What are the treatment and monitoring recommendations for a patient with Peutz-Jeghers syndrome?

Treatment and Monitoring for Peutz-Jeghers Syndrome

Patients with Peutz-Jeghers syndrome require comprehensive lifelong surveillance starting at age 8 years with small bowel imaging, combined with aggressive endoscopic polypectomy of polyps >1 cm to prevent both life-threatening intussusception (50% risk by age 20) and malignancy (93% lifetime cancer risk). 1, 2, 3

Genetic Testing and Diagnosis

• Offer STK11/LKB1 gene testing to at-risk first-degree relatives starting at age 8 years, as this allows identification of true carriers who need surveillance versus non-carriers who can be reassured 1
• If a mutation is identified in an affected family member, at-risk relatives who test negative have general population risk and do not require PJS-specific surveillance 1
• Patients with characteristic melanotic pigmentation but negative genetic testing should still follow full surveillance protocols, as current testing does not detect all mutations 1, 2

Gastrointestinal Polyp Management

Treatment Approach

• Remove all polyps >1 cm in the stomach and colon during endoscopic surveillance 1, 2
• For small bowel polyps >10-15 mm, perform polypectomy to prevent intussusception, as 95% of intussusceptions occur in the small intestine and are caused by polyps with median size 35 mm 3
• Polypectomy is the cornerstone of preventing intussusception, which occurs in 47-69% of patients and requires surgical intervention in 92.5% of cases 2, 3

Small Bowel Surveillance Modality

The British Society of Gastroenterology (2020) recommends video capsule endoscopy (VCE) as the preferred small bowel surveillance method, as it is better tolerated than barium studies and avoids repeated radiation exposure 1. MRI enterography can be complementary for accurate polyp localization and sizing 1.

Age-Specific Surveillance Protocol

Birth to Age 12 (Males Only)

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

Age 8 Years (Both Sexes)

• Baseline upper endoscopy and small bowel imaging (VCE or small bowel series) 1
• The British guidelines specify that if baseline colonoscopy and upper endoscopy are normal at age 8, these can be safely deferred until age 18, but small bowel surveillance should continue every 3 years regardless 1
• Earlier investigation is warranted if symptomatic, as 15-30% of patients require surgery before age 10 for intussusception 1

Age 18 Years

• Colonoscopy every 2-3 years (39% lifetime colorectal cancer risk) 1, 2
• Upper endoscopy and small bowel imaging every 2-3 years (if polyps were found at baseline age 8 examination) 1
• Monthly breast self-examination (females) 1, 2

Age 21 Years (Females)

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

Age 25 Years and Beyond

• Semiannual clinical breast examination (females) 1, 2
• Annual mammography or breast MRI (females)—54% lifetime breast cancer risk, comparable to BRCA1/2 carriers, with mean diagnosis age 37 years (range 19-48) 1, 2
• Annual transvaginal ultrasound with CA-125 for ovarian (21% lifetime risk) and uterine (9% lifetime risk) cancer screening (females) 1, 2
• Endoscopic ultrasound (EUS) every 1-2 years for pancreatic surveillance (36% lifetime pancreatic cancer risk, mean diagnosis age 41 years) 1, 2
• CT scan and/or CA-19-9 are offered as alternative options to EUS, though EUS is superior for detecting early pancreatic lesions 1, 2

Age 75 Years

• Surveillance can be discontinued at age 75 years or tailored based on individual health status 1

Cancer Risk Justification

The comprehensive surveillance protocol is justified by markedly elevated cancer risks:

• Overall cancer: 93% lifetime risk (relative risk 15.2-18 versus general population) 2, 4
• Colorectal: 39% (justifies colonoscopy starting age 18) 2, 4
• Pancreatic: 36% (strongest risk factor except hereditary pancreatitis) 2, 4
• Breast: 54% (equivalent to BRCA1/2 mutation carriers) 1, 2
• Gastric: 29% 2, 4
• Small intestine: 13% 2

Critical Clinical Pitfalls

Adenoma Malignum Detection

Do not miss adenoma malignum on Pap smears—this aggressive cervical adenocarcinoma is overrepresented in PJS (28 cases reported, mean age 34 years) and has poor prognosis 1, 2. Twenty-two of these were adenoma malignum specifically 1.

Pancreatic Surveillance Modality

Recognize that EUS is superior to CT/MRI for pancreatic surveillance, as it has higher sensitivity for early lesions and allows fine-needle aspiration for histologic diagnosis of dysplasia and precancerous lesions 2.

Emergency vs. Elective Surgery

Proactive small bowel surveillance and polypectomy reduces the morbidity of emergent laparotomy for intussusception (which occurs in 30% of patients by age 10) versus planned endoscopic management 1. The cumulative intussusception risk reaches 50% by age 20 years 3.

Short Bowel Syndrome Prevention

Repeated emergency bowel resections can lead to short bowel syndrome—aggressive endoscopic polypectomy and intraoperative enteroscopy when surgery is necessary can prevent this devastating complication 5, 6.