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, Andreas Rosenwald

Research output: Contribution to journalArticle

27 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2060-2064
Number of pages5
JournalBlood
Volume131
Issue number18
DOIs
Publication statusPublished - May 3 2018
Externally publishedYes

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Lymphoma, Large B-Cell, Diffuse
B-Cell Lymphoma
Non-Hodgkin's Lymphoma
Tumors
Cells
Fluorescence In Situ Hybridization
Fluorescence
Neoplasms
Immunohistochemistry
Testing
Germinal Center
Biopsy
Registries
Screening
B-Lymphocytes
Health
Clinical Trials
Population
Proteins

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Scott, D. W., King, R. L., Staiger, A. M., Ben-Neriah, S., Jiang, A., Horn, H., ... Rosenwald, A. (2018). High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements with diffuse large B-cell lymphoma morphology. Blood, 131(18), 2060-2064. https://doi.org/10.1182/blood-2017-12-820605

High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements with diffuse large B-cell lymphoma morphology. / Scott, David W.; King, Rebecca L.; Staiger, Annette M.; Ben-Neriah, Susana; Jiang, Aixiang; Horn, Heike; Mottok, Anja; Farinha, Pedro; Slack, Graham W.; Ennishi, Daisuke; Schmitz, Norbert; Pfreundschuh, Michael; Nowakowski, Grzegorz S.; Kahl, Brad S.; Connors, Joseph M.; Gascoyne, Randy D.; Ott, German; Macon, William R.; Rosenwald, Andreas.

In: Blood, Vol. 131, No. 18, 03.05.2018, p. 2060-2064.

Research output: Contribution to journalArticle

Scott, DW, King, RL, Staiger, AM, Ben-Neriah, S, Jiang, A, Horn, H, Mottok, A, Farinha, P, Slack, GW, Ennishi, D, Schmitz, N, Pfreundschuh, M, Nowakowski, GS, Kahl, BS, Connors, JM, Gascoyne, RD, Ott, G, Macon, WR & Rosenwald, A 2018, 'High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements with diffuse large B-cell lymphoma morphology', Blood, vol. 131, no. 18, pp. 2060-2064. https://doi.org/10.1182/blood-2017-12-820605
Scott, David W. ; King, Rebecca L. ; Staiger, Annette M. ; Ben-Neriah, Susana ; Jiang, Aixiang ; Horn, Heike ; Mottok, Anja ; Farinha, Pedro ; Slack, Graham W. ; Ennishi, Daisuke ; Schmitz, Norbert ; Pfreundschuh, Michael ; Nowakowski, Grzegorz S. ; Kahl, Brad S. ; Connors, Joseph M. ; Gascoyne, Randy D. ; Ott, German ; Macon, William R. ; Rosenwald, Andreas. / High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements with diffuse large B-cell lymphoma morphology. In: Blood. 2018 ; Vol. 131, No. 18. pp. 2060-2064.
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T1 - High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements with diffuse large B-cell lymphoma morphology

AU - Scott, David W.

AU - King, Rebecca L.

AU - Staiger, Annette M.

AU - Ben-Neriah, Susana

AU - Jiang, Aixiang

AU - Horn, Heike

AU - Mottok, Anja

AU - Farinha, Pedro

AU - Slack, Graham W.

AU - Ennishi, Daisuke

AU - Schmitz, Norbert

AU - Pfreundschuh, Michael

AU - Nowakowski, Grzegorz S.

AU - Kahl, Brad S.

AU - Connors, Joseph M.

AU - Gascoyne, Randy D.

AU - Ott, German

AU - Macon, William R.

AU - Rosenwald, Andreas

PY - 2018/5/3

Y1 - 2018/5/3

N2 - 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.

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.

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