脑脊液流式细胞术在诊断非霍奇金淋巴瘤累及软脑/脊膜中的应用

Identification of Leptomeningeal Disease in Aggressive B-Cell Non-Hodgkin′s Lymphoma by Flow Cytometry

目的探讨脑脊液流式细胞术(CSF-FCM)在诊断非霍奇金淋巴瘤(NHL)脑脊膜转移(LM)中的价值。方法回顾性分析3例影像学检查及脑脊液(CSF)病理检查均不典型的继发中枢神经系统淋巴瘤(SCNSL)的临床资料并复习相关文献。结果病例1诊断为睾丸弥漫大B细胞淋巴瘤,查体无神经系统症状,CSF细胞学检查阴性,但CSF-FCM检到少量单克隆B淋巴细胞(CD19+B细胞10个,表达kappa,不表达lambda),予R-CHOP-HD-MTX化疗及腰穿鞘内注射治疗,患者停化疗7月复发,脑组织活检证实中枢复发。病例2诊断为小B细胞淋巴瘤(脾边缘区淋巴瘤可能性大),查体有神经系统症状,CSF细胞学检查阴性,CSF-FCM检测到单克隆B细胞占CSF有核细胞65.8%,表达CD19 kappa,不表达lambda,确诊NHL脑脊膜累及。病例3确诊小B细胞淋巴瘤(淋巴浆细胞淋巴瘤可能),停化疗8月后出现神经系统症状,骨髓检查﹑CSF细胞学检查及脑活检均未明确诊断,CSF-FCM提示脑脊液单克隆B细胞增多,表达CD45dim+CD19+CD20dim+CD5-CD10-CD22dim+CD2部分+FMC7部分+KAPPA-LAMBDA+CD200+CD79b+CD25+CD103-CD11C-CD38部分+,确诊NHL的脑脊膜受累。结论所有存在CNS受累风险的淋巴瘤患者均应接受腰椎穿刺(LP)检查,CSF的流式细胞术分析有助于隐匿性脑脊膜受累的诊断。CSF样本的全面评估还包括二代测序基因检测、免疫球蛋白重链(IgH)或T细胞受体基因重排检测及细胞因子检测。

Objective In the current study,we evaluated 4-parameter flow cytometry(FCM)with conventional cytology(CC)to identify neoplastic cells in stabilized CSF samples from aggressive B-cell non-Hodgkin′s lymphoma.Methods We retrospectively summarized the clinical and biological characteristics of 3 cases of B-cell non-Hodgkin′s lymphoma involving the leptomeningeal and also reviewed the previous literatures.Results All three patients were diagnosed as SCNSL by cerebrospinal fluid flow cytometry,and received the treatment for central nervous system lymphoma.Conclusion FCM can significantly improve the sensitivity of CC to identify aggressive B-NHL with a higher risk of central nervous system disease,especially in paucicellular samples.The comprehensive evaluation of CSF samples also includes next-generation sequencing(NGS),immunoglobulin heavy chain(IgH)or T cell receptor gene rearrangement and cytokines.