Burkitt lymphoma, BL

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.

Epidemiology

Clinical features

CNS involvement may be seen in all types.

Histopathology

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

Immunohistochemistry

CD5

negative

 

CD10

positive, 30/312

CD19†

positive

CD20

positive

CD21

positive in endemic form

CD22

positive

CD23†

negative

bcl-2

negative, 5/312

bcl-6

positive, 30/312

CD10+/bcl-6+/bcl-2-

25/312

c-myc

positive

TdT

negative

SIg

IgM with light chain restriction

cIg

positive in plasmacytoid variant

Ki-67

>85 % of cells, 95-99%2

any myc breakpoint

30/312

 

myc breakpoint alone

28/312

 

bcl-2 breakpoint

1/312

 

bcl-6 breakpoint

2/312

 
 
 

†: 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.

Differential diagnosis

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:

Prognosis

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.

1 Leoncini, L., Lazzi, S., Bellan, C. and Tosi, P. Cell kinetics and cell cycle regulation in lymphomas. J Clin Pathol 2002;55:648-55.

2 Haralambieva E, Boerma EJ, van Imhoff GW, et al. Clinical, immunophenotypic, and genetic analysis of adult lymphomas with morphologic features of Burkitt lymphoma. Am J Surg Pathol 2005; 29:1086-94

This page last revised 2.10.2005.

©SMUHT/PW Bishop