Objective
Make a diagnosis for a 69-year-old patient presenting a bilateral necrotic angina for 2 weeks treated with amoxicillin/clavulanic acid without improvement.  
On physical examination, small indurated purple nodules were visible on the skin without other symptoms.
Blood count showed macrocytic anemia without B9/B12 deficiency (Hemoglobin 104g/L), mild thrombocytopenia (110G/L) and some circulating blasts (0.09G/L) without other biological abnormality.
Methods
Bone marrow aspiration/biopsy and skin biopsy were performed. 
Results
Bone marrow cytology showed hypercellularity with multi-lineage dysplasia and significant excess of small blasts (>30%). Rare cells showed an elongated cytoplasm with a tail-shaped structure. Skin biopsy revealed also a tumor infiltration.
Flow cytometric analysis displayed positivity for one immature marker (CD34-, HLA-DR++, CD117-, TdT-) without lineage-specific markers (cMPO-, cCD3-, CD19-, cCD79a-). However, CD56 was positive. Extended immunophenotype showed CD13-, CD33-, CD4+/-, CD5+(bimodal), CD7(15%), CD10-/+, CD36(heterogeneous), CD38+, CD123+, FceR1+, CD64-, CD14-, Ki67(50%). Blastic plasmacytoid dendritic cell proliferations (BPDCP) are rare (<1% of all malignant hemopathies) and need to be confirmed by specific markers (CD303, CD304 or cTCL1) in order to distinguish them from an Acute Myeloid Leukemia with monocytic differentiation or from an immature AML. Our patient was CD303 negative (flow and histology) and TCL1 positive (confirmation on the skin biopsy).
Mutations in ASXL1, TET2, ZRSR2 and EZH2 genes were highlighted. TET2 is the most commonly mutated gene in BPDCN. The other mutations are frequently found in myelodysplasia. 
Caryotype and FISH analysis didn’t reveal any abnormality.
Thoraco-abdominal CT-scan didn’t show any tumor dissemination.
Conclusion
Blastic plasmacytoid dendritic cell proliferation is an aggressive malignant hemopathy derived from precursors of plasmacytoid dendritic cells with a median survival of 15 months. There is no consensus for chemotherapy which gives a frequent initial response but leads to recurrent relapse with drug resistance. 
BPDCN diagnosis is a challenge for clinical laboratories requiring extensive immunophenotyping assessment with specific confirmation markers.

Blastic plasmacytoid dendritic cell neoplasm : an uncommon CD4±CD5+CD10±CD303- presentation