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). 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.

• Age
  • ∼ 30% of individuals > 50 years
  • Incidence increases with age.
• Frequency
  • ∼ 70%: adenomatous polyps
  • ∼ 20%: hyperplastic polyps
  • < 10%: other kinds of polyps (traditional serrated adenomas, sessile serrated adenomas, and mixed mucosal polyps)
• Sex: ♂ > ♀

References:^[1]

Epidemiological data refers to the US, unless otherwise specified.

The exact etiology is unknown. Risk factors include the following. ^[2]

• Lifestyle
  • Diet: high in red meat and fat; low in fiber and folic acid
  • Obesity and lack of exercise
  • Cigarette smoking
  • Alcohol consumption
• Genetic predisposition
  • Black populations
  • Hereditary polyposis syndromes

Macroscopic classification of colonic polyps

• Pedunculated: attached to the GI mucosa by a stalk
• Sessile: have a broad base (no stalk)

Histologic classification of colonic polyps

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

Villous adenomas are villains because they have the highest malignant potential.

• Mostly asymptomatic
• If symptomatic:
  • Hematochezia (the most common symptom)
  • Change in bowel habits (constipation/diarrhea)
  • Mucus in stool
  • Pallor
  • Palpable rectal polyps on digital rectal exam

Hereditary polyposis syndrome

• Adenomatous polyposis syndromes
• Hamartomatous polyposis syndromes

Adenomatous polyposis syndromes

Familial adenomatous polyposis (FAP)

• Etiology
  • Autosomal dominant mutations of the APC gene, a tumor suppressor gene on chromosome 5q22
  • 20–25% of cases have a negative family history. ^[7]
• Epidemiology
  • Polyposis typically develops within the second or third decade of life.
  • 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
• Clinical features
  • Most are initially asymptomatic until progressing to colon cancer.
  • Altered bowel habits (constipation/diarrhea), blood in stool, and abdominal pain
• Diagnostics
  • Flexible sigmoidoscopy/colonoscopy
    • Polyps develop in the entire colon, always including the rectum.
    • > 100 polyps are typically detected in classic FAP.
  • Genetic testing: Detection of germline mutations in the APC gene establishes the diagnosis.
  • Histology
    • Tubular, tubulovillous, and villous adenomas
    • Desmoid tumors (aggressive fibromatosis): extremely rare musculoaponeurotic fibromatoses
• Treatment ^[8]
  • Prophylactic proctocolectomy and ileoanal anastomosis at the time of diagnosis
  • Celecoxib, sulindac, and aspirin can induce regression of polyps. ^[9]
• Prognosis: The lifetime risk of colorectal cancer is 100% by 45 years of age.
• Prevention
  • Annual screening sigmoidoscopy/colonoscopy starting at 10 years of age ^[10]
  • Screening upper endoscopy starting at 25 years of age

Variants of FAP

• Gardner syndrome
  • FAP and extracolonic bony and/or soft tissue tumors; (e.g., osteomas of the mandible or skull, desmoid tumors, sebaceous cysts, lipomas, fibromas)
  • Dental abnormalities (e.g., supernumerary and/or impacted teeth) present in ∼ 30% of cases ^[11]
  • Associated with congenital hypertrophy of the retinal pigment epithelium
    • Round or oval darkly pigmented lesions on fundoscopy
    • The presence of multiple (> 4) lesions bilaterally indicates Gardner syndrome.
    • Solitary lesions have low diagnostic value and are not pathognomonic for a disease.
  • APC gene mutation with autosomal dominant inheritance
  • The lifetime risk of developing colorectal cancer is 100%.
• Turcot syndrome
  • FAP/Lynch syndrome and malignant brain tumors (e.g., gliomas or medulloblastomas)
  • Medulloblastomas are associated with FAP; and gliomas with Lynch syndrome.
  • Increased risk of colorectal cancer
• Attenuated FAP
  • Lesser polyps (10–100), mainly in the right colon
  • More advanced age at presentation
  • Lower risk (∼ 80%) of developing colorectal cancer than with classic FAP

The Turban covers the head: Turcot syndrome is associated with malignant brain tumors.

MYH-associated polyposis ^[12]

• Etiology: autosomal recessive mutation in the MUTYH gene
• Diagnostics
  • Colonoscopy: < 100 colorectal adenomatous polyps
  • Genetic testing
• Prognosis: The lifetime risk of colorectal cancer is 80–90%.

Hamartomatous polyposis syndromes

Peutz-Jeghers syndrome ^[13]

• Etiology: autosomal dominant mutation of the STK11 gene on chromosome 19p13.3 → loss of tumor suppressor function → hyperactive serine‑threonine kinase
• Clinical features: ∼ 95% of patients have hyperpigmented macules; that typically affect the lips (perioral lentigines), buccal mucosa, genitals, palms, and soles
• Diagnostics: multiple hamartomatous polyps throughout the gastrointestinal tract on endoscopy
• Prognosis ^[14]
  • The lifetime risk of colorectal cancer is ∼ 40%.
  • Increased risk of:
    • Breast cancer
    • Ovarian cancer
    • Other GI cancers: pancreatic, small bowel, stomach

Juvenile polyposis syndrome (JPS) ^[14]

• Etiology: autosomal dominant with incomplete penetrance ^[15]
• Epidemiology: : onset within the first decade of life (most commonly affects children < 5 years of age)
• Clinical features: gastrointestinal bleeding and anemia
• Diagnostics: > 10 hamartomatous polyps throughout the gastrointestinal tract (e.g., colon, stomach, small bowel) on endoscopy
• Prognosis: increased lifetime risk of colorectal cancer (∼ 20%)

Cowden syndrome ^[16]

• Etiology: most commonly due to autosomal dominant mutations of the PTEN gene
• Clinical features
  • Multiple GI polyps with skin manifestations such as papules and hyperkeratosis of the skin
  • Most patients have thyroid disorders (e.g., multinodular goiter, adenomas) and breast disorders (e.g., fibroadenomas, intraductal papillomas).
• Prognosis
  • Increased risk of breast (∼ 85%), thyroid (∼ 35%), and endometrial cancers (∼ 30%)
  • Increased risk of colorectal cancer (up to 20% before the age of 50)

Cronkhite-Canada syndrome ^[17]

• Etiology: probably immune-mediated (rare, nonfamilial disorder)
• Clinical features: GI polyposis with alopecia and cutaneous hyperpigmentation
• Treatment: immune suppression with glucocorticoids and azathioprine
• Prognosis: high mortality rate due to GI bleeding, sepsis, and congestive heart failure

• Laboratory tests
  • Fecal occult blood test
  • CBC: anemia
  • Genetic studies: in patients with a strong family history of hereditary polyposis syndromes
• Imaging
  • Virtual colonoscopy
  • Air contrast barium enema: can detect left-sided colonic polyps
• 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.
• Flexible sigmoidoscopy
  • Allows visualization of the rectum and sigmoid, where the majority of colonic polyps/cancers are located
  • Advantage: does not require extensive bowel preparation before the procedure
  • Disadvantage: The rest of the colon is not visualized.

Treatment depends on the etiology and nature of the polyp or polyps.

• Snare polypectomy: cold snaring for diminutive lesions (≤ 5 mm in size) ^[18][19]
• Endoscopic mucosal resection: large sessile polyps
• Surgical resection ^[3]
  • For large polyps (> 2 cm)
  • For suspected malignancy, see “Colorectal cancer”.
  • Hereditary polyposis syndromes

These recommendations are consistent with the US Multi-Society Task Force on Colorectal Cancer 2020 guidelines. ^[20][21]