Familial Adenomatous Polyposis (FAP)

Johnathan W. Cain, DO
The Operative Review of Surgery. 2023; 1:103-111.

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Table of Contents

Pathophysiology
Extracolonic Manifestations
Variations
Diagnosis and Screening
Surgical Management

Other Colorectal Cancer and Polyposis Syndromes
References

Pathophysiology

Genetic Mutation 1

  • Mutation in the APC Gene
    • APC: Adenomatous Polyposis Coli
    • Tumor Suppressor Gene
  • Autosomal Dominant

Incidence 2

  • Incidence: 1/8,300 Births
  • Accounts for < 1% of All Colorectal Cancer Cases

Presentation

  • Hallmark is 100’s-1,000’s of Colorectal Polyps 3
  • 100% Lifetime Risk of Colorectal Cancer
  • 70-80% of Tumors Occur in the Left Colon 4

Histology

  • Numerous Sessile Polyps Throughout the Colon
  • Generally ≤ 1 cm
  • Various Histologic Features, Similar to Sporadic Colorectal Cancers 5
  • The Adenomas Themselves are More Abundant but Do Not Have an Individually Higher Risk of Malignancy

Timing and Progression

  • Onset of Polyps: 6
    • 50% by Age 15
    • 95% by Age 35
  • Average Age of Colorectal Cancer Diagnosis: 35-40 7

FAP on Colonoscopy 8

Extracolonic Manifestations

Duodenum Polyps
  • Incidence: 30-70% 3
  • Second Most Common Site of Adenomas 3
  • Second Most Common Cause of Death 9
  • Predilection for the Ampulla and Periampullary Region 10
  • Spigelman Staging of Duodenal Polyps in FAP 11
    • Stage 0: 0 Points
    • Stage I: 1-4 Points
    • Stage II: 5-6 Points
    • Stage III: 7-8 Points
    • Stage IV: 9-12 Points
Factor 0 Points 1 Point 2 Points 3 Points
Number of Polyps 0 1-4 5-20 > 20
Polyp Size No Polyps 1-4 mm 5-10 mm > 10 mm
Histology No Adenomas Tubular Adenoma Tubulovillous Adenoma Villous Adenoma
Dysplasia None Low Grade NA High Grade
Stomach Polyps
  • Incidence: 30-88% 3,12
  • Most Commonly Benign Fundic Gland Polyps (FGPs) 3
  • 60% Sporadic but 40-80% Have > 100 Polyps 13
Desmoid Tumors
  • Incidence: 21% 14
  • Generally Benign with Low Risk of Distant Metastases 14
  • Locally Aggressive with High Recurrence Rates 3,14
  • Third Most Common Cause of Death in FAP 15
  • Intraabdominal/Mesenteric Fibromatosis is the Most Common Subtype 16
Osteomas
  • Incidence: 65-80% 3
  • Most Common in the Frontal Bones 17
    • Can Also Affect the Mandible, Maxilla, or Long Bones
  • Range in Size from Slight Thickening to Large Palpable Masses 3
Brain Tumors
  • 3x Overall Increased Risk 18
  • Associated Tumors: 18
    • Medulloblastoma – Most Common (13x Increased Risk)
    • Astrocytoma
    • Less Commonly: Ependymoma, Pinealblastoma, Ganglioglioma
  • Most Commonly Develop During Childhood 18
  • Previously Described as Turcot Syndrome – Now Only Considered a Part of the FAP Spectrum

Congenital Hypertrophy of Retinal Pigment Epithelium (CHRPE)

  • Incidence: 90% 19
  • The Most Common and Earliest Extraintestinal Manifestation of FAP 20,21
  • Described as At Least One Dark Pigmented Lesion with a Halo in the Retina 22
  • No Malignant Potential 23

Dental Abnormalities

  • Incidence: 30-75% 25
  • Include Impacted Teeth, Tooth Ankylosis, Missing Teeth, Supernumerary Teeth, Hypercementosis, or Compound Odontomas 25,26

Other Less Common Associations 3

  • Thyroid Cancer
  • Nasopharyngeal Angiofibroma
  • Benign Skin Tumors
    • Epidermal Cyst
    • Fibroma
    • Lipoma
    • Pilomatricoma
  • Hepatoblastoma
  • Pancreatic Cancer
  • Adrenal Tumors

CHRPE 24

Variations

Classical FAP

  • FAP as Described Above

Attenuated FAP (AFAP)

  • Less Aggressive Phenotypic Variant
  • Develop Fewer Polyps; Defined as < 100 Polyps (Oligopolyposis) 27
  • Later Age of Diagnosis 28
  • Later Age of Onset of Colorectal Cancer: Average Age 55 29
  • Lower Risk of Colorectal Cancer (70-80%) 29,30
  • Extracolonic Manifestations are Less Frequent 27

Gastric Adenocarcinoma and Proximal Polyposis of the Stomach (GAPPS)

  • Defined as > 100 Polyps in the Proximal Stomach 27,31
  • Polyps are Restricted to the Body and Fundus 31
    • Spares the Antrum 31
  • Predominantly Benign Fundic Gland Polyps (FGPs) 31
    • Some Have Regions of Dysplasia with High Risk of Cancer
  • No Evidence of Colorectal or Duodenal Polyps 27

Historical Variants

  • Gardner’s Syndrome: FAP with Extracolonic Manifestations
  • Turcot’s Syndrome: FAP with Brain Tumors
  • *Originally Described Colonic Polyposis with Extracolonic Manifestations but Gardner’s Syndrome and Turcot’s Syndrome are Now Considered a Part of the FAP Spectrum 32

GAPPS on Upper Endoscopy: (A) GE Junction, (B) Cardia, (C) Fundus, (D) Body, (E) Spared Antrum, (F) Spared Duodenum 31

Diagnosis and Screening

Diagnosis

  • Clinical Diagnosis Can Be Clear on Colonoscopy
    • Flexible Sigmoidoscopy Alone is Often Sufficient
  • Primary Diagnosis is Made by an APC Gene Mutation
  • Patients with a Family History of FAP Should Undergo Genetic Counseling/Screening by Age 10-12 33

Colonoscopy

  • High-Quality Colonoscopy Starting at Age 10-15 Years 34
  • Repeat Every Year 34
  • Flexible Sigmoidoscopy May Be Considered Based on patient and Family preference or Clinical Judgment 34
    • Risk for Missing Transverse or Right-Sided Colon Polyps

Upper Endoscopy

  • Start Screening at Age 20-25 34
    • Start Immediately if Any Colon Polyps are Seen
  • Repeat Endoscopy Based on Spigelman Stage 34
    • Stage 0: Every 3-5 Years
    • Stage I: Every 2-3 Years
    • Stage II: Every 1-2 Years
    • Stage III: Every 6-12 Months
    • Stage IV: Expert Surveillance Every 3-6 Months

Other Screening Considerations

  • May Also Consider Screening with Thyroid Ultrasound Every 2-5 Years Starting in Late Teenage Years 34
  • No Specific Guidelines for Desmoid Tumor or Brain Tumor Surveillance

Surgical Management

Indications for Colectomy

  • Absolute Indications (2015 ACG Guidelines): 35
    • Documented or Suspected Colorectal Cancer
    • Significant Symptoms
  • Relative Indications (2015 ACG Guidelines): 35
    • Multiple Large Adenomas > 6 mm
    • Significant Increase in Adenoma Number on Consecutive Exams
    • Adenoma with High-Grade Dysplasia
    • Inability to Adequately Survey the Colon Because of Multiple Diminutive Polyps
  • Consider Prophylactic Colectomy if Otherwise Not Indicated 36
    • Exact Timing is Debated
    • Most Patients Undergo Surgery Between Ages 15-25 Years 36

Surgical Options

  • Total Abdominal Colectomy with Ileorectal Anastomosis (TAC/IRA)
    • Spares Rectum
    • Advantages:
      • Technically Easier
      • Lower Risk of Complications
      • No Risk for Sexual or Bladder Dysfunction
      • No Permanent Stoma
    • Highest Risk of Metachronous Cancer in the Remaining Rectum (5-25% Future Risk)
    • Generally Contraindicated for Severe Rectal Disease or if the Patient is Not Reliable for Follow-Up Surveillance
    • Requires Flexible Proctoscopy Every 6-12 Months 34
  • Total Proctocolectomy with Ileal Pouch Anal Anastomosis (IPAA)
    • Resects the Majority of the Rectum – More Complex Operation
    • Advantages:
      • Lower Risk of Metachronous Cancer than TAC/IRA
      • No Permanent Stoma
    • Risk for Sexual or Bladder Dysfunction and Possible Fecal Incontinence
    • Requires Flexible Pouchoscopy Every 6-12 Months 34
  • Total Proctocolectomy with End Ileostomy
    • Requires a Permanent Stoma
    • Risk for Sexual or Bladder Dysfunction
    • Requires Flexible Endoscopy of Ostomy Every Year 34

Other Colorectal Cancer and Polyposis Syndromes

Syndromes

  • Familial Adenomatous Polyposis (FAP)
  • Lynch Syndrome
  • Juvenile Polyposis Syndrome (JPS)/Familial Juvenile Polyposis
  • MUT Y Homolog (MUTYH)-Associated Polyposis (MAP)
  • Peutz-Jeghers Syndrome (PJS)
  • Serrated Polyposis Syndrome (SPS)
  • PTEN Hamartoma Tumor Syndromes: (PHTS)

Comparisons

References

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