Radiation Oncology/NHL/Burkitt lymphoma

Burkitt's Lymphoma

Overview

 * 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

 * 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

 * 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

 * 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