Blastic Plasmacytoid Dendritic Cell Neoplasm: Progress in Cell Origin, Molecular Biology, Diagnostic Criteria and Therapeutic Approaches

Abstract

SummaryBlastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematological malignancy characterized by recurrent skin nodules, an aggressive clinical course with rapid involvement of hematological organs, and a poor prognosis with poor overall survival. BPDCN is derived from plasmacytoid dendritic cells (pDCs) and its pathogenesis is unclear. The tumor cells show aberrant expression of CD4, CD56, interleukin-3 receptor alpha chain (CD123), blood dendritic cell antigen 2 (BDCA 2/CD303), blood dendritic cell antigen 4 (BDCA4) and transcription factor (E protein) E2-2 (TCF4). The best treatment drugs are based on experience by adopting those used for either leukemia or lymphoma. Relapse with drug resistance generally occurs quickly. Stem cell transplantation after the first complete remission is recommended and tagraxofusp is the first targeted therapy. In this review, we summarize the differentiation of BPDCN from its cell origin, its connection with normal pDCs, clinical characteristics, genetic mutations and advances in treatment of BPDCN. This review provides insights into the mechanisms of and new therapeutic approaches for BPDCN.

Cytomorphological and immunophenotypic characteristics of blastic plasmacytoid dendritic cell neoplasm involving central nervous system: a case report and review of literature

“…1 The immunophenotypic heterogeneity and the association of myeloid disorder suggests a multilineage potential. 2,3 In 2016, the World Health Organization modified the classification and categorised it as a distinct entity under myeloid neoplasm. 2 BPDCN can occur at any age; however, it most commonly occurs in patients in their seventh decade of life.…”

Skin Lesions on the Face and Chest

“…Blastic plasmacytoid dendritic cell neoplasm affects males older than 60 years. 1 It is characterized by the clonal proliferation of precursor plasmacytoid dendritic cells-otherwise known as professional type I interferonproducing cells or plasmacytoid monocytes-of myeloid origin. Plasmacytoid dendritic cells have been renamed on several occasions, reflecting uncertainties of their histogenesis.…”

“…2,3 Tumor cells morphologically show an immature blastic appearance, and the diagnosis rests upon the demonstration of CD4 and CD56, together with markers more restricted to plasmacytoid dendritic cells (eg, BDCA-2, CD123, T-cell leukemia/lymphoma protein 1, CD2AP, BCL11A) and negativity for lymphoid and myeloid lineage-associated antigens. 1,4 Blastic plasmacytoid dendritic cell neoplasms account for less than 1% of all hematopoietic neoplasms. Cutaneous lesions occur in 64% of patients with the disease and often are the reason patients seek medical care.…”

Application of single cell transcriptomics to characterize the progression of hematopoietic cells to myeloid malignancies

“…Chromosomal abnormalities are also frequent. The most recurrent ones are deletions of fragments of the long arm of chromosome 5, short arm of chromosome 12 and short arm of chromosome 13 [71].…”

“…Their development is complex, as they can originate from both lymphoid and myeloid precursors. The pDC subset that originates BPDCN, referred to as pDC-like, belongs to the myeloid branch [71]. Specifically, it has been proven that malignant cells arise from resting pDCs of myeloid origin [72].…”