Blastic plasmacytoid dendritic cell neoplasm

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Haematolymphoid Tumours (WHO Classification, 5th ed.)

editContent Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification
This page was converted to the new template on 2023-12-07. The original page can be found at HAEM4:Blastic Plasmacytoid Dendritic Cell Neoplasm.

(General Instructions – The focus of these pages is the clinically significant genetic alterations in each disease type. This is based on up-to-date knowledge from multiple resources such as PubMed and the WHO classification books. The CCGA is meant to be a supplemental resource to the WHO classification books; the CCGA captures in a continually updated wiki-stye manner the current genetics/genomics knowledge of each disease, which evolves more rapidly than books can be revised and published. If the same disease is described in multiple WHO classification books, the genetics-related information for that disease will be consolidated into a single main page that has this template (other pages would only contain a link to this main page). Use HUGO-approved gene names and symbols (italicized when appropriate), HGVS-based nomenclature for variants, as well as generic names of drugs and testing platforms or assays if applicable. Please complete tables whenever possible and do not delete them (add N/A if not applicable in the table and delete the examples); to add (or move) a row or column in a table, click nearby within the table and select the > symbol that appears. Please do not delete or alter the section headings. The use of bullet points alongside short blocks of text rather than only large paragraphs is encouraged. Additional instructions below in italicized blue text should not be included in the final page content. Please also see Author_Instructions and FAQs as well as contact your Associate Editor or Technical Support.)

Primary Author(s)*

Hao Liu, MD and Daynna J. Wolff, PhD

WHO Classification of Disease

Structure Disease
Book Haematolymphoid Tumours (5th ed.)
Category Histiocytic/Dendritic cell neoplasms
Family Plasmacytoid dendritic cell neoplasms
Type Plasmacytoid dendritic cell neoplasms
Subtype(s) Blastic plasmacytoid dendritic cell neoplasm

WHO Essential and Desirable Genetic Diagnostic Criteria

(Instructions: The table will have the diagnostic criteria from the WHO book autocompleted; remove any non-genetics related criteria. If applicable, add text about other classification systems that define this entity and specify how the genetics-related criteria differ.)

WHO Essential Criteria (Genetics)*
WHO Desirable Criteria (Genetics)*
Other Classification

*Note: These are only the genetic/genomic criteria. Additional diagnostic criteria can be found in the WHO Classification of Tumours.

Related Terminology

(Instructions: The table will have the related terminology from the WHO autocompleted.)

Acceptable
Not Recommended

Gene Rearrangements

Put your text here and fill in the table (Instructions: Details on clinical significance such as prognosis and other important information can be provided in the notes section. Please include references throughout the table. Do not delete the table.)

Driver Gene Fusion(s) and Common Partner Genes Molecular Pathogenesis Typical Chromosomal Alteration(s) Prevalence -Common >20%, Recurrent 5-20% or Rare <5% (Disease) Diagnostic, Prognostic, and Therapeutic Significance - D, P, T Established Clinical Significance Per Guidelines - Yes or No (Source) Clinical Relevance Details/Other Notes
EXAMPLE: ABL1 EXAMPLE: BCR::ABL1 EXAMPLE: The pathogenic derivative is the der(22) resulting in fusion of 5’ BCR and 3’ABL1. EXAMPLE: t(9;22)(q34;q11.2) EXAMPLE: Common (CML) EXAMPLE: D, P, T EXAMPLE: Yes (WHO, NCCN) EXAMPLE:

The t(9;22) is diagnostic of CML in the appropriate morphology and clinical context (add reference). This fusion is responsive to targeted therapy such as Imatinib (Gleevec) (add reference). BCR::ABL1 is generally favorable in CML (add reference).

EXAMPLE: CIC EXAMPLE: CIC::DUX4 EXAMPLE: Typically, the last exon of CIC is fused to DUX4. The fusion breakpoint in CIC is usually intra-exonic and removes an inhibitory sequence, upregulating PEA3 genes downstream of CIC including ETV1, ETV4, and ETV5. EXAMPLE: t(4;19)(q25;q13) EXAMPLE: Common (CIC-rearranged sarcoma) EXAMPLE: D EXAMPLE:

DUX4 has many homologous genes; an alternate translocation in a minority of cases is t(10;19), but this is usually indistinguishable from t(4;19) by short-read sequencing (add references).

EXAMPLE: ALK EXAMPLE: ELM4::ALK


Other fusion partners include KIF5B, NPM1, STRN, TFG, TPM3, CLTC, KLC1

EXAMPLE: Fusions result in constitutive activation of the ALK tyrosine kinase. The most common ALK fusion is EML4::ALK, with breakpoints in intron 19 of ALK. At the transcript level, a variable (5’) partner gene is fused to 3’ ALK at exon 20. Rarely, ALK fusions contain exon 19 due to breakpoints in intron 18. EXAMPLE: N/A EXAMPLE: Rare (Lung adenocarcinoma) EXAMPLE: T EXAMPLE:

Both balanced and unbalanced forms are observed by FISH (add references).

EXAMPLE: ABL1 EXAMPLE: N/A EXAMPLE: Intragenic deletion of exons 2–7 in EGFR removes the ligand-binding domain, resulting in a constitutively active tyrosine kinase with downstream activation of multiple oncogenic pathways. EXAMPLE: N/A EXAMPLE: Recurrent (IDH-wildtype Glioblastoma) EXAMPLE: D, P, T
editv4:Chromosomal Rearrangements (Gene Fusions)
The content below was from the old template. Please incorporate above.

A recurrent balanced translocation t(6;8)(p21;q24) involving the MYC locus was exclusively identified in BPDCN[1][2][3][4][5]. The prevalence of MYC translocation in BPDCN is 5% -12%[2]. 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[2]. 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[1]. SUPT3H, a TATA-binding protein-associated factors (TAF)-associated protein, was identified as a novel 8q24/MYC partner in BPDCN[3].

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%[1][2][3][4][5][6]
t(8;var)(q24;var) ? / 5'MYC ?increased expression MYC
End of V4 Section


editv4:Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications).
Please incorporate this section into the relevant tables found in:
  • Chromosomal Rearrangements (Gene Fusions)
  • Individual Region Genomic Gain/Loss/LOH
  • Characteristic Chromosomal Patterns
  • Gene Mutations (SNV/INDEL)
  • BPDCN is extremely aggressive, with a median survival of 10-19.8 months[7].
  • Age is an adverse impact factor for prognosis[7].
  • Diagnosis is usually established through skin biopsy with immunohistochemistry or flow cytometry[8].
  • Traditional therapeutic approaches include multi-agent chemotherapy, such as CHOP, hyper-CVAD[9][10][8]. However, the traditional chemotherapy is associated with high relapse rate and death[11].
  • 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[9][8][11].
  • For the patients in first complete remission after induction therapy, allogeneic hematopoietic stem cell transplantation (HSCT) is recommended to achieve long-term survival[7][8].
End of V4 Section

Individual Region Genomic Gain/Loss/LOH

Put your text here and fill in the table (Instructions: Includes aberrations not involving gene rearrangements. Details on clinical significance such as prognosis and other important information can be provided in the notes section. Can refer to CGC workgroup tables as linked on the homepage if applicable. Please include references throughout the table. Do not delete the table.)

Chr # Gain, Loss, Amp, LOH Minimal Region Cytoband and/or Genomic Coordinates [Genome Build; Size] Relevant Gene(s) Diagnostic, Prognostic, and Therapeutic Significance - D, P, T Established Clinical Significance Per Guidelines - Yes or No (Source) Clinical Relevance Details/Other Notes
EXAMPLE:

7

EXAMPLE: Loss EXAMPLE:

chr7

EXAMPLE:

Unknown

EXAMPLE: D, P EXAMPLE: No EXAMPLE:

Presence of monosomy 7 (or 7q deletion) is sufficient for a diagnosis of AML with MDS-related changes when there is ≥20% blasts and no prior therapy (add reference).  Monosomy 7/7q deletion is associated with a poor prognosis in AML (add references).

EXAMPLE:

8

EXAMPLE: Gain EXAMPLE:

chr8

EXAMPLE:

Unknown

EXAMPLE: D, P EXAMPLE:

Common recurrent secondary finding for t(8;21) (add references).

EXAMPLE:

17

EXAMPLE: Amp EXAMPLE:

17q12; chr17:39,700,064-39,728,658 [hg38; 28.6 kb]

EXAMPLE:

ERBB2

EXAMPLE: D, P, T EXAMPLE:

Amplification of ERBB2 is associated with HER2 overexpression in HER2 positive breast cancer (add references). Add criteria for how amplification is defined.

editv4:Genomic Gain/Loss/LOH
The content below was from the old template. Please incorporate above.

1).Deletion of the 9p21.3 locus[12]:

·        Most recurrent event in cases of BPDCN

·       Associated with a poor prognosis when biallelic

2).  12p13/ETV6 deletions[13]:

·       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[10].

End of V4 Section

Characteristic Chromosomal or Other Global Mutational Patterns

Put your text here and fill in the table (Instructions: Included in this category are alterations such as hyperdiploid; gain of odd number chromosomes including typically chromosome 1, 3, 5, 7, 11, and 17; co-deletion of 1p and 19q; complex karyotypes without characteristic genetic findings; chromothripsis; microsatellite instability; homologous recombination deficiency; mutational signature pattern; etc. Details on clinical significance such as prognosis and other important information can be provided in the notes section. Please include references throughout the table. Do not delete the table.)

Chromosomal Pattern Molecular Pathogenesis Prevalence -

Common >20%, Recurrent 5-20% or Rare <5% (Disease)

Diagnostic, Prognostic, and Therapeutic Significance - D, P, T Established Clinical Significance Per Guidelines - Yes or No (Source) Clinical Relevance Details/Other Notes
EXAMPLE:

Co-deletion of 1p and 18q

EXAMPLE: See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference). EXAMPLE: Common (Oligodendroglioma) EXAMPLE: D, P
EXAMPLE:

Microsatellite instability - hypermutated

EXAMPLE: Common (Endometrial carcinoma) EXAMPLE: P, T
editv4:Characteristic Chromosomal Aberrations / Patterns
The content below was from the old template. Please incorporate above.
  • Chromosomal abnormalities are identified in the majority of BPDCN cases; about two thirds of BPDCN patients have an abnormal karyotype[7].
  • About 75% of BPDCN patients have a complex karyotype, which is defined by three or more abnormalities, including at least one structural abnormality[10].
  • 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)[7][10].
  • Chromosome 6 (6q23-qter, in 50% patients) and chromosome 13 (13q13-21, in 64% patients) are also frequently involved[7][10].
  • Six major recurrent chromosomal targets were defined in one study[6]. 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.
End of V4 Section

Gene Mutations (SNV/INDEL)

Put your text here and fill in the table (Instructions: This table is not meant to be an exhaustive list; please include only genes/alterations that are recurrent or common as well either disease defining and/or clinically significant. If a gene has multiple mechanisms depending on the type or site of the alteration, add multiple entries in the table. For clinical significance, denote associations with FDA-approved therapy (not an extensive list of applicable drugs) and NCCN or other national guidelines if applicable; Can also refer to CGC workgroup tables as linked on the homepage if applicable as well as any high impact papers or reviews of gene mutations in this entity. Details on clinical significance such as prognosis and other important information such as concomitant and mutually exclusive mutations can be provided in the notes section. Please include references throughout the table. Do not delete the table.)

Gene Genetic Alteration Tumor Suppressor Gene, Oncogene, Other Prevalence -

Common >20%, Recurrent 5-20% or Rare <5% (Disease)

Diagnostic, Prognostic, and Therapeutic Significance - D, P, T   Established Clinical Significance Per Guidelines - Yes or No (Source) Clinical Relevance Details/Other Notes
EXAMPLE:EGFR


EXAMPLE: Exon 18-21 activating mutations EXAMPLE: Oncogene EXAMPLE: Common (lung cancer) EXAMPLE: T EXAMPLE: Yes (NCCN) EXAMPLE: Exons 18, 19, and 21 mutations are targetable for therapy. Exon 20 T790M variants cause resistance to first generation TKI therapy and are targetable by second and third generation TKIs (add references).
EXAMPLE: TP53; Variable LOF mutations


EXAMPLE: Variable LOF mutations EXAMPLE: Tumor Supressor Gene EXAMPLE: Common (breast cancer) EXAMPLE: P EXAMPLE: >90% are somatic; rare germline alterations associated with Li-Fraumeni syndrome (add reference). Denotes a poor prognosis in breast cancer.
EXAMPLE: BRAF; Activating mutations EXAMPLE: Activating mutations EXAMPLE: Oncogene EXAMPLE: Common (melanoma) EXAMPLE: T

Note: A more extensive list of mutations can be found in cBioportal, COSMIC, and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.

editv4:Gene Mutations (SNV/INDEL)
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  • Common gene mutations in BPDCN: TET2, ASXL1, NRAS, ATM, and NPM1[7][10][2][14].
  • Less common mutations in BPDCN: APC, BRAF, IDH2, KIT, KRAS, MET, MLH1, RB1, RET, TP53, and VHL[10].

Other Mutations

End of V4 Section

Epigenomic Alterations

  • Multiple mutated epigenetic modifier genes have been identified in BPDCN[12][14], 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)[12][14]

Genes and Main Pathways Involved

Put your text here and fill in the table (Instructions: Please include references throughout the table. Do not delete the table.)

Gene; Genetic Alteration Pathway Pathophysiologic Outcome
EXAMPLE: BRAF and MAP2K1; Activating mutations EXAMPLE: MAPK signaling EXAMPLE: Increased cell growth and proliferation
EXAMPLE: CDKN2A; Inactivating mutations EXAMPLE: Cell cycle regulation EXAMPLE: Unregulated cell division
EXAMPLE: KMT2C and ARID1A; Inactivating mutations EXAMPLE: Histone modification, chromatin remodeling EXAMPLE: Abnormal gene expression program
editv4:Genes and Main Pathways Involved
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·        BCL-2 and NF-ĸB pathways[12][15]

End of V4 Section

Genetic Diagnostic Testing Methods

  • A dual-color TCF4/CD123 immunohistochemistry stain has been reported to have both high sensitivity and specificity for the diagnosis[16].
  • 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.

Familial Forms

Additional Information

Links

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References

(use the "Cite" icon at the top of the page) (Instructions: Add each reference into the text above by clicking where you want to insert the reference, selecting the “Cite” icon at the top of the wiki page, and using the “Automatic” tab option to search by PMID to select the reference to insert. If a PMID is not available, such as for a book, please use the “Cite” icon, select “Manual” and then “Basic Form”, and include the entire reference. To insert the same reference again later in the page, select the “Cite” icon and “Re-use” to find the reference; DO NOT insert the same reference twice using the “Automatic” tab as it will be treated as two separate references. The reference list in this section will be automatically generated and sorted.)

  1. ↑ Jump up to: 1.0 1.1 1.2 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.
  2. ↑ Jump up to: 2.0 2.1 2.2 2.3 2.4 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.
  3. ↑ Jump up to: 3.0 3.1 3.2 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.
  4. ↑ Jump up to: 4.0 4.1 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.
  5. ↑ Jump up to: 5.0 5.1 Boddu, Prajwal C.; et al. (2018). "8q24/MYC rearrangement is a recurrent cytogenetic abnormality in blastic plasmacytoid dendritic cell neoplasms". Leukemia Research. 66: 73–78. doi:10.1016/j.leukres.2018.01.013. ISSN 1873-5835. PMID 29407586.
  6. ↑ Jump up to: 6.0 6.1 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.
  7. ↑ Jump up to: 7.0 7.1 7.2 7.3 7.4 7.5 7.6 Fachetti F, et al., (2017). Blastic plasmacytoid dendritic cell neoplasm, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4th edition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Arber DA, Hasserjian RP, Le Beau MM, Orazi A, and Siebert R, Editors. IARC Press: Lyon, France, p174-177.
  8. ↑ Jump up to: 8.0 8.1 8.2 8.3 Kerr, Daniel; et al. (2019). "Blastic Plasmacytoid Dendritic Cell Neoplasm". Current Treatment Options in Oncology. 20 (1): 9. doi:10.1007/s11864-019-0605-x. ISSN 1534-6277. PMID 30715612.
  9. ↑ Jump up to: 9.0 9.1 Sapienza, Maria Rosaria; et al. (2019). "Blastic Plasmacytoid Dendritic Cell Neoplasm: State of the Art and Prospects". Cancers. 11 (5). doi:10.3390/cancers11050595. ISSN 2072-6694. PMC 6562663. PMID 31035408.
  10. ↑ Jump up to: 10.0 10.1 10.2 10.3 10.4 10.5 10.6 Khoury, Joseph D. (2018). "Blastic Plasmacytoid Dendritic Cell Neoplasm". Current Hematologic Malignancy Reports. 13 (6): 477–483. doi:10.1007/s11899-018-0489-z. ISSN 1558-822X. PMID 30350260.
  11. ↑ Jump up to: 11.0 11.1 Pemmaraju, Naveen; et al. (2019). "Tagraxofusp in Blastic Plasmacytoid Dendritic-Cell Neoplasm". The New England Journal of Medicine. 380 (17): 1628–1637. doi:10.1056/NEJMoa1815105. ISSN 1533-4406. PMID 31018069.
  12. ↑ Jump up to: 12.0 12.1 12.2 12.3 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.
  13. ↑ 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.
  14. ↑ Jump up to: 14.0 14.1 14.2 Sapienza, Maria Rosaria; et al. (2019). "Blastic plasmacytoid dendritic cell neoplasm: genomics mark epigenetic dysregulation as a primary therapeutic target". Haematologica. 104 (4): 729–737. doi:10.3324/haematol.2018.202093. ISSN 1592-8721. PMC 6442957. PMID 30381297.
  15. ↑ Chang, Kung-Chao; et al. (2019). "Blastic plasmacytoid dendritic cell neoplasm with immunoblastoid morphology and MYC rearrangement and overexpression". Pathology. 51 (1): 100–102. doi:10.1016/j.pathol.2018.09.058. ISSN 1465-3931. PMID 30482401.
  16. ↑ 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.


Notes

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*Citation of this Page: “Blastic plasmacytoid dendritic cell neoplasm”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 02/11/2025, https://ccga.io/index.php/HAEM5:Blastic_plasmacytoid_dendritic_cell_neoplasm.

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