Blastic Plasmocytoid Dendritic Cell Neoplasm With Pseudo‐Lymphoid Morphology Mimicking Lymphoid Malignancy

A 60-year-old male presented with spontaneous hematomas and cervical adenopathy. Laboratory workup revealed hemoglobin 12.3 g/dL, platelet 56 × 109/L, and leukocyte 14.7 × 109/L. The automated cell counter (Sysmex XN) reported 9% neutrophils (1.32 × 109/L) and 86% lymphocytes (12.6 × 109/L), suggestive of a lymphoproliferative disorder. Blood smear showed atypical lymphoid cells with normal size, mature chromatin, and scant cytoplasm Figure 1 (Panel A), while numerous lysed cells were also observed (Panel B). About 10% of these cells displayed cytoplasmic vacuoles, occasionally coalescing, and 10% appeared larger with grayish cytoplasm (Panel C and D). Due to the apparent lymphocytosis, flow cytometry immunophenotyping was performed (Navios EX, Beckman-Coulter). Surprisingly, 62% of the leukocytes consisted of a CD45+low blastic population. These cells were negative for common lymphoid (CD19/CD20/CD22/CD24/cCD79a/CD3/CD5/CD8/CD10) and myeloid antigens (CD34/CD38/CD13/CD14/CD42b/CD61/CD64/CD65/CD117/cMPO), but were positive for CD4(weak)/CD56/CD123(strong)/HLA-DR(strong)/CD33 (Panel E and F). A cutaneous lesion was found on the patient's back, and bone marrow aspiration confirmed 82% of the same population with additional phenotypic markers indicative of pDC lineage (CD303+weak/CD304+/cTCL1+/BadLamp+), supporting the diagnosis of Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN). The neurological examination was normal, and cerebrospinal involvement was inconclusive due to hemorrhagic cerebrospinal fluid samples. Furthermore, the mutational profile performed on bone marrow aspirate was consistent with BPDCN, revealing mutations in TET2, ASXL1, and NF1, as well as a subclonal NRAS mutation and deletions in the IKZF1 and ETV6 loci. BPDCN is a rare hematologic malignancy, with diverse morphological presentations. While the classic blastic morphology, often exhibiting “pearl necklace” cytoplasmic appearances and “hand-mirror-like” projections, is the most common presentation, this case displayed an unusual morphology dominated by pseudo-lymphoid cells. Although a subset of pseudo-lymphoid cells is commonly observed in BPDCN, this case was remarkable in that nearly all cells exhibited this distinctive morphology. Such atypical presentation can be deceptive, initially mimicking lymphoid malignancies. Here, the immunophenotypic profile was crucial in establishing the accurate diagnosis. R.R.-C.: analyzed date and wrote the paper. O.B., G.B., C.B., F.G.O., A.R., and F.R.: analyzed data. V.B.: coordinated the study, wrote the paper and supervised analysis. All data has been anonymized to ensure confidentiality and privacy. The authors declare no conflicts of interest.