Burkitt Lymphoma



Burkitt Lymphoma


Carlos E. Bueso-Ramos, MD, PhD










Clinical photograph shows a large tumor of the mandible in an African boy. (Courtesy R. Craig, CDC.)






Burkitt Lymphoma. Low-power magnification shows sheets of uniform lymphoma cells with evenly interspersed, reactive, tingible-body macrophages imparting a characteristic “starry sky” pattern.


TERMINOLOGY


Abbreviations



  • Burkitt lymphoma (BL) Synonyms


  • Small noncleaved cell lymphoma, Burkitt type (Working Formulation)


  • Undifferentiated, Burkitt’s type (Rappaport classification)


  • Acute lymphoblastic leukemia, L3 type (French-American-British classification)


Definitions



  • BL is highly aggressive lymphoma that has very short doubling time (˜ 25 hours)


  • World Health Organization (WHO) states that there is no “gold standard” for diagnosis



    • Features considered typical of BL



      • Extranodal sites of involvement


      • Monomorphic, intermediate-sized cells with basophilic cytoplasm and numerous mitoses


      • Chromosomal translocations involving MYC


  • There are 3 clinicopathologic variants of BL



    • Endemic


    • Sporadic


    • Immunodeficiency-associated


ETIOLOGY/PATHOGENESIS


Infectious Agents



  • There is evidence that BL is a polymicrobial disease



    • This is particularly true for endemic BL


  • Association of BL with Epstein-Barr virus (EBV) infection



    • EBV(+) in



      • > 95% of cases of endemic BL


      • ˜ 30-40% of immunodeficiency-associated BL


      • ˜ 10-20% of cases of sporadic BL


  • Endemic BL is associated with Plasmodium falciparum infection



    • Geographic distribution of endemic BL corresponds to distribution of malaria


    • Impact on immunity and viral persistence leading to reactivation of latently infected memory B cells


  • Endemic BL may be associated with infection by arboviruses



    • Mosquitoes carry arboviruses as they carry malaria


    • Arboviruses are RNA viruses, and some have oncogenic properties


  • Chronic antigenic stimulation may exhaust EBVspecific cytotoxic T cells



    • Impairment of immunosurveillance &/or antigenpresenting function


    • May thereby allow EBV-driven lymphomagenesis


    • In endemic BL, malaria or arboviruses provide chronic antigenic stimulation


    • In immunodeficiency-associated BL, immunosurveillance is impaired by other mechanisms



      • Human immunodeficiency virus (HIV) is most common


Dietary Factors



  • Diet may be relevant to endemic BL



    • In Africa, link to ingestion of plant, Euphorbia tirucalli



      • Plant has phorbol ester-like substance that may act as tumor promoter


MYC Proto-oncogene



  • Translocations juxtapose intact MYC gene with enhancer elements of Ig genes, resulting in MYC upregulation



    • MYC is involved in many cell pathways: Proliferation, transcription, apoptosis



CLINICAL ISSUES


Epidemiology



  • Incidence



    • Endemic BL



      • Common in equatorial Africa, northern South America, Papua New Guinea


      • Most common type of lymphoma in equatorial Africa


    • Sporadic BL



      • ˜ 1-2% of lymphomas in industrialized nations


  • Age



    • Endemic BL



      • Children > 2 years of age and adolescents


      • Median age = 8 years


    • Sporadic BL



      • Children and young adults; median age = 30 years


      • ˜ 30-50% of childhood lymphomas in USA


    • Immunodeficiency-associated BL



      • Age corresponds to cause of immunodeficiency


      • Most patients are HIV(+)


  • Gender



    • Male:female ratio = 2:5 to 1


Site



  • Most patients with BL present with extranodal disease


  • Endemic BL



    • Jaws and other facial bones are involved in ˜ 50% of patients


    • Viscera, gonads, gastrointestinal tract


    • Central nervous system involved in up to 20% of patients


  • Sporadic BL



    • Abdomen, particularly the gastrointestinal tract


    • Lymph nodes are involved in subset of patients


    • ± bone marrow, central nervous system (CNS), or paraspinal mass


    • Facial bones rarely involved


    • Small subset of cases can present in leukemic phase



      • Bone marrow usually extensively involved in these patients


  • Immunodeficiency-associated BL



    • Lymph nodes are commonly involved


    • Bone marrow commonly involved in HIV(+) BL


Presentation



  • Patients present with rapidly growing mass


  • B-type symptoms are common Laboratory Tests


  • Indirect indicators of tumor burden and proliferation



    • High serum B2-microglobin level


    • High serum lactate dehydrogenase level


  • Hyperuricemia can occur due to high tumor cell turnover


Natural History



  • In absence of therapy, prognosis of BL patients is poor



    • Rapidly growing progressive disease; often CNS involvement Treatment


  • Drugs



    • Approach is rapid administration of multiple chemotherapeutic agents with prophylaxis to CNS &/or testes



      • Prevent emergence of chemoresistance


      • Eliminate disease in privileged or sanctuary sites


    • BL is very sensitive to chemotherapy



      • Rapid release of intracellular contents following cell death can result in tumor lysis syndrome


Prognosis



  • With highly intensive therapy, most patients with BL have complete response



    • Overall survival rate



      • ˜ 80-90% for localized disease


      • ˜ 60-80% for advanced-stage disease



IMAGE FINDINGS


CT Findings



  • F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT)



    • All untreated BL are highly FDG avid


    • Extranodal involvement is identified in > 50% of BL patients


    • Most patients with sporadic BL have disease localized to abdomen and pelvis


MACROSCOPIC FEATURES


Gross Pathology



  • Resection specimens of BL often show large extranodal mass, often in abdomen


  • Fleshy cut surface with areas of necrosis and hemorrhage


MICROSCOPIC PATHOLOGY


Histologic Features



  • Histologic features of endemic, sporadic, and immunodeficiency-associated BL are identical



    • Diffuse growth pattern


    • “Starry sky” pattern is prominent due to presence of numerous tingible-body macrophages with phagocytosed debris


    • Extremely high mitotic rate


    • Numerous apoptotic cells and often large areas of necrosis


    • In subset of cases, BL can be associated with numerous sarcoid-like granulomas

Jul 8, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Burkitt Lymphoma
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