Aggressive B-cell lymphomas—from morphology to molecular pathogenesis

Abstract

Abstract: The 2016 revised World Health Organization (WHO) classification of lymphoid malignancies recognizes several distinct entities within the group of diffuse large B-cell lymphoma (DLBCL) characterized by unique clinical and pathological features. Nevertheless, diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS) is the most common aggressive B-cell lymphoma. In the last 20 years our understanding of the genetic changes and biology of DLBCL has increased tremendously. According to the 2016 WHO classification, the diagnosis of DLBCL, NOS, should include cell of origin (COO); germinal centre B-cell (GCB) or activated B-cell (ABC)/non-GCB subtypes, because of their different molecular features, biologic behavior, prognosis and treatment. High-grade B-cell lymphoma (HGBL) with MYC and BCL2 and/or BCL6 rearrangements (i.e., double-hit or triple-hit lymphoma, DHL or THL) as well as HGBL, NOS, are two new categories in the 2016 revised WHO classification that substituted the provisional category of B-cell lymphoma, unclassifiable (BCLU) with features intermediate between DLBCL and Burkitt lymphoma (BL), which was introduced in the 2008 WHO classification. The pathogenesis and molecular changes of BL are better understood and led to the recognition of a new provisional entity called Burkitt-like lymphoma with 11q aberration. In this article, we will review the progress made in the last years within the most commonly encountered aggressive B-cell lymphomas, highlighting the better understanding of the underlying disease mechanisms that eventually might be translated into more rational and effective therapeutic strategies. Controversial issues about fluorescent in situ hybridization (FISH) for the detection of MYC, BCL2 and BCL6 translocations will be addressed, as well as new molecular techniques used to improve diagnosis and prognostication in aggressive B-cell lymphomas.