Pathobiology

Colorectal lesions may be cancerous or noncancerous polyps. Some polyps that begin noncancerous may still hold malignant potential and become cancerous (adenomas and serrated polyps).1-3

About 75% of patients with CRC have no family history of CRC4

The evolution of colorectal adenoma to early-stage CRC typically takes more than 10 years, providing an important opportunity for screening and early detection4,5

Polyps larger than 5 mm in size were shown to have a 3% chance of harboring cancer, and the chance increases with increasing polyp size2

Basic Anatomy of Colon and Rectum1

Illustration of the basic anatomy of colon and rectum emphasizing key areas. Areas labelled are the ascending colon, cecum, rectum, anus, sigmoid colon, small intestine, descending colon, and the transverse colon.

The colon begins at the cecum and is divided into four parts:1

  • Ascending
  • Transverse
  • Descending
  • Sigmoid

Understanding Colon Pathology

Simple descending flowchart describing colon pathology related to polyps. The top of the flowchart describes colorectal polyps as non-cancerous growths in the inner lining of the colon/rectum. From there, the colorectal polyp box is sub-divided into non-neoplastic and neoplastic forms. The flowchart describes that non-neoplastic polyps are not considered malignant but neoplastic polyps have malignant potential and can progress into colorectal cancer. Examples of polyps that have malignant potential are adenomas, serrated polyps, and sessile serrated polyps.

Stages of Colorectal Cancer1

Illustrated cross-section of the colon showing multiple adenomas at varying stages of growth, with the final stage showing a stage 4 cancerous adenoma that has spread cancerous cells to other organs. Text within the graphic highlights that this type of progression from adenoma to colorectal cancer can happen over ten-plus years.
  • CRC usually begins as a polyp1
  • When a polyp progresses to cancer, it can grow into the wall of the colon/rectum (local)1
  • It may invade lymph vessels and spread to nearby lymph nodes (regional)1
  • Cancer cells may also be carried via blood vessels to other organs such as the liver or lung (distant)1
  • Exfoliation of cellular material occurs in advanced adenoma and CRC that is not seen in normal mucosa7
  • Learn more about risk factors and genetic contributions

Right-Sided Vs Left-Sided CRC8

Basic colon and rectum anatomy visual describing differences between right- and left-sided colorectal cancer. Right-sided, also known as proximal, colon cancer occurs in older ages and includes features such as microsatellite instability, hypermutation, and flat tumor morphology. Left-sided, also known as distal, colon cancer occurs in younger ages and includes features such as chromosomal instability pathway, and polyploid-like tumor morphology.

Characteristic Features of CRC by Anatomic Subsite8

Right-sided (proximal) CRC Left-sided (distal) CRC
Mucinous adenocarcinomas, sessile serrated adenomas Tubular, villous adenocarcinomas
Flat like morphology Polypoid like morphology
MSI-high and mismatch repair deficient tumors CIN-high tumors
Highly immunogenic, high T cell infiltration Low immunogenic
Metastases in peritoneal region Liver and lung metastases
More common in >50 year old More common in <50 year old
Predominantly occur in females Predominantly occurs in males
Better prognosis at early stages (stage I and II) Better prognosis at late stages (stage III and IV)

Related Topics

References

CRC: colorectal cancer; CSI/CIN: chromosomal instability pathway; MSI: microsatellite instability; SSP/A: sessile serrated polyp/adenoma; TSA: traditional serrated adenoma.


References

  1. ACS. Colorectal cancer facts and figures 2023-2025. Atlanta: American Cancer Society; 2023.
  2. Shussman N, Wexner SD. Colorectal polyps and polyposis syndromes. Gastroenterol Rep. 2014;2(1):1-15.
  3. Rex DK, Boland CR, Dominitz JA, et al. Colorectal cancer screening: recommendations for physicians and patients from the U.S. Multi-Society Task Force on Colorectal Cancer. Am J Gastroenterol. 2017;112(7):1016-1030.
  4. National Cancer Institute. Genetics of Colorectal Cancer (PDQ®)-Health Professional Version. Last Updated February 2, 2024. Accessed March 12, 2024. https://www.cancer.gov/types/colorectal/hp/colorectal-genetics-pdq
  5. Winawer SJ, Fletcher RH, Miller L, et al. Colorectal cancer screening: clinical guidelines and rationale. Gastroenterol. 1997;112:594-642.
  6. Gupta S, Lieberman D, Anderson JC, et al. Recommendations for follow-up after colonoscopy and polypectomy: a consensus update buy the US Multi-Society Task Force on colorectal cancer. Gastrointest Endosc. 2020;91(3):463-485.e5
  7. Ebner DW, Kisiel JB. Stool-based tests for colorectal cancer screening: performance benchmarks lead to high expected efficacy. Curr Gastroenterol Rep. 2020;22(7):32.
  8. Baran B, Mert Ozupek N, Yerli Tetik N, et al. Difference between left-sided and right-sided colorectal cancer: a focused review of literature. Gastroenterol Res. 2018;11(4):264-273.