Non-Hodgkin Lymphomas (Burkitt Lymphoma)

Burkitt lymphoma is a malignancy of lymphoid origin and the commonest specific subtype of non-Hodgkin lymphoma in children. It is among the fastest growing of all human malignancies. It is a paediatric oncological emergency because of its aggressive biology and the well established risk of tumour lysis syndrome.

Epstein-Barr virus infection is strongly and well associated with the disease. The association is near-universal in the endemic, African variant. Its geographic distribution overlaps with holoendemic malaria transmission. This is believed to reflect chronic B-cell stimulation and immune dysregulation from the parasitic co-infection.

The molecular hallmark is a chromosomal translocation involving the MYC oncogene, most commonly t(8;14). It drives the extremely rapid tumour growth. The clinical priority is immediate recognition and urgent treatment.

Pathophysiology and classification

• The t(8;14) translocation, or less commonly a variant translocation involving alternative immunoglobulin gene loci, places the MYC oncogene under a strong, constitutively active immunoglobulin gene promoter. MYC protein is dysregulated and markedly overexpressed. This drives uncontrolled proliferation, with tumour doubling time frequently measured in days.
• Three clinical and epidemiological variants are described.
  • Endemic (African): jaw or facial bone involvement, near-universal Epstein-Barr virus association, occurring in regions of holoendemic malaria.
  • Sporadic: occurs worldwide, with a lower rate of Epstein-Barr virus association and characteristic abdominal involvement.
  • Immunodeficiency-associated: occurs with HIV infection or other significant immunosuppression.
• The extremely high proliferation rate and frequently substantial tumour bulk at diagnosis make this malignancy especially vulnerable to tumour lysis syndrome once treatment starts. Rapid cell death releases large amounts of intracellular contents (potassium, phosphate and uric acid). This is a defining management consideration.

• Sporadic Burkitt lymphoma characteristically presents with abdominal involvement. Features include a rapidly enlarging abdominal mass, abdominal pain and, in some cases, intestinal obstruction.
• The tumour tends to arise within or adjacent to the ileocaecal region. It can therefore mimic or precipitate intussusception, an important differential in a child with this pattern. Meckel diverticulum is also a differential.
• Endemic Burkitt lymphoma characteristically presents with a rapidly enlarging jaw or facial bone mass. It can also involve the abdomen and other sites. The pattern reflects the epidemiological and geographic context.
• The defining clinical feature across all variants is extremely rapid tumour growth. A mass may have been absent only days to weeks previously. This is a distinctive clue and prompts urgent diagnostic evaluation and treatment.
• Central nervous system involvement occurs when tumour infiltrates the central nervous system or meninges. Features include cranial nerve palsies and other neurological signs.
• Bone marrow involvement produces cytopenias, with pallor, bruising and susceptibility to infection.
• Central nervous system and marrow involvement indicate more advanced or disseminated disease. Their presence and extent inform staging and treatment intensity.
• Systemic symptoms, including fever and significant, rapid weight loss, frequently accompany the localised mass. They reflect the metabolic burden of this rapidly proliferating malignancy.

• Tissue biopsy is the essential, definitive diagnostic approach. Histopathology shows the characteristic "starry sky" appearance. Scattered macrophages containing phagocytosed apoptotic tumour cell debris lie against a background of densely packed, uniform malignant lymphoid cells. This reflects the extremely high rates of proliferation and spontaneous cell death.
• Immunohistochemical and molecular characterisation confirms the diagnosis and the characteristic MYC translocation.
• Tumour growth is extremely rapid. Once the diagnosis is clinically suspected, proceed with urgency. Prompt biopsy and pathological assessment avoid unnecessary delay in treatment.
• Staging investigation informs treatment planning. It includes bone marrow aspiration and biopsy, cerebrospinal fluid examination (assessing for central nervous system involvement) and cross-sectional imaging to assess the full extent of disease.
• Pre-treatment assessment includes baseline renal function, electrolytes (including potassium, phosphate and calcium) and uric acid. This is critical for anticipating and proactively managing the substantial risk of tumour lysis syndrome once treatment starts.

• Intensive, short-duration, dose-dense combination chemotherapy is standard treatment. Modern protocols achieve excellent overall survival, particularly for localised disease. This reflects the paradoxical vulnerability of this aggressive malignancy to intensive chemotherapy, since rapidly dividing cells are generally highly sensitive to cytotoxic agents.
• Proactive, aggressive prevention and management of tumour lysis syndrome is critical. Start before or with definitive chemotherapy. The risk is life-threatening hyperkalaemia, hyperphosphataemia and acute kidney injury as the massive tumour burden lyses in response to treatment.
• Tumour lysis prevention comprises aggressive intravenous hydration, plus either allopurinol (reducing new uric acid production) or rasburicase. Rasburicase is a recombinant urate oxidase that rapidly reduces existing uric acid levels. Use it for patients with significant existing tumour burden or renal impairment, who carry higher risk.
• Monitor biochemistry closely and frequently (potassium, phosphate, calcium and renal function) throughout the initial treatment period.
• Central nervous system prophylaxis with intrathecal chemotherapy is a standard, essential component of the great majority of protocols. The malignancy has a recognised propensity for central nervous system involvement or relapse. Give it whether or not overt central nervous system involvement is identified at diagnosis.
• Rituximab, an anti-CD20 monoclonal antibody, is increasingly incorporated into standard protocols with chemotherapy. It has demonstrated benefit in improving outcomes for this CD20-expressing B-cell malignancy.
• Significant tumour bulk causing mechanical complications, including intestinal obstruction or, less commonly, airway compromise from jaw or facial involvement, may need urgent surgical or supportive intervention alongside prompt chemotherapy.
• Close supportive care is needed throughout intensive treatment. It covers profound treatment-related cytopenias, infection risk, and the nutritional and psychosocial demands of intensive, though generally short, treatment.
• Structured long-term follow up addresses disease surveillance and potential late treatment effects. With prompt and appropriately intensive treatment, this aggressive childhood malignancy is generally highly curable.