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The “Burkitt-like” immunophenotype and genotype is rarely encountered in diffuse large B cell lymphoma and high-grade B cell lymphoma, NOS

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Abstract

Burkitt lymphoma (BL) is a B cell lymphoma composed of monomorphic medium-sized blastic cells with basophilic cytoplasm and a high proliferation index. BL has a characteristic immunophenotype of CD10 and BCL6 positive and BCL2 negative and harbours MYC gene rearrangements (MYCR) in >90% of the cases. Owing to its highly aggressive nature, intensified chemotherapy regimens are usually administered, requiring an exact diagnosis. Since the diagnosis usually warrants an integration of morphologic, immunophenotypic and genetic findings and because there is a morphologic overlap with the new WHO category of high-grade B cell lymphoma, not otherwise specified (HGBL, NOS) and some cases of diffuse large B cell lymphoma (DLBCL), we wanted to test the distinctiveness of the CD10+, BCL6+, BCL2- and MYCR positive immunopheno-genotype in a large cohort of >1000 DLBCL and HGBL. Only 9/982 DLBCL classified by an expert panel of haematopathologists (0.9%) displayed a single MYCR and were CD10+, BCL6+ and BCL2-. In a similar fashion, only one out of 32 HGBL, NOS (3%) displayed the “Burkitt-like” genetic/immunophenotypic constitution. The samples of non-BL showing the BL-typic immunopheno-genotype, interestingly, harboured higher copy number variations (CNV) by OncoScan analysis (mean 7.3 CNVs/sample; range: 2–13 vs. 2.4; range 0–6) and were also distinct from pleomorphic BL cases regarding their mutational spectrum by NGS analysis. This implies that the characteristic immunophenotype of BL, in concert with a single MYCR, is uncommon in these aggressive lymphomas, and that this constellation favours BL.

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Acknowledgements

The authors wish to thank Petra Hitschke, Daniela Pumm, Hanna Laurich and Hannah-Lena Schnitzer for expert technical assistance.

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The datasets generated during and/or analysed during the current study are available from the corresponding author upon request.

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This work was funded by the Robert-Bosch-Stiftung (project O3), Stuttgart, Germany.

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Katrin S. Hüttl, M. Michaela Ott and German Ott designed research and analysed data. Katrin S. Hüttl and German Ott wrote the paper. Katrin S. Hüttl, Andreas Rosenwald, Julia Richter, Wolfram Klapper, Anne-Sophie Biesdorf and German Ott provided and reviewed cases. Annette M. Staiger, Sabrina Kalmbach, Julia Richter and Heike Horn performed and interpreted molecular analyses. Marita Ziepert was responsible for statistical analyses. Marita Ziepert and Lorenz Trümper provided and analysed data from clinical trials. All authors read and approved the final manuscript.

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Correspondence to German Ott.

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Hüttl, K.S., Staiger, A.M., Richter, J. et al. The “Burkitt-like” immunophenotype and genotype is rarely encountered in diffuse large B cell lymphoma and high-grade B cell lymphoma, NOS. Virchows Arch 479, 575–583 (2021). https://doi.org/10.1007/s00428-021-03050-4

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