AssessmentsFamilial adenomatous polyposis
Familial adenomatous polyposis
The genetic inheritance of familial adenomatous polyposis is .
USMLE® Step 1 style questions USMLE
A 35-year-old man presents to the office for a preventative health exam. He had asthma as a child and a benign skull osteoma. He is on no current medications. His family history is significant for his mother who had colon cancer diagnosed at age 29, his father who passed away from a heart attack, and his maternal aunt who passed away at 38 from colon cancer. He does not smoke or drink. He had a flexible sigmoidoscopy last year that showed over 100 polyps in his colon which were subsequently diagnosed as tubular adenomas. This patient is most likely to have inherited an abnormality in which of the following genes?
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, 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.