甲状腺微小乳头状癌的形态学和免疫组织化学研究

时间:2017-06-23 编辑:weian123321 手机版

   【摘要】  目的:观察甲状腺微小乳头状癌的临床病理并检测其免疫表型,探讨相关疾病的鉴别诊断。方法:光学显微镜下观察223例甲状腺微小乳头状癌的组织形态;对74例甲状腺微小乳头状癌、32例甲状腺增生性病变行免疫组织化学方法标记细胞角蛋白19(CK19)、间皮细胞(MC)、细胞黏附凝集素3(Galectin-3)、CD56,复习相关文献。结果:在223例甲状腺微小乳头状癌中以滤泡状排列为主者占38.6%(86/223),核的特征不典型者占13.9%(31/223)。在74例甲状腺微小乳头状癌中CK19、MC、Galectin-3、CD56阳性表达率分别为100.0%、98.6%、98.6%、4.1%;在32例增生性病变中4者阳性表达率分别为37.5%、12.5%、18.8%、68.8%。结论:部分甲状腺微小乳头状癌细胞以滤泡状排列为主,核的特征不够典型,诊断较为困难。根据滤泡细胞增生活跃,细胞核具有乳头状癌的基本特点,病变与周围滤泡截然不同,且肿瘤性滤泡穿插于硬化间质或正常滤泡之间,可与增生性病变鉴别。CK19、Galectin-3、MC弥漫性中强阳性表达,CD56阴性表达对其诊断有重要价值,联合应用可以提高诊断的准确性和特异性。
    【关键词】  甲状腺肿瘤·癌,乳头状·微小癌·细胞角蛋白19·半乳凝素-3·上皮·分化抗原簇56·免疫组织化学
    Immunohistochemical and morphological characteristics of the papillary thyroid microcarcinoma  REN Yu-bo, ZHOU Geng-yin, ZHANG Xue-dong, LI Yu-hong, JIA Ai-hua, DONG Xin-qian 1Department of Pathology, People’s Hospital of Liaocheng (Liaocheng 252000, China)2Department of Pathology, Qilu Hospital of Shandong University (Jinan 250012, China)
  【ABSTRACT】 Objctive: To investigate the immunohistochemical and morphological characteristics of the papillary thyroid microcarcinoma(PTM), and differential diagnosis of the related disease. Methods: The morphological characteristics of 223 patients with PTM were observed under light microscope. Seventy-four cases of PTM and 32 cases of proliferative lesion of thyroid were observed under light microscope with stains of hematoxylin and eosin and immunohistochemical staining. The antibody included CK19, MC, Galectin-3 and CD56. Results: Eighty-six cases were follicular-patterned and 31 cases nuclear features were untypical in 223 cases of PTM. The positive expression rates of CK19、MC、Galectin-3、CD56 were 100.0%, 98.6%, 98.6% and 4.1% in 74 cases of PTM, and were 37.5%, 12.5%, 18.8%, 68.8% in proliferative lesion of thyroid, respectively. Conclusion: Some cases of PTM show a follicular-patterned and the nuclear features. It is untypical compared with classical papillary thyroid carcinoma. It can be differentiated from proliferative lesion with absence of envelope, obviously various and unusually proliferated follicular cells, sclerotic stroma, neoplastic follicles among the collagen and normal follicles. The wide and intensive expression of CK19, Galectin-3, and the negative expression of CD56 are extremely useful in the diagnosis of PTM, four-marker panel with CK19, Galectin-3, MC and CD56 can improve the specificity and accuracy of the differential diagnosis of PTM.
  【KEY WORDS】 Thyroid neoplams·Carcinoma, papillary·Microcarcinoma·Cytokeratin 19·Epithelium·Cluster differentiation 56
  甲状腺微小癌是指直径1 cm以下的甲状腺癌,其中绝大多数是甲状腺乳头状癌(papillary thyroidcarcinoma,PTC),称为甲状腺微小乳头状癌(papillary thyroid microcarcinoma,PTM)。随着健康体检工作对甲状腺疾病的重视和超声引导下甲状腺结节细针抽吸细胞学技术的日臻成熟和广泛开展,PTM的检出率逐渐升高,手术切除的肿瘤越来越微小,病理诊断越来越困难。观察PTM的病理组织学特点,寻找特异性标志物,建立可靠、可行的检测手段,对于甲状腺肿瘤的早期诊断具有重要临床价值。近年来关于PTC的免疫组织化学(immunohistochemical,IHC)研究已有较多报道,主要是细胞角蛋白19(cytokeratin 19,CK19)、细胞黏附凝集素3(Galectin-3)、E-钙粘连素(E-cadherin)、HBME-1等抗体[1],关于间皮细胞(mesothelial cell,MC)、CD56的报道较少。本研究复习相关文献,探讨PTM的病理组织学和免疫表型特点及其鉴别诊断。
1 材料与方法
  1.1 材料 
  收集聊城市人民医院病理科2006年1月—2008年12月行甲状腺手术患者的病理标本1 491例。3名病理医师复查所有病例。其中PTC 441例, 符合PTM者223例,其中男28例,女195例,男女之比为1∶6.96。年龄为20~78岁,平均年龄45.7岁。选取32例甲状腺增生性病变(包括腺瘤样增生26例、乳头状增生6例)作为对照组,74例PTM作为研究组,进行IHC检测。
  1.2方法 
  所有病例均经4%甲醛固定,组织块由全自动脱水机处理。IHC预实验选取经典型PTC、滤泡型PTC、增生性结节各4例制备组织芯片,分别行48种抗体IHC检查,包括常用抗体和科室常备抗体。针对预实验结果选取CK19、MC、Galectin-3、CD56作为实验抗体。采用即用型非生物素ElivisionTM Plus检测试剂盒,所用单克隆抗体均购于福州迈新生物技术开发有限公司,按产品说明书步骤进行染色操作。PBS替代一抗作为阴性对照。
  1.3  PTC的组织学观察指标 
  肿瘤大小、生长方式、组织结构、核的特征、细胞质表现等。
  1.4  PTC的诊断标准

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