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.



  • 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)


  • 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


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



  • 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


  • 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


  • 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


  • 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


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


Gross Pathology

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

  • Fleshy cut surface with areas of necrosis and hemorrhage


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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