Hamartomatous polyps are growths composed of a disorganized collection of mature cells and tissues normally found in the area where they develop. They are considered benign. While these polyps are not cancerous, their presence is significant because they are frequently linked to specific inherited conditions and can increase an individual’s lifetime risk of developing various cancers. Understanding these polyps involves recognizing their characteristics and health implications.
What Are Hamartomatous Polyps?
Hamartomatous polyps are abnormal tissue growths that are essentially malformations of normal tissue components, appearing as a disorganized mix of mature cells, connective tissue, and smooth muscle. This structural disorganization differentiates them from adenomatous polyps, which are characterized by abnormal glandular tissue and are recognized as precancerous.
These polyps are most commonly found within the gastrointestinal tract, including the colon, small intestine, and stomach. They can also occur in other parts of the body. While often small, measuring only a few millimeters, they can sometimes grow larger or appear in multiple numbers. The presence of these polyps can lead to symptoms such as rectal bleeding, abdominal pain, or diarrhea, although many individuals remain without symptoms and their polyps are discovered incidentally during medical examinations.
Genetic Syndromes Linked to Polyps
Hamartomatous polyps are frequently associated with inherited genetic syndromes. Peutz-Jeghers syndrome (PJS) is one such condition, characterized by hamartomatous polyps throughout the digestive system. PJS is caused by germline mutations in the STK11 gene, which functions as a tumor suppressor and plays a role in regulating cell growth. This mutation can lead to polyps with a characteristic branching, tree-like appearance under a microscope.
Cowden syndrome, also known as PTEN hamartoma tumor syndrome, is another inherited disorder linked to these polyps. It is caused by mutations in the PTEN gene, a tumor suppressor that helps control cell growth and division. Individuals with Cowden syndrome develop multiple hamartomas that can affect various organs, including the skin, mucous membranes, and gastrointestinal tract. The genetic alterations in PTEN can lead to uncontrolled cell division and the formation of these growths.
Juvenile Polyposis Syndrome (JPS) is an autosomal dominant condition characterized by the development of multiple juvenile polyps in the gastrointestinal tract. JPS is caused by constitutional variants in the SMAD4 or BMPR1A genes, which are involved in the TGFβ signaling pathway. These genetic changes can lead to polyps appearing predominantly in the colorectum, but also in the stomach and small intestine.
Cancer Risk and Other Manifestations
While hamartomatous polyps are benign, their presence, especially with hereditary syndromes, significantly increases the risk of developing cancer over time. The increased risk extends to colorectal cancer, with reported lifetime risks ranging from 39% to 68% for Juvenile Polyposis Syndrome, 39% to 57% for Peutz-Jeghers syndrome, and approximately 18% for PTEN Hamartoma Tumor Syndrome.
Beyond colorectal cancer, individuals with these syndromes face elevated risks for various extra-colonic cancers. Peutz-Jeghers syndrome is associated with increased risks for stomach, small intestine, pancreatic, breast, ovarian, and lung cancers. Cowden syndrome carries an increased risk for breast, thyroid, endometrial, kidney, and skin cancers, often appearing at younger ages. Juvenile Polyposis Syndrome also increases the risk for gastric and small bowel cancers, in addition to colorectal cancer.
These syndromes also present with various non-cancerous issues outside the digestive tract, known as extra-intestinal manifestations. Peutz-Jeghers syndrome is characterized by distinctive dark blue to dark brown mucocutaneous pigmentations, typically found around the lips, mouth, nostrils, and fingers. Cowden syndrome can manifest with skin lesions such as trichilemmomas, oral papillomas, and acral keratoses, along with macrocephaly. Juvenile Polyposis Syndrome may be associated with congenital abnormalities like cleft palate, extra fingers or toes, heart or brain abnormalities, and a twisting of the intestines.
Detection and Ongoing Care
The diagnosis of hamartomatous polyps often involves endoscopic procedures, such as colonoscopy, gastroscopy, and enteroscopy, which allow for direct visualization and biopsy of the growths. Imaging techniques like video capsule endoscopy or magnetic resonance enterography are also used, particularly for evaluating the small bowel. These methods help pinpoint the location, size, and number of polyps.
Genetic testing is an important step for individuals suspected of having an associated hereditary syndrome. This testing can confirm the presence of specific germline pathogenic variants, such as STK11 for Peutz-Jeghers syndrome, PTEN for Cowden syndrome, and SMAD4 or BMPR1A for Juvenile Polyposis Syndrome. Identifying these genetic mutations is important for accurate diagnosis and for guiding the management of the patient and their family members.
Ongoing surveillance protocols monitor for polyp recurrence and the early detection of associated malignancies. For Peutz-Jeghers syndrome, regular upper and lower endoscopies are recommended every 2 to 3 years, with small bowel screening starting between ages 8 and 10. Cowden syndrome surveillance includes frequent colonoscopies, starting at age 35, along with monitoring of other organs like the breasts and thyroid. For Juvenile Polyposis Syndrome, colonoscopies with polypectomies are often initiated between ages 12 and 15, with intervals depending on the polyp burden. Management strategies primarily involve endoscopic polypectomy to remove polyps, but in cases of numerous polyps, advanced dysplasia, or cancer development, more extensive surgical resection may be necessary.