Gastric Burkitt Lymphoma: A Rare Cause of Upper Gastrointestinal Bleeding in a Child With HIV/AIDS

Abstract

Upper gastrointestinal (UGI) bleeding is an uncommon manifestation of acquired immune deficiency syndrome (AIDS) despite frequent involvement of the gastrointestinal tract by infections, malignancies, and other disorders (1). Primary gastric Burkitt lymphoma is rare in children; only 4 pediatric cases of gastric Burkitt lymphomas have been reported previously (2–4). According to our review of the literature, this is the first case report of a child with human immunodeficiency virus (HIV)/AIDS presenting with upper gastrointestinal bleeding due to gastric Burkitt lymphoma. An 11-year-old African American male with congenital HIV/AIDS, noncompliant with a highly active antiretroviral regimen for at least 2 months, was admitted to the hospital with a 5-day history of fever and abdominal pain. The patient was noted to have guaiac-positive stools and subsequently developed frank melena. He was started on intravenous lansoprazole. A nasogastric tube was inserted and bloody gastric contents were aspirated. The patient appeared malnourished and had periorbital edema. He was pale and tachycardic with a blood pressure of 108/65 mmHg. His abdomen was soft, flat, and nontender. The liver was palpated 4 cm below the right costal margin in the midclavicular line. The spleen measured 6 cm below the left costal margin. A gastrostomy tube was in place and the peristomal site showed the presence of granulation tissue. Laboratory investigations revealed hemoglobin of 6 g/dL. The white blood count was 23.5 × 109/L, and the platelet count was 420 × 109/L. The prothrombin time was 14.2 seconds with a partial thromboplastin time of 27.4 seconds and an International Normalized Ratio of 1.4. His CD4 count was 1138/mm3 and the viral load was >750,000 HIV copies per milliliter. The serum uric acid level was high at 13 mg/dL and the lactate dehydrogenase was elevated at 900 U/L. Both blood urea nitrogen and creatinine were elevated at 28 mg/dL and 2.2 mg/dL, respectively. The AST and ALT were 143 U/L and 43 U/L, respectively, with a total bilirubin of 0.2 mg/dL. Total protein was normal at 6 g/dL, but the albumin was low at 2.1 g/dL. The patient received 2 units of packed red blood cells. An upper endoscopy revealed diffusely thickened gastric folds and numerous large ulcers with deep craters in the body of the stomach (Fig. 1A). Multiple gastric erosions and ulcers also were noted, showing stigmata of recent bleeding (Fig. 1B). These lesions were treated with injections of 1:10,000 epinephrine via a 25-gauge sclerotherapy needle. The esophageal and duodenal mucosa appeared normal. After this procedure, there was no further active bleeding from the gastrointestinal tract.FIG. 1: (A) Diffusely thickened, beefy gastric folds and numerous large ulcers with deep craters in the body of the stomach. (B) Multiple gastric erosions and ulcers can be seen with stigmata of recent bleeding.Histological examination of the gastric biopsy specimens revealed diffuse infiltration of the mucosa by monomorphic, medium-size, neoplastic-appearing lymphocytes showing a “starry sky” pattern (Fig. 2). Immunostains using the anti–CD20 antibodies (a pan–B cell marker) showed positive cells infiltrating the gastric mucosa. Immunostains for anti–CD 10 (a marker of germinal center cells and Burkitt lymphoma cells) showed the presence of infiltrative neoplastic lymphocytes within the gastric mucosa. There also were scattered CD3–positive T lymphocytes present within the mucosa. The findings were indicative of a B cell Burkitt type lymphoma. Immunostains for Helicobacter pylori, Epstein-Barr virus, and cytomegalovirus in duodenal, gastric, and esophageal biopsies were negative.FIG. 2: Different degree of infiltration by the neoplastic lymphocytes. Normal glands with preserved architecture (*) are present in the left lower corner. Infiltration of the lymphoma cells between the gastric glands and loss of the normal architecture are present in the right lower corner (triangles). The classic lymphoma area—with a diffuse lymphocytic infiltration, superficial ulceration, and disappearance of the gastric glands—is present in the top of the microphotography (arrows). The classic “starry sky” appearance is created by the tangible body macrophages containing phagocytozed cell debris.A bone marrow biopsy showed a markedly hypercellular marrow with a moderate increase in megakaryocytes. Foci of small to medium-sized atypical lymphocytes with pleomorphic changes were present. The myeloid-erythroid ratio was 2:1. Flow cytometry showed immunophenotypic evidence of an expanded population of mature B cell lymphocytes. These cells were characterized by the presence of CD19, CD79A, CD22, and cytoplasmic immunoglobulin M and were negative for CD23, CD5, and TdT. There were foci of strongly CD20+ atypical lymphocytes. CD138 was positive in numerous scattered plasma cells (a marker of activated B cell). Immunostain for Epstein-Barr virus–encoded nuclear antigen 1 was negative. The patient was found to be persistently hypoglycemic during his hospitalization, with an elevated insulin level of 4 U/L even with serum glucose measurements below 40 mg/dL. He was started on diazoxide with partial correction of his hypoglycemia. After a discussion with the oncologists about the lack of curative therapy, the boy's parents agreed to palliative care. The patient ultimately died after 1 month of hospitalization. DISCUSSION In adult patients with HIV/AIDS, gastrointestinal bleeding is uncommon. The likelihood of upper gastrointestinal bleeding due to a cause related to HIV/AIDS is inversely proportional to the CD4 count (1). Interestingly, our patient had a high CD4 count, which is associated with a lower risk for bleeding. In a study of 453 consecutive adult patients with AIDS, the cumulative probability of acute bleeding was 3% and 6% at 6 and 14 months, respectively (2). In HIV patients who do bleed, the rates of rebleeding and mortality are high (1–3). UGI bleeding in patients with AIDS may be related to opportunistic infections with cytomegalovirus, herpes simplex, and candida, or to accompanying tumors such as non-Hodgkin lymphoma and Kaposi sarcoma. In other patients, the cause may not be directly related to HIV infection as in patients with Mallory Weiss tears, peptic ulcer disease, or portal hypertension. There are few reports of UGI bleeding in children with HIV/AIDS (5). To date, only 4 pediatric cases of gastric Burkitt lymphoma have been reported, and none of the patients were infected with HIV or presented with UGI bleeding (4,6–8). We considered other potential causes of gastritis and gastric ulcers in patients immunocompromised immune systems, including cytomegalovirus and ulceration related to Epstein-Barr virus. However, neither of these pathogens was detected by immunostaining in the gastric biopsy tissue or in the bone marrow. Cytomegalovirus appears to be the chief pathogen associated with gastric ulcers in patients with AIDS (9). Large gastric ulcers and UGI bleeding also are well documented in posttransplant lymphoproliferative disorder associated with Epstein-Barr virus infections in immunosuppressed transplant patients (10). However, posttransplant lymphoproliferative disorder is not a described complication in patients with HIV, even in those with low CD4 counts. We also searched for H pylori infection because of the presence of severe gastritis noted on endoscopy. B cell lymphomas occurring in mucosa-associated lymphoid tissue lymphomas occur in the stomach, and 70% of gastric mucosa-associated lymphoid tissue lymphomas are associated with H pylori infection (11–13). An unusually low prevalence of H pylori infection has been reported in patients with AIDS, and there are no reported cases of mucosa-associated lymphoid tissue lymphomas in patients who are HIV positive (9,14,15). Non-Hodgkin lymphoma develops in approximately 10% of pediatric patients with HIV infection, primarily in those with advanced AIDS and a CD4 count below 100 copies per microliter (16,17). Coanalysis of the pediatric cancer and pediatric AIDS registries showed that 34% of all cancers in children with AIDS were Burkitt lymphomas (18). The gastrointestinal tract is the presenting site of Burkitt lymphoma in approximately 45% of those children and is the most frequent site of extranodal disease (16,19–21). Gastrointestinal Burkitt lymphoma is found most frequently in the small intestine and has not been reported in the stomach. In the larger cohort of patients without AIDS, a 44-year retrospective review of a large pediatric tumor registry revealed no cases of primary gastric Burkitt lymphoma (22). Even in the few adult patients with HIV/AIDS with gastric Burkitt lymphoma, the major presenting symptoms are abdominal pain and weight loss, and gastrointestinal bleeding is uncommon (1,2). We describe a child with HIV/AIDS who presented with UGI bleeding due to gastric Burkitt lymphoma. Upper gastrointestinal bleeding is an uncommon manifestation of HIV/AIDS. Patients with advanced AIDS usually bleed from AIDS-related infections or nonspecific esophageal or gastric mucosal injuries. The case presented suggests that the presence of large gastric ulcers with deep craters and beefy margins in a child with HIV/AIDS should suggest the possibility of a gastric malignancy such as Burkitt lymphoma.