What are the management and surveillance recommendations for a patient with Peutz-Jeghers syndrome?

Management of Peutz-Jeghers Syndrome

Patients with Peutz-Jeghers syndrome require intensive, lifelong multi-organ cancer surveillance starting in childhood, with aggressive endoscopic polyp removal to prevent both malignancy (93% lifetime cancer risk) and life-threatening intussusception. 1

Genetic Testing and Diagnosis

• Perform STK11/LKB1 gene testing in all suspected cases, ideally by age 8 years to prevent emergency laparotomy for small bowel obstruction from intussusception (occurs in 30% by age 10). 2
• If a mutation is identified in an affected family member, test all first-degree relatives—those testing negative have general population risk and do not need surveillance. 2
• If genetic testing is uninformative but clinical features are present (melanotic pigmentation, hamartomatous polyps), proceed with full surveillance protocols regardless. 2

Polyp Management Strategy

Remove all polyps >1 cm in the stomach and colon during surveillance endoscopy to prevent intussusception and potential malignant transformation. 2, 1

• Intussusception occurs in 47% of PJS patients, with 95% involving the small intestine. 1
• Double balloon enteroscopy (DBE) is now preferred over intraoperative enteroscopy for small bowel polyp removal, as it is less invasive and prevents short bowel syndrome from repeated resections. 3

Age-Specific Surveillance Protocol

Birth to Age 12 (Males)

• Annual history and physical examination with testicular examination and routine blood tests. 2, 1
• Optional: Testicular ultrasound every 2 years until age 12 to detect Sertoli cell tumors (mean diagnosis age 9 years, range 3-20 years). 2, 1

Age 8 (Both Sexes)

• Baseline upper endoscopy and small bowel series (radiography or MR enterography). 2, 1

Age 18 and Beyond (Males)

• Every 2-3 years: Colonoscopy, upper endoscopy, and small bowel series. 2, 1

Age 18 and Beyond (Females)

• Monthly breast self-examination starting at age 18. 2, 1
• Every 2-3 years: Colonoscopy, upper endoscopy, and small bowel series starting at age 18. 2, 1

Age 21 and Beyond (Females)

• Annual pelvic examination with Pap smear—maintain high suspicion for adenoma malignum, a rare aggressive cervical adenocarcinoma with mean diagnosis age 34 years. 2, 1

Age 25 and Beyond (Both Sexes)

• Every 1-2 years: Endoscopic ultrasound (EUS) for pancreatic surveillance (36% lifetime risk). 2, 1
  • EUS is superior to CT/MRI for detecting early pancreatic lesions and allows fine-needle aspiration for histologic diagnosis. 1
  • Alternative options include CT scan and/or CA-19-9, though EUS is preferred. 2

Age 25 and Beyond (Females Only)

• Semiannual clinical breast examination. 2, 1
• Annual mammography (or MRI if mammography is technically limited due to dense breast tissue). 2, 1
  • Initiate earlier if family history suggests earlier onset. 2
• Annual transvaginal ultrasound with serum CA-125 for ovarian (21% lifetime risk) and uterine (9% lifetime risk) cancer screening. 2, 1

Cancer Risk Justification

The surveillance protocol is driven by dramatically elevated cancer risks:

• Overall cancer: 93% lifetime risk (relative risk 15.2 vs. general population). 1, 4
• Breast cancer: 54% lifetime risk (comparable to BRCA1/2 mutation carriers, justifying identical surveillance). 2, 1
• Colorectal cancer: 39% lifetime risk (cancers reported even in teenage years, justifying colonoscopy starting at age 18). 2, 1, 4
• Pancreatic cancer: 36% lifetime risk (strongest risk factor except hereditary pancreatitis; 95% occur after age 24). 2, 1
• Gastric cancer: 29% lifetime risk. 1
• Small intestine cancer: 13% lifetime risk. 1

Critical Clinical Pitfalls

Adenoma Malignum

• Do not dismiss abnormal Pap smears—adenoma malignum is an aggressive cervical adenocarcinoma overrepresented in PJS with poor prognosis. 1
• Mean diagnosis age is 34 years, with 22 of 28 cervical tumors in one series being adenoma malignum. 2

Pancreatic Surveillance

• EUS is the preferred modality over CT/MRI for pancreatic surveillance due to higher sensitivity for early lesions and ability to perform fine-needle aspiration. 1
• CA-19-9 alone is not recommended as a screening test. 5

Prophylactic Surgery

• Discuss prophylactic mastectomy on a case-by-case basis given the 54% breast cancer risk, counseling regarding degree of protection and reconstruction options. 2
• The benefit of chemoprevention is unclear. 2

Emergency Complications

• Maintain high vigilance for intussusception symptoms (abdominal pain, obstruction) as this occurs in nearly half of patients and requires urgent intervention. 1, 3
• Aggressive endoscopic polyp clearance reduces the need for emergency laparotomy and prevents short bowel syndrome from repeated resections. 2, 3