Blastic Plasmacytoid Dendritic Cell Neoplasm

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Primary Author(s)*

Hao Liu, MD and Daynna J. Wolff, PhD

Cancer Category/Type

Myeloid neoplasms/Acute myeloid leukemia

Cancer Sub-Classification / Subtype

Blastic plasmacytoid dendritic cell neoplasm (BPDCN)

Definition / Description of Disease

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare, clinically aggressive hematologic malignancy that derives from precursors of plasmacytoid dendritic cells (pDCs)[1][2].

Synonyms / Terminology

  • Agranular CD4+ NK cell leukaemia (obsolete)[1]
  • Blastic NK leukaemia/lymphoma (obsolete)[1]
  • Agranular CD4+ CD56+ hematodermic neoplasm/tumor[1][2]

Epidemiology / Prevalence

  • BPDCN is rare, estimated to represent < 1% of all hematologic malignancies[1].
  • The incidence of BPDCN in the USA: 0.04 cases per 100,000 individuals[3].
  • BPDCN has no known racial or ethnic predilection.
  • Though BPDCN can occur at any age, it more commonly occurs in elderly patients with a mean/median patient age at diagnosis of 61-67 years[1][4].
  • It most often affects males, with a male-to-female ratio of 3.3:1[1].

Clinical Features

Typical BPDCN patients may have two stages[1]:

o  First stage: affects the skin , usually contained or indolent

o  Second stage:  rapid leukemic spread and multi-organ involvement that eventually leads to death[1].

Sites of Involvement

  • Multiple sites are frequently involved by BPDCN. The three most common are the skin (in 60–100% cases), followed by the bone-marrow and peripheral blood (in 60–90% of cases), and thirdly the lymph nodes (in 40–50% of cases)[1].
  • Upon diagnosis, the central nervous system (CNS) is also frequently found to be involved, and up to one third of patients have CNS involvement at relapse[3].

Morphologic Features

  • BPDCN is commonly characterized by a diffuse, monomorphous infiltrate of small or medium-sized blasts[1].
  • The morphology of the neoplastic cells is similar to lymphoblasts or myeloblasts:  high N: C ratio, eccentrically located nucleus, fine chromatin, a prominent nucleolus and scant amphophilic cytoplasm[1].
  • Mitoses are variable in number, and the Ki-67 rate ranges from 20 to 80%[1].
  • Necrosis may present.


  • BPDCN cells express CD4, CD43, CD45RA, CD56, and the pDC associated antigens, including CD123 (IL3 α chain receptor), CD303, TCL1A, CD2AP, and TCF4[1][2][3].
  • BPDCN is characterized by high expression levels of CD123 and weak expression of CD45[1].
  • BPDCN cells are negative for lineage-specific markers including CD3, CD19, and myeloperoxidase[1][3].
  • BPDCN cells also do not express myeloid cell nuclear differentiation antigen (MNDA)[3].
  • BPDCN cells in some cases variably express CD2, CD5, CD7, CD33, CD38, CD68, CD117, HLA-DR, and TdT[1][3].

Chromosomal Rearrangements (Gene Fusions)

A recurrent balanced translocation t(6;8)(p21;q24) involving the MYC locus was exclusively identified in BPDCN[5][6][7][8][9]. The prevalence of MYC translocation in BPDCN is 5% -12%[6]. Rearrangements involving the MYC locus on 8q24 are associated with MYC protein overexpression and specific clinical features, including older onset age and shorter median survival[6]. RUNX2, located on chromosome 6p21, is strongly expressed in pDCs and BPDCN cells. The t(6,8) generates mutant-allele super-enhancer of RUNX2 which may increase the expression of MYC and lead to the development of BPDCN[5]. SUPT3H, a TATA-binding protein-associated factors (TAF)-associated protein, was identified as a novel 8q24/MYC partner in BPDCN[7].

Chromosomal Rearrangement Genes in Fusion (5’ or 3’ Segments) Pathogenic Derivative Prevalence
t(6;8)(p21;q24) 5'RUNX2 super enhancer / 5'MYC increased expression MYC 5-12%[5][6][7][8][9][10]
t(8;var)(q24;var) ? / 5'MYC ?increased expression MYC

Characteristic Chromosomal Aberrations / Patterns

  • Chromosomal abnormalities are identified in the majority of BPDCN cases; about two thirds of BPDCN patients have an abnormal karyotype[1].
  • About 75% of BPDCN patients have a complex karyotype, which is defined by three or more abnormalities, including at least one structural abnormality[3].
  • Abnormalities involving the short arm of chromosome 12, the 12p13 locus which contains ETV6 gene, are the one of the most frequent findings in BPDCN (in 64% patients)[1][3].
  • Chromosome 6 (6q23-qter, in 50% patients) and chromosome 13 (13q13-21, in 64% patients) are also frequently involved[1][3].
  • Six major recurrent chromosomal targets were defined in one study[10]. These were 5q, 12p, 13q, 6q, 15q, and 9, which were involved in 72% (5q), 64% (12p and 13q), 50% (6q), 43% (15q), and 28% (monosomy 9) of cases, respectively.

Genomic Gain/Loss/LOH

1).Deletion of the 9p21.3 locus[11]:

·        Most recurrent event in cases of BPDCN

·       Associated with a poor prognosis when biallelic

2).  12p13/ETV6 deletions[12]:

·       Monoallelic or biallelic

·        May represent early clonal events

3). Del(5q), del(7q), del(9q), del(11q), del(12p) and del(13q) are frequently identified in BPDCN patients with myelodysplastic syndrome or acute myeloid leukemia with myelodysplasia-related changes[3].

Gene Mutations (SNV/INDEL)

  • Common gene mutations in BPDCN: TET2, ASXL1, NRAS, ATM, and NPM1[1][3][6][13].
  • Less common mutations in BPDCN: APC, BRAF, IDH2, KIT, KRAS, MET, MLH1, RB1, RET, TP53, and VHL[3].

Other Mutations

Epigenomics (Methylation)

  • Multiple mutated epigenetic modifier genes have been identified in BPDCN[11][13], which include those participate in:

o  DNA methylation: TET2, IDH2

o  Chromatin accessibility: ARID1a, CHD8, SMARCA1

o  Histone modification: methylation (ASXL1, SUZ12, MLL), demethylation (KDM4D), acetylation (EP300, EP400), ubiquitination (PHC1, PHC2), dephosphorylation (EYA2) and exchange (SRCAP)[11][13]

Genes and Main Pathways Involved

·        BCL-2 and NF-ĸB pathways[11][14]

Diagnostic Testing Methods

  • A dual-color TCF4/CD123 immunohistochemistry stain has been reported to have both high sensitivity and specificity for the diagnosis[15].
  • Immunophenotyping showing expression of pDC antigens and no lineage specific markers is relatively specific for this entity.
  • Chromosome analysis and/or copy number assessment by whole genome microarray or other technology can identify recurrent aberrations.

Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications)

  • BPDCN is extremely aggressive, with a median survival of 10-19.8 months[1].
  • Age is an adverse impact factor for prognosis[1].
  • Diagnosis is usually established through skin biopsy with immunohistochemistry or flow cytometry[4].
  • Traditional therapeutic approaches include multi-agent chemotherapy, such as CHOP, hyper-CVAD[2][3][4]. However, the traditional chemotherapy is associated with high relapse rate and death[16].
  • A new targeted therapy, Tagraxofusp (SL-401, ELZONRIS) was recently approved.  This agent is a CD123-directed cytotoxin consisting of recombinant human interleukin-3 fused to a truncated diphtheria toxin[2][4][16].
  • For the patients in first complete remission after induction therapy, allogeneic hematopoietic stem cell transplantation (HSCT) is recommended to achieve long-term survival[1][4].

Familial Forms

Other Information


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  5. 5.0 5.1 5.2 Kubota, Sho; et al. (2019). "Lineage-specific RUNX2 super-enhancer activates MYC and promotes the development of blastic plasmacytoid dendritic cell neoplasm". Nature Communications. 10 (1): 1653. doi:10.1038/s41467-019-09710-z. ISSN 2041-1723. PMC 6458132. PMID 30971697.
  6. 6.0 6.1 6.2 6.3 6.4 Sumarriva Lezama, Lhara; et al. (2018). "An analysis of blastic plasmacytoid dendritic cell neoplasm with translocations involving the MYC locus identifies t(6;8)(p21;q24) as a recurrent cytogenetic abnormality". Histopathology. 73 (5): 767–776. doi:10.1111/his.13668. ISSN 1365-2559. PMID 29884995.
  7. 7.0 7.1 7.2 Nakamura, Y.; et al. (2015). "Identification of SUPT3H as a novel 8q24/MYC partner in blastic plasmacytoid dendritic cell neoplasm with t(6;8)(p21;q24) translocation". Blood Cancer Journal. 5: e301. doi:10.1038/bcj.2015.26. ISSN 2044-5385. PMC 4450326. PMID 25860292.
  8. 8.0 8.1 Sakamoto, Kana; et al. (2018). "Recurrent 8q24 rearrangement in blastic plasmacytoid dendritic cell neoplasm: association with immunoblastoid cytomorphology, MYC expression, and drug response". Leukemia. 32 (12): 2590–2603. doi:10.1038/s41375-018-0154-5. ISSN 1476-5551. PMID 29795241.
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  10. 10.0 10.1 Leroux, Dominique; et al. (2002). "CD4(+), CD56(+) DC2 acute leukemia is characterized by recurrent clonal chromosomal changes affecting 6 major targets: a study of 21 cases by the Groupe Français de Cytogénétique Hématologique". Blood. 99 (11): 4154–4159. doi:10.1182/blood.v99.11.4154. ISSN 0006-4971. PMID 12010820.
  11. 11.0 11.1 11.2 11.3 Lezama, Lhara; et al. (2019). "Expounding on the essence of epigenetic and genetic abnormalities in blastic plasmacytoid dendritic cell neoplasms". Haematologica. 104 (4): 642–643. doi:10.3324/haematol.2018.211557. ISSN 1592-8721. PMC 6442968. PMID 30930334.
  12. Tang, Zhenya; et al. (2018). "Genomic aberrations involving 12p/ETV6 are highly prevalent in blastic plasmacytoid dendritic cell neoplasms and might represent early clonal events". Leukemia Research. 73: 86–94. doi:10.1016/j.leukres.2018.09.006. ISSN 1873-5835. PMID 30248580.
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  15. Sukswai, Narittee; et al. (2019). "Dual Expression of TCF4 and CD123 Is Highly Sensitive and Specific For Blastic Plasmacytoid Dendritic Cell Neoplasm". The American Journal of Surgical Pathology. 43 (10): 1429–1437. doi:10.1097/PAS.0000000000001316. ISSN 1532-0979. PMID 31261288.
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