Evolving molecular classification of aggressive B-cell lymphoma

Abstract

This review aims to provide an overview of the latest developments in the classification and molecular understanding of aggressive B-cell lymphomas, specifically focusing on diffuse large B-cell lymphoma (DLBCL) and high-grade B-cell lymphoma (HGBL). Advances in molecular techniques have led to novel ways to classify these lymphomas based on clinical, histological, transcriptional, and genetic properties. While these methods have predominantly focused on the malignant compartment, recent studies emphasize the value of profiling the tumour microenvironment for a more comprehensive disease classification. Additionally, the integration of liquid biopsies represents a promising advancement, offering less invasive and dynamic insights into tumour characteristics and treatment response. Although molecular profiles are not yet routinely used to guide therapy, emerging data highlight their potential to predict responses to novel treatments. It is our belief that integrating molecular profiling and liquid biopsies into clinical practice and research now will pave the way for more personalized and effective therapies in the future.

Figure 1

Updates on the main differences between LBCL and HGBL from ICC‐2022 and WHO‐HAEM5 Classifications. DLBCL, diffuse large B‐cell lymphoma; FL, follicular lymphoma; HGBL, high‐grade B‐cell lymphoma; ICC, International Consensus Classification; LBCL, large B‐cell lymphoma; NOS, not otherwise specified; PCNSL, primary central nervous system large B‐cell lymphoma; WHO‐HAEM5, 5th edition of the WHO Classification of Hematolymphoid Tumours.

Figure 2

Overview of genetic classes, landmark alterations, and associated cell‐of‐origin subtypes. ABC, activated B‐cell DLBCL subtype; GCB, germinal centre B‐cell DLBCL subtype.

Figure 3

Recommended workup of aggressive lymphoma. IHC, immunohistochemistry; FISH, fluorescence in‐situ hybridization; GEP, gene‐expression profiling; COO, cell‐of‐origin; FFPE, formalin‐fixed paraffin‐embedded; WES, whole‐exome sequencing; ctDNA, circulating tumour DNA; MRD, minimal residual disease.