Case 131 – Summary

This week, we followed a patient with HIV-associated Burkitt’s lymphoma. Burkitt’s lymphoma is one of a handful of true haematological emergencies and thankfully it’s very rare in the general population. However, in HIV-positive patients, it has a high incidence despite effective anti-retroviral therapy.

Epidemiology (in HIV-positive patients)

  • 25% of systemic NHLs
  • 10-20% lifetime risk
    • Incidence static despite effective ART
  • 25-40% EBV-positive


Pathogenesis

  • Not associated with low CD4 count
  • MYC re-arrangement – universal finding
    • t(8;14) > t(2;8) > t(8;22)
    • Leads to MYC overexpression
  • Other potential mutations
    • TP53, ID3, TCF3, CCND1
  • HIV lymphomagenesis
    • Burkitt’s associated with higher CD4 counts compared to other NHLs
    • Chronic B cell dysregulation
    • HIV protein Tat promotes MYC translocation
    • Role of EBV co-infection in proportion of cases


Clinical features

  • Higher rates of nodal disease compared to endemic and sporadic forms
  • Extra-nodal disease common at presentation
    • GI tract
    • Bone marrow (previously called ALL L3)
    • CNS (leptomeningeal disease)
  • Advanced stage disease
  • B symptoms
  • Symptoms of HIV/AIDS
  • Spontaneous tumour lysis syndrome


Pathology

  • Morphology
    • Medium-sized, monomorphic cells
    • Round nuclei, multiple nucleoli
    • Deeply basophilic cytoplasm
  • Histology
    • ‘Starry-sky’ appearance
      • Benign macrophages (stars) on background of sheets of basophilic Burkitt’s cells (sky)
    • Ki-67 index 100%
  • Immunophenotype
    • Positive: IgM, Bcl-6, CD19, CD20, CD22, CD10 and CD79a
    • Negative: CD5, CD23 and TdT
  • Cytogenetics
    • MYC re-arrangement (as above)


Baseline investigations

  • Bloods
    • Routine (FBC, U/Es, LFTs, etc.)
    • LDH, urate
    • HIV serology (viral load and CD4 count if HIV-positive)
    • Hep B/C serology
  • Imaging
    • CT neck/chest/abdomen/pelvis
    • PET-CT
    • Echocardiogram
  • Other investigations
    • Tumour histology
    • Bone marrow biopsy if suspected marrow disease
    • CSF for cytospin and flow cytometry


Treatment

  • Continue antiretroviral therapy
    • Involve infectious diseases team throughout treatment
  • Chemotherapy regimens (for medically-fit patients)
    • R-CODOX-M/R-IVAC
    • R-Hyper-CVAD
    • DA-EPOCH-R
  • High risk for CNS relapse – most regimens have intrathecal chemotherapy and high dose methotrexate and/or cytarabine built in
  • Rituximab – avoid if CD4 count < 50 (rare in Burkitt’s)
  • Tumour lysis syndrome (can occur spontaneously)
    • Prophylaxis
      • IV hydration (at least 3 L per day) and prophylactic rasburicase
      • Frequent blood monitoring
    • Treatment of established TLS
      • Early recognition
      • Treatment dose rasburicase
      • IV fluid resuscitation
      • Treat hyperkalaemia
      • May require dialysis
    • Curable disease but outlook worse than non-HIV infected counterparts
    • Prognosis for relapsed or refractory disease is especially poor


References

Atallah-Yunes SA, Murphy DJ, Noy A. HIV-associated Burkitt lymphoma. Lancet Haematol. 2020;7(8):e594-e600. doi:10.1016/S2352-3026(20)30126-5

Blum KA, Lozanski G, Byrd JC. Adult Burkitt leukemia and lymphoma. Blood. 2004;104(10):3009-3020. doi:10.1182/blood-2004-02-0405

Freedman AS, Aster JC. Epidemiology, clinical manifestations, pathologic features, and diagnosis of Burkitt lymphoma. UpToDate. Updated: 08/01/2020.

Kaplan LD, Ai W. HIV-related lymphomas: Epidemiology, risk factors, and pathobiology. UpToDate. Updated: 23/08/2019.

 

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