Detection of Minimal Bone Marrow involvement of Blastic Plasmacytoid Dendritic Cell Neoplastic Cells - CD303 immunostaining as a diagnostic tool-

Abstract

JC EH lin xp ematopathol Original article INTRODUCTIONBlastic plasmacytoid dendritic cell neoplasm (BPDCN) is a relatively rare hematological malignancy, 1 accounting for 0.44% of all hematological malignancies and 0.7% of all cutaneous lymphomas.2 BPDCN is a clinically aggressive tumor derived from the precursors of plasmacytoid dendritic cells (pDC).1 It usually occurs at the age of 50-70 and is rare in pediatric patients; the ratio of male to female patients is 2.5-2.7:1, and the median survival is 12-14 months. 1-4The clinical features and evolution of BPDCN are rather homogenous and categorized into dermatopathic (>90% of cases) and leukemic patterns. 5 The dermatopathic pattern is characterized by a deceptive indolent onset dominated by skin lesions, which is the prominent and only detectable clinical feature in nearly 50% of patients, followed by tumor dissemination. Conversely, the leukemic variant is characterized by an elevated white blood cell count, circulating neoplastic cells, and massive bone marrow (BM) infiltration. Pure leukemic presentation is very rare (7% of 756 cases) and is mostly associated with multiple skin lesions. Other manifestations are related with tumor infiltration into the lymph nodes (localized and generalized lymphadenopathy), spleen, and liver. Notably, BPDCN can be precisely diagnosed by the immunohistochemical scoring system using CD4, CD56, and Blastic plasmacytoid dendritic cell (pDC) neoplasm (BPDCN) is a relatively rare hematological malignancy with significantly complex clinicopathological features that are still unclear. This study aimed to analyze the clinicopathological data of BPDCN and evaluate immunohistochemical detection of minimal bone marrow (BM) involvement. In this study, we examined skin and BM lesions from 6 patients with BPDCN. Neoplastic cells tested positive for CD303 (polyclonal, 100%; monoclonal, 40%) in the skin lesions and for CD303 (polyclonal, 100%; monoclonal, 67%) in the BM clots. Although immunostaining of CD4, CD56, CD123, CD303, and TCLl detected minimal BM involvement in 3 patients, morphological identification was challenging in the BM clots stained with hematoxylin-eosin. In conclusion, our results demonstrate the significance of observing BM smears to detect neoplastic cells and that immunohistochemical examination, including CD303 antibodies, is useful to detect minimal BM involvement. This study is the first to report the expression of thymic stromal lymphopoietin (TSLP) and its receptor in BPDCN cells. Therefore, the TSLP/TSLP receptor axis may be associated with the proliferation of BPDCN, and consequently, the survival of patients.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN): A promising future in the era of targeted therapeutics

“…CD303 is one such specific marker located exclusively on the surface of plasmacytoid dendritic cells (pDCs). CD303 is a dendritic cell antigen that when bound perpetuates a series of phosphorylation cascades which eventually lead to Toll‐like receptor‐7 or Toll‐like receptor‐9 induced interferon‐1 (IFN‐1) production 53–55 . IFN‐1 production then sets off the recruitment of a host of inflammatory mediators involved in the innate and adaptive immune response.…”

“…IFN‐1 production then sets off the recruitment of a host of inflammatory mediators involved in the innate and adaptive immune response. The role of CD303 in the inflammatory pathway has led to the development of the anti‐CD303 molecule, BIIB059/24F4, in the treatment of cutaneous lupus erythematous 53, 56 . Binding to this monoclonal antibody facilitates endocytosis of the surface antigen, thereby attenuating the immune response by restricting the IFN‐1 cascade.…”

Blastic plasmacytoid dendritic-cell neoplasia: a challenging case report

“…We started treatment with the recently FDA-approved CD123 cytotoxin Tagraxofusp (Elzonris®) (Pemmaraju 2020) in November 2020. Due to the poor prognosis and high-risk cytogenetic mutations, a hematopoietic allogenic stem cell transplantation was planned in first remission (Ohe et al 2018). Unfortunately, Tagraxofusp had to be discontinued after two cycles due to inacceptable hepatic toxicity and a relevant capillary leak syndrome, though clinically primary treatment response seemed to be very good.…”

Cancer stem cell marker-positive tumour nests in intrahepatic cholangiocarcinoma are related to epithelial type CD1a-positive dendritic cell infiltration and to high Sox9 expression

“…Three µm-thick tissue sections were prepared from para n-embedded blocks. Immunohistochemistry was performed as previously described (24). In brief, after depara nization, the endogenous peroxidase activity was stopped by immersion in methanol containing 0.3% H 2 O 2 at 4 °C for 30 min.…”