Hum Pathol. 2020 Sep 2:S0046-8177(20)30170-2. doi: 10.1016/j.humpath.2020.08.008. Online ahead of print.
EBV-negative aggressive NK-cell leukemia/lymphoma (ANKL) is a recently recognized, rare NK-cell neoplasm that preferentially affects non-Asians and has a fulminant clinical course. Little is known about the genetic alterations of this disease. In this study, we performed comprehensive molecular genetic studies, including chromosomal analysis, fluorescence in-situ hybridization (FISH), SNP microarray and next generation sequencing (NGS) on 4 patients diagnosed in our institution. The results
demonstrated that our EBV-negative ANKLs have highly complex genomic profiles characterized by near triploid/tetraploid karyotype (3 of 3) with numerous structural abnormalities, inactivation of TP53 (3 of 3), overexpression of c-Myc (4 of 4), strong expression of PD-L1 in neoplastic cells (2 of 4), and gain of 11q23-ter region (2 of 2). Our study provides important insights of EBV-negative ANKL, which share many of the genetic features with their EBV-positive counterpart. The strong expression of PD-L1 suggests that immune checkpoint inhibitors may be further explored as a potential therapeutic option for this highly aggressive, chemotherapy-resistant NK-cell neoplasm.