Translocations Involving 8q24 in Burkitt Lymphoma and Other Malignant Lymphomas: A Historical Review of Cytogenetics in the Light of Todays Knowledge
Authors: Boerma Evert-Jan , Siebert Reiner , Baudis Michael , Kluin Philip 
Published: April 2020

Abstract
Burkitt lymphoma (BL) has a characteristic clinical presentation, morphology, immunophenotype and primary chromosomal aberration, i.e. the translocation t(8;14) (q24;q32) or its variants. However, diagnostic dilemmas may arise in daily practice due to overlap of BL with subsets of other aggressive, mature B cell lymphomas such as a small subset of diffuse large B cell lymphomas (DLBCL). Recently, two gene expression studies have described a distinct molecular profile for BL, but also showed the persistence of some cases intermediate between BL and DLBCL. An alternative approach to define BL is to consider (cyto)genetic data, in particular chromosomal abnormalities other than the t(8;14) or its variants. In this study the “Mitelman Database of Chromosome Aberrations in Cancer”, harboring the majority of all published neoplasia related karyotypes, was explored to define a cytogenetic profile of “true” BL. To that end a core subset of BL was defined by
a histologic diagnosis of BL, the presence of a t(8;14), t(2;8) or t(8;22) indicating a MYC/IG breakpoint, and the absence of a 3q27/BCL6, 18q21/BCL2 or 11q13/CCND1 breakpoint additional to the 8q24/MYC breakpoint.
These core BL (N=481) showed a very low complexity of chromosomal changes, with 40% of the cases having the IG-MYC fusion as the sole abnormality; in the remaining cases additional recurrent and partially exclusive abnormalities included gains at chromosomes 1q, 7 and 12, and losses of 6q, 13q32-34 and 17p. No differences were found between pediatric (N=205) and adult patients (N=215). Moreover, no differences were found between such core BL cases published before (N= 280) and after 1994 (N=201) indicating that historical changes in classification systems had no major impact on this profile.
The genetic profiles and age distribution of the core subset were significantly different from BL with an 8q24 breakpoint not affecting one of the three IG loci (N=13), lymphomas that were diagnosed as BL but had a translocation involving 18q21/BCL2, 3q27/BCL6 or 11q13/BCL1 additional to a breakpoint at 8q24/MYC (“double hit BL”; N=44), and from other morphological types of lymphomas with an 8q24/MYC breakpoint (N=327; 256/327 cases had an IG-MYC breakpoint). These groups showed an other age distribution and a higher cytogenetic complexity than the core subset of BL. BL without a detectable 8q24/MYC breakpoint (N=108) might have been heterogeneous and deserves further studies. We suggest that, concordant with the WHO classification to be published in 2008, the diagnosis of BL should be restricted to cases with expression of CD10 and BCL6, absence or very weak expression of BCL2 protein, a homogeneously very high proliferation index, and a proven IG-MYC translocation without evidence of a chromosomal translocation typical for other lymphoma entities. Additionally, a high number of non-specific cytogenetic abnormalities should suggest need for a critical review of the diagnosis of BL. Finally, the steady increase in age of lymphomas that mimic BL strongly emphasizes that there is no distinct age at which a pathologist can safely make a diagnosis of BL without any ancillary cytogenetic or molecular studies.