A case of disseminated blastic plasmocytoid dendritic cell neoplasm
Authors: Giuseppe G. Loscocco, Matteo Piccini, Federica Vergoni, Alessandro M. Vannucchi, Alberto Bosi
Journal: American Journal of Hematology (2018)

Blastic plasmocytoid dendritic cell neoplasm (BPDCN) is a rare aggressive neoplasm originating from plasmocytoid dendritic cell (pDC) precursors typically presenting with primary cutaneous dissemination and involvement of bone marrow (BM) along with disease progression. A 64-year-old male patient was referred to our Institution with a 4 months history of non-painful skin lesions, initially presenting on the left leg as a “bruise like” brown nodule (Image 1A) and then spreading to the trunk, chest, head, and limbs as red-brown partly fused plaques and papules (Image 1B,C). The patient reported significant weight loss. Physical examination revealed the presence of left inguinal lymphadenopathy; laboratory tests, including full blood counts and chemistry, were within normal ranges. Bruise-like brown nodule under left knee (A); disseminated partly fused red-brown plaques and papules on the chest, neck, and back (B,C). Nodular infiltration of tumor cells dissecting between collagen bundles sparing the epidermis with a grenz zone; the dermis is massively involved with extension to the subcutaneous fat (D, Hematoxylin & Eosin, 53). Medium-sized blastic plasmocytoid dendritic cells containing vesicular nucleus, fine chromatin, and inconspicuous nucleoli (E*, Giemsa, 603). Immunohistochemical staining revealed positivity for CD4 (F*, 203), CD123 (G*, 203), and CD303 (H*, 203). In Image (I) bone marrow smear (1003) shows blast cells with basophilic cytoplasm and microvacuoles, eccentric nucleus, fine chromatin, and prominent nucleoli. *courtesy of Prof. Stefano A. Pileri, Milan, Italy A skin biopsy was performed on the lesion shown in Image 1A; histopathology documented a nodular infiltration of the dermis by blastic, medium-sized elements with scanty cytoplasm, vesicular nuclei with finely dispersed chromatin, and inconspicuous nucleoli (Image 1D,E). Immunohistochemistry revealed positivity for CD4 (Image 1F), CD56, CD123 (Image 1G), BCL2, CD303 (Image 1H) and negative reactions for MPO, CD68, CD20, CD79a, CD3, CD5, CD8, CD10, BCL6, cyclin D1, CD23, CD21 and EMA; such features were consistent with BPDCN. BM aspirate revealed blast cell infiltration (30% of BM nucleated cells) with basophilic cytoplasm and microvacuoles, eccentric nucleus, finely dispersed chromatin, and prominent nucleoli (Image 1I). Flow-cytometry evaluation confirmed the presence of a blastic pDC population (CD45dim/SSClow), representing 20% of total BM cellularity, showing positivity for CD4, CD56, CD123, CD303, and HLA-DR and negativity for CD34, CD117, CD19, CD5, CD7, CD22, CD14, CD13, CD15, cyCD3, MPO, and TdT. Cytogenetic evaluation documented a normal (46XY) karyotype. No mutations in NPM1 and FLT3 were found. A fluorodeoxyglucose (FDG)-positron emission tomography (PET) scan showed multiple foci of intense metabolic activity on skin and left inguinal lymph nodes. Patient received multi-agent induction chemotherapy with fractionated cyclophosphamide, vincristine, adriamycin, and dexamethasone (hyper-CVAD)1; skin lesions resolved promptly following the first treatment course and bone marrow aspiration documented morphological complete remission with positive cytofluorimetric minimal residual disease (MRD 0.01%). Due to the unavailability of fully matched or haploidentical sibling donors, a donor search in the international bone marrow donor registries was initiated, but was ultimately unsuccessful. Therefore, the patient went on to receive three additional hyper-CVAD courses. Now the patient is MRD negative, without any skin lesion. Early recognition of BPDCN still remains a challenge because of its large phenotypic overlap with other hematologic malignancies and heterogeneous clinical presentation. Due to the lack of disease-defining molecular and cytogenetic lesions, extensive flow-cytometry and immunohistochemistry characterization play a pivotal role in BPDCN diagnosis,2 ultimately guiding therapy.3 Nothing to report.