Endemic Burkitt Lymphoma in a Child: Diagnostic Workup and Treatment Protocol

Background and Clinical Context

Step 1: Recognizing the Clinical Presentation

• Jaw/facial bone mass - the hallmark of the endemic form; produces the "floating tooth sign" on jaw X-ray due to destruction of tooth crypts
• Orbital mass causing proptosis
• Abdominal masses - involvement of kidneys, ovaries, and adrenal glands
• Paraspinal/epidural disease - presenting as paraplegia in up to 15%
• Rapid onset - symptoms progress over days to weeks

Red flag: Spontaneous tumor lysis syndrome (TLS) can occur even before chemotherapy due to the extraordinarily high proliferative rate.

Step 2: Initial Assessment and Blood Tests

Step 3: Definitive Tissue Diagnosis (Biopsy)

Histology (H&E)

• Diffuse infiltrate of intermediate-sized monomorphic cells (10-25 µm)
• Round or oval nuclei with coarse chromatin and 3-5 prominent nucleoli in relatively clear parachromatin
• Moderate basophilic cytoplasm that "squares off" between adjacent cells
• Lipid-containing cytoplasmic vacuoles visible on imprints
• Near 100% mitotic rate (among the highest of any human tumor)
• Numerous apoptotic cells ingested by benign macrophages = the "starry sky" pattern

Immunophenotype (IHC Panel)

Cytogenetics/FISH (Mandatory)

• t(8;14)(q24;q32) in ~80% - MYC with IGH locus
• t(2;8) in ~15% - MYC with kappa light chain
• t(8;22) in ~5% - MYC with lambda light chain

In Touch Imprints/CSF Cytology

• Burkitt cells in peripheral blood or bone marrow aspirate: medium-sized cells with deep blue vacuolated cytoplasm on Wright stain (characteristic)

Step 4: Staging Workup

• Bilateral iliac crest trephine biopsy is mandatory

• 25% blast replacement = reclassified as Burkitt leukemia

• Mandatory for all patients
• Cell count, protein, cytospin cytology
• CSF involvement = Stage IV disease, requires intensified CNS-directed therapy

Step 5: Pre-Treatment Risk Stratification

• Tumor lysis syndrome risk - virtually all endemic BL children are high-risk given bulky disease
• Performance status and organ function
• CNS involvement (LP result)
• Bone marrow involvement

• IV hydration (3 L/m²/day without potassium or phosphate)
• Allopurinol (xanthine oxidase inhibitor); rasburicase preferred if already elevated uric acid
• Close monitoring of electrolytes every 6-8 hours

Step 6: Treatment Protocol

Preferred Regimens for Pediatric Endemic BL

• COPAD (pre-phase): Cyclophosphamide + Vincristine + Prednisone + Doxorubicin
• COPADM (induction): Above + high-dose Methotrexate (3 g/m²)
• CYM or CYVE (consolidation): Cytarabine + Etoposide (for CNS disease)
• Intrathecal therapy (IT) with methotrexate + cytarabine ± hydrocortisone is given with each cycle
• Duration: ~4-6 months total

• Group A (Stage I/II, completely resected): 2 cycles COPAD
• Group B (Stage I/IV, non-resected, no CNS/BM): COPADM x2 + CYM x2
• Group C (CNS or BM involvement): COPADM + CYVE + BM consolidation

• CODOX-M: Cyclophosphamide + Vincristine + Doxorubicin + high-dose Methotrexate
• IVAC: Ifosfamide + Etoposide + high-dose Cytarabine (alternating cycles)
• Widely used internationally; excellent results in children and adults
• All regimens incorporate CNS prophylaxis - intrathecal methotrexate ± systemic high-dose methotrexate

• Etoposide + Vincristine + Doxorubicin (continuous infusion) + Cyclophosphamide + Prednisone + Rituximab
• Emerging strong data in adolescents and adults; used at major centers
• Less data in young children

Rituximab note: All modern regimens now incorporate rituximab (anti-CD20) in children ≥2 years with adequate CD20 expression (essentially all BL). It significantly improves outcomes.

CNS-Directed Therapy (Mandatory for ALL Patients)

• Intrathecal chemotherapy with methotrexate ± cytarabine ± hydrocortisone given at every cycle
• High-dose systemic methotrexate (3-8 g/m² with leucovorin rescue) penetrates the blood-brain barrier
• Cranial radiation is generally avoided in pediatric patients due to neurocognitive late effects; it is reserved for frank CNS relapse

Tumor Lysis Syndrome Management During Treatment

• Must be anticipated before every cycle
• Hyperhydration, rasburicase, electrolyte monitoring, cardiac monitoring
• ICU admission may be required for severe TLS

Expected Outcomes

Summary Diagnostic Pathway

Clinical suspicion (jaw mass / abdominal mass in African child)
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Urgent bloods: CBC, LDH, uric acid, electrolytes, creatinine, EBV serology, HIV
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Tissue biopsy (excisional preferred) → H&E + immunohistochemistry + FISH for MYC
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Bone marrow biopsy (bilateral) + LP (CSF cytology)
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Imaging: CT chest/abdomen/pelvis ± PET-CT ± MRI
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Stage using IPNHLSS (I-IV) → Risk group (A/B/C)
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Immediate TLS prophylaxis + urgent initiation of pediatric BL chemotherapy
(LMB protocol or Modified Magrath/CODOX-M IVAC ± rituximab)
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Mandatory CNS prophylaxis at every cycle

• Robbins, Cotran & Kumar Pathologic Basis of Disease (10th ed.), pp. 563-564
• Harrison's Principles of Internal Medicine 22E (2025), p. 906
• Goldman-Cecil Medicine (International Edition)
• Scott-Brown's Otorhinolaryngology Head & Neck Surgery, Vol. 2
• Henry's Clinical Diagnosis and Management by Laboratory Methods
• Grainger & Allison's Diagnostic Radiology
• López C et al. "Burkitt lymphoma." Nat Rev Dis Primers 2022. PMID: 36522349