Peutz-Jeghers syndrome – causes, symptoms, diagnosis, treatment, pathology

Peutz-Jeghers syndrome – causes, symptoms, diagnosis, treatment, pathology

November 2, 2019 25 By Bertrand Dibbert


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. 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. 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. 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. 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. 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. 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.