, Alastair (2016). "Sessile serrated adenoma/polyps: Where are we at in 2016?". World Journal of Gastroenterology. 22 (34): 7754. doi:10.3748/wjg.v22.i34.7754. ISSN 1007-9327.
  4. Kahi, Charles J.; Vemulapalli, Krishna C.; Snover, Dale C.; Abdel Jawad, Khaled H.; Cummings, Oscar W.; Rex, Douglas K. (2015). "Findings in the Distal Colorectum Are Not Associated With Proximal Advanced Serrated Lesions". Clinical Gastroenterology and Hepatology. 13 (2): 345–351. doi:10.1016/j.cgh.2014.07.044. ISSN 1542-3565.
  5. 5.0 5.1 Li SC, Burgart L (2007). "Histopathology of serrated adenoma, its variants, and differentiation from conventional adenomatous and hyperplastic polyps". Arch. Pathol. Lab. Med. 131 (3): 440–5. doi:10.1043/1543-2165(2007)131[440:HOSAIV]2.0.CO;2. PMID 17516746.
  6. Zbuk KM, Eng C (2007). "Hamartomatous polyposis syndromes". Nat Clin Pract Gastroenterol Hepatol. 4 (9): 492–502. doi:10.1038/ncpgasthep0902. PMID 17768394.
  7. Kambara T, Simms LA, Whitehall VL, Spring KJ, Wynter CV, Walsh MD, Barker MA, Arnold S, McGivern A, Matsubara N, Tanaka N, Higuchi T, Young J, Jass JR, Leggett BA (2004). "BRAF mutation is associated with DNA methylation in serrated polyps and cancers of the colorectum". Gut. 53 (8): 1137–44. doi:10.1136/gut.2003.037671. PMC 1774130. PMID 15247181.
  8. Bettington, Mark; Walker, Neal; Clouston, Andrew; Brown, Ian; Leggett, Barbara; Whitehall, Vicki (2013). "The serrated pathway to colorectal carcinoma: current concepts and challenges". Histopathology. 62 (3): 367–386. doi:10.1111/his.12055. ISSN 0309-0167.
  9. O'Connell, Brendon M; Crockett, Seth D (2017). "The clinical impact of serrated colorectal polyps". Clinical Epidemiology. Volume 9: 113–125. doi:10.2147/CLEP.S106257. ISSN 1179-1349.
  10. "File:Image of resected colon segment with cancer & 4 nearby polyps plus schematic of field defects with sub-clones.jpg - Wikimedia Commons".

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