CD4+/CD56+ hematodermic neoplasm ("blastic natural killer cell lymphoma"): neoplastic cells express the immature dendritic cell marker BDCA-2 and produce interferon.

CD4+/CD56+ hematodermic neoplasm ("blastic natural killer [NK]-cell lymphoma") is a rare highly aggressive neoplasm associated with cutaneous manifestations followed by dissemination to blood, bone marrow, and other tissues. Neoplastic cells exhibit a lineage-negative CD4+/CD56+/CD43+/HLA-DR+ immunophenotype, initially suggesting an NK-cell derivation. The recent discovery of CD123 antigen expression by tumor cells has provided evidence for a relationship to immature dendritic cells (DCs), a group of myeloid and lymphoid early-committed progenitors capable of differentiating into antigen-presenting DCs. Based on flow cytometric analysis, myeloid DCs represent the majority of human peripheral blood DCs and are positive for blood dendritic cell antigen (BDCA)-1 (or CD1c), CD13, CD11c(high), CD33, and CD123(low). Plasmacytoid DCs are BDCA-2+/ CD123(high)+/CD13-/CD33- and produce interferon (IFN)-alpha when triggered by antigens. IFN-alpha production may be detected in tissue sections using antibodies for myxovirus A (MxA) protein, a surrogate marker. This report describes the clinical, histologic, immunophenotypic, cytogenetic, and molecular genetic findings for 3 cases of CD4+/CD56+ hematodermic neoplasms. In all cases, neoplastic cells were reactive for CD123, BDCA-2, and MxA protein, providing strong evidence for an immature plasmacytoid DC derivation for this rare neoplasm.