Colonic polyps

Colonic polyps are abnormal colonic mucosal overgrowths. They are a common finding in people over the age of 50. In rare cases, they may be seen in younger individuals as part of hereditary polyposis syndromes (e.g., familial adenomatous polyposis, Peutz‑Jeghers syndrome, etc.). On macroscopic examination, colonic polyps are either pedunculated (with a stalk) or sessile (without a stalk). Histologically, colonic polyps are most commonly adenomas (∼ 70%), followed by hyperplastic polyps, and, rarely, serrated polyps and hamartomatous polyps. Colonic polyps may be benign or have malignant potential. Adenomas have the highest malignant potential (5%) and most colonic carcinomas arise from them (adenoma‑carcinoma sequence). Most patients are asymptomatic, but they may present with altered bowel habits, blood/mucus in stool, and iron deficiency anemia. Colonoscopy is the diagnostic modality of choice, since it allows for direct visualization of the polyps, biopsy, and therapeutic snare polypectomy (of pedunculated polyps) or endoscopic submucosal resection (of sessile polyps). Large polyps (> 2 cm) or malignant polyps require surgical resection.

Malignant potential	Histological type	Subtypes	Characteristics
Low malignant potential	Hamartomatous polyps	Juvenile polyposis syndrome Peutz-Jeghers syndrome Cowden syndrome Cronkhite-Canada syndrome	Increased risk of colonic and extra-colonic malignancies Polyps throughout the GIT Autosomal dominant inheritance
	Inflammatory polyps (pseudopolyps)		Seen in ulcerative colitis Multiple, benign polyps
	Mucosal polyps		Benign Typically small < 5 mm
	Submucosal polyps		Benign Submucosal lipoma (most common)
Moderate malignant potential	Serrated polyps	Hyperplastic polyps Hyperplasia of normal cellular components and sawtooth/serrated pattern of crypt epithelium	Minimal risk of malignancy Small (< 5 mm) Common in distal colon (rectosigmoid)
		Sessile serrated polyps Morphology similar to hyperplastic polyps	Risk of malignancy: ∼ 5% Sessile lesions > 5 mm in size Common in proximal colon (ascending colon)
		Traditional serrated adenoma Serrated architecture with dysplasia	Risk of malignancy: ∼ 5% Common in rectosigmoid
High malignant potential	Adenomatous polyps	Tubular adenoma Histology: proliferating cells form tubules	Risk of malignancy: < 5% Frequency: ∼ 80% Location: anywhere in the colon
		Tubulovillous adenoma Histology: Mixture of tubular and villous histological picture	Risk of malignancy: ∼ 20% Frequency: 5–15%
		Villous adenoma Histology: finger-like projections lined by dysplastic epithelium	Risk of malignancy: ∼ 50% Frequency: 5–15% Location: common in the rectum Larger than other adenomas (cauliflower-like), and often sessile.

The majority of colon carcinomas develop from adenomas (adenoma‑carcinoma sequence). However, only ∼ 5% of adenomas develop into colon cancers!

Although villous adenoma is rarer than tubular adenoma, it has the highest malignant potential!

References:^{[1][2][5][6][7]}

Hereditary polyposis syndrome

• Adenomatous polyposis syndromes
• Hamartomatous polyposis syndromes

Adenomatous polyposis syndromes

Familial adenomatous polyposis (FAP)

• Inheritance
  • Mutation of the tumor suppressor gene APC (adenomatous polyposis coli)
  • Autosomal dominant; (positive family history)
  • Up to 25% of cases have a negative family history.
• Epidemiology
  • Occurs in one in 10,000–30,000 live births
  • < 1% of colorectal cancers in the U.S. are due to FAP
  • Both sexes equally affected
  • Polyposis typically develops within the third decade of life
• Clinical features
  • Most are initially asymptomatic until progressing to colon cancer
  • Altered bowel habits (constipation/diarrhea), blood in stool, and abdominal pain
  • Congenital hypertrophy of the retinal pigment epithelium (CHRPE): multiple lesions in both eyes appearing in infancy
• Diagnosis
  • Flexible sigmoidoscopy/colonoscopy: > 100 polyps are typically detected in the classic FAP ^[8]
  • Genetic testing: detection of germline mutations in the APC gene establishes the diagnosis ^[9]
  • Histology: tubular, tubulovillous, and villous adenomas
    • Desmoid tumors (aggressive fibromatosis): extremely rare musculoaponeurotic fibromatoses.
• Treatment
  • Screening beginning at 10 years of age
  • Prophylactic proctocolectomy + ileoanal anastomosis at time of diagnosis
  • Screening upper endoscopy beginning at 25 years of age
  • Medical adjuncts: Celecoxib; (a COX-2 inhibitor) and sulindac (an NSAID) can cause regression of polyps.
• Prognosis: The lifetime risk of colorectal cancer is 100% by 45 years of age.
• Variants of FAP
  • Attenuated FAP
    • Lesser polyps (> 10 but < 100), mainly in the right colon
    • More advanced age at presentation
    • Lower risk (80%) of developing colorectal cancer than with classic FAP
  • Gardner syndrome
    • FAP + extracolonic bony and/or soft tissue tumors (e.g., osteomas, desmoid tumors, sebaceous cysts, lipomas, fibromas)
    • APC gene mutation with autosomal dominant inheritance
    • The lifetime risk of developing colorectal cancer is 100%.
  • Turcot Syndrome
    • Adenomatous colonic polyps + brain tumors
    • Associated with FAP and Lynch syndrome
    • Medulloblastomas are associated with FAP and gliomas with Lynch syndrome.

Primarily hamartomatous

Peutz-Jeghers syndrome

• Inheritance
  • Autosomal dominant
  • New mutations: 20% of cases
• Clinical features: 95% of patients have mucocutaneous hyperpigmentation that typically affects the lips (perioral lentigines), buccal mucosa, palms, and soles
• Enteroscopy: multiple hamartomatous polyps throughout the gastrointestinal tract
• Prognosis
  • The lifetime risk of colorectal cancer is ∼40%.
  • Increased risk of ovarian, breast, and pancreatic cancer

Juvenile polyposis syndrome (JPS)

• Etiology: autosomal dominant with incomplete penetrance
• Clinical features: Onset is within the first decade of life, often with gastrointestinal bleeding and anemia
• Colonoscopy: > 10 polyps throughout the gastrointestinal tract

Cowden syndrome

• Etiology: autosomal dominant
• Clinical features
  • Multiple GI polyps + skin manifestations such as papules and hyperkeratosis of the skin and mucous membranes
  • Changes in the thyroid and mammary glands: > 50% of patients have thyroid disorders (e.g., multinodular goiter, adenomas, etc.) and benign breast disorders (e.g., fibroadenomas, intraductal papillomas, etc.).

Cronkhite-Canada syndrome

• Etiology: : probably immune-mediated (rare, nonfamilial disorder)
• Clinical features: GI polyposis with alopecia and cutaneous hyperpigmentation
• Treatment: immune suppression with glucocorticoids and azathioprine

References:^{[2][9][8][10][11][12][13][14][15]}

• Laboratory tests
  • Fecal occult blood test
  • Hemoglobin levels: Anemia
  • Genetic studies: in patients with a strong family history of polyposis syndromes
• Imaging
  • Virtual colonoscopy:
  • Air contrast barium enema: can detect left-sided colonic polyps
• Flexible sigmoidoscopy
  • Advantage: does not require extensive bowel preparation before the procedure.
  • Disadvantage: The rest of the colon is not visualized.
• Colonoscopy (confirmatory test)
  • Preferred screening tool for diagnosed cases of hereditary polyposes/colonic cancer
  • Advantages: Enables biopsy, histological confirmation, and therapeutic polypectomy (see “Classification” above)
  • Disadvantages: Requires bowel preparation with laxatives; Risk of bowel perforation.

References:^[1]