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中华临床实验室管理电子杂志 ›› 2017, Vol. 05 ›› Issue (02) : 81 -88. doi: 10.3877/cma.j.issn.2095-5820.2017.02.005

所属专题: 文献

专题笔谈

流式细胞术在成熟淋巴细胞肿瘤诊断中的应用
王卉1,(), 王爱先1, 甄军毅1, 吴雪英1, 陈曼1, 宫美维1, 宋雨竹1, 魏国新1, 杜晴1   
  1. 1. 065201 三河市,河北燕达陆道培医院病理与检验医学科
  • 收稿日期:2017-01-23 出版日期:2017-05-28
  • 通信作者: 王卉

Diagnostic application of flow cytometry in mature lymphoid neoplasm

Hui Wang1,(), Aixian Wang1, Junyi Zhen1, Xueying Wu1, Man Chen1, Meiwei Gong1, Yuzhu Song1, Guoxin Wei1, Qing Du1   

  1. 1. Department of Pathology and Clinical Laboratory, Hebei Yanda Lu Daopei Hospital, Sanhe 065201, China
  • Received:2017-01-23 Published:2017-05-28
  • Corresponding author: Hui Wang
  • About author:
    Corresponding author: Wang Hui, Email:
引用本文:

王卉, 王爱先, 甄军毅, 吴雪英, 陈曼, 宫美维, 宋雨竹, 魏国新, 杜晴. 流式细胞术在成熟淋巴细胞肿瘤诊断中的应用[J/OL]. 中华临床实验室管理电子杂志, 2017, 05(02): 81-88.

Hui Wang, Aixian Wang, Junyi Zhen, Xueying Wu, Man Chen, Meiwei Gong, Yuzhu Song, Guoxin Wei, Qing Du. Diagnostic application of flow cytometry in mature lymphoid neoplasm[J/OL]. Chinese Journal of Clinical Laboratory Management(Electronic Edition), 2017, 05(02): 81-88.

流式细胞术根据抗原抗体反应结合激光激发荧光素显色检测细胞免疫学标志的表达,在临床疾病检测,尤其是急性白血病诊断与分型中起到了举足轻重的作用。但是在成熟淋巴细胞肿瘤诊断中,因取材不易,存在大量正常细胞背景等原因,其应用有待进一步加强。本文从流式细胞术与病理免疫组化的异同、成熟淋巴细胞肿瘤检测常用免疫学标志、临床常见成熟淋巴细胞肿瘤的免疫表型、流式细胞术检测的常见问题与注意事项4方面阐述流式细胞术在成熟淋巴细胞肿瘤诊断中的作用,以帮助临床工作者深入了解该技术与病理相结合正确诊断成熟淋巴细胞肿瘤的意义。

Flow cytometry (FCM) uses flow cytometer to detect the expression of immunological markers on cells based on antigen-antibody binding and laser activating fluorescence. FCM plays a very important role in clinical diagnosis especially in acute leukemia diagnosis and subclassification. However, due to the difficulty in acquiring the sample and the existence of normal lymphocytes in the background, its application and improvement should be further strengthened in the diagnosis of mature lymphoid neoplasm. This paper focuses on the similarity and differences between FCM and pathology immunohistology, immune makers in lymphoma detection, immunophenotypic features of common mature lymphoid neoplasm, common issues and key points in FCM detection, to study the diagnostic application of flow cytometry in mature lymphoid neoplasm. This will help clinicians understand this technic, and make a correct diagnosis by FCM combining with pathology.

表1 成熟淋巴细胞肿瘤检测的常用标志
表2 常见成熟B淋巴细胞肿瘤免疫分型
分组 主要亚型 主要免疫表型特点 辅助免疫表型特点 其他诊断信息
CD5/CD10- CLL/SLL/MBL CD5、CD23、CD22或者CD79bdim、FMC7-/dim、sIgdim(上述五项每项1分,≥4分为典型CLL/SLL表型) CD20dim、CD81dim、CD200bri、CD43、CD200/CD148高,FSC和SSC小于正常淋巴细胞 形态学有典型特点
MCL CD5、CD23-/+、CD22或者CD79bbri、FMC7、sIgbri CD20bri、CD81bri、CD200-/dim、CD43int、CD200/CD148低 主要为t(11;14)CCND1/IgH重排,少数为CCND2,轻链重排;SOX11阳性
PLL 表型多样化。CLL幼淋变可能伴有CLL表型,原发PLL除了强表达免疫蛋白和B细胞标志以外没有特殊免疫表型 57%病例表达ZAP70,46%病例表达CD38,并且与免疫球蛋白基因突变状态无关 大(多数)细胞有明显核仁,没有t(11;14)CCND1重排
DLBCL 见下述CD5-/CD10-DLBCL ? 占DLBCL的10%,大多数为原发,极少数是CLL/SLL转化(Richter综合征)
MZL 见下述CD5-/CD10-MZL ? ?
LPL 见下述CD5-/CD10-LPL ? ?
CD5-/CD10 FL FSC小,ki67阴性,bcl-2阳性 CD43-;可表达或者部分表达CD23 典型病例伴有t(14;18)bcl-2/IgH重排
BL FSC和SSC中等大小,CD45/SSC设门不在淋巴细胞门内;ki67阳性(大多数病例表达率超过90%),bcl-2阴性 CD43、CD44-、CD54 典型病例伴有t(8;14)c-myc/IgH重排;或者c-mgc/轻链重排
DLBCL FSC和SSC大,CD45/SSC设门不在淋巴细胞门内。ki67部分阳性(大多数病例表达率30%~70%),部分表达bcl-2和/或bcl-6 CD43+/-、CD44、CD54bri CD10型占DLBCL30%~60%,需要做FISH检测c-myc、bcl-2、bcl-6重排,即是否为伴c-myc和bcl-2和/或bcl-6重排的高级别B细胞成熟淋巴细胞肿瘤(双打击或者三打击成熟淋巴细胞肿瘤)
HCL 见下述CD5-/CD10-HCL免疫表型 ? CD10HCL大约占HCL的10%
分组 主要亚型 主要免疫表型特点 辅助免疫表型特点 其他诊断信息
CD5-/CD10- HCLa CD25、CD103、CD11c、CD123+/- FSC中等偏大,ki67-、强表达B细胞标志和免疫球蛋白 多数病例外周血白细胞少;形态学细胞绒毛长,细胞核有切迹。大多数病例(大约76%)中有BRAF V600E突变或者MAP2K1突变
HCLva CD25-、CD103、CD11c、CD123-/+ FSC中等偏大;Ki67- 外周血白细胞中等或者多;形态学细胞绒毛短,细胞核圆无切迹;约50%病例有MAP2K1突变
除HCLv以外的其他SLVLa CD25-、CD103-、CD11c、CD123-/+ ? 外周血白细胞中等或者多。形态学细胞绒毛短,细胞核圆无切迹。无上述遗传学异常
MZL 无特殊。有浆细胞分化的可能会表达CD38和/或CD138 ? ?
CD5-MCL 为典型CD5/CD10-MCL变异型,流式诊断困难 ? ?
CD10-FL 为典型CD5-/CD10FL变异型,流式诊断困难 ? ?
LPLb 大多数IgM阳性。部分病例可以检测出单克隆浆细胞,部分病例肿瘤性B淋巴细胞会表达CD38和/或CD138 ? 虽然并不特异,但是因为大多数LPL都有MYD88 L265P突变,因此被2016年WHO纳入诊断标准
MALTb 无特殊表型,部分病例属于有浆细胞分化的成熟淋巴细胞肿瘤 ? t(11;18), t(1;14), t(14;18), t(3;14)/MALT-1重排
DLBCL FSC和SSC大,CD45/SSC设门不在淋巴细胞门内;绝大多数病例部分表达ki67(表达率>20%) ? ?
CD5/CD10 此型并不常见,除了DLBCL,一般是其他成熟淋巴细胞肿瘤的变异型,如CD5FL、CD10MCL特点见各自成熟淋巴细胞肿瘤
表3 肿瘤性浆细胞异常表型发生频率
表4 常见成熟NK/T淋巴细胞肿瘤免疫表型
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