Abstract
To define reproducible criteria for subgroups of diffuse large B-cell lymphomas (DLBCL), including lymphomas with plasmablastic/plasmacytoid features (PB/PC-Fs), we investigated 66 DLBCL; the samples were categorized as either centroblastic (CB), immunoblastic (IB) or PB/PC-F applying standardized morphologic criteria. Blinded specimens were reviewed by three independent pathologists. The final consensus classification included 44 CB (67%), seven IB (10%) and 15 PB/PC-F (23%). The interobserver agreement between two centers (Vienna, Würzburg) was 93.5%. Most PB/PC-F were CD20+, cIgM+, MUM-1+, CD138±, bcl-6−, corresponding to an activated B-cell phenotype. Immunoglobulin-VH gene mutation analysis was consistent with a germinal or postgerminal center-cell origin. By fluorescence in situ hybridization analysis, 11/13 (85%) PB/PC-F had a monoallelic TP53 deletion. The pretreatment characteristics of patients with PB/PC-F included a tendency for more B symptoms, extranodal disease and a higher IPI. Importantly, PB/PC-F were resistant to standard chemotherapy (complete remission rate 47%, relapse rate 71%) and even autologous stem-cell transplantation. The median overall survival (OS) (14 months, P<0.002) and disease-free survival (6 months, P=0.02) were significantly shorter compared to patients with CB and IB. The OS difference was pronounced within the low and low-intermediate IPI risk group (P<0.001). Our data indicate a strong association of plasmablastic/plasmacytoid morphology with TP53 deletions, poor response to chemotherapy and short survival.
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Acknowledgements
IS-K and IH contributed equally to this work and should both be considered first authors. This work was supported by a grant from the ‘ICP Program of the Austrian Federal Ministry for Education, Science and Culture, by Grant P13984-GEN from the ‘Fonds zur Förderung der wissenschaftlichen Forschung’ and by a grant from the Kommission Onkologie of the Medical Faculty of the University of Vienna. Expert technical assistance by Susanne Hagmann, Ulrike Zeman and Isabella Mosberger is gratefully acknowledged.
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Simonitsch-Klupp, I., Hauser, I., Ott, G. et al. Diffuse large B-cell lymphomas with plasmablastic/plasmacytoid features are associated with TP53 deletions and poor clinical outcome. Leukemia 18, 146–155 (2004). https://doi.org/10.1038/sj.leu.2403206
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DOI: https://doi.org/10.1038/sj.leu.2403206
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