Blastic plasmacytoid dendritic cell neoplasm (ORPHA:86870)
A rare and highly aggressive myeloid malignancy characterized by predominant cutaneous involvement with concomitant or subsequent bone marrow, lymph node and visceral involvement, as well as central nervous system (CNS) disease. It derives from the precursors of plasmacytoid dendritic cells (pDC).
Epidemiology
US incidence ranges from 500 to 1000 cases per year; global point prevalence is estimated at 12/100,000. Incidence is higher in patients aged ≥ 60 years and in males; ~10% of cases occur in children.
Clinical description
BPDCN affects patients of all ages but is most common in the elderly. Median age at onset is 60-70 years. It is characterized by skin and bone marrow involvement, but may involve lymph nodes, peripheral blood, liver, spleen and the CNS. The most common clinical presentation is asymptomatic solitary or multiple skin lesions (either isolated purplish nodules, isolated bruise-like papules, or disseminated purplish nodules/macules/papules). Some patients may present with leukemia.
Etiology
BPDCN derives from the precursors of pDC. There is no single cytogenetic or molecular change characteristic of BPDCN.
Diagnostic methods
Diagnosis requires biopsy of the affected area(s) with morphologic assessment and immunophenotyping. Skin biopsy shows a diffuse, monomorphous infiltrate of medium-sized blast cells resembling lymphoblasts or myeloblasts with massive dermis. Immunohistochemical diagnostic criteria are expression of CD123 (in all cases), CD4 and/or CD56, or one other pDC marker; or expression of any three pDC markers (CD123, TCF4, TCL1, CD303, CD304, CD4, CD56) and no expression of CD3, CD14, CD19, CD34, lysozyme, and myeloperoxidase.
Differential diagnosis
The differential diagnosis includes acute myeloid leukemia (AML), chronic myelomonocytic leukemia, nasal-type extranodal NK/T cell lymphoma, subcutaneous panniculitis-like T cell lymphoma, and cutaneous T cell lymphoma.
Management and treatment
Tagraxofusp, a CD123-directed therapy, is the only drug approved for patients aged ≥2 years with newly diagnosed and relapsed/refractory BPDCN in the USA, or for adults with newly diagnosed BPDCN in Europe. Tagraxofusp, typical chemotherapy regimens for acute myeloid leukemia and acute lymphocytic leukemia, or lymphoma induction chemotherapies, are recommended as first-line treatment by the NCCN AML guideline. However, the chemotherapy regimens are associated with more toxicities, as well as lower survival rates and are not FDA/EMA-approved. Intrathecal chemotherapy should be considered for patients with documented CNS disease at diagnosis. Management strategies should vary according to patients' age and fitness. Off protocol approaches and participation in clinical trials can be considered in young/fit patients. Hematopoietic stem cell transplantation (HSCT) offers the best chance of long-term disease-free survival and should be considered in first remission for all eligible patients.
Prognosis
Historically, prognosis is poor. Median overall survival (OS) ranges from 8 to 12 months following chemotherapy and is 15.7 months following tagraxofusp. Median OS is longer in patients who were bridged to HSCT.

                            Last update: 
                            March 2023


                            - Expert reviewer(s): 
                            Dr Naveen PEMMARAJU