What is the management approach for Peutz-Jeghers syndrome?

Management of Peutz-Jeghers Syndrome

Patients with Peutz-Jeghers syndrome require comprehensive age- and gender-specific cancer surveillance combined with aggressive endoscopic polyp management to reduce mortality from both malignancy (93% lifetime cancer risk) and acute complications like intussusception. 1

Genetic Testing and Diagnosis

• STK11 gene sequencing should be performed in suspected cases, with testing available for $975-$1400 for probands and reduced cost for at-risk family members once a pedigree mutation is identified 1
• Genetic testing enables presymptomatic identification of at-risk first-degree relatives 2
• Patients with characteristic melanotic pigmentation but uninformative genetic testing should still follow full surveillance protocols 1

Polyp Management Strategy

Endoscopic polypectomy is the cornerstone of preventing life-threatening complications, particularly intussusception which occurs in 47% of patients (95% in small intestine) 1

Treatment Approach:

• Remove all polyps >1 cm in the stomach and colon during surveillance endoscopy 1
• Prophylactic polypectomy of the entire small bowel is the gold standard to prevent intussusception, bleeding, and obstruction 2
• Endoscopic ischemic polypectomy (EIP) demonstrates superior safety compared to conventional polypectomy, with significantly lower bleeding rates (0.28% vs 2.83%, p=0.042) 3
• Double balloon enteroscopy (DBE) allows complete small bowel examination and treatment, avoiding repeated emergency surgeries and short bowel syndrome 2

Critical pitfall: 36.4% of pediatric patients have polyps >15 mm before age 8, so surveillance must begin early despite older guideline recommendations 3

Age-Specific Surveillance Protocol

Birth to Age 12 (Males and Females):

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

Age 8:

• Baseline upper endoscopy and small bowel series for both sexes 1
• Continue every 2-3 years if polyps detected 1

Age 18 (Males):

• Colonoscopy, upper endoscopy, and small bowel series every 2-3 years 1

Age 18 (Females):

• Monthly breast self-examination begins 1
• Annual history and physical examination 1

Age 21 (Females):

• Annual pelvic examination with Pap smear (high suspicion for adenoma malignum, a rare aggressive cervical adenocarcinoma with mean diagnosis age 34 years) 1
• Upper endoscopy and small bowel series every 2-3 years if not already initiated 1

Age 25 and Beyond:

Males:

• Endoscopic ultrasound (EUS) every 1-2 years for pancreatic surveillance (36% lifetime risk) 1
• CT scan and/or CA-19-9 offered as alternative options 1
• Continue colonoscopy, upper endoscopy, and small bowel series every 2-3 years 1

Females (all of the above PLUS):

• Semiannual clinical breast examination 1
• Annual mammography (or MRI if mammography technically limited) - 54% lifetime breast cancer risk, comparable to BRCA1/2 carriers 1
• Annual transvaginal ultrasound with CA-125 for ovarian (21% lifetime risk) and uterine (9% lifetime risk) cancer screening 1
• Discuss prophylactic mastectomy on case-by-case basis given breast cancer risk equivalent to hereditary BRCA mutations 1

Cancer Risk Justification

The surveillance intensity is justified by extraordinary cancer risks 1:

• Overall cancer: 93% lifetime risk (relative risk 15.2 vs general population) 1
• Colorectal: 39% (justifies colonoscopy starting age 18, as cancers reported in teenage years) 1
• Pancreatic: 36% (strongest risk factor except hereditary pancreatitis; EUS preferred modality for early detection) 1
• Gastric: 29% 1
• Breast: 54% (equivalent to BRCA1/2 mutation carriers) 1
• Small intestine: 13% 1

Key Clinical Pitfalls

Do not delay surveillance until traditional screening ages - colorectal cancers occur in teenagers, and 68.2% of pediatric patients experience intussusception before first DBE 3

Do not miss adenoma malignum on Pap smears - this aggressive cervical adenocarcinoma is overrepresented in PJS and has poor prognosis 1

Do not rely solely on imaging for small bowel - combined approach using wireless capsule endoscopy, MR enterography, and device-assisted enteroscopy is most effective for polyp burden reduction 4

Recognize that EUS is superior to CT/MRI for pancreatic surveillance - it has higher sensitivity for early lesions and allows fine-needle aspiration for histologic diagnosis of dysplasia and precancerous lesions 1

Surveillance Rationale

While these recommendations are based on expert consensus rather than randomized trials 5, 4, the magnitude of cancer risk (93% lifetime) and acute complication rates (47% intussusception) mandate aggressive surveillance 1. The goal is detecting malignancies early and removing premalignant polyps to improve outcomes and prevent emergency surgeries that lead to short bowel syndrome 2, 4.