Etiology

Adenomatous polyps are recognized as a precursor to colorectal cancer.[2] However, most polyps never develop into colorectal cancer.[12]

The risk of colorectal cancer in polyps <10 mm in size is extremely small. In a prospective study of 42,630 polyps, less than 1% of polyps <10 mm had high-grade dysplasia, and there were no cancers.[13] Other studies have confirmed a very low rate of advanced histology in polyps <10 mm.[14] 

There is a progressive increase in the proportion of polyps with advanced histology with increasing polyp diameter ≥10 mm. In a study of asymptomatic people (n=13,992) receiving screening colonoscopy, the proportion of polyps with advanced histology was 18.9% in 10 to 14 mm diameter polyps, 31.7% in 15 to 19 mm diameter polyps, 42.3% in 20 to 24 mm polyps, and 75% in polyps ≥25 mm.[14]

The risk of colorectal polyps increases with age.[8][9] Male sex, family history of colorectal cancer or polyps, previous polyps, and acromegaly also increase risk.

Pathophysiology

Colorectal cancers arise from dysplastic adenomatous polyps in the majority of cases. There is a multi-step process involving the inactivation of a variety of tumor-suppressor and DNA repair genes, along with simultaneous activation of oncogenes.[15] This confers a selective growth advantage to the colonic epithelial cell, and drives the transformation from normal colonic epithelium to adenomatous polyp to invasive colorectal cancer.[16]

Some of the most common genetic alterations occur in the oncogenes KRAS, PI3KCA, BRAF, and NRAS, and the tumor-suppressor genes TP53 and APC.[2]

In normal colorectal mucosa, cellular proliferation is limited to the lower half of the tubule. Cellular maturation and differentiation take place from the base of the crypt up to the mucosal surface. In adenomatous polyps this proliferation is not limited to the base of the tubule and the differentiation of cells is absent, leading to dysplasia.

The adenoma-carcinoma sequence is thought to take 10 years or more to complete.[1]

Classification

Histologic classification of colorectal polyps[1]

Conventional adenomas

  • Dysplasia grade

    • High grade

    • Low grade (most common)

  • Villousity

    • Tubular (most common)

    • Tubulovillous (contains >25% villous elements)

    • Villous (>75% villous elements)

Serrated lesions

  • Hyperplastic polyps (not considered precancerous)

  • Sessile serrated polyps

    • With cytologic dysplasia

    • Without cytologic dysplasia

  • Traditional serrated adenoma

Adenomas ≥10 mm in size or containing high-grade dysplasia or villous elements are considered advanced adenomas. Advanced adenomas are much more likely to evolve into colorectal cancer compared with nonadvanced adenomas.

Classification by size[2]

Diminutive: 1-5 mm diameter

Small: 6-9 mm diameter

Large: ≥10 mm diameter

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