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. 2018 May 3;131(18):2060-2064.
doi: 10.1182/blood-2017-12-820605. Epub 2018 Feb 23.

High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements with diffuse large B-cell lymphoma morphology

David W Scott  1   2 , Rebecca L King  3 , Annette M Staiger  4   5 , Susana Ben-Neriah  1 , Aixiang Jiang  6 , Heike Horn  5 , Anja Mottok  1   7 , Pedro Farinha  1 , Graham W Slack  1 , Daisuke Ennishi  1 , Norbert Schmitz  8 , Michael Pfreundschuh  8 , Grzegorz S Nowakowski  9 , Brad S Kahl  10 , Joseph M Connors  1   2 , Randy D Gascoyne  1 , German Ott  4 , William R Macon  3 , Andreas Rosenwald  7
Affiliations

High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements with diffuse large B-cell lymphoma morphology

David W Scott et al. Blood. .

Abstract

High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements (HGBL-DH/TH) is a newly defined entity in the latest World Health Organization Classification. Accurate diagnosis would appear to mandate fluorescence in situ hybridization (FISH) for all tumors with diffuse large B-cell lymphoma (DLBCL) morphology. We present the results of FISH, cell-of-origin, and immunohistochemistry (IHC) testing from 1228 DLBCL biopsies from 3 clinical trials and a population-based registry. HGBL-DH/TH made up 7.9% of the DLBCL, confined primarily to the germinal center B-cell-like (GCB; 13.3%) compared with activated B-cell-like (ABC; 1.7%) subtype (P < .001). HGBL-DH/TH with BCL2 rearrangement is a GCB phenomenon with no cases observed in 415 ABC DLBCL. A screening strategy restricting FISH testing to tumors of GCB subtype (by Lymph2Cx or Hans IHC) plus dual protein expression of MYC and BCL2 by IHC could limit testing to 11% to 14% of tumors, with a positive predictive value of 30% to 37%; however, this strategy would miss approximately one-quarter of tumors with HBGL-DH/TH with BCL2 rearrangement and one-third of all HGBL-DH/TH. These results provide accurate estimation of the proportion of HGBL-DH/TH among tumors with DLBCL morphology and allow determination of the impact of various methods available to screen DLBCL tumors for FISH testing.

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Conflict of interest statement

Conflict-of-interest disclosure: D.W.S has performed consultancy for Janssen and Celgene. B.S.K. has performed consulting for, and received research funding from, Genentech and Celgene. D.W.S., J.M.C., R.D.G., G.O., and A.R. are named inventors on a patent that has been licensed to NanoString Technologies. The remaining authors declare no competing financial interests.

Figures

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Graphical abstract
Figure 1.
Figure 1.
Characteristics of tumors with DLBCL morphology that have MYC rearrangement with or without BCL2 and/or BCL6 rearrangements. (A) Percentages of tumors that harbor MYC rearrangement in the presence or absence of concomitant BCL2 and/or BCL6 rearrangements. Analyses involving COO are based on the 1098 tumors in the cohort in which COO was determined using the Lymph2Cx gene expression-based assay. (B) COO and IHC results for tumors with MYC rearrangement. Each column represents an individual tumor, with the exception of the total cohort in the bottom left corner, included to show percentages of the characteristics in the 1228 patients. P values are for Fisher’s exact tests comparing the frequency of the characteristic in the group vs the total cohort. Additional comparisons were: *P: HGBL-DH/TH with BCL2 rearrangement group vs the total cohort; **P: all HGBL-DH/TH vs the total cohort; ***P: MYC rearrangement group vs the total cohort.
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References

    1. Swerdlow SH, Campo E, Harris NL, et al. WHO Classification of Tumours of the Haematopoietic and Lymphoid Tissues. Revised 4th ed Lyon, France: IARC; 2017.
    1. Obermann EC, Csato M, Dirnhofer S, Tzankov A. Aberrations of the MYC gene in unselected cases of diffuse large B-cell lymphoma are rare and unpredictable by morphological or immunohistochemical assessment. J Clin Pathol. 2009;62(8):754-756. - PubMed
    1. Ye Q, Xu-Monette ZY, Tzankov A, et al. Prognostic impact of concurrent MYC and BCL6 rearrangements and expression in de novo diffuse large B-cell lymphoma. Oncotarget. 2016;7(3):2401-2416. - PMC - PubMed
    1. Pedersen MO, Gang AO, Poulsen TS, et al. MYC translocation partner gene determines survival of patients with large B-cell lymphoma with MYC- or double-hit MYC/BCL2 translocations. Eur J Haematol. 2014;92(1):42-48. - PubMed
    1. Copie-Bergman C, Cuillière-Dartigues P, Baia M, et al. MYC-IG rearrangements are negative predictors of survival in DLBCL patients treated with immunochemotherapy: a GELA/LYSA study. Blood. 2015;126(22):2466-2474. - PubMed

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