高免疫球蛋白血症多发性骨髓瘤临床与实验室综合分析

Clinical and laboratory analysis of multiple myeloma with hyperimmunoglobulinemia

目的分析多发性骨髓瘤(MM)的临床症状特征和实验室相关指标,了解MM的发病特点,减少临床及实验室误诊、漏诊。方法选择2014年5月—2019年12月在曲靖市第二人民医院住院的20例高免疫球蛋白血症MM患者作为研究对象,另选本院20例健康体检人群作为正常对照组。使用Olympus BX53显微镜观察原始、幼稚浆细胞形态学及比例;使用日本Sysmex-XT 4000 I、Sysmex-XN9000血细胞分析仪及配套试剂进行血液细胞分析;使用法国Sebia-Hydrays 2全自动电泳分析仪和配套试剂进行血清蛋白电泳和血清免疫固定电泳检测,根据检测结果进行免疫球蛋白分型;使用美国BD公司BD FACS Cantoll三激光八色通道进行骨髓流式细胞免疫分型;使用德国SIEMENS BNⅡ特定蛋白仪及配套试剂进行免疫球蛋白、血κ和血λ定量检测。分析所有受检者的临床症状及实验室检查资料。结果20例MM患者均有不同程度贫血表现,以中度正细胞贫血最多见(占45%);临床以骨质疏松、骨痛、腰椎痛最常见(占85%);MM组免疫球蛋白G(IgG)升高12例,IgA升高7例,IgM升高1例。MM组IgG型的IgG水平和IgA型的IgA水平均较正常对照组明显升高〔IgG(g/L):62.05±19.50比8.33±6.59,IgA(g/L):33.99±23.63比1.57±1.12,均P<0.05〕。MM组κ型14例,血清κ为(21.53±12.53)g/L;λ型6例,血清λ为(15.26±6.27)g/L。20例骨髓涂片均检出原始和幼稚浆细胞,平均(32.27±20.41)%;20例血清蛋白电泳均检出M蛋白,平均(46.32±14.88)%。免疫固定电泳显示:20例MM患者中,IgGκ型8例,λ型4例;IgAκ型5例、λ型2例;IgMκ型1例。MM组10例行流式细胞免疫分型患者均检出单克隆浆细胞,9例表达CD38,9例表达CD56,5例表达CD138,2例表达CD27,1例表达CD13,1例表达CD200,胞质κ限制表达7例,胞质λ限制表达3例。尿蛋白和本周蛋白以两者均阳性最多见(占40%),其次为尿蛋白定性阴性+本周蛋白阳性(占25%)。结合临床及实验室相关指标确诊Ⅲ期MM患者15例、ⅡA期4例,ⅡB期1例。结论MM临床表现复杂多样,首诊入住科室多,临床误诊、漏诊率较高,诊断MM时依据细胞形态学结合流式细胞免疫分型、蛋白电泳,能提高MM诊断及分期的准确性,为临床提供可靠依据。

Objective To analyze the clinical symptoms and laboratory indicators of multiple myeloma(MM),to understand the pathogenesis of MM,and to reduce misdiagnosis and missed diagnosis in clinic and laboratory.Methods Twenty-two MM patients with hyperimmunoglobulinemia admitted to the Second People’s Hospital of Qujing City from May 2014 to December 2019 were selected as the study subjects,and 20 healthy subjects in our hospital were selected as the normal control group.The morphology and proportion of primary and juvenile plasma cells were observed by Olympus BX53 Microscope.Japanese Sysmex-XT 4000 I,Sysmex-XN 9000 Hematological Analyzer and auxiliary reagents were used for blood cell analysis.Serum protein electrophoresis and serum immunofixation electrophoresis were carried out by Sebia-Hydrays 2 Automatic Electrophoresis Analyzer and its supporting reagents,and the immunoglobulin typing was carried out according to the test results.Bone marrow flow cytometry(FCM)immunotyping was performed using BD FACS Cantoll Three-laser Eight-color Channel.The quantitative detection of immunoglobulin,bloodκand bloodλwere performed using Germany SIEMENS BNⅡSpecific Protein Analyzer and auxiliary reagents.The clinical symptoms and laboratory examination data of all subjects were analyzed.Results All the 20 MM patients showed anemia of different degrees,and moderate positive cell anemia was the most common symptoms(45%).Osteoporosis,bone pain and Lumbar pain were the most common(accounting for 85%)in clinic.In the MM group,immunoglobulin G(IgG)was increased in 12 cases,IgA in 7 cases and IgM in 1 case.IgG and IgA in MM group were significantly higher than those in normal control group[IgG(g/L):62.05±19.50 vs.8.33±6.59,IgA(g/L):33.99±23.63 vs.1.57±1.12,both P<0.05].There were 14 cases ofκtype,the serumκwas(21.53±12.53)g/L;6 cases ofλtype,the serumλwas(15.26±6.27)g/L.Primary and juvenile plasma cells[(32.27±20.41)%]were detected in all the 20 cases of bone marrow smear.M protein was detected by protein electrophoresis in all 20 cases,with an average of(46.32±14.88)%.Immunofixation electrophoresis showed that among the 20 MM patients,8 had IgGκtype,4 hadλtype,5 had IgAκtype,2 hadλtype,and 1 had IgMκtype.Monoclonal plasma cells were detected in 10 patients undergoing FCM immunotyping,9 cases expressing CD38,9 cases expressing CD56,5 cases expressing CD138,2 cases expressing CD27,1 case expressing CD13,1 case expressing CD200,7 cases with cytoplasmκrestrictive expression and 3 cases with cytoplasmλrestrictive expression.Urine protein and Bence-Jones protein both positive were the most(40%),followed by urine protein negative+weekly protein positive(25%).Combined with clinical and laboratory indicators,15 patients were diagnosed with stageⅢMM,4 patients with stageⅡA MM and 1 patient with stageⅡB MM.Conclusions The clinical manifestations of MM are complex and diverse,with many first-admitted departments,and the rate of clinical misdiagnosis and missed diagnosis is high.The accuracy of MM diagnosis and staging can be improved by combining cell morphology with FCM immunotyping and protein electrophoresis,which can provide reliable basis for clinical practice.