Colon Polyps

Overview

Types of colon polyps

• Benign:
  • Hyperplastic: no neoplastic potential
  • Hamartomatous: mixture of normal tissues but growing in a disorganized mass
    • Juvenile: usually solitary, can be seen in children, not associated with an increased risk of colorectal cancer (CRC)
    • Phosphatase and tensin homolog (PTEN) hamartoma tumor syndrome: comprised of the Cowden and Bannayan-Riley-Ruvalcaba syndromes
    • Peutz-Jeghers polyps: usually associated with Peutz-Jeghers syndrome
  • Inflammatory: common in ulcerative colitis
• Neoplastic:
  • Tubular adenoma
  • Villous adenoma
  • Mixed tubulovillous
  • Sessile serrated

Prevalence of colon polyps

• Colon polyps are found in 15%–40% of adults.
• Most neoplastic colon polyps are adenomas (approximately ⅔):
  • 30%–50% of individuals with 1 adenoma ≥ 1 other adenoma.
  • Less common in Asia, but increasing as Western diets are adopted.
• Most colorectal cancers (CRCs) arise from sporadic adenomatous polyps:
  • Early detection of adenomatous polyps by screening decreases the risk of CRC.
  • Lifetime incidence (in individuals with average risk) of CRC in the United States: about 4%.

Risk factors

• Increasing age is a risk factor for developing adenomas.
• Diet: high in red meat and fat, low in fiber
• Inflammatory bowel disease:
  • Ulcerative colitis
  • Crohn’s disease
• Family history
• Tobacco and alcohol use
• Obesity
• African heritage
• Uncontrolled type 2 diabetes

Hereditary polyposis syndromes

Each syndrome occurs in < 1% of the population and accounts for 5%–10% of CRCs.

• Hereditary nonpolyposis colorectal cancer (HNPCC, or Lynch syndrome):
  • Most common inherited cause of cancer 
  • Accounts for 2%–4% of CRCs
  • Autosomal dominant inheritance
  • Prevalence: 1 in 279 people
  • DNA mismatch repair (MMR) gene mutations
  • Cancer occurs at multiple sites.
  • Slightly higher number of neoplastic polyps than normal; also, higher rate of progression to CRC
  • Associated cancers in individuals with HNPCC and/or in 1st-degree relatives, especially endometrial, ovarian
• Familial adenomatous polyposis (FAP) syndrome and variants: 
  • Autosomal dominant inheritance or sporadic mutations
  • Gene affected: APC
  • Classic FAP: prevalence 1 in 7000 people; each has ≥ 100 polyps.
  • Attenuated FAP: a mild form of FAP (10–99 polyps) 
• Juvenile polyposis syndrome:
  • 1st polyps appear at < 5 years of age
  • Autosomal dominant
• Peutz-Jeghers syndrome (PJS): 
  • Presents in childhood
  • Autosomal dominant 

Pathophysiology

Benign polyps

• Hyperplastic polyps: benign reactive epithelial proliferation
• Hamartomatous polyps: may occur sporadically or be genetically determined
  • Have different proportions and placement of normal colonic tissues
  • Cowden syndrome: mostly in PTEN hamartoma tumor syndrome group 
  • Cronkhite-Canada syndrome: nonhereditary; unknown cause
  • Tuberous sclerosis: TSC1 (hamartin, TSC (tuberin), mTOR pathway)
  • Juvenile polyposis: sporadic or autosomal dominant, with mutations in SMAD4, BMPR1A; transforming growth factor β 
  • PJS: autosomal dominant
• Inflammatory polyps: due to chronic cycles of injury and healing (e.g., inflammatory bowel disease)

Neoplastic polyps

• Adenomatous polyp: low-grade dysplasia
  • May transform to high-grade dysplasia/carcinoma in situ (over several years to decades) and eventually to colon cancer as it gathers more mutations 
  • Precursors to the majority of colon cancers
  • Usually follow the chromosomal instability (APC mutation) pathway
  • Can have tubular, villous, or tubulovillous architecture
  • Correlation with invasive CRC increases with:
    • Size (most important factor): rare if adenoma < 1 cm; 40% of adenomas > 4 cm contain foci of invasive cancer.
    • High-grade dysplasia
    • Villous architecture
  • Initial mutation event causing adenoma/dysplasia: more common in regenerating epithelium (e.g., inflammatory bowel disease)
• Sessile serrated adenomas:
  • 15% of sporadic CRCs
  • No cytologic features of dysplasia as in other adenomas, but similar malignant potential
• Hereditary polyposis syndromes with neoplastic polyps:
  • Lynch syndrome: mutations in MMR genes
  • FAP and variants: initial mutation in APC gene

Clinical Presentation

Most colon polyps are asymptomatic and discovered on routine colon cancer screening.

• Symptomatic polyps may present with:
  • Blood or mucus in stool
  • Change in bowel movements:
    • Constipation
    • Diarrhea
  • Obstruction or intussusception if polyp large enough
• Hereditary syndromes:
  • Lynch syndrome:
    • Present with a higher number of polyps than in the general population
    • CRC may develop without first forming a visible precursor polyp.
    • Typically, have sessile serrated adenomas in the right colon
  • FAP:
    • Positive family history of the disease
    • Present with CRC early, at 20–50 years of age (median age: 39 years)
    • Have ≥ 100 (or > 1000) colorectal polyps 
  • PJS:
    • May present with hamartomatous polyps elsewhere (stomach and small bowel)
    • Pigmented skin lesions: melanotic macules of the skin and mucous membranes
  • Cowden syndrome:
    • Presents with multiple hamartomas in the colon
    • Facial mucocutaneous lesions 

Diagnosis and Management

The definitive diagnosis and treatment of colon polyps are achieved by endoscopic removal of the entire polyp.

Diagnosis

• Screening colonoscopy or other forms of colon cancer screening to detect polyps early:
  • Starting at age 50 years in people of average risk:
    • Age 45 in African Americans
    • Earlier if 1st-degree family member has CRC at age < 60 years
  • Earlier and more frequently in individuals at higher risk:
    • Inflammatory bowel disease
    • Hereditary at-risk syndromes 
• Colonoscopy is needed for polyp removal if detected by other studies:
  • CT colonography
  • Sigmoidoscopy
  • Positive stool testing for occult blood and DNA mutations
• Baseline colonoscopy findings:
  • No adenomas: 3.3%
  • 1–2 adenomas < 10 mm: 4.9%
  • High-risk adenoma: 17.3%
• Molecular testing indicated in suspected hereditary polyposis or CRC syndromes

Management

Follow-up guidelines after colonoscopy and polypectomy (based on 2020 Consensus Update by the U.S. Multi-Society Task Force on Colorectal Cancer):

• Based on the findings at 1st colonoscopy:
  • Risk of CRC in the 10 years following a normal colonoscopy: < 0.5%, based on findings in 4.3 million individuals
  • Quality assumptions: 
    • Complete exam to cecum
    • Adequate prep
    • Skilled colonoscopist with adequate adenoma detection rate 
• Normal colonoscopy → repeat in 10 years
  • No adenomatous polyps
  • Hyperplastic polyps < 10 mm
• Low-risk adenomas → repeat in 7–10 years
  • Number: only 1 or 2 found
  • Size: < 10 mm
  • Histology: low-grade dysplasia
• Sessile serrated polyps (SSPs) → repeat in 5–10 years
  • 1–2 SSPs
  • Size: < 10 mm 
• Abnormal findings below → repeat in 3–5 years
  • > 3 adenomatous polyps < 10 mm
  • 3–4 SSPs < 10 mm
  • Hyperplastic polyp > 10 mm
• Advanced neoplasia or high-risk adenomas → repeat in 3 years
  • 5–10 adenomas
  • 5–10 SSPs
  • Adenoma or SSP > 10 mm
  • Histology:
    • Tubulovillous or villous
    • High-grade dysplasia
• > 10 adenomas → repeat in 1 year
• Segmental colonic resection for large (> 2 cm) polyps or lymphovascular invasion