Plasmacytoid dendritic cell proliferations and neoplasms involving the bone marrow
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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.
KeywordsPlasmacytoid dendritic cells Neoplasm BPCDN Bone marrow biopsy EAHP workshop BCL2 CD123 CD303 Ikaros PTPN11 MYC
A.T. thanks Prof. Stephan Dirnhofer from the Institute of Pathology at the University Hospital of Basel for putting his immeasurable efforts to organize and host the 18th EAHP meeting in Basel; Petra Huber from the Institute of Pathology at the University Hospital of Basel for her inestimable logistic sustenance; and Rumyana Todorova, a talented young member of the European Bone Marrow Working Group, for her enthusiastic support at the initial examination of all cases submitted for the bone marrow workshops—such young people invigorate and inspire our working group.
The panel acknowledges the case submitters Dr. Corina Dommann-Scherrer from Winterthur, Switzerland (case 103); Dr. Jie Xu from Houston, USA (case 134); Dr. Juehua Gao from Chicago, USA (case 143); Dr. Lauren Smith from Ann Arbor, USA (case 190); Dr. Vathany Sriganeshan from Miami, USA (case 222); Dr. Raymond E. Felgar✞ from Pittsburgh, USA (case 272); Dr. Prashanti Reddy from Carlsbad, USA (case 296); Dr. Konnie Hebeda from Nijmegen, the Netherlands (case 303); Dr. Alexandar Tzankov from Basel, Switzerland (case 310); and Dr. Rahul Matnani from New York, USA (case 184).
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Conflict of interest
The authors declare that they have no conflict of interest.
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