Colonic Polyps and Neoplastic Diseases

  • Discussed by Ana Tchania on January 8, 2025.

Topics Overview

  • Colonic Polyps and Neoplastic Disease
  • Inflammatory Polyps
  • Hamartomatous Polyps
    • Juvenile Polyps
    • Peutz-Jeghers Syndrome
  • Hyperplastic Polyps
  • Adenomas
  • Familial Colonic Neoplasia Syndromes
    • Familial Adenomatous Polyposis
    • Hereditary Nonpolyposis Colorectal Cancer
  • Adenocarcinoma
  • Appendix
  • Acute Appendicitis
  • Tumors of the Appendix
  • Reference: Kumar, Abbas, Aster. (2022). Robbins & Kumar Basic Pathology. 11th ed. - Ch. 13, pages 520-528

Types of Polyps

  • Neoplastic vs Non-neoplastic Polyps

    • Neoplastic Polyps:
    • Adenomatous
    • Carcinomas
    • Non-neoplastic Polyps:
    • Inflammatory Polyps
    • Hyperplastic Polyps
    • Hamartomatous Polyps (associated with Peutz-Jeghers syndrome and juvenile polyposis)

  • Adenomatous Polyps

    • Most common type of colonic polyp associated with neoplastic changes.

  • Inflammatory Polyps

    • Associated with inflammatory bowel diseases.
Specific Types of Polyps
  • Prespectives on Cell Turnover
    • Hyperplastic Polyps:
      • Typically less than 5 mm and multiple, primarily found in the left colon.
      • Clinical significance due to resemblance with sessile serrated adenomas.
      • Pathogenesis involves decreased epithelial cell turnover and accumulation of goblet cells.
      • They show serrated architecture limited to the surface epithelium.

Inflammatory Polyps

  • Characteristics
    • Clinical triad:
    • Rectal bleeding
    • Mucus discharge
    • Inflammatory lesion of the anterior rectal wall
    • Causes:
    • Impaired relaxation of anorectal sphincter leading to recurrent mucosal trauma, ulceration, and subsequent repair resulting in polyp formation
    • Morphology:
    • Mixed inflammatory cells, erosion, and induced lamina propria prolapse.

Polyposis Syndromes

  • Syndromes Associated with Polyps:

    • Familial Adenomatous Polyposis (FAP)
    • Gardner Syndrome
    • Turcot Syndrome
    • Peutz-Jeghers Syndrome
    • Tuberous Sclerosis
    • Cronkhite-Canada Syndrome
    • Cowden Syndrome
    • Juvenile Polyposis Syndrome

  • Hamartomatous Polyps

    • Definition: Disorganized mass of normal tissue elements without dysplasia.
    • Characteristics: Often pedunculated; may autoamputate and cause painless bleeding.

Genetic Basis of Polyposis Syndromes

  • Gene mutations lead to various polyposis syndromes affecting cancer risk:
    • Lynch Syndrome:
    • Associated neoplasms include colorectal cancer, endometrial cancer, and others
    • Genes involved: MSH2, MLH1, MSH6, PMS2
    • Familial Adenomatous Polyposis (FAP):
    • Gene: APC
    • 100% risk of colorectal cancer if untreated by age 30
    • Other syndromes linked to genetic mutations include Li-Fraumeni (TP53), and multiple endocrine neoplasia type 1 (MEN1).

Epidemiology and Clinical Presentation

  • Juvenile Polyposis
    • Predominantly found in children under 5 years.
    • Presentation: Painless rectal bleeding, potential prolapse through anal sphincter
    • Molecular Genetics: Involves germline mutations in TGF-β/BMP pathway genes, such as SMAD4.
    • Cancer Risk: Increased in juvenile polyposis syndrome compared to sporadic juvenile polyps, with risk for several types of adenocarcinoma.

Peutz-Jeghers Syndrome

  • Characteristics

    • Autosomal dominant inheritance; rare occurrence
    • Genetics: Mutations in STK11/LKB1 gene.
    • Triad of clinical features:
    • Multiple GI hamartomatous polyps
    • Mucocutaneous hyperpigmentation
    • Increased risk for multiple malignancies, including gastrointestinal cancers
    • Complications include intussusception and multiple cancers.

  • Morphology

    • Common in the small intestine characterized by large, pedunculated lobulated polyps with arborizing networks of smooth muscle and glands lined by normal epithelium.

Cowden Syndrome

  • Major and Minor Diagnostic Criteria
    • Major criteria:
    • Breast and thyroid cancer (usually follicular)
    • Macrocephaly
    • Lhermitte-Duclos disease (dysplastic cerebellar gangliocytoma)
    • Endometrial cancer
    • Minor criteria:
    • Other thyroid lesions, mental retardation, fibrocystic disease of breast, lipomas, GU tumors, or malformations.
Adenomatous Polyps
  • Characteristics
    • Colonic adenomas are benign polyps that give rise to the majority of colorectal adenocarcinoma.
    • They are premalignant/dysplastic, and prevalence increases with age with no significant gender difference.
    • Morphology: Ranges from 0.3 cm to 10 cm, either pedunculated or sessile, presenting a velvety, bumpy surface.
    • Size >4 cm correlates heavily with malignancy risk.
Types of Adenomas
  • Tubular Adenomas
    • Most common type (80%); characterized by small, pedunculated polyps with rounded or tubular glands.
  • Tubulovillous Adenomas
    • Involves a mix of tubular and villous elements, larger and sessile, covered with slender villi.
  • Villous Adenomas
    • Less common; characterized by long projections, usually sessile, with high risk of colon cancer.
    • Can cause excessive mucous secretion and, rarely, secretory diarrhea.
Sessile Serrated Adenomas (SSA)
  • Often overlap with hyperplastic polyps but often lack dysplasia.
  • Malignant Potential: similar to conventional adenomas.
  • Distinguishing Feature: Serrated architecture extends through the entire gland length, associated with crypt dilation and lateral growth.
Risk of Progression from Adenoma to Carcinoma
  • Related factors include size >2 cm, sessile growth, and villous histology.
  • Risk escalates as follows:
    • <1 cm: extremely rare for cancer
    • 4 cm: up to 40% may harbor invasive carcinoma.
Adenocarcinoma
  • Epidemiology and Characteristics
  • Most common malignancy of the gastrointestinal tract and the third most common cause of cancer deaths.
    • Peaks in incidence at 60 to 70 years of age; less than 20% of cases occur before age 50.
    • More common among males and in high-income countries (e.g., USA, Canada).
Risk Factors for Colorectal Cancer
  • Includes adenomatous and serrated polyps, familial cancer syndromes, inflammatory bowel disease (IBD), tobacco use, and diet high in processed meats and low in fiber.
Pathogenesis and Genetic Factors
  • Adenoma-Carcinoma Sequence:
    • Involves mutation in APC/β-catenin leading to FAP and most sporadic colorectal cancer (CRC).
    • Lynch Syndrome pathogenesis involves mutations in mismatch repair genes (MSH1 or MLH1) causing the serrated polyp pathway.
    • COX-2 overexpression linked to colorectal cancer, with NSAIDs considered potential chemopreventive agents
Patterns of Colorectal Neoplasia
  • Familial adenomatous polyposis predominantly from APC mutations.
  • Lynch syndrome involves MMR (mismatch repair) mutations.
  • Sporadic cancer arises from either adenoma-carcinoma or MMR defects, with varying levels of gland formation based on histology (well, moderately, poorly differentiated).

Diagnosis of Polyps

  • Colonoscopy:
    • Recommends screening every 10 years starting at ages 45 to 50, with biopsies usually performed.
  • Fecal Occult Blood Testing (FOBT):
    • Detects occult blood, useful for screening.

Acute Appendicitis

  • Causes:
    • Obstruction by fecalith or gallstone in adults; in children, lymphoid hyperplasia often due to various infections.
Symptoms and Diagnosis
  • Progressively increasing abdominal pain, nausea, and fever manifest in stages leading to perforation.
  • Physical exam reveals classic signs such as McBurney's point tenderness and Rovsing’s sign.
  • Labs show neutrophilic leukocytosis with left shift.
Complications of Appendicitis
  • Periappendiceal abscess, risk of seeding through the portal vein, and potential hydronephrosis due to ureteral compression.

Tumors of the Appendix

  • Carcinoids:
    • Most common and often incidental discoveries during examinations.
    • Characterized by serotonin production and associated with various symptoms such as flushing and valvular lesions depending on metastasis to other areas.

Summary of Molecular Events in Colorectal Cancer

  • Key mutations include APC (early event), KRAS (adenoma progression), and TP53 (carcinoma progression).
  • MMR gene defects in Lynch syndrome lead to microsatellite instability, while BRAF mutations are found in serrated pathway lesions.