Tumors of the GI Tract in Children
There are many different tumors that affect the gastrointestinal (GI) tract in the pediatric population.
This chapter will serve to highlight the major features of the most relevant tumors and syndromes including familial adenomatous polyposis (FAP), hereditary nonpolyposis colorectal cancer (HNPCC), juvenile polyposis syndrome (JPS), Peutz-Jeghers syndrome (PJS), Cowden syndrome (CS), Burkitt lymphoma (BL), and appendiceal carcinoid.
Familial Adenomatous Polyposis
EPIDEMIOLOGY AND ETIOLOGY
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.
Associated Syndromes (Gardner, Turcotte, and APCC)
Closely related polyposis syndromes that are associated with the APC mutation include Gardner syndrome and Turcotte syndrome.
Gardner syndrome is characterized by the aforementioned colorectal adenomatous polyps plus dental abnormalities, osteomas, epidermoid cysts, and desmoid tumors. Turcotte syndrome is associated with medulloblastomas.
A milder variant of the FAP syndrome is attenuated familial adenomatous polyposis (AFAP), which is notable for fewer polyps, more right-sided than left-sided polyps, and a later age of polyposis onset in the fourth decade of life.
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
Recommendations are largely based on expert opinion and observational data.
Screening for cancers associated with FAP should occur in patients with known APC mutations as well as in patients at risk for FAP, including first-degree relatives of those with FAP who either have not yet undergone genetic evaluation or who have indeterminate genetic testing results.
Flexible sigmoidoscopy is recommended, and if adenomas are found, then complete colonoscopy is indicated.
Several biopsies should be obtained to sample for dysplasia.
Notes should be made of size, number, and distribution of polyps to guide surgical planning.
Endoscopic control is unrealistic except in cases of AFAP where the number of polyps is multiple orders less in scale, and polypectomy can obviate the need for colectomy.
Screening for AFAP is recommended to begin at the age of 25 years and every 1 to 2 years thereafter.
Screening of the upper GI tract is recommended for both classic FAP and AFAP, given the high prevalence of gastric and duodenal polyps and risk of cancer.
Screening with upper endoscopy should begin at the onset of polyposis or at the age of 25 years whichever comes first.5,6
If no polyps are detected, screening is repeated every three years if the patient remains asymptomatic.
Unlike lower endoscopy, screening for the upper GI tract has not been consistently shown to decrease mortality.
MEDICAL AND SURGICAL MANAGEMENT
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.
Lynch Syndrome—Hereditary Nonpolyposis Colorectal Cancer
EPIDEMIOLOGY AND ETIOLOGY
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.
A pedigree should be drawn of each patient considered for HNPCC or any familial cancer syndrome, for that matter.
Lynch syndrome is a diagnosis given to patients AND their families who fulfill the Amsterdam criteria, best memorized and applied in the 3-2-1 rule.12
Three or more family members with HNPCC-related cancers, one of whom is a first-degree relative of the other two.
Two successive affected generations (one of the patients is a first-degree family member of the other patients).
One or more of the HNPCC-related cancers diagnosed younger than 50 years.
FAP has been excluded.
Additionally, Lynch syndrome refers to any patients and their families who have a documented germ line mutation in one of the DNA mismatch repair genes.
MEDICAL AND SURGICAL MANAGEMENT
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.
Juvenile Polyposis Syndrome
EPIDEMIOLOGY AND ETIOLOGY
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.
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