Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type: Basic Science and Clinical Progress

Abstract

Extranodal natural killer (NK)/T-cell lymphoma, nasal type (NNKTL) has very unique epidemiological, etiologic, histologic, and clinical characteristics. It is commonly observed in Eastern Asia, but quite rare in the United States and Europe. The progressive necrotic lesions mainly in the nasal cavity, poor prognosis caused by rapid local progression with distant metastases, and angiocentric and polymorphous lymphoreticular infiltrates are the main clinical and histologic features. Phenotypic and genotypic studies revealed that the lymphoma is originated from either NK- or γδ T-cell, both of which express CD56. In 1990, the authors first reported the presence of Epstein-Barr virus (EBV)-DNA and EBV-oncogenic proteins, and EBV has now been recognized to play an etiological role in NNKTL. in vitro studies revealed that a wide variety of cytokines, chemokines, and micro RNAs, which may be produced by EBV-oncogenic proteins in the lymphoma cells, play important roles for tumor progression in NNKTL, and could be therapeutic targets. In addition, it was revealed that the interaction between NNKTL cells and immune cells such as monocytes and macrophages in NNKTL tissues contribute to lymphoma progression. For diagnosis, monitoring the clinical course and predicting prognosis, the measurements of EBV-DNAs and EBV-micro RNAs in sera are very useful. For treatment with early stage, novel concomitant chemoradiotherapy such as DeVIC regimen with local radiotherapy and MPVIC-P regimen using intra-arterial infusion developed with concomitant radiotherapy and the prognosis became noticeably better. However, the prognosis of patients with advanced stage was still poor. Establishment of novel treatments such as the usage of immune checkpoint inhibitor or peptide vaccine with molecular targeting therapy will be necessary. This review addresses recent advances in the molecular understanding of NNKTL to establish novel treatments, in addition to the epidemiologic, clinical, pathological, and EBV features.

Outcomes of patients treated with SVILE <i>vs</i>. P-GemOx for extranodal natural killer/T-cell lymphoma, nasal type: a prospective, randomized controlled study

“…These 2 groups of patients are currently closely monitored. In the event of recurrence of the disease, lymphoma specimens will be tested for molecular biology-related indicators, and new treatments such as chemotherapy combined with monoclonal antibodies to programmed cell death protein 1 or programmed cell death ligand 1; histone deacetylase inhibitors; monoclonal antibody to CD38; or immunomodulator lenalidomide will be administered according to the molecular tests and literature findings 17 . To date, we have 2 clinical trials registered for relapsed and refractory ENKTL.…”

“…Studies have also shown promising results of treatments with monoclonal antibodies against cluster of differentiation (CD)52 and the protein deacetylase inhibitor romidepsin 15 , 16 . Furthermore, many molecular targets for ENKTL are being introduced 17 . Although newer regimens have demonstrated positive outcomes in the treatment of ENKTL, they still do not always meet patients’ needs.…”

Photohyperthermal therapy using liposomally formulated indocyanine green for feline nasal lymphoma: A case report

“…In human medicine, nasal lymphoma is known as extranodal natural killer/T-cell lymphoma, nasal type (26). The lymphoma originates from either natural killer cells or γδ T-cells, both of which express CD56 (26).…”

“…In human medicine, nasal lymphoma is known as extranodal natural killer/T-cell lymphoma, nasal type (26). The lymphoma originates from either natural killer cells or γδ T-cells, both of which express CD56 (26). Conversely, a B-cell phenotype comprises 40% of feline nasal lymphomas, and a T-cell phenotype comprises 47% (27).…”

Extranodal NK/T cell lymphoma

“…The lymphoma cells originate from either NK cells or γδ T cells [ 3 ]. T cell receptor gene rearrangement is observed in 10–35% of patients [ 4 ]. Therefore, in the latest World Health Organization classification, these lymphomas are referred to as ENKTLs, to reflect their putative cellular origins from NK cells and T cells [ 5 ].…”