What is Peutz-Jeghers syndrome?

Updated: Jun 06, 2020
  • Author: Jaime Shalkow, MD, FACS; Chief Editor: Cameron K Tebbi, MD  more...
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familial adenomatous polyposis (FAP) and Turcot syndrome; the familial hamartomatous polyposis syndromes include Peutz-Jeghers syndrome and juvenile polyposis.

Although juvenile polyps are common in children, adenomas are quite unusual. The latter are considered dysplastic precancerous lesions that are commonly seen in late adulthood. When discovered in children, they suggest one of several types of inherited CRC. [4]

Although the nomenclature is confusing, diffuse juvenile polyposis differs from juvenile polyposis coli. Diffuse juvenile polyposis is a syndrome with multiple polyps spread throughout the GI tract and presents in younger children (aged 6 months to 5 years); in juvenile polyposis coli, the polyps are confined to the rectosigmoid area and are typically found in older patients (aged 5-15 years). Hamartomatous polyps may also be found in patients with Cowden disease, Cronkhite-Canada syndrome, Bannayan-Riley-Ruvalcaba syndrome, and basal cell nevus syndrome. [5]

Colonic polyposis syndromes

Colonic polyposis syndromes include the following:

  • Nonfamilial polyposis - Isolated juvenile polyps (inflammatory polyps)

  • Familial polyposis - Adenomas (FAP, Gardner syndrome, Turcot syndrome) and hamartomas (juvenile polyposis, Peutz-Jeghers syndrome, Cowden disease, Cronkhite-Canada syndrome)

The lesions can be isolated to the intestine (eg, juvenile, lymphoid, familial adenomatous) or can involve other areas of the body (eg, Peutz-Jeghers syndrome, Gardner syndrome, Turcot syndrome). Most polyps of the GI tract are benign and result from hamartomas of the mucosa or lymphoid hyperplasia of the submucosal layer. However, adenomatous polyps represent a genetic alteration in the mucosa and have substantial malignant potential.

For study purposes, only the hamartomatous lesions and other nonfamilial lesions are discussed in this section. FAP is presented in detail below, with other cancer-predisposing entities.

Polyps occur in 1% of preschool-aged and school-aged children and are the most frequent cause of rectal bleeding in toddlers and infants aged 2-5 years. Juvenile polyps are the most common (80%), followed by lymphoid polyps (15%). [6]

Isolated juvenile polyps (nonmalignant) involve no family history of juvenile polyposis and fewer than 5 polyps confined to the colon.

Juvenile polyposis syndromes with malignant potential are classified as follows [7] :

  • Diffuse juvenile polyposis of infancy - Widespread polyposis of the entire GI tract in patients younger than 6 months.

  • Diffuse juvenile polyposis - Multiple polyps throughout the GI tract but concentrated in the stomach, distal colon, and rectum; usually occurs in patients aged 6 months to 5 years.

  • Juvenile polyposis coli - Multiple polyps confined to the distal colon and rectum in patients aged 5-15 years.

Lymphoid polyps (lymphoid nodular hyperplasia)

Lymphoid polyps (present in 15% of patients) are hyperplastic submucosal lymphoid aggregates, most likely due to a nonspecific infection (exposure to bacteria and viruses). Submucosal lymphoid tissue is prominent in children, particularly in the distal ileum (Peyer patches). These non-neoplastic polyps may occur in the rectum, colon, and terminal ileum.

Macroscopically, they appear as firm, round, submucosal nodules that are smooth or lobulated. They are never pedunculated. They often have a volcano-like appearance with mucosal ulceration, which leads to occult blood loss. Histologically, they are hyperplastic lymphoid follicles with a large germinal center covered by colonic mucosa. They develop in young children, with a peak incidence at age 4 years.

Patients present with anemia or, less frequently, with severe rectal bleeding. Barium enema and colonoscopy findings are helpful (in 50% of patients), and biopsy findings confirm the diagnosis.

Surgery is indicated only for uncontrolled bleeding and intussusception that does not respond to enema treatment. Otherwise, expectant measures are adequate because these polyps are benign and spontaneously regress.

Isolated juvenile polyps

Juvenile polyps are mucosal tumors that consist of excessive lamina propria and dilated cystic glands. They usually occur between 2 and 10 years of age and constitute 80% of all polyps in children, with a slight male predominance (3:2). [8]

Juvenile polyps typically present as painless rectal bleeding after defecation. A small percentage debut with prolapse. Prolapsed polyps appear as dark, beefy-red, pedunculated masses, in contrast to the lighter pink mucosal appearance of rectal prolapse. Most prolapsed polyps are erythematous and friable. Abdominal pain is uncommon and is primarily associated with intussusception. [9]

Colonoscopy is the procedure of choice for evaluation of juvenile polyps because those identified in the distal GI tract can be removed at the same time.

Juvenile polyps are solitary in half of patients. The majority are located proximal to the rectosigmoid junction. However, those distally located tend to cause more symptoms. Removal for histologic confirmation is indicated. The typical isolated juvenile polyp with no adenomatous changes has no potential for malignancy and tends not to recur.

Juvenile polyposis syndromes

Juvenile polyposis syndrome (JPS) is a genetic disorder associated with an increased risk of colorectal cancer. It is diagnosed in patients with more than 5 polyps at the colon/rectum, multiple polyps throughout the upper and lower GI tract, or any number of lesions with a family history of juvenile polyposis.

Surgery may be offered when the patient has too many polyps to treat endoscopically, or for patients with GI bleeding, anemia, diarrhea, or protein-losing enteropathy. [8]

Diffuse juvenile polyposis of infancy

This entity occurs within the first months of life and is not familial. Patients may present with diarrhea, rectal bleeding, intussusception, prolapse, bowel, protein-losing enteropathy, macrocephaly, clubbing of fingers and toes, and hypotonia. [10]

The entire GI tract is involved. One third of these patients have other congenital abnormalities such as Meckel diverticulum, malrotation, and heart lesions. [7]

Patients require total parenteral nutrition (TPN) and bowel rest, followed by selective resection.

Despite appropriate treatment, this disease is almost universally fatal; only 2 patients have been reported to survive after age 2 years. [10]

Diffuse juvenile polyposis

Diffuse or familial juvenile polyposis was originally identified as isolated or multiple hamartomatous polyps that occur in the colon and rectum of children aged 6 months to 5 years.

Patients present with bright red blood per rectum, anemia, abdominal pain, and rectal prolapse. Diffuse juvenile polyposis is inherited as an autosomal dominant trait [7] ; thus, if a parent has the condition, the risk of having an affected child is 50%.

Hamartomas are malformed colonic mucosa arranged in a bizarre fashion. Typically, hamartomas are not considered premalignant unless they are part of a polyposis syndrome.

Patients with diffuse juvenile polyposis have a 50% lifetime risk of colorectal carcinoma. This may be due to chronic inflammation that produces reactive hyperplasia, which then progresses to dysplasia or adenomatous changes. These polyps often have an ulcerated surface and demonstrate more epithelium with a villous or papillary configuration.

In addition to the epithelial dysplasia that occurs in juvenile polyps, adenomas are also often present. Thus, the approach to affected patients is similar to that taken in patients with FAP. Some authors recommend monitoring these patients with an annual complete blood cell (CBC) count (to detect anemia due to GI bleeding), semiannual colonoscopy, and subsequent colectomy if severe dysplasia, bleeding, or rapid polyp formation occurs. Others advocate for prophylactic colectomy.

Associated congenital defects include cleft palate, malrotation, polydactyly, and cranial abnormalities.

Juvenile polyposis coli

A child with 3-10 colonic polyps, any number of polyps in the GI tract outside of the colon, or one polyp and a family history of juvenile polyposis is considered to have the syndrome.

Most patients have 50-100 colorectal polyps; they may also have gastric and small intestinal polyps.

Identifying patients with this syndrome is fundamental because of the high risk for carcinoma (17%) at an early age; the mean age at diagnosis of carcinoma is 35.5 years. [11]

Close long-term surveillance is important. The amount of polyps increases the risk of chronic bleeding, which subsequently leads to iron deficiency anemia, hypoproteinemia, and failure to thrive. [12, 13]

Macroscopically, these polyps resemble the isolated juvenile polyps; however, histologically, they have more epithelium with a villous or papillary configuration. Epithelial dysplasia can occur. Adenomas can also be found in conjunction with juvenile polyps. [10] Lobular polyps have a higher propensity for a more severe dysplasia (47%) than non-lobular polyps (10%). [14]

According to the St. Mark's Polyposis Registry in London, the cumulative risk of cancer in patients with a juvenile polyposis syndrome is 68% by age 60 years. [15] Because the entity is transmitted in an autosomal dominant fashion, patients with a juvenile polyposis syndrome and their families must receive long-term follow-up. [16]

Some authors advocate prophylactic total colectomy and rectal mucosectomy with an endorectal pull-through (ERPT), [14] whereas others recommend regular screening with colonoscopy and subsequent colectomy if severe dysplasia, rapid polyp formation, or bleeding occurs. [17]

When intussusception occurs in children older than 2 years, the discovery of a specific lead point is not uncommon (22%); however, lead points are only found in 2-8% of children within the usual age range (6-18 months). [9] When a polyp is demonstrated as a lead point in a patient with intussusception, an evaluation may be indicated to identify polyposis syndromes.

Some hamartomas do not appear to have any malignant potential. However, germline mutations and somatic inactivation of STK11, SMAD4, BMPR1A, and PTEN genes in hamartomatous polyposis syndromes create an epithelial environment favorable for neoplastic transformation. [4]

Peutz-Jeghers syndrome

Peutz-Jeghers syndrome is a cancer-predisposing disorder that is inherited as an autosomal dominant trait. It is characterized by mucocutaneous pigmentation and hamartomatous polyps of the GI tract. Since the tumors tend to recur, extensive bowel resection should be avoided to prevent short bowel syndrome. [18]

In 1921, Peutz reported on the association of intestinal polyps with mucocutaneous pigmented spots of the mouth, hands, and feet. [19] From 1944-1949, in a study of 20 patients, Jeghers defined the 2 main features of the syndrome as melanotic spots on the buccal mucosa and lips (with variable melanin pigmentation on the face and digits) and polyposis of the intestinal tract. [10] The melanotic spots range from brown to black and occur in the rectum, around the mouth, and on the lips, buccal mucosa, feet, nasal mucosa, and conjunctivae. These spots are typically present at puberty. [10]

The polyps most commonly appear in the small intestine (55%), followed by stomach and duodenum (30%) and the colorectal area (15%).

Although adenomas can occur concurrently in the syndrome, these polyps are mostly hamartomas of the muscularis mucosa. They appear as pedunculated lobulated lesions, measuring from a few millimeters to several centimeters. Peutz-Jeghers syndrome is inherited as an autosomal dominant trait, [19] but de novo cases can also develop. It affects all ethnic groups with equal sex distribution [10] ; however, symptoms appear earlier in males (at age 5-10 years) than in females (at age 10-15 years). [19]

GI disturbances become apparent later, usually during early adolescence. Some patients present with an increased frequency of defecation, rectal bleeding, anemia, abdominal pain, vomiting, or recurrent episodes of intussusception. [19] Prolapse of rectal polyps in the first year of life, even in the absence of pigmentation, may indicate Peutz-Jeghers syndrome, at least in the familial cases.

Compared with the general population, patients with Peutz-Jeghers syndrome have a 13-fold increased risk of death due to GI cancer and a 9-fold increased risk for all other cancers. [10] The risk of death due to cancer by age 60 years is 50%, and it reaches 85% by age 70. Adenomatous and carcinomatous changes in the hamartomas have been reported. [20]

Peutz-Jeghers syndrome is closely related to early-onset non-GI malignancies, including breast, ovary, cervix, fallopian tube, thyroid, lung, gallbladder, bile duct, pancreatic, and testicular tumors. [5]

Screening tests to detect all these forms of cancer are recommended in children who present with abdominal pain or occult anemia and melanotic-pigmented spots. An aggressive screening and biopsy program should be undertaken, including an annual examination with CBC count, breast and pelvic examinations (with cervical smears and pelvic ultrasonography) in females, mammography at age 25 years, testicular examination in males, pancreatic ultrasonography, and biennial upper and lower endoscopy.

Extensive intestinal resections are contraindicated because of the recurrent nature of the polyps and the ensuing short-bowel syndrome that may result. Rapid growth, induration, severe dysplasia, villous changes, or polyps larger than 15 mm (which present a much higher risk of malignant transformation) suggest the need for a more aggressive intervention. [10]

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