Intravascular NK/T-cell lymphoma: clinicopathological and integrated molecular analysis of two cases provides a clue to disease pathogenesis.

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 (, , and histone deacetylase (), two helicases ( and ), two methylation-related enzymes ( and ) and the SNI/SWF pathway (). Copy number analysis identified driver gene alterations comprising the loss of , and , and the gain of 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.