In contrast to the adult population, neoplasms of the gastrointestinal tract and liver are rare in children. Often the diagnosis is made while exploring the cause of nonspecific gastrointestinal symptoms. Having an understanding of chronic conditions from which neoplasms can arise is important; however, most encountered neoplasms will be unanticipated, and the ability to arrive at a prompt and correct diagnosis can be crucial to the survival of the patient. Consequently, this chapter reviews the most common gastrointestinal neoplasms encountered in childhood.
Neoplasms of the Luminal Gastrointestinal Tract
The gastrointestinal tract is a relatively common site for involvement by childhood cancers, with approximately 5% of childhood cancers presenting in this organ system. Primary gastrointestinal cancer in the pediatric population is rare, however. When neoplasms do arise from the gastrointestinal tract, the presenting symptoms are variable and relatively nonspecific. The symptoms or signs may include abdominal pain, abdominal distension, vomiting, a palpable mass, anemia, gastrointestinal bleeding, or weight loss. Neoplasms are also found at surgery for intussusception, bowel obstruction, or perforation, as well as incidentally during a surgical or radiologic procedure for other reasons. Definitive diagnosis usually requires a biopsy for histopathologic examination and possibly immunotyping and cytogenetics, depending on the tumor.
Neoplasms of the gastrointestinal tract can be divided into categories based on their tissue of origin ( Table 47-1 ). The most commonly encountered tumors in children arise from the lymphoid or epithelial tissues. Mesenchymal tumors are less frequent. Both benign and malignant tumors can be found within all of these categories. In the following sections, we discuss the most commonly encountered neoplasms within these categories: their epidemiology, pathology, molecular biology, prognosis, and treatment.
| Tissue of Origin | Tumor | Most Common GI Sites |
|---|---|---|
| Lymphoid | Lymphonodular hyperplasia | Ileum, colon |
| Lymphoma | Ileum, appendix, colon | |
| Epithelial | Carcinoid | Appendix |
| Adenocarcinoma | Colon | |
| Mesenchymal | Leiomyoma/leiomyosarcoma | Colon |
| Gastrointestinal stromal tumor | Stomach, small intestine | |
| Primitive neuroectodermal tumor | Small intestine | |
| Schwannoma/malignant nerve sheath tumor/neurofibroma | Small intestine | |
| Hemangioma/vascular malformation | All levels | |
| Lipoma | Colon |
Neoplasms of Lymphoid Origin
The gastrointestinal tract is a lymphoid tissue–rich organ system, beautifully adapted to respond in a stimulatory or repressive fashion to recognized luminal antigens. Although there is lymphoid tissue throughout the gastrointestinal tract, in the form of lymphoid follicles or scattered T and B lymphocytes in the lamina propria, they are particularly prominent in the ileum where they aggregate into Peyer’s patches, well-organized germinal follicles of B lymphocytes with T lymphocytes in the interfollicular zones.
Lymphonodular Hyperplasia
Lymphonodular hyperplasia (LNH) is a common condition that can affect children of all ages. Its peak ages of occurrence are in early childhood and adolescence, as these are times of developmental lymphoid proliferation. Male children are more commonly affected; patients usually present with right lower quadrant abdominal pain, diarrhea, intussusception, or gastrointestinal bleeding. Endoscopy reveals patchy exaggeration of lymphoid nodules in the large and small bowel, at times distorting the overlying mucosa into prominent folds. Histologically there is reactive hyperplasia with prominent germinal center formation, but no disruption in the normal lymphoid architecture or cellular pleomorphism ( Figure 47-1 ). Assuming that acute management of symptoms is unnecessary, this condition is usually benign with no specific therapy required and an excellent prognosis.
In the setting of primary immunodeficiencies (hypogammaglobulinemias), however, LNH may occur with associated diarrhea, malabsorption, and chronic intestinal infections such as giardiasis. In adults, this lesion complicates primary hypogammaglobulinemia in approximately 20% of patients. The presence of intestinal lymphomas of either the B- or T-cell type is now well described adjacent to hyperplastic nodules in some of these patients.
Lymphoma
The gastrointestinal tract is the most common site of primary extranodal lymphomas. Primary gastrointestinal lymphomas are defined as tumors originating from the mucosa-associated lymphoid tissue (MALT) and contiguous lymph nodes, where the main bulk of the disease is located in that particular region of the gastrointestinal tract (i.e., stomach and ileum). Lymphoma accounts for approximately 15% of all small bowel malignancies in individuals from North America and Western Europe. In people younger than the age of 20 years, lymphoma, the most common malignant neoplasm of the gastrointestinal tract, is almost universally non-Hodgkin’s lymphoma. In children younger than 15 years of age, however, lymphoma is the third most common malignant neoplasm and accounts for 10% of all neoplasms. The gastrointestinal distribution differs between adults and children. Whereas 40% to 50% of primary gastrointestinal lymphomas occur in the stomach of adults, the most common sites in children are the terminal ileum, appendix, and cecum, with the frequency decreasing distally such that 10% to 20% occur in the colon.
Some 80% of primary intestinal non-Hodgkin’s lymphomas are of B-cell origin, collectively classified by the World Health Organization (WHO) as precursor or mature B-cell lymphomas, or proliferations of uncertain malignant potential, as are seen in secondary immunodeficiency states. In this same population, or in those individuals immunosuppressed by medications, Epstein-Barr virus (EBV)–associated B-cell lymphoma can be a complicating development in their care. EBV is also tightly linked to Burkitt’s lymphoma in equatorial Africa, but there is a much weaker association in patients from North America. Celiac disease is associated with a variety of small bowel neoplasms, but the most common is T-cell lymphoma (70%). The mean age of presentation in the setting of celiac disease is in the fifth decade, with the jejunum being the most common location. No pediatric cases have been reported.
Diagnosis usually requires surgical biopsy of a mass lesion; however, many lymphomas of the gastrointestinal tract can be diagnosed through endoscopic biopsies if the lesion involves mucosa or submucosa. Rapid ascertainment of tumor distribution with abdominal computed tomography (CT), bone scan, lumbar puncture, and bone marrow aspirate is required, and consultation with an oncologist is mandatory.
The most common lymphoma arising in the pediatric gastrointestinal tract is Burkitt’s lymphoma, which most frequently involves the ileocecal region where it presents as an abdominal mass or as the lead-point for intussusception. Burkitt’s lymphoma is a highly aggressive tumor, composed of sheets of mitotically active monomorphic medium-sized cells with scanty cytoplasm and round to oval nuclei containing small nucleoli. Within the sheets, there is apoptotic debris and numerous macrophages, producing a “starry-sky” appearance ( Figure 47-2 ). The lymphoma invades through all layers of the bowel, eroding surface mucosa and infiltrating mesenteric lymph nodes ( Figure 47-3 ). Genetic abnormalities, typically translocations involving the C-MYC gene at chromosome 8q24 leading to deregulation of the oncogene, are crucial in lymphomagenesis. The tumor cells have clonal immunoglobulin heavy- and light-chain rearrangements and TP53 -inactivating mutations in up to 25%.
The gastrointestinal tract is the most common extranodal site for diffuse large B-cell lymphoma (DLBCL), which develops in the pediatric ileocecal region, like Burkitt’s, or commonly the stomach in adults, where it may result from secondary transformation of a less aggressive lymphoma. This latter phenomenon is virtually unheard-of in children, given the exceedingly low incidence of extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (“MALT” lymphoma) that is associated with Helicobacter pylori infection. DLBCL in the gastrointestinal tract is indistinguishable from that arising within lymph nodes. The intestinal architecture is often destroyed by medium to large cells with vesicular nuclei and typically prominent nucleoli ( Figure 47-4 ). Most cases have clonal rearrangement of the immunoglobulin heavy- and light-chain genes and display often complex but not specific cytogenetic abnormalities. BLC2 gene translocation (t(14;18)) occurs in 20% to 30% of adult cases but has not been described in pediatric DLBCL. Abnormalities involving the BCL6 protooncogene localized to the 3q27 region are identified in more than 30% of adult cases of DLBCL, but extensive investigations have not been carried out in childhood DLBCL.
Treatment of gastrointestinal lymphoma is largely chemotherapy based, augmented with radiation therapy. Surgical resection is limited only to the rare circumstance of focal disease. The length and type of chemotherapeutic intervention depends on the extent of disease ( Table 47-2 ) but generally requires systemic therapy as well as intrathecal delivery of agents to prevent or treat involvement in the cerebrospinal fluid. The most commonly employed chemotherapeutic agents include cyclophosphamide, doxorubicin, vincristine, prednisone, and intrathecal methotrexate. The best prognosis is with stage A and B lymphoma (greater than 90% long-term survival), with stage AR having an equally favorable prognosis. Involvement with unresectable abdominal tumor carries a less favorable prognosis. With large tumor burden, the potential for tumor-lysis syndrome due to rapid cell turnover and consequent release of uric acid, potassium, and phosphorus into the bloodstream must be anticipated with the initiation of therapy.
| Stage | Description |
|---|---|
| A | Single extraabdominal site |
| B | Multiple extraabdominal sites |
| C | Intraabdominal |
| D | Intraabdominal with multiple extraabdominal sites |
| AR | Intraabdominal with more than 90% of the tumor surgically resected |
Carcinoma of the Colon
Colorectal cancer is the second leading cause of death in the United States, with an average lifetime risk, equal in men and women, of 6%. Most colon cancer occurs in older adults, with only 1% to 4% occurring in individuals younger than 30 years of age. Despite this infrequency, however, carcinoma of the colon is the most common primary solid malignancy of the gastrointestinal tract among children, occurring in less than 0.1 cases per million children younger than 20 years of age and 0.7 cases per million among children 10 to 19 years of age. The youngest reported case was in a 9-month-old female infant.
Some 70% to 80% of adult colon cancer is sporadic, with environmental factors playing a significant role in its development. Overall, the incidence is higher among developed countries in northwestern Europe, the United States, and Canada, compared with Asia and Africa. Furthermore, immigrants acquire the incidence of their adopted country, assuming that their diet similarly changes. The exact reason for this has not been elucidated; however, high-fat, low-fiber diets have been implicated. Environmental factors are not the only contributor, because 10% to 20% of cases are in individuals with at least two first-degree relatives with the cancer but no obvious inheritance pattern.
In some families, there is an autosomal dominant inheritance pattern to the development of colon cancer in the absence of any predisposing polyposis syndromes. Lynch syndrome I is characterized as an autosomal dominant pattern to the development of colon cancer only, whereas in Lynch syndrome II there is development of colon adenocarcinoma and extracolonic cancers that may involve the female genital tract, breast, and pancreas. These patients may develop multiple primary tumors, do so at a younger age, and have a high rate of subsequent tumors. Pediatric cases have been described with this inheritance pattern.
The possible development of colon cancer as a complication of an underlying bowel condition fosters angst in both the patient and the care provider. Predisposing diseases such as inflammatory bowel disease and hereditary polyposis syndromes, however, account for only 2% of the total cases of colon cancer. In children, however, 10% of those with colon cancer have an underlying condition of colitis or polyposis. The polyposis syndromes and their relative risk to the development of gastrointestinal cancer are discussed elsewhere in this volume. Underlying colitis of a duration of 10 years increases the cumulative risk of colorectal cancer by approximately 0.5% to 1% per year, with an overall increased relative risk of 20% in individuals with ulcerative colitis (UC) compared with the general population. The age of colitis onset is not important, but more extensive colon involvement increases the risk, as does having primary sclerosing cholangitis. In contrast to sporadic colorectal carcinomas, those developing from underlying colitis can be multifocal and develop frequently from flat mucosa rather than adenomas, most likely contributing to their early mean occurrence in the fourth decade of life. The risk of developing colorectal cancer in subjects with colitis due to Crohn’s disease (CD) is thought recently to be as high as with UC. Additionally, patients with CD do have an increased risk of small bowel cancer; their risk of anorectal cancer does not appear to be significantly elevated, however, but data remain conflicting. Furthermore, whereas the carcinoma develops in areas inflamed or previously inflamed in UC, those that develop in the setting of CD may do so in grossly normal intestine; however, most have either adjacent or distant dysplasia. In addition to the risk factors outlined previously for UC, smoking is an important variable leading to increased risk of colon cancer in Crohn’s colitis.
The clinical presentation in children with colon cancer is similar to those of other gastrointestinal neoplasms. Children report vague abdominal pain in approximately 95% of cases with less-frequent reports of altered bowel habits (17% to 32%) and rectal bleeding (14% to 23%). Physical findings most commonly include an abdominal mass in 59% and abdominal distension in 48%, with emaciation and anemia found in less than 25%. The infrequency of physical findings and the vagueness of symptoms probably contribute to the relative lengthy median time (2 to 6 months) between the onset of symptoms and diagnosis. Hence, malignancy should be considered in the differential diagnosis of chronic abdominal pain.
The diagnosis of GI carcinoma starts by including its possibility in the differential of vague abdominal complaints. Depending on the presenting symptoms, the mass lesion may be found at endoscopic evaluation or by abdominal CT or magnetic resonance imaging (MRI). Consequently, if the etiology of persistent abdominal symptoms has not been forthcoming, an abdominal CT or MRI is an appropriate method of assessment. Definitive diagnosis is made by histologic evaluation of tissue. Laparotomy is generally required and is mandatory for proper staging with sampling of regional lymph nodes. Because the mainstay of therapy is surgical resection, a careful attempt at complete, radical resection with primary anastomosis, without seeding of the peritoneum and viscera, is of greatest prognostic value to the subject. The staging evaluation is then completed with a CT of the chest and a bone scan ( Table 47-3 ).
Related posts:
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
