ABSTRACT
Introduction 633 Natural killer cell development 634 Immunophenotype and genotype of NK cells 634 Natural killer cell neoplasms 635 Extranodal natural killer/T cell lymphoma 636 Definition 636 Epidemiology 637 Clinical manifestations 637 Clinical course and treatment 637 Prognostic factors 637 Disease monitoring 638 Morphology 638 Immunophenotype 638 Genetics features 639 Differential diagnosis 639 Etiology and pathogenesis 640 Aggressive natural killer cell leukemia 640 Definition 640 Epidemiology and etiology 640 Clinical manifestations 640
Treatment and clinical course 641 Morphology 641 Immunophenotype and molecular findings 641 Differential diagnosis 641 Chronic lymphoproliferative disorder of NK cells 642 Definition 642 Clinical manifestation and clinical course 642 Pathologic, immunophenotypic and molecular features 642 Is this a neoplastic or reactive natural killer cell 642
proliferation? Differential diagnosis 643 So-called blastic natural killer cell lymphoma 643 Definition 643 Heterogeneity of ‘blastic natural killer cell lymphoma’ 643
and misnomer Epidemiology and etiology 643 Blastic plasmacytoid dendritic cell neoplasm 643 CD4-negative subset of blastic natural killer cell lymphoma 644 Key points 645 References 645
Natural killer (NK) cells are lymphocytes with the morphology of large granular lymphocyte (LGL), immunophenotype of surface CD3, CD56 and germline configuration of T cell receptor (TCR) genes.1,2 They are termed ‘natural killer’ because of their ability to lyse viralinfected cells and tumor cells in a major histocompatibility complex (MHC) unrestricted manner without prior sensitization. In contrast to B and T lymphocytes, they lack the ability to generate antigen-specific receptors by somatic gene rearrangements. Phenotypically, NK cells resemble activated cytotoxic CD8 T cells with respect to cell surface receptors and effector molecules, but in contrast to the latter, the cytotoxic molecules and cytokines are already present and do not have to be synthesized upon antigenic stimulation, enabling the cells to provide early rapid
important arm of the innate immune system. On the other hand, the cytokines, e.g. interferon γ (IFN-γ), tumor necrosis factor α (TNF-α), and granulocyte macrophage colony-stimulating factor (GM-CSF) produced by NK cells can regulate the development of acquired specific immunity. Thus, NK cells can be conceived as the third lymphocyte lineage bridging the innate and adaptive immune systems.3
