Pathobiology of Burkitt lymphoma
- Jennifer R Brown, MD, PhD
Jennifer R Brown, MD, PhD
- Associate Professor
- Harvard Medical School
- Arnold S Freedman, MD
Arnold S Freedman, MD
- Section Editor — Lymphoproliferative Disorders
- Professor of Medicine
- Harvard Medical School
- Jon C Aster, MD
Jon C Aster, MD
- Professor of Pathology
- Harvard Medical School
Burkitt lymphoma (BL) is a highly aggressive B cell neoplasm characterized by the translocation and deregulation of the c-MYC gene on chromosome 8. Three distinct clinical forms of BL are recognized: endemic, sporadic, and immunodeficiency-associated. Although they are histologically identical and have similar clinical behavior, there are differences in epidemiology, clinical presentation, and genetic features between the three forms. (See "Epidemiology, clinical manifestations, pathologic features, and diagnosis of Burkitt lymphoma", section on 'Clinical features'.)
BL and Burkitt leukemia are classified as different manifestations of the same disease in the World Health Organization (WHO) classification of hematologic malignancies . The WHO classification also recognizes the existence of tumors with features intermediate between BL and diffuse large B cell lymphoma, which remain difficult diagnostic challenges. (See "Classification of the hematopoietic neoplasms".)
The pathogenesis of BL will be discussed here. Information regarding the diagnosis and treatment of BL is presented separately. (See "Epidemiology, clinical manifestations, pathologic features, and diagnosis of Burkitt lymphoma" and "Treatment of Burkitt leukemia/lymphoma in adults".)
CELL OF ORIGIN
BL is derived from germinal or post-germinal center B cells. The germinal or post-germinal center ancestry of these cells is principally supported by the identification of somatic mutations in the variable region of the immunoglobulin genes (IgV), which serve as a marker of germinal center transit, as well as the tumor cell immunophenotype. Some studies have demonstrated ongoing somatic mutation, a process that is normally restricted to germinal center B cells. (See "Normal B and T lymphocyte development" and "Epidemiology, clinical manifestations, pathologic features, and diagnosis of Burkitt lymphoma", section on 'Other genetic abnormalities'.)
The different clinical subtypes of BL (ie, endemic, nonendemic, and immunodeficiency-related) likely arise from B cells at different stages of development. Specifically, Epstein-Barr virus (EBV)-negative BLs show a low level of somatic hypermutation of their variable region heavy chain genes and no signs of antigen selection, whereas EBV-positive (generally endemic or AIDS-related) BLs have significantly higher levels of somatic hypermutation and evidence of antigen selection . These findings suggest that EBV-negative BL may arise from an early centroblast, while EBV-positive BL may arise from a memory B cell or late germinal center B cell. This difference in cell of origin may also relate to the observed difference in c-MYC translocation breakpoints described below. Despite these differences, these clinical subtypes have many similarities in gene expression suggesting a common pathogenesis . (See 'Chromosomal translocations' below.)To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
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- CELL OF ORIGIN
- c-MYC in normal cells
- c-MYC overexpression
- - Chromosomal translocations
- - Other mechanisms
- Consequences of c-MYC overexpression
- Other genetic lesions
- Other tumors with c-MYC translocations
- - General
- - Epstein-Barr virus (EBV) infection