During a Targeted Oncology case-based roundtable event, Jeffrey E. Lancet, MD, discussed the clinical presentation of blastic plasmacytoid dendritic cell neoplasm and how it came to be recognized as a distinct rare hematologic malignancy. This is the first of 2 articles based on this event.
Targeted OncologyTM: What is blastic plasmacytoid dendritic cell neoplasm (BPDCN) and how does it present in patients?
LANCET: BPDCN is a very aggressive but rare hematologic malignancy that accounts for less than a half of 1% of all hematologic malignancies and less than 1% of cutaneous lymphoid types of family malignancies.1 The incidence in the United States population is exceedingly rare. But maybe the true epidemiology is not clear either because of the rarity of the disease and the fact that the diagnostic criteria have changed over the years with difficulty homing in on the diagnosis. Perhaps we’ll see a change in the current era of diagnostic assessments of hematologic malignancies with more specific criteria for this disorder. Nonetheless, it remains a very rare condition.
This was not always a clear-cut diagnosis and the nomenclature and classification has evolved over time. Twenty [or more] years ago, we thought of this as more of a blastic NK [natural killer] cell lymphoma, and eventually we became more refined in our ability to understand it and pick out specific markers…to the point where in 2008 it became a subset of AML [acute myeloid leukemia], and then in 2016 the WHO classified it as a unique myeloid neoplasm unto itself.2 The 2022 update categorized BPDCN in a category of dendritic cell and histiocytic neoplasms and it falls under the category of plasmacytoid dendritic cell neoplasm—the immature forms, the blastic form—as opposed to more mature form that can also be associated with myeloid neoplasms, further refining of the diagnosis and the uniqueness of the actual cell of origin.3
The clinical presentation is [not] classic, but it’s well described. It can mimic other disease states as well. The typical clinical presentations is a patient aged 60 to 70. The majority of patients are men, and there may be a history of an antecedent hematologic myeloid malignancy in up to 20% of patients before diagnosis of BPDCN is established.4 The primary sites of disease are the skin, bone marrow, lymph nodes, and central nervous system. The skin is the most common site with 85% to 90% of patients having initial primary presentation with the skin. Secondary sites can be other extramedullary sites that can involve the liver, spleen, or potentially other organs. Early recognition is challenging because it can overlap with other malignancies.5 There’s not always an immediate onset of symptoms collaboratively that establish the diagnosis, so it’s important that physicians in general be aware of this potential diagnosis to ensure that the proper referrals are made. [Then] the patient can undergo care sooner rather than later. This disease, as is the case of many hematologic cancers, has a tendency to be rapidly progressive in the setting of no treatment. So I think even internists need to be aware of the fact that if a patient presents with skin nodules and hematologic abnormalities, there should be some urgency to the case.
How does the disease advance at the time it presents symptomatically?
A typical journey would involve the initial presentation of cutaneous lesions that over time can be associated with progressive pancytopenia, indicating blood and bone marrow involvement. This can then progress into multi-organ involvement with potentially the lymph nodes, liver, spleen, central nervous system, etc. Usually by this time, there’s a lot more attention [on the patient], and the BPDCN diagnosis can be established. There is a short time between diagnosis and death in the absence of treatment. [This is] a fairly conventional natural history that typically starts with skin manifestations. [That is] not to say that there may not be hematologic manifestations at the time of diagnosis, but not necessarily rampant. But eventually, over time the disease becomes more widespread and more obviously involves multiple organs.
The clinical presentation is primarily through the skin.5 The vast majority of patients present with skin lesions, and it may precede other organ involvement or other signs and symptoms by 2 to 3 months. The skin manifestations can be somewhat heterogeneous, and you can see patches, plaques, nodules, tumors, various stages of discoloration.6 [There is] not a specific dermatologic presentation, unfortunately. These lesions can be isolated, solitary, or they can be diffuse. They typically involve the epidermis and spare the dermis, so you want to make sure that the skin biopsy is inclusive of the dermis because that can be an important component of ruling in and ruling out BPDCN morphologically.
1. Bueno C, Almeida J, Lucio P, et al. Incidence and characteristics of CD4(+)/HLA DRhi dendritic cell malignancies. Haematologica. 2004;89(1):58-69.
2. Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127(20):2391-2405. doi:10.1182/blood-2016-03-643544
3. Khoury JD, Solary E, Abla O, et al. The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms. Leukemia. 2022;36:1703-1719. doi:10.1038/s41375-022-01613-1
4. Pemmaraju N. Blastic plasmacytoid dendritic cell neoplasm. Clin Adv Hematol Oncol. 2016;14(4). Accessed November 4, 2022. https://bit.ly/3fy7w69
5. Deconinck E, Petrella T, Ottou FG, et al. Blastic plasmacytoid dendritic cell neoplasm clinical presentation and diagnosis. Hematol Oncol Clin NA. 2020;34(3):491-500. doi:10.1016/j.hoc.2020.01.010
6. Julia F, Petrella T, Beylot-Barry M, et al. Blastic plasmacytoid dendritic cell neoplasm: clinical features in 90 patients. Br J Dermatol. 2013;169(3):579-586. doi:10.1111/bjd.12412