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

David W. Scott, Rebecca L. King, Annette M. Staiger, Susana Ben-Neriah, Aixiang Jiang, Heike Horn, Anja Mottok, Pedro Farinha, Graham W. Slack, Daisuke Ennishi, Norbert Schmitz, Michael Pfreundschuh, Grzegorz S. Nowakowski, Brad S. Kahl, Joseph M. Connors, Randy D. Gascoyne, German Ott, William R. Macon and Andreas Rosenwald

Key points

  • HGBL-DH/TH makes up 8% of de novo diffuse large B-cell lymphoma with HGBL-DH/TH with BCL2 rearrangement being a GCB phenomenon.

  • Restricting FISH testing to tumors with dual protein expression and GCB subtype results in testing <15% of tumors but missing ~35% of HGBL-DH/TH.

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 three clinical trials and a population-based registry. HGBL-DH/TH made up 7.9% of DLBCL, confined primarily to the germinal centre B-cell-like (GCB – 13.3%) compared with activated B-cell-like (ABC – 1.7%) subtype (P<0.001). 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 11-14% of tumors, with a positive predictive value of 30-37%; however, this strategy would miss approximately a quarter of tumors with HBGL-DH/TH with BCL2 rearrangement and a 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.

  • Submitted December 20, 2017.
  • Accepted February 13, 2018.