What testing can be done to assess for hamartomatous polyp diseases, such as Peutz-Jeghers Syndrome (PJS) or Juvenile Polyposis Syndrome (JPS)?

From the Guidelines

Testing for hamartomatous polyp diseases should include genetic testing, endoscopic evaluation, and imaging studies, with a focus on specific gene mutations and surveillance intervals personalized according to phenotype, as recommended by the most recent guidelines 1. To assess for hamartomatous polyp diseases, the following tests can be done:

• Genetic testing for specific gene mutations associated with each syndrome, such as PTEN for Cowden syndrome, STK11/LKB1 for Peutz-Jeghers syndrome, SMAD4 or BMPR1A for juvenile polyposis syndrome, and GREM1 for hereditary mixed polyposis syndrome.
• Endoscopic procedures, including:
  • Upper endoscopy and high-quality colonoscopy with polypectomy, repeated every 2-3 years or at shorter intervals based on polyp size, number, and pathology, as recommended for Peutz-Jeghers Syndrome 1.
  • Video capsule endoscopy or CT/MRI enterography for small bowel visualization, with follow-up interval based on findings, but at least by age 18 years, then every 2-3 years 1.
• Imaging studies, such as MRI, CT scans, and ultrasound, to detect extraintestinal manifestations in organs like the thyroid, breast, and brain. It is essential to start testing with a thorough family history assessment and physical examination, looking for characteristic features such as mucocutaneous pigmentation in Peutz-Jeghers syndrome or macrocephaly in Cowden syndrome, and to personalize surveillance intervals according to colorectal and upper GI tract phenotype, as suggested by guidelines 1. Early and comprehensive testing is crucial, as these syndromes carry increased cancer risks, and identification allows for appropriate surveillance and preventive measures for patients and potentially affected family members.

From the Research

Testing for Hamartomatous Polyp Diseases

To assess for hamartomatous polyp diseases, several testing methods can be employed:

• Endoscopic sampling and molecular testing can be used for diagnosis 2
• Double contrast studies are the preferred radiologic procedures for the diagnosis of gastrointestinal polyps in these diseases 3
• Genetic testing can be used to confirm the presence of a germline pathogenic variant, which can help in diagnosing the syndrome 4, 5, 6
• Surveillance of organs at increased risk for cancer is also an important aspect of management 5, 6

Types of Testing

The following types of testing can be used:

• Endoscopy to remove polyps and examine the gastrointestinal tract 4
• Push-enteroscopy, device-assisted enteroscopy, or surgery to remove polyps in the small bowel 4
• Molecular genetic testing to identify germline pathogenic variants 4, 5, 6
• Imaging studies to monitor for extraintestinal manifestations and cancers 5, 6

Importance of Early Diagnosis

Early diagnosis of hamartomatous polyp diseases is crucial to:

• Optimize malignancy surveillance and reduce morbidity and mortality 2
• Identify at-risk family members and provide them with appropriate surveillance and management 2
• Prevent complications such as bleeding and mechanical obstruction of the small bowel by polyps 5, 6