BPDCN is a rare disease that comprises <1% of all cutaneous hematologic malignancies. Elderly patients are most commonly affected (mean age 60 to 70 years), but it can occur at any age, including in infants.^1,2,3,4 There is a male predominance with a reported male:female ratio of approximately 4:1.¹ No difference in predisposition based on race or ethnicity has been reported.

Cutaneous lesions are the primary presentation in >60% of cases,^1,5 and about half of cases have isolated cutaneous involvement at presentation.⁶ Skin lesions can be multiple (>60% of the time) or single. The lesions range from tumors and nodules to plaques and patches that are brown, erythematous, or violaceous. A characteristic clinical finding is that the lesions are bruise-like or hemorrhagic in appearance. They may be found anywhere on the body, especially the scalp, face, trunk, and extremities (Fig. 56-1). Clinically, the skin lesions can simulate other entities including vascular neoplasms, vasculitis, and traumatic bruises.^1,5,7

Bone marrow and peripheral blood involvement eventually develop in nearly all cases but are often absent or present at very low levels initially.^3,5,8 Thrombocytopenia and other cytopenias are common at the time of presentation, but B symptoms are unusual.³ Around 10% to 20% of cases have associated myelomonocytic leukemia at the time of presentation. Some cases are associated with myelodysplastic syndromes.^1,5,8 Lymph node involvement also occurs in 40% to 50% of cases.^1,8 The spleen, liver, mucosal surfaces, and the central nervous system (in order of decreasing frequency) may also be involved.⁸

BPDCN is an aggressive neoplasm with a generally poor prognosis. Patients with disease limited to the skin at presentation do not have a better prognosis than those presenting with bone marrow dissemination.⁹ Therefore, aggressive therapy should be employed even in the setting of isolated cutaneous involvement.¹⁰ Most patients initially achieve complete remission with a number of different chemotherapy regimens. However, >80% of patients have systemic relapse with cutaneous and extracutaneous dissemination usually in less than 2 years and often with bone marrow involvement.^1,3,10 Of the few patients who achieve sustained clinical remission, most have received acute leukemia regimens and allogeneic stem cell transplantation.^3,9,11 Therapy regimens used for lymphoblastic leukemia tend to give better outcomes than therapies used for acute myeloid leukemia, despite the apparent closer relationship that PDCs have to the myeloid lineage.^3,6,9 Overall, the median survival is around 14 months.¹⁰ Age seems to be a significant prognostic factor,⁹ with the best outcomes occurring in children.^12,13

Cutaneous lesions of BPDCN are characterized by a dermal infiltrate composed of sheets of neoplastic cells (Fig. 56-2). The infiltrate is typically diffuse, but can often show an accentuated periadnexal or perivascular distribution (Fig. 56-3). The epidermis is characteristically spared with an underlying Grenz zone.⁷ The cells are typically intermediate to large with round nuclei and finely dispersed “blastic” chromatin (Fig. 56-4). Nuclear contours are irregular and may be notched, folded, or occasionally show moderate pleomorphism. Nucleoli are usually inconspicuous, but one to several prominent nucleoli can be present.^5,7,14 With hematoxylin and eosin staining, the cytoplasm is pale to eosinophilic, agranular, and usually scant, but can be moderate to abundant in some cases.^3,8 There may also be significant erythrocyte extravasation, but little or no inflammatory response.⁸ The erythrocyte extravasation accounts for the clinical bruise-like or hemorrhagic appearance. Necrosis is generally absent.⁶