Increased plasma D-2-hydroxyglutarate in isocitrate dehydrogenase 2-mutated blastic plasmacytoid dendritic cell neoplasm

Blastic plasmacytoid dendritic cell neoplasm is an exceedingly rare hematologic malignancy derived from the precursors of plasmacytoid dendritic cells. Mutations in isocitrate dehydrogenase (IDH) 1 and 2 genes have been discovered in a range of neoplasms including glioma, acute myeloid leukemia, chondrosarcoma, and intrahepatic cholangiocarcinoma. Mutant IDH acquires neomorphic enzymatic activity to generate the oncometabolite D-2-hydroxyglutarate (D-2HG). Here, we describe the first case of an IDH2 R140Q-mutated blastic plasmacytoid dendritic cell neoplasm in a patient with markedly elevated plasma D-2HG. This finding expands the spectrum Of neoplasms with increased D-2HG in association with IDH mutation. The roles of IDH mutation and D-2HG in disease pathogenesis and assessment of clinical response are discussed. (C) 2015 Elsevier Inc. All rights reserved.