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

David W. Scott, Rebecca 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

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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 (US)
Pages (from-to)2060-2064
Number of pages5
JournalBlood
Volume131
Issue number18
DOIs
StatePublished - May 3 2018

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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

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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; 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, R, 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 ; 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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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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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

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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