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

doi: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

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

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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 language	English (US)
Pages (from-to)	2060-2064
Number of pages	5
Journal	Blood
Volume	131
Issue number	18
DOIs	https://doi.org/10.1182/blood-2017-12-820605
State	Published - May 3 2018

ASJC Scopus subject areas

Biochemistry
Immunology
Hematology
Cell Biology

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Scott, D. W., King, R. L., Staiger, A. M., Ben-Neriah, S., Jiang, A., Horn, H., Mottok, A., Farinha, P., Slack, G. W., Ennishi, D., Schmitz, N., Pfreundschuh, M., Nowakowski, G. S., Kahl, B. S., Connors, J. M., Gascoyne, R. D., Ott, G., Macon, W. R., & 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

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

@article{7435ebc2543648529da076539615dcf2,

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

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.",

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

note = "Publisher Copyright: {\textcopyright} 2018 by The American Society of Hematology",

year = "2018",

month = may,

day = "3",

doi = "10.1182/blood-2017-12-820605",

language = "English (US)",

volume = "131",

pages = "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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AN - SCOPUS:85047870486

SN - 0006-4971

VL - 131

SP - 2060

EP - 2064

JO - Blood

JF - Blood

IS - 18

ER -

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

Abstract

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