Familial adenomatous polyposis

Definitions & Key takeaways

Familial adenomatous polyposis (FAP) is a rare, autosomal dominant condition characterized by the development of many polyps in the colon and rectum. These polyps can become cancerous over time, leading to a high risk of developing colorectal cancer. Surgery is often recommended to remove the polyps and prevent cancer from developing.

FAP is caused by mutations in the adenomatous polyposis coli (APC) gene. This gene normally helps to suppress tumor growth in the colon. When it is mutated, this function is lost, resulting in an increased risk of developing tumors. FAP can be diagnosed through genetic testing.

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With familial adenomatous polyposis, or simply FAP, familial refers to the fact that the disease runs in the family, and adenomatous polyposis refers to the fact that people affected develop multiple polyps that arise from the glands in the large intestine, which includes the colon and the rectum.
Now, the walls of the gastrointestinal tract are composed of four layers. The outermost layer is called serosa.
Then there’s the muscular layer, which contracts in a synchronized way to move food through the bowel. Then there is the submucosa, which consists of a dense layer of tissue through which blood vessels, lymphatics, and nerves run and branch into the mucosa and the muscular layer.
Finally, the inner lining of the intestine is called the mucosa; it surrounds the lumen of the gastrointestinal tract, and comes into direct contact with digested food.
The mucosa is organized as invaginations called the intestinal glands or colonic crypts, lined with large cells that are specialized in absorption.
Familial adenomatous polyposis is caused by an autosomal dominant mutation in the adenomatous polyposis coli gene or APC gene on chromosome 5q, which is a tumor suppressor gene.
Tumor suppressor genes stop cells from dividing uncontrollably. But if the gene is mutated and the cell is without a functioning APC s, the intestinal gland cells are more likely to accumulate mutations and start dividing faster than usual - ultimately giving rise to polyps, which are benign outgrowths of intestinal gland tissue.
Even though for any single polyp the chance that it evolves into cancer is generally quite low, polyps might accumulate additional mutations in other genes like the p53 gene (another tumor suppressor) or K-ras gene (a proto-oncogene), and with enough mutations, a cell might become completely unregulated and might start invading nearby tissue and become malignant.
Polyps can be classified by their gross appearance. Some are flat, which means that they don’t protrude into the lumen and are flat up against the mucosa.
Some are pedunculated which means that they do protrude into the lumen and remain attached to the wall by a stalk, just like a mushroom.
And some are sessile which means that they also protrude into the lumen, but have their base firmly attached to the mucosa.
People with familial adenomatous polyposis develop a specific kind of polyp called adenomatous polyps or simply adenomas, and they’re usually pedunculated or sessile.
Under the microscope, the cells look like normal colonic mucosa cells. There are three types of adenomas based on histology: tubular, with little hollow tubes within it, villous, with tiny tree-like branches, and tubulovillous, which look like a mix of the two with hollow tubes and tree-like branches.
Tubular adenomas are the most common type and have less malignant potential than villous adenomas, while tubulovillous adenomas have intermediate malignant potential.
In familial adenomatous polyposis, polyps usually begin to develop during puberty, and by the age of 30, a person might have hundreds to thousands of them, mostly in the descending colon and rectum.
Because they have so many polyps, there is a great chance that some of them will accumulate additional mutations and become malignant.
By the age of 40, most individuals will develop colorectal cancer, and by the age of 50, all of them will have colorectal cancer.
Familial adenomatous polyposis may be associated with extraintestinal manifestations like jaw cysts, sebaceous cysts (or cysts of the skin), and osteomas which are benign bone tumors.
In particular, the combination of polyposis, osteomas, and sebaceous cysts is known as Gardner’s syndrome. Some individuals develop attenuated familial adenomatous polyposis or AFAP, which is like a milder version of familial adenomatous polyposis.
People with attenuated familial adenomatous polyposis typically end up with fewer than 100 polyps, and these are typically in the ascending colon.
Also, the time course for when individuals develop polyps and cancer is less aggressive compared to familial adenomatous polyposis.
Most people with familial adenomatous polyposis don’t initially have symptoms. However, over time, if a polyp becomes big enough to obstruct the intestine, it can cause abdominal pain and constipation.
Also, some polyps can ulcerate and cause gastrointestinal bleeding, which can lead to iron deficiency anemia in the long run.
Diagnosis is usually done with colonoscopy, which is when a camera is inserted into the rectum and colon, and if there’s a polyp then a small biopsy is usually taken.
Fecal occult blood testing can be done to look for gastrointestinal bleeding. Ultimately, genetic testing has to be done to confirm the diagnosis of familial adenomatous polyposis.
Individuals with familial adenomatous polyposis need to be monitored regularly for signs of colorectal cancer. The only treatment option is prophylactic colectomy, which means surgically removing the part of the colon that has adenomas before they evolve into carcinomas.
Oftentimes, the entire colon has to be removed. All right, as a quick recap, familial adenomatous polyposis is an autosomal dominant condition caused by a mutation of the APC gene.
People affected develop many adenomatous polyps along the large intestine, which ultimately evolve into colorectal carcinoma.
For this reason, they have regular colonoscopic monitoring, and sometimes have a prophylactic colectomy.