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Blastic plasmacytoid dendritic cell neoplasm


Topic Completed: 10 September 2020

Minor changes: 10 September 2020

Copyright: 2003-2020, PathologyOutlines.com, Inc.

PubMed search: blastic plasmacytoid dendritic cell neoplasm [title] skin bone marrow pathology


Narittee Sukswai, M.D.
Joseph Khoury, M.D.
Page views in 2020 to date: 2,668
Cite this page: Sukswai N, Khoury J. Blastic plasmacytoid dendritic cell neoplasm. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/bonemarrowneoplasticBPDCN.html. Accessed October 21st, 2020.
Definition / general
  • Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a highly aggressive hematologic malignancy derived from plasmacytoid dendritic cells (pDC) (Curr Hematol Malig Rep 2018;13:477)
Essential features
  • Nonneoplastic counterpart: plasmacytoid dendritic cells (Adv Anat Pathol 2009;16:392)
  • Over 80% of patients present with skin lesions; other common sites include the bone marrow and lymph nodes
  • Expression of CD123 and TCF4 is required for diagnosis; in addition, most cases are positive for CD4, CD56 and TCL1
  • Distinction from acute myeloid leukemia (AML) in particular is critical for appropriate therapy selection
Terminology
  • Blastic plasmacytoid dendritic cell neoplasm
  • Agranular CD4+ / CD56+ hematodermic neoplasm / tumor
  • Agranular CD4+ NK cell leukemia
  • CD56+ TdT+ blastic NK cell lymphoma
ICD coding
  • ICD-O: 9727/3 - blastic plasmacytoid dendritic cell neoplasm
Epidemiology
  • Rare, representing < 1% of hematologic malignancies (Leuk Res 2018;73:21)
  • Incidence is 0.04 cases per 100,000 in U.S.
  • M:F = 3:1
  • Most patients are in fifth or sixth decades of life but the disease can affect any age group, including pediatric
Sites
  • Skin, bone marrow, lymph nodes and spleen are most common but any anatomic site can be involved
  • CSF involvement at presentation in up to 10% of patients, more at relapse (Oncotarget 2016;7:10174)
Pathophysiology
  • Postulated cell of origin is pDC, which plays an important role in bridging the innate and adaptive immune systems (Curr Hematol Malig Rep 2018;13:477)
  • Monoallelic and biallelic 12p / ETV6 deletions seem to represent an early pathogenic event (Leuk Res 2018;73:86)
  • BPDCN specific transcriptional network regulated by the E-box transcription factor TCF4 (also known as E2-2) that plays a master regulatory role in BPDCN cells and appears to be in turn regulated by the bromodomain and extraterminal domain (BET) protein BRD4 (Cancer Cell 2016;30:764)
  • Epigenetic dysregulation is very common and results from mutations in genes involved in DNA methylation, histone methylation and chromatin remodeling (Haematologica 2019;104:729)
  • Frequent NR3C1 haploinsufficiency linked to aberrant overexpression of a novel long noncoding RNA (lncRNA) gene, lincRNA-3q, whose product is involved in G1/S cell cycle transition through E2F (Blood 2016;127:3040)
  • BPDCN cells are highly dependent on BCL2 for survival (Cancer Discov 2017;7:156)
  • Neoplastic cells in BPDCN have features of nonactivation state and seem to arise in a background of immunodeficiency (Blood Cancer J 2019;9:99)
Etiology
  • No known etiology
  • Frequent association with other myeloid malignancies, including chronic myelomonocytic leukemia and myelodysplastic syndrome
  • No bacterial or viral pathogen (Blood Adv 2020;4:1006)
Diagrams / tables

Contributed by Joseph Khoury, M.D.
Markers expressed by pDCs

Markers expressed by pDCs

Clinical features
  • Skin lesions, with heterogeneous manifestations of bruise-like, violaceous maculopapular lesions, nodules, plaques or exanthema
  • ~10% of patients have an overt leukemic presentation (Am J Hematol 2013;88:1055)
  • B symptoms
  • Lymphadenopathy
  • Splenomegaly
Diagnosis
  • Malignant infiltrate of blastoid cells; need to distinguish from mature pDC proliferations (MPDCP)
  • Confirmation of pDC immunophenotype by flow cytometry or immunohistochemistry
  • Cytogenetic and molecular studies usually not required for diagnosis
Laboratory
  • Cytopenias are common but some patients have normal CBC findings
Prognostic factors
  • No known pathologic or molecular prognostic factors
Case reports
  • 62 year old woman with BPDCN exhibiting unusual lymphoid features and macrovacuoles (Ann Hematol 2019;98:2221)
  • 63 year old man with disseminated blastic plasmacytoid dendritic cell neoplasm (Blood 2015;126:558)
Treatment
  • Tagraxofusp, a CD123 targeted immunotoxin, is the first FDA approved treatment for BPDCN (N Engl J Med 2019;380:1628)
  • ALL type induction chemotherapy regimens are associated with better outcomes compared with AML type regimens
  • Allogeneic stem cell transplant is recommended for patients who achieve first complete remission and are fit (Hematol Oncol Clin North Am 2020;34:621)
Microscopic (histologic) description
  • Diffuse infiltrate seen on bone marrow biopsy (trephine) and clot preparation with replacement of hematopoietic elements
  • On Wright-Giemsa preparations, the neoplastic cells are elongated with a tapered lightly basophilic agranular cytoplasm that ends with a tail shaped structure; the nucleus has blastoid features with open chromatin and a prominent nucleolus
  • In some cases, neoplastic cells have cytoplasmic microvacuoles with a peculiar arrangement along the cytosolic aspect of the cell membrane resembling a pearl necklace
  • Skin involvement is characterized by infiltrates of immature neoplastic cells with blastoid morphology involving the superficial and deep dermis, often with extension into the subcutis; the epidermis is typically spared; mitotic figures are usually identified readily
Microscopic (histologic) images

Contributed by Joseph Khoury, M.D.
Cytomorphology of BPDCN cells

Cytomorphology of BPDCN cells

Bone marrow involvement by BPDCN

Skin involvement by BPDCN Skin involvement by BPDCN

Skin involvement by BPDCN


TCF4 / CD123 dual color stain in bone marrow

TCF4 / CD123 dual color stain in bone marrow

 TCF4/CD123 dual color stain in skin

TCF4/CD123 dual color stain in skin

CD123

CD123

CD4

CD4

CD56

Positive stains
Negative stains
Flow cytometry description
  • 3 primary diagnostic aims (Haematologica 2020 Apr 2 [Epub ahead of print]):
    • Distinguish between BPDCN and other types of acute leukemia, mainly AML
    • Detect mature pDC proliferations in the context of other myeloid neoplasms, primarily chronic myelomonocytic leukemia
    • Detection of measurable / minimal residual disease (MRD)
  • Neoplastic cells fall into the blast gate on CD45 / SSC
  • Detection of MRD requires careful distinction between BPDCN cells and nonneoplastic pDCs
Flow cytometry images

Contributed by Joseph Khoury, M.D.
Flow cytometry findings in BPDCN

Flow cytometry findings in BPDCN

Molecular / cytogenetics description
  • Complex karyotype is common
  • Many adult patients have MDS associated chromosomal abnormalities and gene mutational profile
  • Gene rearrangements detected commonly: ETV6, MYC
  • Structural chromosomal losses, commonly involving 13q14 (RB1), 9p21.3 (CDKN2A/CDKN2B), 12p13.2-p13.1 (CDKN1B, ETV6), 7p12.2 (IKZF1)
  • Mutations detected commonly: TET2, ASXL1, IDH1, IDH2, DNMT3A, EZH2, SF3B1, SRSF2, ZRSR2, FLT3, KIT, KRAS, NRAS
Sample pathology report
  • Bone marrow, aspiration, clot and core biopsy:
    • Diagnosis: blastic plasmacytoid dendritic cell neoplasm (see comment)
    • Comment:
      • Immunohistochemistry: positive for TCF4 / CD123 coexpression
      • Flow cytometry: large population of neoplastic cells, positive for CD123, CD4, CD56, CD303 (decreased), HLA-DR and TdT; negative for CD3 (surface and cytoplasmic), CD19 and myeloperoxidase
      • Karyotype: 48, XY, t(6;8)(p12;q24.2), add(7)(p11.2), del(13)(q12q22), +16, add(20)(q11.2), +21[10]/46, XY[10]
      • Mutation profile: ASXL1, TET2, NRAS
Differential diagnosis
Board review style question #1
Which of the following immunophenotypic markers is typically negative in blastic plasmacytoid dendritic cell neoplasm?

  1. CD56
  2. CD123
  3. CD3
  4. CD4
  5. CD45
Board review answer #1
C. CD3. All others are typically positive in BPDCN but can also be positive in other neoplasms including acute myeloid leukemia.

Comment Here

Reference: Blastic plasmacytoid dendritic cell neoplasm
Board review style question #2
Which of the following dual stains are specific and sensitive for differentiating blastic plasmacytoid dendritic cell neoplasm from acute leukemia, both of which may show overlapping features?

  1. CD56 and CD4
  2. CD123 and TCF4
  3. CD123 and CD19
  4. TCF4 and MPO
  5. TCL1 and CD3
Board review answer #2
B. CD123 and TCF4. Highly sensitive and specific tool for differentiating blastic plasmacytoid dendritic cell neoplasm from acute leukemia.

Comment Here

Reference: Blastic plasmacytoid dendritic cell neoplasm
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