PMID- 29475959 OWN - NLM STAT- MEDLINE DCOM- 20190521 LR - 20240207 IS - 1528-0020 (Electronic) IS - 0006-4971 (Print) IS - 0006-4971 (Linking) VI - 131 IP - 18 DP - 2018 May 3 TI - High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements with diffuse large B-cell lymphoma morphology. PG - 2060-2064 LID - 10.1182/blood-2017-12-820605 [doi] AB - 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. CI - (c) 2018 by The American Society of Hematology. FAU - Scott, David W AU - Scott DW AD - Centre for Lymphoid Cancer, British Columbia Cancer Agency, Vancouver, Canada. AD - Department of Medicine, University of British Columbia, Vancouver, Canada. FAU - King, Rebecca L AU - King RL AD - Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN. FAU - Staiger, Annette M AU - Staiger AM AD - Department of Clinical Pathology, Robert-Bosch-Krankenhaus, Stuttgart, Germany. AD - Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart and University of Tuebingen, Tuebingen, Germany. FAU - Ben-Neriah, Susana AU - Ben-Neriah S AD - Centre for Lymphoid Cancer, British Columbia Cancer Agency, Vancouver, Canada. FAU - Jiang, Aixiang AU - Jiang A AD - Department of Molecular Biology and Biochemistry, Simon Fraser University, Vancouver, Canada. FAU - Horn, Heike AU - Horn H AD - Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart and University of Tuebingen, Tuebingen, Germany. FAU - Mottok, Anja AU - Mottok A AD - Centre for Lymphoid Cancer, British Columbia Cancer Agency, Vancouver, Canada. AD - Institute of Pathology, Wurzburg University and Comprehensive Cancer Center Mainfranken, Wurzburg, Germany. FAU - Farinha, Pedro AU - Farinha P AD - Centre for Lymphoid Cancer, British Columbia Cancer Agency, Vancouver, Canada. FAU - Slack, Graham W AU - Slack GW AD - Centre for Lymphoid Cancer, British Columbia Cancer Agency, Vancouver, Canada. FAU - Ennishi, Daisuke AU - Ennishi D AD - Centre for Lymphoid Cancer, British Columbia Cancer Agency, Vancouver, Canada. FAU - Schmitz, Norbert AU - Schmitz N AD - Department of Medicine, Hematology and Oncology, University Hospital Muenster, Muenster, Germany. FAU - Pfreundschuh, Michael AU - Pfreundschuh M AD - Department of Medicine, Hematology and Oncology, University Hospital Muenster, Muenster, Germany. FAU - Nowakowski, Grzegorz S AU - Nowakowski GS AD - Department of Internal Medicine I, Saarland University Medical School, Homburg/Saar, Germany. FAU - Kahl, Brad S AU - Kahl BS AD - Department of Oncology, Mayo Clinic, Rochester, MN; and. FAU - Connors, Joseph M AU - Connors JM AD - Centre for Lymphoid Cancer, British Columbia Cancer Agency, Vancouver, Canada. AD - Department of Medicine, University of British Columbia, Vancouver, Canada. FAU - Gascoyne, Randy D AU - Gascoyne RD AD - Centre for Lymphoid Cancer, British Columbia Cancer Agency, Vancouver, Canada. FAU - Ott, German AU - Ott G AD - Department of Clinical Pathology, Robert-Bosch-Krankenhaus, Stuttgart, Germany. FAU - Macon, William R AU - Macon WR AD - Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN. FAU - Rosenwald, Andreas AU - Rosenwald A AD - Institute of Pathology, Wurzburg University and Comprehensive Cancer Center Mainfranken, Wurzburg, Germany. LA - eng GR - U24 CA196172/CA/NCI NIH HHS/United States GR - U10 CA180790/CA/NCI NIH HHS/United States GR - U10 CA180794/CA/NCI NIH HHS/United States GR - U10 CA180799/CA/NCI NIH HHS/United States GR - U10 CA180820/CA/NCI NIH HHS/United States GR - U10 CA180833/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20180223 PL - United States TA - Blood JT - Blood JID - 7603509 RN - 0 (Proto-Oncogene Proteins c-bcl-2) RN - 0 (Proto-Oncogene Proteins c-bcl-6) RN - 0 (Proto-Oncogene Proteins c-myc) SB - IM CIN - Blood. 2018 May 3;131(18):1997-1998. PMID: 29724715 MH - Cell Line, Tumor MH - *Gene Rearrangement MH - Humans MH - In Situ Hybridization, Fluorescence MH - Lymphoma, Large B-Cell, Diffuse/*diagnosis/drug therapy/*genetics MH - Neoplasm Grading MH - Proto-Oncogene Proteins c-bcl-2/*genetics MH - Proto-Oncogene Proteins c-bcl-6/*genetics MH - Proto-Oncogene Proteins c-myc/*genetics PMC - PMC6158813 COIS- 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. EDAT- 2018/02/25 06:00 MHDA- 2019/05/22 06:00 PMCR- 2019/05/03 CRDT- 2018/02/25 06:00 PHST- 2017/12/20 00:00 [received] PHST- 2018/02/13 00:00 [accepted] PHST- 2018/02/25 06:00 [pubmed] PHST- 2019/05/22 06:00 [medline] PHST- 2018/02/25 06:00 [entrez] PHST- 2019/05/03 00:00 [pmc-release] AID - S0006-4971(20)32263-1 [pii] AID - 2017/820605 [pii] AID - 10.1182/blood-2017-12-820605 [doi] PST - ppublish SO - Blood. 2018 May 3;131(18):2060-2064. doi: 10.1182/blood-2017-12-820605. Epub 2018 Feb 23.