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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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Submitted October 12, 2007
Accepted January 5, 2008

Novel markers of normal and neoplastic human plasmacytoid dendritic cells

Teresa Marafioti*, Jennifer C Paterson, Erica Ballabio, Kaaren K Reichard, Sara Tedoldi, Kevin Hollowood, Michael Dictor, Martin-Leo Hansmann, Stefano A Pileri, Martin J Dyer, Silvano Sozzani, Ivan Dikic, Andrey S Shaw, Tony Petrella, Harald Stein, Peter G Isaacson, Fabio Facchetti, and David Y Mason

Leukaemia Research Fund Immunodiagnostics Unit, Nuffield Department of Clinical Laboratory Sciences, John Radcliffe Hospital, Oxford, United Kingdom
Department of Pathology, University of New Mexico, Albuquerque, NM, United States
Department of Cellular Pathology, John Radcliffe Hospital, Oxford, United Kingdom
Department of Pathology, Lund University Hospital, Lund, Sweden
Senckenberg Pathology Institute, Johann Wolfgang Goethe-University Clinic Frankfurt am Main, Frankfurt am Main, Germany
Haematopathology, "L&A Seragnoli" Institute of Haematology, University of Bologna, Bologna, Italy
MRC Toxicology Unit, University of Leicester, Leicester, United Kingdom
Department of Pathology and General Pathology, University of Brescia, Brescia, Italy
Institute of Biochemistry II, Goethe University School of Medicine, University Clinic Frankfurt am Main, Frankfurt am Main, Germany
Department of Pathology, Washington University School of Medicine, St. Louis, MO, United States
Department of Pathology and Centre of Pathology, Hospital-University Centre, Dijon, France
Institute for Pathology, Campus Benjamin Franklin, Charite University Medicine Berlin, Berlin, Germany
Department of Pathology, University College London, London, United Kingdom

* Corresponding author; email: teresa.marafioti{at}ndcls.ox.ac.uk.

Plasmacytoid dendritic cells (pDC) are involved in innate immunity (e.g. by secreting interferons) and also give rise to "CD4+CD56+ hematodermic neoplasms". We report extensive characterisation of human pDC in routine tissue samples, documenting the expression of 19 immunohistologic markers, including signaling molecules (e.g. BLNK), transcription factors (e.g. ICSBP/IRF8 and PU.1) and Toll-like receptors (TLR7 and TLR9). Many of these molecules are expressed in other cell types (principally B cells), but the adaptor protein CD2AP was essentially restricted to pDC, 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 pDC are greatly increased (e.g. Kikuchi's disease). Most of the molecules were retained in the majority of pDC neoplasms, and three (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 pDC in tissues and peripheral blood (where pDC 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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