OVERVIEW: What every practitioner needs to know

Are you sure your patient has Juvenile polyposis (JP)? What are the typical findings for this disease?

Juvenile polyposis is a rare autosomal dominant condition characterized by multiple juvenile polyps primarily in the colorectum but can also be found throughout the upper gastrointestinal tract. The diagnosis of JP can be challenging because of the overlap with other hamartomatous polyposis syndromes. The term ‘juvenile’ refers to the type of polyps and not the age of onset of polyps. Patients with JP have an increased risk of developing colorectal cancer.

Painless rectal bleeding presenting in the first decade of life is the most common presentation of JP. Anemia may be present. Polyps are most frequently found in the colorectum but can develop in the stomach and small bowel. Patients can present with blood and mucus passed rectally making the differentiation from an inflammatory condition such as infection or inflammatory bowel disease important.

It is important to take a family history. Presence of early onset colorectal cancer or history of polyps in relatives raises the possibility of an inherited polyposis syndrome. A juvenile polyp can prolapse through the rectum. A patient may be referred as a “rectal prolapse”. It can be helpful to ask parents to take a photograph of the prolapse to help differentiate these conditions. The polyps of JP usually appear by the third decade.

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A combined syndrome of Juvenile polyps and hereditary hemorrhagic telangiectasia (HHT) has recently been reported. Characteristics of HHT include skin and mucosal telangiectases, pulmonary, cerebral and hepatic arteriovenous malformations. Patients with HHT frequently have a history of recurrent epistaxsis.

It is important to make the distinction that a solitary juvenile polyp very likely does not increase the risk of colorectal cancer. In contrast patients with multiple juvenile polyps have a significantly increased risk of malignancy. Patients with JP require life long cancer surveillance.

Rarely infants can present with diarrhea, rectal bleeding and protein-loosing enteropathy due to an extensive polyposis burden secondary to juvenile polyposis.

Patients with JP have been reported with other morphologic characteristics such as digital clubbing, congential heart disease, cleft lip or palate and alopecia. These phenotypes likely represent a spectrum of underlying mutations not currently identified/characterized.

Diagnosis of Juvenile polyposis

A colonoscopy is recommended at the onset of symptoms or in early teens if there is a family history of JP.

The number of polyps required to classify a patient with JP has been debated. Most experts accept the following clinical criteria to classify a patient with JP. At least one of:

1. Five or more juvenile polyps in the colorectum

2. juvenile polyps throughout the gastrointestinal tract

3. any number of juvenile polyps with a family history of juvenile polyps

In young pediatric patients with two or three juvenile polyps who may not currently meet the diagnostic criteria for JP, close follow up is suggested. These patients may be developing JP and only reevaluation will determine the ultimate phenotype.

Most juvenile polyps can be safely removed endoscopically using snare polypectomy.

Histologic review by the pathologist is imperative to make the diagnosis. It is often helpful to discuss possible JP cases with the pathologist as the interpretation of the histology can be challenging.

Pathology of the polyps

The term juvenile refers to the type of polyps and not the age of onset of polyps.

Juvenile polyps have a smooth surface, are often covered by exudate and may be sessile or pedunculated. Size is variable ranging from a few millimeters up to 5 centimeters. Histologically juvenile polyps exhibit an expansion of the lamina propria, with dilated cysts filled with mucin. There is often a prominent inflammatory infiltrate.

What other disease/condition shares some of these symptoms?

Solitary juvenile polyps are a frequent cause of gastrointestinal bleeding in children. There is not strong evidence to support an increased risk of gastrointestinal cancer in children with a solitary juvenile polyp.

If a child has two or three juvenile polyps this raises the possibility of juvenile polyposis.

Careful clinical evaluation including examination of the patient’s skin and review of the polyp pathology usually makes the specific polyposis syndrome diagnosis possible. Sometimes in children when the phenotype has not fully developed it may take longer to characterize the underlying condition. Identification of a specific mutation confirms the diagnosis. Unfortunately uninformative genetic results do not rule out an underlying mutation and/or predisposition to gastrointestinal cancer.

Juvenile polyps may cause challenges in the evaluation of patients with polyps. The diagnosis of JP can be difficult because of the phenotypic overlap with other hamartomatous polyposis syndromes. Patients with Peutz-Jegher’s syndrome (see PJS section) may develop small gastric or colonic polyps without the classic smooth muscle histology and appear more juvenile-like.

Polyps found in Cowden’s syndrome consist of a variety of types of polyps including juvenile (most commonly), lipomas, inflammatory and ganglioneuromas. There are no pathological distinguishing features in the juvenile polyps seen in JP or Cowden’s syndrome. Additionally, the polyps found in Cronkite-Canada syndrome can be difficult to distinguish from the polyps in JP. Clinical evaluation is important to distinguish these polyposis syndromes. The hallmark of Cowden syndrome is multiple facial trichilemmomas most commonly found adjacent to the mouth, nose and eyes.

What caused this disease to develop at this time?

JP is a genetic condition. Within family members who carry the same mutation, the disease expression can be variable. There may be other mutations or environmental factors that affect phenotypic expression of polyposis syndromes.

What laboratory studies should you request to help confirm the diagnosis? How should you interpret the results?

A complete blood count is done to screen for iron deficiency anemia. Serum total protein and albumin may be indicated if one suspects protein loosing enteropathy in an infant.

Would imaging studies be helpful? If so, which ones?

A small bowel series was recommended in the past to assess the small bowel for polyps. The sensitivity of a small bowel series is low and it carries the disadvantage of exposing the patient to radiation. Video capsule enteroscopy (VCE) and magnetic resonance enterscopy (MRE) will likely become the imaging studies of choice to evaluate the small bowel. Sensitivity in both studies appears to be higher than a small bowel series and has the benefit of avoiding ionizing radiation. Prospective VCE and MRE trials involving pediatric patients with polyposis syndromes are underway.

If you are able to confirm that the patient has Juvenile Polyposis, what treatment should be initiated?

Clinical management consists mainly of prevention of malignant complications. Most juvenile polyps can be removed endoscopically.

Periodic surveillance colonoscopy should begin with the onset of symptoms or in early teens if there is a family history of JP. The interval between colonoscopies is determined by number of polyps. Generally a colonoscopy at least every 3 years is indicated once surveillance has started. Upper endoscopy for gastric and duodenal polyps should begin in the early teens.

Colectomy can be considered if polyps are too difficult to control endoscopically or if dysplasia occurs. If dysplasia is present, polyposis is unmanageable by endoscopy, or surveillance is not feasible, then the clinician should have a low threshold for recommending colectomy. Surgical options include subtotal colectomy with ileorectal anastomosis, or total proctocolectomy with pouch.

The extremely rare JP phenotype associated with protein-loosing enteropathy in infancy can be a very challenging situation. Assessment of the extent of the polyposis is important. Surgical intervention is often required.

What are the possible outcomes of Juvenile Polyposis?

Risk of cancer in JP

As seen in other inherited syndromes of colorectal neoplasia increased risk of colorectal cancer (CRC) is associated with early onset of cancer. Mean age at diagnosis of CRC is in the third or fourth decade in most studies of JP patients. CRC in JP has been reported during adolescence.

There is a marked increased risk of CRC in JP. The Hopkin’s group performed a person-year analysis comparing incidence rates of CRC in patients with JP to the general population. The life-time risk of colorectal cancer was calculated at 39%. The RR (95% CI) of CRC was 34.0 (14.4 to 65.7).

Other malignancies including gastric, small bowel and pancreatic cancer have been reported in JP. The frequency appears to be much lower than the risk of colorectal cancer. No formal risk estimates are currently available.

What causes this disease and how frequent is it?

JP is an autosomal dominant condition. The incidence is approximately 1 in 100 000 individuals. Isolated juvenile polyps occur in 2% of children. Depending on the series reported between 30 to 50% of patients meeting the JP clinical criteria have a mutation identified.

Genetics of JP

As mentioned above between 30 and 50% of JP patients have a mutation identified. Previously some centers did not recommend genotyping for JP patients arguing that the frequency of identifying a mutation was low. There are two reasons to support genotyping in JP. The first reason is if a mutation is identified in a proband other at risk family members can be tested with near 100% accuracy. Secondly, the recent discovery that a subgroup of JP patients may have a treatable syndrome-HHT supports identification of JP patients at risk.

About half of the patients with JP and a mutation identified have a mutation in the SMAD4 gene on chromosome 18. Recent literature has reported that JP patients with SMAD4 mutations are at very high risk of having the combined JP-HHT syndrome and therefore have the JP cancer risks but are at risk of HHT complications. Classifying a patient with HHT can be challenging and may require numerous investigations. Therefore, knowing which JP patients are at risk of HHT by genotype is important so patients can be evaluated by HHT experts. Mutations of the bone morphogenetic protein receptor 1A (BMPR1A) gene are found in about 1/3 of JP patients with a mutation found. Commercial genetic testing is available for JP.

How can Juvenile Polyposis be prevented?

Including genetic counseling is important. Currently no chemoprevention agents have been proven to be effective in JP.

What is the evidence?

“Risk of colorectal cancer in juvenile polyposis”. Gut. vol. 56. 2007. pp. 965-967. (Provides cancer rates and outcomes in a large JP cohort.)

“Juvenile Polyposis Syndrome”. World J Gastroenterol. vol. 17. 2011. pp. 4839-44. (A valuable review of JP.)