[Burkitt's and Burkitt-like lymphoma. Molecular definition and value of the World Health Organisation's diagnostic criteria]

Abstract

Among aggressive mature B-cell lymphomas, a reproducible morphological and immunohistological distinction between Burkitt's lymphoma and diffuse large B-cell lymphoma (centroblastic variant) is impossible in a substantial number of cases. The German reference centres for hematopathology collected 220 retrospective cases of aggressive mature B-cell lymphoma whose classification according to the current World Health Organisation criteria was reviewed. Gene expression analysis (Affymetrix) was performed in all cases and chromosomal translocations were determined using fluorescence in situ hybridization. Chromosomal losses and gains were analysed by matrix comparative genomic hybridisation and clinical data were successfully collected for most patients. The application of a novel bioinformatics method led to the identification of a stable and reproducible gene expression signature specific for Burkitt's lymphoma. A total of 44 cases were identified by this molecular signature [designated molecular Burkitt's lymphoma (mBL)]. These molecular Burkitt's lymphomas showed the morphology and immunohistology of classical or atypical Burkitt's lymphoma cases in 29 instances. However, 15 of the molecular Burkitt's lymphoma cases had the morphology of diffuse large B-cell lymphoma or could not be further specified. All molecular Burkitt's lymphomas showed an expression of BCL-6 and CD10, but a MYC translocation was not demonstrable in more than 10% of cases. Of significance is that more than 20% of the molecular Burkitt's lymphomas expressed BCL-2, although weakly in most instances. Our data demonstrate that: (1) the morphological, immunophenotypical and genetic spectrum of Burkitt's lymphoma is broader than previously expected, and (2) our molecular Burkitt's lymphoma signature enables a more precise and extended definition this lymphoma.