A man in his 60s with no significant past medical history presented with fever, shortness of breath, severe pancytopenia (hemoglobin, 50 g/L, platelet, 9 × 109/L, neutrophil, 0.1 × 109/L) and circulating unclassified cells. Bone marrow aspirate smears revealed a predominance of two mononuclear cell populations: a population of blasts with round nuclei, dispersed chromatin, prominent nucleoli and scant cytoplasm, and a second population of cells with oval nuclei and elongated blue cytoplasmic pseudopods, morphologically compatible with plasmacytoid dendritic cells (pDCs) (Figure 1A–C). Dysplastic megakaryocytes were present. Blasts comprised approximately 40% of the marrow cellularity by CD34 immunostain (Figure 1D) and were positive for CD117 (Figure 1E), CD123 (moderate, Figure 1F), CD19 (moderate, Figure 1G), CD79a (dim/minor subset), myeloperoxidase (subset, Figure 1H), lysozyme (subset), and CD4 (dim/subset, Figure 1I), and negative for CD10 and CD20. pDCs comprised approximately 50% of the cellularity with bright expression of CD123 (Figure 1F), and were positive for CD4 (bright, Figure 1I), and CD19 (dim, Figure 1G), and negative for CD34 (Figure 1D), CD117 (Figure 1E), myeloperoxidase (Figure 1H), and lysozyme. Both populations were negative for CD56 (Figure 1J) and TCL1. Interestingly, pDCs formed sheets that were spatially separated from the sheets of blasts. Cytogenetic study showed a trisomy 11. Next-generation sequencing revealed mutations in RUNX1 (variant allele frequency (VAF), 34%), U2AF1 (VAF, 48%), and FLT3-ITD (allele ratio, 0.970). Expression of B-lymphoid markers was insufficient for a mixed phenotype classification, and a diagnosis of acute myeloid leukemia with pDC expansion (pDC-AML) was established. pDC-AML is defined by pDC differentiation more than 2% of the marrow elements 1 and is characterized by a high frequency of RUNX1 alterations 1-3 and poor prognosis 1. Other common mutations in pDC-AML include ASXL1, DNMT3A, SRSF2, BCOR, NRAS, FLT3, TET2, PHF6, IDH1, SF3B1, and TP53 1, 2. The frequency of pDCs can be variable, ranging from 2% to 36%, with a median of approximately 7% 1-3, and they often show interstitial distribution intermixed with blasts 1, 2. Here we report an unusual case of pDC-AML with florid pDC proliferation in sheets that are spatially separated from the sheets of blast. In addition to the RUNX1 mutation, the leukemia harbored FLT3-ITD mutation that has been linked with increased pDC frequency in AML. We noted an unusual expression of CD19 both on blasts (strong) and pDCs (dim). Cross-lineage expression of B and T lymphoid markers such as cytoplasmic CD3, CD5, CD7, CD19, and cytoplasmic CD79a is commonly seen in pDC-AML 1-3 with these markers are typically expressed at lower intensity on pDCs compared with blasts 3. It has been shown that up to 20% of pDC-AML cases meet the immunophenotypic criteria for mixed phenotype acute leukemia 1. Importantly, the immunophenotype of pDCs in pDC-AML is distinct from that of blastic plasmacytoid dendritic cell neoplasm by common expression of CD34 and absence of CD56 and TCL1 expression 2. The authors have nothing to report. The authors declare no conflicts of interest. The data that support the findings of this study are available from the corresponding author upon reasonable request.
Shameli et al. (Wed,) studied this question.