筛状桑葚型甲状腺乳头状癌临床病理及分子生物学特征  

Clinicopathologic and molecular features of cribriform morular variant of papillary thyroid carcinoma

作　　者：崔秀杰 赵海鸥 苏鹏 陈劼[3] 张仁亚[4] 潘毅 欧阳小明[6] 刘军[7] 张健强 杨阳[9] 杨荣[10] 丁岚[11] 刘志艳 Cui Xiujie;Zhao Haiou;Su Peng;Chen Jie;Zhang Renya;Pan Yi;Ouyang Xiaoming;Liu Jun;Zhang fianqiang;Yang Yang;Yang Rong;Ding Lan;Liu Zhiyan(Department of Pathology, Shandong University School of Basic Medical Sciences, finan 250012, China;Department of Pathology, First Affiliated Hospital of Yancheng City, Jiangsu Province, Yancheng 224005, China)

机构地区：[1]山东大学基础医学院山东大学齐鲁医院病理学系,济南250012 [2]江苏省盐城市第一人民医院病理科 [3]南京中医药大学附属医院病理科 [4]山东省济宁医学院附属医院病理科 [5]天津市肿瘤医院病理科 [6]广州医学院第二附属医院病理科 [7]北京大学深圳医院病理科 [8]江苏省滨海县人民医院病理科 [9]湖北省枣阳市第一人民医院病理科 [10]甘肃省肿瘤医院病理科 [11]江苏省扬州市江都人民医院病弹科

出　　处：《中华病理学杂志》2018年第5期354-359,共6页Chinese Journal of Pathology

基　　金：教育部留学回国科研启动基金（2013693）

摘　　要：目的探讨筛状桑葚型甲状腺乳头状癌（cribriform morular variant of papillary thyroid carcinoma，CMV．PTC）的细胞学特点、临床病理及分子生物学特征。方法收集10例CMV—PTC患者存档资料，行细胞学、组织学观察及免疫组织化学（LASB法）染色。采用Sanger测序法检测其腺瘤性息肉病（adenomatous polyposis coli，APC）基因突变，采用突变扩增系统（ARMS）法检测BRAFV600E基因突变，分析其临床病理及分子生物学特征。结果10例患者均为女性，平均年龄27岁。肿瘤主要位于甲状腺右叶。3例行术前甲状腺细针穿刺细胞检查，2例诊断为可疑甲状腺乳头状癌（PTC），1例诊断为PTC。8例均为孤立性结节，2例为双叶多发结节，3例呈浸润性生长。平均直径2．6cm。细胞学上缺乏炎性病变、坏死背景，肿瘤细胞特点为乳头状、筛状、实性、腺状排列，胶质稀少或缺无。PTC细胞核特点不典型，可见核内包涵体和核沟。桑葚体可有或无。组织形态学上复杂多变，肿瘤细胞特点与细胞学一致，细胞核多呈柱状或高细胞状，桑葚体细胞核多透明。免疫组织化学染色结果显示肿瘤细胞及桑葚体甲状腺球蛋白（TG）、p63阴性。甲状腺转录因子（TTF）1、雌激素受体（ER）、细胞角蛋白（CK）、CK19阳性表达于肿瘤细胞。B—catenin特异性阳性表达于肿瘤细胞质和细胞核。以上抗体桑葚体仅表达CK。Ki-67阳性指数1％～30％。随访未发现肿瘤复发和转移。APC基因检测发现1例结直肠癌相关性基因体细胞突变，该例血清学检查发现家族性腺瘤性息肉病（familial adenomatous polyposis．FAP）相关性胚系突变，肠镜证实多发性息肉病．其母亲死于肠癌。所有肿瘤均无BRAFV600E基因突变。结论CMV—PTC因罕见、细胞学、病理学及临床病理学特点不被熟知，容易漏诊、误诊或过诊。TG、TTF1、β-catenin、ER是诊断CMV—PTC较为Objective To investigate the clinicopathologic and molecular features of the rare cribriform morular variant of papillary thyroid carcinoma （ CMV-PTC ） . Methods The clinicopathologic data of 10 patients with CMV-PTC were retrospectively reviewed. Immunohistochemical （IHC） staining was done using LSAB method. DNA sequencing for APC were applied using Sanger method. BRAF V600E mutation was examined using ARMS method. The cytological, morphological, IHC and molecular features were analyzed. Results All patients were female at an average age of 27 years old. The tumors were mostly located in the right lobe of thyroid. Fine needle aspiration cytology was performed in three patients ; two were diagnosed as suspicious for PTC and one as PTC. Nine tumors presented as solitary nodule and two as multiple nodules in both lobes. Infiltration was demonstrated in three cases. The average size was 2.6 cm. The neoplastic cells were arranged in papillary, cribriform, solid and glandular patterns, with rare or without colloid inside the lumen. The number of morula varied, ranging from zero to many. The neoplastic ceils were variably enlarged, showing round, oval or spindle shape. Nuclear irregularity was identified as irregular membrane, nuclear grooves or pseudoinclusion, but no typical ground glass feature. Peculiar nuclear clearing could be observed in the morular cells. IHC staining showed the neoplastic ceils were negative for thyroglobulin and p63, but positive for TTF1, cytokeratin 19 and estrogen receptor. Diffuse staining with cytokeratin was seen in the neoplastic ceils and the morula. Specific cytoplasmic and nuclear staining of 13-catenin was seen in the neoplastic cells but not the morula. Ki-67 proliferation index was 1%-30%. No recurrence or metastasis was observed. One patient was demonstrated to harbor both somatic and germline mutations of the APC gene, who was found to have adenomatous polyposis and her mother died of colonic carcinoma. No BRAF V600E mutation was detected. Conclusions CMV-PTC is rare an

关 键 词：甲状腺肿瘤 乳头状癌 筛状桑葚型 临床病理学 分子特点 

分 类 号：R736.1[医药卫生—肿瘤]