Radiation Oncology/NHL/Burkitt lymphoma

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Burkitt's Lymphoma

Overview edit

  • Burkitt's lymphoma and Burkitt cell leukemia (BL) are classified as different manifestations of the same disease by WHO
  • It is a highly aggressive B-cell neoplasm, typically with extranodal presentation
  • Epidemiology
    • In children: 30-50% of lymphomas
    • In adults: ~1 of lymphomas
    • Male predominance 3-4:1
  • Burkitt's lymphoma has several subtypes:
    • Endemic (young children, Africa, associated with EBV and translocation of the MYC gene)
    • Sporadic (older kids, not associated with EBV but has MYC translocation)
    • Immunocompromised hosts
    • Burkitt's-like lymphoma (older age, not associated with MYC gene)

Clinical Presentation edit

  • Endemic
    • Prevalence 100/1,000,000 children
    • Typically presents with jaw or facial bone tumor
    • Common extranodal spread to bone marrow, meninges, mesentery, ovary/testis, kidney, breast
  • Sporadic
    • Prevalence 1/1,000,000 children
    • Typically with abdominal presentation, often with massive bulk and ascites
    • Extranodal spread as above, including CNS spread
  • Immunocompromised
    • Typically involves lymph nodes, and may present as acute leukemia
    • Frequently in patients with high CD4 count and no opportunistic infections
  • Burkitt-like lymphoma
    • Typically involves lymph nodes, nasopharynx, or GI tract
    • High propensity for bone marrow and CNS as above
    • B-symptoms in ~30% patients
  • All types tend to have very high serum LDH, and serum electrolyte imbalances

Pathology edit

  • On microscopy has "starry sky" pattern (generated by phagocytic histiocytes engulfing apoptotic nuclear debris)
  • Medium-sized cells, very high mitotic fraction, frequent apoptosis
  • Translocation is chromosome 8 myc locus with 3 possible partners (accounting for 90% of translocations):
    • The Ig heavy chain region on chromosome 14 : t(8;14)
    • The kappa light chain locus on chromosome 2: t(2;8)
    • The lambda light chain locus on chromosome 22: t(8;22).
    • However, 5-10% of DLBCL also have t(8;14) translocation. Because DLBCL is 20x more prevalent in adults, having t(8;14) creates a diagnostic challenge between Burkitt's and DLBCLC
  • Originates from germinal center B-cells (like Germinal B-cell DLBCL, but has different molecular signature)
  • Distinction between Burkitt's lymphoma and DLBCL is imprecise. Gene profiles appear to differentiate the diseases better
    • Only 53% concordance among expert hematopathologists
    • Molecular signatures: 17% and 34% of Burkitt's cases (see below) were classified by pathologists as DLBCL
    • WHO committees suggest the following
      • If morphologic features are intermediate, diagnosis of Burkitt's should only be made if the Ki-67 fraction of viable cells is at least 99 percent.
      • If morphologic features suggest DLBCL, but have with a high proliferation fraction or t(8;14), they should be classified as DLBCL.

  • Charite, 2006 (Germany) PMID 16760442 -- "A biologic definition of Burkitt's lymphoma from transcriptional and genomic profiling." (Hummel M, N Engl J Med. 2006 Jun 8;354(23):2419-30.)
    • Gene analysis. 220 mature aggressive B-cell lymphomas. Molecular Burkitt's lymphoma (mBL) signature developed: 58 gene set. Some patients with this signature had morphologic appearance of DLBCL
    • 5-year OS: mBL 75%, GCB-DLBCL 51%, ABC-DLBC 12%
    • Myc locus survival: breakpoint 15% vs. no breakpoint 44%
    • Conclusion: molecular definition of Burkitt's lymphoma
  • Molecular Profiling Project, 2006 PMID 16760443 -- "Molecular diagnosis of Burkitt's lymphoma." (Dave SS, N Engl J Med. 2006 Jun 8;354(23):2431-42.)
    • Gene analysis. 303 patients with aggressive lymphomas, 25 pathological Burkitt's. Gene profile developed. Some samples submitted as DLBCL had molecular profile of Burkitt's
    • Survival (28 patients): better with intensive chemo vs CHOP (SS)
    • Conclusion: Gene-expression profiling is accurate to differentiate BL and DLBCL

Treatment edit

  • Intense chemotherapy such as CODOX/IVAC-M necessary; CHOP insufficient
  • Prophylactic intrathecal chemotherapy or chemotherapy that crosses BBB essential
  • Adults benefit from intense pediatric protocols, but often do not tolerate side effects
  • Risk of developing tumor lysis syndrome is high
  • Complete remission rates very high, but ultimate cure rate less than DLBCL
    • Long-term survival may be as high as 50-70% in selected patients
    • Bone marrow or CNS involvement results in poor prognosis, with long-term survival 0-30%
  • RT was initially used for patients with initial CNS involvement, but use now is minimal