PMC6174068_01
Bone marrow at presentation (MDS) and skin lesions after transformation (BPDCN). Photomicrographs of bone marrow core biopsy specimens at presentation show a erythroid-predominant trilineage hematopoiesis and dysplastic megakaryopoiesis with an increased number of small monolobated megakaryocytes (H&E x400), and b megakaryocytes with widely separated nuclear lobes (Giemsa, x1000). c Photographs show violaceous plaques on the abdomen at BPDCN diagnosis, including a truncal skin lesion on the central abdomen demarcated with blue ink, enlarged for inset. Photomicrographs of skin biopsy of the abdominal lesion showing d extensive dermal infiltrate of immature-appearing mononuclear cells (H&E x40), and e infiltrate that is uniformly and strongly positive for CD123 (immunohistochemistry with hematoxylin counterstain, x20). f Photograph of same abdominal area showing resolving lesions after 1 month of CD123-targeted therapy with SL-401
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Fig1
A BM core biopsy and aspiration on initial evaluation demonstrated hypercellular marrow with trilineage dysplasia, moderate reticulin fibrosis, and 2% blasts (Fig. 1a, b). After 1 year of decitabine treatment, he experienced increasing fatigue and developed scattered violaceous plaques on his abdomen, upper chest, and forearms (Fig. 1c) in addition to bilateral discoloration of the inferior conjunctiva. Biopsy of an abdominal wall lesion showed BPDCN skin involvement (Fig. 1d, e). After 1 cycle, he experienced a decrease in BM blasts to 22%, resolution of skin lesions (Fig. 1f) and ophthalmic lesions, and marked improvement in performance status.
Emergence of aberrant CD123+ CD56+ CD4+ and HLA-DR + cells during the treatment period for MDS. Flow cytometry dot plots are shown for 3 longitudinal bone marrow aspirate samples: at presentation (top panel), after six courses of oral decitabine (middle panel), and at the time of fully developed BPDCN (bottom panel). The y-axis for each plot shows CD123 expression, and the x-axis shows HLA-DR, CD4 and CD56 from left to right, respectively. At presentation, the majority of PDCs had an unremarkable immunophenotype (CD123bright/HLA-DR+/CD4+/CD56-). In the interim marrow, there is the emergence of a minor, but more prominent population of aberrant PDCs that are CD56+ (0.79%). At diagnosis, a large population of CD123+ CD4+ CD56+ cells has become clearly evident
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Fig2
HLA-DR+, CD56- immunophenotype were 0.2% of all analyzed cells (Fig. 2, top panel). Cytogenetic studies showed a normal diploid karyotype, and no mutations were identified on next-generation sequencing of 28 leukemia-associated genes. He was treated on clinical protocol with oral decitabine and had decreased transfusion requirements. Flow cytometry of a surveillance BM aspirate sample approximately 8 months after decitabine initiation showed the emergence of a minimal population of aberrant plasmacytoid dendritic cells (CD123bright, CD4+, HLA-DR+, CD56+), comprising 0.79% of cells (Fig. 2, middle panel). These cells were CD4+, HLA-DR+, CD56+, CD34-, CD117-, CD64-, CD14-, and made up 35% of analyzed events (Fig. 2, bottom panel).