Aims To elucidate the clinicopathological and molecular features of intravascular NK/T-cell lymphoma (IVNKTCL).
Methods Two cases of IVNKTCL were retrieved from a single-centre cohort composed of 25 intravascular lymphomas. Whole-exome and RNA sequencing and immunohistochemistry were performed.
Results We identified somatic mutations in the following epigenetic regulators: four histone genes (HIST1H2AN, HIST1H2BE, HIST1H2BN and H3F3A), histone deacetylase (HDAC5), two helicases (WRN and DDX3X), two methylation-related enzymes (TET2 and DNMT1) and the SNI/SWF pathway (ARID1A). Copy number analysis identified driver gene alterations comprising the loss of ARID1B, HACE1 and SMAD4, and the gain of SOX2 and histone clusters. RNA sequencing analysis did not indicate the presence of any fusion gene. Both cases were positive for Epstein-Barr virus (EBV) and showed strong expression of programmed death-ligand 1 (PD-L1).
Conclusions This study raises the possibility that, at least for some patients, IVNKTCL may be considered an epigenetic disease with EBV infection-associated aetiopathogenesis.
- intravascular nk/t-cell lymphoma
- whole-exome sequencing
- somatic mutation
- copy number alteration
- RNA sequencing
- epigenetic regulator
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Handling editor Mary Frances McMullin.
Contributors KF and YI designed and supervised the study. KF performed the experiments, interpreted the data and wrote the draft manuscript. DY, ToI and YI were responsible for the final pathological diagnosis. TaI was responsible for clinical data. RS participated in the radiological examination of patients. S-SC contributed to analysing the clinical information. All authors read and approved the final manuscript.
Funding This study was supported by the Kasahara Cancer Research Fund (H28, to KF) and internal funding.
Competing interests None declared.
Patient consent for publication Not required.
Ethics approval This study was approved by the Kobe City Medical Center General Hospital Ethics Committee (2016), and conducted according to the World Medical Association Declaration of Helsinki ethics principles.
Provenance and peer review Not commissioned; externally peer reviewed.