Aggressive mature natural killer cell neoplasms: from epidemiology to diagnosis

Abstract

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.

Novel Targets for Natural Killer/T-cell Lymphoma Immunotherapy

“…In recent years, the epidemiology of NKTL has undergone a gradual shift. Originally, NKTL was endemic to East Asia, Central and South America and was extremely rare in Europe and the United States [3].…”

The first report of a previously undescribed EBV-negative NK-cell lymphoma of the GI tract presenting as chronic diarrhoea with eosinophilia

“…These lymphomas, by definition, require EBV infection as a pre-requisite for diagnosis, and are very occasionally found elsewhere in the GI system 20–22. Aggressive NK-cell lymphoma, also known as aggressive NK-cell leucaemia, is a fulminant form of the disease, and manifests in the third to fourth decade of life, with multiorgan involvement, rapid disease progression and a prognosis in the order of weeks 23. These cancers are routinely associated with EBV infection and CD56 expression, distinguishing it from the lymphoma described in this case 24.…”

Molecular Genetic Abnormalities in the Pathogenesis of Hematologic Malignancies and Corresponding Changes in Cell Signaling Systems

“…Характерных хромосомных аномалий не отмечено, могут присутствовать генетический нарушения, присущие классу Т-клеточных лимфом в целом (преимущественно, различные реаранжировки в гене TCR и связанные с ними нарушения сигнальных путей) [83]. Наблюдается активация множественных сигнальных путей, таких как JAK/STAT3, сфинголипидов и MEK/ERK, что приводит к подавлению апоптоза и устойчивости к нормальным путям активации индуцированной клеточной гибели [92] Агрессивный лейкоз из NK-клеток Реаранжировки TCR, IG Может наблюдаться гиперэкспрессия различных проонкогенов, характерных для Т-клеточных лейкозов/лимфом в целом [83,93]. Геномная потеря локуса CD58.…”