Makindo Medical Notes

Related Subjects: |Colorectal cancer |Colorectal polyps |Cancer Frequency and Red flags

Peutz-Jeghers syndrome (PJS) is a rare genetic condition characterized by distinctive pigmented macules, most commonly seen around the mouth, lips, face, hands, and feet, along with the development of numerous hamartomatous polyps throughout the gastrointestinal tract. These features often present in early childhood or adolescence.

About

• Autosomal dominant inheritance: Peutz-Jeghers syndrome is passed on in an autosomal dominant pattern, meaning that a single copy of the mutated gene is sufficient to cause the condition.
• Hamartomatous polyps: A hallmark of the disease is the presence of numerous hamartomatous polyps, primarily in the gastrointestinal (GI) tract, particularly in the small intestine, but also in the stomach and colon.
• High risk of malignancy: Individuals with PJS have an increased risk of developing various types of cancers, including gastrointestinal, breast, pancreas, and reproductive organ cancers.

Aetiology

• Genetic mutation: Caused by mutations in the serine/threonine kinase LKB1 or STK11 gene, which is involved in regulating cell growth and apoptosis.
• Germline mutation: The germline mutation of the STK11/LKB1 gene is located on chromosome band 19p13.3.
• Increased malignancy risk: Patients with Peutz-Jeghers syndrome have a higher lifetime risk of developing malignancies in various organs, including the pancreas, ovaries, cervix, lungs, and GI tract. Lifetime risk for cancer is estimated to be up to 90% by age 60.

Clinical Features

• Characteristic pigmentation: Hyperpigmented macules (brown or black spots) are commonly seen on the lips, perioral region, mucous membranes (including the inside of the mouth), and skin of the hands, feet, and sometimes other areas.
• Hamartomatous polyps: Numerous polyps typically develop in the gastrointestinal tract, most often in the small intestine but also in the stomach and colon. These polyps can be benign but have a risk of malignancy.
• Intestinal complications: Polyps can lead to complications such as rectal bleeding (PR), bowel obstruction, intussusception (when a part of the intestine folds into another section), and abdominal pain.
• Malignant transformation: The hamartomatous polyps in PJS can transform into cancerous lesions, necessitating regular surveillance.
• Associated benign tumours: PJS is also associated with benign tumours, including adenomas, leiomyomas (smooth muscle tumours), and lipomas (fatty tumours) in various tissues.

Investigations

• Anaemia: Patients may present with iron deficiency anaemia due to chronic gastrointestinal blood loss from polyps.
• Tumor markers: Carcinoembryonic antigen (CEA) and other tumour markers may be elevated, although they are non-specific.
• Small bowel imaging: Imaging studies such as small bowel series, capsule endoscopy, and magnetic resonance enterography (MRE) can be used to identify polyps in the small intestine.
• Histology: On histological examination, polyps show smooth muscle "arborization," a branching pattern of smooth muscle interspersed within the polyp, which is characteristic of Peutz-Jeghers syndrome.
• Genetic testing: Molecular genetic testing can confirm the presence of STK11/LKB1 mutations, aiding in diagnosis and screening of family members.

Management

• Conservative management: Regular surveillance is essential, including endoscopic and radiologic monitoring to detect complications early and reduce cancer risk.
• Endoscopic polypectomy: Polyps that are large or symptomatic (e.g., causing bleeding or obstruction) should be removed via endoscopic polypectomy.
• Surgical intervention: In cases of intussusception, bowel obstruction, or if polyps are inaccessible via endoscopy, laparotomy and resection may be necessary.
• Cancer surveillance: Due to the increased risk of malignancy, individuals with PJS require lifelong cancer screening for gastrointestinal, pancreatic, breast, and gynecological cancers.
• Genetic counseling: Recommended for affected individuals and their family members, as PJS has autosomal dominant inheritance, increasing the risk for offspring.

Complications

• Intestinal obstruction and intussusception: Polyps can cause bowel obstruction or invagination (intussusception), especially in younger patients, requiring urgent intervention.
• Rectal bleeding: Chronic or acute gastrointestinal bleeding from polyps can lead to significant anaemia and may require intervention.
• Increased cancer risk: A high lifetime risk of developing multiple malignancies, including gastrointestinal, breast, pancreatic, lung, and gynecological cancers.