High-Grade B-cell Lymphomas: Double Hit and Non-Double Hit

Abstract

The classification of high-grade B-cell lymphoma (HGBL) has continuously evolved over past decades. These neoplasms, as currently defined, represent about 2% of all non-Hodgkin lymphomas and patients with these neoplasms are often refractory or relapse following standard therapy. The 5th edition of the World Health Organization classification of hematologic neoplasms (WHO-HAEM5) has refined the classification of HGBL and recognizes two types: (1) Diffuse large B-cell lymphoma (DLBCL)/HGBL with MYC and BCL2 rearrangements, with or without BCL6 rearrangements; and (2) HGBL, not otherwise specified (HGBL-NOS). WHO-HAEM5 excluded DLBCL/HGBL with concurrent MYC and BCL6 rearrangements from this category and reclassified them into DLBCL or HGBL-NOS categories respectively based on morphology. The International Consensus Classification (ICC) takes a slightly different approach. In addition to recognizing the two WHO-HAEM5 categories, they recognize HGBL with concurrent MYC and BCL6 rearrangements as a provisional entity. In this review, we provide an update of HGBL and its subgroups, focusing on their clinicopathologic features, diagnosis, molecular genetic features, and pathogenesis. Our diagnostic approach and caveats for differential diagnosis are also discussed with an emphasis on the differential diagnosis with B lymphoblastic leukemia/lymphoma.

Keywords: BCL2; BCL6; High-grade B-cell lymphoma; double hit lymphoma.