Burkitt lymphoma

Overview

•Highly aggressive mature B-cell non-Hodgkin lymphoma - fastest doubling time (~24-48 hours) of any human malignancy

•Defined by translocation of c-MYC oncogene (chromosome 8) to an immunoglobulin gene locus

•Despite aggressive biology, potentially curable with intensive chemotherapy

Presentation

•Endemic - rapidly enlarging jaw/facial bone mass, may displace dentition, often bilateral

•Sporadic/HIV-associated - abdominal mass (ileocaecal region), abdominal pain, intestinal obstruction or intussusception

•B symptoms - fever, drenching night sweats, weight loss >10% over 6 months

•CNS involvement - cranial nerve palsies, meningism, raised ICP (up to 15% at diagnosis)

•Bone marrow involvement - cytopenias; if >25% marrow replaced, presents as leukaemic phase (higher TLS risk)

Investigations

🥇 First-line

•FBC, LDH and uric acid (markedly elevated - reflect tumour burden), U&E, phosphate, calcium (TLS baseline), LFTs, coagulation; HIV serology in all adults

•Imaging: CT chest/abdomen/pelvis for staging; PET-CT increasingly used

•Bone marrow trephine - upstages to Stage IV if positive

•CSF examination (lumbar puncture) - cytology for CNS involvement; also route for intrathecal prophylaxis

🏆 Gold standard

•Excisional biopsy - starry sky pattern on H&E; immunophenotype: CD19+, CD20+, CD10+, BCL6+, BCL2-, Ki-67 ~100%

•FISH/cytogenetics - confirms c-MYC translocation t(8;14) or variant

Management

•Pre-treatment priorities (before chemotherapy): aggressive IV hydration + allopurinol (or rasburicase) to prevent tumour lysis syndrome, and histological confirmation

•Chemotherapy: intensive multi-agent regimens (e.g. R-CODOX-M/IVAC)

•CNS prophylaxis mandatory - intrathecal methotrexate and/or cytarabine, often with systemic high-dose methotrexate

•HIV-associated disease - optimise antiretroviral therapy concurrently with chemotherapy

🚨

Tumour lysis syndrome can occur spontaneously BEFORE treatment begins in Burkitt lymphoma (unlike most malignancies) due to c-MYC-driven proliferation and spontaneous apoptosis. Always check electrolytes at presentation.

Complications

•Tumour lysis syndrome - hyperkalaemia, hyperphosphataemia, hypocalcaemia, hyperuricaemia, AKI; can be fatal

•CNS involvement - cranial nerve palsies, meningeal disease; worsens prognosis

•Intestinal obstruction or perforation - bulky abdominal disease; may be the presenting emergency

•Relapsed/refractory disease - poor prognosis; salvage with high-dose chemotherapy + autologous stem cell transplantation in eligible patients

Prognosis

•Limited-stage disease: 5-year overall survival >90% with modern intensive protocols

•Advanced-stage/CNS involvement/HIV co-infection: 5-year survival ~50-70%

•Relapsed disease: significantly worse prognosis

Pathophysiology and genetics

•t(8;14) - c-MYC juxtaposed to IgH gene on chromosome 14; ~80% of cases (canonical)

•t(2;8) - kappa light chain; t(8;22) - lambda light chain (variant translocations)

•c-MYC overexpression drives continuous proliferation AND primes cells for apoptosis - produces the classic starry sky histological pattern (macrophages engulfing apoptotic debris against a background of densely packed malignant B cells)

Variants

Burkitt lymphoma variants

Feature	Endemic	Sporadic	Immunodeficiency-associated
Geography	Sub-Saharan Africa	Worldwide (most common in UK)	HIV-positive patients
Age	Children 4-7 years	Children and young adults	Adults
Typical site	Jaw/facial bone mass	Ileocaecal/abdominal mass	Abdominal mass
EBV association	~100%	20-30%	30-40%