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.
Pilichowska
Monika E
ME
Brigham and Women's Hospital and Harvard Medical School, boston, MA 02115, USA.
Fleming
Mark D
MD
Pinkus
Jack L
JL
Pinkus
Geraldine S
GS
D000293:Adolescent; D000368:Aged; D015704:CD4 Antigens / Q000378:metabolism*; D019002:CD56 Antigen / Q000378:metabolism*; D003713:Dendritic Cells / Q000378:metabolism; D005260:Female; D019204:GTP-Binding Proteins / Q000032:analysis; D006801:Humans; D016130:Immunophenotyping; D037181:Lectins, C-Type / Q000378:metabolism*; D008228:Lymphoma, Non-Hodgkin / Q000175:diagnosis* / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008875:Middle Aged; D064547:Myxovirus Resistance Proteins; D011971:Receptors, Immunologic / Q000378:metabolism*
D015704:CD4 Antigens; D019002:CD56 Antigen; C443299:CLEC4C protein, human; D037181:Lectins, C-Type; C579071:MX1 protein, human; D008562:Membrane Glycoproteins; D064547:Myxovirus Resistance Proteins; D011971:Receptors, Immunologic; D019204:GTP-Binding Proteins