Polyps and Tumors of the Intestines: Introduction
An intestinal polyp is defined as a tissue mass that projects from the wall of the bowel into the lumen. It can be broadly classified into two main categories, neoplastic and non-neoplastic. Within each category, there are multiple potential types of lesions, some of which are associated with a syndrome including multiple polyps, some of which may carry a risk of cancer, and others which are less numerous and unlikely to cause future problems. The neoplastic polyps typically have an abnormal epithelial component resulting from abnormal proliferation. Non-neoplastic polyps can be either hamartomas, with involvement of all three germ layers, or inflammatory in nature.
A child with polyps typically presents with painless rectal bleeding, although larger polyps can be associated with pain if they cause obstruction, if motility-induced traction on the polyp results in stretching of mesenteric attachments, or if a polyp serves as a lead point for intussusception. Polyps may be encountered in any region of the intestine, although the region most commonly affected is the colon. They may occur sporadically, or there may be a strong familial component. It is therefore important to obtain a thorough family history of polyps and gastrointestinal cancers.
The most common of the intestinal polyps encountered in childhood is the juvenile polyp, a benign non-neoplastic tissue growth with a marked propensity for causing rectal bleeding.1 These are relatively common, with most cases occurring before age 10 years and peaking at around ages 2–5 years. Isolated juvenile polyps are not associated with a genetic disorder and therefore not typically associated with a family history of polyps. If such history exists, other conditions must be suspected.
The etiology of isolated juvenile polyps is not well understood. In contrast to juvenile polyposis, in which multiple similar polyps occur throughout the GI tract (see below), there is no associated known gene mutation. Similar-appearing polyps (inflammatory polyps) are seen in children and adults with intestinal inflammation, and it is therefore likely that these lesions are in some way related to an inflammatory process. Long-term follow-up of patients with isolated juvenile polyps reveals no evidence of increased risk of intestinal malignancy,2 which is in marked contrast to juvenile polyposis syndrome.
Children with juvenile polyps typically present with recurring episodes of small-volume, bright red rectal bleeding, not associated with any abdominal discomfort or significant anemia. Bleeding appears to be caused by intestinal contents moving across the friable surface of these polyps, causing mechanical trauma and resulting in bleeding. Occasionally, more brisk bleeding can occur if the head of the polyp is avulsed from its stalk, creating a very brief and hemodynamically insignificant higher volume bleeding episode.
At endoscopy, no lesions are found in the upper gastrointestinal tract, and fewer than five polyps are seen during colonoscopy. These polyps typically have a smooth surface and a deep red color with very friable surface, often covered with mucus (Figure 22–1). Juvenile polyps vary in size considerably, and are often quite large, sometimes >2 cm. There is frequently evidence of recent bleeding on the head of the polyp, which has a markedly friable surface. The colonic mucosa surrounding the polyp typically is mildly nodular in appearance, giving a “chicken skin”-like appearance.3 Most of these polyps are easily removed during colonoscopy; even the larger ones can be removed piecemeal using a snare with electrocautery. After removal, bleeding ceases and seldom recurs. In young children, new polyps are occasionally found at repeat endoscopy, but new polyps are rarely seen in older children.
The major potentially confusing condition is juvenile polyposis syndrome, described in detail below. Painless rectal bleeding may also be caused by other conditions, such as arteriovenous malformations, other types of polyps, Meckel’s diverticulum, and inflammatory bowel disease. In the case of Meckel’s diverticulum and arteriovenous malformations, the bleeding is often massive and hemodynamically significant, in contrast to the minor bleeding typically seen with juvenile polyps. Patients with rectal bleeding secondary to inflammatory bowel disease typically suffer from diarrhea and cramping along with the rectal bleeding, which is almost never the case with juvenile polyps.
The diagnosis of rectal bleeding secondary to juvenile polyps depends on clinical suspicion, followed by colonoscopy and histological diagnosis. A complete colonoscopy should be performed, as polyps may be found throughout the length of the colon. Juvenile polyps are composed of cystic glands filled with mucus, with an intense inflammatory stroma and no smooth muscle elements. The surface epithelium may be slightly flattened but is otherwise normal. A degree of reactive atypia is often seen within the glands, probably due to the juxtaposition of epithelial elements with intense inflammation, but no true dysplasia is seen in these lesions.
The typical clinical presentation of recurrent, painless rectal bleeding that is not associated with diarrhea or weight loss should trigger colonoscopy. Because polyps may occur more proximal than the sigmoid colon, the patient should be adequately prepped and a full colonoscopy performed. All polyps should be removed with a snare and electrocautery, retrieved, and submitted for histopathological analysis. Accurate diagnosis depends on demonstration of the typical histological features described above (Figure 22–2).
A child with typical juvenile polyps is managed by colonoscopy with snare removal of the polyps. Rarely, an extremely large polyp or one in a difficult-to-reach location may need to be removed surgically.4 So long as bleeding stops, there are fewer than five polyps, there is no family history of polyposis, and histology is consistent with benign juvenile polyps, no further investigation or intervention is required. If bleeding does recur, repeat colonoscopy is indicated, and the possibility of juvenile polyposis syndrome should be considered.
This syndrome consists of the presence of multiple juvenile polyps occurring throughout life and not limited to the colon and rectum. The diagnostic criteria for juvenile polyposis are listed in Table 22–1.5,6 The diagnosis does not depend on the histological features, which typically are not distinguishable from isolated juvenile polyps. It must be remembered that a child with an initial diagnosis of simple juvenile polyp(s) may go on to meet criteria for juvenile polyposis syndrome. As a result, a child with a history of juvenile polyps who goes on to develop further symptoms of gastrointestinal bleeding or abdominal pain should be re-evaluated with colonoscopy and upper endoscopy.
|Diagnosis of JPS requires at least one of the following:|
|• >5 polyps in the colon and rectum|
|• Presence of any juvenile polyps in the stomach or small intestine|
|• Any number of juvenile polyps with a family history of juvenile polyposis|
Unlike typical juvenile polyps, about 30% of patients with a juvenile polyposis syndrome are found to have a gene mutation7 (Table 22–2). Currently, two causative genes have been found to be involved: MADH4 (also known as SMAD4) and BMPR1A. MADH4 codes for a protein in TGF-beta signaling pathway. BMPR1A codes for a membrane receptor in the TGF-beta super family. When activated, the TGF-beta pathway tends to suppress epithelial cell proliferation. Obviously, other, as yet unidentified, mutations or other alterations affecting expression of these genes must be involved in pathogenesis of juvenile polyposis syndromes to account for the 70% of patients who do not have identifiable mutations. Despite this statistic, 85% of patients with juvenile polyposis report a family history of polyps.8 Although 75% of patients will have an affected parent, approximately 25% of new cases are the result of a new gene mutation.
Children with juvenile polyposis syndrome have a very different course than patients with isolated juvenile polyps. Presenting symptoms are more severe than in isolated juvenile polyps, with prominent mucus present in the stools, and sometimes hypokalemia and hypoalbuminemia secondary to protein-losing enteropathy, as well as anemia from significant blood loss. These symptoms appear later than in isolated juvenile polyps, with a mean age at diagnosis of 18.5 years. The stomach is involved in 14%, the duodenum in 2%, and jejunum or ileum in 7%.8 There is a tendency for juvenile polyps to occur throughout life in these patients. Some patients with the MADH4 mutation also have hereditary hemorrhagic telangiectasia (HHT), a syndrome characterized by multiple systemic arteriovenous malformations, mucocutaneous telangiectasias, epistaxis, and risk of intracranial bleeding.9
A major concern is that patients with juvenile polyposis are at increased risk of gastrointestinal tract tumors, especially of the colon, stomach, and duodenum. A recent review of one Iowa kindred consisting of 29 affected individuals revealed that 11 developed colon cancer, 4 developed gastric cancers, 1 experienced cancer of the duodenum, and 1 had pancreatic cancer. This suggests a lifetime risk of gastrointestinal malignancies of around 55%.10
Affected individuals should undergo both upper endoscopy and colonoscopy to identify and remove as many polyps as possible, as this will reduce the risk of bleeding and protein-losing enteropathy. In severe cases with numerous polyps (Figure 22–3), total colectomy or gastrectomy may be necessary. Screening colonoscopy recommendations for affected individuals and their children are listed in Table 22–3.11
|Clinical Status||Begin Surveillance at Age||Recommended Screening||Interval|
|Proband||Diagnosis||Molecular genetic testing (MADH4, BMPR1A)/genetic counseling||Once; if negative, may repeat as new testing becomes available|
|(1) All affected individuals and (2) all family members with known mutation||Diagnosis, or age 15 years||CBC, colonoscopy, upper endoscopy||Yearly until no new polyps are found, and then every 3 years|
|All at risk individuals with family history but: (a) no family genetic testing done or (b) family genetic testing uninformative||Age 15 years||CBC, colonoscopy, upper endoscopy||Yearly until no new polyps are found, and then every 3 years|
|Family members testing negative for known family mutation||Age 15 years||CBC, colonoscopy, upper endoscopy||Repeat endoscopic studies every 10 years if negative|
Peutz–Jeghers syndrome (PJS) is defined by the association between gastrointestinal polyps and abnormal pigmentation of the skin and oral mucosa. It is inherited in an autosomal dominant fashion. PJS is also frequently sporadic, resulting from a new term line mutation. Affected individuals typically develop prominent freckle-like pigmentation around the mouth, lips, and on oral mucous membranes during the first decade of life, with appearance of rectal bleeding and abdominal pain secondary to polyps typically during the second decade of life. Polyps in this syndrome occur throughout the gastrointestinal tract, and are not limited to the colon and rectum.