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Blood, 1 April 2008, Vol. 111, No. 7, pp. 3778-3792.
Prepublished online as a Blood First Edition Paper on January 24, 2008; DOI 10.1182/blood-2007-10-117531.


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NEOPLASIA

Novel markers of normal and neoplastic human plasmacytoid dendritic cells

Teresa Marafioti1, Jennifer C. Paterson1, Erica Ballabio1, Kaaren K. Reichard2, Sara Tedoldi1, Kevin Hollowood3, Michael Dictor4, Martin-Leo Hansmann5, Stefano A. Pileri6, Martin J. Dyer7, Silvano Sozzani8, Ivan Dikic9, Andrey S. Shaw10, Tony Petrella11, Harald Stein12, Peter G. Isaacson13, Fabio Facchetti8, and David Y. Mason1

1 Leukaemia Research Fund Immunodiagnostics Unit, Nuffield Department of Clinical Laboratory Sciences, John Radcliffe Hospital, Oxford, United Kingdom; 2 Department of Pathology, University of New Mexico, Albuquerque, NM; 3 Department of Cellular Pathology, John Radcliffe Hospital, Oxford, United Kingdom; 4 Department of Pathology, Lund University Hospital, Lund, Sweden; 5 Senckenberg Pathology Institute, Johann Wolfgang Goethe-University Clinic Frankfurt am Main, Frankfurt am Main, Germany; 6 Haematopathology Unit, "L&A Seragnoli" Institute of Haematology, University of Bologna, Bologna, Italy; 7 Medical Research Council Toxicology Unit, University of Leicester, Leicester, United Kingdom; 8 Department of Pathology and General Pathology, University of Brescia, Brescia, Italy; 9 Institute of Biochemistry II, Goethe University School of Medicine, University Clinic Frankfurt am Main, Frankfurt, Germany; 10 Department of Pathology, Washington University School of Medicine, St Louis, MO; 11 Department of Pathology and Centre of Pathology, Hospital-University Centre, Dijon, France; 12 Institute for Pathology, Campus Benjamin Franklin, Charité University Medicine Berlin, Berlin, Germany; and 13 Department of Pathology, University College London, London, United Kingdom

Plasmacytoid dendritic cells (pDCs) are involved in innate immunity (eg, by secreting interferons) and also give rise to CD4+CD56+ hematodermic neoplasms. We report extensive characterization of human pDCs in routine tissue samples, documenting the expression of 19 immunohistologic markers, including signaling molecules (eg, BLNK), transcription factors (eg, ICSBP/IRF8 and PU.1), and Toll-like receptors (TLR7, TLR9). Many of these molecules are expressed in other cell types (principally B cells), but the adaptor protein CD2AP was essentially restricted to pDCs, and is therefore a novel immunohistologic marker for use in tissue biopsies. We found little evidence for activation-associated morphologic or phenotypic changes in conditions where pDCs are greatly increased (eg, Kikuchi disease). Most of the molecules were retained in the majority of pDC neoplasms, and 3 (BCL11A, CD2AP, and ICSBP/IRF8) were also commonly negative in leukemia cutis (acute myeloid leukemia in the skin), a tumor that may mimic pDC neoplasia. In summary, we have documented a range of molecules (notably those associated with B cells) expressed by pDCs in tissues and peripheral blood (where pDCs were detectable in cytospins at a frequency of < 1% of mononuclear cells) and also defined potential new markers (in particular CD2AP) for the diagnosis of pDC tumors.


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