Neoplasms of the Gastrointestinal Tract

Neoplasms of the Luminal Gastrointestinal Tract

Up to 5% of primary childhood cancers will arise in the GI tract in contrast to over 20% in adults. ^, This is a small but important fact for the gastroenterologist who may be the first to discover the problem. When neoplasms do arise from the GI tract, the presenting symptoms are variable and relatively nonspecific. The symptoms or signs may include abdominal pain, abdominal distension, vomiting, a palpable mass, anemia, GI 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 with immunotyping and cytogenetics, depending on the tumor.

Similarly to all neoplasms, tumors of the GI tract are classified based on their tissue of origin and primary site of development ( 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.

Neoplasms of Lymphoid Origin

As 60% of the body’s lymphocytes are located in the GI tract, it is adapted to respond in a stimulatory or repressive manner to recognized luminal antigens. Although there is lymphoid tissue throughout the GI 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 patches, well-organized germinal follicles of B lymphocytes with T lymphocytes in the interfollicular zones.

Lymphonodular Hyperplasia

Lymphonodular hyperplasia (LNH) of the GI tract is a common endoscopic finding in children that regresses over time into early adulthood. It is the result of lymphoid proliferation in the developing immune system and increases at times of infection, as all lymph tissue does. LNH is more prominent in the distal small bowel as well as the colon that corresponds with the high bacterial load of these regions. It can be seen in both symptomatic and asymptomatic children; thus, its role in abdominal pain and diarrhea is not clear. LNH of the distal small bowel can result in a lead point followed by ileocolonic intussusception in children. In addition, LNH of the distal colon is often the only finding in the evaluation of lower intestinal bleeding in children and should not be mistaken for inflammatory bowel disease (IBD). Endoscopy reveals patchy exaggeration of lymphoid nodules in the large and small bowel, at times distorting the overlying mucosa into prominent folds ( Fig. 47.1A ). Histologically, there is reactive hyperplasia with prominent germinal center formation, but no disruption in the normal epithelial or lymphoid architecture and without cellular pleomorphism (see Fig. 47.1B ). Assuming that acute management of symptoms is unnecessary, this finding is usually benign with no specific therapy required.

In the setting of primary immunodeficiencies (hypogammaglobulinemias), however, LNH may occur with associated diarrhea, malabsorption, and chronic intestinal infections such as giardiasis. An immunodeficiency should be suspected with prominent LNH outside of childhood or in the proximal intestinal tract. In adults, this lesion complicates primary hypogammaglobulinemia in approximately 20% of patients. The presence of intestinal lymphomas of either the B-cell or the T-cell type is now well described adjacent to hyperplastic nodules in some of these patients. ^,

Lymphoma

In children, lymphoma accounts for over 10% of all neoplasms, the third most common tumor in this age group, and is most commonly non-Hodgkin mature B-cell lymphoma. Lymphoma is also the most common malignant neoplasm in the GI tract, and the GI tract is the most common site of primary extranodal lymphoma with an annual incidence in children of two per million in the United States. The GI distribution differs between adults and children. Whereas 50% of primary GI 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. In adults, lymphoma accounts for up to 50% of all small bowel malignancies but less than 1% of neoplasms in the GI tract when colorectal neoplasms are included.

The World Health Organization (WHO) categorizes lymphoid neoplasms as mature B-cell neoplasms, mature T-cell and natural killer cell neoplasms, Hodgkin lymphoma, posttransplant lymphoproliferative disorder (PTLD), and histiocytic and dendritic cell neoplasms. Approximately 80% of primary intestinal lymphomas are of B-cell origin, and WHO classification has significantly changed from 2001 to 2016 with no less than 20 subtypes of mature B-cell lymphomas further categorized by types and locations of the B-cell lymphoma including those that may occur in the intestinal tract. ^, T-cell lymphomas comprise less than 10% of all lymphomas in children and are rarely found in the GI tract. Patients with celiac disease have a twofold increased risk of enteropathy-associated T-cell lymphoma with median age of 61 years at diagnosis, with the mid-small bowel being the most common location; conversely, there are no reported cases in pediatrics. PTLD occurs exclusively after patients have received a solid organ transplant, is most commonly associated with Epstein-Barr Virus (EBV), and has a variable incidence based on the type of transplanted organ. Patients on chronic immunosuppression such as a thiopurine also have an increased risk of a B-cell lymphoma, often associated with EBV.

Diagnosis usually requires surgical biopsy of a mass lesion; however, many lymphomas of the GI 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.