Definition
Familial adenomatous polyposis (FAP) is characterized by the development of many tens to thousands of adenomas in the rectum and colon during the second decade of life.
Frequency
FAP has an incidence at birth of about 1/8,300, it manifests equally in both sexes, and accounts for less than 1% of colorectal cancer (CRC) cases. In the European Union, prevalence has been estimated at 1/11,300-37,600.
Symptoms
Most patients are asymptomatic for years until the adenomas are large and numerous, and cause rectal bleeding or even anemia, or cancer develops.
Generally, cancers start to develop a decade after the appearance of the polyps. So, if the colon is left intact, the majority of patients with FAP eventually develop CRC by the ages 40-50 years. However, it should be emphasized that, although uncommon, CRC can develop in children or in older adults.
Nonspecific symptoms may include constipation or diarrhea, abdominal pain, palpable abdominal masses and weight loss.
In the stomach, fundic gland polyps (FGP) develop in 90% of patients with FAP. 40% of these lesions in individuals with FAP have been shown to have adenomatous features, but rarely do progress to cancer
Adenomatous polyps in the duodenum and periampullary region (in duodenum after stomach near pancreas): It is estimated that about 5% of duodenal, and specifically periampulary polyps, progress to cancer within 10 years . While rare in the general population, the risk of duodenal or periampullary cancer is increased several hundred fold in FAP patients
FAP may present with some extraintestinal manifestations such as osteomas, dental abnormalities (unerupted teeth, congenital absence of one or more teeth, supernumerary teeth, dentigerous cysts and odontomas), congenital hypertrophy of the retinal pigment epithelium (CHRPE), desmoid tumors, and extracolonic cancers (thyroid, liver, bile ducts and central nervous system).
A less aggressive variant of FAP, attenuated FAP (AFAP), is characterized by fewer colorectal adenomatous polyps (usually 10 to 100), later age of adenoma appearance and a lower cancer risk. Some lesions (skull and mandible osteomas, dental abnormalities, and fibromas on the scalp, shoulders, arms and back) are indicative of the Gardner variant of FAP.
Causes
Classic FAP is inherited in an autosomal dominant manner and results from a germline mutation in the adenomatous polyposis (APC) gene. Most patients (~70%) have a family history of colorectal polyps and cancer. In a subset of individuals, a MUTYH mutation causes a recessively inherited polyposis condition, MUTYH-associated polyposis (MAP), which is characterized by a slightly increased risk of developing colorectal cancer and polyps/adenomas in both the upper and lower gastrointestinal tract.
Diagnosis
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| Polyposis in the rectum |
When the APC mutation in the family has been identified, genetic testing of all first-degree relatives should be performed.
Presymptomatic and prenatal (amniocentesis and chorionic villous sampling), and even preimplantation genetic testing is possible.
Referral to a geneticist or genetic counselor is mandatory.
Differential diagnoses include other disorders causing multiple polyps (such as Peutz-Jeghers syndrome, familial juvenile polyps or hyperplastic polyposis, hereditary mixed polyposis syndromes, and Lynch syndrome).
Management
Cancer prevention and maintaining a good quality of life are the main goals of management and regular and systematic follow-up and supportive care should be offered to all patients.
By the late teens or early twenties, colorectal cancer prophylactic surgery is advocated.
The recommended alternatives are total proctocolectomy (removing of the whole colon and rectum) and ileoanal pouch or ileorectal anastomosis for AFAP.
Duodenal cancer and desmoids are the two main causes of mortality after total colectomy, they need to be identified early and treated.
Upper endoscopy is necessary for surveillance to reduce the risk of ampullary and duodenal cancer.
Patients with progressive tumors and unresectable disease may respond or stabilize with a combination of cytotoxic chemotherapy and surgery (when possible to perform).
Adjunctive therapy with celecoxib has been approved by the US Food and Drug Administration and the European Medicines Agency in patients with FAP. Individuals with FAP carry a 100% risk of CRC; however, this risk is reduced significantly when patients enter a screening-treatment program.