Mature plasmacytoid dendritic cell proliferation associated with acute myeloid leukemia

A 72-year-old man with known essential thrombocythaemia (ET) with JAK2 p. V617F mutation, treated with hydroxyurea, was referred to the hematologist by the general practitioner. The man presented with recently emerged dizziness, night sweats and significant weight loss exceeding 10 kilograms over several months. Peripheral blood examination showed anemia (hemoglobin 9. 6 g/dL; ref: 13. 5–17 g/dL), mild leukopenia (3. 9 × 109/L; ref: 4. 3–9. 6 × 109/L), thrombocytopenia (125 × 109/L; ref: 163–347 × 109/L) and 10% blasts. A bone marrow punction was performed. Microscopic examination of the bone marrow aspirate revealed 41% blast-like cells. Two different populations could vaguely be discerned, although with much overlap: a first population of medium to large cells (4–6 RBC in size), with fine chromatin and without granulation, and a second population of smaller cells (3 RBC in size), with more mature chromatin and often pseudopodia (Figure 1A). Likewise, flow cytometric analysis revealed two populations: an immature myeloblast cell population (15% of total WBC), characterized by expression of cyCD3-/sCD3-/CD4-/CD7+bright/CD13+/CD19-/CD34+/CD43+/CD45+/CD56-/CD117+/CD123+/HLADR+bright/cyMPO-/cyTCL1- and a second population (20% of total WBC) with immunophenotype cyCD3-/sCD3-/CD4+low/CD7+bright/CD13-/CD19-/CD34+low/CD43+/CD45+/CD56-/CD117-/CD123+bright/HLADR+bright/cyMPO-/cyTCL1- (Figure 2). Based on morphological features and expression of CD4+low/CD56-/CD123+bright/cTCL1-, the second population was identified as mature plasmacytoid dendritic cells and a diagnosis of mature plasmacytoid dendritic cell proliferation (MPDCP) associated with acute myeloid leukemia (AML-M0) was established. This was later confirmed by immunohistochemistry showing nodules of CD123+/CD34- cells (Figure 1B, C). Next Generation Sequencing (NGS) using a QiaSeq Targeted DNA custom panel was performed with the MiSeq system and revealed variants in several genes, including ASXL1 c. 1900₁922del p. (Glu635ArgfsTer15) (VAF: 35%), FLT3 c. 1788₁811dup p. (Tyr597Glu604dup), KIT c. 2447A>T p. (Asp816Val) (VAF: 10%) and RUNX1 c. 485G>A p. (Arg162Lys) (VAF: 84%). The absence of the JAK2 mutation in the AML-sample, made it impossible to formally distinguish between a blast phase of the previously treated ET and a de novo AML. Given the advanced age and comorbidities, venetoclax-azacitidine therapy was chosen. Following 4 cycles, morphological remission was initially attained. Unfortunately, however, the patient relapsed and passed away 7 months post-AML diagnosis. Plasmacytoid dendritic cells (pDCs) represent a specialized subset of dendritic cells known for their role in producing type I interferons, fostering antiviral immune responses, and their implication in autoimmune diseases. 1 In the 2022 WHO classification, neoplasms involving pDCs are categorized into two distinct types: blastic plasmacytoid dendritic cell neoplasm (BPDCN) and mature pDCs proliferation (MPDCP) associated with myeloid neoplasms. BPDCN is identified as a solitary hematological malignancy, often accompanied by skin lesions, and is diagnosed based on morphology alongside flow cytometry or immunohistochemistry employing the WHO 2022 updated immunophenotypic diagnostic criteria. Conversely, MPDCP is always associated with a myeloid neoplasm, predominantly chronic myelomonocytic leukemia (CMML), and less commonly myelodysplasia (MDS) or AML. MPDCP exhibits a more mature morphology with sometimes pseudopodia, unlike the blastic presentation of BPDCN. Immunophenotypically pDCs typically express CD123, CD4, CD303, CD304, and cyTCL1, while lacking CD3, CD14, CD19, and MPO expression. A recent study investigated 21 cases of BPDCN and 15 cases of AML patients with pDC expansion (pDC-AML). The authors conclude that the phenotype of MPDCP differs from that of BPDCN by absence of expression of CD56, higher expression of CD303, lower expression of cyTCL1, and the possible expression of CD34. 2 pDCs are clonally related to the leukemic blasts and pDC-AML is characterized by a high frequency of RUNX1 mutations (especially in AML-M0). 2, 3 However, there is still a need for in-depth research on the immunophenotype and genomic landscape of pDC-AML and its therapeutic and prognostic impact. Data sharing is not applicable to this article as no new data were created or analyzed in this study.