The pathology of the nodular goiter

Pathologic studies of thyroid nodules indicate that a definite percentage of nodular goiters are malignant, and that an even higher percentage are true neoplasms. Malignant tumors may arise from adenomas, involutionary nodules or possibly from nodules of the unclassified type. Some carcinomas of the thyroid gland are undoubtedly malignant processes from the start. Because of the high incidence of neoplasms, benign and malignant, in a group of single nodules of the thyroid gland, the presence of such nodules should warrant radical resections of the involved lobe and adjacent isthmus. The high incidence of epithelial growth activity in nodular involutionary goiters may revise the accepted practice of removing non-toxic nodular goiters only when clinical evidence of growth or local pressure is present.     

THE PATHOLOGY OF THE NODULAR GOITER

Pathologic studies of thyroid nodules indicate that a definite percentage of nodular goiters are malignant, and that an even higher percentage are true neoplasms. Malignant tumors may arise from adenomas, involutionary nodules or possibly from nodules of the unclassified type. Some carcinomas of the thyroid gland are undoubtedly malignant processes from the start. Because of the high incidence of neoplasms, benign and malignant, in a group of single nodules of the thyroid gland, the presence of such nodules should warrant radical resections of the involved lobe and adjacent isthmus. The high incidence of epithelial growth activity in nodular involutionary goiters may revise the accepted practice of removing non-toxic nodular goiters only when clinical evidence of growth or local pressure is present.     

分子生物学法分析青少年甲状腺肿物临床病理及特点

探讨青少年甲状腺肿物的临床病理学特点,甲状腺癌的复发、转移和结节性甲状腺肿复发的可能相关因素。按WHO病理分型标准和国际抗癌联盟(UICC)TNM分期标准回顾性分析青少年甲状腺肿物124例及其中部分甲状腺癌和结节性甲状腺肿的随访资料。124例甲状腺肿物患者男女比例约为1 3,甲状腺癌39例(31.5%),其中乳头状癌35例,滤泡癌3例,髓样癌1例;甲状腺腺瘤59例(47.6%),结节性甲状腺肿11例(8.9%),结节性甲状腺肿伴腺瘤7例(5.6%),甲状腺炎5例(4%),甲状舌管囊肿3例(2.4%)。本组资料显示,青少年甲状腺癌以乳头状癌为主,其复发、转移与组织学亚型为弥漫硬化型及甲状腺包膜和其外软组织受侵状态相关。虽然常见淋巴结转移、肺转移以及局部侵犯周围软组织,但患者总体预后较好。结节性甲状腺肿的复发与病变弥漫位于双叶有关,而与患者性别、年龄和是否伴有乳头样及腺瘤样增生关系不密切。     

超声诊断结节性甲状腺肿合并甲状腺微小乳头状癌的价值

目的:探讨超声诊断结节性甲状腺肿合并甲状腺微小乳头状癌的价值。方法:2010年1月至2014年12月选择来我院进行诊治的结节性甲状腺肿患者80例,病理诊断为结节性甲状腺肿合并甲状腺微小乳头状癌30例(恶性组)和单纯结节性甲状腺肿50例(良性组),都进行常规二维超声、超声弹性成像和超声造影检查。结果:恶性组结节多呈现单发、内部低回声、钙化形态不规则特征,与良性组对比差异有统计学意义(P0.05)。恶性组病灶内的血流最小流速明显小于良性组(P0.05),阻力指数与搏动指数明显高于良性组(P0.05)。良性组弹性成像多为2~3分,恶性组多为4~5分,组间对比差异都有统计学意义(P0.05)。恶性组的造影剂平均通过时间明显少于对照组(P0.05),两组的显影时间、达峰时间、峰值强度对比差异无统计学意义(P0.05)。结论:常规超声诊断结节性甲状腺肿合并甲状腺微小乳头状癌的良恶性有一些特异性的征象,超声弹性成像与超声造影可为临床诊断提供补充,有助于提高甲状腺微小乳头状癌的诊断准确率。     

Potential diagnostic markers in nodular lesions of the thyroid gland: an immunohistochemical study

Aims: The differential diagnosis of thyroid nodules in routine practice can be problemmatic for both pathologists and clinicians. Effective treatment requires a determination of the biological nature of the lesions. For this reason, ancilliary diagnostic markers along with histological examination of the nodules may be useful. The objective of this study was to evaluate the diagnostic usefulness of novel markers in the diagnosis of hyperplastic and neoplastic nodules. Methods: Forty eight thyroid lesions forming four diagnostic groups including adenomatous goiters (AS), follicular adenomas (FA), follicular (FC) and papillary carcinomas (PC) were examined using standard immunohistochemical methods. Monoclonal antibodies against galectin-3, matrix metalloproteinases (MMPs) -2 and -7 and endothelial markers CD31 and CD105 were used. Results: The cytoplasmatic expression of galectin-3 was positive in all cases of papillary carcinoma. Moreover, statistically significant differences between fused groups of benign (AS and FA) and malignant lesions (FC and PC) were found Fischer's exact test (p = 0.0001). No significant differences in cytoplasmic expression of MMPs -2 and -7 and in vascular density assessed by using of both endothelial markers between benign lesions and malignant tumors were revealed. Conclusions: Galectin-3 appears to be a useful marker in the diagnosis of papillary carcinoma only. The matrix metalloproteinases-2 and -7 are not helpful in distinguishing hyperplastic and neoplastic thyroid nodules. Endothelial markers do not appear to be suitable for thyroid differential diagnosis. A panel of antibodies in the differential diagnosis of thyroid nodular lesions would seem most suitable and further studies with larger sets of patients are awaited.     

H-RAS gene expression in human multinodular goiter

The RAS protooncogene has an important, although not yet established role in thyroid neoplasia. In this study, we evaluated the H-RAS mRNA and protein levels in human samples of nontoxic and toxic multinodular goiter samples, according to serum TSH levels. The mean of H-RAS mRNA levels in nodules of nontoxic nodular goiter were significantly increased compared to nonnodular tissue (1.49+/-1.21 vs. 0.94+/-0.81 AU, P=0.016). Nine of the 18 specimens (50%) of nontoxic multinodular goiter exhibited increased levels of H-RAS mRNA. The increased H-RAS mRNA levels were paralleled by inRAcreased H-Ras protein levels in about 90% of the cases. Interestingly, no differences were observed in H-RAS expression between nodules and adjacent nonnodular tissue in toxic nodular goiters (0.58+/-0.27 vs. 0.58+/-0.20 AU, P=0.88). None of the 10 samples from toxic multinodular goiters exhibited overexpression of H-RAS. The H-RAS expression was positively correlated with thyroglobulin expression (r2=0.51; P=0.04). In conclusion, we demonstrated increased levels of H-RAS mRNA and protein in samples of nontoxic multinodular goiter, indicating that it might be involved in goiter pathogenesis. In contrast, H-RAS overexpression was not detected in any of the samples of toxic multinodular goiter, suggesting different mechanisms for cell proliferation in nodular goiter according to thyroid status.     

Follicular Adenomas Exhibit a Unique Metabolic Profile. 1H NMR Studies of Thyroid Lesions

Thyroid cancer is the most common endocrine malignancy. However, more than 90% of thyroid nodules are benign. It remains unclear whether thyroid carcinoma arises from preexisting benign nodules. Metabolomics can provide valuable and comprehensive information about low molecular weight compounds present in living systems and further our understanding of the biology regulating pathological processes. Herein, we applied ¹H NMR-based metabolic profiling to identify the metabolites present in aqueous tissue extracts of healthy thyroid tissue (H), non-neoplastic nodules (NN), follicular adenomas (FA) and malignant thyroid cancer (TC) as an alternative way of investigating cancer lesions. Multivariate statistical methods provided clear discrimination not only between healthy thyroid tissue and pathological thyroid tissue but also between different types of thyroid lesions. Potential biomarkers common to all thyroid lesions were identified, namely, alanine, methionine, acetone, glutamate, glycine, lactate, tyrosine, phenylalanine and hypoxanthine. Metabolic changes in thyroid cancer were mainly related to osmotic regulators (taurine and scyllo- and myo-inositol), citrate, and amino acids supplying the TCA cycle. Thyroid follicular adenomas were found to display metabolic features of benign non-neoplastic nodules and simultaneously displayed a partial metabolic profile associated with malignancy. This finding allows the discrimination of follicular adenomas from benign non-neoplastic nodules and thyroid cancer with similar accuracy. Moreover, the presented data indicate that follicular adenoma could be an individual stage of thyroid cancer development.     

Value of repeated fine needle aspiration cytology in patients with nodular goiter

OBJECTIVE: To assess the value of reaspiration cytology in benign nodular thyroid disease. DESIGN: We prospectively studied 400 patients (365 women, 35 men) aged 46 years (18-89) with nodular thyroid disease and initial benign fine needle aspiration cytology (FNAC). Reaspiration of the same nodule was performed in a median follow-up time of 14 months (6-18). RESULTS: Repeat FNAC was benign in 346 patients (86.5%), insufficient for diagnosis in 42 (10.5%), suspicious in 16 (2.5%) and malignant in 2 (0.5%). All diagnostic changes to suspicious malignant cytology took place in patients with solitary nodules. Surgery confirmed thyroid cancer in the 2 patients with malignant cytology, in 5 of 10 patients with suspicious cytology and in none of 39 patients with benign cytology who underwent surgery for other reasons. Clinical changes (size increase or local symptoms) were not related to changes in cytologic diagnosis after a second aspiration, nor with the results of the biopsy. CONCLUSION: Repeat aspiration cytology of thyroid nodules may correct initial false negative results because of cytologic misdiagnosis, occurring in 1.75% of patients, whereas clinical changes did not contribute to diagnosis change. Repeat aspiration cytology is recommended in all patients with nodular goiter.     

不同性质甲状腺结节与微血管密度关系的研究

目的:探讨不同性质甲状腺结节与微血管密度关系,提高认识.方法:分别选取甲状腺乳头状癌、甲状腺腺瘤、结节性甲状腺肿及正常甲状腺组织,病理切片行常规HE染色及免疫组化SP染色.在高倍视野(×400)下选取5个血管着色密集区进行计数并取其平均数,MVD值=(n1 +n2+n3+n4+n5)/5.结果:(1)甲状腺乳头状癌、甲状腺腺瘤、结节性甲状腺肿及正常甲状腺组织平均MVD值分别为(65.54±19.21)个/HP、(54.54±11.76)个/HP、(47.85± 10.92)个/HP、(21.82±7.43)个/HP,甲状腺乳头状癌MVD值显著高于甲状腺腺瘤、结节性甲状腺肿及正常甲状腺组织(P＜0.05).甲状腺腺瘤、结节性甲状腺肿MVD值显著高于正常甲状腺组织(P＜0.05).(2)伴有淋巴结转移的甲状腺乳头状癌患者MVD值显著高于不伴有淋巴结转移者(P＜0.05);男性甲状腺乳头状癌患者MVD值显著高于女性患者(P＜0.05);＞40岁及≤40岁甲状腺乳头状癌患者MVD值间无统计学差异(P＞0.05).结论:甲状腺乳头状癌MVD值显著高于甲状腺腺瘤、结节性甲状腺肿及正常甲状腺组织,且伴有淋巴结转移的甲状腺乳头状癌患者MVD值显著高于不伴有淋巴结转移者.     

The role of fine needle aspiration biopsy cytology in the evaluation of the clinically solitary thyroid nodule

The imputation that a clinically solitary nodule is a suspicious sign of carcinoma has been the cause of too many surgical procedures as well as the subject of much controversy. This study evaluated the effectiveness of fine needle aspiration (FNA) biopsy cytology in diagnosing the uninodular goiters in 286 patients who presented with clinically solitary nodules. The final diagnoses in these cases included carcinoma (4.7%), adenoma (6.3%), autonomous nodule (11.0%), colloid goiter (45.8%), colloid cyst (17.4%) and chronic thyroiditis (13.4%). The proportion of patients with cancer in this group was the same as in patients with multinodular and diffuse goiters. These findings call attention to (1) the fact that any thyroid disease may appear as a uninodular goiter and (2) the frequency with which lymphocytic thyroiditis was cytologically diagnosed, even in cases with negative antibody titers. The cytologic diagnosis of benign disease has contributed to a reduction in the number of unnecessary surgical procedures; only 24.1% of our patients with uninodular goiters underwent surgery.     

AgNOR染色对甲状腺良、恶性病变诊断价值的研究

本文应用ＡｇＮＯＲ染色技术对７３例甲状腺良恶性病变石蜡切片核仁组成区变化进行观察,其中包括亚急性甲状腺炎５例、腺瘤２５例、结节性甲状腺肿７例、甲状腺癌３６例,结果表明亚急性甲状腺炎、腺瘤、结节性甲状腺肿,细胞核内的ＡｇＮＯＲ颗粒均数及形态与甲状腺癌的均数及形态比较有显著性差异（Ｐ＜０．０１）。我们认为此方法对于区别甲状腺良、恶性病变有一定参考价值。     

Analysis of mitochondrial DNA mutations in D-loop region in thyroid lesions

Background

Mitochondrial defects have been associated with various human conditions including cancers.

Methods

We analyzed the mutations at the mitochondrial DNA (mtDNA) in patients with different thyroid lesions. In particular, in order to investigate if the accumulation of mtDNA mutations play a role in tumor progression, we studied the highly variable main control region of mtDNA, the displacement-loop (D-loop) in patients with non-tumor nodular goiters, with benign thyroid adenomas, and with malignant thyroid carcinomas. Total thyroid tumor or goiter samples were obtained from 101 patients, matched with nearby normal tissue and blood from the same subject.

Results

Noticeably, mitochondrial microsatellite instability (mtMSI) was detected in 2 of 19 nodular goiters (10.53%), and 8 of 77 (10.39%) malignant thyroid carcinomas. In addition, 6 patients, including 5 (6.49%) with malignant thyroid carcinomas and 1 (5.26%) with nodular goiter, were found to harbor point mutations. The majority of the mutations detected were heteroplasmic.

General significance

Our results indicate that mtDNA alterations in the D-loop region could happen before tumorigenesis in thyroid, and they might also accumulate during tumorigenesis.     

Cytoplasmic and serum galectin-3 in diagnosis of thyroid malignancies

In order to address whether galectin-3 in the sera and fine needle aspirates serve as a diagnostic marker distinguishing between benign and malignant thyroid nodules, we developed an enzyme-linked immunosorbent assay. We quantified galectin-3 in fine needle aspirates from a series of 118 patients with thyroid nodules and serum galectin-3 from another series of 46 patients, which were compared with final histology after thyroidectomy. Relative galectin-3 value (ng/mg), defined as galectin-3 concentration (ng/ml) divided by total protein concentration (mg/ml) in fine needle aspirates, was significantly higher in papillary carcinoma than in the other thyroid entities. There was no significant difference in serum galectin-3 level among patients with thyroid nodules and healthy individuals. Accordingly, relative galectin-3 value allows a definitive diagnosis of papillary carcinoma independent of cellular morphology, whereas serum galectin-3 does not serve as a marker for papillary carcinoma.     

甲状腺球蛋白及抗体测定在结节性甲状腺肿与甲状腺癌鉴别诊断中的意义

目的:对结节性甲状腺肿患者和甲状腺癌患者术前的甲状腺球蛋白(TG)、抗甲状腺球蛋白抗体(TG-Ab)水平进行回顾性分析,并对TG、TG-Ab水平在结节性甲状腺肿、甲状腺癌诊断中的意义进行研究。方法:分别选取2011年1月-2013年12月我院收治的结节性甲状腺肿患者、甲状腺癌患者和正常健康者各60例作为本研究的观察对象,对三组观察对象TG、TG-Ab水平进行比较分析。结果:结节性甲状腺肿组、健康组患者TG阳性率分别为6.67%、8.33%,差异无统计学意义(P0.05);两组患者TG-Ab阳性率则分别为8.33%和11.67%,差异无统计学意义(P0.05)。而甲状腺癌组患者TG、TG-Ab阳性率分别为33.33%、40.00%,与其他两组比较差异具有统计学意义(P0.05)。在结节性甲状腺肿患者中,其中结节液化型TG阳性率、TG-Ab阳性率明显高于非结节液化型,差异具有统计学意义(P0.05)。在甲状腺癌患者中,其中颈部淋巴结阳性者TG阳性率、TG-Ab阳性率明显高于颈部淋巴结阴性者,差异具有统计学意义(P0.05);单结节癌灶与多结节癌灶在TG阳性率、TG-Ab阳性率差异无统计学意义(P0.05)。结论:临床上采用TG、TG-Ab阳性率测定的方法对甲状腺肿、甲状腺癌进行鉴别和确诊是比较可靠的,值得推广应用。     

甲状腺良、恶性结节的临床、超声及细胞学特征分析

目的:研究良、恶性甲状腺结节的相关临床因素、超声特征与甲状腺细针穿刺细胞学检查结果之间的关系。方法:收集2010年1月至2013年12月在上海市第一人民医院因甲状腺结节就诊,并进行超声引导下FNAB检查患者的临床资料,以FNAB细胞学诊断结果为诊断标准,分析和比较不同性质甲状腺结节患者的年龄、性别、甲状腺疾病家族史、临床症状、血清甲状腺激素、甲状腺自身抗体(TPOAb和TRAb)水平,超声检查所发现的结节数量、性状、前后径与横径比(AP/TR)、回声类型、钙化类型、边界状态、血流情况等因素,采用Logistic多因素回归,探讨这些临床和超声特征与甲状腺良、恶性结节之间的关系。结果:根据FNAB结果,1592例患者中,良性结节者1492例,恶性结节者77例,结果不确定者23例。以良性组作为对照,年龄40岁、TPOAb(+)是恶性甲状腺结节的独立危险因素(P0.05);出现钙化点、细小钙化斑、边界不规整的超声表现的恶性甲状腺的风险显著升高(P0.05)。结论:超声检查甲状腺结节出现钙化点、细小钙化斑或边界不规整等与FNAB诊断的甲状腺恶性结节之间存在明显的关联。     

Usefulness of fine needle aspiration of the thyroid in an endemic goiter region

The accuracy of fine needle aspiration (FNA) cytology of the thyroid was addressed in 142 nodular goiters from an endemic goiter region. The aspirations and their interpretation were based on the methodology of the Karolinska Hospital. For practical purposes, the follicular lesions were divided into type I (benign), type II (atypical benign) and type III (suspicious). Excluding the follicular lesions, the cytohistologic agreement for the whole series was 87%, with a correlation of 81.5% for carcinomas. The type I and type II follicular lesions were benign on histologic grounds; 39% of the carcinomas were detected in the type III follicular lesions. The 0.7% false-positive diagnoses increased to 15% when type III follicular lesions were included. No false negatives were recorded. These observations, together with the increase of surgically resected thyroid carcinomas after FNA was accepted as a diagnostic modality, indicate that FNA biopsy of the thyroid is an accurate diagnostic method and is useful in selecting patients for subsequent surgery in areas of endemic goiter.     

Twist及Akt2在甲状腺乳头状癌中的表达及意义

目的探讨Twist、Akt2在甲状腺乳头状癌中的表达和相互关系。方法应用免疫组化方法,对60例甲状腺乳头状癌、10例结节性甲状腺肿进行Twist、Akt2表达的研究。结果甲状腺乳头状癌Twist及Akt2阳性表达率分别为81.67%(49/60)及60.00%(36/60),结节性甲状腺肿Twist及Akt2阳性表达率分别为0.00%(0/10)及10.00%(1/10),前者与后者相比差异有统计学意义(P<0.05);Twist及Akt2在甲状腺乳头状癌中的表达水平与病人的年龄及原发肿瘤分期无关,但与有无淋巴结转移相关(P<0.05),且Akt2的表达在T3,4期肿瘤及T1,2期肿瘤相比也具有显著性(P<0.05);Twist及Akt2的表达呈正相关(r=0.492,P=0.000)。结论在大多数甲状腺乳头状癌的上皮细胞中都存在Twist及Akt2的过表达,其淋巴结转移的发生与Twist及Akt2过表达或功能的不正常可能有密切的关系;Twist与Akt2的表达呈正相关。     

乳头状甲状腺癌中线粒体DNA突变的研究

该文探究了线粒体DNA(mtDNA)突变与甲状腺癌的发生发展的相关性,评估了mtDNA拷贝数对甲状腺癌的诊断价值。根据对结节性甲状腺肿、滤泡状甲状腺腺瘤和乳头状甲状腺癌3组病人的mtDNA全基因测序和单倍型分型结果,统计3组病人mtDNA突变率及单倍型的差异,分析乳头状甲状腺癌病人的mtDNA突变率与临床资料的联系,最后通过荧光定量PCR检测3组病人的组织和血液样本中mtDNA的拷贝数。结果显示,乳头状甲状腺癌患者mtDNA的复合体I亚基编码区和tRNA编码区的突变率明显高于结节性甲状腺肿,在乳头状甲状腺癌患者中线粒体单体型M相对于单体型N有更低的淋巴结转移率,荧光定量PCR结果显示,甲状腺腺瘤和甲状腺癌组织中的mtDNA拷贝数明显高于结节性甲状腺肿,而在血液标本中,两者的mtDNA拷贝数均低于结节性甲状腺肿。这些结果表明,mtDNA拷贝数的变化和复合体I亚基编码区的突变可能作为甲状腺癌诊断的生物指标,而线粒体单体型N可能可以作为乳头状甲状腺癌恶性变化的预警指标。     

声触诊组织定量技术鉴别诊断甲状腺微小癌的价值

目的：声触诊组织定量技术（VTQ）是一种新的弹性成像方法,能够定量、无创地评价组织硬度信息。本文的研究目的是探讨声触诊组织定量技术在鉴别诊断甲状腺微小癌（TMCs）中的应用价值。方法：应用VTQ 技术对110 例共114 个结节（最大直径≤1 cm）进行检测,获取并分析结节及周边甲状腺组织的横向剪切波速度（SWV）。利用ROC曲线对测量结果进行分析,评价VTQ技术的诊断价值并确定最佳诊断界值。结果：114 个结节中良性结节32 个（30 个为结节性甲状腺肿,2 个为腺瘤）,恶性结节82 个（均为乳头状癌）。甲状腺良性结节及周边甲状腺组织的SWV 平均值分别为（2.30± 0.49） m/s、（2.08± 0.40） m/s,恶性结节及周边甲状腺组织的SWV 平均值分别为（3.12± 0.97） m/s、（2.06± 0.46） m/s。恶性结节的SWV 值明显高于良性结节,两者之间差异具有统计学意义（t=5.911,P＜0.0001）;恶性结节与其周边甲状腺组织比较有显著差异（P＜0.0001）;而良性结节与其周边甲状腺组织无统计学差异（P＞0.05）。ROC曲线下面积为0.833,以2.30 m/s诊断界值点时,敏感度、特异度分别为90.2%、62.5%。结论：甲状腺恶性结节的SWV 值明显高于良性结节。VTQ 技术能够提供组织硬度信息,在鉴别诊断甲状腺微小癌方面具有一定的临床应用价值。     

Survivin和CD44V6蛋白表达与甲状腺乳头状癌侵袭转移的关系

探讨甲状腺乳头状癌(papillary thyroid carcinoam,PTC)中生存素(survivin)和CD44v6蛋白表达及其意义.应用免疫组织化学方法检测66例PTC、20例甲状腺瘤(TA)、20例结节性甲状腺肿(NG)和15例正常甲状腺组织(NT)中survivin和CD44v6蛋白表达.结果表明,在PTC中,survivin和CD44v6表达阳性率分别为63.6%(42/66)和57.6%(38/66).PTC中survivin和CD44v6阳性表达率显著高于TA、NG和NT(P<0.05).survivin和CD44v6表达与PTC的侵袭转移呈显著正相关(P<0.05).survivin和CD44v6阳性表达与PTC侵袭、转移密切相关,检测survivin和CD44v6蛋白的表达可作为判断PTC生物学行为的参考指标.