Diffuse Large B-Cell Lymphoma/High Grade B-Cell Lymphoma with MYC and BCL6 Rearrangements: a study of 60 Cases.

in Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc by Do Hwan Kim, L Jeffrey Medeiros, Jie Xu, Guilin Tang, Lianqun Qiu, Sa A Wang, Chi Y Ok, Wei Wang, C Cameron Yin, M James You, Sofia Garces, Pei Lin, Shaoying Li

TLDR

  • The study investigated the classification of BCL6-DHL and found that patients with this type of lymphoma have aggressive clinical features and may benefit from more aggressive therapy.
  • Compared to DLBCL and BCL2-DHL, patients with BCL6-DHL had similar aggressive clinical features but distinct immunophenotypic and gene expression profiles.

Abstract

Classification of cases of diffuse large B-cell lymphoma (DLBCL)/high-grade B-cell lymphoma (HGBL) with MYC and BCL6 rearrangements, also known as BCL6 double hit lymphoma (DHL), is controversial. We assessed 60 cases of BCL6-DHL and compared this cohort to 224 cases of DHL with MYC and BCL2 rearrangements (BCL2-DHL) and 217 cases of DLBCL not otherwise specified. Compared with the DLBCL cohort, BCL6-DHL patients had more aggressive clinical features such as frequent extranodal involvement, high-stage disease, high IPI score and elevated serum lactate dehydrogenase level (p <0.01 for all). Compared with the BCL2-DHL cohort, BCL6-DHL patients had similarly aggressive clinical features but a lower frequency of germinal center B-cell (GCB) immunophenotype and MYC and BCL2 double expression. Patients with BCL6-DHL showed an overall survival (OS) intermediate between patients with DLBCL and BCL2-DHL. Following induction with R-CHOP chemotherapy, BCL6-DHL patients demonstrated a poor OS similar to BCL2-DHL patients and worse than that of DLBCL patients (p = 0.024). However, among patients who received R-EPOCH, there was no significant difference in OS among the three groups (p = 0.146). Gene expression profiling showed that 60% of BCL6-DHL cases had a double hit (DH)-like signature compared with 10% of DLBCL-GCB and 93% of BCL2-DHL. The DH-like signature in BCL6-DHL cases was associated with a GCB immunophenotype. Based on these data, we suggest that BCL6-DHL cases are clinically more aggressive than DLBCL and patients may benefit from a more aggressive therapy than R-CHOP. The data also suggest that BCL6-DHL as currently defined, is heterogeneous and that neoplasms with a GCB immunophenotype are more likely to have DH-like signature and behave more aggressively. Lastly, we suggest that BCL6-DHL cases deserve to be recognized separately in a lymphoma classification to facilitate further understanding of these neoplasms and for optimal patient management.

Overview

  • The study aimed to investigate the classification of diffuse large B-cell lymphoma (DLBCL)/high-grade B-cell lymphoma (HGBL) with MYC and BCL6 rearrangements, also known as BCL6 double hit lymphoma (DHL).
  • The study included 60 cases of BCL6-DHL, 224 cases of DLBCL not otherwise specified, and 217 cases of DHL with MYC and BCL2 rearrangements (BCL2-DHL).
  • The primary objective of the study was to compare the clinical features, treatment outcomes, and gene expression profiles among these patient groups.

Comparative Analysis & Findings

  • Compared to DLBCL, BCL6-DHL patients had more aggressive clinical features, including frequent extranodal involvement, high-stage disease, high IPI score, and elevated serum lactate dehydrogenase level.
  • Compared to BCL2-DHL, BCL6-DHL patients had similar aggressive clinical features, but lower frequency of germinal center B-cell (GCB) immunophenotype and MYC and BCL2 double expression.
  • Patients with BCL6-DHL showed an overall survival (OS) intermediate between patients with DLBCL and BCL2-DHL.

Implications and Future Directions

  • The study suggests that BCL6-DHL cases are clinically more aggressive than DLBCL and may benefit from a more aggressive therapy than R-CHOP.
  • The data indicate that BCL6-DHL is heterogeneous, and neoplasms with a GCB immunophenotype are more likely to have DH-like signature and behave more aggressively.
  • The study suggests that BCL6-DHL cases deserve to be recognized separately in a lymphoma classification to facilitate further understanding of these neoplasms and for optimal patient management.
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