9. Colorectal malignancies and their relationship to polypous lesions

Last updated on April 24, 2020 at 11:10

Colorectal carcinoma

Colorectal carcinoma (CRC) is an umbrella term for all cancers that can affect the colon and rectum. Carcinomas in the colon are the most common malignancy in the GI-tract, accounting for 95% of all GI cancers. Paradoxically, the small intestine accounts for 75 % of the overall length of the whole GI-tract, but somehow the tumors accumulate in the colon anyway. Three forms exist depending on the cause:

  • Sporadic CRC
  • Hereditary CRC
    • HNPCC
    • FAP
  • IBD-associated CRC

The most common histological type is the adenocarcinoma.

The symptoms of CRC are:

  • Haematochezia
  • Fatigue, anaemia – due to occult bleeding
  • Stenosis/occlusion
  • Diarrhoea or constipation. Or both, alternating
  • Perforation

The ascending colon has a larger lumen than the descending colon, so cancers in the ascending usually cause fewer symptoms and are therefore discovered later. The risk for occlusion is therefore also higher in the descending colon.

People above 50 should be screened with colonoscopy.

Adenocarcinoma of the colon

Adenocarcinoma accounts for 95% of all CRCs.

Pathogenesis: In 80% of cases is there a mutation in the APC gene. This gene codes for the protein APC, which inhibits a proto-oncogene called β-catenin. β-catenin activates Myc and cyclin D1 proteins, which are involved in the cell cycle. The remaining 20% of cases involve microsatellite instability (MSI). MSI is a condition where the DNA repair mechanism is impaired so that genes mutate more easily. Microsatellite instability in the case for colorectal carcinoma is commonly due to mutations in the genes MLH1 and MSH2. Both genes code for proteins involved in DNA repair. The presence of MSI can be shown with PCR.

Risk factors: The incidence of this type of cancer peaks at 60-70 years of age and is more frequent in men and in developed countries. What are the risk factors for this? The diet gets almost the whole blame. A low intake of vegetable fiber and high intake of refined carbohydrates and fat increases the risk and is the reason why it’s so frequent in the western countries.

Other risk factors:

  • Red meat
  • Alcohol
  • Processed meat
  • Obesity
  • Smoking
  • Lack of physical activity
  • Crohn’s disease
  • Ulcerative colitis

NSAIDs on the other hand, especially aspirin, are said to be protective against colorectal cancers as they inhibit the enzyme cyclooxygenase-2 (COX-2), which is highly expressed in the carcinomas.

Morphology: Adenocarcinomas are usually solitary masses, either polypoid or ulcerated. Tumors in the right colon are usually polypoid and exophytic while those in the left colon tend to be endophytic and annular, or circle-forming.

Grading: Like all cancers they are graded based on their differentiation. Well differentiated tumors are low grade and form well-formed glands or tubules that somewhat resembles adenomatous epithelium. Moderately differentiated tumors are the most frequent type, where glands and tubules are irregular and abnormal. Poorly differentiates tumors produce few glands, and the majority of the tumor consists of sheets of cells without glands.

Staging: The staging system TNM is used.

Complications: This type of cancer can metastasize by the lymphogenic way to regional lymph nodes. It can also spread by the portal circulation to the liver, or by the caval circulation to the lung if the tumor originated in the lower third of the rectum. Peritoneal seeding is uncommon.

Treatment: Surgical removal. There are some new immunotherapy treatments for different types of colorectal cancer. Cetuximab, panitumumab, pembrolizumab and nivolumab are all, as their names suggest, monoclonal antibodies. These antibodies target and bind to cell surface proteins like EGFR and PD-1, which are important for the cancer, if it expresses them.

Hereditary Nonpolyposis colorectal cancer (Lynch syndrome)

HNPCC is an autosomal dominant genetic disease which is associated with a very increased risk of colorectal cancer – they have an 80% risk of developing it in their lifetime. In addition to that, it’s also associated with cancer in endometrium, ovaries, small intestine, brain, ureters, hepatobiliary tract and skin. Patients with this disease tend to get colorectal cancer at much younger ages than for sporadic colon cancer and are often located in the right colon.

HNPCC is caused by germline mutations in the genes that code for proteins responsible for detection, excision and repair of errors during DNA replication. The majority of patients with HNPCC have mutations in the MSH2 and MLH1 genes, but the mutations can also happen in the MSH6 and PMS2 genes.

Despite the name of this disease, patients with this disease have a few polyps, but not as many as in FAP. Blood test can be taken to find out if a young person has these mutations. Some prevention of the disease can be achieved by taking small doses of aspirin every day. Prophylactic surgery is more used. Females with HNPCC are advised to perform a hysterectomy and remove the ovaries as well as the risk for cancer in these organs are very high.

Non-epithelial colorectal tumors

The same tumors discussed in the earlier topics of the GI-tract can occur in the colon and rectum as well. The most frequent one is the lipoma, which is most often submucous and benign. The others are rare, but can be:

  • Leiomyomas
  • GIST
  • Leiomyosarcoma
  • Angiosarcoma
  • Kaposi sarcoma
  • Lymphoma

Cancers from the stomach, lungs, the prostate, the breasts, ovaries can metastasize to the colon. Melanoma can also spread to the colon.

Tumors of the anal canal

1. Adenocarcinoma

Adenocarcinomas can appear in the upper part of the anal canal, where the mucosa is still the same as in the rectum.

2. Squamous cell carcinoma

The squamous cell carcinomas in the anal canal are induced by HPV and starts with a lesion just like in the CIN III slide of the cervix. Here it’s called anal intraepithelial neoplasia (AIN) and has the same staging.

This cancer is treated with radiotherapy.

3. Anorectal melanoma

Very rare and has a poor prognosis.

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8. Crohn's disease and ulcerative colitis

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10. Diseases of the appendix and the peritoneum

6 thoughts on “9. Colorectal malignancies and their relationship to polypous lesions”

  1. Hello 🙂
    I think you mean it can spread by the caval circulation to the lung* if the tumor originated in the lower third of the rectum.

  2. Hey!
    According to Robbins Adenomatous polyps are present in HNPCC, but not in excessive numbers (polyposis) as in FAP.

  3. Hi!
    APC doesnt code for b-catenin, but rather for a protein that inhibits it.

    Keep up the good work!

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