甲状腺滤泡型乳头状癌的超声特征研究

目的探讨甲状腺滤泡型乳头状癌的超声特征,提高超声诊断的准确率。方法对40例经手术及病理诊断为甲状腺滤泡型乳头状癌的声像图特点进行研究。同时选取同期45例甲状腺良性病变作为对照。结果甲状腺滤泡型乳头状癌的超声表现与甲状腺良性结节对比,其超声表现为实性结节(97.2%)、形态不规则(52.8%)、微小钙化(19.4%)、低回声结节(83.4%)及探及肿大淋巴结(25.0%)。良恶性结节的各征象对比均有统计学差异(P<0.005)。Logistic回归多因素分析显示,回声(OR=3.13,95%CI:1.58~6.19)和微小钙化(OR=2.03,95%CI:1.19~3.48)是诊断甲状腺滤泡型乳头状癌的独立性预测因素。结论甲状腺滤泡型乳头状癌的超声声像图表现存在很大的差异性,只有在充分了解了其超声表现特征的前提下,才能提高其诊断的准确率。     

合并肿瘤结节的弥漫性硬化型甲状腺乳头状癌的影像学特征分析

目的:分析合并肿瘤结节的弥漫性硬化型甲状腺乳头状癌的影像学特征.方法:分析6例弥漫性硬化型甲状腺乳头状癌(DSVPTC)的高频超声表现、弹性成像技术、X线摄影表现及CT表现,并与经典型甲状腺乳头状癌(CPTC)进行对比.结果:6例(100%)DSVPTC患者甲状腺实质均有砂砾样钙化,3例(75%)累及甲状腺双侧叶,3例(75%)合并淋巴结转移或肺转移;结节血流信号Ⅰ-Ⅱ级,弹性分级Ⅲ级;CT显可显示肿瘤结节内的营养不良性钙化,但不能显示微钙化,X线摄影能更好的显示微钙化.结论:合并肿瘤结节的弥漫性硬化型甲状腺乳头状癌兼具CPTC与DSVPTC的超声特征,超声能为临床提供重要的诊断依据,超声联合X线摄影有重要的诊断价值.     

甲状腺微小乳头状癌的超声声像及病理特征分析

目的探讨甲状腺微小乳头状癌的超声声像特征及病理特征。方法回顾性分析2009年4月-2013年12月期间收治的107例甲状腺微小乳头状癌患者的超声声像图像和病理特征。结果甲状腺微小乳头状癌患者彩超征象形态表现不规则、边界不清晰、实性不均质低回声、周边无声晕;看见微小钙化,且主要以内部血流为主。经病理检查发现,在镜下表现为形态不规则、边界不清晰,同时还存在纤维假包膜情况,内部可见砂粒状,且患者病灶内部组织由滤泡状和乳头状结构所排列的纤维间质及癌细胞组成。恶性结节数为115个,其中Ⅰ和Ⅱ型占28.70%(33/115)、Ⅲ型占71.30%(82/115);良性结节数为134个,其中Ⅰ和Ⅱ型占88.81%(119/134)、Ⅲ型占11.19%(15/134);2组比较,P<0.05。结论临床上,甲状腺微小乳头状癌患者的临床超声声像图主要由患者病理组织学特征来决定,同时联合超声及病理检查可为临床甲状腺微小乳头状癌检出提供重要价值。     

甲状腺乳头状腺癌的声像图表现

目的探讨二维超声对甲状腺乳头状腺癌的诊断价值.方法总结52例经手术和/或超声导向穿刺活检并经病理证实的甲状腺乳头状癌的声像图表现.结果甲状腺乳头状癌特征性声像图表现为边界不清,不规整,无包膜,实性肿块多呈低回声,其内及囊性肿物的实性突起内均见沙粒状微钙化.但甲状腺各种病灶在声像图上表现交叉现象严重,且有多源性,复杂性特点,导致单凭声像图难以鉴别,尤其对微小癌的诊断尚缺乏有力依据.本组10例依靠超声导向穿刺活检明确诊断.结论二维超声在甲状腺乳头状癌的诊断中有着重要应用价值,超声导向穿刺活检可协助诊断.     

彩超对甲状腺乳头状微癌的诊断价值

目的：探讨彩色超声对甲状腺乳头状微癌的诊断价值.方法：对48例甲状腺乳头状微癌的彩色多普勒声像图特征及颈淋巴结转移的特点进行分析.结果：根据超声图像的边界、包膜、内部回声、微钙化及颈部淋巴结的特征可以对甲状腺乳头状微癌进行诊断，超声诊断符合率72.9%.按声像图特征分为两种类型：低回声型和低晕环型.两种类型在出现毛刺征和颈部淋巴结转移上比较差异有统计学意义（P＜0.05），在血流程度分级、微钙化发生率上比较差异无统计学意义（P＞0.05）.结论：彩超可以对甲状腺乳头状微癌的诊断及手术治疗提供有价值的参考依据.     

甲状腺滤泡癌、髓样癌超声表现的初步探讨

 目的 探讨甲状腺滤泡癌、髓样癌的超声声像图特点。方法 与病理结果对照，回顾性分析了18例甲状腺滤泡癌和19例髓样癌的二维及彩色多普勒超声特征。结果 甲状腺滤泡癌女性多见，其中16例癌结节呈不均匀回声，10例伴有液化或囊性成分，11例伴有钙化，部分占位可见包膜。甲状腺髓样癌男女无发病率明显差异，13例呈不规则实性低回声结节，并伴有散在砂粒状钙化点，12例边界欠清楚，髓样癌结节均无明显包膜及液化，结节内部血供丰富。结论 甲状腺滤泡癌、髓样癌各有一定的声像图特点, 对其特征的分析有助于甲状腺癌的分型诊断。     

桥本甲状腺炎合并甲状腺乳头状癌的诊断与治疗

目的：分析桥本甲状腺炎合并甲状腺乳头状癌的诊断及治疗。方法：对我院收集的56例桥本甲状腺炎合并甲状腺乳头状癌的病例资料进行回顾性分析。结果：回顾性分析桥本甲状腺炎合并甲状腺癌56例患者的临床资料,45例为乳头状癌,8例为滤泡状癌,3例为髓样癌。超声检查发现大多数患者结节呈低回声和极低回声,边界不清,形态不规则,纵横比大于1,回声不均匀,41例患者的结节内见细点状强回声钙化,4例患者出现颈部淋巴结肿大,高度可疑为恶性。结论：桥本甲状腺炎合并甲状腺乳头状癌的发病基础和发病因素存在一定的交叉,常联合发病,但其术前诊断困难,常易造成漏诊误诊,故综合术前甲状腺功能检查和超声检查对预判此病有重要意义。     

甲状腺乳头状癌与甲状腺结节钙化的关系研究

[目的]探讨甲状腺结节合并钙化与甲状腺乳头状癌的关系。[方法]回顾性分析240例甲状腺结节患者的彩色超声资料与病理诊断结果。[结果 ]240例甲状腺结节中,甲状腺良性疾病钙化率为23.3%（38/163）,而甲状腺乳头状癌中钙化率达75.3%（58/77）,两组差异有统计学意义（χ2=58.947,P〈0.001）。钙化诊断甲状腺乳头状癌的ROC曲线下面积为0.811（95%CI：0.750~0.871）。微钙化患甲状腺乳头状癌的风险是非微钙化者的5.348倍（95%CI：2.804~10.200）,而粗钙化患甲状腺乳头状癌的风险是非粗钙化者的4.000倍（95%CI：1.564~10.230）。[结论]钙化尤其是微钙化对于诊断甲状腺癌的特异性较高。当彩超发现甲状腺结节中有微小钙化时应提高警惕,尤其是微钙化,应进一步做针吸细胞学检查。     

弥漫硬化型甲状腺乳头状癌临床病理特征分析

目的 探讨弥漫硬化型甲状腺乳头状癌(DSVPTC)的临床病理特征。方法 回顾性分析1例DSVPTC患者的临床病理资料,并结合文献对DSVPTC的临床病理特征和免疫表型特征进行分析,并以经典甲状腺乳头状癌(CPTC)作为对照。结果 DSVPTC有独特的临床病理特征,好发年轻女性,肿瘤常弥漫性的累及一侧或双侧甲状腺组织且伴有颈部淋巴结转移。镜下肿瘤大多位于扩张的淋巴管裂隙内,肿瘤细胞围绕砂粒体或疏松的结蹄组织排列,呈现乳头状的结构,部分癌细胞呈鞋钉样改变,可见大量砂砾体、周围可见大量淋巴细胞浸润及淋巴滤泡形成,上皮细胞出现鳞状上皮化生,区域出现间质纤维化,纤维化背景中可见少量瘤巢。但是缺乏或相对缺乏乳头状癌的诊断性细胞核特征。淋巴结转移率较高,需要根治性手术治疗加上术后辅助治疗和定期检查。结论 DSVPTC是甲状腺乳头状癌的罕见亚型,与CPTC相比,具有独特的临床病理特征,另外,DSVPTC很少有BRAF的突变,更多检测到的为RET的重排。     

甲状腺乳头状癌BRAF基因突变及表达的临床意义研究

目的探讨BRAF基因点突变及B-raf蛋白表达在甲状腺乳头状癌发生中的临床意义。方法应用聚合酶链式反应(PCR)技术检测65例甲状腺病变石蜡组织中BRAF点突变,应用免疫组化方法检测112例甲状腺病变组织中B-raf蛋白的表达情况,并比较BRAF基因突变和B-raf蛋白表达的相关性。结果在46例甲状腺乳头状癌中有21例发生BRAF的点突变,突变率为45.7。BRAF基因突变位于第15外显子的1799位点,胸腺嘧啶突变为腺嘌呤(T1799A)。在结节性甲状腺肿和滤泡状癌中未检测到BRAF的突变。乳头状癌BRAF基因突变率与结节性甲状腺肿比较,差异具有统计学意义(P<0.05)。但是与患者的性别、年龄、组织学类型、淋巴结转移和肿瘤分期无相关性(P>0.05)。在乳头状癌、滤泡状癌和结节性甲状腺肿中B-raf蛋白表达阳性率分别为65.1、47.6和15.4。结果显示,乳头状癌B-raf蛋白阳性表达率与良性病变比较,差异具有统计学意义(P<0.05)。在乳头状癌中BRAF基因突变与B-raf蛋白表达水平呈正相关(P<0.05)。乳头状癌与滤泡状癌比较,B-raf蛋白表达水平两组间无统计学意义(P>0.05)。结论甲状腺乳头状癌BRAF基因突变率和蛋白表达水平的增高,提示BRAF基因在乳头状癌发病中可能发挥重要的作用。对甲状腺肿瘤的病理诊断也具有辅助价值。     

细胞周期素H在乳头状甲状腺癌中的表达

目的探讨乳头状甲状腺癌组织中细胞周期素H的表达及意义。方法采用免疫组织化学S-P法检测46例乳头状甲状腺癌组织和26例正常甲状腺组织细胞周期素H的蛋白表达;对所获得的检测结果进行图像分析处理。结果乳头状甲状腺癌组织和正常甲状腺组织之间,细胞周期素H的阳性表达差异有显著性(P<0.05);且有淋巴结转移的乳头状甲状腺癌组织和无淋巴结转移的乳头状甲状腺癌组织之间,细胞周期素H的阳性表达差异也有显著性(P<0.05)。结论细胞周期素H与乳头状甲状腺癌发生发展密切相关。     

Karyotypic characterization of papillary thyroid carcinomas.

BACKGROUND: Cytogenetic studies performed in papillary thyroid carcinoma (PTC) identified chromosome 10q rearrangements with breakpoints at 10q11.2 as the most frequent aberrations in these tumors. In the current study, the authors aimed to identify other chromosomal abnormalities nonrandomly associated with papillary thyroid carcinomas. METHODS: Cytogenetic analysis was performed on 94 papillary thyroid carcinomas after short-term culture of the tumors sterile fragments. RESULTS: Clonal chromosomal changes were found in 37 tumors (40%). Structural cytogenetic abnormalities were observed in 18 carcinomas. Chromosomes 1, 3, 7, and 10 were the most frequently involved in rearrangements. Pooled results of the breakpoints detected in these tumors, as well as those described in the literature, allowed the authors to verify as the most common breakpoint loci 1p32-36, 1p11-13, 1q, 3p25-26, 7q34-36, and 10q11.2. The correlation between the karyotype features of the 94 PTCs and the histologic data revealed that some PTC follicular variants were characterized by chromosomal aberrations commonly found in thyroid follicular adenomas: a del(11)(q13q13), a t(2;3)(q13;p35), and gains of chromosomes 3, 5, 7, 9, 12, 14, 17, and 20. In the tall cell PTC variant group, 4 of the 7 tumors presented clonal cytogenetic changes, 3 (75%) of which were characterized by anomalies of chromosome 2 that lead to a overrepresentation of the long arm of this chromosome. Noted also in these series was an association between complex karyotypes and tumors with poorly differentiated histiotypes. CONCLUSIONS: In this study, the authors report chromosome 1p32-36, 1p11-13, 3p25-26, and 7q32-36 as novel breakpoint cluster regions in PTC, and they suggest that there are cytogenetic changes preferentially associated with the follicular and tall cell PTC variants.     

Multicentric papillary and follicular carcinomas of the thyroid

A 63-year-old female, complaining of a swelling in the neck, was diagnosed as having a thyroid carcinoma. Thus, a subtotal thyroidectomy was performed, leaving a part of the right lobe. Two thyroid carcinomas were found in the left lobe, and one carcinoma in the right lobe with a right cervical lymph nodal involvement. Each carcinoma was small and encapsulated by thick fibrous tissue, but there was no continuity among them. The three carcinomas were regarded as being multicentric in origin, and not an intraglandular metastasis.     

BRAF mutations in papillary carcinomas of the thyroid

BRAF is a serine/threonine kinase that receives a mitogenic signal from RAS and transmits it to the MAP kinase pathway. Recent studies have reported that mutations of the BRAF gene were detected with varying frequencies in several cancers, notably more than 60% in melanoma. We analysed mutations of BRAF and RAS genes in 100 cases of thyroid carcinoma to investigate genetic aberrations in the RAS/RAF/MEK/MAP kinase pathway. BRAF mutations were detected exclusively in papillary carcinomas (40 in 76 cases: 53%), and were exclusively V599E, a mutation frequently observed in other carcinomas. NRAS mutation was observed in six cases (6%), all in histological types other than papillary carcinoma, and was exclusively Q61R. No mutations were found in KRAS or HRAS. Our results suggest that BRAF mutations may play a critical role in the carcinogenesis of papillary carcinoma of the thyroid.     

RET rearrangements in familial papillary thyroid carcinomas

Familial papillary thyroid carcinoma (FPTC) is an inherited tumor characterized by a more aggressive phenotype than that of its sporadic counterpart. Its mode of inheritance as well as its genetic and molecular bases are still poorly understood. On the contrary, genetic alterations in sporadic papillary thyroid carcinoma (PTC) are better characterized, the most common one involving the activation of the proto-oncogene RET through somatic rearrangements. In the present study, we investigated by interphase fluorescence in situ hybridization the presence of RET rearrangements in a series of 20 FPTC. We show that one FPTC and the adenoma from the same patient carry a RET rearrangement (type PTC1) and that this rearrangement is absent in the germline. Furthermore, we excluded a RET haplotype sharing in two brothers of the same family. These results show that RET rearrangements can indeed be found in FPTC and confirm that RET is not involved in the inherited predisposition to FPTC.     

Chromatin changes in papillary thyroid carcinomas may predict patient outcome

Purpose

New insights in prognostic predictions are urgently needed for papillary thyroid carcinoma (PTC). The present study aimed to investigate whether computerized analysis of chromatin texture allows the identification of PTC patients with a poor prognosis.

Methods

We randomnly selected paraffin-embedded blocks from surgical specimens of 103 classic cases of PTC. During follow-up, 68 of the patients were classified as free of disease, whereas 35 presented with recurrences. Characteristics of chromatin were obtained from digitized images of at least 100 randomly selected tumor nuclei per patient. An independent series of 30 goiters was used to validate our observations.

Results

Stage, age and distant metastases were found to serve as independent prognostic factors for survival. In addition, multivariate Cox regression confirmed variable cluster prominence as an independent prognostic factor. By comparing malignant and benign nodules, we found that the PTC lesions presented with higher nuclear perimeters, nuclear areas, Minkowski fractal dimensions, optical densities and nuclear longest chords.

Conclusion

From our results we conclude that, in conjunction with clinical and histopathological data, morphometric data may provide relevant prognostic information in PTC patients.     

NATH,a novel gene overexpressed in papillary thyroid carcinomas

In this study a replica cDNA screening (RCS) approach to identify genes differentially expressed in papillary thyroid carcinomas (PTC) was used, as compared to non-neoplastic thyroid tissues. RCS is based on hybridization of radioactively labeled cDNA probes made from the biopsies to replica membranes with 15 000 clones from a PTC cDNA library. Among the genes overexpressed in PTC, and especially in clinically aggressive tumors with histologic evidence of poorly differentiated or undifferentiated areas, a novel gene named NATH was found. NATH has two mRNA species, 4.6 and 5.8 kb, both harboring the same open reading frame encoding a putative protein of 866 amino acids. The NATH protein is homologous to yeast N-acetyltransferase (NAT)1 and to mouse NARG1 (mNAT1) and contains four tetratricopeptide repeat (TPR) domains, suggesting that NATH may be part of a multiprotein complex. Overlapping RT-PCR fragments from several PTC biopsies confirmed the NATH mRNA sequence. Northern blots, semiquantitative RT-PCR experiments, TaqMan real-time RT-PCR experiments, and in situ hybridization verified the overexpression of NATH mRNA localized to tumor cells in PTC biopsies. NATH was expressed at a low level in most human adult tissues, including the normal thyroid gland. Increased NATH expression was seen especially in a Burkitt lymphoma cell line and in adult human testis. Recombinant in vitro expression showed that NATH protein was located mainly in the cytoplasm, and was present as a single protein band of the expected 105 kDa molecular weight. Heterologous expression of NATH in the papillary carcinoma cell line (NPA) and 293 cells did not alter the cellular proliferation rate. The biological function of NATH remains to be elucidated, but the overexpression in classic PTC and especially in poorly differentiated or undifferentiated components may indicate a function in the progression of papillary thyroid carcinomas.