Peutz-Jeghers syndrome

Definitions & Key takeaways

Peutz-Jeghers syndrome (PJS), also known as hereditary intestinal polyposis syndrome, is an autosomal dominant disease characterized by polyps throughout the gastrointestinal tract, along with melanotic macules in the skin and mucosa, and a high risk of developing malignancy in various organs, including cancers of the GI tract, pancreas, breasts, lungs, ovaries, uterus, and testicles.

People with PJS have a higher risk of developing certain types of cancer, particularly in the colon, stomach, small intestine, pancreas, and breast. Regular surveillance and screening for these cancers are recommended for people with PJS. Treatment of PJS usually involves surgically removing the polyps, and regular surveillance with colonoscopies, upper endoscopies, and other imaging studies.

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Introduction0:00–0:26

Peutz-Jeghers syndrome, named after Dr. Jan Peutz, who first described it, and Dr.
Harold Joseph Jeghers, who later reported on it, is a rare autosomal dominant condition in which individuals develop polyps throughout their gastrointestinal tract, as well as dark spots called melanotic macules in their mouth, lips, genitalia, palms, and soles.

Physiology0:26–1:52

The large intestine is found in the abdominal cavity, which can be thought of as having two spaces - the intraperitoneal space and the retroperitoneal space.
The intraperitoneal space contains the first part of the duodenum, all of the small intestines, the transverse colon, sigmoid colon, and the rectum; the retroperitoneal space contains the distal duodenum, ascending colon, descending colon, and anal canal.
So the large intestines essentially weave back and forth between the intraperitoneal and retroperitoneal spaces. Now, the walls of the gastrointestinal tract are composed of four layers.
The outermost layer is the called serosa for the intraperitoneal parts, and the adventitia for the retroperitoneal parts.
Next is the muscular layer, which contracts to move food through the bowel. After that is the submucosa, which consists of a dense layer of tissue that contains blood vessels, lymphatics, and nerves.
And finally, there’s the inner lining of the intestine called the mucosa; which surrounds the lumen of the gastrointestinal tract, and comes into direct contact with digested food.
The mucosa has invaginations called intestinal glands or colonic crypts, and it’s lined with large cells that are specialized in absorption.

Pathology1:52–4:07

Peutz-Jeghers syndrome is caused by a mutation of the STK11 gene, which is a tumor suppressor gene that codes for a protein called STK11.
So without a functioning STK11 gene, the gastrointestinal cells are more likely to accumulate mutations and start dividing faster than usual - ultimately giving rise to polyps.
These polyps are benign outgrowths that arise along the gastrointestinal tract, mostly in the small intestine, but also in the stomach and large intestine as well.
Some polyps then go on to accumulate additional mutations in other tumor suppressor genes like the K-ras gene and p53 gene, and at that point they might evolve into cancer.
The chance for any single polyp to develop into cancer is generally quite low, but with people with many polyps, like those suffering from juvenile polyposis syndrome, the risk for cancer becomes significant.
The STK11 gene is expressed in a number of tissues, so individuals with Peutz-Jeghers syndrome also have an increased risk of developing extraintestinal cancers without polyps, such as pancreatic, breast, lung, ovarian, uterine, and testicular cancer.
Polyps can be classified by their gross appearance. Some are flat, which means that they don’t protrude into the lumen from the mucosa.
Some are pedunculated, which means that they do protrude into the lumen and remain attached to the mucosa by a stalk, just like a mushroom.
And some are sessile, which means that they also protrude into the lumen, but there’s no stalk and the entire tumor is attached to the mucosa.
People with juvenile polyposis syndrome develop hamartomatous polyps, sometimes just called hamartomas, and these are either sessile or pedunculated.
People with Peutz-Jeghers syndrome also have flat, dark mucocutaneous spots called melanotic macules, which appear during childhood and often fade as the person gets older.
These macules look a bit like freckles, but arise in different areas, like the mough, lips, genitalia, palms, and soles.

Symptoms and complications4:07–4:29

Individuals with Peutz-Jeghers syndrome often don’t have any symptoms; however, if a polyp becomes big enough to obstruct the intestine, it can cause abdominal pain and constipation.
Some polyps can also ulcerate and cause gastrointestinal bleeding, which can lead to iron deficiency anemia in the long run.

Diagnosis4:29–5:17

Diagnosis of Peutz-Jeghers syndrome is usually suspected in individuals with melanotic macules and typically requires colonoscopy, which is when a camera is inserted retrograde into the colon and rectum and to take pictures of abnormal looking polyps and a biopsy.
The presence of hamartomas is key in making the diagnosis. In addition, fecal occult blood testing is often done to look for evidence of gastrointestinal bleeding.
Ultimately, genetic testing has to be done to look for a mutation in the STK11 gene. If cancer is suspected, tumor marker screening in blood may be done, especially CEA for colon cancer, CA19-9 for pancreatic cancer, and CA-125 for ovarian cancer.

Treatment5:17–5:41

It’s important for individuals with Peutz-Jeghers syndrome to have frequent endoscopies to screen for colon cancer. Some individuals also undergo prophylactic surgery, which means removing the part of the intestine that has hamartomas before they evolve into carcinomas.
Some individuals also get prophylactic surgery for breasts and gonads, but that can affect childbearing. All right, as a quick recap, Peutz-Jeghers syndrome is an autosomal dominant syndrome caused by a mutation of the STK11 gene.

Review5:41–6:26

It is characterized by multiple hamartomas throughout the gastrointestinal tract, along with melanotic macules in the skin and mucosa, and a high risk of developing malignancy in various organs, including cancers of the GI tract, pancreas, breasts, lungs, ovaries, uterus and testicles.
For this reason, people with Peutz-Jeghers syndrome need regular monitoring through endoscopy and imaging techniques, and sometimes have prophylactic surgery.