One Case Report of A Child With CD56 Negative Blastic Plasmacytoid Dendritic Cell Neoplasm(BPDCN)Lei Ma1, Yanyan Wang1, Haiyan Ye1*, Jinshen Wang1, Yueqin Han1, Daogang Qin11. Department of Pediatrics, Liaocheng People’s Hospital, Liaocheng 252000, Shandong Province, China.* Corresponding Author: Haiyan Ye. Email: 366115886@qq.com.The authors hereby declare that there is no competing interest with the research.Tables: 0Figures: 0Text Word Count: 753Brief Running Title: Child BPDCN Case ReportKey Words: BPDCN; Blastic Plasmacytoid Dendritic Cell Neoplasm; CD123 +, CD4 +, CD56 - hematopoietic tumor; child; Acute lymphoblastic leukemia protocol, Chemotherapy; misdiagnose.To the editor:BPDCN is a very rare and highly invasive hematological malignancy with an extremely poor prognosis[1,2].The etiology, pathogenesis, and prognostic factors of BPDCN are unknown, and it is easily misdiagnosed. No standard treatment regimen exists[1,2]. Fewer than 100 cases of BPDCN in children have been reported worldwide[3,4,5], and the number of children with CD56-negative BPDCN is even rarer[6]. We have diagnosed 1 child with CD56 negative BPDCN and report it as follows.A six-year-old boy was admitted to the hospital with fever and pain from a mass on the left side of his neck. Physical examination showed hepatosplenomegaly. Hematologic examination revealed a white cell count of 147.31×109/L, a hemoglobin concentration of 102g/L, and a platelet count of 92×109/L. Leukocyte classification of blood smear showed 90% abnormal cells. Bone marrow morphologic analysis showed primitive cells, accounting for 91% of nuclear cells. 43 fusion genes in bone marrow were negative. Gene analysis showed high CRLF2 expression. Bone marrow chromosome examination showed 46XY. Bone marrow immunotyping before treatment was consistent with BPDCN but did not express CD56 (these tumor cells were positive for CD7, HLA-DR, CD33, CD123, CD4, CD99, CD304, and CD303, but negative for TDT, CD34, CD5, CD8, CD3, CD10, CD19, CD20, cCD79a, and CD64). The patient received chemotherapy according to the CCLG-2018-Acute lymphoblastic leukemia (ALL) regimen from March 7, 2020. After treatment (day 5 of oral prednisone), the bone marrow immunotyping test at the second testing institution showed BPDCN, but no CD56 expression. From these findings, a diagnosis of BPDCN was made. The patient completed chemotherapy more than 7 months ago, and repeated bone marrow MRD tests were negative.In 1994, Adachi et al. reported the first case of BPDCN[7] .In 2008, BPDCN was officially classified as acute myeloid leukemia (AML) and related precursor cell tumors as a separate type in WHO Classification criteria for Hematopoietic and lymphoid tissue tumors[8]. BPDCN was officially listed as an independent disease in WHO classification criteria for Hematopoietic and lymphoid tissue tumors in 2016[9].BPDCN has a very poor prognosis in elderly patients, and relatively good prognosis in children and young patients [10,11]. Most BPDCN patients have skin lesions as the first symptom, and the skin manifestations lack specificity, so it is easy to misdiagnose clinically. BPDCN may involve skin, bone marrow, lymph nodes, spleen, and other sites [11,12]. In this case, cervical lymph node enlargement was the initial presentation, accompanied by bone marrow invasion.As BPDCN is a rare disease, its pathogenesis is still unclear[1,2]. BPDCN tumor cells were derived from plasmacytoid dendritic cell (pDC) precursors[1,2,3].The diagnosis was based on histopathological and immunohistochemical markers. Tumor cells did not express myeloid, lymphocyte, or NK cell specific markers, but expressed CD4, CD56, CD123, TCL1A, and CD303, which could be used to diagnose the disease; CD123 was considered a specific marker for the diagnosis of BPDCN[3,4,5,10]. In a few rare cases, plasmacytoid dendritic cell associated antigens CD123, TCL1A or CD303 were positive, and CD4 negative or CD56 negative[6,11,12]. In this case, the bone marrow immunotyping of the two institutions expressed CD123, CD4 and CD303, but did not express CD56, and both supported BPDCN (CD56 negative). Cytogenetic abnormalities can be seen in about 60% of BPDCN patients, but there is no specific change[13,14].Currently, there is no standard treatment regimen, and high-intensity chemotherapy combined with hematopoietic stem cell transplantation (HSCT) is mostly used for treatment; new, targeted therapy and immunotherapy drugs have been successively put into clinical use[15]. The chemotherapy regimen is mainly based on chemotherapy for lymphoma, ALL and AML. Currently, most studies[16] recommend high-risk ALL-like chemotherapy for pediatric patients, and those without skin involvement have a better prognosis than those with skin involvement[17]. Pediatric HSCT is recommended for recurrent/refractory children[19,20]. The application of targeted drugs provides a new option for the treatment of BPDCN. CD123 is a specific marker on the surface of BPDCN tumor cells, and Tagraxofusp (SL401) with CD123 as a target is used for the treatment of newly treated or refractory BPDCN patients (age ≥2 years) [18]. The patient received ALL chemotherapy and the treatment course concluded more than 9 months ago.Children with CD56 negative BPDCN are extremely rare. Compared with adults, BPDCN in children is less invasive and has a better prognosis. At present, high-risk ALL chemotherapy is the first choice. Allogeneic HSCT can significantly improve the prognosis, but the risk of transplantation is higher than that of chemotherapy. More basic research and clinical trials are needed to provide more valuable references for treatment selection of CD56-negative BPDCN in children.
