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

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.