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.

Mycosis fungoides and Sézary syndrome comprise the majority of cutaneous T cell lymphomas (CTCLs), disorders notable for their clinical heterogeneity that can present in skin or peripheral blood. Effective treatment options for CTCL are limited, and the genetic basis of these T cell lymphomas remains incompletely characterized1. Here we report recurrent point mutations and genomic gains of TNFRSF1B, encoding the tumor necrosis factor receptor TNFR2, in 18% of patients with mycosis fungoides and Sézary syndrome. Expression of the recurrent TNFR2 Thr377Ile mutant in T cells leads to enhanced non-canonical NF-ºB signaling that is sensitive to the proteasome inhibitor bortezomib. Using an integrative genomic approach, we additionally discovered a recurrent CTLA4-CD28 fusion, as well as mutations in downstream signaling mediators of these receptors.

Xenotransplantation models provide powerful tools for the investigation of human normal and malignant hematopoiesis. However, current models do not extensively recapitulate human bone marrow (BM) microenvironment components and exhibit limited engraftment of many human leukemias and other disorders. Here, we describe a xenotransplantation model bearing subcutaneous humanized ossicles with an accessible BM microenvironment formed by in situ differentiation of human BM-derived mesenchymal stromal cells. In these humanized ossicles, we observed robust engraftment of normal human hematopoietic stem and progenitor cells, and detected extensive engraftment of diverse primary acute myeloid leukemia samples at levels much greater than in unmanipulated mice. Direct intraossicle transplantation accelerated engraftment and resulted in substantially higher leukemia-initiating cell frequencies. We also observed robust engraftment of acute promyelocytic leukemia and myelofibrosis leading to the identification of leukemia-initiating cells in hematopoietic stem cells in myelofibrosis. This humanized ossicle xenotransplantation approach provides a novel system to model human hematologic disease.

We conclude that LMO2 protein expression is a prognostic marker in DLBCL patients treated with anthracycline-based regimens alone or in combination with rituximab. After further validation, immunohistologic analysis of LMO2 protein expression may become a practical assay for newly diagnosed DLBCL patients to optimize their clinical management.