Combined ultrasonographic and cytological studies in the diagnosis of thyroid nodules.

Many aspects of thyroid nodule evaluation and management remain controversial. Widespread application of ultrasonography has resulted in frequent discovery of incidental nodules in the general population which has created a management dilemma for physicians. In this paper we have introduced a novel approach for evaluation of solid nodules, using an index derived from ultrasonographic and cytologic studies. Briefly thyroid nodules were classified ultrasonographically into four grades, with increasing score numbers (1-4) as progression to malignantly suspicious lesions was present. Similarly, four grades of a cytologic classification of fine needle biopsy aspirates were introduced with scores of 1-6 (benign to malignant diagnosis). The sum of the ultrasonographic and cytologic scores were the basis of a diagnostic index: benign (2-4), doubtful (5), suspicious (6) and malignant (7-10). Sixty patients with an index equal or higher than 6 were submitted to thyroidectomy and the prevalence of thyroid cancer (n = 46) in the excised nodules was 76.6%. Most series report a 10% to 30% incidence of malignancy in excised nodules with suspicious diagnosis. We concluded that using an index derived from combined ultrasonographic and cytologic studies will result in a better patient selection for surgery.     

Thyroid Nodule Evaluation and Management in Older Adults: A Review of Practical Considerations for Clinical Endocrinologists

ObjectiveContextualizing the evaluation of older adults with thyroid nodules is necessary to fully understand which management strategy is the most appropriate. Our goal was to summarize available clinical evidence to provide guidance in the care of older adults with thyroid nodules and highlight special considerations for thyroid nodule evaluation and management in this population.MethodsWe conducted a literature search of PubMed and Ovid MEDLINE from January 2000 to November 2020 to identify relevant peer-reviewed articles published in English. References from the included articles as well as articles identified by the authors were also reviewed.ResultsThe prevalence of thyroid nodules increases with age. Although thyroid nodules in older adults have a lower risk of malignancy, identified cancers are more likely to be of high-risk histology. The goals of thyroid nodule evaluation and the tools used for diagnosis are similar for older and younger patients with thyroid nodules. However, limited evidence exists regarding thyroid nodule evaluation and management to guide personalized decision making in the geriatric population.ConclusionConsidering patient context is significant in the diagnosis and management of thyroid nodules in older adults. When making management decisions in this population, it is essential to carefully weigh the risks and benefits of thyroid nodule diagnosis and treatment, in view of older adults’ higher prevalence of high-risk thyroid cancer as well as increased risk for multimorbidity, functional and cognitive decline, and treatment complications.     

Solitary thyroid nodules in 93 children and adolescents. a 35-years experience

Over a period of 35 years from 1963 to 1998, 93 patients under the age of 18 years, 74 girls and 19 boys, were seen for evaluation of a solitary nodule of the thyroid gland. All patients had preoperative scintiscans of the thyroid gland and had their solitary nodule excised. Seventy-seven of the patients had a cold nodule on scintiscanning. The most common cause of solitary thyroid nodules was follicuar adenoma (68.9%). Fifteen of the 77 cold nodules were malignant (19.9%). The frequency of carcinoma in males was 26.3%, while in females it was 13.5%. Our experience suggests that the incidence of thyroid carcinoma may be decreasing in pediatric patients not exposed to known risk factors. Available diagnostic methods for attempting differentiation of benign from malignant solitary nodules are reviewed and recommendations to the clinical management are presented.     

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。     

Management of thyroid cytological material,preanalytical procedures and bio‐banking

Thyroid nodules are common and are increasingly detected due to recent advances in imaging techniques. However, clinically relevant thyroid cancer is rare and the mortality from aggressive thyroid cancer remains constant. Fine needle aspiration cytology (FNAC) is a standard method for diagnosing thyroid malignancy and the discrimination of malignant nodules from goitre. As the examined nodules on thyroid FNAC are often small incidental findings, it is important to maintain a low rate of undetermined diagnoses requiring further clinical work up or surgery. The most important factors determining the accuracy of the cytological diagnosis and suitability for biobanking of thyroid FNACs are the quality of the sample and availability of adequate tissue for auxiliary studies. This article discusses technical aspects (preanalytics) of performing thyroid FNAC, including image guidance and rapid on‐site evaluation, sample collection methods (conventional slides, liquid‐based methods, cell blocks) and storage (bio‐banking). The spectrum of special studies (immunocytochemistry on direct slides or liquid‐based cytology, immunohistochemistry on cell blocks and molecular methods) required for improving the precision of the cytological diagnosis of the thyroid nodules is also discussed.     

Thyroid Nodules and Thyroid Cancer

A review of clinical and laboratory features of thyroid cancer, designed to help in a more precise selection of patients for operation, showed that factors contributing to a high index of suspicion of cancer include previous exposure to low doses of radiation, the presence of a firm, solitary thyroid nodule clearly different from the rest of the gland, a young patient, nodules that are “cold” on scan with radioiodine, and nodules that fail to regress after an adequate trial of thyroxine therapy. Factors contributing to a low index of suspicion of thyroid cancer include soft or cystic lesions, multinodular goiters, nodules that are “hot” on ¹³¹ I scan, and those that regress during thyroxine treatment.When these factors are used to select patients for surgical operation, about 30 percent are found to have thyroid cancer.Until more precise methods for preoperative diagnosis are established, it is suggested that this type of clinical selection may be very helpful in the management of patients with thyroid nodules or nontoxic goiter.     

甲状腺结节的现代诊疗进展

绝大多数甲状腺结节都是经影像学检查无意间发现的,即使是良性甲状腺结节,也有必要进行治疗。临床医生需要综合患者的病史、体格检查及实验室、影像学或细胞学穿刺活检等检查结果尽可能明确诊断结节的良恶性。非手术微创治疗方法对于多数的良性结节行药物或放射性碘治疗如无水酒精注射(PEI)、激光光凝(ILP)、放射性碘消融(RFI)和微波消融(MWA)效果较好;而恶性或高度怀疑恶性及部分较大良性结节需行外科手术切除,根据结节的具体类型并结合各高危因素选择适当的切除范围,某些恶性结节术后还需进一步辅助碘131放射治疗并跟踪随访。本文综述了有关甲状腺结节的最新诊断和治疗进展,重点阐述了美国甲状腺协会关于甲状腺结节和分化型甲状腺癌的诊治指南的相关主张。     

A Retrospective Study of Clinicopathologic Outcomes of Nodules With Hürthle Cell Cytology and the Thyroid Nodule App (TNAPP) Ultrasound Recommendations

ObjectivesHürthle cells are a common finding on thyroid fine-needle aspiration, but when they are the predominant cytology, they represent a difficult diagnostic challenge. The Thyroid Nodule App (TNAPP) is a new, publicly available web application utilizing ultrasound (US) features based on the updated 2016 American Association of Clinical Endocrinologists clinical practice guidelines for thyroid nodule management. This pilot study was performed to assess the TNAPP recommendations and surgical pathology outcomes of Hürthle cell-predominant thyroid nodules.MethodsA retrospective review of nodules with Bethesda III (atypia of undetermined significance with Hürthle cells) or Bethesda IV (suspicious for Hürthle cell neoplasm) cytology, for which surgery was performed between 2017 and 2021, was conducted. TNAPP US categories 1, 2, and 3 (low, intermediate, and high risk, respectively) were assigned based on nodule characteristics, and clinical management recommendations were recorded. Results were compared with histology-proven diagnoses.ResultsFifty-nine nodules in 57 patients where surgical pathology was available were analyzed with the TNAPP algorithm. Of the 59 nodules, 4 were US category 1 (low risk/suspicion), 40 were US category 2 (intermediate risk/suspicion), and 15 were US category 3 (high risk/suspicion). All US category 1 nodules were benign, while 30% of the US category 2 and 40% of the US category 3 nodules were malignant. Of the patients who had molecular marker testing with ThyroSeq, 22 out of 29 (76%) were positive, indicating either an intermediate or high risk of malignancy, 7 of which were malignant.ConclusionThis preliminary study suggests that TNAPP is a useful clinical tool for sonographic assessment of thyroid nodules with Hürthle cell cytology.     

甲状腺结节良恶性的彩色多普勒超声特征及其诊断价值分析

目的:研究甲状腺结节良恶性的彩色多普勒超声特征及其诊断价值。方法:选取从2016年3月~2019年2月于我院接受手术治疗的甲状腺疾病患者300例作为研究对象,均予以彩超检查,比较甲状腺良恶性结节的超声特征(主要包括直径、钙化情况、边界、回声、血流状况)。以病理活检结果为金标准,分析彩超诊断甲状腺结节良恶性的敏感性、特异性以及准确度。对比甲状腺良恶性结节的血流分型情况以及各项血流动力学参数。结果:恶性结节超声特征直径≥2 cm、有钙化、边界模糊、无回声/低回声、血流丰富人数占比均高于良性结节(均P<0.05)。以手术病理组织活检结果作为金标准,彩色多普勒超声诊断甲状腺结节的敏感性、特异性以及准确度分别为97.73%、86.11%、96.33%。甲状腺良性结节血流分型为Ⅰ型、Ⅱ型人数占比高于恶性结节,而Ⅲ型、Ⅳ型人数占比低于恶性结节(均P<0.05)。甲状腺良性结节的收缩期峰值血流速度(PSV)、阻力指数(RI)均低于恶性结节,而舒张末期血流速度(EDV)高于恶性结节(均P<0.05)。结论:彩色多普勒超声对甲状腺结节良恶性的鉴别价值较高,且具有较高的敏感性、特异性以及准确度,可为甲状腺良恶性结节的早期诊断、临床治疗提供重要的参考依据。     

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.     

补肾益气活血汤对小鼠血清雌、孕激素浓度 及其受体表达的影响

目的：探讨中药补肾益气活血汤促进着床的机理。方法：在以吲哚美辛建立小鼠着床障碍模型的基础上,将动物分为正常组,吲哚美辛组,中药组和黄体酮组,用放射免疫、免疫组织化学及Westem—blot方法检测各组小鼠妊娠d5（围着床期）血清皿,P4浓度及子宫内膜ER,PR表达。结果：补肾益气活血中药对E2、P4水平无明显影响,对PR表达也无明显影响,但有轻度促进ERα表达作用,此外,实验发现治疗对照组注射黄体酮虽然使P4水平升高,但ERα、PR表达却都有一定下降。结论：提示中药补肾益气活血汤可能主要通过雌激素样活性加强E2与其受体作用而有利于发动蜕膜化从而促进着床,黄体酮辅助生殖治疗失败可能与孕酮一定程度上抑制ERα和PR表达有关。     

Q-Elastography in the Presurgical Diagnosis of Thyroid Nodules with Indeterminate Cytology

Quantitative ultrasound (US) elastography (Q-USE), able to evaluate tissue stiffness has been indicated as a new diagnostic tool to differentiate benign from malignant thyroid lesions. Aim of this prospective study, conducted at the Department of Surgical Sciences, of the “Sapienza” University of Rome, was to evaluate the diagnostic accuracy of Q-USE, compared with US parameters, in thyroid nodules with indeterminate cytology (Thy3).The case study included 140 nodules from 140 consecutive patients. Patient’s thyroid nodules were evaluated by Q-USE, measuring the strain ratio (SR) of stiffness between nodular and surrounding normal thyroid tissue, and conventional US parameters prior fine-needle aspiration cytology. Those with Thy3 diagnosis were included in the study. Forty of the nodules analyzed harbored a malignant lesion. Q-USE demonstrated that malignant nodules have a significant higher stiffness with respect to benign one and an optimun SR cut-off value of 2.05 was individuated following ROC analysis. Univariate analysis showed that hypoechogenicity, irregular margins and SR >2.05 associated with malignancy, with an accuracy of 67.2%, 81,0% and 89.8%, respectively. Data were unaffected by nodule size or thyroiditis. These findings were confirmed in multivariate analysis demonstrating a significant association of the SR and the irregular margins with thyroid nodule’s malignancy. In conclusion, we demonstrated the diagnostic utility of Q-USE in the differential diagnosis of thyroid nodules with indeterminate cytology that, if confirmed, could be of major clinical utility in patients’ presurgical selection.     

Serum metabolic profiling and features of papillary thyroid carcinoma and nodular goiter

Thyroid carcinoma is a common endocrine malignancy worldwide, accounting for approximately 1% of all diagnosed cancers and about 91.5% of the malignancies of head and neck. However, differentiating malignant thyroid nodules from benign ones remains a diagnostic challenge. Thus, novel molecular markers that enable non-invasive diagnostics for malignant thyroid nodules are urgently needed. In the present study, a metabonomic investigation based on liquid chromatography-LTQ Orbitrap mass spectrometry was employed for serum metabolic profiling of 30 cases of papillary thyroid carcinomas (PTC), 80 cases of nodular goiters (benign thyroid nodules) and 30 cases of healthy controls. According to the results of multivariate statistical data analysis, the significantly changed metabolites among these three groups were defined. It was found that most of these metabolites decreased in the sera of both malignant and benign thyroid cases due to the increased metabolic rate, which is in accordance with clinical features. The major metabolic differences between benign and malignant nodules occurred in lipid metabolism. Especially, the content of 3-hydroxybutyric acid, an intermediate product of fatty acid metabolism, was much higher in the PTC group than that in the nodule goiter and control groups, indicating its potential as a diagnostic marker for PTC and nodular goiters. These results show that the serum metabolic profiling method is a powerful tool for distinguishing thyroid carcinoma from nodular goiter and healthy controls.     

甲状腺结节数对钙化甲状腺病变良恶性的鉴别价值

目的:通过甲状腺病变术前超声声像图与术后病理间的对照,分析结节单发或多发在鉴别伴钙化甲状腺病变良恶性中的意义。方法:回顾性分析我院2010年1月至2013年12月收治的218例甲状腺病变患者的临床资料,将患者术前超声声像图与术后病理结果进行对比。结果:术前超声探及甲状腺单发结节伴钙化其术后病理恶性比例显著高于多发结节伴钙化,差异具有统计学意义(P0.05);多发结节伴钙化其术后病理恶性比例显著高于多发结节不伴钙化,差异具有统计学意义(P0.05)。结论:术前超声探及甲状腺单发结节伴钙化其术后病理恶性比例较高,应积极手术治疗,多发结节伴钙化因其术后病理恶性病理较低,不宜作为手术治疗甲状腺病变的绝对指征。     

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.     

彩色多普勒超声联合血清P53、midkine、S-TK1鉴别甲状腺结节良恶性的临床价值研究

摘要 目的：研究彩色多普勒超声联合血清P53、midkine及胸苷激酶1（S-TK1）鉴别甲状腺结节良恶性的临床价值。方法：将2015年1月～2020年1月我院收治的420例甲状腺结节患者纳入研究。将其按照术后病理学检查结果的不同分成恶性结节组150例与良性结节组270例。比较两组各项超声图像特征,血清P53、midkine及S-TK1水平。以受试者工作特征（ROC）曲线分析彩色多普勒超声联合血清P53、midkine、S-TK1或以上方式单独检测诊断甲状腺恶性结节的能效。结果：恶性结节组超声图像特征中形态不规则,边界不清晰,无包膜,内部钙化以及血流分级为2～3级人数占比均高于良性结节组（P＜0.05）。恶性结节组血清P53、midkine及S-TK1水平均高于良性结节组（P＜0.05）。经ROC曲线分析可得：彩色多普勒超声联合血清P53、midkine、S-TK1诊断甲状腺恶性结节的曲线下面积为0.895、灵敏度为0.92以及特异度为0.88均高于上述方式单独检测。结论：彩色多普勒超声联合血清P53、midkine及S-TK1鉴别甲状腺结节良恶性的临床价值较高。     

Beyond the suspicious thyroid fine needle aspirate. A review

Fine needle aspiration (FNA) is currently the best diagnostic tool for thyroid nodules. However, the cytologic category of indeterminate or suspicious lesion, which is found in 10-15% of cases, remains a challenge. Since neither clinical presentation nor intraoperative frozen section is often helpful in differentiating these lesions and since surgical procedures for benign and malignant lesions differ, there is a clear need to develop ancillary tests. In this review we identify 12 potential markers of thyroid malignancy that have been examined in thyroid cytologic samples. Although many of these markers hold promise as adjuncts to FNA cytology, multicenter studies have often shown limitations in the predictive value of these assays due to lack of specificity, sensitivity or both. The recent development, however, of tissue microarray techniques to validate promising new markers suggests that improvements in the approach to indeterminate thyroid FNA samples may soon be at hand. This review presents a summary of the issues facing the development of a clinically useful diagnostic test in the differential diagnosis of thyroid nodules.     

超声造影检查对早期甲状腺单发结节良恶性的鉴别诊断价值

目的:建立以甲状腺单发结节超声诊断为变量的回归模型,分析比较超声造影与常规超声检查对甲状腺单发结节良恶性的鉴别诊断价值。方法:选择来我院就诊的甲状腺单发结节患者274例,让所有患者均接受常规超声检查和超声造影检查,并手术后进行病理诊断,建立相应回归模型,评价超声造影对甲状腺单发性良恶性结节的鉴别诊断价值,为临床检查及治疗提供参考。结果:超声造影检查的良恶性检出率均优于常规超声检查。超声造影检查良性结节检出率为65.69%,恶性检出率为34.31%,敏感度96.70%,特异度95.65%,准确率96.35%,均优于常规超声检查。Logistic回归分析显示,钙化、达峰时间、增强程度及最大灌注强度以上四项特征出现的越多,待测的甲状腺结节越有可能是恶性结节。结论:超声造影对良、恶性甲状腺单发结节的鉴别具有重要的临床诊断意义。     

甲状腺影像报告与数据系统(TI-RADS)分类鉴别良恶性甲状腺结节的临床应用价值

摘要 目的：探讨甲状腺影像报告与数据系统(TI-RADS)分类鉴别良恶性甲状腺结节(TN)的临床应用价值。方法：选取2016年5月至2019年12月我院收治的182例TN患者的临床资料进行回顾性分析,所有患者均完成超声检查和TI-RADS分类,以病理结果为金标准,比较良恶性结节超声征象及TI-RADS分布情况,并采用ROC曲线分析TI-RADS分类对TN良恶性的鉴别价值。结果：182例患者247个甲状腺结节中,良性172个,占比69.64%,恶性75个,占比30.36%;良性TN中实性结节、极低回声、边界模糊、微钙化和纵横比<1发生率以及结节直径均低于恶性TN,差异有统计学意义(P<0.05);良性TN的TI-RADS分类主要为1类（59.30%）和2类（31.40%）,恶性TN主要为3类（42.67%）和4类（46.67%）,两组分布比较差异有统计学意义(P<0.05);ROC曲线分析结果显示TI-RADS分类鉴别良恶性TN的AUC=0.939(95%CI：0.904~0.973,P<0.05),以TI-RADS 2类和3类为良性,4类和5类为恶性进行诊断,其灵敏度为0.893,特异度为0.907,准确率为0.903,一致性Kappa值为0.777。结论：TI-RADS分类鉴别良恶性甲状腺结节具有较高的临床应用价值,但也还存在一定误诊的可能性。     

Thyroid cytopathology: Bethesda and beyond

Thyroid nodules are commonly encountered in clinical practice. Although the overwhelming majority of them turn out to be benign, the small subset of cancerous nodules needs to be accurately identified for optimal and timely surgical management. Fine-needle aspiration has proven to be the most valuable diagnostic modality for pre-operative distinction of benign from malignant nodules. The recently introduced and much anticipated Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) has standardized our diagnostic approach to reporting and cytomorphological criteria. TBSRTC has well-defined and rational management algorithms with implicit risk of malignancy in each of the 6 diagnostic categories. Recently published data supports the clinical utility and wide acceptance of TBSRTC by both practicing pathologists and clinicians. The problematic category of 'indeterminate' cytopathologic diagnoses has led to the discovery and development of unique and useful molecular markers, such as BRAF, which have displayed promising potential in recently published studies. As a result of the publication of TBSRTC, in 2009 the American Thyroid Association revised its clinical guidelines for the management of patients with thyroid disease and TBSRTC offers a useful source of information for the pathologist as well.