甲状腺乳头状癌的原癌基因参数概貌

作者研究20例甲状腺乳头状癌中ras、ret／PTC和erbB－2／neu3种原癌基因的表达或突变情况。用聚酶链反应（PCR）观察H、N和K－ras密码子,用逆转录（RT）－PCR检定ret／PTC,erbB－2基因扩增则用特异PCR分析。顺序排列erbB－2透膜区以激发突变,用竞争性RT－PCR定量erbB－2／neumRNA,用免疫组化法测定蛋白表达。在20例甲状腺乳头状癌中,肿瘤位于甲状腺内13例,已伴颈淋巴结转移6例,l例已有肺转移。3例有局灶性本分化表现,2例有Hurthle细胞表现。单股结构多态性（SSCP）和顺序测定仅发现2例ras突变：l倒在甲状腺外肿瘤和…     

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目的 探讨甲状腺乳头状癌的诊断及并发症的处理。方法 回顾性分析1995—2004年南昌大学第二附属医院经手术和病理证实的136例甲状腺乳头状癌的临床资料。结果 术中冰冻切片诊断符合率为98．2％（111／113），显著高于术前B超、CT和细针穿刺细胞学检查，上述三者的正确诊断率分别为25．8％（16／62）、80．0％（24／30）和78．1％（25／32）。术后低钙血症、喉返神经麻痹及乳糜漏的发生率分别为8．8％（12／136）、2．2％（3／136）和1．5％（2／136）。结论 术中冰冻快速切片是诊断甲状腺乳头状癌的可靠依据；胸导管漏口-大隐静脉-颈内静脉搭桥吻合术是治疗高流量乳糜漏的好方法。     

BRAF基因突变辅助甲状腺结节诊断为甲状腺乳头状癌的价值研究进展

目的总结BRAF基因突变辅助甲状腺结节诊断为甲状腺乳头状癌(PTC)的价值研究进展。方法收集近年来国内外有关BRAF基因突变及其联合细针穿刺细胞学检查(FNAC)诊断甲状腺良恶性结节、PTC的相关文献并作综述。结果 BRAF基因突变是PTC遗传分子中最常见的基因突变类型,BRAF基因检测联合FNAC可以提高甲状腺良恶性结节特别是PTC诊断的准确性,但BRAF基因突变检测阴性也并不能排除PTC的可能,BRAF基因突变检测对鉴别甲状腺结节良恶性仍存在一定的争议。结论 BRAF基因突变检测在不同类别的甲状腺结节中诊断价值不同,在其突变发生率较高类别的甲状腺结节(可疑的恶性肿瘤、意义不明确的细胞非典型性病变或滤泡性病变结节)中具有较高的诊断价值,而在突变发生率极低类别的甲状腺结节中很大程度上会出现假阴性,尽管如此,BRAF基因检测还是有望成为提高PTC诊断率的高特异性诊断分子标志物。     

双侧甲状腺乳头状癌的临床诊治分析

目的探讨双侧甲状腺乳头状癌（PTC）的临床诊断及手术治疗的有关问题。方法回顾分析2005年1月至2010年6月收治的19例PTC患者的临床资料,总结其术前诊断、术中病理及手术治疗的特点。结果167例甲状腺癌患者中共发现PTC19例（11．4％）;术前通过超声造影和CT检查拟诊为双侧甲状腺癌仅1例（5．3％）;术中冰冻切片检查确诊为双侧乳头状癌17例（89．5％）。其中行双侧甲状腺切除术11例,行一侧腺叶切除加峡部及对侧甲状腺次全或部分切除7例,双侧甲状腺近全切除1例。同时行双侧中央区淋巴结清扫术5例,一侧中央区淋巴结清扫术7例,一侧功能性颈淋巴结清扫术1例。术后病理证实为中央区淋巴结转移共7例（36．8％）。结论双侧甲状腺乳头状癌的术前诊断较为困难,术前超声造影结合CT检查可提高甲状腺癌的诊断符合率。PTC手术时应以全甲状腺切除为主,并行双侧中央区淋巴结清扫。对明确有中央区淋巴结转移者,可同时行一侧功能性颈淋巴结清扫术。     

超声引导下细针穿刺在甲状腺小结节诊断中的应用

目的探讨超声引导下细针穿刺（fineneedleaspiration,FNA）在甲状腺小结节诊断中的价值。方法2013年1月-2014年1月对38例毗邻周围重要脏器的39枚甲状腺小结节（直径0．6～1．2cm,平均0．8cm）超声引导下行FNA检查,以手术病理为标准,判定超声引导下细针穿刺的准确性,同时评估本方法的安全性。结果均未发生出血、毗邻脏器及神经损伤等并发症。手术病理证实甲状腺癌33枚,包括术前FNA诊断恶性结节28枚,无法判断病理类型2枚,取材过少无法诊断3枚;良性结节6枚,包括FNA诊断良性结节2枚,无法判断病理类型1枚,取材过少无法诊断3枚。FNA取材过少无法进行病理诊断6枚,取材不足率15．4％（6／39）。FNA诊断敏感性、准确性分别为93．3％（28／30）和93．9％（30／33）;与手术病理的一致性Kappa=0．718,McNemarz。检验,P=0．500。结论超声引导下FNA活检甲状腺小结节是一种安全准确的检查方法。     

甲状腺乳头状癌中BRAF^V600E基因突变的临床意义

目的总结BRAFV600E基因突变对甲状腺乳头状癌（papillary thyroid cancer,PTC）辅助诊断、治疗及预后评估的意义。方法收集近年来国内外有关BRAFV600E基因突变与PTC形成与进展关系的文献并作综述。结果 BRAFV600E基因突变是PTC组织中最常见的突变类型,是促使PTC形成与进展的重要分子改变,其与PTC的高侵袭性及复发,甚至与预后不良均有密切关系。检测甲状腺结节中的BRAFV600E基因突变,不仅能辅助术前细针穿刺细胞学检查（fine needle aspiration cytology,FNAC）对良恶性结节的鉴别诊断,同时能提高FNAC对PTC的诊断准确率,而且对PTC复发危险程度的分级、手术方式及随访计划的制定均具有重要的指导价值。结论 PTC中BRAFV600E基因突变较常见,该基因突变对PTC的诊断及预后评估均具有重要意义。     

仅根据细针穿刺能否对甲状腺乳头状癌作出手术处理

甲状腺乳头状癌约占甲状腺上皮癌的75％，细针穿刺细胞学检查（FNA）的敏感性很高，已广泛应用于临床，但其特异性较低，仅56％。有的作者提出仍需作冰冻切片，借其敏感性和特异性不优于FNA。为了明确仅根据FNA能否作出手术决定，作者复习于1989～1995年所施行甲状腺切除的82例乳头状癌资料。诊断以最后病理切片为准，FNC的诊断结果分为“确诊为乳头状癌”（PT）、“PTC滤泡型变异”（FVPTC）和“可疑PTC”三类。平均年龄44岁，66％为女性。结果FNA诊断甲状腺癌的总特异性为85％，其中确诊为PTC53例、FVPTC5例和可疑者24例。…     

C MET蛋白在有颈部淋巴结转移的甲状腺癌中的表达和意义

目的探讨C-MET蛋白在有或无颈部淋巴结转移的甲状腺乳头状癌、甲状腺滤泡状癌及良性甲状腺组织中的表达及其临床意义。方法采用免疫组织化学方法检测有颈部淋巴结转移的甲状腺乳头状腺癌（PTC1组）62例，无颈部淋巴结转移的甲状腺乳头状腺癌（PTC2组）50例，甲状腺滤泡状腺癌（FTC组）l0例及良性甲状腺组织（良性组）30例中的C—MET蛋白的表达。结果PTCI组的C—MET表达明显高于其它3组（P〈0．001）。两两比较C—MET表达结果：PTC1组与PTC2组比较，P〈0．001；PTC1组与FTC组比较，P〈0．001；PTC1组与良性组比较，P〈0．001；PTC2组与FTC组比较，P=0．002；PTC2组与良性组比较，P〈0．001；皆有显著性差异。结论C—MET的表达是甲状腺乳头状癌是否有淋巴结转移的预测因子，是肿瘤的囊外扩展和直接侵犯的标记。该指标对甲状腺乳头状癌淋巴结转移的术前评估，决定手术方式均有一定指导意义。     

BRAF突变与甲状腺乳头状癌临床病理学特征关系研究

目的 探讨BRAF基因在甲状腺乳头状癌（PTC）中的突变率,及其与临床病理学特征的关系。方法 选取2018年1月至2019年12月经手术治疗的253例甲状腺乳头状癌患者作为研究对象,分析BRAF基因突变与甲状腺乳头状癌患者临床病理学特征的关系。结果 81%的PTC患者中发现有BRAF基因的突变。BRAF突变率随着年龄的增长而增加,BRAF 突变与PTC的淋巴转移以及临床分期间比较,差异有统计学意义（P<0.05）。多因素Logistic回归分析显示年龄≥45岁、高肿瘤分期、区域淋巴结转移是BRAF突变的独立影响因素（均P<0.05）。结论 BRAF基因突变与PTC淋巴结转移、临床分期相关,而且对于甲状腺肿瘤良恶性的诊断具有重要价值。     

90例甲状腺乳头状癌的针吸细胞学诊断

目的 总结甲状腺乳头状癌的针吸细胞学特征，为诊断与鉴别诊断提供重要依据。方法 回顾性分析90例甲状腺乳头状癌针吸细胞学特征。结果 甲状腺乳头状癌的针吸细胞学特征有：乳头状结构91．1l％(82／90)；核内包涵体85．56％(77／90)；毛玻璃样核67．78％(61／90)；核沟61．11％(55／90)；多核巨细胞56．67％(51／90)；砂粒体14．44％(13／90)。结论 乳头状结构、核内包涵体为诊断甲状腺乳头状癌的重要指征；毛玻璃样核、核沟、多核巨细胞、砂粒体等在甲状腺乳头状癌的诊断中亦具重要价值。     

When fine-needle aspiration biopsy cannot exclude papillary thyroid cancer: a therapeutic dilemma

HYPOTHESIS: Clinical or cytologic factors predictive of malignancy can be identified and incorporated into a treatment algorithm for patients with a fine-needle aspiration biopsy (FNAB) specimen interpreted as "suspicious for" papillary thyroid cancer (PTC). DESIGN: Retrospective review of a prospectively maintained database. SETTING: University-affiliated tertiary care hospital. PATIENTS: Seven hundred thirty-eight patients with nodular thyroid disease evaluated between 1990 and 2004. INTERVENTIONS: Patients with an FNAB specimen suspicious for PTC were identified. The frequency of carcinoma was determined. Clinical features were reviewed. The FNAB specimens suspicious for PTC were examined in a blinded fashion to determine if specific cytologic features were important in distinguishing benign vs malignant disease. MAIN OUTCOME MEASURES: The presence of specific clinical and cytologic features was correlated with the incidence of carcinoma. A secondary outcome measure was to determine the value of frozen section examination in establishing the extent of thyroidectomy. RESULTS: Forty-five patients (7%) had an FNAB specimen suspicious for PTC; 18 (40%) of these patients had carcinoma. Prominent nuclear inclusions and/or grooves, papillary formations, and the absence of colloid were features associated with PTC (P<.05). No clinical features reliably identified malignant disease. Frozen section examination results altered treatment in 15 (56%) of 27 patients. CONCLUSIONS: An FNAB specimen suspicious for PTC is associated with a 40% incidence of carcinoma. Extensive nuclear inclusions and/or grooves, papillary formations, and the absence of colloid are predictive of carcinoma. Rare intranuclear inclusions and/or grooves alone in an otherwise benign-appearing specimen are uniformly associated with benign disease. Frozen section examination is of value in determining the extent of thyroidectomy.     

利用高通量测序技术检测甲状腺乳头状癌基因变异的临床研究

目的利用高通量测序技术(next-generation sequencing technology,NGS)检测甲状腺乳头状癌(papillary thyroid carcinoma,PTC)病人癌组织(cancer tissue,CA)及转移淋巴结(metastatic lymph node,MLN)的基因突变情况,分析基因变异与CA、MLN组织及癌旁组织(normal tissues,NT)的相关性,以期为甲状腺乳头状癌的个体化治疗提供依据。方法利用高通量测序技术对天津医科大学肿瘤肿瘤医院自2020年5月至2020年6月收治入院的20例配对的PTC病人CA、MLN及NT进行基因检测。结果 CA和MLN中BRAF V600E突变率分别为80%(16/20)和55%(11/20)。在NT中未发现任何基因变异。1例CA和MLN均检测到ZNF33B-RET和CCDC6-RET融合。1例多灶性甲状腺微小乳头状癌(papillary thyroid microcarcinoma,PTMC)病人的MLN中发现ATM基因突变,其形态学特征与癌组织相同。结论 BRAF V600E基因是最常见基因突变...     

Significance of Papillary Lesions at Percutaneous Breast Biopsy

Background The management of nonpalpable papillary lesions found in specimens obtained by percutaneous breast biopsy is controversial. We reviewed the treatment of patients found to have papillary lesions by stereotactic, sonographic, or fine-needle aspiration breast biopsy to identify indications for surgical excision. Methods Consecutive patients with intraductal papilloma, atypical papilloma/papilloma with atypical ductal hyperplasia, papillary neoplasm, and papillomatosis according to percutaneous breast biopsy were identified from radiology records. The charts were reviewed to identify patients who had subsequent surgical excision, and the pathologic findings were correlated with the biopsy method and indications for surgery. Results Papillary lesions were found in 120 biopsy samples from 109 patients. Malignancy was found at operation in 19 (24%) of 80 lesions that underwent surgical excision: 12 (63%) were ductal carcinoma-in-situ, 4 (21%) were infiltrating ductal carcinoma, 2 (11%) were infiltrating papillary carcinoma, and 1 (5%) was intracystic papillary carcinoma. Malignancy was found in 9 (30%) of 30 fine-needle biopsy papillary lesions, 6 (35%) of 17 core biopsy papillary lesions, and 4 (12%) of 33 stereotactic biopsy papillary lesions. Malignancy was missed significantly less frequently with stereotactic biopsy (P < .05). Conclusions Malignancy is frequently found at surgical excision for papillary lesions found on percutaneous breast biopsy. Malignancy is missed significantly less frequently with stereotactic biopsy.     

Thyroglobulin antibodies as a potential predictive marker of papillary thyroid carcinoma in patients with indeterminate cytology

Backround

We investigated the efficacy of thyroglobulin antibodies (TgAb) in detecting malignancy in indeterminate thyroid nodules and evaluated the possible association between TgAb and autoimmunity in papillary thyroid carcinoma (PTC).

Methods

This retrospective, nonrandomized study included 1,646 patients who had undergone preoperative fine-needle aspiration biopsy to evaluate their thyroid nodules, and then standard total thyroidectomy. Of 194 patients (11.8%) with indeterminate nodules, 61 (31.4%) had PTC and 133 (68.6%) had benign nodules at the final histologic examination.

Results

Univariate analysis showed that multifocality (P = .002), bilaterality (P = .003), lymph-node metastasis (P = .030), and capsule penetration (P = .003) were significantly associated with positive TgAb in patients with indeterminate cytology and histopathologic diagnosis of PTC. The multivariate analysis showed that TgAb positivity (P < .001) and preoperative thyroid-stimulating hormone levels (P = .022) were independent predictive factor for PTC diagnosis in patients with indeterminate cytology.

Conclusions

Preoperative TgAb could be a marker for PTC in patients with indeterminate thyroid nodules, increasing diagnostic accuracy. TgAb positivity could also influence the clinical assessment and subsequent selection of total thyroidectomy.     

甲状腺乳头状癌中BRAFT1799A基因点突变及其与临床病理特征的关系分析

目的:探讨甲状腺乳头状癌(PTC)组织中BRAF~(T1799A)基因点突变情况及其与PTC临床病理特征之间的关系。方法:选取97例PTC组织以及52例PTC癌旁正常组织与49例结节性甲状腺肿组织,采用巢式PCR法检测甲状腺组织中BRAF~(T1799A)基因位点突变情况,分析BRAF~(T1799A)基因位点突变与PTC临床病理因素的关系。结果:97例PTC组织中,59例(60.82%)出现BRAF~(T1799A)位点突变,而癌旁正常组织与结节性甲状腺肿组织均无BRAF~(T1799A)位点突变,差异有统计学意义(P0.05)。BRAF~(T1799A)位点突变与PTC患者性别、年龄、肿瘤大小无明显关系(均P0.05),与肿瘤临床分期、肿瘤多发灶、包膜外侵犯、淋巴结转移、规范化治疗6个月甲状腺球蛋白值及远处转移密切有关(P0.05)。PTC组织进行亚型分型结果显示,嗜酸细胞型1例,高细胞亚型1例,普通型46例,滤泡型49例;普通型与滤泡型突变率差异无统计学意义(63.04%vs.61.22%,P0.05)。结论:PTC中BRAF~(T1799A)位点突变率高,且BRAF~(T1799A)位点突变可能与PTC术后的复发转移密切相关。     

细胞角蛋白19、半乳糖凝集素3、HBME-1和BRAF V600E表达在甲状腺结节的临床应用价值

目的探讨甲状腺结节患者中细胞角蛋白19（CK19）、半乳糖凝集素3（Galectin-3）、HBME-1、BRAF V600E的表达水平,从而分析4种分子标志物在鉴别甲状腺结节良恶性和甲状腺乳头状癌（PTC）的临床应用价值。 方法用免疫组织化学法检测746例甲状腺恶性结节（恶性组）及287例甲状腺良性结节（良性组）患者术后病理标本中CK19、HBME-1、Galectin-3和BRAF V600E的表达,评估各标志物单独及联合检测对PTC的诊断效能及意义。 结果（1）CK19、HBME-1、Galectin-3及BRAF V600E在恶性组的表达阳性率明显高于良性组（P<0.05）。（2）单独诊断PTC时,Galectin-3敏感度和准确性最高,BRAF V600E特异度最高;CK19+HBME-1+Galectin-3联合检测敏感度和准确性最高,分别为93.60%、94.49%。（3）CK19、Galectin-3、HBME-1及BRAF V600E表达阳性率均与PTC合并甲状腺良性病变呈正相关（r_s>0,P<0.05）。CK19、Galectin-3及BRAF V600E表达与病灶数目相关（P<0.05）,且Galectin-3、BRAF V600E表达与微小癌病灶大小呈负相关（r_s<0,P<0.05）。BRAF V600E表达与淋巴结转移、促甲状腺激素水平相关（P<0.05）。（4）与单纯PTC比较,合并良性病变的PTC不易发生淋巴结转移,合并桥本甲状腺炎的PTC多灶癌所占比例较高。 结论CK19、Galectin-3、HBME-1、BRAF V600E是甲状腺良恶性结节鉴别诊断重要的辅助指标,也是诊断PTC的肿瘤标志物,其中Galectin-3诊断效能最高,CK19、Galectin-3、HBME-1联合检测可提高PTC的诊断准确性。