What is Puetz-Jeghers syndrome?

Peutz-Jeghers Syndrome: Definition and Clinical Implications

Peutz-Jeghers syndrome (PJS) is an autosomal dominant disorder characterized by hamartomatous polyps throughout the gastrointestinal tract and distinctive mucocutaneous melanin pigmentation, with a 93% lifetime risk of developing cancer. 1

Clinical Features

Mucocutaneous Pigmentation

• Dark brown or blue-brown melanotic pigmented macules (1-5 mm in size)
• Locations and frequency:
  • Vermilion border of the lips (94% of patients)
  • Buccal mucosa (66%)
  • Hands (74%)
  • Feet (62%)
  • Also found in periorbital, perianal, and genital regions
• Usually appears in infancy and may fade during late adolescence
• Present in >95% of affected patients 1

Hamartomatous Polyps

• True hamartomas with unique histopathologic characteristics:
  • Branching framework of connective tissue and smooth muscle
  • Lined by normal intestinal epithelium rich in goblet cells
  • Elongated and convoluted glands with arborizing growth pattern
• Distribution in the GI tract:
  • Small intestine (64%)
  • Colon (64%)
  • Stomach (49%)
  • Rectum (32%)
  • Can also occur in renal pelvis, urinary bladder, lungs, and nares 1

Genetic Basis

• Caused by germline mutations in the STK11/LKB1 gene on chromosome 19p13.3
• STK11 is a tumor suppressor gene encoding a serine/threonine kinase
• Mutations detected in 66-94% of PJS cases 1
• Acts as a regulator of cell-cycle metabolism and cell polarity 1

Clinical Presentation

• Most patients become symptomatic between ages 10-30 years
• Average age of diagnosis: 23 years in men, 26 years in women
• Presenting complaints:
  • Intestinal obstruction (43%)
  • Abdominal pain (23%)
  • Blood in stool (14%)
  • Anal extrusion of polyp (7%)
  • Diagnosis due to melanin pigmentation (13%)
• Most frequent complication: intussusception (47% of patients), primarily in small intestine 1

Cancer Risk

• Relative risk for all cancers: 15.2 times the general population
• Lifetime risk of any cancer by age 64: 93% 1
• Cumulative cancer risk by age 70: 81% 1

Specific Cancer Risks by Age 64:

• Breast: 54%
• Colon: 39%
• Pancreas: 36%
• Stomach: 29%
• Ovary: 21%
• Lung: 15%
• Small intestine: 13%
• Cervix: 10%
• Uterus: 9%
• Testes: 9% 1

Unusual Associated Tumors:

• Sex-cord tumors with annular tubules of the ovary
• Adenoma malignum of the cervix
• Testicular tumors of sex-cord and Sertoli-cell type (may be associated with sexual precocity and gynecomastia) 1

Diagnostic Criteria

PJS diagnosis can be made in patients with hamartomatous polyp(s) plus at least 2 of the following:

1. Labial melanin deposits
2. Family history of the syndrome
3. Small bowel polyposis 1

Management Implications

• Patients with PJS or STK11 variants should be referred to specialized teams 1
• Regular surveillance for polyps and various cancers is essential
• Endoscopic polypectomy is recommended to prevent complications like intussusception and obstruction 1
• Cancer screening should include:
  • Colonoscopy and upper endoscopy
  • Pancreatic imaging (CT, MRI, or ultrasound)
  • Chest imaging
  • Breast cancer screening
  • Gynecologic examination with ultrasound for women
  • Testicular examination for men 1, 2

Epidemiology

• Estimated incidence: 1/50,000 to 1/200,000 live births
• Equal distribution between males and females
• Found in all racial groups 1

PJS is a rare but significant hereditary syndrome requiring lifelong surveillance due to its high cancer risk. Early recognition of the characteristic mucocutaneous pigmentation and hamartomatous polyps is crucial for timely diagnosis and implementation of appropriate cancer screening protocols.