浆膜腔积液肿瘤标志物及脱落细胞学在恶性肿瘤伴浆膜腔积液患者中的变化及联合诊断价值.pdf

Hainan Med J,Aug.2023,Vol.34,No.15海南医学2023年8月第34卷第15期浆膜腔积液肿瘤标志物及脱落细胞学在恶性肿瘤伴浆膜腔积液患者中的变化及联合诊断价值王雷1，蔡冰2，牛云霞31.延安大学咸阳医院病理科，陕西咸阳716000；2.渭南市中心医院病理科，陕西渭南714000；3.陕西中医药大学第二附属医院病理科，陕西咸阳716000【摘要】目的探讨恶性肿瘤伴浆膜腔积液患者的浆膜腔积液肿瘤标志物和脱落细胞学水平变化及两者联合诊断的价值。方法回顾性分析2020年12月至2022年11月在延安大学咸阳医院诊治的185例肿瘤伴浆膜腔积液患者的临床资料，按照组织活检病理及免疫组织化学检查结果分为良性病变组118例和恶性肿瘤组67例。所有患者均行浆膜腔积液肿瘤标志物包括癌胚抗原(CEA)、糖类抗原(CA)199检测及脱落细胞学检查，比较两组患者浆膜腔积液中CEA、CA199水平及脱落细胞学检查结果。分析浆膜腔积液肿瘤标志物及脱落细胞学单独及两者联合对恶性肿瘤伴浆膜腔积液的诊断价值。结果恶性肿瘤组患者浆膜腔积液CEA、CA199水平分别为(85.747.49)ng/mL、(64.927.14)U/mL，明显高于良性病变组的(5.331.65)ng/mL、(26.082.39)U/mL，差异均有统计学意义(P0.05)；恶性肿瘤组患者脱落细胞学检查结果为恶性54例，漏诊13例，良性病变组被诊断为恶性12例；两者联合诊断恶性肿瘤伴浆膜腔积液的准确度、特异性、敏感性分别为98.38%、98.31%、98.51%，均高于浆膜腔积液肿瘤标志物的90.27%、88.98%、92.54%及脱落细胞学的78.92%、77.97%、80.60%，差异均有统计学意义(P0.05)。结论恶性肿瘤伴浆膜腔积液患者浆膜腔积液肿瘤标志物明显高于良性病变伴浆膜腔积液患者，且浆膜腔积液及脱落细胞学联合诊断恶性肿瘤伴浆膜腔积液的价值较高。【关键词】恶性肿瘤；浆膜腔积液；癌胚抗原；糖类抗原199；脱落细胞学；诊断价值【中图分类号】R730.4【文献标识码】A【文章编号】10036350（2023）15221704Changes of tumor markers and exfoliative cytology in patients with malignant tumors complicating serouseffusion and their diagnostic value.WANG Lei1,CAI Bing2,NIU Yun-xia3.1.Department of Pathology,XianyangHospital of Yanan University,Xianyang 716000,Shaanxi,CHINA;2.Department of Pathology,Weinan Central Hospital,Weinan 714000,Shaanxi,CHINA;3.Department of Pathology,the Second Affiliated Hospital of Shaanxi University ofTraditional Chinese Medicine,Xianyang 716000,Shaanxi,CHINA【Abstract】ObjectiveTo investigate the changes of tumor markers and exfoliative cytology in patients withmalignant tumors complicating serous effusion and their diagnostic value.MethodsThe clinical data of 185 patientswith tumor complicating serous effusion who were diagnosed and treated in Xianyang Hospital of Yanan Universityfrom December 2020 to November 2022 were retrospectively analyzed.According to the results of biopsy pathology andimmunohistochemistry,they were divided into benign lesions group(118 cases)and malignant tumor group(67 cases).Tumor markers including carcinoembryonic antigen(CEA)and carbohydrate antigen(CA)199 in serous cavity effu-sion were detected in all patients,and the levels of CEA and CA199 in serous cavity effusion and the results of cytologi-cal examination were compared between the two groups.The diagnostic value of tumor markers and exfoliative cytologyalone and in combination for malignant tumors with serous effusion were analyzed.ResultsThe levels of CEA andCA199 in serosal cavity effusion in malignant tumor group were(85.747.49)ng/mL and(64.927.14)U/mL,whichwere significantly higher than(5.331.65)ng/mL and(26.082.39)U/mL in benign lesion group(P0.05).The resultsof exfoliated cytology showed that 54 cases were malignant and 13 cases were missed in the malignant tumor group,and 12 cases were malignant in the benign lesion group.The accuracy,specificity,and sensitivity of the combined diag-nosis for malignant tumor with serous effusion were 98.38%,98.31%,and 98.51%,which were significantly higherthan 90.27%,88.98%,and 92.54%of tumor markers and 78.92%,77.97%,and 80.60%of ablative cytology(P10 ng/mL、CA19937 U/mL即诊断为阳性，且有一项诊断为阳性就判断为恶性肿瘤。(2)脱落细胞学检查：收集10 mL浆膜腔积液，将离心半径、转速设置为15 cm、1 118 g，离心5 min。将上清倒掉，将0.2 mL沉淀物制作成无尾厚片、有尾厚片、有尾薄片各两张，在室温条件下自然干燥，选择瑞氏-姬姆萨复合染液进行染色。加两滴染液于涂片，然后加34滴蒸馏水或磷酸盐(PBS)缓冲液，等待2 min，用流水冲洗并自然晾干。之后，使用显微镜 Olym-pus-BX53对细胞形态及分类进行观察，镜下发现恶性肿瘤细胞就诊断为恶性。1.3统计学方法应用SPSS20.0统计软件进行数据分析。计量资料以均数标准差(x-s)表示，组间比较采用t检验，计数资料比较采用2检验。以P0.05)，见表1。2.2两组患者浆膜腔积液 CEA、CA199水平比较恶性肿瘤组患者浆膜腔积液CEA、CA199水平明显高于对照组，差异均有统计学意义(P0.05)，见表2。2.3两组患者浆膜腔积液脱落细胞学检查结果比较恶性肿瘤组患者中脱落细胞学检查结果为恶性54例，漏诊13例，其中7例由于肿瘤细胞没有突破包膜，镜下没有发现肿瘤细胞，2例肿瘤细胞不典型；良性病变组有12例被诊断为恶性，分别为良性神经纤维瘤5例、肺炎性假瘤6例、肉芽肿1例，见图1图3。表1两组患者的临床资料比较例(%)，x-sTable 1Comparison of clinical data between the two groups n(%),x-s组别良性病变组恶性肿瘤组2/t值P值例数11867男性61(51.69)32(47.76)女性57(48.31)35(52.24)0.2650.607年龄(岁)55.514.0255.184.170.5240.601病程(月)6.140.286.080.371.1530.251性别表2两组患者浆膜腔积液CEA、CA199水平比较(x-s)Table 2Comparison of the levels of CEA,CA199 in serous cavityeffusion between the two groups(x-s)组别良性病变组恶性肿瘤组t值P值例数11867CEA(ng/mL)5.331.6585.747.4986.6890.001CA199(U/mL)26.082.3964.927.1443.1740.001图1腹腔积液，卵巢来源，查见腺癌细胞Figure 1Abdominal effusion,ovarian origin,adenocarcinoma注：A为显微镜10倍；B为显微镜20倍。Note:A,microscope at 10 times;B,microscope at 20 times.2218Hainan Med J,Aug.2023,Vol.34,No.15海南医学2023年8月第34卷第15期2.4浆膜腔积液肿瘤标志物及脱落细胞学联合对恶性肿瘤伴浆膜腔积液的诊断价值两者联合诊断恶性肿瘤伴浆膜腔积液的准确度、特异性、敏感性均高于浆膜腔积液肿瘤标志物及脱落细胞学单独诊断，差异有统计学意义(P0.05)，见表3。表3浆膜腔积液肿瘤标志物及脱落细胞学联合对恶性肿瘤伴浆膜腔积液的诊断价值(%)Table 3Diagnostic value of tumor markers in serous cavity effusionand exfoliative cytology in combination for malignanttumors complicating serous effusion(%)项目浆膜腔积液肿瘤标志物脱落细胞学两者联合2值P值准确度90.27(167/185)78.92(146/185)98.38(182/185)36.6640.001特异性88.98(105/118)77.97(92/118)98.31(116/118)23.8890.001敏感性92.54(62/67)80.60(54/67)98.51(66/67)12.0850.002图2癌细胞腺腔样、乳头状结构，可见胞质内空泡(显微镜40倍)Figure 2Adenoluminal,papillary structure of cancer cells withintracytoplasmic vacuoles(microscope at 40)图3胸腔积液查见腺癌，肺来源，癌细胞腺管样排列，呈三维立体状，核大，深染，可见巨大核仁，胞质内有黏液空泡。Figure 3Adenocarcinoma,pulmonary origin,cancer cells arranged in a three-dimensional adenocarcinoma,with large,hyperchromaticnuclei,giant nucleoli,and mucous vacuoles in the cytoplasm注：A为显微镜10倍，B为显微镜20倍，C为显微镜40倍。Note:A,microscope at 10 times;B,microscope at 20 times;C,microscope at 40 times.3讨论在正常状态下，成人胸腔、腹腔、心包积液分别小于20 mL、100 mL、50 mL，主要是发挥润滑功能，在病理状态下，上述3种积液留存量提升引发浆膜腔积液，进而导致患者表现出相关症状9。大部分浆膜腔积液均发生于肿瘤患者，癌细胞于浆膜积液内，借助其营养，生长不被限制，且极易同间皮细胞混淆，增加临床诊断的困难10。浆膜腔积液致病因素诸多，若肠壁、腹膜、肠系膜、胸膜等遭遇肿瘤侵袭，会增加淋巴液流体静压、损伤血管内皮细胞、提升毛细血管通透性，导致低蛋白血症，进而造成蛋白及水的吸收降低，使其潴留于胸腹腔而发生积液11。肿瘤标志物为细胞恶变或肿癌组织生长时，抑癌基因、癌基因或其他有关产物不正常表达，出现的生物活性物质或抗原12。经体液及血清肿瘤标志物检测，能在一定程度上了解肿瘤的生长状况及肿瘤细胞的特性，也就是说恶性肿瘤于转移、复发期间，相关肿瘤标志物水平会显著升高，浆膜在遭遇恶性细胞侵犯时会释放大量相关肿瘤标志物，同血清相比，积液内此类物质水平提升会更早，同时因为浆膜腔具有封闭性，难以参与血液循环，因此积液内的相关肿瘤标志的表达及血清与积液两者中肿瘤标志物表达的差异，能够成为评估患者是否遭遇浆膜侵犯的指标13-14。本研究结果显示，恶性肿瘤伴浆膜腔积液患者的浆膜腔积液CEA、CA125、CA724、CA199水平均明显高于良性病变伴浆膜腔积液的患者。于机制方面，CEA 属于现在最可靠且常用的一种肿瘤标志物，于正常状态下含量极微，同时在诊断肺癌方面有较高的特异度及敏感度，且于腺癌中升高更明显，同临床分型相关15。CA199属于糖蛋白之一，其相对分子质量比较大，为同腺癌有关的一种抗原物质，且产生于腺癌2219海南医学2023年8月第34卷第15期Hainan Med J,Aug.2023,Vol.34,No.15细胞，CA199于消化道肿瘤诊断方面有较高的特异性，同时与浸润深度、肿瘤直径及淋巴结转移等息息相关16。本研究还显示，浆膜腔积液肿瘤标志物及脱落细胞学两者联合对恶性肿瘤伴浆膜腔积液诊断的准确度、特异性、敏感性均高于两者单独诊断。这主要是由于脱落细胞学能够对病灶处的细胞形态进行直接观察，使肿瘤标志物间接测定的不足得以弥补，同时肿瘤标志物间的联合，也弥补了各自的缺点，同时也对脱落细胞学查看细胞形态期间的局限性进行弥补，因此，两种检测方式联合使诊断价值有效提高。综上所述，恶性肿瘤伴浆膜腔积液患者浆膜腔积液、血清肿瘤标志物明显高于良性病变伴浆膜腔积液患者，且浆膜腔积液肿瘤标志物及脱落细胞学联合诊断恶性浆膜腔积液的价值较高。参考文献1Pinto D,Chandra A,Crothers BA,et al.The international system forreportingserousfluidcytopathology-diagnosticcategoriesandclinical management J.JAm Soc Cytopathol,2020,9(6):469-477.2Song JX,Li X,Li ZY,et al.Analysis of etiological distribution andclinical characteristics of patients with pericardial effusion andmultiple serous effusions J.Chin Circul J,2021,36(3):305-309.宋俊贤,李晓,李忠佑,等.以心包积液为主多浆膜腔积液患者的病因学分布和临床特征分析J.中国循环杂志,2021,36(3):305-309.3Wang XY,Jing CB,Zhang Q,et al.The diagnostic value of threetumor 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