Burkitts lymphoma

Burkitt's lymphoma is a very high-grade B-cell malignancy. Pathologically it is characterized by small, non-cleaved cells. The presence of many apoptotic malignant cells gives rise to tangible-body macrophages and the 'starry sky' appearance characteristic of this and other very rapidly dividing tumors. Frequent mitotic figures demonstrate the rapid cell division characteristic of this tumor. Though rapidly dividing, it is one of the most curable lymphomas, and more than 90% of adults enjoy long-term survival when treated with a regimen similar to that proposed by MacGrath. As the MacGrath regimen is quite different and yields much improved results when compared with the CHOP regimen that is used for other aggressive B-cell lymphomas, it is important to make the diagnostic distinction between Burkitt's and large B-cell lymphoma.

Genetic testing plays a key role in making the diagnosis of Burkitt's lymphoma. The genetic hallmark of Burkitt's lymphoma is overexpression of the c-MYC oncogene due to a translocation which places c-MYC transcription under the control of elements at an immunoglobulin locus. The most common translocation, t(8;14), is a chromosomal rearrangement involving c-MYC and the immunoglobulin heavy chain locus. Other translocations involve c-MYC with the K [t(2;8)]

Table 10.2 Chromosomal translocations in non-Hodgkin's lymphomas.

% of cases

Proto-onco-

Mechanism of activation of

NHL histological type

Translocation

involved

gene

Function

oncogene

Burkitt's lymphoma

t(8;14)

80%

c-MYC

Cell proliferation

Transcriptional deregulation

t(2;8)

15%

and growth

(t8;22)

5%

Diffuse large cell lymphoma

der(3)

35%

BCL-6

Transcriptional

Transcriptional deregulation

repressor, required for

GC formation

Mantle cell lymphoma

t(11;14)

>70%

BCL-1

Cell cycle regulator

Transcriptional deregulation

Follicular lymphoma

t(14;18)

90%

BCL-2

Anti-apoptotic

Transcriptional deregulation

Lymphoplasmacytic lym-

t(9;14)

50%

PAX-5

Transcription factor

Transcriptional deregulation

phoma

regulation

B-cell proliferation

MALT lymphoma

t(11;18)

50%

API-2-MLT

API-2 is anti-apoptotic

Fusion protein

t(1;14)

Rare

BCL-10

? Anti-apoptotic

Transcriptional deregulation

Anaplastic large T-cell lym-

t(2;5)

60% in adults

NPM-ALK

ALK is a tyrosine

Fusion protein

phoma

85% in children

kinase

DLBL BL

MALT LPL

Molecular pathogenesis ?

IgH [bCL-1

IbCL-2 IgH

IgH [c-MYC

API-2 MLT

IgH PAX-5

? Cell of origin

B1 B2

CD5+CD20+ slgM+ slgD+

? Cell of origin

B1 B2

CD5+CD20+ slgM+ slgD+

MALT

Fig. 10.3 Molecular and cytological pathogenesis of the most common types of lymphomas

MALT

Immunophenotype

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Fig. 10.3 Molecular and cytological pathogenesis of the most common types of lymphomas or X [t(8;22)] light chain loci. It is difficult to make the diagnosis of Burkitt's lymphoma in the absence of evidence for a c-MYC translocation by cytogenetics, FISH, or PCR. The c-MYC (myelocytomatosis) oncogene is a helix-loop-helix, zinc finger-containing transcription factor. The expression of the transcriptional targets of c-MYC is associated with a proliferative phenotype.

There is a type of lymphoma which lies histologically and clinically between the Burkitt's and the diffuse large B-cell lymphomas. These Burkitt's-like lymphomas lack c-MYC translocations. Thirty percent possess rearrangements involving the BCL-2 gene. The prognosis of these tumors is generally inferior to that of the true Burkitt's lymphomas.

Evidence for latent Epstein-Barr virus infection is found in nearly all of the African endemic Burkitt's lymphoma but in only 20% of the sporadic form found outside Africa. It has been suggested that Epstein-Barr virus plays a causative role by opposing apoptosis.

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