Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy with an aggressive clinical course and poor prognosis. BPDCN is most often characterized by its presentation with cutaneous lesions which are often asymptomatic, can be solitary or multiple lesions, can be distributed widely, and may range from bruise-like lesions to plaques or nodules. Bone marrow involvement, central nervous system (CNS) infiltration, lymphadenopathy, splenomegaly, and/or cytopenias are also seen to varying degrees.
The nomenclature has changed many times over the years, making descriptions of the epidemiology more challenging. It was first described in 1995 as acute agranular CD41 natural killer (NK) cell leukemia. In the most recent WHO 2022 classification, BPDCN is classified under dendritic cell and histiocytic neoplasms along with plasmacytoid dendritic cell proliferation associated with myeloid BPDCN is more common in older men, with a sex ratio of 3:1 to 5:1 and a median age of diagnosis between 60 and 70 years. A bimodal age distribution was recently described, with higher incidence in patients aged ,20 and .60 years.
BPDCN cells characteristically express CD123, CD4, CD56, CD303, TCF4, and TCL-1, whereas certain specific lineage markers such as CD14, cCD3, CD19, and MPO are not expressed.
Genetic mutations implicated in the pathogenesis of BPDCN include inactivating tumor suppressors (ie, TP53, RB1, CDKN1B, and CDKN2A), activating oncogenes (ie, NRAS, KRAS, FLT3, RUNX2, and HES6), activated NF-κB pathway, mutated RNA spliceosomes (ie, ZRSR2 and others), immune response gene dysregulation (IFNGR, TGFB, CLEC4C, and IFNA cluster), and epigenetic dysregulation (ie, IDH1, IDH2, TET1, TET2, and ASXL1).
Historically, BPDCN treatments have been based on multi- agent chemotherapy regimens for lymphoma, acute lymphoblastic leukemia, and AML. In addition, acute leukemia regimens achieve high complete response (CR) rates ranging from 40–90% and allogeneic hematopoietic cell transplantation (allo-HCT) can result in durable remission in some patients. However, their rarity and heterogeneity make it difficult to determine the most effective therapeutic strategies.
Owing to recent advances in molecular biology and genetics, targeted treatment strategies have been developed. In 2018, the FDA approved tagraxofusp, a firstin-class CD123-targeting therapy for treatment- naïve or relapsed/refractory BPDCN.However, unfit, relapsed, or refractory patients continue to require effective therapeutic strategies.
Besides CD123 Targeted therapy; many other modalities are considered e.g. Venetoclax-based therapy, Transplantation and many new potential therapeutic targets under investigation.
