Definition
A highly aggressive lymphoma, often presenting extranodally or as a leukaemia. A translocation involving the myc gene is a constant finding. The cell of origin is thought to be an early germinal centre blast from the dark zone of the germinal centre2. Sporadic childhood BL is a distinct B-cell lymphoma characterized by BL morphology, a uniformly high proliferating fraction of tumor cells, a consistent immunophenotype, a classic IG/MYC pattern by FISH analysis, and an excellent prognosis with treatment.
Sporadic BL occurs worldwide in children and young adults, accounting for 1-2% of all lymphomas, 30-50% of all childhood lymphomas. The male to female ratio is 2-3:1.
Immunodeficiency-associated BL, associated with HIV infection. EBV is identified in 25-40% of cases.
Endemic BL is found in equatorial Africa and New Guinea. This variant often involves the jaw or orbit, less often the distal ileum, caecum, omentum, ovaries, kidneys or breast.
Sporadic BL most commonly presents as an abdominal mass, frequently involving the ileocaecal region. Ovaries, kidneys may be involved. Breast involvement is associated with puberty, pregnancy or lactation. Lymph node involvement is more common in adults.
Immunodeficiency-associated BL is often nodal with bone marrow involvement.
CNS involvement may be seen in all types.
There is a diffuse monotonous infiltrate of medium sized cells, which may appear cohesive. The nuclei contain multiple central nucleoli. The cytoplasm is basophilic with lipid vacuoles. Mitotic figures are numerous. A "starry sky" pattern is usually present.
Variants
BL with plasmacytoid differentiation; some cells have eccentric basophilic cytoplasm. There is often a large single central nucleolus. Monotypic cIg is demonstrable. This type is most associated with AIDS.
Atypical Burkitt-like; the growth fraction is close to 100%. There is greater nuclear pleomorphism, with more prominent but less numerous nucleoli. This type is seen in association with AIDS
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negative |
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positive, 30/31 (10/10 typical and 20/21 atypical Burkitt lymphomas)2 |
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positive |
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positive |
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positive in endemic form |
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positive |
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negative |
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negative, 5/31 (0/10 typical and 5/21 atypical Burkitt lymphomas)2 |
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positive, 30/31 (10/10 typical and 20/21 atypical Burkitt lymphomas)2 |
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25/31 (10/10 typical and 15/21 atypical Burkitt lymphomas)2 |
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c-myc |
positive |
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negative |
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SIg |
IgM with light chain restriction |
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cIg |
positive in plasmacytoid variant |
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>85 % of cells, 95-99% (97-99% for typical and 95-99% for atypical Burkitt lymphoma)2 |
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any myc breakpoint |
30/31 (10/10 typical and 20/21 atypical Burkitt lymphomas)2 |
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myc breakpoint alone |
28/31 (10/10 typical and 18/21 atypical Burkitt lymphomas)2 |
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bcl-2 breakpoint |
1/31 (0/10 typical and 1/21 atypical Burkitt lymphomas)2 |
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bcl-6 breakpoint |
2/31 (10/10 typical and 2/21 atypical Burkitt lymphomas)2 |
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†: fresh frozen tissue only
Cytogenetics
There is a reciprocal translocation, t(8;14)(q24;q32) or one of its variants, resulting in the deregulation of the myc oncogene. Although cytogenetically indistinguishable, the breakpoints are slightly different at the molecular level in endemic and sporadic Burkitt lymphoma2.
The myc translocation is not entirely specific to BL, having also been reported in secondary lymphoblastic leukaemia / lymphoma following follicular lymphoma. There appear to be genetically determined disturbances in the nuclear localisation signal for Rb2, such that it becomes purely cytoplasmic, possibly thereby loosing its growth suppressor function1.
Infiltrating T-cells are less common than in DLBCL.
The differential between Burkitt lymphoma, atypical Burkitt lymphoma, Burkitt-like lymphoma and DLBCL is particularly problematic in adult cases. The problematic cases consist of small to medium size cells with a high proliferation rate, cohesive growth pattern and a "starry sky" appearance. Cytogenetic and molecular evidence may be superior to consensus review by expert haemtopathologists in resolving these grey-zone cases2.
Strict criteria proposed for the diagnosis of Burkitt lymphoma, all of which should be fulfilled, are2:
Ki-67 showing a high proliferation rate of at least 90%
the presence of a breakpoint in the myc region
positivity for CD10 (positivity for bcl-6 may add little additional value to CD10)
lack of bcl-2 expression
possibly the demonstration of the absence of bcl-2 or bcl-6 breakpoints
BL is highly aggressive but potentially curable. Relapses usually occur in the first year and after two years without relapse, a patient may be considered cured. Burkitt leukaemia has an 80-90% survival with treatment.
References
World Health Organization Classification of Tumours, Tumours of the haematopoietic and lymphoid tissues, IARC Press 2001.
This page last revised 2.10.2005.
©SMUHT/PW Bishop