Burkitt lymphoma
Description
- The fastest-growing human tumour - doubling time ~24-48 h, Ki-67 ~100%
- -> a medical emergency; days matter, not weeks
- Mature B-cell neoplasm, MYC-driven
| Variant | Setting | Typical site |
|---|---|---|
| Endemic | Equatorial Africa, malaria belt. EBV in ~95% | Jaw / facial bones, orbit; abdominal |
| Sporadic | Western, children + young adults. EBV ~15-30% | Ileocaecum, abdominal mass, ascites; ovary, kidney, breast |
| Immunodeficiency-associated | HIV (often at preserved CD4), post-transplant | Nodal, marrow, CNS |
- *Curable even when widely disseminated* - do not palliate on stage alone
- Marrow +/- CNS involvement = Burkitt leukaemia (formerly L3 ALL)
Epidemiology
- Sporadic: ~1-2% of adult lymphomas but ~30-40% of childhood lymphoma
- Bimodal - children/young adults, and a second rise in older adults
- M>F ~3-4:1
- Endemic form: commonest childhood cancer in equatorial Africa, ~5-10/100,000/yr, peak age 4-7
- HIV: ~1000x inc risk, and unlike other AIDS lymphomas occurs with relatively preserved CD4
Aetiopathogenesis
- MYC rearrangement to an immunoglobulin locus - constitutive MYC -> unrestrained cell cycle entry
| Translocation | Partner | Frequency |
|---|---|---|
| t(8;14)(q24;q32) | IGH | ~80% |
| t(2;8) | IGK (kappa) | ~10-15% |
| t(8;22) | IGL (lambda) | ~5% |
- Cooperating lesions: TCF3 / ID3 (~70%), CCND3, TP53
- Germinal-centre B-cell origin
- Cofactors: EBV (endemic), *chronic P. falciparum malaria* (polyclonal B expansion + dec EBV-specific T-cell control), HIV
- *MYC rearrangement alone is not diagnostic* - also in high-grade B-cell lymphoma and some DLBCL
- Burkitt-like lymphoma with 11q aberration - WHO-5 entity, MYC-negative, otherwise identical morphology
Diagnosis
Urgency
- *Get tissue and start treatment within days.* Bloods for tumour lysis before anything else
- FNA insufficient; core or excisional biopsy, fresh tissue for cytogenetics
Morphology
- Medium-sized monomorphic cells, basophilic vacuolated cytoplasm, multiple small nucleoli
- "Starry sky" - tingible-body macrophages clearing apoptotic debris
- Ki-67 ~95-100% (anything below ~90% argues against Burkitt)
Immunophenotype
- CD20+, CD10+, BCL6+, CD19+, sIg+
- BCL2 negative and TdT negative
- BCL2 positivity -> think high-grade B-cell lymphoma with MYC and BCL2 rearrangement instead
- TdT positivity -> B-lymphoblastic leukaemia/lymphoma
- FISH: MYC rearrangement, with BCL2 and BCL6 negative
Staging and baseline
- LDH, urate, K+, phosphate, calcium, creatinine - repeat at least daily
- PET-CT; marrow aspirate/trephine and CSF cytology + flow in everyone (CNS and marrow involvement are common and change therapy)
- HIV, HBV, HCV serology; echo (anthracycline); fertility preservation if it does not delay treatment
Management
Short, intensive, CNS-directed multi-agent chemoimmunotherapy. Standard-dose R-CHOP is inadequate and must not be used.**
A. Before the first dose - tumour lysis
- The commonest way to lose a Burkitt patient is TLS, not lymphoma
- Rasburicase (not allopurinol) if bulky disease, high LDH, urate high or renal impairment
- Screen for G6PD deficiency - rasburicase causes haemolysis and methaemoglobinaemia
- Aggressive IV hydration; no potassium in fluids; do not alkalinise
- 4-6 hourly electrolytes; early renal/ICU involvement
- Prephase low-dose cyclophosphamide + steroid to debulk gently before full-intensity therapy
B. Regimens - by fitness, not stage
| Regimen | Population |
|---|---|
| R-CODOX-M / R-IVAC | Fit adults, high risk. Alternating; high-dose methotrexate + cytarabine give CNS coverage |
| DA-EPOCH-R | HIV-associated, older or less fit; better tolerated, similar outcomes in low-risk disease. Needs added intrathecal prophylaxis |
| R-hyper-CVAD/MA | Alternative intensive option |
| CODOX-M alone x3 | Low-risk disease only (single extra-abdominal mass <10 cm, normal LDH, ECOG 0-1, stage I-II) |
- Intrathecal prophylaxis in every patient (methotrexate +/- cytarabine); intensified if CNS involved at diagnosis
- Rituximab added to all CD20+ regimens - clear survival benefit
- Continue ART through chemotherapy in HIV - outcomes now approach HIV-negative
- G-CSF with every cycle; expect profound mucositis and prolonged neutropenia
- *No maintenance and no consolidative transplant in first remission*
C. Relapsed disease
- Very poor - the main determinant is that relapse is usually early and chemorefractory
- Salvage (R-ICE, R-GDP) -> autologous or allogeneic SCT if chemosensitive
- CD19 CAR-T in selected patients; clinical trial preferred
D. Surgery and radiotherapy
- Surgery has essentially no role beyond biopsy and relief of obstruction/perforation
- Do not delay chemotherapy for elective debulking
- Radiotherapy not part of standard curative therapy
Associations
- EBV (endemic ~95%, HIV-associated ~30-40%, sporadic ~15-30%)
- *Chronic P. falciparum malaria*
- HIV - AIDS-defining, occurs at relatively preserved CD4
- Post-transplant lymphoproliferative disorder
- Coeliac disease and other chronic immune stimulation (weak)
- Jaw/orbital mass in a child from an endemic region
- Ileocaecal mass causing intussusception in a Western child
Natural history & complications
- Untreated: death within weeks
- Treated: cure ~80-90% in children and young adults; ~60-70% in adults; lower over 60 and with CNS or marrow involvement
- Relapses occur within the first year, almost never after 2 years - a patient in remission at 2 years is cured
Adverse markers
- Age >40, CNS involvement, marrow involvement, LDH >2x ULN, ECOG >=2, bulky (>10 cm)
- HIV with low CD4 or no ART
Complications
- Tumour lysis syndrome - AKI, hyperkalaemia, hypocalcaemia, arrhythmia, death
- Bowel obstruction, intussusception, perforation as the tumour responds
- Ureteric obstruction, cord compression, jaw/orbital destruction
- Treatment: severe mucositis, prolonged cytopenias, sepsis, methotrexate nephrotoxicity
- Late: infertility, secondary malignancy, neurocognitive effect of CNS-directed therapy
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