Blastic Plasmacytoid Dendritic Cell Neoplasm in Children, Adolescents, and Young Adults

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematological malignancy typically seen in the elderly and carries a poor prognosis. The aggressive neoplasm however can also occur in the pediatric population and as cutaneous manifestations of the disease are often the first presenting symptoms, it behooves dermatologists particularly those in training to better familiarize themselves with this rare but devastating disease in order to timely implement appropriate treatment and management in this patient population.

“Even though I am an adult hematologist oncologist, I routinely see adolescent and young adult patients in my practice. In truth, this rare leukemia subtype is more common than we think but is not being actively thought of in the diagnosis. Instead, patients are often erroneously being diagnosed with other types of blood-based cancers that also have cutaneous involvement,” said Naveen Pemmaraju MD, hematologist oncologist and associate professor of the department of leukemia at the Division of Cancer Medicine of the University of Texas MD Anderson Cancer Center in Houston, Texas.

Because BPDCN is rare in adults and even more exceedingly rare in the pediatric population, clinicians will not at first consider the disease as a potential diagnosis or differential diagnosis. Therein the importance to raising awareness of this extremely rare yet very aggressive neoplasm and underscoring the need for timely diagnosis and treatment. Moreover, the nomenclature of the disease has changed several times over the past decades and a diagnostic algorithm hasn’t been set Dr. Pemmaraju said, further adding to diagnostic confusion.

Whether occurring in adults or the pediatric population, BPDCN represents a unique cancer in that it will typically involve multiple organ sites, most commonly affecting the skin with deep purple to red-brown macules, plaques, or tumors, followed by bone marrow and peripheral blood, lymph nodes, and CNS. There is no standard of care for the treatment of BPDCN; various treatment regimens have been used including those for acute myeloid leukemia, acute lymphoblastic leukemia, and lymphoma, with or without stem cell transplantation.

In 2018, the FDA approved tagraxofusp (Stemline) as the first targeted BPDCN therapy in adults as well as patients 2 years and older. The novel agent specifically targets interleukin-3 receptor alpha unit (CD123), which is highly expressed by the neoplasm. In the study¹ leading to its approval, it was found feasible to administer tagraxofusp to children as well. According to Pemmaraju, tagraxofusp showed some efficacy in the pediatric population, and there weren’t any new safety signals other than what is already known about the drug from the adult experience.

“Interestingly, there are pediatric BPDCN patients who are doing well either with chemotherapy or chemotherapy and a stem cell transplant. Both treatment paths could be tried in this patient population however to really know the prognostic outcomes, larger studies are needed to gain a similar understanding as we have with the older patient population,” Pemmaraju said.

For the optimal treatment and management of patients with BPDCN, multidisciplinary care is of paramount importance and should include consultation with the hematologist oncologist, dermatologist, pathologist, as well as a stem cell transplant physician. A multidisciplinary approach is the most optimal way to approach these ultra-rare diseases, Pemmaraju said, because so little is known, and every patient case helps to generate more data for the literature.

There are so many aspects to the diagnosis and identification of skin cancers and the dermatologist’s expertise is essential in the timely diagnosis of these rare blood and bone marrow cancers. According to Pemmaraju, BPDCN is but one of several blood and bone marrow cancers that tend to involve the skin, and so the importance of dermatologic involvement in research, pathology, and clinical decision-making is paramount. As such, BPDCN should be highlighted at dermatology conferences and be included in educational materials, fellowship and residency training, board tests, and pathology diagnostic algorithms.

“Dermatologists are essential to getting the word out about BPDCN, helping us to identify and timely treat those patients in the clinic, and then helping us with the research on this disease going forward,” Pemmaraju said.

Reference

1. Pemmaraju N, Lane AA, Sweet KL, et al. Tagraxofusp in blastic plasmacytoid dendritic cell neoplasm. N Engl J Med. 2019;380(17):1628-1637.