About BPDCN

History

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) was first reported by Adachi et al. as a CD56-positive cutaneous lymphoma that expressed CD4, but lacked expression of other T/B-cell lineage markers. It used to be called “agranular CD4+ CD56+ hematodermic neoplasm” or “blastic natural killer (NK) cell lymphoma.”

It was established as a disease entity in the 4th edition of the WHO classification of Tumours of Haematopoietic and Lymphoid Tissues (2008) and named BPDCN because the normal counterpart of BPDCN cells is believed to be plasmacytoid dendritic cells (pDCs).

Clinical presentation

BPDCN is a rare hematopoietic neoplasm. In Japan, only 10–20 new cases are diagnosed each year. Males are more commonly affected. Most patients are elderly, but it can occur at any age. Characteristically, 60–100% of patients have skin lesions. Bone marrow involvement is found in 50–90% of patients at diagnosis. Lymph nodes, spleen, and liver are often involved. Most cases initially respond to chemotherapy but then undergo relapse. The prognosis is poor, with a median survival of 10–27 months.

Diagnosis

Diagnosis of BPDCN is made through morphological evaluation, immunohistochemistry, or flow cytometry of histopathological specimens or fresh samples. BPDCN is suspected when tumor cells express CD4 and CD56 without expressing other lineage markers of B/T cells and myeloid cells. Expression of markers specific to pDCs (e.g. CD123, BDCA2/CD303, BDCA4, TCL1, and TCF4) is important for confirming the diagnosis. The differential diagnosis includes acute myeloid leukemia and myeloid sarcoma. For a description of the morphology of BPDCN cells, please refer to the “Research” page.

Genetic abnormalities

The majority of BPDCN cases with analyzable karyotyping results show complex karyotypes. Copy number losses, associated with tumor suppressor genes such as CDKN2A/CDKN2B, RB1, and CDKN1B, are more frequently found than copy number gains. Mutations in genes involved in DNA methylation, histone modification, and splicing have been identified. Suzuki et al. reported that MYB rearrangement is observed in a fraction of cases, more commonly in children. We have reported 8q24 rearrangement and MYC expression in BPDCN. Please refer to the “Research” page.

Treatment

The efficacy of acute lymphoblastic leukemia-oriented regimens has been demonstrated through retrospective studies. Hematopoietic stem cell transplantation in first remission can promote long-term survival. However, most patients are elderly, and treating them with intensive therapy can be difficult. Tagraxofusp, a CD123-directed cytotoxin, was approved by the FDA for BPDCN patients in 2018, but has not yet been approved in Japan.