Plasmacytoid dendritic cell proliferations and neoplasms involving the bone marrow

Alexandar Tzankov, Konnie Hebeda, Markus Kremer, Roos Leguit, Attilio Orazi, Jon van der Walt, Umberto Gianelli

Two distinct forms of neoplasms derived from plasmacytoid dendritic cells (PDC) exist: mature PDC proliferations associated with myeloid neoplasms and blastic PDC neoplasms (BPDCN). Ten cases of PDC proliferations and neoplasms in the bone marrow have been submitted to the bone marrow workshop held at the 18th EAHP meeting. Based on observations from the submitted cases, scattered PDC (≤1% of cells) and PDC aggregates (≤10 PDC/HPF) reflect the normal bone marrow composition, while in myelodysplastic syndromes (MDS), there is a propensity for larger/more PDC aggregates (1-5% and 35 PDC/HPF). A shared PTPN11 mutation between a mature PDC proliferation and an accompanying MDS provides evidence of clonal relationship in such instances and shows that PDC are a part of the malignant clone. CD123 and CD303 should be considered backbone markers to histopathologically establish the diagnosis of BPDCN, since they are detectable in almost all cases and properly well on biopsies subjected to different fixations. Expression of some T-cell markers (e.g., CD2 and CD7 but not CD3), B-cell markers (e.g., CD79a but not CD19 and CD20), and myeloid markers (e.g., CD33 and CD117 but not myeloperoxidase) can be observed in BPDCN. Genetical data of the summarized cases corroborate the important role of chromosomal losses in BPDCN. Together with five previously reported instances, one additional workshop case with MYC rearrangement proposes that translocations of MYC may be recurrent. The frequent nature of deleterious mutations of IKZF3 and deletions of IKZF1 suggests a role for the Ikaros family proteins in BPDCN.