Plasmacytoid Dendritic Cell Proliferation Associated with Acute Myeloid Leukemia, Case Report and Review of Literature

Review Article

Ann Hematol Onco. 2023; 10(4): 1430.

Plasmacytoid Dendritic Cell Proliferation Associated with Acute Myeloid Leukemia, Case Report and Review of Literature

Qian YW¹*; Shalaby K²; Griffiths EA²; Fu K¹; Ali S¹

¹Department of Pathology, Roswell Park Cancer Institute, USA

²Department of Medicine, Roswell Park Cancer Institute, USA

*Corresponding author: You-Wen Qian Department of Pathology and Laboratory Medicine, Roswell Park Cancer Center, Basic Science Building, Room 529, Elm St and Carlton St, Buffalo, NY, 14203, USA. Tel: 716-845-2300x5631 Email: [email protected]

Received: June 06, 2023 Accepted: July 03, 2023 Published: July 10, 2023


We present a typical case of plasmacytoid dendritic cell proliferation associated with acute myeloid leukemia (pDC-AML). The patient was a 65-year-old male admitted for new onset progressive pancytopenia over the course of three weeks. Diagnostic marrow revealed 27% myeloblasts. In addition, flow cytometry and immunohistochemistry studies identified an 18% population of immature plasmacytoid dendritic cells. Baseline next-generation sequencing identified pathogenic mutations in ASXL1, EZH2, FLT3, and RUNX1. The patient underwent induction chemotherapy for a diagnosis of pDC-AML. One month after chemotherapy, evaluation for Measurable Residual Disease (MRD) using multiparameter flow cytometry was interpreted as negative with changes related to treatment.

pDC-AML is a newly described rare subtype of acute myeloid leukemia which can impose diagnostic challenges. Clinical, pathologic, and molecular correlation are important to render an accurate final diagnosis. We review the published literature on pDC-AML cases and discuss pDC biology, and the process for differentiating the diagnosis of pDC-AML from those of blastic plasmacytoid dendritic cell neoplasm or mature plasmacytoid dendritic cell proliferations associated with other myeloid neoplasms. The AML MRD evaluation for pDC-AML is a particular challenge. To this end, additional molecular studies, including MRD tests using next-generation sequencing, can be of great help.

Keywords: Acute myeloid leukemia; Flow cytometry; Immunophenotyping; Measurable/minimal residual disease; Plasmacytoid dendritic cells

Abbreviations: AML: Acute Myeloid Leukemia; DC: Dendritic Cell; Pdc: Plasmacytoid Dendritic Cell; Cdc: Classic/Conventional DC; MFC: Multiparameter Flow Cytometry; BPDCN: Blastic Plasmacytoid Dendritic Cell Neoplasm; MRD: Measurable/Minimal Residual Disease; IRF: Interferon Regulator Factors; CBC: Complete Blood Count; WBC: White Blood Cell; NGS: Next-Generation Sequencing; RPMI: Roswell Park Memorial Institute; PBS: Phosphate-Buffered Saline; MPDCP: Mature Plasmacytoid Dendritic Cell Proliferation; ICC: International Consensus Classification; WHO: World Health Organization; HSCT: Hematopoietic Stem Cell Transplantation; LAIP: Leukemia-Associated Immunophenotype; LLOD: Low Limit Of Detection


Recent studies describe a subtype of Acute Myeloid Leukemia (AML) that is associated with proliferation of Plasmacytoid Dendritic Cells (pDC). These pDCs can range from 2% to 36% of bone marrow cellularity and the entity has been named pDC associated AML (pDC-AML) [1-3]. Zalmai et al [1] compared 15 cases of pDC-AML with 21 cases of Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) using pDCs from 11 healthy donors as comparators. They concluded that the pDCs from pDC-AML are in the pre-DC stage and are phenotypically different from those seen in BPDCN. pDCs in pDC-AML carry the same mutations as those in mature monocytes and conventional dendritic cells. They also observed a high frequency of mutations in RUNX1 associated with these cases which are often minimally differentiated (previously described as the FAB M0-AML subtype). Xiao et al. [2] described an additional 26 cases of pDC-AML. They confirmed that the pDCs and myeloblasts are clonally related and share the same gene mutations. RUNX1 mutations were also observed in 70% of their cases. A third group, Wang et al. [3] described 53 cases of pDC-AML. They identified cases from their cohort using a cutoff of at least 2% pDCs and compared the immunophenotypic and molecular features of pDC-AML with cases of BPDCN. The pDCs from pDC-AML are more likely to express CD34 (96% vs 0%) and less likely to express CD56 (8% vs 97%) and TCL1 (12% vs 98%) compared with pDCs from patients with BPDCN. Molecularly, RUNX1 mutations were detected in 64% of pDC-AML cases and only rarely (2%) in patients with a diagnosis of BPDCN.

pDC-AML, as an emerging subset of AML, still has many details to be parsed out. The current WHO classification (5th edition, 2022) [4] places pDC-AML under the category of “plasmacytoid dendritic neoplasms”. However, the above-mentioned literature indicate that pDC-AML is quite distinct, both in terms of immunophenotype and molecular character, from other “plasmacytoid dendritic neoplasms.” Immunophenotyping by flow cytometry and/or immunohistochemistry plays a central role in recognizing this subtype of AML. We present here a typical case of pDC-AM, highlighting Multiparameter Flow Cytometry (MFC) routine and Measurable Residual Disease (MRD) evaluation, and Next-Generation Sequencing (NGS) findings. This case presentation and literature review aims to raise the awareness of this rare disease entity in our daily practice.

Case Report

A 65-year-old male presented with pancytopenia for three weeks. A Complete Blood Count (CBC) showed pancytopenia with White Blood Cell (WBC): 34 x10^9/L, Hg: 6.8 g/dl and platelets: 36 x10^9/L. A manual differential showed blasts: 1%, neutrophils: 34%, eosinophils: 4%, monocytes: 17%; lymphocytes; 37%, large granular lymphocytes 7%. A baseline chest CT revealed scattered ground glass, with patchy opacities bilaterally suggesting pneumonitis/pneumonia, for which the patient was treated with Zosyn and azithromycin. An outside bone marrow pathology report was suspicious for BPDCN; it was noted the patient did not have the classic skin manifestations of this disease. A bone marrow aspirate and biopsy were performed. Representative histomorphology is presented in Figure 1. Following standard operating procedures, MFC was performed by an FDA-approved ClearLLab 10-color system. Flow cytometry data was collected on the Navios EX flow cytometer (Beckman Coulter Life Sciences, IN, US), and analyzed by Kaluza software (Kaluza C1.2). Intracytoplasmic staining tube was performed on an eight-color FACS Canto (Becton Dickinson, San Jose, CA) flow cytometer using a one-tube eight-color antibody panel developed at our institution. Antibodies used are MPO-FITC; CD79a-PE; CD22-PCP; CD34-PECY7; TdT-APC; CD45-APCH7; CD3-BV421; CD10-BV510. Data were acquired with FACS Diva software (Becton Dickinson, San Jose, CA), and analyzed via WinList software. Phenotypic findings by MFC were depicted in Figure 2.