# Radiation Oncology/NHL/Burkitt lymphoma

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* Non-Hodgkin lymphoma: Main Page | Randomized
* Overview: Overview |
* Follicular |
* Diffuse large B-cell |
* MALT |
* Nodal marginal zone |
* Mantle cell |
* CLL/SLL |
* Lymphoblastic |
* Burkitt |
* NK/T cell |
* Anaplastic large cell |
* Primary CNS Lymphoma
* Treatment:
* Aggressive |
* Specific sites |
* Radioimmunotherapy
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