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Tumors of the Digestive Tract
Tumors of the digestive tract in children are mostly polypoid. They are also commonly syndromic tumors and tumors with known genetic identification ( Table 372.1 ). They usually manifest as painless rectal bleeding, but when large they can cause obstruction or serve as lead points for intussusception. Most intestinal tumors can be generally classified into 2 groups: hamartomatous or adenomatous.
Table 372.1
General Features of the Inherited Colorectal Cancer Syndromes
| SYNDROME | POLYP DISTRIBUTION | AGE OF ONSET | RISK OF COLON CANCER | GENETIC LESION | CLINICAL MANIFESTATIONS | ASSOCIATED LESIONS |
|---|---|---|---|---|---|---|
| HAMARTOMATOUS POLYPS | ||||||
| Juvenile polyposis | Large and small intestine, gastric polyps | 1st decade | ~10–50% | PTEN, SMAD4, BMPR1A Autosomal dominant |
Possible rectal bleeding, abdominal pain, intussusception | Congenital abnormalities in 20% of the nonfamilial type, clubbing, AV malformations |
| Peutz-Jeghers syndrome | Small and large intestine | 1st decade | Increased | LKB1/STK11 Autosomal dominant |
Possible rectal bleeding, abdominal pain, intussusception | Orocutaneous melanin pigment spots |
| Cowden syndrome | Colon | 2nd decade | Not increased | PTEN gene | Macrocephaly, breast/thyroid/endometrial cancers, developmental delay | |
| Bannayan-Riley-Ruvalcaba syndrome | Colon | 2nd decade | Not increased | PTEN gene | Macrocephaly, speckled penis, thyroid/breast cancers, hemangiomas, lipomas | |
| ADENOMATOUS POLYPS | ||||||
| Familial adenomatous polyposis (FAP) | Large intestine, often >100 | 16 yr (range: 8-34 yr) | 100% | 5q ( APC gene), autosomal dominant | Rectal bleeding, abdominal pain, bowel obstruction | Desmoids, CHRPE, upper GI polyps, osteoma, hepatoblastoma, thyroid cancer |
| Attenuated familial adenomatous polyposis (AFAP) | Colon (fewer in number) | >18 yr | Increased | APC gene | Same as FAP | Fewer associated lesions |
| MYH-associated polyposis | Colon | >20 yr | High risk | MYH autosomal recessive | Same as FAP | May be confused with sporadic FAP or AFAP; few extraintestinal findings |
| Gardner syndrome | Large and small intestine | 16 yr (range: 8-34 yr) | 100% | 5q ( APC gene) | Rectal bleeding, abdominal pain, bowel obstruction | Desmoid tumors, multiple osteomas, fibromas, epidermoid cysts |
| Hereditary nonpolyposis colon cancer, (Lynch syndrome) | Large intestine | 40 yr | 30% | DNA mismatch repair genes (MMR) Autosomal dominant |
Rectal bleeding, abdominal pain, bowel obstruction | Other tumors (e.g., ovary, ureter, pancreas, stomach) |
APC, adenomatous polyposis coli; AV , arteriovenous; CHRPE , congenital hypertrophy of the retinal pigment epithelium; GI, gastrointestinal; PTEN , phosphatase and tensin homolog.
Hamartomatous Tumors
Hamartomas are benign tumors composed of tissues that are normally found in an organ but that are not organized normally. Juvenile, retention, or inflammatory polyps are hamartomatous polyps, which represent the most common intestinal tumors of childhood, occurring in 1–2% of children. Patients generally present in the 1st decade, most often at ages 2-5 yr, and rarely at younger than 1 yr. Polyps may be found anywhere in the gastrointestinal (GI) tract, most commonly in the rectosigmoid colon; they are often solitary but may be multiple.
Histologically, juvenile polyps are composed of hamartomatous collections of mucus-filled glandular and stromal elements with inflammatory infiltrate, covered with a thin layer of epithelium. These polyps are often bulky, vascular, and prone to bleed as their growth exceeds their blood supply with resultant mucosal ulceration, or autoamputation with bleeding from a residual central artery.
Patients often present with painless rectal bleeding after defecation. Bleeding is generally scant and intermittent; rarely presenting findings can include iron deficiency anemia and/or hypoalbuminemia. Extensive bleeding can occur but is generally self-limited, requiring supportive care until the bleeding stops spontaneously after autoamputation. Occasionally endoscopic polypectomy is required for control of bleeding. Abdominal pain or cramps are uncommon unless associated with intussusception. Patients can present with prolapse, with a dark, edematous, pedunculated mass protruding from the rectum. Mucus discharge and pruritus are associated with prolapse.
Patients presenting with rectal bleeding require a thorough workup; differential diagnosis includes anal fissure, other intestinal polyposis syndromes, Meckel diverticulum, inflammatory bowel disease, intestinal infections, Henoch-Schönlein purpura, or coagulopathy.
Diagnosis and therapy are best accomplished via endoscopy. Polyps may be visualized via ultrasound or cross-sectional imaging, but this provides no therapeutic advantage. Colonoscopy affords opportunity for biopsy, polypectomy by snare cautery, and visualization of synchronous lesions; up to 50% of children have one or more additional polyps, and approximately 20% may have more than 5 polyps. Retrieved polyps should be sent for histologic evaluation for definitive diagnosis.
Juvenile Polyposis Syndrome
Patients with juvenile polyposis syndrome (JPS) present with multiple juvenile polyps, ≥5 but typically 50-200. Polyps may be isolated to the colon or distributed throughout the GI tract. There is often a family history (20–50%) with an autosomal dominant pattern of variable penetrance. Alterations in transforming growth factor-β pathways have been identified in some JPS patients and families; mutations in SMAD4 or BMPR1A are found in 50–60% of patients with JPS. Genetic testing is available for both of these mutations. Clinical diagnosis of JPS is established by presence of one of the following: a lifetime total of 5 or more juvenile polyps in the colon, juvenile polyps outside the colon, or any number of juvenile polyps in a patient with a family history of JPS.
Histologically, these polyps are identical to solitary juvenile polyps; however, the GI malignancy risk is greatly increased (10–50%). Most malignancy is colorectal, although gastric, upper GI, and pancreatic tumors have been described. The risk of malignancy is greater in patients with increased polyp burden and a positive family history. These patients should therefore undergo routine esophagogastroduodenoscopy, colonoscopy, and upper GI contrast studies. Serial polypectomy or polyp biopsy should be undertaken if possible. If dysplasia or malignant degeneration is found, a total colectomy is indicated.
Juvenile polyposis of infancy is characterized by early polyp formation (younger than 2 yr of age) and may be associated with protein-losing enteropathy, hypoproteinemia, anemia, failure to thrive, and intussusception. Early endoscopic or surgical intervention may be needed.
Peutz-Jeghers Syndrome
Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant disorder (incidence: ~1 : 120,000 total population) characterized by mucocutaneous pigmentation and extensive GI hamartomatous polyposis. Macular pigmented lesions may be dark brown to dark blue and are found primarily around the lips and oral mucosa, although these lesions may also be found on the hands, feet, or perineum. Lesions can fade by puberty or adulthood.
Polyps are primarily found in the small intestine (in order of prevalence: jejunum, ileum, duodenum) but may also be colonic or gastric. Histologically, polyps are defined by normal epithelium surrounding bundles of smooth muscle arranged in a branching or frond-like pattern. Symptoms arising from GI polyps in PJS are similar to those of other polyposis syndromes—namely bleeding and abdominal cramping from obstruction or recurrent intussusception. Patients can require repeated laparotomies and intestinal resections.
The diagnosis of PJS is made clinically in patients with histologically proven hamartomatous polyps if 2 of 3 conditions are met: positive family history with an autosomal dominant inheritance pattern, mucocutaneous hyperpigmentation, and small bowel polyposis. Genetic testing can reveal mutations in LKB1/STK11 (19p13.3), a serine-threonine kinase that acts as a tumor-suppressor gene. Up to 94% of patients with clinical characteristics of PJS have a mutation at this locus. Only 50% of patients with PJS have an affected family member, suggesting a high rate of spontaneous mutations.
Patients with PJS have increased risk of GI and extraintestinal malignancies. Lifetime cancer risk has been reported to be in the range of 47–93%. Colorectal, breast, and reproductive tumors are most common. GI surveillance should begin in childhood (by age 8 yr or when symptoms occur) with upper and lower endoscopy. The small bowel may be evaluated radiographically, with magnetic resonance enterography, endoscopically with balloon or push enteroscopy, or with video capsule endoscopy. Polyps larger than 1.5 cm should be removed, although resection does not lower the cancer risk and is mainly to avoid complications. Screening for breast, gynecologic, and testicular cancers should be routine after age 18 yr.
Phosphatase and Tensin Homolog Hamartoma Tumor Syndromes
Mutations in the tumor-suppressor gene protein tyrosine phosphatase and tensin homolog (PTEN) are associated with several rare autosomal dominant syndromes, including Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome. These patients present with multiple hamartomas in skin (99%), brain, breast, thyroid, endometrium, and GI tract (60%). Other extraintestinal manifestations include macrocephaly, developmental delay, lipomas, and genital pigmentation. Patients are at increased risk for breast and thyroid malignancies; the risk of GI cancer does not appear to be elevated.
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