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 and and/or 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 ( < .001). HGBL-DH/TH with 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 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.

A large single-institution retrospective analysis of aggressive B-cell lymphomas according to the 2016/2017 WHO classification

“…[2][3][4] The inclusion of DLBCL DE/TE for additional molecular assessment is clearly substantiated by recent reports on DLBCL DH cases within the DLBCL DE/TE group. 3,4,15,16 Most of the morphological and immunohistochemical characteristics identified in the group were consistent with those presented in previous reports; however, 2 were found to be intriguingly different. Firstly, almost 70% of the HGBL/DLBCL group displayed an ABC subtype phenotype when we assessed the COO using the Hans algorithm.…”

“…3,5,17,18 However, it must be emphasized that trials of more intensive or novel regimens in HGBL have reported inconsistent results, and the evidence is still not strong enough to prepare distinct treatment guidelines for HGBL patients. 2,3,15,[19][20][21][22][23] This further emphasizes the need for better distinction of HGBL as a highly heterogeneous, provisional category of lymphomas, which should be investigated further.…”

Double‐hit lymphoma: So what?

“…In contrast, the NCCN guidelines recommend a more focused approach based upon biological predictors, suggesting patients with a GCB‐like immunophenotype and the expression of MYC and BCL2 or BCL6 by immunohistochemistry should undergo FISH detection . This is based on the observation that the majority of DHL will be of the GCB‐like pheonotype . This strategy would however miss approximately one quarter of tumours with DHL or THL with BCL2 rearrangements and one‐third of all HGBL‐DH/TH.…”

MYC protein expression scoring and its impact on the prognosis of aggressive B-cell lymphoma patients

“…However, it should be noted that roughly 10% of HGDH have a lower expression of MYC. In such cases, FISH should be recommended 11 .…”