Named after Jan Peutz, a Dutch physician, and Harold Jeghers, an American physician, who described the syndrome in the early 20th century.
AKA
PJS
What is it?
A rare autosomal dominant disorder characterized by gastrointestinal hamartomatous polyps and mucocutaneous hyperpigmentation (26).
Caused by:
Germline mutations in the STK11/LKB1 gene located on chromosome 19p13.3, leading to defective tumor suppression (23, 24).
Resulting in:
Increased risk of gastrointestinal and extra-gastrointestinal malignancies, including colorectal, pancreatic, breast, and ovarian cancers (24, 27).
Premalignant Potential:
Approximately 50% of patients develop cancer by the age of 60.
Common cancers include colorectal, gastric, pancreatic, breast, and gynecological tumors (23, 24).
Hamartomatous polyps may undergo dysplastic transformation into adenocarcinomas, particularly in the gastrointestinal tract (26).
Penetrance of STK11 Gene:
High Penetrance:
Nearly all individuals with pathogenic STK11 mutations develop clinical features of PJS, including gastrointestinal polyps and mucocutaneous pigmentation (23, 27).
Environmental factors, genetic modifiers, and lifestyle choices (e.g., smoking, diet) can influence cancer development.
Proactive screening and polyp management significantly reduce complications (24).
Structural Changes:
Development of hamartomatous polyps primarily in the small intestine, but also in the stomach, colon, and rectum (24, 26).
Parts:
Gastrointestinal tract involvement, with polyps most common in the jejunum, ileum, and duodenum (23, 29).
Size:
Polyps can vary in size, ranging from millimeters to several centimeters, with larger polyps more likely to cause complications (24).
Shape:
Typically pedunculated or sessile with lobulated surfaces (29).
Position:
Predominantly located in the small intestine, but involvement of the stomach and colon is frequent (23, 27).
Character:
Benign hamartomatous polyps with potential for neoplastic transformation (23, 24).
Time:
Onset is typically in childhood or adolescence, with clinical manifestations becoming more prominent over time (26).
Clinical Freckles:
Mucocutaneous hyperpigmented macules (freckles) are often the earliest sign, typically seen in the perioral region, lips, buccal mucosa, palms, soles, and genital area. These freckles may fade after puberty (27, 28).
Other Clinical Features:
Abdominal Pain: Recurrent and often associated with intussusception or partial bowel obstruction.
Small Bowel Obstruction (SBO): A common complication due to large polyps or intussusception.
Rectal Bleeding: Secondary to polyp ulceration or trauma.
Iron-Deficiency Anemia: Chronic blood loss from ulcerated polyps.
Intussusception: Can occur repeatedly, presenting as acute abdominal pain and requiring urgent intervention (16, 17, 24).
Pathophysiology:
Loss of STK11/LKB1 function leads to dysregulation of cellular growth and polarity, promoting the development of polyps and malignancies (23, 24).
Pathology:
Histologically, polyps consist of disorganized epithelial, smooth muscle, and connective tissue components (27).
Diagnosis:
Based on clinical criteria, family history, genetic testing, and characteristic findings on imaging and endoscopy (23, 26).
Radiology and Imaging:
CT:
Findings: Detects small bowel polyps as intraluminal masses with or without bowel obstruction or intussusception (24, 29).
Associated Findings: Intussusception may show the “target” or “sausage” sign (16, 17).
MRI:
Superior for evaluating small bowel polyps, intussusception, and differentiating benign and malignant lesions (18, 20).
US:
Detects polyps and intussusception in children, showing a “coiled spring” sign (21).
Barium Studies:
The “coiled spring” sign on contrast studies represents intussusception (16, 17). Effective in evaluating obstructions and larger polyps.
Video Capsule Endoscopy:
Preferred for non-invasive evaluation of small bowel polyps, allowing detailed visualization (24).
Surveillance Schedule:
Polyps: Start small bowel imaging (CT/MRI or video capsule endoscopy) by age 8-10 and repeat every 1-3 years depending on polyp burden.
Cancer: Initiate endoscopic screening for colorectal and gastric cancers in adolescence, and begin pancreatic cancer surveillance with MRI or endoscopic ultrasound by age 30 (24, 27).
Management of Intussusception:
Acute Episodes: Immediate reduction via endoscopy or surgical resection in cases of obstruction (17).
Prevention: Prophylactic polypectomy during surveillance endoscopy or laparotomy (24).
Labs:
Genetic testing for STK11 mutations. Routine blood work may reveal anemia due to chronic gastrointestinal bleeding (23).
Recommendations:
Multimodal imaging and regular endoscopic surveillance to minimize cancer risks. Collaboration among gastroenterologists, radiologists, and surgeons is critical (24, 28).
Key Points and Pearls:
Early detection of polyps and malignancies is crucial.
MRI and video capsule endoscopy are preferred imaging modalities for small bowel surveillance.
Prophylactic polypectomy is essential to prevent complications like intussusception and obstruction.
