FAP is the most common adenomatous polyposis syndrome in children.

It is characterized by early onset of hundreds, possibly thousands, of adenomatous polyps in the colon beginning in early adolescence.

Most patients with FAP will develop colorectal adenocarcinoma by age 40 years without intervention.

The disease is inherited in an autosomal dominant fashion.

The genetic defect is due to a germ line mutation in the APC gene (adenomatous polyposis coli), which is a tumor suppressor gene located on chromosome 5q21-22.¹

Patients with FAP are also at increased risk of periampullary cancers and mesenteric fibromatosis (desmoid tumors), which are the second and third most lethal complications of this syndrome, respectively.

Most patients with FAP are asymptomatic until the development of cancer, occurring at a mean age of 39 years.²

Early diagnosis allows rigorous screening and affords colectomy before the onset of adenocarcinoma.

Nonspecific symptoms include unexplained hematochezia, abdominal pain, or diarrhea in adolescent patients.

A slit lamp examination may reveal congenital hypertrophy of the retinal pigment epithelium, which are discrete flat and pigmented lesions of the retina and are highly specific for FAP.

Nearly 80% of patients will report a family history of early-onset colorectal cancer (CRC), but 20% with spontaneous APC mutations will have no remarkable family history.³

Colectomy is indicated for documented or suspected cancer, any biopsy of high-grade dysplasia, recurrent bleeding, multiple adenomas larger than 6 mm, marked increase in polyp number on consecutive endoscopies, inability to adequately survey the colon due to diminutive polyps (Figure 53.2).

Surgical options include total proctocolectomy with end ileostomy, proctocolectomy with ileal pouch-anal anastomosis, or subtotal colectomy with ileorectal anastomosis.

For patients with few rectal polyps (<10) and low risk of desmoid tumors, subtotal colectomy with ileo-rectal anastomosis may offer better quality of life.⁷

Postoperatively, routine screening continues annually to survey the remaining rectal mucosa.

Up to 20% of patients will develop desmoid tumor after colectomy, and this is the second most lethal complication of FAP, as it encases bowel, arteries, veins, and ureters.

Life expectancy is greatly expanded in patients who undergo colectomy.

Desmoid tumors and upper GI cancers are the next most common causes of death postcolectomy.⁸

The cumulative probability of developing any non-CRC, mostly periampullary cancer, is 11% at 50 years and 52% at 75 years.⁹

Screening for non-CRCs must be continued throughout life in FAP patients, including annual thyroid ultrasound to screen for thyroid nodules and abdominal CT scan to screen for desmoid tumor in the patient with bowel obstruction or a palpable abdominal mass.

The most common form of hereditary CRC is known as Lynch syndrome and accounts for up to 5% of all colorectal carcinomas.¹⁰

The disease is inherited in an autosomal dominant fashion as a result of defective DNA mismatch repair genes.

HNPCC is divided into 2 groups, Lynch I and Lynch II (Figure 53.3).

Patients with HNPCC Lynch I and Lynch II are at higher risk for CRC at much earlier ages.

However, those with Lynch II are at increased risk of many other cancers including endometrial carcinoma and cancers of other sites such as small bowel, ureter, renal pelvis, ovary, and stomach.

Despite the name of the disease containing the term “nonpolyposis,” HNPCC patients do have polyps with the average age of polyp onset in the late second or early third decade of life.¹¹

Making the diagnosis of HNPCC requires family history, tumor testing, and genetic evaluation.

Patients often are asymptomatic in early stages.

May have nonspecific symptoms such as fatigue, anemia, or change in bowel habits.

The diagnosis of CRC or the presence of an endoscopically unresectable polyp is an indication for total abdominal colectomy with ileorectal anastomosis, followed by annual surveillance of the rectal stump.¹⁴

In addition, women with Lynch syndrome who do not plan to have future children should be offered prophylactic hysterectomy and bilateral salpingo-oophorectomy at the time of colectomy.

A screening program should also be established for the other cancer types in the family. Women with Lynch syndrome are recommended to receive annual pelvic examinations and endometrial biopsies, plus transvaginal ultrasound for ovarian cancer starting at 30 to 35 years of age, or 3 to 5 years earlier than the earliest age of cancer diagnosis in the family.¹¹,¹³

Screening for gastric cancer is recommended to begin at age 30 to 35 years and repeated every 2 to 3 years for those with gastric cancer risk factors.

Treatment of Helicobacter pylori has been shown to significantly reduce the risk of gastric cancer in Lynch syndrome.¹⁵

For urinary tract cancers, annual random urinalysis is recommended to begin at age 30 to 35 years.¹⁶

Microscopic analysis of the urine is controversial.

Note that these recommendations are based largely on expert opinion and observational studies, and any screening program should be individualized to the patient and family history.

JPS is an autosomal dominant condition characterized by multiple hamartomatous polyps in the GI tract and confers an increased risk for colon and gastric cancer.⁵

This is differentiated from sporadic juvenile polyps, which can occur in up to 2% of children younger than 10 years and confer no increased risk of malignancy.