112例淋巴系统恶性肿瘤骨髓免疫表型分析

Bone Marrow Immunophenotypes of 112 Cases of Lymphoid System Malignant Diseases

背景与目的:淋巴细胞白血病和淋巴瘤骨髓侵犯的诊断以细胞形态学为基础,而免疫分型可通过获得肿瘤细胞分化和发育阶段的信息使淋巴系统恶性肿瘤的诊断更为准确,为临床合理治疗和预后判断提供重要的科学依据。本研究应用多参数流式细胞术(flow cytometry,FCM)探讨淋巴细胞白血病和非霍奇金淋巴瘤(non-Hodgkin's lymphoma,NHL)骨髓侵犯的免疫表型特点。方法:收集112例病理确诊NHL并伴骨髓侵犯和淋巴细胞白血病患者的骨髓标本。应用FCM检测肿瘤细胞的免疫表型。结果:45例前驱B淋巴母细胞白血病/淋巴瘤(precursor B lymphoblastic lymphoma/leukemia,B-ALL/LBL)主要表达CD19、CD10、TdT、CD34、HLA-DR和CD20;32例前驱T淋巴母细胞白血病/淋巴瘤(precursor T lymphoblastic lymphoma/leukemia,T-ALL/LBL)主要表达胞内CD3(cytoplasmicCD3,CyCD3)、CD7、CD5、TdT、膜表面CD3(surfaceCD3,sCD3)和HLA-DR。77例前驱淋巴细胞肿瘤中,28例(36%)有髓系抗原CD13、CD33的表达;9例(20%)B-ALL/LBL病例有CD20与CD34共同表达,28例(87.5%)T-ALL/LBL病例有CyCD3与TdT共同表达。成熟淋巴细胞肿瘤35例,其中17例慢性淋巴细胞白血病/小淋巴细胞淋巴瘤主要表达CD19、CD20、CD5和HLA-DR,并有CD19与CD5共同表达。4例弥漫大B细胞性淋巴瘤主要表达CD19、CD20、CD10和HLA-DR。3例伯基特淋巴瘤主要表达CD19、CD10、CD20、SIgM。1例套细胞淋巴瘤表达CD5、CD19、CD20、HLA-DR。5例外周T细胞淋巴瘤(PTCL)主要表达sCD3、CD5、CD7、CD4或CD8。1例间变性大细胞淋巴瘤主要表达sCD3、HLA-DR。4例NK/T细胞肿瘤表达CD56、HLA-DR,也表达CD7或CD4或CD8。成熟淋巴细胞肿瘤不表达早期抗原如CD34、TdT。成熟淋巴细胞肿瘤可伴有髓系抗原CD13、CD33的表达。结论:淋巴系统恶性肿瘤侵犯骨髓采用形态学结合FCM免疫学分型可获得T、B细胞来源、肿瘤细胞分化阶段和异常抗原表达等参数,有助于临床诊断和微小残留病灶的检测。

BACKGROUND ＆ OBJECTIVE： Diagnosis of lymphocytic leukemia and non-Hodgkin＇s lymphoma （NHL） is based on bone marrow morphology. Immunophenotyping will make diagnosis more precise through analyzing the origin and differentiation status of tumor, which is necessary for treatment and prognosis prediction. This study was to analyze the immunophenotypic characteristics of lymphocytic leukemia and NHL with bone marrow involvement using flow cytometry （FCM）. METHODS： Bone marrow specimens from 112 patients with lymphocytic leukemia or NHL with bone marrow involvement were detected by FCM using antibodies of T, B and myeloid cell series. Using CD45/SSC gating strategy, the samples were analyzed with 5 parameters （FSC, SSC, McAb1-FITC, McAb2-PE, CD45-cytochrome）. RESULTS： In 45 cases of precursor B lymphoblastic leukemia/lymphoma （B-ALL/LBL）, the antigens were mainly CD19, CD10, TdT, CD34, HLA-DR, and CD20. In 32 cases of precursor T lymphoblastic leukemia/lymphoma （T-ALL/LBL）, the antigens were mainly CD7, CD5, cytoplasmic （Cy）CD3, TdT, CD34, surface CD3 （sCD3）, and HLA-DR. Of the 77 cases of precursor ALL/LBL, 28（36.4%） expressed myeloid-associated antigens, such as CD13 and CD33; 9 （20.0%） cases of B-ALL/LBL coexpressed CD20 and CD34; 28（87.5%） cases of T-ALL/LBL coexpressed cyCD3 and TdT. Among the 35 cases of mature B-cell malignancies, 17 cases of chronic lymphocytic leukemia/small lymphocytic lymphoma （CLL/SLL） mainly expressed CD19, CD20, CD5, HLA-DR, with coexpression of CD19 and CD5; 4 cases of diffuse large B-cell lymphoma （DLBCL） mainly expressed CD19, CD20, CD10, and HLA-DR; 3 cases of Burkitt＇s lymphoma （BL） mainly expressed CD19, CD10, CD20, and slgM; 1 case of mantle cell lymphoma （MCL） expressed CD5, CD19, CD20, and HLA-DR. Among the 10 mature T-cell malignancies, 5 cases of unspecialied peripheral T-cell lymphoma （PTCL） mainly expressed sCD3, CD5 and CD7, CD4 or CD8; 1 case of anaplastic large cell lymphoma （ALCL） expressed sCD3 and HLA- DR; 4 cases of NK/T-cell malignancies expressed CD56 and HLA-DR, CD4 or CD8 or CD7. Mature lymphoid system malignancies didn＇t express early antigens, such as CD34 and TdT, but expressed myeloid-associated antigens, especially CD13 and CD33. CONCLUSION： Multiparameter FCM can not only provide data of cell lineage and differentiation status but also detect phenotypic aberrancies, which is helpful for minimal residual disease detecting.