Abstract
Extranodal NK/T-cell lymphoma is a neoplasm of NK cells or cytotoxic T cells presenting in extranodal sites, most often in the nasal cavity. The typical immunophenotypes are cCD3+, sCD3−, CD4−, CD5−, CD8−, CD16−, and CD56+ with the expression of cytotoxic molecules. Tumor subsets express NK cell receptors, CD95/CD95L, CD30, MYC, and PDL1. Virtually all the tumor cells harbor the EBV genome, which plays a key role in lymphomagenesis as an epigenetic driver. EBV-encoded oncoproteins modulate the host-cell epigenetic machinery, reprogramming the viral and host epigenomes using host epigenetic modifiers. NGS analysis revealed the mutational landscape of ENKTL, predominantly involving the JAK–STAT pathway, epigenetic modifications, the RNA helicase family, the RAS/MAP kinase pathway, and tumor suppressors, which indicate an important role of these pathways and this group of genes in the lymphomagenesis of ENKTL. Recently, three molecular subtypes were proposed, the tumor-suppressor/immune-modulator (TSIM), MGA-BRDT (MB), and HDAC9-EP300-ARID1A (HEA) subtypes, and they are well-correlated with the cell of origin, EBV pattern, genomic alterations, and clinical outcomes. A future investigation into the function and interaction of discovered genes would be very helpful for better understanding the molecular pathogenesis of ENKTL and establishing better treatment strategies.
Highlights
Extranodal NK/T-cell lymphoma (ENKTL) is an EBV-associated NK or cytotoxicT-cell lymphoma occurring at the extranodal site, predominantly in the nasal region [1]
An in vitro study showed that the constitutive activation of the JAK3/STAT3 pathway plays a major role in ENKTL cell growth and survival, and in the invasive phenotype [101]
Tumors with mutated DDX3X exhibit decreased RNA unwinding activity, a loss of suppressive function on cell-cycle progression, and the transcriptional activation of the NF-kB and MAPK pathways [88]. These findings indicate that DDX3X in ENKTL is a negative regulator of NK cell proliferation and mutation; disrupting this critical function contributes to ENKTL pathogenesis
Summary
T-cell lymphoma occurring at the extranodal site, predominantly in the nasal region [1]. Because of its characteristic clinical and histological presentations, ENKTL has various names, including “lethal midline granuloma”, “rhinitis gangrenosa progressiva”, “polymorphic reticulosis”, “reticulum cell sarcoma”, “midline malignant reticulosis”, “angiocentric immunoproliferative lesions”, and “angiocentric lymphoma” [3,4,5,6,7,8]. The nature of this entity was unknown, and the clinical course was aggressive.
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