Hamartomatous Polyposis Syndromes

Covers Peutz-Jeghers syndrome and juvenile polyposis syndrome — the two hamartomatous hereditary CRC syndromes. See Hereditary Colorectal Cancer Syndromes for how these fit among the other syndromes. Content below is from a textbook reference chapter (Sabiston Ch52 - Colorectal Neoplasia & Colon Cancer Surgery), not primary literature.

Peutz-Jeghers syndrome (PJS)

Autosomal dominant hereditary cancer syndrome carrying a 39% lifetime CRC risk. Characterized by benign hamartomatous, primarily GI, polyps plus mucocutaneous pigmentation (dark blue or brown macules on the vermillion lip border, buccal mucosa, hands, feet). High predisposition to many intestinal and extraintestinal cancers — nearly 90% of PJS patients develop hamartomatous polyps, most commonly in the small bowel, followed by the colon, stomach, and rectum in decreasing frequency. Overall lifetime cancer risk is 90%, including colorectal (most common), gastric, pancreatic, lung, breast, uterine, cervical, testicular, and ovarian cancer.

Caused by mutation of the STK11/LKB1 gene (chromosome 19p). About half of PJS cases are inherited from a parent; the remainder occur with no family history (de novo).

Diagnosis (clinical, per WHO criteria — any one of):

1. Three or more histologically confirmed Peutz-Jeghers polyps.
2. Any number of PJ polyps with a family history of PJS.
3. Characteristic, prominent mucocutaneous pigmentation with a family history of PJS.
4. Any number of PJ polyps plus characteristic, prominent mucocutaneous pigmentation.

Histologically, PJ polyps differ from adenomatous polyps in that they arise from an overgrowth of the muscularis mucosa rather than the lamina propria.

Surveillance (given the multi-organ cancer risk):

• Small bowel evaluation begins ages 8–10; if normal, repeat at 18, then every 2–3 years.
• Males: annual testicular physical exam starting age 10.
• Females: annual pelvic exam plus Pap smear starting age 18–20; breast exams every 6 months plus yearly mammogram/breast MRI starting age 25.
• Colonoscopy and upper endoscopy start in the late teens, repeated every 2–3 years, both genders.
• Pancreatic cancer screening via endoscopic ultrasound or MRCP plus serum CA19-9 every 1–2 years starting age 25–30.

Management: polypectomy plays a key role. Asymptomatic gastric or colonic polyps >1 cm should be removed endoscopically. Small bowel polyps >1–1.5 cm, or those growing rapidly, should be removed to reduce future complications (bleeding, intussusception). Surgery is most commonly reserved for symptomatic disease — most often obstruction (from intussusception) or bleeding in the small bowel. Goal: remove the affected segment while preserving as much bowel as possible; may require push enteroscopy or combined laparoscopy/laparotomy with intraoperative endoscopy, since small bowel polyps aren’t reliably visualized by other means.

Juvenile polyposis syndrome (JPS)

Autosomal dominant inheritance, characterized by hamartomatous intestinal polyps. Lifetime colon cancer risk 10–38%; average age at diagnosis 34 years. Clinically diagnosed when there are 5 or more juvenile polyps in the colorectum, any number of juvenile polyps throughout the GI tract with a family history, or juvenile polyposis itself. Symptoms relate to the polyps: acute or chronic GI bleeding, iron-deficiency anemia, prolapsed rectal polyps, abdominal pain, diarrhea.

Two genes linked to JPS: SMAD4 (chromosome 18q) and BMPR1A (chromosome 10q). A pathogenic mutation in one of these two genes is detected in only 40–50% of JPS patients (i.e. genetic testing is far from fully sensitive). There is an increased cancer risk in affected individuals, with a malignant potential of at least 10% in patients with multiple juvenile polyps.

Screening: colonoscopy begins ages 12–15. Interval depends on findings — if no polyps, repeat in 2–3 years; when polyps are present and removed, colonoscopy should be repeated yearly.

Surgical indications: presence of high-grade dysplasia or cancer, or if the polyp burden cannot be effectively managed endoscopically. Prophylactic colectomy may be considered for patients with poor surveillance compliance or a family history of CRC. Surgical options for colorectal disease: subtotal colectomy with IRA, segmental colectomy, or total colectomy with IPAA.

Open items / gaps

• No primary literature yet on either syndrome — all content is the textbook’s summary.
• SMAD4-associated JPS overlaps with hereditary hemorrhagic telangiectasia (JPS-HHT overlap syndrome) in some patients — not mentioned in this chapter chunk, worth checking if it appears elsewhere or needs a dedicated source.