BPDCN: More Than Just a Rash

Blastic plasmacytoid dendritis cell neoplasm (BPDCN) is a rare and aggressive form of cancer that usually makes its appearance in the form of red to violet papules and plaques that can be confused for a number of other skin conditions.¹

Most often appearing in older men, the skin lesions that first signal this cancer can be initially responsive to a combined treatment regimen of chemotherapy, focal radiation, and systemic glucocorticoids. This early response is not a sign of overall improvement, though. People who experience strong initial responses to therapy often relapse quickly, and current treatments do little to improve the overall prognosis for this cancer.¹

What is BPDCN?

Also known as a blastic natural killer cell lymphoma or CD4+/CD56+ hematodermic neoplasm, this cancer develops from plasmacytoid dendritic cells—a type of myeloid cell.¹ The cells that BPDCN evolves from are usually found in the lymph nodes and tonsils, and more rarely in the thymus, bone marrow, spleen, and lymphoid tissues. Exposure to stimuli like viral or autoimmune conditions can trigger genetic reorganization that leads to malignancy.²

BPDCN was first recognized in the 1998 as a cutaneous lymphoma, and then as its own distinct diagnosis in 2016.² With a long history of misdiagnosis, bruise-like lesions on the upper body are the most common skin presentation.

This type of cancer is very rare, limiting the available data for research. BPDCN only has an incidence of about 0.04 per 100,000 people, and general affects older men between the ages of 53 and 68.² There is no clear racial or ethnic connection, according to current literature.²

Although most patients with BPDCN—about 90%—present with symptoms that are apparent only on the skin, bone marrow involvement is common and eventually leads to the development of leukemia.³ Overt acute leukemia is the initial presentation that leads to diagnosis in about 10% of patients, according to one 2019 report.³

The initial skin-only appearance of this disease and its insidious progression carries an poor prognosis, with a median survival of less than two years.² Without treatment, BPDCN spreads quickly through peripheral blood and bone marrow and can lead to death in under a year regardless of the initial presentation.⁵

Management and treatment

The rare and aggressive nature of BPDCN has made creating effective treatment guidelines difficult, and there was no standard of care in treating it until the U.S. Food and Drug Administration approved the targeted therapy tagraxofusp in 2018.⁴ When tagraxofusp isn’t an option, other treatments can include things like:

• acute lymphoblastic leukemia (ALL)-inspired intensive chemotherapy regimen with CNS prophylaxis
• allogeneic hematopoietic stem cell transplantation (alloHSCT)
• CD123-based targeted therapies

While high-dose chemotherapy regimens are generally the treatment of choice for patients with BPDCN, they aren’t often well-tolerated by the frail, elderly population the condition targets. For this reason, lower-dose treatment regimens that aren’t as effective may be substituted.^3,5

Patients who developed this condition before age 60 and who received treatments with early hematopoietic stem cell transplantation (HSCT) had better outcomes, according to one study.²

Additional studies on newer, more effective treatments for delicate populations are ongoing.

References

1. Gurbuxani S. Blastic plasmacytoid dendritic cell neoplasm. StatPearls. January 2022.
   https://www.uptodate.com/contents/blastic-plasmacytoid-dendritic-cell-neoplasm/print?search=Core%20binding%20factor%20alpha%201&selectedTitle=10~10
2. Venugopal S, Zhou S, El Jamal S. (2019.) Blastic plasmacytoid dendritic cell neoplasm–current insights. Clin Lymphoma Myeloma Leuk. September 2019;19(9):545-554.
   https://www.sciencedirect.com/science/article/abs/pii/S2152265019303246
3. Kerr, D., Zhang, L. & Sokol, L. Blastic Plasmacytoid Dendritic Cell Neoplasm. Curr. Treat. Options in Oncol. 20, 9 (2019). https://doi.org/10.1007/s11864-019-0605-x
4. U.S. Food and Drug Administration. FDA approves first treatment for rare blood disease. December 2018.
   https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-rare-blood-disease