Stains & CD markers
CD123
Copyright: 2002-2024, PathologyOutlines.com, Inc.
PubMed Search: CD123
CD123
Authors: Narittee Sukswai, M.D., Joseph Khoury, M.D.
Editorial Board Members: Christian M. Schürch, M.D., Ph.D., Patricia Tsang, M.D., M.B.A.
Last author update: 15 August 2022
Last staff update: 15 August 2022
Copyright: 2002-2024, PathologyOutlines.com, Inc.
PubMed Search: CD123
Table of Contents
Definition / general | Essential features | Terminology | Pathophysiology | Clinical features | Interpretation | Uses by pathologists | Prognostic factors | Microscopic (histologic) images | Positive staining - normal | Positive staining - disease | Negative staining | Board review style question #1 | Board review style answer #1Cite this page: Sukswai N, Khoury J. CD123. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/cdmarkerscd123.html. Accessed April 24th, 2024.
Definition / general
- Interleukin 3 receptor alpha chain (IL3Rα)
- Upregulated and overexpressed in a variety of myeloid and lymphoid neoplasms
- CD123 is a biomarker for targeted therapy
Essential features
- CD123 serves as a diagnostic, prognostic and therapeutic marker in some hematologic malignancies, especially acute leukemia
- CD123 and TCF4 coexpression by immunohistochemistry is highly specific and sensitive for blastic plasmacytoid dendritic cell neoplasm (BPDCN)
- Tagraxofusp (SL-401) is a CD123 targeted therapy for BPDCN
Terminology
- IL3Rα
Pathophysiology
- Membrane receptor that heterodimerizes with the β common (βc) subunit to constitute the functional IL3 receptor (IL3R)
- IL3R is the IL3 specific member of the beta βc family of receptors, which also includes IL5R and granulocyte monocyte colony stimulating factor (GM CSF) receptor
- Functions in regulating growth, proliferation, survival and differentiation of hematopoietic cells, along with immunity and inflammatory response
- Downstream signaling is primarily through JAK / STAT, RAS / MAPK and phosphatidylinositol 3 kinase pathways (Cancers (Basel) 2020;12:3087)
Clinical features
- CD123 is a biomarker for targeted therapy in certain diseases, including blastic plasmacytoid dendritic cell neoplasm (BPDCN), acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) (N Engl J Med 2019;380:1628, Clin Cancer Res 2017;23:3385, Haematologica 2019;104:749)
Interpretation
- Strongest level of CD123 staining is on plasmacytoid dendritic cells
- CD123 is expressed by endothelial cells
- CD123 is a membrane bound protein, resulting in a membranous pattern of staining by immunohistochemistry and surface expression by flow cytometry
- CD123 expression in normal karyotype AML is associated with FLT3-ITD and NPM1 mutations (Br J Haematol 2020;188:181)
- Reference: Am J Surg Pathol 2019;43:1429
Uses by pathologists
- Blastic plasmacytoid dendritic cell neoplasm (BPDCN) (Am J Surg Pathol 2019;43:1429)
- Mature plasmacytoid dendritic cell proliferations (Curr Hematol Malig Rep 2018;13:477)
- Systemic mastocytosis (Leukemia 2016;30:914)
- Hairy cell leukemia (Am J Clin Pathol 2011;136:625)
- Increased plasmacytoid dendritic cells in Kikuchi lymphadenitis and discoid (cutaneous) lupus erythematosus
Prognostic factors
- Prognostic impact of CD123 expression has not been established
Microscopic (histologic) images
Contributed by Joseph Khoury, M.D.
Tonsil
Blastic plasmacytoid dendritic cell neoplasm
Positive staining - normal
- Hematopoietic stem cells
- Endothelial cells
- Plasmacytoid dendritic cells
Positive staining - disease
- Blastic plasmacytoid dendritic cell neoplasm (BPDCN), with marked enhancement in specificity when used alongside TCF4, CD4, CD56, TCL1 and CD303, though CD303 can be negative in up to 56% (Am J Surg Pathol 2019;43:1429, Am J Surg Pathol 2014;38:673, Haematologica 2021;106:1047, Blood Adv 2019;3:4238)
- Mature plasmacytoid dendritic cell proliferations
- Systemic mastocytosis (Leukemia 2016;30:914)
- Hairy cell leukemia
- Acute myeloid leukemia (AML) subset, typically negative for TCF4 and positive for lineage markers
- Rare B cell acute lymphoblastic leukemia (B ALL) cases
Negative staining
- Lymphoma, including most cases of chronic lymphocytic leukemia (CLL), mantle cell lymphoma, follicular lymphoma and mycosis fungoides (Biomark Res 2014;2:4, Postepy Dermatol Alergol 2021;38:994)
- Hairy cell leukemia variant and splenic marginal zone lymphoma with villous lymphocytes (Biomark Res 2014;2:4)
- Carcinoma
- Various soft tissue neoplasms
- Merkel cell carcinoma
Board review style question #1
Patient presents with a skin tumor comprised of blastoid neoplastic cells involving the dermis and subcutaneous tissue without epidermotropism. Which immunohistochemical profile suits the diagnosis of blastic plasmacytoid dendritic cell neoplasm?
- AE1 / AE3 positive, chromogranin positive
- CD21 positive, CD23 positive
- CD34 positive, MPO positive
- TCF4 / CD123 positive, CD4 positive, CD56 positive, CD303 positive
Board review style answer #1
D. TCF4 / CD123 dual expression is highly sensitive and specific for blastic plasmacytoid dendritic cell neoplasm. Such staining is rarely encountered in other malignancies.
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Reference: CD123
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Reference: CD123
