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Hematopoiesis
Immunophenotypic characterization of reactive and neoplastic plasmacytoid dendritic cells permits establishment of
a ten-color flow cytometric panel for initial workup and residual disease evaluation of blastic plasmacytoid dendritic cell neoplasm
Ferrata Storti Foundation
Haematologica 2021 Volume 106(4):1047-1055
Wei Wang,1 Joseph D. Khoury,1 Roberto N. Miranda,1 Jeffrey L. Jorgensen,1 Jie Xu,1 Sanam Loghavi,1 Shaoying Li,1 Naveen Pemmaraju,2 Than Nguyen,1 L. Jeffrey Medeiros1 and Sa A. Wang1
1Department of Hematopathology, The University of Texas MD Anderson Cancer Center, and 2Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
ABSTRACT
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematopoietic neoplasm whose immunophenotype remains incom- pletely characterized, particularly with regards to its distinction from reactive plasmacytoid dendritic cells (PDC). This limitation compli- cates detection of low-level involvement by BPDCN as well as minimal residual disease (MRD) assessment following therapy. We conducted the current study to characterize the immunophenotype of BPDCN in a cohort of 39 patients, and compared it to that of reactive PDC. We found that, in addition to CD56 expression (97%), BPDCN showed a number of aberrancies, including decreased/negative CD38 (82%), positive CD7 (64%), negative CD2 (81%), negative CD303 (56%), increased HLA-DR (69%) and decreased CD123 (78%) expression. Although BPDCN cells were characterized by CD56 expression, reactive PDC consistently included a CD56+ subset, ranging from 1.3%-20% (median 4.5%) of all PDC, challenging the detection of MRD. These CD56+ reactive PDC were, however, consistently positive for CD2 and CD303, brightly posi- tive for CD38, and negative for CD7, distinctively different from BPDCN. Based on these findings, we set up a ten-color flow cytometry assay for BPDCN and validated it to a sensitivity of 0.01%. This panel was prospectively tested in 19 bone marrow samples from seven patients with BPDCN, and it effectively distinguished BPDCN cells from background reactive PDC in all cases. In summary, by understanding the immunophe- notype of reactive and neoplastic PDC, BPDCN can be effectively detect- ed by flow cytometry to a very low level using a panel of markers in addi- tion to CD56. Such an assay could be used for initial bone marrow workup as well as MRD detection after therapy.
Introduction
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare, clinically aggres- sive neoplasm derived from non-activated precursors of plasmacytoid dendritic cells (PDC).1,2 Patients often present with a widespread disease involving multiple anatomic sites, most commonly the skin, followed by bone marrow (BM), periph- eral blood and lymph nodes.1,3-5 BPDCN can occur at any age, but mostly affects patients in their seventh decade of life.
The diagnosis of BPDCN relies on morphology in combination with immunophenotypic studies.6 BPDCN cells are medium-sized with immature chro- matin, resembling lymphoblasts or myeloblasts. They often show cytoplasmic vacuoles and pseudopodia, but these are neither sensitive nor specific features as they may also be present in a variety of other hematolymphoid neoplasms.7
Correspondence:
WEI WANG
wwang13@mdanderson.org
SA A. WANG
swang5@mdanderson.org
Received: January 16, 2020. Accepted: March 26, 2020. Pre-published: April 2, 2020.
https://doi.org/10.3324/haematol.2020.247569
©2021 Ferrata Storti Foundation
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