Physical Address
304 North Cardinal St.
Dorchester Center, MA 02124
Pediatric Polyposis Syndromes
Introduction
Children and adolescents with gastrointestinal polyps may present symptomatically with rectal bleeding, abdominal pain, or intussusception. Alternatively, they may be asymptomatic and referred either because an adult family member has been affected with early-onset colorectal cancers (CRC) or there is a known family history of a polyposis syndrome. Many children fall into the latter category; they are asymptomatic and polyps are detected only as part of a screening program for an inheritable polyposis syndrome. Managing these children and families requires knowledge of the different polyposis syndromes, their inheritance and genetics, potential for malignant change, and pediatric complications.
Polyp Types
Gastrointestinal polyps in children fall into two major categories: hamartomas and adenomas ( Table 41.1 ). Solitary polyps in children are most commonly hamartomas, predominantly of the juvenile type, and such polyps are benign. Of the inherited syndromes, familial adenomatous polyposis (FAP) is more common than juvenile polyposis or Peutz-Jeghers polyposis. Table 41.2 outlines the different histological features of the polyps.
TABLE 41.1
Polyps and Polyposis Syndromes Seen in Childhood
Adenomatous Polyposis Syndromes
Hamartomatous Polyps
Inflammatory Polyps |
TABLE 41.2
Pathological Features of Gastrointestinal Polyps Seen in Children
| Polyp Type | |
| Juvenile polyp | Pedunculated, multilobulated, very vascular and may have ulcerated surface from autoinfarction. 1–3 cm in size. At microscopy, dilated cysts filed with mucin, abundant lamina propria with prominent inflammatory infiltrate, haphazardly arranged. |
| Peutz-Jeghers | Sessile or pedunculated with lobulated surface. At microscopy, frond-like structure, elongated branching arborizing strands of smooth muscle. |
| Tubular and villous adenoma | Pedunculated smooth, red, lobulated surface. 0.5–5 cm in size. At microscopy, glands and tubules ± inflammatory infiltrate. Villous adenomas are sessile and broad based. Dysplasia is always present. |
Clinical Presentation of Gastrointestinal Polyps
The most common clinical presentation of a large bowel polyp is painless rectal bleeding. Other symptoms attributed to polyps include abdominal pain, altered bowel habit, and prolapse of the polyp or the rectum. Diagnosis will be made upon full colonoscopy and polypectomy. The clinical presentation, family history, endoscopic appearance, pathological finding, and histological description of the polyp are all necessary to establish the correct diagnosis of a polyposis syndrome. Once a polyp has been identified at endoscopy, a carefully targeted family history must be taken to inquire if there are family members who have developed cancer, including the site of the cancers and age of onset. It is of particular importance to ascertain if cancer or polyps have occurred in first- or second-degree relatives before the age of 50 years. Table 41.3 summarizes key historical and physical exam findings in a patient with a suspected GI tract polyp. Taking such a history to develop a detailed family cancer pedigree may require the expertise of a multidisciplinary familial cancer clinic or polyposis registry.
TABLE 41.3
History and Examination in a Child With Possible Gastrointestinal Polyps
History
|
Examination
|
FAP, Familial adenomatous polyposis; GI, gastrointestinal.
∗ See Table 41.5 .
The Single Hamartomatous Polyp (the Juvenile Polyp)
The single hamartomatous (or juvenile) polyp has been reported to have a prevalence of 0.1% to 2%. The commonest presentation is painless bright red rectal bleeding with blood seen on wiping or mixed in the stool. Occasionally, parents will report seeing the polyp prolapsing out of the rectum at defecation or passing into the diaper after spontaneous auto amputation. They measure 0.5 cm to 5 cm and should be removed at pancolonoscopy and polypectomy.
Seventy percent of juvenile polyps are found in the rectum, or rectosigmoid. The rest are found more proximally—hence the need for pancolonoscopy. Single or solitary juvenile polyps are benign and confer no future risk of malignancy. Dysplasia has rarely been described in children with solitary juvenile polyps. However, presently it is unknown whether children who present with a single polyp in childhood may continue to form polyps over time. One series suggests recurrence of a juvenile polyp after removal of a solitary hamartomatous polyp in up to 16% of patients.
Polyps should be removed even when discovered incidentally. If a polyp is found to be solitary after full colonoscopy, and there is no relevant family history, endoscopic polypectomy should be sufficient treatment. After polypectomy, parents must be made aware that juvenile polyps may be the first feature of a hamartomatous polyposis syndrome. If fresh symptoms arise, the child should be reinvestigated. If multiple juvenile polyps are found (>3) or there is a positive family history (e.g., colonic polyps or early onset CRC), a hamartomatous or juvenile polyposis syndrome (JPS) should be considered and an alternative approach considered.
Hamartomatous Polyposis Syndromes
Hamartomatous polyposis syndromes are a rare group of hereditary autosomal dominant disorders. The polyps themselves are benign but the polyposis syndromes confer a potential for developing CRC and extracolonic cancers mediated through a hamartoma–carcinoma sequence. The hamartomatous polyposis syndromes include JPS, Peutz-Jeghers syndrome (PJS), and PTEN hamartoma tumor syndrome.
Juvenile Polyposis Syndrome
JPS is a rare condition affecting between 1 in 100,000 and 1 in 160,000 people and is inherited in an autosomal dominant manner. It is characterized by the development of multiple hamartomatous polyps of the gastrointestinal (GI) tract. The GI tract phenotype is variable, and extraintestinal manifestations can occur in patients with JPS ( Table 41.4 ).
TABLE 41.4
Extraintestinal Findings in Patients With Juvenile Polyposis Syndrome
| Cardiac: Mitral valve prolapse Ventricular septal defect (VSD) + pulmonary stenosis, bicuspid aortic valve |
12%–13% |
| Vascular/Skin: Telangiectasia, pigmented nevi, splenic artery aneurysm Bilateral iliac artery aneurysm, pulmonary AVM |
9%–56% |
| Cranial/Skeletal: Macrocephaly, hydrocephalus, cleft palate, polydactyly, hypertelorism |
12%–70% |
| Endocrine/Behavioral: Thyroid disease, Attention Deficit Hyperactivity Disorder (ADHD)/autism |
9% |
| Neurology :Epilepsy | 22% |
| Urologic: Undescended-testes |
17% |
AVM, Arteriovenous malformation.
JPS is diagnosed by use of the following criteria (in the absence of extraintestinal features consistent with PTEN hamartoma tumor syndrome):
-
Five or more juvenile polyps of the colon or rectum, or
-
Juvenile polyps in other parts of the GI tract, or
-
Any number of juvenile polyps and a positive family history.
There are three phenotypic forms:
- 1.
Juvenile polyposis of infancy (JPI) characterized by diarrhea, protein-losing enteropathy, bleeding, and rectal prolapse
- 2.
Juvenile polyposis coli where polyp growth involves only the colon
- 3.
Generalized juvenile polyposis in which polyp growth can affect the colon, stomach, and small bowel
JPI has an onset in infancy presenting with anemia and hemorrhage, diarrhea, protein-losing enteropathy, intussusception, and rectal bleeding. The course in such infants is fulminant and, even despite colectomy, in severe cases death occurs usually before the age of 2 years. These patients often have gene mutations identified within both the PTEN and BMPR1A region.
Patients with juvenile polyposis coli and generalized juvenile polyposis develop 50 to 200 polyps in their lifetime. The total number of polyps needed to make the diagnosis remains controversial—between 3 and 5 polyps. Patients present with chronic and acute gastrointestinal bleeding, anemia, prolapsed rectal polyps, abdominal pain, and diarrhea.
Cancer Risk in Juvenile Polyposis Syndrome
There is little doubt that juvenile polyposis is a premalignant condition. JPS carries an increased risk of GI malignancy, with a lifetime risk of 38% to 68% (including patients who were participating in a JPS surveillance program and those diagnosed with JPS at the time of cancer diagnosis). The Johns Hopkins Polyposis Registry data identified a relative risk (RR) for colorectal cancer of 34.0 in individuals with JPS, a mean age of diagnosis of 43.9 years, and a cumulative lifetime risk of 38.7%. Similarly, the St Mark’s Hospital UK Polyposis Registry described a cohort in which 8.3% of polyps in JPS contained mild/moderate dysplasia and 14% of patients developed cancers. Referral bias may be a factor in these registry populations. From the pediatric perspective, it is harder to quantify the risk of cancer during childhood. One series reported on a single cohort of 257 children with one or more juvenile polyps. Nearly 4% of children with juvenile polyps had neoplasia, with nine children having low-grade dysplasia and one 11.8-year-old boy having adenocarcinoma. All of the patients with neoplasia had more than 5 polyps detected during the initial colonoscopy, with a range of 7 to more than 100. Malignancy in children or teenagers with JPS under 18 years is exceptionally rare.
Genetics of Juvenile Polyposis
Individuals with JPS may harbor germline mutations in the SMAD4 (18q21.1) or BMPR1A (10q23.2) genes. A gene mutation ( SMAD4 or BMPR1A ) will be identified in 40% to 60% of patients with JPS. Approximately 25% of patients have de novo mutations. Germline missense mutations in ENG were identified in 2/14 very young patients with JPS in whom there was no identified mutation in the SMAD4 and BMPR1A genes. Genotype-phenotype correlations are inconsistent, with variable age at presentation and number of polyps even in the same family with JPS. When consulting a family known to have JPS, it is beneficial to isolate the specific family gene mutation so that predictive genetic testing can be employed to test other at-risk family members, enabling appropriately timed screening colonoscopies.
SMAD4—HHT.
JPS patients with SMAD4 mutation may have features of hereditary hemorrhagic telangiectasia (HHT). HHT is an autosomal dominant disorder of vascular dysplasia characterized by mucocutaneous telangiectasias and organ arteriovenous malformations (AVMs), mainly affecting the lungs, liver, and brain. Telangiectasias and AVMs are prone to bleeding, leading to chronic epistaxis and/or GI bleeding. Pulmonary and brain AVMs have the potential for life-threatening hemorrhage. HHT susceptibility genes encode proteins in the transforming growth factor β pathway, to which pathway SMAD4 and BMPR1A belong. A report of a cohort of 41 juvenile polyposis families described that nearly all juvenile polyposis SMAD4 patients have the overlap syndrome with HHT and concluded that systematic HHT screening is recommended for all JPS patients with SMAD4 mutations. ,
BMPR1A with PTEN.
BMPR1A is located in the same chromosomal region as PTEN , and larger deletions involving both genes have been reported. Children with deletions in both BMPR1A and PTEN genes may present with JPI. JPI is a distinct, aggressive subtype of JPS characterized by severe gastrointestinal symptoms, including diarrhea, intestinal bleeding, rectal prolapse, protein-losing enteropathy, and increased risk of intussusception resulting in high infant mortality. , JPI patients have been reported with congenital abnormalities, including macrocephaly and generalized hypotonia.
You're Reading a Preview
Become a Clinical Tree membership for Full access and enjoy Unlimited articles
If you are a member. Log in here