Core needle biopsy for thyroid nodules assessment-a new horizon?

Ultrasound-guided fine-needle aspiration is the standard for evaluating thyroid nodules with a high safety profile and a relatively low number of non-diagnostic cytological findings.Nevertheless,this diagnostic method traditionally has its weak points.Several diagnostic categories such as BethesdaⅠ,ⅢandⅣare not reliable for thyroid carcinoma risk assessment.Recent advancements in a core needle biopsy made it possible to use this tool as a new method for thyroid nodules evaluation.The main feature of this method is the use of thin needles(18-21G)and guns with an automatic trigger mechanism.The histological material collected with the use of a core needle biopsy is usually superior to cytological.Therefore,the core needle biopsy can be used as a complementary technique to a standard fine needle aspiration in difficult and dubious cases of thyroid neoplasia with uncertain malignant potential.

Difference between papillary and follicular thyroid carcinoma outcomes:an experience from Egyptian institution

Objective： Differentiated thyroid carcinomas （DTCs） are classified into papillary thyroid carcinoma （PTC） and follicular thyroid carcinoma （FTC）. DTCs are analyzed as a single group in clinical studies that investigated the prognostic factors and prognosis of these malignancies. However, the biological behaviors of these carcinomas significantly differ. In the present study, we aimed to detect differences in the outcomes between PTC and FTC in Mansoura University Hospital in Egypt. Methods： A total of SS8 patients with histologically proven thyroid carcinomas from January 2003 to December 2012 were retrospectively enrolled. The clinical and pathological data of patients were reviewed. Results： Large primary tumor size, lymph node involvement, extrathyroid extension, and distant metastasis were significant poor prognostic factors for overall survival （OS） in old PTC patients. Cox hazard analysis showed that the patient＇s age, extra thyroid extension, and distant metastasis were the only independent prognostic factors. In FTC patients, only the distant metastasis and degree of tumor invasion were significant poor prognostic factors in OS univariate analysis. However, these factors were nonsignificant in multivariate analysis. The 10-year OS rates were 97% and 89% for PTC and FTC, respectively （P=0.003）. The 10-year disease-free survival （DFS） rates were 77.2% in PTC vs. 65% in FTC （P=0.179）. Conclusion： The significant prognostic factors vary between the two types of DTCs. Therefore, PTC and FTC patients need to be analyzed and reported independently. PTC survival is widely and significantly affected by age, extrathyroid extension, and distant metastasis. By contrast, these factors were nonsignificant in FTC, which showed poorer survival than PTC.

Photoacoustic detection of follicular thyroid carcinoma using targeted Nano-Au-Tripods

Follicular thyroid carcinoma(FTC)is the second most common form of thyroid malignancy,and it is associated with more aggressive growth and worse long-term survival outcomes relative to papillary thyroid carcinoma(PTC).Reliable approaches to preoperative FTC detection,however,remain to be established.Herein,a targeted Affibody-Au-Tripod nanoprobe was developed and successfully utilized to facilitate the targeted photoacoustic imaging(PAI)of epidermal growth factor receptor(EGFR)-positive cells and tumors.These Affibody-Au-Tripods were found to be highly sensitive and specific for cells expressing EGFR when used as a PA contrast agent in vitro,and studies conducted in an FTC-133 subcutaneous tumor model system in mice further revealed that these Affibody-Au-Tripods were able to specifically target these EGFR-expressing tumors while providing a strong photoacoustic signal in vivo.Importantly,these nanoprobes exhibited negligible cytotoxicity and robust chemical and physical stability,making Affibody-Au-Tripods promising candidates for targeted PAI-based FTC diagnosis.In addition,these nanoprobes have the potential to facilitate the individualized treatment of patients harboring EGFRpositive tumors.

A Surgical Case of Bilateral Pulmonary Metastases from Thyroid Follicular Cancer

An 80-year-old woman underwent a bilateral lung resection for metastases originating from follicular thyroid cancer. The resection was performed 30 years after right hemithyroidectomy to remove the follicular adenoma. Chest X-ray revealed a 30-mm mass shadow in the right lower lung filed. Chest computed tomography revealed a 32-mm mass shadow in right lung segment 10 (S10) and a 15-mm nodular shadow in left S10. Another partial lung resection of left S10 and a right lower lobectomy were performed 3 months later. Although rarely performed, resection of bilateral pulmonary metastases arising from follicular thyroid cancer was conducted for this patient.

Thyroid follicular renal cell carcinoma excluding thyroid metastases:A case report

BACKGROUND Thyroid follicular renal cell carcinoma is a special type of renal cell carcinoma newly recognized in recent years.It has attracted attention because of its unique histology,immunophenotype,and clinical characteristics.It has a very low incidence,and the number of case reports available for review is limited.Moreover,a thyroid mass with type of tumour is rare.CASE SUMMARY We report a case of a renal mass with a bilateral thyroid mass that was accidentally discovered in a 60-year-old man during physical examination.B-mode ultrasound showed a hypoechoic mass in the middle and lower parenchyma of the right kidney,and computed tomography showed an iso-density shadow tumour in the right kidney.Contrast agents had a significant continuous enhancement effect on the tumour,and the enhancement was not uniform.After partial nephrectomy,pathological analysis was performed to rule out the possibility that the renal tumour was caused by thyroid tumour metastasis.Needle biopsy of the thyroid tumour confirmed that the renal cell carcinoma was not related to the thyroid tumour.The patient was alive at the last postoperative follow-up.CONCLUSION This is the third published case in which thyroid tumour biopsy was performed to confirm that thyroid follicular renal cell carcinoma is not thyroid related.

The Utility of Fine-Needle Aspiration in the Diagnosis and Management of Follicular Thyroid Neoplasms:One Institution’s 10-Year Experience

Background: Classical teaching dictates that follicular adenoma (FA) can be distinguished from follicular carcinoma (FC) based on histologic features only. We retrospectively reviewed our institution’s 10-year experience in the use of fine-needle aspiration (FNA) to diagnose follicular thyroid neoplasms. Methods: Patients who had FNA of a thyroid neoplasm from 2000 to 2010 were reviewed. Diagnoses of FA, FC, or follicular neoplasm-not otherwise specified (NOS) were included. Cytopathological results were correlated with surgical pathology. Results: Of 138 patients, 65% underwent surgery. FNA diagnosis for FA had a sensitivity of 50% and specificity of 71%. 25% of patients with an FNA diagnosis of FA were found to have cancer after surgical specimen examination. FNA diagnosis for FC had a sensitivity of 60% and specificity of 94%. Conclusions: FNA has a low sensitivity for diagnosing FA. Surgical pathology remains the gold standard for differentiating follicular carcinoma from adenoma.

Trefoil Factor 3 (TFF3) mRNA Expression Level in Follicular Thyroid Tumors Using Formalin-Fixed, Paraffin-Embedded (FFPE) Blocks

Background: Differential diagnosis of follicular thyroid carcinoma (FTC) from follicular thyroid adenoma (FTA) is often difficult since presence or absence of capsular/vascular invasion can not be determined by preoperative fine needle aspiration cytology, and may not be judged unanimously on permanent sections even among experienced pathologists. Determination of molecular-genetic factors such as trefoil factor 3 (TFF3) mRNA in the follicular thyroid tumors may be useful aid to improve the accuracy of diagnosis, though it is considered to be unstable and relatively low concentrated genetic substance. Purpose of our study is to investigate expression level of TFF3 mRNA of thyroid follicular tumors using formalin-fixed, paraffin-embedded (FFPE) tissue. Methods: Study population included FFPE sections from 19 FTC cases, 20 FTA cases, 11 adenomatous goiter (G) cases and 12 samples of normal thyroid tissue (N) adjacent to thyroid tumors. RNeasy FFPE kit was used for extraction of total RNA. Purification and concentration values were determined by spectrophotometer. Extracted RNA was used for cDNA synthesis in reverse transcription. Synthesized cDNA subsequently proceeded for relative quantification of TFF3 mRNA by RT-qPCR using TFF3 primers. Glyceroldehyde-3-phosphate dehydrogenase (GAPDH) and hypoxanthin phosphorobosyltransferase1 (HPRT1) were used as control genes. The mean and standard deviation of TFF3 mRNA expression level were analyzed by software Multiplate RQ. Results: Extraction by the FFPE kit yielded high concentration of RNA in all cases. Purification values were 1.8 in average. Concentration values were significantly higher in FTC and FTA relative to G and N tissues, possibly due to high density of thyrocytes in the samples. Relative quantification of TFF3 mRNA expression level showed broad ranges both in FTC and FTA, while the analyses in G and N tissues indicated narrow ranges. Conclusion: FFPE tissues from thyroid follicular tumors can be used for measurement of unstable and low concentrated genetic substances such as TFF3 mRNA. Its diagnostic value yet remains to be determined.

Therapeutic challenges in metastatic follicular thyroid cancer occurring in pregnancy:A case report

BACKGROUND Hormones could play a role in the evolution of follicular thyroid cancer(FTC)for which we discuss an unusual presentation of FTC occurring during pregnancy.CASE SUMMARY A pregnant woman was admitted with FTC metastasis resulting in a gluteal mass.Preoperative abdominal computed tomography revealed liver metastasis for which the patient underwent total thyroidectomy and liver resection,oral radioiodine therapy and radiotherapy,followed by embolization of the pelvic mass.The patient died of cerebral hemorrhage 16 mo after the initial diagnosis.CONCLUSION Human chorionic gonadotropin and estrogen stimulation might have a role in cancer growth,especially during pregnancy.FTC management aims to stop disease progression and overcome hormonal imbalances after thyroidectomy thus reducing fetal complications.It is still under debate whether it is possible to combine optimal timing for treatment to ensure the best possible outcome with reduction of fetal complications and risk of cancer growth.

Progress in the Pathologic Diagnosis of Borderline Follicular Thyroid Tumor

With the progress of science and technology as well as the development of ultrasound technology,more and more thyroid tumors have been found.Follicular tumor is one of the most common thyroid tumors,but borderline follicular tumors are relatively rare.At present,the diagnosis of borderline follicular thyroid tumor is unclear prior to surgery,and it is difficult to identify in frozen section or even conventional section.In order to effectively improve the diagnostic sensitivity and specificity of borderline follicular thyroid tumor,this paper summarizes the new WHO(World Health Organization)classification of borderline follicular thyroid tumor along with diagnostic methods,including clinical fine needle aspiration cytology,histopathology,and molecular biology,and reviews the research progress.

Case Report of a Clear-Cell Variant of Follicular Thyroid Carcinoma

Clear-cell variants of follicular carcinoma are rare subtypes of thyroid cancer. There is no unified view of the histopathological features of clear cell variants, but follicular carcinomas composed predominantly of clear cells are distinguished from clear cell variants. In clinical practice, it is important to determine whether clear cell variants arise primarily from the thyroid gland or are thyroid metastases of other clear cell carcinomas, such as renal cell carcinoma. We present a case in which a patient with initially suspected anaplastic thyroid carcinoma due to a rapidly progressive anterior neck mass was diagnosed with a clear cell variant of follicular carcinoma after a tissue biopsy. The patient was treated with lenvatinib, then his performance status improved, and he was discharged from the hospital. On day 188 after discharge, a contrast-enhanced computed tomography (CECT) scan of the neck showed further shrinkage of the tumor. However, a CECT scan of the chest revealed multiple lung metastases. On day 233 after discharge, the patient developed severe pneumonia resulting from tracheal rupture due to intratumoral necrosis. It was difficult to decide whether lenvatinib should have been discontinued or reduced when lung metastasis appeared. It is necessary to accumulate additional cases to make informed decisions about continuing lenvatinib therapy.

Unusual Scalp Process Revealing a Thyroid Cancer: “Illustrative Case”

Background: Thyroid cancers commonly display slow evolution with local and or regional extension. The classic presentation is a painless nodule of the thyroid region in a euthyroid patient. Sometimes, the nodule is discovered only on ultrasonography. Cervical lymph node is often seen in papillary thyroid cancer due to their propensity to invade lymph node. This means that follicular thyroid cancers are more insidious. Observation: We report a painless slow-growing lesion of the scalp revealing a skull metastasis of thyroid cancer. Despite catastrophic intraoperative bleeding, a total removal was achieved. Lessons: Thus, in addition to local and regional control in the management of thyroid cancers, distant metastasis should be surgically removed to provide the best chance to prolong the patient’s survival. Moreover, neurosurgeon must be prepared to deal with massive bleeding in skull metastasis of thyroid cancer.

甲状腺滤泡性肿瘤的诊断研究进展

甲状腺滤泡状癌(FTC)不同于甲状腺滤泡性腺瘤,其特征为细胞的异型性以及包膜和血管浸润。由于肿瘤的良恶性只能通过术后病理鉴别,绝大部分滤泡性腺瘤患者采取诊断性腺叶切除,但接受腺叶切除的患者术后绝大部分为良性,因此目前亟须寻找一种针对FTC的额外诊断补充依据。术前评估肿瘤的良恶性可减少不必要的手术伤害和短期甚至长期的药物补充治疗。未来全面了解甲状腺滤泡性肿瘤的诊断进展,可以为疾病的治疗提供新思路。

基于Akt/mTOR信号通路探讨洋地黄毒苷调控甲状腺滤泡上皮细胞自噬与凋亡的机制

目的探究洋地黄毒苷对脂多糖刺激下的人甲状腺滤泡上皮细胞系Nthy-roi3-1凋亡与自噬的影响及其作用机制。方法①将Nthy-roi3-1细胞分为对照组、脂多糖组、脂多糖+洋地黄毒苷低剂量组、脂多糖+洋地黄毒苷中剂量组及脂多糖+洋地黄毒苷高剂量组,各组进行对应处理后,CCK-8法检测各组细胞活力,免疫荧光染色观察各组细胞自噬标志物微管相关蛋白1轻链3(LC3)表达情况,流式细胞术检测各组细胞凋亡率,Western blot法检测各组细胞中LC3Ⅱ/LC3Ⅰ、Bcl-2同源结构域蛋白抗体(Beclin 1)、磷酸化蛋白激酶B(p-Akt)、蛋白激酶B(Akt)、磷酸化哺乳动物雷帕霉素靶蛋白(p-mTOR)、哺乳动物雷帕霉素靶蛋白(mTOR)、p70S6K蛋白表达情况。②将Nthy-roi3-1细胞分为对照组、脂多糖组、脂多糖+洋地黄毒苷组、脂多糖+洋地黄毒苷+自噬抑制剂组,各组进行对应处理后,流式细胞术检测各组细胞凋亡率,Western blot法检测各组细胞中LC3Ⅱ/LC3Ⅰ、Beclin1、p-Akt、Akt、p-mTOR、mTOR及p70S6K蛋白表达情况。结果①与脂多糖组比较,脂多糖+洋地黄毒苷各组的细胞活力均明显升高(P均<0.05);LC3荧光染色强度随洋地黄毒苷剂量增加逐渐增强,细胞凋亡率均明显降低(P均<0.05);细胞中LC3Ⅱ/LC3Ⅰ和Beclin1蛋白相对表达量均明显升高(P均<0.05),细胞中p-Akt/Akt、p-mTOR/mTOR、p70S6K蛋白相对表达量均明显降低(P均<0.05)。②与脂多糖组比较,脂多糖+洋地黄毒苷组细胞凋亡率明显降低(P<0.05);细胞中LC3Ⅱ/LC3Ⅰ和Beclin1蛋白相对表达量均明显升高(P均<0.05),细胞中p-Akt/Akt、p-mTOR/mTOR、p70S6K蛋白相对表达量均明显降低(P均<0.05)。与脂多糖+洋地黄毒苷组比较,脂多糖+洋地黄毒苷+自噬抑制剂组细胞凋亡率明显升高(P<0.05),细胞中LC3Ⅱ/LC3Ⅰ和Beclin1蛋白相对表达量均明显降低(P均<0.05),细胞中p-Akt/Akt、p-mTOR/mTOR、p70S6K蛋白相对表达量均明显升高(P均<0.05)。结论洋地黄毒苷能够促进脂多糖刺激下Nthy-roi3-1细胞自噬,抑制细胞凋亡,该作用可能与其抑制Akt/mTOR信号通路的激活有关。

滤泡亚型及经典型甲状腺乳头状癌的临床特征和颈部淋巴结转移的相关因素分析

目的探讨滤泡亚型甲状腺乳头状癌(FVPTC)及经典型甲状腺乳头状癌(CPTC)的临床特征和颈部淋巴结转移(CLNM)的相关影响因素。方法回顾性分析2013-01—2022-10郑州大学第一附属医院行手术治疗并经术中和术后病理学检查确诊的116例FVPTC患者(FVPTC组)及110例CPTC患者(CPTC组)的临床资料。应用二元Logistic回归模型分析FVPTC及CPTC患者CLNM的独立影响因素。结果FVPTC组的肿瘤直径、彩超分级、BRAF基因突变率、淋巴结转移个数、甲状腺过氧化物酶抗体(TPOAb)、促甲状腺激素受体抗体(TRAB)均低于CPTC组,差异均有统计学意义(P<0.05)。FVPTC组中肿瘤大小和彩超分级是CLNM的独立危险因素,年龄是CLNM的独立保护因素。CPTC组中彩超分级是CLNM的独立危险因素,年龄是CLNM的独立保护因素。结论FVPTC的多项临床特征与CPTC存在差异,可协助鉴别诊断。肿瘤体积大、彩超分级高的年轻患者CLNM可能性较大,应采取更积极的治疗方案。

右侧卵巢甲状腺肿伴甲状腺滤泡癌1例

患者女,46岁,体检发现盆腔肿物5个月;10年前接受甲状腺手术,具体不详。查体:右附件区触及约6cm×6cm质软肿物,边界清,活动可,无明显压痛。实验室检查:甲状腺球蛋白60.58ng/ml、糖类抗原12557.29U/ml。腹部超声:右附件区5.9cm×2.8cm混合回声包块,边界清,形态规则,内见多个囊性回声团;CDFI于其内探及较丰富血流信号。

甲状腺滤泡性腺瘤与滤泡癌的超声检查特征分析

目的 探讨甲状腺滤泡癌(FTC)和滤泡性腺瘤(FA)的临床特点与超声检查表现。方法 选取经病理证实为FTC或FA的157例甲状腺肿瘤患者资料。根据病理结果将其分为FTC和FA两组,并对其超声检查特征进行对照分析。结果 两组在年龄、结节形态、边缘、晕征、回声质地、实性成分的位置、局灶性强回声及血流分级等差异均有统计学意义(P <0.05)。将单因素分析结果有统计学意义的变量(P <0.05)作为自变量纳入多因素logistic回归模型,结果显示模型具有统计学意义(模型χ^(2)=88.54,P <0.001,R^(2)=0.60)。其中结节边缘模糊、周边不规则低回声厚晕征、血流为中央血管型或混合型与FTC诊断密切相关。结论 FTC与FA在超声检查表现上相似性很高,应充分了解其超声检查特征,结节边缘模糊、周边不规则低回声厚晕征、中央血管型或混合型血流是FTC诊断与鉴别诊断的重要征象。

基于SEER数据库的滤泡状甲状腺癌发生远处转移风险预测模型

目的探讨滤泡状甲状腺癌(FTC)发生远处转移的风险预测的模型。方法筛选2004~2015年SEER数据库中被诊断为滤泡状甲状腺癌的患者信息。符合纳入和排除标准的1275例患者为研究对象,分析各项预测因素,利用ROC获取年龄及诊断至治疗间隔时间(TDT)的最佳截断值。选择单因素分析中有统计学意义的变量采用Lasso回归及十折交叉验证初步筛选变量,再用多因素Logistic回归构建预测模型,并用ROC曲线及AUC评价模型诊断效能。结果4.6%的FTC(59例)发生远处转移。其中性别、年龄、是否微浸润癌、肿瘤分期(T分期)、淋巴结分期(N分期)、TDT、淋巴结转移比率(LNR)、肿瘤大小、原发灶浸润情况及是否多灶性10个变量单因素分析中差异有统计学意义,Lasso回归及十折交叉验证筛选出其中6个变量纳入多因素Logistic回归,采用逐步法向前向后法筛选年龄、T分期、TDT、LNR4个变量纳入最终模型。模型ROC的曲线下面积(AUC)为0.8815,95%CI为0.8353~0.9276。结论年龄、T分期、TDT、LNR 4个变量构建的预测模型有很高的预测价值,可以为临床诊疗决策提供帮助,其中LNR及TDT对FTC发生远处转移的预测,在以往的研究中不曾有过,亦是本文的亮点。

RAS基因在甲状腺滤泡状癌中的表达及其临床意义

目的探讨RAS基因在甲状腺滤泡状癌(FTC)中的表达与FTC患者临床特征的相关性。方法收集34例甲状腺滤泡状癌患者年龄、性别、结节纵横比、结节回声、结节钙化、甲状腺影像报告和数据系统的分级(TI-RADS)分类、肿瘤大小、淋巴结转移情况、体质量指数(BMI)及临床分期资料,检测术前甲状腺过氧化物酶抗体(TPOAb)、甲状腺球蛋白抗体(TGAb)、促甲状腺激素(TSH)及甲状腺激素(TH)水平,采用扩增阻滞突变系统多聚酶链式扩增(ARMS-PCR)技术检测RAS(KRAS/HRAS/NRAS)的突变状态,实时荧光定量PCR技术(qPCR)检测KRAS、NRAS、HRAS基因突变情况,采用单因素分析基因突变与临床特征的相关性。结果15例发生RAS基因突变(NRAS、KRAS、HRAS),突变率为44.1%,其中NRAS突变10例(29.4%)、KRAS突变4例(11.8%)、HRAS突变1例(3.0%);<55岁患者有18例、≥55岁有16例,且与RAS基因突变有关(P<0.05),TI-RADS分类4类及以上25例;肿瘤<1 cm患者有11例、1~4 cm 10例,>4 cm 13例,均与RAS基因突变有关(P<0.05)。结论RAS的突变状态与患者年龄及肿瘤大小相关,与其他临床特征无相关性。

白藜芦醇对高碘诱导的甲状腺滤泡细胞内质网应激和凋亡的影响

目的探讨白藜芦醇对高碘诱导的甲状腺滤泡细胞内质网应激和凋亡的影响。方法体外培养甲状腺滤泡细胞系Nthy-ori 3-1,根据不同培养方法分为正常培养组(Normal组)、高碘组(HI组)、白藜芦醇组(RES组)和高碘联合白藜芦醇组(HI+RES组)。采用CCK-8法检测各组细胞增殖活性,采用TUNEL法检测各组细胞凋亡情况,采用实时荧光定量聚合酶链反应(PCR)检测各组细胞BIP、CHOP、IRE1 mRNA表达,采用蛋白质印迹法(Western blot)检测BIP、CHOP、IRE1蛋白表达。结果与Normal组相比,HI组细胞培养72 h后增殖活性下降,凋亡细胞占比升高,TUNEL染色阳性细胞占比升高,BIP、CHOP、IRE1 mRNA相对表达量升高,BIP、CHOP蛋白相对表达量升高,差异有统计学意义(P<0.001或P<0.05);与HI组相比,HI+RES组细胞培养72 h后增殖活性升高,凋亡细胞占比降低,TUNEL染色阳性细胞占比降低,BIP、CHOP mRNA相对表达量降低,BIP、CHOP蛋白相对表达量降低,差异有统计学意义(P<0.001或P<0.01)。结论白藜芦醇对高碘诱导的甲状腺滤泡细胞具有保护效应,可显著抑制碘过量摄入引起的内质网应激和细胞凋亡。

3D Gray Level Co-Occurrence Matrix Based Classification of Favor Benign and Borderline Types in Follicular Neoplasm Images

Since the efficiency of treatment of thyroid disorder depends on the risk of malignancy, indeterminate follicular neoplasm (FN) images should be classified. The diagnosis process has been done by visual interpretation of experienced pathologists. However, it is difficult to separate the favor benign from borderline types. Thus, this paper presents a classification approach based on 3D nuclei model to classify favor benign and borderline types of follicular thyroid adenoma (FTA) in cytological specimens. The proposed method utilized 3D gray level co-occurrence matrix (GLCM) and random forest classifier. It was applied to 22 data sets of FN images. Furthermore, the use of 3D GLCM was compared with 2D GLCM to evaluate the classification results. From experimental results, the proposed system achieved 95.45% of the classification. The use of 3D GLCM was better than 2D GLCM according to the accuracy of classification. Consequently, the proposed method probably helps a pathologist as a prescreening tool.