BPDCN: Epidemiology, Pathophysiology, and Diagnosis


Opening the discussion on the management of BPDCN, an expert panel consisting of two hematologist-oncologists and a pathologist, considers the causes, incidence and diagnostic approach to this rare disease.


Naveen Pemmaraju, MD: Hi everyone, I’m Dr Naveen Pemmaraju, an associate professor of leukemia and the director for the program on blastic plasmacytoid dendritic cell neoplasm [BPDCN] at MD Anderson [Cancer Center in Houston, Texas]. I’m happy to present on behalf of my colleagues, Dr Gru and Dr McCloskey, our program titled, “Advances in the Diagnosis and Treatment of BPDCN,” a Virtual Tumor Board® discussion. As I mentioned, I’m really happy to be joined by my colleagues Dr James McCloskey and Dr Alejandro Gru. Here are a few words on each of our presenters today as I welcome them to this distinguished panel. Dr James McCloskey serves as the chief of the division of leukemia at the Hackensack University Medical Center in Hackensack, New Jersey. James, thanks for joining us.

James McCloskey, MD: Thanks for having me.

Naveen Pemmaraju, MD: Wonderful. Then we’re also honored to be joined by our colleague Dr Alejandro Gru, who’s a professor of pathology in the dermatopathology section of the University of Virginia School of Medicine in Charlottesville, Virginia. Dr Gru, how are your today?

Alejandro Gru, MD: Great, thank you for having me too, it’s a pleasure to be here.

Naveen Pemmaraju, MD: Thank you to both of you for your time away from your family and busy work life as we focus on BPDCN today. For our colleagues out there, in today’s presentation we will go over an overview of this rare disease, BPDCN, and present a few clinical scenarios. Then we’ll discuss in an informal conversational way approaches that we’re all using at the dermatologic, pathologic, and clinical levels to try to understand this rare disease and why it’s important in the modern era. Again, thanks to everyone out there for joining us, let’s go ahead and get started.

Since BPDCN is such an ultra-rare disease, and I’ve specialized and dedicated my career to this, here are a few slides on background so everyone is on the same page. So we have blastic plasmacytoid dendritic cell neoplasm, BPDCN. Essentially it has changed hands and classifications multiple times over the last few years. Most recently it was placed as an aggressive leukemia under the AML [acute myeloid leukemia]-related family of neoplasms in 2008, then in its own category in 2016, and now in its own category in even dendritic cell and histiocytic neoplasms.

In the clinic, patients with BPDCN present in several different ways and they require a multidisciplinary panel, and that’s why you see one here today. The majority of our patients present with skin involvement, but also bone marrow and blood and lymph node involvement. Unfortunately, a high number of our patients we’re realizing can have CNS, or central nervous system, involvement. Many of our patients will have other sites involved, and very commonly it’s extramedullary, which is a contra-distinction to AML, which is a bit less frequent.

There’s no recurrent cytogenetic or molecular marker, but the hallmark of this disease has been the overexpression of a marker, IL-3 [interleukin-3] receptor alpha, better known as CD123+. That is a surface marker that’s virtually present in 100% of our patients. This helps our dermatopathologists and pathologists to not only diagnose the disease, but as we’ll talk about in a moment, it’s given us a therapeutic target that is very attractive for novel treatments. In addition to CD123, positivity of CD4 and CD56 is common. We always say in this triad, “Think 1, 2, 3, 4, 5, 6.” But in and of itself, it may not be specific enough, so we add in other markers, some of them listed here: TCL-1, TCF-4, for example. Molecular markers can range but are usually centered around myeloid markers, that’s kind of interesting. TET2, in my own series, has been by far the most common, followed by ASXL1, RAS, and ZRSR2.

For overview, we know historically, outcomes have been poor. So whatever category, whatever name we give to BPDCN, unfortunately it has less than 1- or 2-year overall survival. Many of these patients transform to an acute leukemic phase. One of the reasons we’re meeting here together is that this class of drugs, CD123-based therapies, led by the first-in-class tagraxofusp and now in clinical trials with IMGN632 and others, are in the active clinical trials phase.

It brings us to this question that Dr Gru, Dr McCloskey, and I were discussing earlier, which is how do you even know what the incidence and prevalence of an ultra-rare disease is? You have this triad, and it is a rare disease; we think maybe only 500 to 1000 Americans a year. The nomenclature and classifications change as I mentioned, and as Dr Gru well knows, there’s a difficulty even among us as experts in diagnosing and identifying BPDCN and distinguishing it from related conditions, such as AML leukemia cutis, CMML [chronic myelomonocytic leukemia] with skin lesions, etc. Dr Gru, I want to pause and bring you into this. You’ve done quite a bit of work for us in this field in nailing down the diagnosis, which I still believe is one of the most important things. I want to hear your comments on how our practice has changed, just naming this and understanding how to tell someone in the clinic they have it. Dr Gru?

Alejandro Gru, MD: You’ve made some excellent points, Dr Pemmaraju. The true incidence of the disease is very difficult to estimate. It’s based on SEER [surveillance, epidemiology, and end results] data and case series. It’s also difficult to estimate because the disease has carried so many names in the past. Initially it was believed to be some type of NK-cell malignancy because a lot of the cases have CD56 expression. Then in the previous WHO [World Health Organization] classification it was considered a subtype of acute myeloid leukemia, and then more recently it was separated out as its own category, its own classification. The disease has many problems in the diagnosis, one of them being the fact that these patients sometimes carry somewhat non-specific clinical lesions on the head and neck areas and other parts of the body, and they can be subtle. A lot of times the clinicians and usually dermatologists or other people who see patients clinically don’t think about this entity, and they don’t have it in the diagnostic mind. More so, it’s such a rare entity that dermatopathologists and even hematopathologists a lot of times don’t think about it. Sometimes the infiltrates can be sparse and subtle, making the diagnosis even more challenging.

It is critical to have a high index of suspicion clinically. It’s important to understand that when you are seeing these patients with lesions on the skin, most of them are going to have disease in the blood, so they are going to be diagnosed by the time you see it on the skin with an acute leukemia. It is critical to have a prompt referral to a clinician, a hematologist, who’s going to do more testing, look at the blood, look at other compartments the disease involves. A complete phenotypic work-up is necessary, [looking for] the right markers, to be able to nail it down into a specific diagnosis and making sure that the patient gets the right treatment.

Transcript edited for clarity.

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