Successful treatment of pediatric primary hepatic Burkitt lymphoma using rituximab: A case report

Abstract

To the Editor: Non-Hodgkin lymphoma (NHL) is one of the most common malignancy groups diagnosed in children. Burkitt lymphoma (BL) accounts for approximately 30% of NHL diagnoses.1 Primary hepatic lesions, however, are exceedingly rare in children with only a handful of cases described in the literature (Table S1).2–7 Here we describe the clinical course of a child diagnosed with primary hepatic Burkitt lymphoma (PHBL). A 5-year-old previously well male presented to the emergency department with a 12-day history of abdominal pain and fatigue. Physical examination revealed nontender hepatomegaly with the liver edge palpable 10 cm below the right costal margin. There was no associated lymphadenopathy and he was otherwise asymptomatic. Bloodwork performed on admission showed a mild transaminitis with no signs of synthetic liver dysfunction. Uric acid was elevated at 560 μmol/L and lactate dehydrogenase was markedly elevated at 2747 U/L. A complete blood count revealed a mild normocytic anemia (hemoglobin 99 g/L) but was otherwise unremarkable. Computed tomography (CT) of the liver revealed innumerable large, hypoattenuating lesions involving the entire liver, with the largest lesion measuring approximately 7.3 × 6.7 × 6.1 cm (Figure 1A). Multiple small hypodense nodules involving both kidneys were foundwith no adrenal involvement. Bilateral bone marrow aspirates and biopsies, and cerebrospinal fluid were unremarkable. An ultrasound-guided liver biopsy demonstrated intermediate-sized neoplastic cells with abundant mitotic and apoptotic forms and an absence of normal liver parenchyma. Admixed macrophages demonstrated a characteristic “starry-sky” appearance. On immunohistochemistry, the neoplastic cells showed positivity for CD20, CD10, C-MYC, BCL6, and PAX5 markers as well as over 90% Ki67 proliferation index. Fluorescence in situ hybridization demonstrated the presence of the C-MYC rearrangement, confirming the diagnosis of Burkitt lymphoma. The patient was risk stratified as stage III Group B and began chemotherapy as per the COG ANHL1131 protocol (Protocol Inter-BNHL Ritux 2010) with COP prephase (cyclophosphamide, vincristine, prednisone).8 He demonstrated good response at his day 7 reassessment with a reduction in size of his hepatic lesions by more than 50% and therefore continued with Group B treatment with the addition of rituximab.8 This treatment consisted of two induction courses of RCOPADM (rituximab, cyclophosphamide, vincristine, prednisone, doxorubicin, methotrexate 3 g/m2) and a single consolidation course of R-CYM (rituximab, cytarabine, methotrexate 3 g/m2). CT imaging performed after the consolidation course demonstrated persistent liver lesions (Figure 1B). He was therefore upgraded to the Group C1 treatment arm. He received two consolidation courses of R-CYVE (rituximab, cytarabine, etoposide), and two maintenance courses: M1 (vincristine, prednisone, methotrexate 8 g/m2, cyclophosphamide, doxorubicin, triple intrathecal), and M2 (cytarabine, etoposide). A positron emission tomography (PET) scan at the completion of therapy showed no signs of active disease. CT imaging demonstrated regression of hepatic lesions (Figure 1C). The patient’s treatment course was complicated by three uneventful admissions for febrile neutropenia. At 8 months post therapy completion, the patient required intravenous immunoglobulin replacement for recurrent hypogammaglobulinemia in the context of frequent viral upper respiratory tract infections. One year following completion of chemotherapy, he remained clinically well and disease-free with two persisting stable hepatic lesions. Pediatric PHBL is exceptionally rare, only having been described six times in the literature (Table S1).Most casesof pediatricPHBL in the literature had nonspecific presentations including abdominal distension, low-grade fever, and weight loss. In only one case did the child present as clinically unwell with signs of liver failure.6 All patients have been male with significant hepatomegaly and liver involvement on imaging despite a symptomatic period of less than 2 weeks. This timeline reflects the aggressive nature of BL with evolution from asymptomatic to obvious abdominal distention.9 We initially suspected a diagnosis of neuroblastoma given the patient’s age, liver involvement, and normal AFP levels.4 Despite the significant hepatic involvement, all but one of the cases in the literature had normal synthetic liver function and either normal liver enzymes or amild transaminitis. This suggests that despite a high burden of disease in the liver, function is not significantly impaired for themajority of presentations in PHBL. This is reassuring, as adult data suggest worse outcomes for NHL presenting with liver failure.10 This is the first reported case of rituximab being used in the management of pediatric PHBL. Rituximab has been shown to improve survival rates for children with BL and is now included in the Children Oncology Group’s protocol for mature B-cell NHL.8,11,12 Our review of the literature demonstrates favorable outcomes for pediatric PHBL. In our review, the only death reported was in a child who did not survive to begin treatment and whose diagnosis of PHBL was madepost-mortem.3 Theother patientswere treated successfullywith chemotherapy (Table S1). Therewas variability in how long liver lesions persisted following treatment initiation, ranging from 1.5 months to over a year in those studies that reported long-term follow-up.2,4 In our