Colonic Manifestations

As the name implies, FAPS is predominantly associated with the development of adenomas. In the colon, where the polyposis is most severe, the polyps are usually tubular or tubulovillous adenomas. Occasionally, villous adenomas are also seen. The polyps usually appear at or near puberty and, eventually, an average of about 1000 colonic adenomas will develop. The adenomas of FAPS are usually small (80% are <5 mm in diameter) and sessile. The polyps involve all portions of the colon but may first appear distally. Rectal sparing occasionally may be seen.

A milder phenotype of FAPS, known as attenuated familial adenomatous polyposis syndrome (AFAPS), has recently been described. These patients generally present with 100 or fewer colonic adenomas. The adenomas tend to be located more proximally than those in classic FAPS, so sigmoidoscopy alone is inadequate for evaluating these patients. Colonic carcinoma also develops at an older age, with an average age of 55 years in patients with AFAPS versus an average age of 40 years in patients with classic FAPS. There is no current consensus on the diagnostic criteria for AFAPS, but it should be considered in a patient with a personal history of colorectal cancer before 60 years of age and a family history of multiple adenomatous polyps and in those with more than 10 but less than 100 polyps.

The most common clinical symptoms encountered in FAPS are rectal bleeding and diarrhea, which occur in more than 75% of patients. Abdominal pain, anemia, and mucous discharge are less frequently noted. However, many patients with FAPS are asymptomatic. Regardless of symptoms, colonic carcinomas develop in almost every untreated patient and at a much younger age than in the general population. The average age of colon cancer in untreated patients is 39 years. Thus, DNA testing or serial colonic examinations after 10 years of age are recommended for other family members at risk for the disease.

Total colectomy with mucosal proctectomy and ileoanal anastomosis is the procedure of choice for treatment because it eliminates all colonic and rectal mucosa. Surgical intervention should be performed by the late teenage years. After surgery, continued surveillance is necessary because any surgical procedure that restores intestinal continuity bears a continued risk of malignancy in the surgical remnant. For patients who have undergone ileorectal anastomoses prior to current surgical recommendations for total colectomy with mucosal proctectomy and ileoanal anastomosis, completion surgery should be considered because recurring adenomas in the remaining rectal mucosa cannot be adequately controlled endoscopically.

The radiographic appearance of the colon in FAPS varies. Typically, innumerable small or moderate-sized sessile filling defects carpet the entire colon ( Fig. 61-1A ). Larger pedunculated polyps are less common. In some younger patients, however, the polyps may be more widely scattered ( Fig. 61-1B ). Correlation with colectomy specimens has shown that barium enemas markedly underestimate the number of polyps, especially in young patients, whose polyps are often smaller than 3 mm in diameter. Unfortunately, carcinomas still develop because of inadequate screening of family members at risk for the disease. Carcinoma may be manifested by a dominant polyp ( Fig. 61-2 ), saddle lesion, or advanced annular lesion ( Fig. 61-3 ). As in the general population, carcinomas are usually found in the left side of the colon.

Various appearances of colonic involvement by familial adenomatous polyposis syndrome.

A. In a 10-year-old boy, a double-contrast barium enema demonstrates innumerable small polyps in the colon, particularly carpeting the rectosigmoid region. B. In a 17-year-old girl, a double-contrast barium enema shows scattered, small to moderate-sized polyps ( arrows ) in the sigmoid colon.

Colonic carcinoma in a 30-year-old man who presented with abdominal pain.

A, B. Intravenous and oral contrast-enhanced CT shows liver metastases ( arrowheads in A ) and colocolic intussusception in the transverse colon. The lead point is a polypoid mass ( arrow in B ). C. Photograph of the resected colon shows a large polypoid adenocarcinoma and numerous small polyps.

Colonic carcinoma in familial adenomatous polyposis syndrome.

An annular lesion is present in the sigmoid colon ( arrow ). Scattered small polyps are also present.

Extracolonic Gastrointestinal Manifestations

Extracolonic gastrointestinal (GI) manifestations of FAPS are well recognized. Fundic gland polyps are the most common gastric manifestation of FAPS in Western countries, occurring in up to 84% of patients. In FAPS, both genders are equally involved, whereas in the absence of FAPS, fundic gland polyps are more common in females. The polyps are frequently discovered in asymptomatic patients at an average age of 25 to 30 years and are almost invariably multiple, appearing as small sessile lesions ranging from 1 to 5 mm in diameter. They are almost always confined to the fundus and body of the stomach. They are characteristically small (5-10 mm), smooth, sessile nodules protruding into the gastric lumen. There may be few or hundreds, which carpet the gastric fundus. On subsequent examinations, the polyps may progress, remain stable, or even resolve. These polyps have little tendency for malignant transformation, although gastric cancer has occasionally been reported in patients with preexisting fundic gland polyps.

Tubular and villous adenomas are also found in the stomach in patients with FAPS. In Japan, the incidence of gastric adenomas in FAPS ranges from 40% to 50%, whereas in Europe and North America, a lower incidence is reported. The higher incidence of adenomas associated with FAPS in Japan may be related to the higher frequency of adenomas and adenocarcinomas in the general population of that country. Gastric adenomas are typically sessile polyps, ranging from 5 to 10 mm in diameter, and are multiple in over 50% of reported cases. The adenomas are usually located in the distal stomach. Unlike fundic gland polyps, gastric adenomas are premalignant lesions, so that periodic surveillance of the stomach is required.

The duodenum is the second most common site of GI disease in FAPS. Endoscopic examinations of asymptomatic patients in Japan have revealed tubular adenomas in more than 90% of cases. Other screening studies from Western countries have revealed adenomas in 47% to 72% of cases. The adenomas range from microscopic to 2 cm in diameter, with most being 5 mm or less. The polyps are usually found in the second portion of the duodenum, clustered around the papilla. This differs from the typically bulbar distribution of adenomas in patients without FAPS. Villous adenomas are also commonly found and, as in patients without FAPS, they tend to be located in the periampullary region of the duodenum. Villous adenomas are typically large and are even more likely to undergo malignant degeneration. It has been estimated that the lifetime incidence of periampullary carcinoma is as high as 12%, and that it is now the leading cause of cancer deaths in patients who have had a colectomy. It is therefore advocated that surveillance of the upper GI tract be performed in asymptomatic patients with FAPS beginning at 25 years of age.

Adenomas in the jejunum and ileum have been identified in most patients in Japan who have undergone intraoperative small bowel endoscopy. Small bowel endoscopy performed through a cutaneous ileostomy or ileoproctostomy has also revealed adenomas in approximately 20% of FAPS patients in Western countries. As in the duodenum, these premalignant lesions are typically small and numerous. Although several cases of adenocarcinoma of the jejunum or ileum have been reported—coexisting adenomas have been found in all of these cases—the need for routine screening of the small bowel beyond the duodenum has not been established. Ileal lymphoid hyperplasia occurs more frequently in patients with FAPS than in the general population. The gross appearance of these lesions is similar to that of adenomas. However, lymphoid hyperplasia has no apparent clinical significance in these patients.

Biliary polyps are often found in patients with FAPS studied by endoscopic retrograde cholangiopancreatography. Not surprisingly, cholangiocarcinoma and gallbladder carcinoma have also been reported in FAPS. Several cases of pancreatic carcinoma have been reported, and there is an increased incidence of pancreatitis in these patients.

Extraintestinal Manifestations

It was not until the 1950s that the extraintestinal manifestations of FAPS were well established. Gardner and Richards initially described a family of patients with adenomatous polyps of the colon, sebaceous cysts, and osteomas. Later, fibrous tumors and dental abnormalities were added to the list of lesions included in what was subsequently called Gardner syndrome. Numerous reports have subsequently confirmed the occurrence of these and other extraintestinal manifestations that have a tendency to appear in certain kindred affected by FAPS. The location of the defect in the APC gene and other intracellular factors appear to determine whether these manifestations are likely to appear. It is unusual to see all manifestations in the same patient.

Epidermoid (sebaceous) cysts are the skin lesions usually encountered in patients with FAPS. The cysts tend to be located on the face and scalp rather than on the back, as in the general population. They are uncommon before puberty, but the presence of these cysts often precedes the recognition of colonic polyps. Otherwise, they have no clinical significance. Lipomas and small fibrous tumors of the skin are also found in FAPS.

Osteomas are another well-known manifestation of FAPS. Like epidermoid cysts, osteomas are usually unimportant unless they cause symptoms because of mass effect. In FAPS patients, these dense cortical lesions are usually found in the angle of the mandible, sinuses, and outer table of the skull ( Fig. 61-4 ). Other flat bones and long bones may be involved. Bone islands are also quite common in the maxilla and mandible and may be seen in other flat bones as well. In one series, localized or diffuse cortical thickening of the long bones was the most commonly identified bone abnormality in FAPS. Dental abnormalities, particularly unerupted teeth, supernumerary teeth, dentigerous cysts, and odontomas, are also common.

Multiple osteomas in a 23-year-old man with familial adenomatous polyposis syndrome.

Lateral radiograph of the face and skull demonstrates two dense bony lesions ( white arrows ) arising from the mandible. A subtle lesion ( black arrow ) is also seen in the frontal bone.

Fibrous proliferation is a less common but more important feature of FAPS. An increased incidence of postoperative peritoneal adhesions occurs in FAPS, and retroperitoneal fibrosis has also been reported. Usually, these patients develop fibrous tumors (particularly desmoid tumors of the abdominal wall) and mesenteric fibromatosis ( Fig. 61-5 ). Histologically, desmoids are benign lesions but are nonencapsulated. In FAPS, these tumors often develop postoperatively, occurring within abdominal incisions, the peritoneal cavity, or the retroperitoneum. They usually develop in women of childbearing age and may grow rapidly or may first appear during pregnancy or after exposure to oral contraceptives. These tumors may recur locally after resection, and invasion of bowel is common. Death may result from intestinal or vascular obstruction, particularly when the lesions are located within the peritoneal cavity. With improvements in computed tomography (CT), more subtle, diffuse soft tissue infiltration of the mesentery can be identified, but this appearance is less likely to be associated with symptoms than is an actual mesenteric mass.

Mesenteric fibromatosis in a 25-year-old woman with familial adenomatous polyposis syndrome.

She is status post total colectomy with ileoanal anastomosis. Intravenous and oral contrast-enhanced CT shows a large heterogeneous mass ( arrow ) arising in the small bowel mesentery adjacent to the ileoanal anastomosis.

Congenital pigmented lesions of the retina are common in patients with FAPS; the prevalence of these lesions may be higher than 90%. Although similar lesions are occasionally found in the general population, the presence of large, multifocal, or bilateral pigmented lesions on funduscopic examination is a strong indicator of FAPS. These lesions may occur before the development of colonic polyposis, serving as a marker for FAPS, but the absence of these lesions does not exclude FAPS.

Much has been learned about the association between colonic carcinoma and central nervous system malignancies, a condition traditionally known as Turcot syndrome. Evidence suggests that many, if not most, of these cases (including those in the family first described by Turcot) are actually related to the hereditary nonpolyposis colon cancer syndrome (HNPCCS) and do not have abnormalities of the APC gene. Nevertheless, central nervous system tumors are important extraintestinal manifestations of FAPS. There is clearly an increased incidence of medulloblastomas. There have also been case reports of benign intracranial tumors associated with FAPS, including intracranial epidermoid cysts and meningiomas. Glial tumors such as ependymomas and astrocytomas also occur in FAPS. However, many cases of glioblastoma multiforme associated with colonic adenomas or carcinomas that were reported in the past were probably related to HNPCCS.

The prevalence of thyroid carcinoma in FAPS has been calculated to be 160 times greater than that in the general population. Almost all reported cases are papillary, and they are frequently multifocal. In most series, affected individuals are girls or young women, and the thyroid carcinoma is usually detected before colonic polyposis becomes apparent. FAPS therefore should be suspected in young women with papillary carcinoma of the thyroid. In one series, however, there was no female predominance in patients with thyroid carcinoma and FAPS. Other endocrine tumors, including multiple endocrine neoplasia type 2, carcinoid tumors, and adrenocortical adenomas and carcinomas, have also been reported in patients with FAPS.

Several tumors of the pancreas and liver have been reported in FAPS, including pancreatic carcinoma. Solid and papillary epithelial neoplasm, neuroendocrine tumors, and intraductal papillary mucinous tumors of the pancreas have also been reported. Because of the rarity of these tumors, screening of FAPS patients for pancreatic lesions does not appear to be warranted. Hepatoblastomas have also been reported with increased frequency in the children of patients with FAPS.