Colonic polyps in children:
From benign to serious

Edward J. Hoffenberg, MD

Polyps in the colon may be either harmless or precancerous. In both cases, symptoms are usually frightening to patients and parents. This review of four of the most common diagnoses in children with colonic polyps provides a rational approach to evaluating and managing these growths.

Blood in the stool. Visible rectal mass. Abdominal pain. Anemia. Four common pediatric conditions, each with a differential diagnosis that includes gastrointestinal polyps.

If you have ever cared for a child who, it turns out, has colonic polyps, you have probably supported parents as they struggled with fear stirred up by repeated episodes of visible blood in the stool—by far the most common presenting sign of polyps in the bowel. After diagnosis, parents continue to struggle with guilt about transmitting a disease to their children and with ongoing anxiety about malignancy.

To help patients and parents, pediatricians need to adopt a rational approach to evaluating and managing colonic polyps. This article provides an update on these growths in children and serves as a resource for delivery of care.

When to consider colonic polyps

As noted, passage of blood per rectum is the most common presenting sign of polyps in the colon. Other common signs are visible (prolapsed) polyp and unexplained anemia (Table 1). Less frequent manifestations include unexplained abdominal pain (due to traction of a pedunculated polyp on the intestinal wall) and recurrent intussusception (a complication of distal small bowel polyps). Colorectal cancer is rarely a presentation in children, although parents may bring their child to you because of a family history of polyps or colon cancer.

TABLE 1
When to consider colonic polyps

The blood per rectum is typically bright red, coating and mixed in with stool. It is usually visible only with defecation. Bleeding may be daily, intermittent, or quite infrequent. Large volume blood loss is extremely rare. Chronic blood loss may, however, lead to anemia and iron deficiency.

About 10% to 20% of children with polyps have a prolapsed polyp. Parents often report a strawberry-like mass that extrudes with straining but withdraws into the rectum within a few minutes.

Colonic polyps may present at any time, from the neonatal period into adulthood (Figure 1). Most commonly, patients are about 4 years old when their condition is diagnosed. Causes of rectal bleeding vary by age, so your evaluation should be tailored to the individual patient (Table 2). The main disorders to consider, in addition to polyps, are protein allergy, intussusception, fissure, infection, Meckel's diverticulum, inflammatory bowel disease, and lymphonodular hyperplasia.

TABLE 2
Age and the changing nature of rectal bleeding

Initial assessment of rectal bleeding

In a healthy child with intermittent rectal bleeding, begin your evaluation with a physical examination, including a digital rectal exam. Table 3 lists key areas of the exam.

TABLE 3
Initial evaluation of suspected colonic polyps

Always test fecal material for occult blood, even when blood appears obvious and the stool looks normal. Other laboratory tests to consider include a complete blood count with differential, prothrombin time, and a stool culture for bacterial and parasitic pathogens. These tests are usually normal.

If bleeding persists beyond a few weeks, further evaluation is warranted. Colonoscopy has largely replaced barium enema as the procedure of choice for evaluating diseases of the colon that cause bleeding.

Most children with polyps have one of four entities (Table 4), each of which is described in the discussion that follows. Other conditions characterized by polyps, such as Cowden disease and lipomas, are exceedingly rare and are not discussed here.

TABLE 4
Frequency of most common diagnoses

Juvenile polyps

Between 75% and 90% of children with polyps have juvenile polyps— the most common childhood polyp. Also known as "retention," "inflammatory," or "hamartomatous" polyps, such polyps occur singly or in clusters of two to four, typically in the rectosigmoid colon (Figure 2). Sometimes, another juvenile polyp (JP) develops a few years after initial diagnosis.

A JP is usually pedunculated: It has a stalk with a cap, like a mushroom (Figure 3). A polyp without a stalk is called a sessile polyp, and it may develop into a pedunculated polyp. On histologic evaluation, a JP contains well-differentiated, mature epithelial cells; dilated, disordered glands; and abundant acute and chronic inflammation.

A typical JP is not considered a risk factor for colorectal cancer. However, histologic evaluation is essential to exclude other disorders, especially adenomas. As many as 5% of juvenile polyps in children have focal areas showing adenomatous changes.¹ These are not adenomas, but they are worrisome because such polyps may be predisposed to malignant transformation. If smooth muscle is prominent, Peutz-Jeghers syndrome should be considered (this condition is discussed later in this article).

Juvenile polyps should be removed during colonoscopy via electrocautery. Children with one to four juvenile polyps in the rectosigmoid colon probably do not need follow-up after polypectomy unless rectal bleeding or another clinical manifestation of a JP recurs. Follow-up colonoscopy in six to 12 months may be indicated if any of the following applies:

• Family history of colon polyps.

• Five or more polyps identified at one colonoscopy or over several colonoscopies.

• Unusual features, such as a polyp in the right colon (proximal to transverse colon) or an adenomatous change in a JP.

Juvenile polyposis coli

JPC is a condition in which more than five (some experts say more than 10) juvenile polyps develop. A first-degree relative of an index case is considered to have the syndrome even if he (or she) has only one polyp.

In JPC, polyps are limited to the colon. In the rare case in which polyps are present in the upper and lower GI tracts, the syndrome is called generalized juvenile polyposis. Persons with this generalized form of juvenile polyposis may have protein-losing enteropathy and anemia and are at high risk for malignancy.

The exact frequency of JPC is unknown. According to published reports, however, as many as 10% of children with polyps have JPC.^1,2,3 Assuming that number is accurate, JPC may be the second most common polyp condition, although this is not often recognized in textbooks. Some of the difficulty distinguishing JPC from juvenile polyps arises from the fact that polyps may develop in the left colon in patients with either condition. Unless complete colonoscopy is performed in a child with one or two rectal polyps, polyps in the proximal colon may be missed and the condition misdiagnosed.

The genetic basis of JPC has been a source of confusion recently. In a study of 13 families with JPC, an association was made with mutations in chromosome 10q22-23.⁴ Other studies have been unable to confirm this finding, however. The 10q22-23 region is the site coding for a protein tyrosine phosphatase gene that has been linked to Cowden syndrome, a disorder associated with polyps and multiple hamartomas of skin, mucous membranes, thyroid, and breast.⁵ Some subjects in that study were subsequently found to have features that suggest Cowden syndrome.

Another association, this time with 18q21, was reported from a large kindred with juvenile polyps.⁶ This region is associated with regulation of TGF-B, a protein important in mediating growth-inhibiting signals. Whether this mutation is present in other affected families is unknown, and the genetic basis for JPC remains unclear. It is possible that different mutations may lead to the same phenotypic expression, which we call juvenile polyposis coli.

It is important to distinguish patients with juvenile polyps from those with JPC because evidence suggests that JPC increases the risk of colorectal cancer.⁷ My approach to managing children with JPC is to establish a surveillance program with the following goals:

• Make the correct diagnosis over time on the basis of the location, number, and histologic features of polyps

• Prevent complications such as malignancy, bleeding, anemia, and abdominal pain.

These goals are achieved by removing polyps as they form. For that reason, once JPC is diagnosed, I schedule another colonoscopy in six months to remove remaining polyps and monitor the rate of formation of new polyps. That is also the time to assess the rest of the GI tract with upper endoscopy and an upper GI series with small bowel follow-through.

The next colonoscopy is usually performed one year later. If no new polyps are noted, follow-up colonoscopy can be performed every two or three years. If exuberant formation of polyps continues, if adenomatous changes are observed within the polyp, or if the polyp is an adenoma, consider colectomy.

Peutz-Jeghers syndrome

PJS is characterized by the association of mucocutaneous pigmentation and hamartomatous polyps of the GI tract. PJS may be diagnosed during childhood or adolescence, although most patients are in their 20s when their condition is diagnosed. The syndrome has an incidence of about 1 in 80,000. Inheritance is thought to be autosomal dominant with variable penetrance. There is no known gender or ethnic predominance. The melanosis is most commonly noted on the lips (95%) and buccal mucosa (65% to 85%), and may also be evident on the nose, hands, and feet. Look for brown to black macules, 1 to 5 mm in diameter, which may be perceived as multiple freckles. Pigmented macules may fade around the time of puberty.

More than 90% of patients have multiple hamartomatous polyps, most commonly in the small bowel (65% to 95%), colon (60%), and stomach (50%). The small bowel polyps lead to the most common presentation: intermittent colicky abdominal pain, intussusception with intestinal obstruction, and GI bleeding and anemia. Extraintestinal polyps are sometimes found in the bronchi and genitourinary tract. The polyps in PJS contain smooth muscle in prominent bands, a feature that distinguishes them from juvenile polyps. There may, however, be a significant overlap in the histologic features of the two types of polyps.⁸

About 50% of persons with PJS develop extracolonic cancers, usually of the breast, cervix, ovary, testes, or pancreas. Adenomatous changes are seen in about 5% of PJS polyps, and the risk of colon cancer in patients with PJS is 2% to 13%.⁹

Guidelines for managing PJS, based on the fairly limited data available, have recently been published.⁹ Beginning at the age of 10 years, surveillance for upper GI tract lesions should be performed every two years by endoscopy and an upper GI series with small bowel follow-through. Identified polyps may be removed by endoscopy or enteroscopy, although surgery may be required for symptomatic distal small bowel polyps. Also starting at age 10 in male patients, a testicular exam should be performed yearly to detect tumors. If feminizing features develop, testicular ultrasonography is indicated to search for Sertoli cell tumor.

Once a patient reaches adulthood, emphasize the need for routine yearly evaluation for breast cancer (exam, mammography), uterine cancer (pelvic exam, Pap smear, ultrasonography), and pancreatic cancer (ultrasonography).

Familial adenomatous polyposis syndromes

The FAP syndromes, caused by mutations in the adenomatous polyposis coli (APC) gene on chromosome 5q2l-22, are the most important colonic polyps to diagnose because they almost always undergo malignant transformation. Mean age of onset of malignancy is 39 years, but cancer has been found in the first and second decades of life. In addition to adenocarcinoma of the colon, cancers of the ampulla of Vater, thyroid gland, stomach, pancreas, and brain (medulloblastoma and glioblastoma, called Turcot syndrome) and hepatoblastoma occur. Because the disease can affect areas outside the colon, "adenomatous polyposis coli" is a misnomer; I prefer "FAP syndromes."

FAP mutations occur in about 1 in 10,000 people and are usually inherited in an autosomal dominant fashion. Approximately one third of patients have no family history, however, and represent new germline mutations. The mean age at which the first adenomatous polyp develops is 16 years (Figure 4). Polyps are usually small (<5 mm diameter) and range from several to innumerable, sometimes carpeting the entire colonic mucosa.

The term Gardner syndrome is traditionally applied to patients with FAP who also have prominent extraintestinal tumors. The prevalence of these extraintestinal manifestations depends in part on how aggressively they are sought. Many patients with FAP have minor extraintestinal lesions. Therefore, FAP and Gardner are terms that probably represent variations of the same phenotypic spectrum derived from mutations in the APC gene.

The soft-tissue lesions in patients with FAP or Gardner syndrome include sebaceous and epidermoid cysts, lipomas, and subcutaneous fibromas. Osteomas of the skull and jaw, supernumerary teeth, and congenital hypertrophy of the retinal pigment epithelium are also common. Desmoid tumors may develop after surgical colectomy or other surgery and can cause obstruction, perforation, and abscess.

Diagnosis of FAP is based either on the presence of numerous adenomatous polyps in the colon or on genetic testing; the latter identifies about 80% of mutations¹⁰ (more than 100 mutations have been identified). The index case usually undergoes evaluation for FAP by having a protein truncation test, which screens for alterations in the protein product of the APC gene. If the test is positive, then analysis for identifiable mutations can be performed. If a specific mutation is identified, family members can undergo testing for that specific mutation. If, however, the index case tests negative on the protein truncation test, all family members should undergo monitoring for FAP (see next paragraph). For persons in whom FAP is suspected but who do not have known affected family members (that is, they are a probable de novo mutation), genetic testing may be confirmatory. Remember, however, that a negative test does not exclude FAP.

In patients with FAP, surveillance for adenomas by annual colonoscopy should begin no later than 10 to 12 years of age, or 10 years before the youngest diagnosis of colorectal cancer in the family.⁹ Once adenomas develop, the conservative approach is to recommend total colectomy and a permanent ileostomy. Ileorectal anastomosis preserves continence but retains a small area of affected tissue that requires continued surveillance. Ileoanal anastomosis removes the entire colonic mucosa and, in recent years, has gained favor. Less invasive techniques such as laparoscopic colectomy and one-step colectomy that avoids temporary ileostomy are increasingly popular.

Medical management of FAP is also evolving. Two published short-term trials have shown a decrease in the number and size of adenomatous polyps with sulindac (Clinoril) 150 mg orally bid¹¹ or celecoxib (Celebrex) 400 mg orally bid.¹² The mechanism is thought to be inhibition of the enzyme cyclooxygenase-2. A third drug, exisulind (Aptosyn), which is thought to act by inhibiting a novel enzyme, cGMP phosphodiesterase, is undergoing clinical trials in adults and children (For more information, see www.cellpathways.com , the Web site of the manufacturer of exisulind.) Until long-term data on safety and on efficacy of medical therapy for preventing cancer are available, such therapy should not replace colectomy and careful surveillance.

Once FAP is diagnosed, lifelong screening for extracolonic disease is required.⁹ Hepatoblastoma, which occurs in the first decade of life in about 1.6% of children with FAP, merits annual examination and consideration of a-fetoprotein determination and ultrasonography. Beginning at the age of 10 years, a thyroid exam should be performed annually to detect thyroid cancer, which occurs in about 2% of those with FAP. After 20 years of age, side-viewing endoscopy should be performed every one to three years to look for gastric, duodenal, and periampullary lesions, which can become malignant. Last, also starting at about 20 years, consider periodic evaluation for pancreatic cancer, which develops in about 2% of affected persons.

Spreading the word

Although polyps in children are often benign, a complete evaluation and timely diagnosis are essential to alleviating worrisome symptoms and detecting polyps that may become malignant. Table 5 summarizes the risk of malignancy by disease entity.

TABLE 5
Risk of malignancy by diagnosis

Pediatricians and parents can take advantage of expanding resources for education, support, and advocacy. The box on the left lists resources selected for their broad appeal. One example is the Hereditary Colon Cancer Association (HCCA, www.hereditarycc.org ), a new support group that has developed an excellent pamphlet for families and is taking a leading role in advocacy and education.

1. Hoffenberg E, Sauaia A, Maltzman T, et al: Symptomatic colonic polyps in childhood: Not so benign. J Pediatr Gastroenterol Nutr 1999;28:175

2. Cynamon H, Milov D, Andres J: Diagnosis and management of colonic polyps in children. J Pediatr 1989;114:593

3. Mestre J: The changing pattern of juvenile polyps. Am J Gastroenterol 1986;81:312

4. Jacoby R, Schlack S, Cole C, et al: A juvenile polyposis tumor suppressor locus at 10q22 is deleted from nonepithelial cells in the lamina propria. Gastroenterology 1997;112:1398

5. Liaw D, Marsh D, Li J, et al: Germline mutations of the PTEN gene in Cowden disease, an inherited breast and thyroid cancer syndrome. Nat Genet 1997;16:64

6. Howe J, Ringold J, Summers R, et al: A gene for familial juvenile polyposis maps to chromosome 18q21.1. Am J Hum Genet 1998;62:1129

7. Giardiello F, Hamilton S, Kern S, et al: Colorectal neoplasia in juvenile polyposis or juvenile polyps. Arch Dis Child 1991;66:971

8. Fulcheri E, Baracchini P, Pagani A, et al: Significance of the smooth muscle cell component in Peutz-Jeghers and juvenile polyps. Human Pathology 1991;22:1136

9. Burt R: Colon cancer screening. Gastroenterology 2000;119:837

10. Powell S, Petersen G, Krush A, et al: Molecular diagnosis of familial adenomatous polyposis. N Engl J Med 1993;329:1982

11. Giardiello F, Hamilton S, Krush A, et al: Treatment of colonic rectal adenomas with sulindac in familial adenomatous polyposis. N Engl J Med 1993;328:1313

12. Steinbach G, Lynch P, Phillips R, et al: The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis. New Engl J Med 2000;342:1946

THE AUTHOR is associate professor of pediatrics at the University of Colorado School of Medicine, Denver, and director, Center for Pediatric Inflammatory Bowel Diseases, The Children's Hospital, Denver. He is a recipient of a research grant from Cell Pathways, Inc., and a member of the scientific advisory board for the Hereditary Colon Cancer Association.

Resources

Hereditary Colon Cancer Association
www.hereditarycc.org

A new organization dedicated to promoting awareness, education, and prevention of hereditary colon cancer.

National Organization for Rare Disorders
www.rarediseases.org
PO Box 8923
New Fairfield, CT 06812-8923
800-999-6673

National organization of rare disorders. Diverse information on rare diseases, their support groups, treatment trials, meetings, etc.

Clinical trials, a service of the NIHwww.clinicaltrials.gov/ct/gui/clb

Provides information about clinical research studies; searchable by disease, location, key word, treatment, and sponsor.

National Center for Biotechnology Information
Online Mendelian Inheritance in Man
www.ncbi.nlm.nih.gov/Omim

Catalog of human genetic disorders with information in text, pictures, links to MEDLINE, and detailed references.

GeneClinicswww.geneclinics.org/profiles/fap/details.html

A resource for information on diagnosis, management, and genetic counseling for families affected with specific inherited disorders.

Kids with Gardners Syndromeclubs.yahoo.com/clubs/kidswithgardnerssyndrome

A place for kids with Gardner syndrome, familial adenomatous polyposis, and their friends.

Association of Cancer Online Resourceslistserv.acor.org/archives/(pjs.html)
listserv.acor.org/archives/(fap-gs.html)
listserv.acor.org/archives/(desmoid.html)

Finds lists of online support groups and allows you to enter your own search terms.

 

Edward Hoffenberg. Colonic polyps in children: From benign to serious. Contemporary Pediatrics 2001;9:118.