Diagnostic approach to blastic plasmacytoid dendritic cell neoplasm: historical perspectives and current understanding

Abstract

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy composed of immature cells that exhibit plasmacytoid dendritic cell (pDC) differentiation. The diagnosis of BPDCN is often challenging due to its rarity and morphologic and phenotypic overlap with other hematologic malignancies, such as acute myeloid leukemia (AML). The emergence of tagraxofusp, a CD123-directed cytotoxin, and other novel therapies has underscored the importance of accurately diagnosing BPDCN. This review initially outlined the clinical and histopathological features of BPDCN, including patients with immunoblastoid morphology. Various proposed diagnostic criteria based on flow cytometry and immunohistochemistry findings were presented, highlighting critical points of caution in the diagnostic process. Strategies for detecting minimal residual disease or microinvasion in BPDCN, a significant clinical issue, were also discussed. Additionally, we reviewed the recurrent 8q24 (MYC) and MYB rearrangements observed in BPDCN, which can aid in diagnosis. Furthermore, we explored mature plasmacytoid dendritic cell proliferation (MPDCP) associated with myeloid neoplasm, which is characterized by a clonal proliferation of pDCs in cases with a defined myeloid neoplasm and may also serve as a potential differential diagnosis for BPDCN. Lastly, we discussed pDC-AML, characterized by pDC proliferation in AML cases, which can also be part of MPDCP and is often associated with frequent RUNX1 mutations. Overall, this review provides insights into BPDCN diagnosis and highlights the current challenges in its detection and differential diagnosis.

Keywords: acute myeloid leukemia with plasmacytoid dendritic cell expansion; blastic plasmacytoid dendritic cell neoplasm; mature plasmacytoid dendritic cell proliferation associated with myeloid neoplasm.

Fig. 1

Correlation between cytomorphology and MYC status in BPDCN (A) A case of classic BPDCN displaying medium-sized tumor cells with irregular nuclei featuring fine chromatin, 0 to a few small nucleoli, and small to moderate amounts of cytoplasm. MYC immunostaining and MYC split FISH yielded negative results. (B) A case of immunoblastoid BPDCN characterized by tumor cells with fine chromatin, round nuclei, moderate amounts of basophilic cytoplasm, and one large prominent central nucleolus. MYC immunostaining and MYC split FISH yielded positive results.

Fig. 2

A bone marrow aspirate from a patient with BPDCN Tumor cells with round-to-irregular nuclei, basophilic cytoplasm with a “cloudy-sky” appearance, and small vacuoles in the cytoplasm (Giemsa staining).

Fig. 3

pDC markers in BPDCN A patient of BPDCN shows positivity for CD123, TCL1, BDCA2, and TCF4.