Familial adenomatous polyposis.

Familial adenomatous polyposis is a hereditary disease that is based on the development of multiple polyps in the colon, leading to colon carcinoma at the age of 40. The disease is usually asymptomatic, but heme-positive stool may be observed. Diagnosis is established by colonoscopy and genetic testing. Treatment of familial adenomatous polyposis is colectomy.

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What causes familial adenomatous polyposis?

Familial adenomatous polyposis (FAP) is an autosomal dominant disorder in which more than 100 adenomatous polyps line the colon and rectum. The disease occurs in 1 in 8,000 to 14,000 people. Polyps are present in 50% of patients at age 15 and in 95% at age 35. Malignancy develops in almost all untreated patients by age 40.

Patients may also have a variety of extraintestinal manifestations (previously called Gardner syndrome), including benign and malignant lesions. Benign lesions include desmoid tumors, osteomas of the skull or mandible, and sebaceous cysts and adenomas elsewhere in the GI tract. Patients have an increased risk of malignancy of the duodenum (5% to 11%), pancreas (2%), thyroid (2%), brain (medulloblastoma <1%), and liver (hepatoblastoma in 0.7% of children <5 years of age).

Diffuse familial polyposis is a hereditary disease manifested by the classic triad: the presence of multiple polyps (about several hundred) from the epithelium of the mucous membrane; familial nature of the lesion; localization of the lesion throughout the gastrointestinal tract. The disease ends with the obligatory development of cancer as a result of malignancy of the polyps.

Symptoms of diffuse (familial) polyposis

Many patients with familial adenomatous polyposis have no symptoms, but rectal bleeding, usually occult, is sometimes observed.

Classification of familial adenomatous polyposis

There are many classifications of polyposis. The classification by V. S. Morson (1974) is popular abroad, in which 4 types are distinguished: neoplastic (adenomatous), hamartomatous (including juvenile polyposis and Peutz-Jeghers polyposis), inflammatory, unclassified (multiple small polyps). The classification of diseases accompanied by the formation of pseudopolyps, such as nonspecific ulcerative colitis and Crohn's disease, as diffuse polyposis raises objections, since the formations are not related to true polyps.

In the domestic literature, the classification of V.D. Fedorov, A.M. Nikitin (1985) has become widespread, taking into account not only morphological changes, but also the stages of disease development. According to this classification, 3 forms of polyposis are distinguished: proliferative diffuse, juvenile diffuse and hamartomatous.

Proliferative diffuse polyposis (prevalence of proliferation processes in polyps) is a form that in turn is divided into 3 stages, allowing us to trace the dynamics of the disease up to the development of cancer. It is in this group of patients that the frequency of malignancy of polyps is highest. In stage I (hyperplastic or miliary polyposis), the mucous membrane is dotted with tiny (less than 0.3 cm) polyps, in which histologically, against the background of unchanged mucous membrane, single crypts with hyperchromic epithelium and forming groups of large glands are detected. As the epithelium proliferates, an increasingly larger group of crypts is involved in the process and polyps are formed. In stage II (adenomatous polyposis), typical tubular adenomas up to 1 cm in size are formed, and in stage III (adenopapillomatous polyposis), typical tubulovillous and villous adenomas are formed. The index of malignancy of polyps in stage I was 17%, and in stage III - 82%. Malignancy sometimes developed in one, and more often in several polyps simultaneously.

In juvenile diffuse polyposis, malignancy is observed much less frequently (no more than 20%), and in Peutz-Jeghers syndrome - in isolated cases.

The morphologist faces particular difficulties when making a diagnosis, or rather when naming the variant of diffuse polyposis, since a single patient may have a combination of all varieties - from hyperplastic to juvenile. It is recommended to make a diagnosis based on the "predominant" polyps. In this case, cancer is sometimes diagnosed in patients with a hamartomatous or juvenile variant of polyposis. In these cases, malignancy occurs in a tubular or tubulovillous adenoma, which were isolated among juvenile and hamartomatous polyps, or malignancy of adenomatous areas in mixed polyps occurred.

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Diagnosis of familial adenomatous polyposis

The diagnosis is established when more than 100 polyps are detected during colonoscopy. The diagnosis requires genetic testing to identify a specific mutation, which must be present in first-degree relatives. If genetic testing is not available, relatives should undergo annual sigmoidoscopy screening starting at age 12, decreasing the frequency of screening every ten years. If polyps are not detected by age 50, the frequency of screening is set as for patients with an average risk of malignancy.

Children of parents with familial adenomatous polyposis should be screened for hepatoblastoma from birth to age 5 years with annual serum fetoprotein levels and possibly liver ultrasound.

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Treatment of diffuse (familial) polyposis

Colectomy is indicated when the diagnosis is made. Total proctocolectomy with ileostomy or proctectomy with ileoanal pouch formation eliminates the risk of cancer. If subtotal colectomy (removal of most of the colon, leaving the rectum) with ileorectal anastomosis is performed, the remaining rectum should be examined every 3 to 6 months; new polyps should be removed or electrocauterized. Aspirin or COX-2 inhibitors may help reduce the incidence of new polyps. If new polyps appear too rapidly or in large numbers, removal of the rectum with permanent ileostomy is necessary.

After colectomy, patients need upper gastrointestinal endoscopy every 6 months for 4 years, depending on the number of polyps (regardless of type) in the stomach and duodenum. Annual physical examination of the thyroid gland and ultrasound as indicated are also recommended.