母细胞性浆细胞样树突状细胞肿瘤的临床分析

Clinical analysis of blastic plasmacytoid dendritic cell neoplasm

目的探讨母细胞性浆细胞样树突状细胞肿瘤（BPDCN）的临床特征、诊断、治疗方法及疗效，以提高临床对该病的认识。方法选择2017年8月21日，清华大学附属北京清华长庚医院血液科收治的1例BPDCN患者为研究对象。本例患者2016年11月于外院被诊断为BPDCN，随后接受5个疗程CHOP（环磷酰胺＋多柔比星＋长春新碱＋泼尼松）-21方案化疗，获得部分缓解（PR）后，于2017年6月复发，为进一步治疗就诊于本院血液科。入院后，结合患者病史，并根据临床表现、骨髓检查及相关实验室检查结果进行诊断。2017年8月25日患者接受VDCP（长春地辛＋柔红霉素＋环磷酰胺＋地塞米松）方案化疗，其中长春地辛的治疗策略为4 mg/d，d1、8、15、22应用；柔红霉素为60 mg/d，d4-5应用，80 mg/d，d6应用，60 mg/d，d15-16应用；环磷酰胺为1.7 g/d，d4、15应用；地塞米松为17 mg/d，d1-7应用；共化疗3个疗程。回顾性分析本例患者的实验室检查结果、进一步确诊及对疾病进展进行评估及疗效，并且对相关文献进行复习，探讨BPDCN诊疗的研究进展。结果①本次入院后，患者骨髓细胞流式细胞术检测结果示，原始细胞分布区域可见异常细胞群，约占有核细胞的9.4%，表达人类白细胞抗原（HLA）-DR、CD4、CD38、CD56、CD123，部分细胞表达CD33。骨髓细胞形态学检查结果示，骨髓细胞增生明显活跃，粒细胞系比例为38.0%、红细胞系比例为24.0%，粒、红细胞系比值为1.58∶1；可见巨核系细胞，以及成片增生的异型淋巴样细胞；原始细胞比例为27.0%，考虑为BPDCN骨髓侵犯。骨髓细胞免疫组织化学检测结果示，CD4（＋）、CD56（＋）、CD123（＋）、CD68（＋）、CD235（红细胞系＋）、髓过氧化物酶（MPO）（粒细胞系＋）、末端脱氧核苷酸转移酶（TdT）（-）、CD117（〈1%）、CD3（-）、CD20（-）、CD23（-）、T细胞内抗原（TIA）-1（＋），颗粒酶B（-）。患者头皮活组织检查结果示，皮肤组织真皮全层可见肿瘤细胞弥漫性单一性浸润，未累及表皮；免疫组织化学检测结果示，CD4（＋）、CD43（＋）、CD56（＋）、CD123（弱＋）、TdT（散在＋）、CD117（-）、CD3（-）、CD20（-）、CD23（-）、TIA-1（-）、颗粒酶B（-）、CD68（散在＋）。②本例患者确诊为BPDCN，入院时患者综合评估为疾病进展（PD）。③ VDCP方案化疗结束后，患者头皮、颜面、躯干皮疹全部消退；粒细胞计数恢复至正常参考值范围内；骨髓涂片结果示，骨髓增生明显活跃，粒细胞系比例为50.0%、红细胞系比例为36.5%，粒、红细胞系比值为1.37∶1，原始粒细胞比例为0.5%，可见异常淋巴细胞比例为3.5%。综合评价患者疗效为完全缓解（CR）。患者拒绝继续治疗，于发病后20个月后（2018年2月）死亡。结论BPDCN非常罕见，病程呈侵袭性，目前尚无标准治疗方案，预后差。

ObjectiveTo investigate the clinical features, diagnosis, treatment and efficacy of blastic plasmacytoid dendritic cell neoplasm （BPDCN） in order to improve the understanding of BPDCN. MethodsOn 21 August 2017, a case of BPDCN patient admitted in Hematology Department of Beijing Tsinghua Changgung Hospital affiliated to Tsinghua University, was included in this study. This patient was diagnosed as BPDCN in other hospital in November 2016, and then received 5 courses of CHOP （cyclophosphamide＋ doxorubicin＋ vincristine＋ prednisone）-21 regimen for chemotherapy. After partial remission （PR）, the patient relapsed in June 2017, and was admitted in Hematology Department of our hospital for further treatment. After admission, combined with the patient′s medical history, diagnosis was made according to the clinical manifestations, bone marrow examination and relevant laboratory examination results. On 25 August 2017, the patient received 3 courses of VDCP （vindesine＋ daunorubicin＋ cyclophosphamide＋ dexamethasone） regimen for chemotherapy. Vindesine 4 mg/d, d1, 8, 15, 22; doxorubicin 60 mg/d, d4-5, 80 mg/d, d6, 60 mg/d, d15-16; cyclophosphamide 1.7 g/d, d4, 15; and dexamethasone 17 mg/d, d1-7 were applied. The laboratory test results, further diagnosis and assesement of disease, and curative effects of this patient were analyzed retrospectively, and related literature was reviewed to explore the research progress of BPDCN diagnosis and treatment.Results① After admission, flow cytometry test results of the patients′ bone marrow cells showed abnormal cell population within original cell distribution area, accounting for about 9.4%. Abnormal cell expressed human leukocyte antigen （HLA）-DR, CD4, CD38, CD56 and CD123, and some expressed CD33. Results of morphological examination of bone marrow cells showed that proliferation of bone marrow cells was significantly active. Proportion of granulocyte was 38.0%, proportion of erythroid was 24.0%, and ratio of granulocyte and erythroid was 1.58∶1. Megakaryotic cells and heteromorphic lymphoid cells could be seen. Ratio of primitive cells was 27.0%, and was BPDCN bone marrow invasion. Bone marrow cell immunohistochemical test results showed CD4 （＋ ）, CD56 （＋ ）, CD123 （＋ ）, CD68 （＋ ）, CD235 （erythroid＋ ）, myeloperoxidase （MPO） （granulocyte＋ ）, terminal deoxynucleotidyl transferase （TdT） （-）, CD117 （〈1%）, CD3 （-）, CD20 （-）, CD23 （-）, T cell intracellular antigen （TIA）-1 （＋ ）, granzyme B （-）. Results of scalp biopsy showed that tumor cells were diffuse in dermal layer of the skin without involving the epidermis. Immunohistochemical results showed that CD4 （＋ ）, CD43 （＋ ）, CD56 （＋ ）, CD123 （weak＋ ）, TdT （scattered＋ ）, CD117 （-）, CD3 （-）, CD23 （-）, TIA-1 （-）, granzyme B （-）, and CD68 （scattered＋ ）. ② The patient was diagnosed with BPDCN, and was comprehensively evaluated as progressive disease （PD） at admission. ③ After the treatment with VDCP regimen, all rashes on the scalp, face and trunk of the patient were eliminated. The granulocyte count returned to the normal reference range. Bone marrow smear results showed that bone marrow hyperplasia was significantly active, with 50.0% granulocytes and 36.5% erythroid. Ratio of granulocytes and red line cells was 1.37∶1. Proportion of primitive granulocytes and abnormal lymphocytes were 0.5% and 3.5%, respectively. The comprehensive evaluation was complete remission （CR）. The patient refused to continue treatment and died 20 months after the onset （February 2018）.ConclusionBPDCN is a rare and highly aggressive disease with poor prognosis, and standard treatment protocols for BPDCN has not been established currently.