CD103 Expression on Blastic Plasmacytoid Dendritic Cell Neoplasms in Peripheral Blood and Bone Marrow Samples

Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) is an aggressive neoplasm with distinctive immunophenotypic features and limited treatment options. Case reports and reviews typically describe BPDCN as CD4+, CD56+, and CD123+, but there is limited and confl icting literature regarding CD103 expression on BPDCN. Here we report our experience with CD103 expression on cases of BPDCN in peripheral blood and bone marrow samples. To our knowledge, this is the only series of such cases specifi cally characterizing CD103 expression on BPDCN. This information may be useful with respect to the diagnosis, prognosis, and/or treatment of BPDCN (e.g. antiCD103 therapy).


Introduction
Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) is an aggressive neoplasm with distinctive immunophenotypic features and limited treatment options. Case reports and reviews typically describe BPDCN as CD4+, CD56+, and CD123+, but there is limited and confl icting literature regarding CD103 expression on BPDCN. Here we report our experience with CD103 expression on cases of BPDCN in peripheral blood and bone marrow samples. To our knowledge, this is the only series of such cases specifi cally characterizing CD103 expression on BPDCN. This information may be useful with respect to the diagnosis, prognosis, and/or treatment of BPDCN (e.g. anti-CD103 therapy).

Materials and methods
Cases of blastic plasmacytoid dendritic cell neoplasm were identifi ed by manual tracking and supplemented by using a word search for "blastic plasmacytoid dendritic" in either the Interpretation or Comment fi elds of completed fl ow cytometry reports for peripheral blood and bone marrow specimens. Six cases of peripheral blood and bone marrow samples submitted to our facility since 2015 were identifi ed which were consistent with blastic plasmacytoid dendritic cell neoplasm based on immunophenotypic, clinical, and morphologic fi ndings and had CD103 performed (all were CD4+, CD56+, CD123+). Tissue samples were excluded as CD103 was not performed on tissue samples.
Samples were processed according to standard accepted fl ow cytometry protocols. Multicolor fl ow cytometry was performed using an 8 color panel of Becton Dickinson antibodies with samples run on Becton Dickinson FCSCanto II fl ow cytometers ( Table 1). Analysis of data was performed with FSC express (De Novo Software) and WinList (Verity Software House) software.
For determination of CD103 expression, abnormal cells were gated using CD45 v SSC and CD4 v SSC; internal lymphocytes in the same tube were used for negative controls and confi rmed with another negative marker, CD23, in separate tubes ( Figures  1,2). The values were compared using the Student's T-test (Microsoft Offi ce Excel).
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Discussion
CD103 (HML-1, Integrin aE-subunit) functions as an adhesion molecule and has a role in cell signaling, adhesion and migration on T-cells [1,2]. It is expressed by intraepithelial T-cells, some peripheral regulatory T-cells, lamina propria T-cells, and a subset of normal dendritic cells [3][4][5][6][7]. With respect to neoplastic entities, it is typically expressed in cases of hairy cell leukemia, hairy cell variant, and enteropathic T-cell lymphoma but may also be seen in some cases of precursor T-cell neoplasms, large B-cell lymphoma, and B-cell prolymphocytic leukemia [8]. While the immunophenotypic of expression of CD4, CD56, and CD123 is well documented on blastic plasmacytoid dendritic cell neoplasms, literature regarding expression of CD103 is limited, some references refer to CD303 positivity, and there are reports which indicated absence of CD103 on blastic plasmacytoid dendritic cell neoplasms [9][10][11].
Normal dendritic cells play an important role in immunity as antigen presenting cells and modulators in immune responses. The cell of origin of blastic plasmacytoid dendritic cell neoplasms is presumed to be plasmacytoid dendritic cells based on the expression of certain markers, production of interferon, maturation capacity, and molecular profi ling [12].
As CD103 is expressed on a subset of normal dendritic cells, it is not surprising to fi nd the expression of CD103 on blastic plasmacytoid dendritic cell neoplasms.
Blastic plasmacytoid dendritic cell neoplasms are aggressive and typically treated with leukemia protocols such as an ALL-based regimen (HCVAD alternating with methotrexate and ARA-C) [13,14]. Anti-CD123 has been used and the FDA approved tagraxofusp-erzs (ELZONRIS, Stemline Therapeutics), a CD123-directed cytotoxin, for blastic plasmacytoid dendritic cell neoplasm (BPDCN) in adults and in pediatric patients 2 years and older on Dec 21, 2018. An anti-CD103 antibody drug conjugate has been used experimentally in mice but has not been used in humans [15]. Given our fi ndings, an anti-CD103 therapy may be worth exploring for cases of blastic plasmacytoid dendritic cell neoplasms demonstrated to be CD103+.