A practical approach to the understanding and diagnosis of lymphoma: an assessment of the WHO classification based on immunoarchitecture and immuno-ontogenic principles

SummaryThis review aims to interrelate the major lymphoma types in the current World Health Organization (WHO) classification to construct a framework for understanding and diagnostic application.Multiple morphological, phenotypical and molecular genotypical data are assessed in order to categorise lymphomas into germinal centre (GC) and extracentric (EC) subgroups.GC entities [lymphocyte-predominant Hodgkin, follicular, Burkitt’s, angioimmunoblastic T-cell and diffuse large B-cell lymphoma (DLBCL) with GC profile] express bcl-6, CD10 and/or the GC-homing chemokine CXCL13, and harbour ongoing somatic hypermutations (SHM), but not Epstein–Barr virus (EBV) in its higher latency states. Post-GC entities [classical Hodgkin, marginal zone and lymphoplasmacytic lymphomas, half of chronic lymphocytic leukaemia (CLL)/small lymphocytic lymphoma (SLL), DLBCL with ‘activated’ or post-GC profile, primary effusion lymphoma, plasmacytoma and myeloma] express, instead, MUM.1 and/or CD138, harbour static rather than ongoing SHM, and may harbour EBV in higher latency states. The remainder of CLL/SLL and the majority of mantle cell lymphoma without SHM constitute the pre-GC (‘naïve’) category, with coexpression of IgD and CD5.Lymphomas can be categorised across lineage (B- or T-cell) and relationship against host immune response (Hodgkin or non-Hodgkin) into GC and EC groups, affording leverage in their differential diagnosis.