Review highlights inroads to understanding blastic plasmacytoid dendritic cell neoplasm

Questions remain about how best to diagnose and treat blastic plasmacytoid dendritic cell neoplasm, as well as about the cancer’s true incidence, according to authors of a review recently published in Current Oncology Reports.¹ But studies are revealing clinical, molecular, diagnostic and therapeutic findings that are leading to a better understanding of the rare and aggressive hematopoietic malignancy. There are promising targeted treatments in the pipeline and a growing social media interest in blastic plasmacytoid dendritic cell neoplasm.

Blastic plasmacytoid dendritic cell neoplasm has had different names and descriptions since it was first introduced in 1994. That has made it challenging for epidemiologists to accurately assess the disease’s incidence. Reports suggest blastic plasmacytoid dendritic cell neoplasm occurs more in males, often happens in the seventh or eighth decade of life (although it does occur in children) and has an incidence of 0.000045%. The prognosis is generally poor.

Dermatologists would be most interested in clinical signs of blastic plasmacytoid dendritic cell neoplasm. The cancer generally presents with skin or skin and bone marrow involvement. Review authors confirm that while blastic plasmacytoid dendritic cell neoplasm’s clinical presentation is diverse, cutaneous involvement is usually the cancer’s first sign, followed by or at the same time as its spread to bone marrow and peripheral blood.

Patients will likely have solitary or multiple skin lesions, including isolated nodules, macules and disseminated macules and nodules. Researchers originally reported a bruise-like pattern on the skin, but review authors suggest a nodular pattern of cutaneous involvement is more common in blastic plasmacytoid dendritic cell neoplasm. Patients often have localized or disseminated lymphadenopathy.

Rarely, blastic plasmacytoid dendritic cell neoplasm patients present first with leukemia, without cutaneous involvement.

These are generalization, but many case reports confirm this cancer presents in various ways. Examples are: blastic plasmacytoid dendritic cell neoplasm has appeared as a renal mass, vision loss because of optic nerve involvement, in the nasal cavity, on the trunk or scalp, as well as in the lungs, colon and elsewhere.

The review authors also reported that blastic plasmacytoid dendritic cell neoplasm originates from precursors of plasmacytoid dendritic cells of two functionally different subsets: plasmacytoid dendritic cells and myeloid dendritic cells. While scientists have yet to clarify blastic plasmacytoid dendritic cell neoplasm’s clonal evolution and diagnosing it remains challenging, CD4, TCL1, CD123, CD56, CD303 are immunophenotypic markers that are indicative of the disease, according to the review.

“Molecular data support the current [World Health Organization] WHO classification of the disease as a myeloid disorder and provide a biological rationale for the incorporation of epigenetic therapies for its treatment,” the authors wrote.

While researchers are characterizing blastic plasmacytoid dendritic cell neoplasm’s mutational landscape, they have yet to pinpoint an obvious molecular target, according to the review.

At this time, chemotherapy alone seems enough to treat children. Although studies suggest hematopoietic stem cell transplantation in children who relapse and achieve a second remission, which can increase survival.

Adult responses tend to be better when they’re treated with adult chemotherapy followed by hematopoietic stem cell transplantation.

“Intensive first-line therapy and ‘lymphoid-type’ chemotherapy regimens have been associated with better outcomes. Despite the fact that [blastic plasmacytoid dendritic cell neoplasm] is often initially limited to the skin, only an aggressive initial therapy may improve the patients’ prognosis,” the authors wrote. “Local treatments, such as radiation therapy, seem useless.”

Future blastic plasmacytoid dendritic cell neoplasm treatment could target the cancer and eliminate the need for cytotoxic chemotherapy. Tagraxofusp (Elzonris, Stemline Therapeutics) is one such treatment, which the FDA approved for blastic plasmacytoid dendritic cell neoplasm in December 2018. The intravenously administered CD123-directed cytotoxin is approved in patients ages 2 years and older, according to the review.

Large retrospective studies are needed to standardize blastic plasmacytoid dendritic cell neoplasm guidelines. There are encouraging signs of a growing awareness and discussion about the cancer, including a social media presence in the Twitter community #BPDCN

Disclosures:
The authors report no relevant disclosures.

Reference:
Tsagarakis, N.J., Paterakis, G. Dendritic Cell Leukemia: a Review. Curr Oncol Rep 22, 55 (2020).