The fifth edition of the WHO classification of mature B-cell neoplasms: open questions for research

Abstract

The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours (WHO-HAEM5) is the product of an evidence-based evolution of the revised 4th edition with wide multidisciplinary consultation. Nonetheless, while every classification incorporates scientific advances and aims to improve upon the prior version, medical knowledge remains incomplete and individual neoplasms may not be easily subclassified in a given scheme. Thus, optimal classification requires ongoing study. There are certain aspects of some entities and subtypes, which require further refinements. In this review, we highlight a selection of these challenging areas to prompt more research investigations. These include: 1) a “placeholder term” of splenic B-cell lymphoma/leukaemia with prominent nucleoli (SBLPN) to accommodate many of the splenic lymphomas previously classified as hairy cell leukaemia variant and B-prolymphocytic leukaemia, a clear new start to define their pathobiology; 2) how to best classify BCL2 rearrangement negative follicular lymphoma including those with BCL6 rearrangement, integrating the emerging new knowledge on various germinal centre B-cell subsets? 3) what is the spectrum of non-IG gene partners of MYC translocation in diffuse large B-cell lymphoma (DLBCL)/ high grade B-cell lymphoma (HGBL), and how they impact MYC expression and clinical outcome? How best to investigate this in a routine clinical setting? 4) how best to define HGBL not otherwise specified and HGBL with 11q aberrations to distinguish them from their mimics and define their molecular pathogenetic mechanism? Addressing these questions would provide more robust evidence to better define these entities/subtypes, improve their diagnosis and/or prognostic stratification, leading to better patient care.