Pathophysiology
Summary
Colorectal polyps can be broadly categorized into neoplastic and non-neoplastic types. Among non-neoplastic polyps, hamartomatous polyps are disorganized yet benign growths of mature cells. Hamartomatous polyps are commonly associated with the autosomal dominant Peutz-Jeghers syndrome and juvenile polyposis syndromes. Juvenile polyps display small cryptic spaces histologically, most commonly affects the rectum, and can increase the risk of developing colon cancer. Hyperplastic polyps are another non-neoplastic polyp, characterized by benign epithelial proliferations rich in goblet cells.
Adenomatous polyps, or adenomas are most common neoplastic polyp. Adenomas have the potential for malignant transformation, especially if they are >1 cm and display higher degrees of dysplasia. Tubular adenomas and villous adenomas represent further categorizations, with villous adenomas having a higher likelihood of becoming cancerous. Sessile serrated polyps are also neoplastic polyps, and are flat, premalignant lesions with a serrated architecture throughout the crypts.
Genetic conditions such as familial adenomatous polyposis (FAP) significantly increase the risk of colorectal cancer. FAP is an autosomal dominant condition triggered by mutations in the APC tumor suppressor gene, which is involved in regulating the concentration of beta-catenin (binds E-cadherin). Nearly 100% of FAP cases progress to colon cancer. Variants of FAP include Gardner syndrome, which manifests with soft tissue tumors like osteomas, as well as cutaneous lesions, hypertrophy of retinal pigment epithelium, and dental abnormalities. Turcot syndrome is a form of FAP that associated with medulloblastomas. Lynch syndrome is an autosomal dominant disorder characterized by mutations in mismatch repair genes like MSH2 and MLH1, and is associated with multiple abdominal and pelvic cancers.
Colorectal cancer most commonly occurs as adenocarcinomas, and is associated with inflammatory bowel diseases and lifestyle factors like smoking & obesity. Genetic factors like APC mutations, which contribute to the initial development of adenomas, and mutations in the K-ras protooncogene, which contributes to the size and malignant potential of adenomas, also play a role. Malignant transformation occurs upon invasion of the basement membrane, resulting in adenocarcinoma. Loss of heterozygosity in the DCC and mutations in the p53 tumor suppressor genes contribute to malignancy.
Clinical features vary depending on the location: right-sided colon cancers are usually non-obstructive exophytic masses and can present with iron deficiency anemia, whereas left-sided colon cancers can are often obstructive, leading to hematochezia altered bowel habits. Colonoscopy is the gold standard for screening, while carcinoembryonic antigen (CEA) is used to monitor progression or recurrence. Preventative strategies include a high-fiber diet and regular aspirin use.
Lesson Outline
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FAQs
Colorectal polyps are mucosal outgrowths predominantly found in the colon. These polyps can be neoplastic or non-neoplastic. The most common neoplastic polyps are adenomatous polyps, also known as adenomas. Certain types of polyps, particularly those linked to familial syndromes, carry an elevated risk for developing into colorectal cancer.
Adenomatous polyps, or adenomas, are the most prevalent type of colon polyps and carry a risk of malignant transformation. This risk increases with the size of the polyp and the degree of cellular dysplasia. Hamartomatous polyps are benign, non-neoplastic growths composed of disorganized but mature cells, often associated with familial syndromes like Peutz-Jeghers and juvenile polyposis syndromes. Hyperplastic polyps are benign epithelial proliferations characterized by an abundance of goblet cells and a serrated architecture limited to the surface.
Familial adenomatous polyposis (FAP) is an autosomal dominant condition caused by a germline mutation in APC, a tumor suppressor gene. In FAP, only one APC allele has a germline mutation, while the second mutation occurs during person’s lifetime. FAP can cause thousands of adenomatous polyps in the colon at an early age, which are confirmed by colonoscopy. Without preventive colectomy, nearly 100% of FAP cases will progress to colorectal cancer.
Colorectal cancer manifests differently depending on its location. Right-sided colon cancers are often non-obstructive and may present with iron deficiency anemia. In contrast, left-sided colon cancers can cause colonic obstruction, leading to altered bowel habits and hematochezia. Risk factors include family history, smoking, alcohol consumption, obesity, and inflammatory bowel disease. Familial syndromes also significantly elevate the risk.
Several genes play pivotal roles in the development of colorectal cancer. The APC gene is often the first to mutate, leading to the initial formation of small adenomatous polyps. Subsequent mutations in the K-RAS proto-oncogene result in uncontrolled cell division and polyp growth. Tumor suppressor genes like p53 and Deleted in Colon Cancer (DCC) also contribute to the malignant transformation of polyps into colorectal cancer.
Lynch syndrome, also known as hereditary non-polyposis colorectal cancer (HNPCC), is the most common familial cause of colorectal cancer, but does not present with adenomatous polyps like FAP. It is an autosomal dominant condition caused by germline mutations in mismatch repair genes such as MSH2 and MLH1. Unlike FAP, which is associated specifically with colorectal cancer, Lynch syndrome also increases the risk of other abdominal and pelvic cancers, including endometrial, ovarian, and stomach cancers.
