The upcoming 5th edition of the World Health Organization (WHO) Classification of Haematolymphoid Tumours is part of an effort to hierarchically catalogue human cancers arising in various organ systems within a single relational database. This paper summarizes the new WHO classification scheme for myeloid and histiocytic/dendritic neoplasms and provides an overview of the principles and rationale underpinning changes from the prior edition. The definition and diagnosis of disease types continues to be based on multiple clinicopathologic parameters, but with refinement of diagnostic criteria and emphasis on therapeutically and/or prognostically actionable biomarkers. While a genetic basis for defining diseases is sought where possible, the classification strives to keep practical worldwide applicability in perspective. The result is an enhanced, contemporary, evidence-based classification of myeloid and histiocytic/dendritic neoplasms, rooted in molecular biology and an organizational structure that permits future scalability as new discoveries continue to inexorably inform future editions.

We herein present an overview of the upcoming 5th edition of the World Health Organization Classification of Haematolymphoid Tumours focussing on lymphoid neoplasms. Myeloid and histiocytic neoplasms will be presented in a separate accompanying article. Besides listing the entities of the classification, we highlight and explain changes from the revised 4th edition. These include reorganization of entities by a hierarchical system as is adopted throughout the 5th edition of the WHO classification of tumours of all organ systems, modification of nomenclature for some entities, revision of diagnostic criteria or subtypes, deletion of certain entities, and introduction of new entities, as well as inclusion of tumour-like lesions, mesenchymal lesions specific to lymph node and spleen, and germline predisposition syndromes associated with the lymphoid neoplasms.

• Bacterial sepsis from contaminated platelet transfusions continues to occur despite recent interventions; additional measures are needed.• STR to platelet transfusion is frequently not recognized or reported; use of recent AABB criteria showed highest diagnostic sensitivity.Septic transfusion reactions (STRs) resulting from transfusion of bacterially contaminated platelets are a major hazard of platelet transfusion despite recent interventions. Active and passive surveillance for bacterially contaminated platelets was performed over 7 years (2007)(2008)(2009)(2010)(2011)(2012)(2013) by culture of platelet aliquots at time of transfusion and review of reported transfusion reactions. All platelet units had been cultured 24 hours after collection and released as negative. Five sets of STR criteria were evaluated, including recent AABB criteria; sensitivity and specificity of these criteria, as well as detection by active and passive surveillance, were determined. Twenty of 51 440 platelet units transfused (0.004%; 389 per million) were bacterially contaminated by active surveillance and resulted in 5 STRs occurring 9 to 24 hours posttransfusion; none of these STRs had been reported by passive surveillance. STR occurred only in neutropenic patients transfused with high bacterial loads. A total of 284 transfusion reactions (0.55%) were reported by passive surveillance. None of these patients had received contaminated platelets. However, 6 to 93 (2.1%-32.7%) of these 284 reactions met 1 or more STR criteria, and sensitivity of STR criteria varied from 5.1% to 45.5%. These results document the continued occurrence of bacterial contamination of platelets resulting in STR in neutropenic patients, failure of passive surveillance to detect STR, and lack of specificity of STR criteria. These findings highlight the limitations of reported national STR data based on passive surveillance and the need to implement further measures to address this problem such as secondary testing or use of pathogen reduction technologies. (Blood. 2016;127(4):496-502)

Aggregation of the high affinity receptor for IgE (FcεRI) induces activation of mast cells. In this study we show that upon low intensity stimulation of FcεRI with monomeric IgE, IgE plus anti-IgE, or IgE plus low Ag, Lyn (a Src family kinase) positively regulates degranulation, cytokine production, and survival, whereas Lyn works as a negative regulator of high intensity stimulation with IgE plus high Ag. Low intensity stimulation suppressed Lyn kinase activity and its association with FcεRI β subunit, whereas high intensity stimulation enhanced Lyn activity and its association with FcεRI β. The latter induced much higher levels of FcεRI β phosphorylation and Syk activity than the former. Downstream positive signaling molecules, such as Akt and p38, were positively and negatively regulated by Lyn upon low and high intensity stimulations, respectively. In contrast, the negative regulators, SHIP and Src homology 2 domain-containing protein tyrosine phosphatase-1, interacted with FcεRI β, and their phosphorylation was controlled by Lyn. Therefore, we conclude that Lyn-mediated positive vs negative regulation depends on the intensity of the stimuli. Studies of mutant FcεRI β showed that FcεRI β subunit-ITAM (ITAM motif) regulates degranulation and cytokine production positively and negatively depending on the intensity of FcεRI stimulation. Furthermore, Lyn-mediated negative regulation was shown to be exerted via the FcεRI β-ITAM.