Oncology: Colorectal Cancer & Polyposis Syndromes

Colorectal Cancer & Polyposis Syndromes

Syndromes

  • Familial Adenomatous Polyposis (FAP)
  • Lynch Syndrome (Hereditary Nonpolyposis Colon Cancer/HNPCC)
  • Juvenile Polyposis Syndrome (JPS/Familial Juvenile Polyposis)
  • MUT Y Homolog (MUTYH)-Associated Polyposis (MAP)
  • Peutz-Jeghers Syndrome
  • Serrated Polyposis Syndrome (SPS)/Hyperplastic Polyposis Syndrome (HPS)
  • PTEN Hamartoma Tumor Syndromes:
    • Cowden Syndrome
    • Bannayan-Riley-Ruvalcaba Syndrome
    • Cronkhite-Canada Syndrome

Familial Adenomatous Polyposis (FAP)

Basics

  • Autosomal Dominant
  • Mutation: APC Gene

Presentation

  • 100’s-1,000’s of Colorectal Polyps
    • Also See Duodenum Polyps with Predilection of the Ampulla/Periampullary Region
  • Colorectal Cancer Risk: Nearly 100% By Age 40
    • The Adenomas Themselves are More Abundant but Do Not Have an Individually Higher Risk of Malignancy
  • Timing/Progression:
    • Onset of Polyps: Puberty
    • Diffuse Polyposis: 20-30’s
    • Colorectal Cancer Diagnosis: Average Age 39
  • Extracolonic Manifestations:
    • Desmoid Tumors
    • Osteomas
    • Sebaceous Cysts

Variants

  • Gardner’s Syndrome: FAP with Extracolonic Manifestations
    • *Originally Described Colonic Polyposis with Extracolonic Manifestations but Now FAP & Gardner Syndrome are Essentially Interchangeable
  • Turcot’s Syndrome: FAP with Brain Tumors
    • Medulloblastoma & Glioma Most Common
  • Attenuated FAP: Oligopolyposis (10-99 Adenomas) with Later Onset (40-50’s)
    • Lower Risk of Colorectal Cancer (80%)
  • Gastric Adenocarcinoma & Proximal Polyposis of the Stomach (GAPPS): 100’s of Stomach Polyps
    • Polyps Develop in the Body & Fundus but Spare the Antrum
    • Generally Do Not See Colorectal Polyps

Diagnosis

  • Clinical Diagnosis Often Clear on Colonoscopy
    • Flexible Sigmoidoscopy Alone is Often Sufficient
  • Primary Diagnosis: APC Gene Mutation

Screening

  • Flexible Sigmoidoscopy Every Year, Starting at Age 10-12
    • *Continues Even After Colectomy
  • Screening EGD Every 2-3 Years After Age 25
    • *Or Start Whenever Colon Polyps are Fist Seen (Whichever Comes First)

Surgical Management

  • Colectomy Indications (2015 ACG Guidelines):
    • Documented or Suspected Colorectal Cancer
    • Significant Symptoms
    • Adenomas:
      • Adenomas with High-Grade Dysplasia
      • Significant Increase in Number of Polyps on Consecutive Exams
      • Multiple Large Adenomas > 6 mm
    • Inability to Adequately Survey the Colon Because of Multiple Diminutive Polyps
  • Consider Prophylactic Colectomy by Age 20-25 if Otherwise Not Indicated
  • Surgery Options:
    • Total Abdominal Colectomy with Ileorectal Anastomosis (IRA)
      • Spares Rectum – 5-25% Risk of Future Rectal Cancer
      • Only Considered for Mild Polyposis Burden
      • Requires Flexible Proctoscopy Every 6-12 Months
    • Total Proctocolectomy with Ileal Pouch Anal Anastomosis (IPAA)
      • Resects Majority of the Rectum
      • Requires Flexible Pouchoscopy Every 6-12 Months
    • Total Proctocolectomy with End Ileostomy
      • Requires Flexible Endoscopy of Ostomy Every Year

FAP on Colonoscopy 1

Lynch Syndrome (Hereditary Nonpolyposis Colon Cancer/HNPCC)

Basics

  • Autosomal Dominant
  • Mutations: MLH1, MLH2, MSH6 or PMS2
    • DNA Mismatch Repair Genes
    • Cause Microsatellite Instability (Genetic Hypermutability)
  • 20% are Sporadic Mutations

Types

  • Type I: Colorectal Cancer
  • Type II: Colorectal Cancer & Extracolonic Malignancy

Presentation

  • Colorectal Cancer
    • Most Common Site: Right Colon (Sporadic Cancers are Most Common on the Left)
    • Lifetime Risk: 12-90% Depending Mutation & Associated Risk Factors
  • Endometrial Cancer
    • Most Common Extracolonic Malignancy
  • Other Less Common Extracolonic Malignancies:
    • Ovarian Cancer
    • Stomach Cancer
    • Small Bowel Cancers
    • Pancreatic Cancer
    • Kidney Cancer
    • Bladder Cancer
    • Brain Tumors

Amsterdam Criteria

  • Family History-Based Criteria to Help Identify Patients at Risk for Lynch Syndrome
  • “3-2-1 Rule”
    • 3 Relatives Affected
    • 2 Generations Affected
    • 1 Before Age 50
  • Low Sensitivity
  • *Amsterdam Criteria is Not Diagnostic, Diagnosis Confirmed by Genetic Screening

Screening

  • Colonoscopy Every 1-2 Years, Starting at Age 20-25
  • EGD Every 2-4 Years, Starting at Age 30-35
  • Pelvic Exam & Endometrial Biopsy Every Year, Starting at Age 30-35

Surgical Management

  • Surgical Options for Colorectal Cancer or Unresectable Adenomas:
    • Total Abdominal Colectomy with Ileorectal Anastomosis (IRA)
      • Requires Flexible Proctoscopy Every Year
    • Total Proctocolectomy with Ileal Pouch Anal Anastomosis (IPAA)
    • Total Proctocolectomy with End Ileostomy
  • Risk-Reducing TAH-BSO is Indicated for Females After Age 40 or at Completion of Childbearing

Other Syndromes

Juvenile Polyposis Syndrome (JPS/Familial Juvenile Polyposis)

  • Mutations: SMAD4 (MADH4) or BMPR1A
    Mn
    • Autosomal Dominant
  • Presents with Multiple Hamartomas Throughout the GI Tract
  • Most Patients Have Symptoms by Age 20 (Anemia/GI Bleeding)
  • Risk or Colorectal Cancer: 10-40%
    • Also at Increased Risk for Stomach & Small Intestinal Cancers
  • Surveillance: Colonoscopy Every 1-3 Years, Starting at Age 12
    • Also Consider Concurrent EGD Surveillance

MUT Y Homolog (MUTYH)-Associated Polyposis (MAP)

  • Mutation: MYHH Gene
    • Autosomal Recessive
  • Characterized by 10-100 Colorectal Adenomatous Polyps
    • Often Right-Side Predominant
  • Risk or Colorectal Cancer: 60-75%
  • Extracolonic Manifestations:
    • Gastric Polyps
    • Duodenal Polyps
    • Desmoid Tumors
    • Osteomas
    • Thyroid Cancer
    • Retinal Pigment Epithelial Hypertrophy
    • Epidermal Cysts
  • Surveillance: Colonoscopy Every 1-2 Years, Starting at Age 20-30

Serrated Polyposis Syndrome (SPS)/Hyperplastic Polyposis Syndrome (HPS)

  • Definitions (WHO Criteria):
    • > 20 Serrated Polyps
    • Any Serrated Polyps Proximal to the Sigmoid Colon with a Family Hx of SPS
    • ≥ 5 Serrated Polyps > 5 mm Proximal to the Rectum with ≥ 2 > 10 mm
  • Mutations: RNF43 (Most Closely Related), SMAD4, BMPR1A, PTEN or MUTYH
    • Most Patients Have No Predisposing Mutation
  • Risk or Colorectal Cancer: 25-40%

Peutz-Jeghers Syndrome

PTEN Hamartoma Tumor Syndrome

Comparisons

Colorectal Cancer & Polyposis Syndromes

Colorectal Stomach/SI Osteoma Desmoid Thyroid Endometrium Breast Other
FAP X X
Turcot X X Brain Tumors
Gardner X X X X Sebaceous Cysts
Lynch X X X
MAP X X X X X Eye & Epidermoid Cyst
Cowden X X X X X Kidney
Peutz-Jeghers X X X X Melanin Spots, Pancreas & Testicles
JPS X X            
SPS X  
  • Not Included: Bannayan-Riley-Ruvalcaba Syndrome & Cronkhite-Canada Syndrome

Mnemonics

Familial Juvenile Polyposis

  • Juveniles Get “MAD” (Mutation: SMAD4/MADH4)

References

  1. Makarewicz W, Bobowicz M, Sawicka W, Rzyman W. The treatment of chronic pleural empyema with laparoscopic omentoplasty. Initial Report. Wideochir Inne Tech Maloinwazyjne. 2014 Dec;9(4):548-53. (License: CC BY-NC-ND-3.0)