Familial Adenomatous Polyposis and Turcot and Peutz Jeghers Syndromes

Holly L. Neibergs and Amy T. Massey


Familial adenomatous polyposis (FAP) is an autosomal dominantly inherited disorder that predisposes affected individuals to colon cancer through the early development of hundreds to thousands of adenomatous polyps (Figure 18-1). Florid polyposis throughout the colon will develop in 50% of affected individuals by age 16, and 95% will have polyposis by age 35.1 If left untreated, colorectal cancer is inevitable in those with FAP, with an average age at diagnosis of 39 years. The incidence of FAP is estimated to be 1 in 8,300 to 1 in 14,025 live births and represents less than 1% of all colon cancers.1 FAP is clinically diagnosed when an individual has greater than 100 colorectal adenomatous polyps.

Individuals affected with FAP may exhibit a host of benign extracolonic maladies. Gastric lesions identified in individuals with FAP are generally of two types: fundic gland hamartomatous polyps (occur in approximately 50% of cases) or adenomatous polyps (found in approximately 10%). The risk for gastric cancer from both types of polyps is small. Adenomatous polyps of the duodenum are much more common (approximately 90% of FAP patients). Adenomatous polyps of the periampullary region occur in 50% of cases, and may result in obstruction of the pancreatic duct, leading to pancreatitis. Visualization of periampull-ary polyps may be difficult due to their size, and so the use of a side-viewing endoscope is recommended.

Benign extraintestinal manifestations of FAP include cutaneous lesions (lipomas, fibromas, and sebaceous and epidermoid cysts), desmoid tumors, osteomas, dental abnormalities, congenital hypertrophy of the retinal pigment epithelium (CHRPE), and nasopharyngeal angiofibromas.1 Desmoid tumors are identified in approximately 10% of individuals with FAP and result from a proliferation of myofibroblasts. The vast majority of desmoids arise after surgery and are present in the small intestine mesentery, retroperitoneum, and abdominal wall. Desmoids are usually slow growing but may become large enough to compress or obstruct organs, resulting in morbidity or mortality for approximately 5% of patients. Mesenteric and retroperitoneal desmoids often are not amenable to surgical or medical therapy, although some desmoid tumors have been successfully treated with antie-strogen medications. Desmoid tumors and duodenal carcinoma are the most common cause of death in FAP patients following prophylactic colectomy. Osteomas are frequently seen in the long bones, mandible, and skull. Dental abnormalities have been reported in approximately 17% of individuals with FAP and may involve unerupted teeth, absence of teeth, or supernumerary teeth. CHRPE are flat pig-mented lesions of the retina believed to be present at birth. CHRPE is a benign condition that may be detected by fun-doscopic examination.

Extracolonic malignancies may be present in individuals with FAP. Duodenum, periampullary area, stomach, pancreas, papillary thyroid, liver, and brain carcinomas are known to occur with greater frequency in FAP patients. Adenocarcinomas of the bile ducts and adrenal glands also have been reported, but the risk of these cancers in individuals with FAP remains low. Carcinomas of the small intestine, predominantly of the duodenum or peri-ampullary area, are seen in 4% to 12% of FAP patients. Gastric adenocarcinoma occurs in 0.5% of FAP patients. Pancreatic and papillary thyroid carcinomas are present in approximately 2% of individuals with FAP. One in 150 children under the age of 5 years with a mutation for FAP will develop hepatoblastoma.1 Tumors of the central nervous system (most commonly medulloblastoma, as seen in Turcot syndrome) occur in less than 1% of individuals with FAP. Individuals with FAP who also have an osteoma, fibroma, or epidermoid cyst have, in the past, been diagnosed with Gardner syndrome. However, since the identification of APC germline mutations in both FAP and Gardner syndrome, it is now recognized that FAP and Gardner syndrome are the same entity with different clinical presentations.

Attenuated FAP is characterized by an average of 30 to 100 cumulative colonic adenomas, although the number of adenomatous polyps varies greatly. Attenuated FAP

Figure 18-1. Adenomatous polyps present in the colon of an individual affected with familial adenomatous polyposis. (Courtesy of Dr.Wayne B.Tuckson.)

patients also have germline mutations in the APC gene, but the location of the mutations often differs from those of classic FAP.2 Polyps tend to present at a later age and in a more proximal location in individuals with attenuated FAP There may be considerable difficulty in distinguishing attenuated FAP from hereditary nonpolyposis colorectal cancer (HNPCC) syndromes based on clinical criteria alone. Endoscopic surveillance may be more challenging in individuals with attenuated FAP because the adenomas tend to be more flat and plaquelike as opposed to polypoid.3 The identification of these lesions may require stains, such as indigo carmine, during colonoscopy for adequate visualization. Colon cancer risk remains high, but with a 10 to 15 year later age of onset than observed in classic FAP. Adenomas and carcinomas of the upper gastrointestinal tract also may be present.4 Attenuated FAP is clinically diagnosed when an individual presents with numerous colonic adenomatous polyps under the age of 60 years. Extracolonic features characteristic of FAP may aid in the diagnosis but are not required.

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