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) 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 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