ICML 2015 Report: Update on the revision of the WHO lymphoma classification

Steven H Swerdlow, University of Pittsburgh Medical Center, USA, / by Maria Dalby.  Knowledge is evolving fast in the field of lymphoma and the 2008 World Health Organization (WHO) classification of malignant lymphomas, 4^th edition (which was a revision of the very first classification published in 2001) is in need of updating. Dr Steven Swerdlow from Pittsburgh was one of the editors on the 2008 edition and is on the editorial team for the new revision; in a special lecture in a joint American Association for Cancer Research (AACR)-ICML session, Dr Swerdlow apprised ICML delegates of where the process has got to and gave a flavour of what changes can be expected in the new revision.

The new revision will be authored by a team consisting of all the authors from the 2008 edition plus a number of new contributors, both haematopathologists and clinical haematologists/oncologists. The new revision will be released as an updated 4^th edition rather than a 5^th edition – the reason for this is that there are other volumes in the 4^th edition of the WHO Classification of Tumours series that have yet to be completed. This means that the new revision can ‘promote’ provisional entities to definite and also introduce new provisional entities, but no completely new definite entities may be included.

Dr Swerdlow stressed that nothing in the new revision should come as a great surprise to anyone who keeps up on lymphoma literature – the purpose of the WHO classification is simply to codify up-to-date existing diagnostic and clinical practices and reflect international consensus on potentially controversial topics. Some of the major changes that the advisory committee have now agreed upon include greater certainty in the classification of monoclonal B-cell lymphocytosis (MBL) and its role as a potential precursor of chronic lymphocytic leukaemia (CLL); promotion of paediatric follicular lymphoma (FL) to a definite entity, and the introduction of ‘large B-cell lymphoma with IRF4 rearrangement’ as a new provisional entity as these are thought to be more aggressive than other forms of paediatric FL. Grade 3B FL will remain in the FL chapter although they have been found to share more features with diffuse large B-cell lymphoma (DLBCL).

The new revision will also reflect recent interest in indolent forms of mantle cell lymphomas (MCL) – in situ MCL will be renamed in situ mantle cell neoplasia and its propensity to disseminate and/or progress will be discussed in more detail. In addition, new data has provided a better understanding of the behaviour of hairy cell leukaemia and lymphoplasmacytic lymphomas which will allow the authors to improve the diagnostic criteria for these conditions.

At the more aggressive end of the clinical spectrum, the 2008 edition introduced a category for unclassifiable B-cell lymphoma with intermediate features between DLBCL and Burkitt lymphoma. A minority of these cases were described as ‘double-hit’ lymphomas with both MYC and BCL2 and/or BCL6 rearrangements. The plan for the new revision is to include all double- and triple-hit lymphomas at the Burkitt-like to DLBCL spectrum in a category for very aggressive lymphomas that need to be treated with something other than R-CHOP.

Other agreed changes include Epstein-Barr virus (EBV)-positive DLBCL of the elderly (meaning >50 years) which will be renamed EBV-positive DLBCL not otherwise specified (NOS); grouping of intestinal T-cell lymphomas into ‘indolent T-cell lymphoproliferative disorder of the gastrointestinal tract’; promotion of anaplastic lymphoma kinase-negative anaplastic large cell lymphoma (ALK-ALCL) to a definite entity that needs to be distinguished from the more indolent form ALK+ALCL; and inclusion of breast implant-associated ALK-ALCL as a new provisional entity. In Hodgkin’s lymphoma (HL), an important update is the recognition of a grey zone between nodular lymphocyte-predominant HL (NLPHL) and classical HL.

The original plan was for the new revision to be web-based only, but this met with objections and in 2014 it was decided that a print version will be released at the same time as the online version. Publication of the new revised classification is expected in August 2016.