Disseminated Burkitt lymphoma presenting as massive gastrointestinal bleed

Abstract

Burkitt lymphoma is a rare, highly aggressive non-Hodgkin lymphoma with increasing incidence. Here we present a 26-year-old man with a history of a recent root canal who presented with 2 days of black, tarry stools, persistent tooth pain, and 2 weeks of fatigue, night sweats, and a 20-pound weight loss. He developed massive hematemesis while hospitalized and an esophagogastroduodenoscopy revealed innumerable, doughnut-shaped masses with central umbilication throughout the stomach, which were also the source of bleeding. Targeted biopsies revealed Burkitt lymphoma. After prompt chemotherapy treatment, repeat endoscopy showed complete resolution of all gastric masses, and the mucosa appeared normal.

Burkitt lymphoma (BL) is a highly aggressive non-Hodgkin lymphoma often presenting in extranodal sites or as an acute leukemia. The World Health Organization describes three clinical variants of BL: endemic, sporadic, and immunodeficiency associated. Endemic BL is seen in African children between 4 and 7 years of age, and immmunodeficiency-associated BL often arises in patients infected with human immunodeficiency virus (HIV). The sporadic variant most commonly presents as an intra-abdominal mass, with a median age of diagnosis of 30 years.¹ The incidence of upper gastrointestinal bleeding secondary to BL appears to be rare based on review of the current literature. We present a young man who presented with fatigue, night sweats, and weight loss, developed massive upper gastrointestinal bleeding, and was found to have disseminated BL through endoscopic evaluation.

CASE PRESENTATION

A 26-year-old white man with a history of a recent root canal presented with 2 days of black, tarry stools and severe tooth pain. He reported taking ibuprofen and aspirin daily for pain. In addition, he reported 2 weeks of fatigue, night sweats, and a 20-pound weight loss, which he attributed to dietary modifications. He had no palpable lymph nodes. His white blood cell count was 34,000 cells/mm³; hematocrit 37.8%; lactate dehydrogenase 4377 U/L; and uric acid 10.0 mg/dL. A peripheral blood smear identified immature myeloid cells and rare blasts and flow cytometry identified a clonal population (17%) of mature B cells with kappa-restricted CD10+/CD19+ phenotype. Contrast-enhanced computed tomography showed an enlarged spleen, numerous hypoattenuating lesions in the kidneys, nodularity of the omentum, and mesenteric lymphadenopathy, with a maximum size of 31 mm. On hospital day 3, he developed hematemesis, associated with a decline in hematocrit to 17.1%. He required transfer to the intensive care unit and transfusion of 7 units of packed red blood cells over a 48-hour span. An esophagogastroduodenoscopy revealed a large clot obscuring the fundus and cardia and innumerable doughnut-shaped masses, ranging in size from 0.4 to 1.5 cm, with central umbilication throughout the entire stomach (Figure 1a, 1b). Targeted biopsies identified CD20-positive B cells that coexpressed CD10 and c-Myc by immunostain, suggesting the diagnosis of BL, without evidence of Epstein-Barr virus (EBV) RNA. Random biopsies from the stomach were devoid of neoplastic cells and negative for Helicobacter pylori infection by modified Giemsa stain. Serologic tests for EBV viral capsid antigen IgM and IgG and HIV 1 and 2 antibody/antigen screen were all negative.

Figure 1.

(a) Representative masses: innumerable doughnut-shaped masses with central umbilication. (b) Mass with overlying adherent clot obscuring the fundus and cardia. (c) Postchemotherapy endoscopy 6 weeks later depicting complete resolution.

The patient received the first dose of cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper-CVAD) along with rituximab. A repeat endoscopy the following day identified a clot in fundus, which appeared to have doubled in size and could not be removed. A third endoscopy was performed the next day, after 2 days of chemotherapy, and the clot had shrunk significantly. The clot was removed with a Roth net and was found to arise from a lymphomatous mass. Six weeks from initiation of chemotherapy, a repeat endoscopy showed complete resolution of all gastric masses and the gastric mucosa appeared normal (Figure 1c).

DISCUSSION

BL is a rare differentiated aggressive B-cell lymphoma characterized by highly proliferative neoplastic changes, with the hallmark being overexpression of the c-MYC gene due to chromosomal rearrangement with IgG heavy chain locus.² BL represents <1% of all cancers in the United States. There is a male predominance, with 22% exhibiting B symptoms. About 78% of cases involve an extranodal site, and only 11% involve the gastrointestinal tract, which defines the rarity of occurrence and the unusual presentation of this disease.¹ The 5-year survival rate for BL with secondary involvement in patients who receive prompt therapy ranges from 39% to 83% depending on the type of chemotherapy employed.³

H. pylori has been linked to causation of gastric lymphoma several times,^4–6 and its eradication may result in complete remission of gastric BL.^7,8 BL seems to have a predisposition in immunosuppressed patients, such as those with HIV or after transplantation.⁹ However, our patient tested negative for H. pylori and HIV and was not immunocompromised. Similarly, EBV has been associated with 98% of endemic cases, 30% to 40% of HIV-associated cases, and 20% of sporadic cases. Our patient tested negative for acute or chronic exposure to EBV, both in serology and lymphoma cells.

Sporadic BL has been most frequently reported as an intraabdominal mass with involvement of bone marrow, liver, kidney, and spleen, which was also observed in our case.¹⁰ The mass usually presents in the ileocecal area with symptoms such as obstruction, visible swelling, and/or pain; however, in our case, there was no such complaint. The first gastrointestinal complaint was melena followed by massive hematemesis, which is an infrequent observation. Though no endoscopic therapy was performed in our patient, endoscopy assisted with diagnosis. Early diagnosis is imperative given the high mortality rates with delays in chemotherapy initiation. The treatment of choice for aggressive BL in all stages is intensive systemic chemotherapy, as long as the patient is stable enough to receive it.¹¹ However, patients with disseminated disease, increasing age, and central nervous system involvement seem to have inferior outcomes.¹² BL presenting with gastrointestinal bleed is considered a hematological emergency and requires prompt treatment. In a study of 105 BL patients, Kasamon et al¹³ concluded that remission can scale up to 60% to 90% in adults if prompt diagnosis, referrals, and adequate early treatment are provided. A repeat endoscopy after 6 weeks of initiation of chemotherapy of our patient suggested complete remission with normalization of the gastric mucosa, thereby emphasizing prompt diagnosis and early adequate treatment of this condition.