title: Expression of the plasmacytoid dendritic cell marker BDCA-2 supports a spectrum of maturation among CD4+ CD56+ hematodermic neoplasms.
abstract: CD4+CD56+ hematodermic neoplasms are rare, aggressive hematopoietic malignancies usually presenting with cutaneous masses followed by a leukemic phase. The blastic morphology, CD56 expression and lack of definitive myeloid or T-cell markers initially resulted in assignment of this tumor to the NK-cell lineage. Accumulating evidence now suggests that these neoplasms represent malignant counterparts to the plasmacytoid dendritic cell. BDCA-2 is a cell surface protein whose expression is restricted to human plasmacytoid dendritic cells, in a differentiation stage-specific manner. In the current study, we assessed expression of BDCA-2 in CD4+CD56+ hematodermic neoplasms using a new antibody reagent we developed for use in fixed tissue sections. In 10 of 19 cases of CD4+CD56+ hematodermic neoplasm, BDCA-2 immunoreactivity was detected, whereas no expression was observed in NK-lineage tumors (0 of six). Interestingly, expression of terminal deoxynucleotidyl transferase, a marker of immaturity/blast stage, was significantly and negatively correlated with BDCA-2 in CD4+CD56+ hematodermic neoplasms whereas a positive correlation was observed between BDCA-2 and CD7. These findings demonstrate that BDCA-2 is expressed predominantly in the CD7+ subset of hematodermic neoplasms, and similar to non-neoplastic plasmacytoid dendritic cells, expression indicates a relatively more mature differentiation state. Clinical follow-up data confirm the aggressiveness of these tumors and suggests that BDCA-2 immunoreactivity, as identified here, may herald a significant reduction in survival.
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA. dljaye@emory.edu
authors.forename: David L
authors.initials: DL
authors.lastname: Jaye
authors.forename: Cissy M
authors.initials: CM
authors.lastname: Geigerman
authors.forename: Marco
authors.initials: M
authors.lastname: Herling
authors.forename: Karen
authors.initials: K
authors.lastname: Eastburn
authors.forename: Edmund K
authors.initials: EK
authors.lastname: Waller
authors.forename: Dan
authors.initials: D
authors.lastname: Jones
mesh_terms: D000951:Antigens, Neoplasm / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism; D015704:CD4 Antigens / Q000378:metabolism*; D019002:CD56 Antigen / Q000378:metabolism*; D004253:DNA Nucleotidylexotransferase / Q000378:metabolism; D003713:Dendritic Cells / Q000378:metabolism* / Q000473:pathology; D019085:Fluorescent Antibody Technique, Direct; D006801:Humans; D007124:Immunoenzyme Techniques; D007694:Killer Cells, Natural / Q000473:pathology; D037181:Lectins, C-Type / Q000378:metabolism*; D008228:Lymphoma, Non-Hodgkin / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008562:Membrane Glycoproteins / Q000378:metabolism*; D010950:Plasma Cells / Q000378:metabolism* / Q000473:pathology; D011971:Receptors, Immunologic / Q000378:metabolism*; D012878:Skin Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D015996:Survival Rate
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D015704:CD4 Antigens; D019002:CD56 Antigen; C443299:CLEC4C protein, human; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; D004253:DNA Nucleotidylexotransferase