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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.

Expression of the plasmacytoid dendritic cell marker BDCA-2 supports a spectrum of maturation among CD4+ CD56+ hematodermic neoplasms