Blastic plasmacytoid dendritic cell neoplasm:Two case reports

BACKGROUND Blastic plasmacytoid dendritic cell tumor(BPDCN)is a rare and highly invasive lymphohematopoietic tumor that originates from plasmacytoid dendritic cells.BPDCN has an extremely poor prognosis.Skin lesions are usually the first manifestation of BPDCN,although the tumor may also invade the bone marrow,lymph nodes,peripheral blood,and other parts of the body,leading to several other manifestations,requiring further differentiation through skin biopsy and immunohistochemistry.CASE SUMMARY In the present paper,the cases of 2 patients diagnosed with BPDCN are discussed.The immunohistochemistry analysis of these 2 patients revealed positivity for CD4,CD56,and CD123.Currently,no standard chemotherapy regimen is available for BPDCN.Therefore,intensive therapy for acute lymphoblastic leukemia was applied as the treatment method for these 2 cases.CONCLUSION Although allogeneic bone marrow transplantation could be further effective in prolonging the median survival the ultimate prognosis was unfavorable.Future treatment modalities tailored for elderly patients will help prolong survival.

Advancing the understanding and management of blastic plasmacytoid dendritic cell neoplasm:Insights from recent case studies

We specifically discuss the mechanisms of the pathogenesis,diagnosis,and management of blastic plasmacytoid dendritic cell neoplasm(BPDCN),a rare but aggressive haematologic malignancy characterized by frequent skin manifestations and systemic dissemination.The article enriches our understanding of BPDCN through detailed case reports showing the clinical,immunophenotypic,and histopathological features that are critical for diagnosing this disease.These cases highlight the essential role of pathologists in employing advanced immunophenotyping techniques to accurately identify the disease early in its course and guide treatment decisions.Furthermore,we explore the implications of these findings for management strategies,emphasizing the use of targeted therapies such as tagraxofusp and the potential of allogeneic haematopoietic stem cell transplantation in achieving remission.The editorial underscores the importance of interdisciplinary approaches in managing BPDCN,pointing towards a future where precision medicine could significantly improve patient outcomes.

Azacitidine maintenance therapy for blastic plasmacytoid dendritic cell neoplasm allograft: A case report

BACKGROUND Blastic plasmacytoid dendritic cell neoplasm(BPDCN)is a rare,highly invasive malignant neoplasm.There is no universally accepted standard of care because of its rarity and the dearth of prospective research.It is still challenging for some patients to achieve persistent clinical remission or cure,despite the success of allogeneic hematopoietic stem cell transplantation(allo-HSCT),indicating that there is still a significant recurrence rate.We report a case of prevention of BPDCN allograft recurrence by azacitidine maintenance therapy and review the relevant literature.CASE SUMMARY We report a 41-year-old man with BPDCN who was admitted to hospital due to skin sclerosis for>5 mo’duration.BPDCN was diagnosed by combined clinical assessment and laboratory examinations.Following diagnosis,the patients underwent induction consolidation chemotherapy to achieve the first complete remission,followed by bridging allo-HSCT.Post-transplantation,azacitidine(75 mg/m2 for 7 d)was administered as maintenance therapy,with repeat administration every 4–6 wk and appropriate extension of the chemotherapy cycle.After 10 cycles,the patient has been disease free for 26 mo after transplantation.Regular assessments of bone marrow morphology,minimal residual disease,full donor chimerism,Epstein–Barr virus,and cytomegalovirus all yielded normal results with no abnormalities detected.CONCLUSION Azacitidine may be a safe and effective maintenance treatment for BPDCN following transplantation because there were no overt adverse events during the course of treatment.

Blastic plasmacytoid dendritic cell neoplasm in Jinhua,China:Two case reports

BACKGROUND Blastic plasmacytoid dendritic cell neoplasm(BPDCN)is a rare and clinically aggressive hematologic malignancy originating from the precursors of plasmacytoid dendritic cells.BPDCN often involves the skin,lymph nodes,and bone marrow,with rapid clinical progression and a poor prognosis.The BPDCN diagnosis is mainly based on the immunophenotype.CASE SUMMARY In this paper,we retrospectively analyzed 2 cases of BPDCN.Both patients were elderly males.The lesions manifested as skin masses.Morphological manifestations included diffuse and dense tumor cell infiltration of the dermis and subcutaneous tissues.Immunohistochemistry staining showed that cluster of differentiation CD4,CD56,CD43,and CD123 were positive.CONCLUSION In this paper,we retrospectively analyzed 2 cases of BPDCN.Both patients were elderly males.The lesions manifested as skin masses.Morphological manifestations included diffuse and dense tumor cell infiltration of the dermis and subcutaneous tissues.Immunohistochemistry staining showed that cluster of differentiation CD4,CD56,CD43,and CD123 were positive.

Blastic Plasmacytoid Dendritic Cell Neoplasm:Progress in Cell Origin,Molecular Biology,Diagnostic Criteria and Therapeutic Approaches

Blastic plasmacytoid dendritic cell neoplasm(BPDCN)is a rare hematological malignancy characterized by recurrent skin nodules,an aggressive clinical course with rapid involvement of hematological organs,and a poor prognosis with poor overall survival.BPDCN is derived from plasmacytoid dendritic cells(pDCs)and its pathogenesis is unclear.The tumor cells show aberrant expression of CD4,CD56,interleukin-3 receptor alpha chain(CD 123),blood dendritic cell antigen 2(BDCA 2/CD303),blood dendritic cell antigen 4(BDCA4)and transcription factor(E protein)E2-2(TCF4).The best treatment drugs are based on experience by adopting those used for either leukemia or lymphoma.Relapse with drug resistance generally occurs quickly.Stem cell transplantation after the first complete remission is recommended and tagraxofusp is the first targeted therapy.In this review,we summarize the differentiation of BPDCN from its cell origin,its connection with normal pDCs,clinical characteristics,genetic mutations and advances in treatment of BPDCN.This review provides insights into the mechanisms of and new therapeutic approaches for BPDCN.

Blastic plasmacytoid dendritic cell neoplasm with skin and bone marrow involvement: Report of three cases

BACKGROUND Blastic plasmacytoid dendritic cell neoplasm(BPDCN)is a rare and highly aggressive hematopoietic malignancy.BPDCN is difficult to diagnose because of the overlap in morphologic and immunophenotypic features with various cutaneous lymphatic hematopoietic tumors.CASE SUMMARY We report on three BPDCN cases,all characterized by skin nodules and examined by histology,immunohistochemical detection,in situ hybridization for Epstein-Barr virus,and follow-up.We also review the relevant literature.All patients were positive for CD56 and negative for Epstein-Barr encoded small RNA.Two patients had bone marrow involvement.Chemotherapy is the main treatment for BPDCN,but case 1 showed bone marrow suppression and case 2 developed recurrence after chemotherapy.Case 1 survived for 7 mo,case 2 for 17 mo,and case 3 for 9 mo.CONCLUSION An accurate pathological diagnosis is a precondition for treatment,and the diagnosis of BPDCN should be based on a combination of clinical symptoms,pathological characteristics,immunophenotype,and other auxiliary examinations.It is necessary to clarify the clinicopathological features and biological behavior of BPDCN to improve its understanding by both clinicians and pathologists.Case 2 survived significantly longer than the other two cases,suggesting that the treatment received by case 2 was more effective.

母细胞性浆细胞样树突状细胞肿瘤临床和病理特征分析

目的:归纳并分析母细胞性浆细胞样树突状细胞肿瘤(BPDCN)的临床资料,为进一步认识该类疾病提供依据。方法:回顾性分析11例BPDCN患者的临床表现、免疫表型及病理特点、治疗与预后。结果:11例明确诊断BPDCN的患者中,男性8例、女性3例,中位年龄44(6-81)岁。临床主要以皮疹、包块等为首发症状,并伴有淋巴结、骨髓受累。肿瘤性母细胞性浆细胞样树突状细胞(pDC)表达HLA-DR、CD4、CD56、CD123,不表达cCD3、cMPO、cCD79a,部分病例可表达CD38、CD99、CD36。临床上手术切除、多次化疗失败的患者复发快,患者生存期短。首次化疗达到完全缓解的患者pDC细胞不表达CD56,且经骨髓移植后具有较长的生存期。结论:BPDCN免疫表型具有异质性,CD56是区分肿瘤性和正常pDC细胞的良好标志物;化疗缓解后进行造血干细胞移植的BPDCN患者预后较好。

母细胞性浆细胞样树突细胞肿瘤2例并文献复习

目的探讨母细胞性浆细胞样树突细胞肿瘤的临床病理特征、治疗及预后。方法结合相关文献,回顾性分析2例母细胞性浆细胞样树突细胞肿瘤患者的临床表现、组织学形态、免疫表型、治疗方案及预后。结果2例组织形态均符合母细胞性浆细胞样树突细胞肿瘤的病理改变,免疫组织标记CD4、CD56、CD123、TCL1阳性,排除淋巴系、髓系及NK细胞来源,2例EBER原位杂交检测结果均为阴性;例l累及骨髓及淋巴结,对症支持治疗,2月后死亡;例2经CHOP方案化疗8周期,半年后病情进展,全身多发红疹,后予吉西他滨、奥沙利铂及培门冬酶化疗9周期,目前病情稳定。结论母细胞性浆细胞样树突细胞肿瘤多以皮肤症状为首发,具有独特的临床病理特点,诊断依靠组织学及免疫表型,目前尚无有效的治疗方案且预后差。

母细胞性浆细胞样树突状细胞肿瘤4例临床病理分析

目的探讨母细胞性浆细胞样树突状细胞肿瘤(BPDCN)的临床病理特征、免疫表型、鉴别诊断、治疗及预后。方法回顾性分析明确诊断的4例BPDCN患者的临床特征、影像学、病理组织学、免疫表型及基因测序结果,复习国内外相关文献。结果4例BPDCN中,男性3例,女性1例;发病年龄17~59岁,中位年龄52岁;4例均以皮肤侵犯为首发症状,2例伴淋巴结转移,3例伴骨髓累及,1例伴中枢及周围神经系统侵犯。免疫组化:肿瘤细胞均表达CD4、CD56、CD43、BCL-2,3例CD123阳性,Ki-67增殖指数20%~90%。EBER原位杂交检测均为阴性。其中1例行基因检测:染色体未见明显异常,髓系74种基因突变分析ASXL124.8%、TET220.6%。T细胞受体基因重排克隆性分析均为阴性。结论BPDCN是一种临床少见的高度侵袭性血液系统恶性肿瘤,病程进展快,预后极差,CD4、CD56、CD123及BCL-2阳性表达是其显著的免疫表型,不表达髓系细胞或B、T淋巴细胞免疫标记。诊断时除了病理形态学,还需结合临床表现、免疫表型、实验室检查等综合分析,必要时借助分子遗传学检测辅助诊断,避免误诊和漏诊。

母细胞性浆细胞样树突细胞肿瘤一例并文献复习

母细胞性浆细胞样树突细胞肿瘤恶性程度极高,多以皮肤为首发表现,皮损表现多样,易误诊漏诊,诊断需结合广泛的免疫表型和组织病理学特点,易复发,预后不良。我院诊治1例76岁老年男性患者,以头颈部暗紫色浸润性结节和肿块为首发表现。免疫表型和组织病理学特点符合母细胞性浆细胞样树突细胞肿瘤。

Inflammation-based Glasgow prognostic score as an independent prognostic factor in patients with angioimmunoblastic T-cell lymphoma

Angioimmunoblastic T-cell lymphoma(AITL)is an aggressive form of peripheral T-cell lymphoma(PIT)associated with poor prognosis.It is characterized by lymph node enlargement,B symptoms(unexplained recurrent fevers(often above 38℃),night sweats,and unexplained weight loss of more than 10%within 6 months),polyclonal hypergammaglobulinemia,and autoimmune hemolysis.[1] C-reactive protein(CRP)synthesized by hepatocytes is an acute-phase protein and an important marker of systemic inflammation.Serum CRP level is not only an independent prognostic factor in Hodgkin lymphoma but also an important independent predictor of AITL.

Sustained release of Semaphorin 3A from a-tricalcium phosphate based cement composite contributes to osteoblastic differentiation of MC3T3-E1 cells

The reinforcement of calcium phosphate materials with silk fibroin （SF） has been one of the strategies to overcome the brittleness. However, the lack of osteoinductivity may still restrict their further use. This study aimed to investigate the biocompatibility and osteogenesis capacity of a novel Semaphorin 3A-loaded chitosan microspheres/SF/a-tricalcium phosphate composite （Sema3A CMs/SF/a-TCP） in vitro. Sema3A was first incorporated into CMs, and the Sema3A CMs/SF/a-TCP composite was then prepared. The morphology of the CMs was observed using SEM. The in vitro release kinetics, cytotoxicity, and cell compatibility were evaluated, and the real-time quantitative polymerase chain reaction （RT-qPCR） and activity of alkaline phosphatase （ALP） were used to evaluate the osteogenesis capacity of the composite. The in vitro release of Sema3A from the Sema3A CMs/SF/a-TCP composite showed a temporally controlled manner. The extract of the Sema3A CMs/SF/a-TCP composite presented no obvious side effect on the MC3T3-E1 cell proliferation, nor promote cell proliferation. The MC3T3-E1 cells were well-spread and presented an elongated shape on the Sema3A CMs/SF/a-TCP composite surface; the ALP activity and the osteogenic-related gene expression were higher than those seeded on the surface of the CMs/SF/a-TCP and SF/a-TCP composites. In conclusion, Sema3A CMslSF/a-TCP has excellent biocompatibility and contributes to the osteoblastic differentiation of MC3T3-E1 cells.

CD4^(-)CD56^(+)母细胞性浆细胞样树突细胞肿瘤的临床特征

目的:探讨CD4^(-)CD56^(+)母细胞性浆细胞样树突细胞肿瘤患者的临床表现、病理特点、免疫表型、诊治经过及预后,以提高对此类罕见疾病的认识。方法:对本院就诊的两例CD4^(-)CD56^(+)母细胞性浆细胞样树突细胞肿瘤患者的临床资料、实验室资料、治疗方案进行回顾性分析。结果:两例患者均为老年男性,肿瘤累及皮肤、骨髓、淋巴结等部位,皮肤病理显示,CD56、CD123均为阳性,而CD4、CD34、TdT、CD3、CD20、MPO、EBER均为阴性。骨髓流式细胞检测结果显示,CD56、CD123、CD304均为阳性,而髓系、淋系特异性免疫标志均为阴性。两例患者初始对急性淋巴细胞白血病或淋巴瘤样化疗方案非常敏感,但短期内复发,生存期分别为36、4个月。结论:CD4^(-)CD56^(+)母细胞性浆细胞样树突细胞肿瘤罕见,该病容易误诊且预后差,应优先采用急性淋巴细胞白血病或淋巴瘤样的治疗方案改善不良预后。

母细胞性浆细胞样树突细胞肿瘤一例

母细胞性浆细胞样树突状细胞肿瘤(BPDCN)是一种罕见的侵袭性血液系统恶性肿瘤,本文报道一例。患者,男,58岁。全身红斑、斑块、结节10个月,加重1个月。皮肤科检查:面部、躯干、四肢多发融合性暗紫红斑块、结节、肿块,浸润明显,触之质韧。皮损组织病理及免疫组化结果提示母细胞性浆细胞样树突细胞肿瘤。予CHOP+西达本胺联合化疗后患者全身皮损明显消退。骨髓涂片、骨髓流式考虑母细胞性浆细胞样树突细胞肿瘤,骨髓活检示:淋巴造血系统肿瘤。全身PET/CT检查示:全身多区域淋巴结稍大,糖代谢增高,以双侧腹股沟及腋窝为著,脾不大,但代谢弥漫均匀略高于肝水平。

中西医结合治疗母细胞性浆细胞样树突状细胞肿瘤伴噬血细胞综合征个案报道

母细胞性浆细胞样树突状细胞肿瘤(BPDCN)起病急,预后差,目前没有特定的诊疗指南及专家共识。本案在疾病确诊后先行3周期噬血细胞综合征-1994(HLH-1994)方案治疗噬血细胞综合征,达到临床完全缓解后选用CHOP方案化疗治疗BPDCN,治疗过程中药及中医适宜技术如火龙灸等全程参与。中医治疗整体可分3期,初期以益气补虚、清热解毒、凉血散瘀为治疗原则,方选犀角地黄汤加减;中期以益气补血、健脾消食、填精益髓为治疗原则,方选归脾汤加减;后期为巩固治疗时期,以益气化痰健脾、补肾壮骨为主要治疗原则,方选香砂六君汤加减。

流式细胞术检测皮肤组织在母细胞性浆细胞样树突细胞肿瘤诊断中的应用

目的:探讨流式细胞术(FCM)检测皮肤组织样本在诊断母细胞性浆细胞样树突细胞肿瘤(BPDCN)中的作用。方法:利用多色流式检测皮肤组织与骨髓,并结合组织病理学、骨髓细胞形态学、遗传学、二代测序(NGS)等检测结果对3例已确诊的BPDCN进行回顾性分析。结果:3例患者均以皮肤损害为首发症状,FCM检测骨髓仅发现1例患者标本存在BPDCN细胞,而3例患者皮肤组织标本中均发现BPDCN细胞;与皮肤组织病理免疫组化结果诊断一致;病例2患者骨髓细胞学和遗传学检查均未发现BPDCN细胞,病例1患者骨髓细胞学中发现BPDCN细胞,病例3患者NGS检测到BPDCN相关基因突变。结论:流式细胞免疫分型是BPDCN诊断的实用辅助手段,可以在早期皮肤组织标本中快速精准地诊断BPDCN,同时进行鉴别诊断。

Is the erythropoietin receptor the key to the identification of the central macrophage in erythroblastic islands?

Erythroblastic islands(EBI)are niches for mammalian erythropoiesis.1 They were first identified in 1958 by Marcel Bessis and consist of a group of differentiating erythroblasts surrounding a central macrophage.2 Over the years,a lot of attention has been paid to understand the role of the central macrophage in regulating the differentiation of the maturing erythroblasts within these islands and in defining the surface proteins thatmediate the interaction between the erythroblasts and the centralmacrophage.3–14While some progress has beenmade in these areas of investigation,the definitive identity of this central macrophage and its function is yet to be fully characterized.

母细胞性浆细胞样树突细胞肿瘤临床特点及治疗分析

目的:探讨母细胞性浆细胞样树突细胞肿瘤(BPDCN)的临床表现、诊断、治疗方案及预后。方法:回顾性分析经骨髓穿刺及淋巴结活检确诊的4例BPDCN患者的临床特征、骨髓形态及免疫表型、治疗及预后。结果:4例患者中均有骨髓及脾脏、淋巴结累及,2例皮肤浸润,3例出现中枢神经系统浸润。骨髓中异常细胞形态可见拖尾状,免疫分型显示4例患者均表达CD56、CD4和CD123,3例患者表达CD304。1例患者拒绝化疗早期死亡;2例患者初始应用DA+VP方案治疗后均达完全缓解,其中1例在复发后应用该方案再次达完全缓解;1例患者应用减低剂量DA+VP化疗无效,之后应用维奈克拉+阿扎胞苷达完全缓解。4例患者无疾病生存期为2-7个月,总生存期为2-33个月。结论:BPDCN患者的恶性细胞多浸润骨髓、脾脏及淋巴结并具有特殊表型,且预后差。治疗方案应兼顾髓系及淋巴系,含新药的方案如BCL-2抑制剂联合去甲基化药物值得尝试。

母细胞性浆样树突细胞肿瘤13例临床病理学特征

目的:分析母细胞性浆样树突细胞肿瘤(blastic plasmacytoid dendritic cell neoplasm,BPDCN)的临床病理学特征。方法:收集2013年1月至2022年3月北京大学第一医院确诊的BPDCN患者的病历资料共13例,回顾性分析患者的临床表现、组织病理学特征、免疫表型及其预后。结果:13例患者男性11例,女性2例,中位年龄62岁(5~78岁)。13例中单器官受累5例,均为皮肤受累;多器官受累8例(皮肤/脑/乳腺+骨髓受累3例,皮肤+骨髓+淋巴结受累3例,皮肤+骨髓+淋巴结+脾受累2例)。组织病理学分析以中等至大型幼稚母细胞一致性增生浸润为特征,浸润皮肤真皮全层,骨髓病变以弥漫性浸润为主,淋巴结受累时淋巴结结构完全破坏,脾累及者主要侵犯脾红髓。免疫组织化学染色显示,13例均不同程度阳性表达CD4、CD56、CD123(13/13),9例均表达TCL1(9/9);部分表达CD68(KP1)(8/13)、TdT(7/12),CD117(2/6),显示高Ki-67增殖指数(40%~80%);不表达CD20、CD3、CD34、MPO、CD30;EBER原位杂交阴性(0/9)。明确诊断后6例接受化疗,其中1例辅以放疗,2例接受后续骨髓移植;另有2例仅维持治疗;随访中位时间14个月(6~36个月),5例死于疾病进展(6~18个月),3例存活(7~36个月),5例失访。结论:BPDCN是罕见的恶性淋巴造血系肿瘤类型,侵袭性强,临床预后较差。诊断需结合临床特征、组织病理学、免疫组织化学表型,并注意与其他母细胞形态或CD4+CD56+淋巴造血系肿瘤相鉴别。

母细胞性浆细胞样树突细胞肿瘤患者的临床分析

目的:探讨母细胞性浆细胞样树突细胞肿瘤(BPDCN)的临床特征、治疗方案及预后。方法:回顾性分析2016年6月至2021年11月在武汉市第一医院和武汉市同济医院诊治的5例BPDCN患者的临床资料。结果:5例患者中,男性3例,女性2例,中位年龄28(10-52)岁。4例起病时有明显皮肤损害,1例以急性白血病起病,无明显皮肤损害,但在复发时累及皮肤。其他病变累及部位包括骨髓(2/5)、外周血(2/5)、淋巴结(3/5)、肝脾(2/5),无中枢神经系统受累。肿瘤细胞特征性的免疫标记物CD4、CD56、CD123均为阳性,中位Ki-67指数为70%。利用高通量测序技术(NGS)发现3例患者分别存在TET2、ASXL1、NRAS基因突变。采用急性淋巴细胞白血病(ALL)、急性髓系白血病(AML)及侵袭性NK/T细胞淋巴瘤的一线诱导化疗方案,1例早期死亡,3例达CR,1例达PR。2例患者复发、进展,更换治疗方案后其中1例再次达CR。1例行自体造血干细胞移植,长期存活,OS时间87个月;3例行异基因造血干细胞移植,1例死亡,2例存活。可评价疗效的4例患者中位随访时间为28.5(9-84)个月,中位OS时间为31.5(10-87)个月。结论:BPDCN异质性强,总体预后不良。造血干细胞移植特别是异基因造血干细胞移植可显著改善BPDCN患者的预后。