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Open Access Review

Aggressive mature natural killer cell neoplasms: from epidemiology to diagnosis

Margarida Lima

Author Affiliations

Department of Hematology, Laboratory of Cytometry, Hospital de Santo António (HSA), Centro Hospitalar do Porto (CHP), Rua D. Manuel II, s/n, 4099-001, Porto, Portugal

Multidisciplinary Unit for Biomedical Investigation (UMIB/ICBAS/UP), Porto, Portugal

Orphanet Journal of Rare Diseases 2013, 8:95  doi:10.1186/1750-1172-8-95

Published: 1 July 2013


Mature natural killer (NK) cell neoplasms are classified by the World Health Organization into NK/T cell lymphoma, nasal type (NKTCL), aggressive NK-cell leukemia (ANKCL) and chronic lymphoproliferative disorders of NK-cells, the latter being considered provisionally. NKTCL and ANKCL are rare diseases, with higher prevalence in Asia, Central and South America. Most NKTCL present extranodal, as a destructive tumor affecting the nose and upper aerodigestive tract (nasal NKTCL) or any organ or tissue (extranasal NKTCL) whereas ANKCL manifests as a systemic disease with multiorgan involvement and naturally evolutes to death in a few weeks. The histopathological hallmark of these aggressive NK-cell tumors is a polymorphic neoplastic infiltrate with angiocentricity, angiodestruction and tissue necrosis. The tumor cells have cytoplasmatic azurophilic granules and usually show a CD45+bright, CD2+, sCD3-, cytCD3epsilon+, CD56+bright, CD16−/+, cytotoxic granules molecules+ phenotype. T-cell receptor genes are in germ-line configuration. Epstein-Barr virus (EBV) -encoded membrane proteins and early region EBV RNA are usually detected on lymphoma cells, with a pattern suggestive of a latent viral infection type II. Complex chromosomal abnormalities are frequent and loss of chromosomes 6q, 11q, 13q, and 17p are recurrent aberrations. The rarity of the NK-cell tumors limits our ability to standardize the procedures for the diagnosis and clinical management and efforts should be made to encourage multi-institutional registries.

NK-cell Neoplasms; NK/T-cell Lymphoma; Nasal-type; Aggressive NK-Cell Leukemia; CD56