Familial Adenomatous Polyposis

Background
Familial adenomatous polyposis (FAP) is the most
common adenomatous polyposis syndrome.
 Familial Adenomatous Polyposis
• Background
• It is an autosomal dominant inherited disorder
characterized by the early onset of hundreds to
thousands of adenomatous polyps throughout the
colon.
 Familial Adenomatous Polyposis

• Background
• If left untreated, all patients with this syndrome
develop colon cancer by age 35-40 years.

• In addition, an increased risk exists for the

development of other malignancies.
 Familial Adenomatous Polyposis

• Pathophysiology
• The APC gene is a tumor suppressor gene that is
located on band 5q21.

• Normal APC protein promotes apoptosis in colonic cells.

 Familial Adenomatous Polyposis
• Pathophysiology
• Its most important function may be to sequester
the growth stimulatory effects of b-catenin, a
protein that transcriptionally activates growth-
associated genes in conjunction with tissue-
coding factors.
 Familial Adenomatous Polyposis

• Pathophysiology
• ► Mutations of the APC gene result in a
truncated/nonfunctional protein.

• The resultant loss of APC function prevents apoptosis

and allows b-catenin to accumulate intracellularly and
to stimulate cell growth with the consequent
development of adenomas.
• Pathophysiology
• Remember
• ► This process is similar to that which occurs in
sporadic adenomas.

• As a result, APC is considered the gatekeeper

of colonic neoplasia. Its mutation/inactivation
is the initial step in the development of colorectal
cancer in patients with FAP.
 Familial Adenomatous Polyposis
• Pathophysiology
• Germline (i.e. inherited) mutations of the APC gene, as
is the case with FAP, result in cells containing 1
mutated and 1 normal copy of the gene.

• Patients inherit one mutated APC allele from an

affected parent, and adenomas develop as the second
allele from the unaffected parent becomes mutated or
lost.
 Familial Adenomatous Polyposis

• Pathophysiology
• Remember
• Consequently, every colonic epithelial cell in
patients with FAP has 1 mutated APC allele.

• Inactivation of the remaining normal copy of the APC

gene, by deletion or mutation, ►completely removes
the tumor suppressive function of APC, ► thus
initiating the growth of adenomatous polyps.
 Familial Adenomatous Polyposis

• Pathophysiology
• Remember
• Inactivation of the second APC allele occurs frequently in
the colon, resulting in the development of numerous
adenomas.
 Familial Adenomatous Polyposis

• Frequency
• The frequency is constant worldwide.
 Familial Adenomatous Polyposis

• Mortality/Morbidity
• The principal cause of mortality is colorectal cancer, which
develops in all patients unless they are treated.

• The mean age at which colorectal cancer develops in patients

with classic FAP is 39 years.

• Patients with adenomatous polyposis itself often are

asymptomatic.
 Familial Adenomatous Polyposis

• Race
• FAP has been described in all races.

• Sex
• The male-to-female ratio is 1:1.

• Age
• The average age of onset of polyposis in FAP is 16
years.
 Familial Adenomatous Polyposis

• Clinical Findings
• History
• Most patients with FAP are asymptomatic until
they develop cancer.

• As a result, diagnosing presymptomatic

patients is essential.
 Familial Adenomatous Polyposis

• Clinical Findings
• History
• Of patients with FAP, 75-80% have a family history
of polyps and/or colorectal cancer at age 40 years or
younger.
 Familial Adenomatous Polyposis

• Clinical Findings
• Nonspecific symptoms, such as:

• ► unexplained:
• rectal bleeding (hematochezia)
• diarrhea.
• Or abdominal pain
• in young patients may be suggestive of FAP.
 Familial Adenomatous Polyposis

• Clinical Findings
• Physical
• Congenital hypertrophy of the retinal pigment
epithelium is highly specific for FAP and is best
seen by slit-lamp examination.

• They are discrete flat pigmented lesions of the retina.

They are often multiple (63%) and bilateral (87%). They
do not cause any clinical problems.
 Familial Adenomatous Polyposis

• Illustration
 Familial Adenomatous Polyposis

• Clinical Findings
• Physical
• They indicate that a family member has inherited
the gene that causes FAP and is at risk.
 Familial Adenomatous Polyposis

• Clinical Findings
• Physical
• ►Extracolonic Symptoms
• 1) Some lesions are indicative of a Gardner variant of
FAP.

• Osteomas (painless bony overgrowth) of the skull and the

mandible may be present.
• They usually precede the clinical or radiologic diagnosis of
intestinal polyposis.
• Clinical Findings
• Physical
• Extracolonic Symptoms
• ► Some lesions are indicative of a Gardner variant of
FAP.

• Dental abnormalities, often diagnosed by using x-ray

films, may include:

• supernumerary teeth
• impacted teeth
• dentigerous cysts
• and odontomas.
• Clinical Findings
• Physical
• Extracolonic Symptoms
• ► Some lesions are indicative of a Gardner variant of FAP.

• In prepubescent patients, epidermoid cysts on the:

• legs
• face
• scalp
• and arms may be present.
 Familial Adenomatous Polyposis

• Clinical Findings
• Extracolonic Symptoms
• Physical
• Fibromas may be present, located on the:
• scalp
• shoulders
• arms
• and back.
• Clinical Findings
• Physical
• Extracolonic Symptoms
• 2) Desmoid tumors.
• (They develop in 10% to 12% in patients with FAP)

• ☼ A palpable abdominal mass in a young patient is

suggestive of FAP.

• A palpable mass upon rectal examination in a

young patient is suggestive of FAP.
 Familial Adenomatous Polyposis

• Clinical Findings
• Physical
• Extracolonic Symptoms
• 3) Turcot syndrome
• Is characterized by colonic polyposis typical of FAP
associated with central nervous system tumors
(medulloblastoma)
 Familial Adenomatous Polyposis

• Clinical Findings
• Physical
• Extracolonic Symptoms
• 4) Gastrointestinal polyps.
• The prevalence of gastric polyps ranges from
34% to 100%. In the fundus of the stomach.

• Most of gastric polyps associated with FAP are

hyperplasic type.
 Familial Adenomatous Polyposis
• Clinical Findings
• Physical
• Extracolonic Symptoms
• Duodenal polyps, most of which are
adenomatous, have been found in 24% to 90%
of patients with FAP.
 Familial Adenomatous Polyposis
• Clinical Findings
• Physical
• Extracolonic Symptoms
• 5) Periampullary carcinoma
• It is estimated that this nonintestinal carcinoma occurs
in 12% of the patients with FAP.
•
• It is one of leading causes of death in patients with
FAP.
 Familial Adenomatous Polyposis
• Causes
FAP is caused by a germline mutation of the APC
tumor suppressor gene, located on band 5q21.

Most mutations of the APC gene are:

• nonsense
• or frameshift mutations

• ► leading to truncation of the APC protein

(nonfunctional protein).
 Familial Adenomatous Polyposis

• Differential diagnosis
Juvenile polyposis syndrome
Hereditary nonpolyposis colon cancer
Hyperplastic polyposis
Nodular lymphoid hyperplasia
Lymphomatous polyposis
Neurofibromatosis
Inflammatory polyposis
 Familial Adenomatous Polyposis

• Workup
• Lab studies
• 1)CBC

• 2) Alpha-fetoprotein (AFP) blood test - For

children with FAP until age 5 years as part of a
screening program for hepatoblastoma.
 Familial Adenomatous Polyposis

• Workup
• Imaging Studies
• 3) Flexible sigmoidoscopy: Visualization of more than
100 polyps usually establishes the diagnosis because
of the diffuse nature of the polyposis.
 Familial Adenomatous Polyposis

• Workup
• Imaging Studies
• 4) Colonoscopy is usually reserved for patients
thought to have AAPC because of the higher
incidence of right-sided polyps (proximal colonic
involvement).
 Familial Adenomatous Polyposis

• Workup
• Imaging Studies
5) esophagogastroduodenoscopy is recommended
if the sigmoidoscopy or the colonoscopy establishes
the diagnosis of FAP.
 Familial Adenomatous Polyposis

• Workup
• Imaging Studies
• 6) Dental and skull x-ray films
• Are recommended in patients thought to have a
Gardner variant of FAP. ( to detect osteomas and
dental abnormalities).
 Familial Adenomatous Polyposis

• Workup
• Imaging Studies
• 6) Barium studies may be performed to visualize
intestinal polyposis.

• 7) Periodic ultrasounds or abdominal computed

tomography scans are used to check for intra-
abdominal desmoid tumors and pancreatic cancer.
 Familial Adenomatous Polyposis

• Workup
• Imaging Studies
• 8) Periodic ultrasound of the thyroid: This
imaging study is considered because of the
increased risk of thyroid cancer.

• It can supplement the recommended annual

physical examination of the thyroid.
 Familial Adenomatous Polyposis

• Other Tests
• 9) genetic tests are available.
• (reserved for research purposes)
 Familial Adenomatous Polyposis

• Treatment
• Medical
• Medical care is mainly based on endoscopic
surveillance to detect the onset of polyposis.

• Surgery
• Consequently, surgery would prevent the development
of colon cancer
• Thanks