What is the management approach for Peutz-Jeghers syndrome?

Management of Peutz-Jeghers Syndrome

Patients with Peutz-Jeghers syndrome require intensive, age-stratified surveillance starting from birth, with aggressive endoscopic polyp removal as the cornerstone to prevent both life-threatening intussusception (occurring in 47% of patients) and the 93% lifetime cancer risk. 1, 2

Immediate Diagnostic Approach

Confirm the diagnosis through STK11 gene sequencing ($975-$1400 for probands), though negative genetic testing does not exclude PJS—proceed with full surveillance if clinical criteria are met (hamartomatous polyps plus ≥2 of: labial melanin deposits, family history, small bowel polyposis). 1, 2

Polyp Management Strategy

Remove all polyps >1 cm during surveillance endoscopy in the stomach and colon to prevent intussusception, which occurs in 47% of patients (95% in small intestine) and represents the most common acute complication in young patients. 1, 2

• Double balloon enteroscopy (DBE) has replaced intraoperative enteroscopy as the preferred method for small bowel polyp removal, being less invasive while allowing complete small bowel examination and polypectomy. 3
• Prophylactic polypectomy of the entire small bowel is the gold standard to prevent both intussusception and potential malignant transformation. 3
• Critical pitfall: Repeated emergency laparotomies lead to short bowel syndrome and chronic complications—aggressive endoscopic surveillance prevents this cascade. 4, 5

Age-Specific Surveillance Protocol

Birth to Age 12 (Males)

• Annual testicular examination with routine blood tests to detect sex-cord tumors with annular tubules and Sertoli cell tumors (mean diagnosis age 9 years, range 3-20), which cause precocious puberty and gynecomastia. 1, 2
• Optional: Testicular ultrasound every 2 years. 2

Age 8 (Both Sexes)

• Baseline upper endoscopy and small bowel series to establish polyp burden before symptomatic complications develop. 2

Age 18 (Males) / Age 21 (Females)

• Colonoscopy, upper endoscopy, and small bowel series every 2-3 years—colorectal cancer risk is 39% lifetime with cases reported in teenage years, justifying early initiation. 1, 2, 6

Age 21 (Females)

• Annual pelvic examination with Pap smear with high suspicion for adenoma malignum, a rare aggressive cervical adenocarcinoma overrepresented in PJS (mean diagnosis age 34 years, 22 of 28 cervical cancers in one series). 1, 2
• Monthly breast self-examination begins at age 18. 2

Age 25 and Beyond (Both Sexes)

Males:

• Endoscopic ultrasound (EUS) every 1-2 years for pancreatic surveillance—36% lifetime pancreatic cancer risk makes this the second-highest risk after colorectal cancer. 1, 2, 6
• Continue gastrointestinal surveillance every 2-3 years. 2

Females:

• Annual mammography (or MRI if mammography technically limited)—54% lifetime breast cancer risk is equivalent to BRCA1/2 mutation carriers, the highest non-GI cancer risk. 1, 2
• Semiannual clinical breast examination. 2
• Annual transvaginal ultrasound with CA-125 for ovarian (21% lifetime risk) and uterine (9% lifetime risk) cancer screening. 1, 2
• Continue annual Pap smears for adenoma malignum surveillance. 2
• EUS every 1-2 years for pancreatic surveillance. 2

Cancer Risk Justification

The meta-analysis data demonstrates a relative risk of 15.2 for all cancers compared to the general population, with 93% lifetime cancer risk by ages 15-64. 1 Specific lifetime risks include:

• Breast: 54% (comparable to hereditary BRCA mutations) 1
• Colorectal: 39% 1
• Pancreatic: 36% 1
• Gastric: 29% 1
• Ovarian: 21% 1
• Small intestine: 13% 1

Mortality data shows median age of death at 51 years, with cancer (particularly metastatic gynecologic malignancies) being the exclusive cause of death in known cases. 4

Critical Clinical Pitfalls

Do not miss adenoma malignum on Pap smears—this aggressive cervical adenocarcinoma is disproportionately represented in PJS (22 of 28 cervical cancers in one series were this subtype) and has poor prognosis. 1, 2

Use EUS, not CT/MRI, for pancreatic surveillance—EUS has superior sensitivity for early pancreatic lesions and allows fine-needle aspiration for histologic diagnosis of dysplasia and precancerous lesions. 2

Avoid the "wait for symptoms" approach—six of seven patients in one registry presented with acute intestinal obstruction requiring emergency laparotomy, demonstrating the failure of reactive management. 5 Proactive endoscopic surveillance prevents this morbidity. 4, 3