Management of the solitary thyroid nodule

Thyroid nodules are common, with up to 8% of the adult population having palpable nodules. With the use of ultrasound, up to 10 times more nodules are likely to be detected. Increasing numbers of nodules are being detected serendipitously because of the rising use of imaging to investigate unrelated conditions. The primary aim in investigating a thyroid nodule is to exclude the possibility of malignancy, which occurs in about 5% of nodules. This begins with a thorough history, including previous exposure to radiation and any family history of thyroid cancer or other endocrine diseases. Clinical examination of the neck should focus on the thyroid nodule and the gland itself, but also the presence of any cervical lymphadenopathy. Biochemical assessment of the thyroid needs to be followed by thyroid ultrasound, which may demonstrate features that are associated with a higher chance of the nodule being malignant. Fine-needle aspiration biopsy is crucial in the investigation of a thyroid nodule. It provides highly accurate cytologic information about the nodule from which a definitive management plan can be formulated. The challenge remains in the management of nodules that fall under the "indeterminate" category. These may be subject to more surgical intervention than is required because histological examination is the only way in which a malignancy can be excluded. Surgery followed by radioactive iodine ablation is the mainstay of treatment for differentiated thyroid cancers, and the majority of patients can expect high cure rates.     

Diagnosis and management of patients with thyroid nodules

Fewer than 5% of all adults will have a palpable thyroid nodule, but this is still a large number of individuals who require evaluation. Although most thyroid nodules are a result of a benign disease process (more than 95%), the possibility of thyroid cancer is always a consideration. Important aspects of history taking with a patient in whom a thyroid nodule has been noted include age, gender, family history of thyroid or endocrine disease, prior low dosage head and neck radiation, recent hoarseness, dysphagia, and symptoms of hypermetabolism. Key features of evaluation by physical examination are the size and location of the thyroid abnormality, the degree of firmness of the nodule, the presence of other nodules in the thyroid, palpable cervical lymph nodes, vocal cord paresis or paralysis, and tachycardia and/or tremor.The major categories of thyroid abnormality in such patients include cysts, adenomas, thyroiditis, and cancer. Although radionuclide scans, ultrasound examination and computer tomography have all been employed in the assessment of thyroid nodules, and thyroid stimulating hormone assay is useful for confirming a euthyroid state, fine needle aspiration biopsy (FNAB) has proved to be the most efficient diagnostic tool. The findings from FNAB allow avoidance of operative treatment for a large portion of these patients with palpable thyroid nodules, but a diagnosis of "follicular neoplasm" on FNAB usually requires operation, despite the fact that many such patients do ultimately prove to have a benign lesion. The extent of operation in patients undergoing surgery will depend on the diagnostic findings before operation, but unilateral thyroid lobectomy is the minimum procedure when surgery is required.     

Multivariate evaluation of Thyroid Imaging Reporting and Data System (TI-RADS) in diagnosis malignant thyroid nodule: application to PCA and PLS-DA analysis

Objective

To explore the significance of ultrasonic features in differential diagnosis of thyroid nodules via combining the thyroid imaging reporting and data system (TI-RADS) and multivariate statistical analysis.

Methods

Patients who received surgical treatment and was diagnosed with single thyroid nodule by postoperative pathology and preoperative ultrasound were enrolled in this study. Multivariate analysis was applied to assess the significant ultrasonic features which correlated with identifying benign or malignance and grading the TI-RADS classification of thyroid nodule.

Results

There were significant differences in the nodule size, aspect ratio, internal, echogenicity, boundary, presence or absence of calcifications, calcification type and CDFI between benign and malignant thyroid nodules. Multivariate analysis showed clear-cut distinction both between benign and malignance and among different TI-RADS categories of malignancy nodules. The shape and calcification of the nodule were important factors for distinguish the benign and malignance. Height of the nodule, aspect and calcification was important factors for grading TI-RADS categories of malignancy thyroid nodules.

Conclusions

Ill-defined boundary, irregular shape and presence of calcification related with highly malignant risk for thyroid nodule. The larger height and aspect and presence of calcification related with higher TI-RADS classification of malignancy thyroid nodule.

     

Evaluation and management of incidentally discovered thyroid nodules

Thyroid nodules are present in 4-10% of the adult population. However, less than 1% of all cancers occur in the thyroid gland. Thyroid nodules are usually an incidental finding in a routine clinical or an ultrasound examination of the neck performed for some other reason. Differentiating a benign nodule, which may require no specific treatment, from a malignant nodule presents a diagnostic dilemma. An individualized approach to a patient with history, risk factors and fine needle cytology is warranted. Molecular markers and immunohistochemical studies done on thyroid nodule cytology may help in differentiating benign from malignant. This article presents a review of the literature for the diagnosis and management of the thyroid nodule.     

超声造影不均匀低增强对甲状腺乳头状癌的诊断价值

目的:探讨超声造影（CEUS）不均匀低增强对甲状腺乳头状癌的诊断价值。方法:选取2015年2月至2017年2月于延安大学附属医院行甲状腺手术并于术前行超声造影检查的患者，回顾性分析，将增强模式表现进行分类，并与病理结果进行对照。结果:72例患者共74个结节。不均匀低增强43个结节，其中31个乳头状癌，9个结节性甲状腺肿，2个桥本氏甲状腺炎，1个髓样癌；超声造影不均匀低增强诊断甲状腺乳头状癌的敏感性、特异性及准确率分别为86.11%(31/36)、68.42%(26/38)和77.03%(57/74)。结论:超声造影诊断甲状腺乳头状癌具有其独特的优势，但是仅仅依靠“不均匀低增强”诊断PTC存在较高的误诊率，所以诊断过程中还应注意结节增强后的边界、形态及甲状腺包膜完整性等观察指标。     

Five-year Follow-up and Clinical Outcome in Euthyroid Patients with Thyroid Nodules

BackgroundThyroid nodule diagnosis has become increasingly frequent. Defining optimum surveillance intervals for patients with unsuspicious thyroid nodules remains a challenge. This was a single centre cohort study in which patients diagnosed with unsuspicious thyroid nodules in whom no treatment was indicated were invited for re-evaluation 5 years after the diagnosis. The primary end point of the study was to estimate the change in nodule size with thyroid ultrasound (US) and the secondary end point was to assess the need for clinical management 5 years after the diagnosis.Patients and methodsBaseline patient parameters and ultrasound characteristics of the nodules were retrospectively collected. At follow-up, thyroid ultrasound was performed.ResultsA hundred and eighteen (107 women / 11 men, aged 56.8 ± 13.4 years) patients were included in the study having 203 nodules at baseline, with mean largest nodule diameter 10.5 ± 7.4 mm. After 5 years, 58 (28.6%) nodules significantly increased in size, 27 (13.3%) decreased, and for 104 (51.2%) of nodules, no change in size was noted. Fourteen (6.9%) nodules disappeared. Additional 26 new nodules (mean largest diameter 7.7 ± 5.0 mm) in 16 patients were identified at follow-up. Regarding the clinical outcome, no new thyroid cancers were found. For 107 (90.7%) patients no further management was indicated. Five (4.2%) patients were referred to thyroidectomy because of the growth of the nodules. Two (1.7%) patients were treated for hyperthyroidism. Four (3.4%) patients did not complete the study.ConclusionsWe report a single centre experience of the natural history of unsuspicious thyroid nodules. Our results showed that 71.4% of such nodules remained stable in size, decreased or even disappeared and that the vast majority of the patients remained clinically stable with no need for treatment 5 years after the diagnosis.Key words: thyroid, nodule, goiter     

Role of ultrasound in the assessment of nodular thyroid disease

The role for ultrasound (US) in the assessment of nodular thyroid disease has increased in recent years. This expanded role has been highlighted in recent consensus guidelines on the management of nodular thyroid disease. In this review, we address the potential roles for US in assessing thyroid nodules and review these recent guidelines. In particular, we review the evidence that US characteristics of thyroid nodules can predict the risk of malignancy. A predominantly solid nodule, hypoechogenicity, microcalcification, macrocalcification, ill‐defined margins, intranodular vascularity, and taller‐than‐wide shape have all been associated with increased risk of malignancy, but no single US characteristic is sufficiently sensitive or specific to exclude or diagnose malignancy by itself. However, the use of combinations of US characteristics to stratify nodules into high and low risk for malignancy appears a promising strategy. Unselected nodules without any suspicious US features have a low risk of malignancy (<2%), whereas malignancy rates are much higher in nodules with at least two suspicious features. Recent guidelines endorse this approach of using combinations of US features to guide nodule selection for fine needle aspiration.     

Thyroid nodules: diagnosis and therapy.

Less than 1% of all cancers are present in the thyroid, yet thyroid nodules are found in 4 to 10% of the adult population. Because thyroid nodules are relatively common, the diagnostic dilemma is to distinguish between a more common benign nodule, which usually does not require specific treatment, and a malignant nodule, which requires thyroidectomy and further treatment. Thyroid nodules usually are an incidental finding on a routine examination by a primary care physician. When patients seek treatment for symptomatic nodules, a more serious problem may be indicated, and thyroid cancer is suggested. However, additional studies have demonstrated the use of genetic markers and immunohistochemistry in the diagnosis of thyroid nodules, which may lead to a more rational approach to the treatment. This article reviews literature published in the last 12 months pertaining to the pathogenesis, diagnosis, and treatment of thyroid nodules.     

超声检查联合基质金属蛋白酶检测对甲状腺癌的诊断价值

目的：探讨超声检查联合基质金属蛋白酶（MMPs）检测诊断甲状腺癌的临床价值。方法：我院收治的476例甲状腺结节患者为研究对象,其中甲状腺癌63例,良性结节者413例。分别对两组患者进行超声弹性成像检查和基质金属蛋白酶检测。观察两组患者的超声表现,对两组患者的血清 MMP －2、MMP －9水平进行比较,并对超声检查以及超声联合基质金属蛋白酶检测两种检查方式在诊断甲状腺癌上的准确度、敏感度及特异度进行对比性分析。结果：从超声结果来看,无包膜、低回声、微钙化和囊性变在鉴别甲状腺良恶性结节上存在显著性差异（P ＜0．05）。甲状腺癌患者的弹性图像上多表现为3～4分,而良性结节组患者的评分多在0～2分,组间差异比较有统计学意义（P ＜0．05）。甲状腺癌组的 MMP －2、MMP －9水平均显著高于良性结节组,组间比较有显著性差异（P ＜0．05）。在鉴别甲状腺良恶性结节上,超声联合基质金属蛋白酶诊断甲状腺癌的阳性率和诊断良性结节的阴性率均明显高于超声诊断（P ＜0．05）。而超声联合基质金属蛋白酶诊断甲状腺癌上的准确度、敏感度和特异度分别为85．50％、90．48％、84．75％,均优于超声诊断（73．32％、76．19％、72．88％）,差异有统计学意义（P ＜0．05）。结论：超声弹性成像对于鉴别甲状腺癌具有一定临床价值,而基质金属蛋白酶在甲状腺癌的侵袭转移过程中发挥较为重要的作用,其过度表达能够作为甲状腺癌患者的预后指标,通过超声弹性成像联合基质金属蛋白酶检测能够显著提高甲状腺癌的诊断准确性。     

Squamous cell carcinoma of esophagus masquerading as solitary thyroid nodule

Secondary neoplasm of the thyroid mimicking a primary thyroid lesion is a rare finding, especially in an individual without a past history of malignancy. A case of squamous cell carcinoma metastatic to the thyroid (presenting as a solitary thyroid nodule), who had an unsuspected primary in the esophagus is described. Usually, multiple areas of the gland are involved in the secondary involvement of the thyroid. The clinical presentation of an apparently asymptomatic mass with neck lymphadenopathy, normal thyroid functions, and a cold nodule on 99mTcO4- thyroid scan can often lead to a misdiagnosis as primary thyroid neoplasm. The present case underscores the fact that due importance to the subtle signs and symptoms and a high degree of suspicion, whenever the histology is unusual for a thyroid primary, is needed and the workup should include ruling out other primary malignancies.     

甲状腺微癌47例临床分析

目的：探讨甲状腺微癌的诊治经验和生物学行为。方法：对我院近10年来收治的47例甲状腺微癌进行回顾性分析。结果：女性40例,男性7例,女：男5.7：1。以甲状腺结节就诊的29例,在健康查体中超声发现甲状腺结节18例。发现结节到就诊时间最长15年。手术前47例均行甲状腺彩色超声检查,其中30例提示甲状腺结节内存在钙化呈细砂粒状。术前行甲状腺结节穿刺19例,有8例诊断为甲状腺癌,4例诊断为甲状腺腺瘤,5例诊断为甲状腺肿,2例诊断为桥本氏甲状腺炎。手术行冰冻快速病理诊断43例（包括术前8例）,误诊4例。结论：甲状腺微癌误诊率较高,彩色超声显示甲状腺结节内细砂粒样钙化对甲状腺微癌的诊断有重要的参考价值。对甲状腺微癌的手术治疗应与甲状腺癌一样对待,甲状腺微癌同样有较高的转移率。     

甲状腺结节细针穿刺分子标志物的研究进展

近年来，甲状腺结节的发病率逐年上升，高分辨率超声和超声引导下细针穿刺细胞学检查（fine needle aspiration biopsy，FNAB）是甲状腺结节术前诊断的最佳手段。但是仍然有一部分结节诊断不明确，于是FNAB结合甲状腺结节细针穿刺分子标志物的研究迅速发展。目前研究较多的分子标志物主要为BRAF基因突变、RAS基因突变、RET/PTC基因重排和PAX8/PPARγ基因重排等；以及使用免疫组织化学（immunohistochemistry，IHC）检测的半乳糖凝集素3（galectin-3，Gal-3）、细胞角蛋白19（cytokera? tin-19，CK-19）、人类骨髓内皮细胞（human bone marrow endothelial cell-1，HBME-1）等。本文对目前甲状腺结节细针穿刺（fine needle aspiration，FNA）分子标志物的一些研究进展进行综述。      

Gene therapy: the end of the rainbow?

Background

Papillary carcinoma is the most common differentiated malignant thyroid neoplasm. The biological course of this cancer is typically indolent with a protracted clinical course. Metastases commonly occur in regional lymph nodes, and distant metastasis is a late and rare occurrence. We report a patient who presented with cerebellar metastasis prior to the diagnosis of papillary thyroid carcinoma and review the literature of brain metastasis from papillary thyroid carcinoma.

Results

A 75-year old female presented at the emergency room with progressive dizziness, headache and vomiting, where a brain CT and MRI showed a posterior cerebellar tumor. Surgical resection revealed papillary carcinoma consistent with thyroid origin. Subsequent ultrasound and CT-scan revealed a thyroid nodule, after which the patient underwent total thyroidectomy. Pathologic evaluation was consistent with papillary thyroid carcinoma.

Conclusion

Brain metastasis may rarely be the initial presentation of papillary thyroid carcinoma. Solitary brain metastasis can completely be resected with better prognosis.     

Prostate biopsy techniques and indications: when, where, and how?

Transrectal ultrasound (TRUS) and prostate biopsy have become one of the most common office-based procedures for the practicing urologist. During the past 50 years, the techniques, indications, and pathologic interpretation of prostate biopsies have evolved. The abandonment of blind finger-guided needle biopsies in favor of systematic TRUS-guided biopsies epitomizes much of this change. Similarly, the indications for prostate biopsy have become more refined. In the past, the presence of a prostatic nodule on digital rectal examination (DRE) was the primary indication for biopsy until the introduction of prostatic-specific antigen (PSA) in the 1980s and its widespread use for prostate cancer screening. Abnormalities of PSA or its derivatives now represent the most common indication for prostate biopsy. Although TRUS initially began as a tool to direct needles into various locations within the prostate, today a great deal of information can be obtained from prostate ultrasound for the discerning clinician. As such, TRUS-guided biopsy of the prostate has become an important staging and diagnostic tool for the practicing urologist. Here we review the current techniques and indications as well as pertinent pathologic and staging data obtained through TRUS and prostate biopsy.     

Radioimmunotherapy of experimental head and neck squamous cell carcinoma (HNSCC) with E6-specific antibody using a novel HPV-16 positive HNSCC cell line

Background

This study aimed to evaluate clinical, laboratory, ultrasound (US) and scintigraphyc parameters in thyroid nodule and to develop an auxiliary model for clinical application in the diagnosis of malignancy.

Methods

We assessed 143 patients who were surgically treated at a single center, 65% (93) benign vs. 35% (50) malignant lesions at final histology (1998-2008). The clinical, laboratory, scintigraphyc and US features were compared and a prediction model was designed after the multivariate analysis.

Results

There were no differences in gender, serum TSH and FT4 levels, thyroid auto-antibodies (TAb), thyroid dysfunction and scintigraphyc results (P = 0.33) between benign and malignant nodule groups. The sonographic study showed differences when the presence of suspected characteristics was found in the nodules of the malignant lesions group, such as: microcalcifications, central flow, border irregularity and hypoechogenicity. After the multivariate analysis the model obtained showed age (>39 years), border irregularity, microcalcifications and nodule size over 2 cm as predictive factors of malignancy, featuring 81.7% of accuracy.

Conclusions

This study confirmed a significant increase of risk for malignancy in patients of over 39 years and with suspicious features at US.     

常规超声联合超声造影鉴别甲状腺结节良恶性的价值

目的 探讨常规超声联合超声造影技术鉴别甲状腺良恶性结节的价值.方法 对62例患者的75个甲状腺低回声结节进行常规超声及超声造影检查,测量结节大小,观察结节形态、边界、位置、有无微小钙化、血流情况及超声造影检查结果.结果 甲状腺结节内部具有多发微小钙化低回声结节13个,形态不规则低回声结节69个,边界不清晰低回声结节69个,结节邻近包膜浸润11个.造影后37个低回声结节呈无增强,38个低回声结节呈低增强,28个低回声结节体积变小.经常规超声检查诊断甲状腺恶性结节65个,经超声造影检查诊断甲状腺恶性结节64个,术后病理证实甲状腺乳头状癌62个,结节性甲状腺肿13个.常规超声联合超声造影诊断甲状腺恶性结节64个,灵敏度为100％,特异度为84.6％,Kappa=0.901.结论 常规超声联合超声造影有助于提高对甲状腺恶性结节的诊断能力.     

高频超声对甲状腺囊实性结节良恶性鉴别的效果

目的 探讨高频超声对甲状腺囊实性结节良恶性鉴别的效果.方法 选取甲状腺囊实性恶性结节患者47例以及甲状腺囊实性良性结节患者47例.所有患者均予以高频超声检查,观察对比良、恶性结节图像特征.结果 高频超声诊断恶性结节的误诊率为8.51％(4/47),高于病理诊断的0.00％(0/47),差异有统计学意义(P<0.05).良性结节高频超声的病灶内部结构、内部回声、边界、形状、钙化与恶性结节对比,差异有统计学意义(P均<0.05).良性结节RI值<0.7人数占比为85.11％(40/47),高于恶性结节的14.89％(7/47),差异有统计学意义(P<0.05).结论 高频超声诊断甲状腺囊实性良性结节的准确度高,有利于鉴别甲状腺囊实性结节良恶性.     

Association of insulin-like growth factor-1 with thyroid nodules

The aim of the present study was to investigate the relationship between insulin-like growth factor-1 (IGF-1) and thyroid nodules. A total of 56 patients with thyroid nodules confirmed by physical examination and ultrasound screening were randomly selected. The patients were divided into three groups by radionuclide scan: the hot nodule group (group 1, n=18); the cold and solid nodule group (group 2, n=18); and the cold and cystic nodule group (group 3, n=20). Cystic fluid samples from patients with cystic cold thyroid nodules were defined as group 4. A control group of 18 healthy adults matched for age, gender and body mass index (group 0) was also included. For all participants, levels of the thyroid hormones, TT3, TT4, TSH and IGF-1, were determined by radioimmunoassay. The measurement data were expressed as the mean ± standard deviation (SD). The analysis of variance was performed by the t-test and the correlation analysis was performed by linear regression. The serum levels of IGF-1 in the solid cold nodule group were significantly higher than those in the hot nodule group (P<0.05). Serum levels of IGF-1 in the cystic cold nodule group were significantly lower than those in the control group (P<0.05). The serum IGF-1 levels in the cystic fluid were significantly lower than those in the cystic cold nodule (P<0.05) and the control groups (P<0.05). Additionally, the mean serum IGF-1 level in patients with thyroid adenoma was significantly higher than that in the control group (P<0.05). The serum IGF-1 level may not be involved in the pathogenesis of hot thyroid nodules and cold and cystic thyroid nodules; however, it may play a significant role in the pathogenesis of certain solid cold thyroid nodules.     

Shorter Distance Between the Nodule and Capsule has Greater Risk of Cervical Lymph Node Metastasis in Papillary Thyroid Carcinoma

Background: The purpose of this study was to assess the relationship between different sonographic featuresof papillary thyroid carcinoma (PTC) on high-frequency ultrasound and cervical lymph node metastasis (CLNM).Materials and Methods: We enrolled 548 patients who underwent initial surgery for PTC between May 2011 andDecember 2012 in our hospital at diagnosis. The sonographic features of 513 PTC nodules in 513 eligible patients,who had single PTC nodules in their thyroid glands, were retrospectively investigated. All patients with a suspectmalignant nodule (d<0.5cm) among multiple nodules were initially diagnosed by fine-needle aspiration biopsy(FNAB) to ascertain if the suspect nodule was PTC. The final diagnosis of all the thyroid nodules and existenceof CLNM were based on postoperative pathology. Patients were divided into two groups: a positive group withCLNM (224 nodules) and a negative group without CLNM (289 nodules). The following factors were investigated:gender, age, echogenicity, echotexture, size, shape, location, margin, contour, calcification morphology, distancebetween the nodule and pre- or post-border of the thyroid capsule, vascularity and the differences between thetwo groups. Results: Correlation analysis showed that shorter distances between the nodule and pre- or postborderof thyroid capsule resulted in greater risk of CLNM (Spearman correlation coefficient=-0.22, p<0.0001).The significant factors in multivariate analysis were age<45yrs, larger size (d>1cm), “wider than tall” shape,extrathyroid extension and mixed flow (internal and peripheral) (p<0.05, OR=0.406, 2.093, 0.461, 1.610, 1.322).Conclusions: Significant sonographic features of PTC nodules in preoperative high-frequency ultrasound arecrucial for predicting CLNM.     

Radiation-induced thyroid changes: A retrospective and a prospective view

Aim of the studyIncidental/therapeutic thyroid irradiation causes hypothyroidism and nodular disease. Increasing numbers of children are being cured of cancers by treatments that include radiation also involving the thyroid bed: these children warrant an early diagnosis and treatment of any radiation-related thyroid changes.MethodsIn 1998 we retrospectively evaluated thyroid parenchyma/function in all patients irradiated between 1975 and 1997; thereafter, we prospectively evaluated all patients given thyroid irradiation by means of thyroid ultrasound and serum fT3, fT4, TSH and thyroglobulin.ResultsOf 596 eligible patients, 468 agreed to the retrospective evaluation: 128/468 had one or more thyroid nodules, and 73 of these 128 had concomitant or previously untreated hypothyroidism, while 22/128 had a differentiated carcinoma. Another 144/157 patients treated between 1998 and 2004 were evaluated and any iatrogenic hypothyroidism was promptly treated: 19/144 had nodules, all smaller than 1 cm in diameter. The first patient group was studied retrospectively, so we have no precise record of the time of nodule occurrence or of their initial sizes. We found, however, that both the number of patients with nodules and the sizes of the nodules were significantly lower (p < 0.01) in the prospectively studied group (after a median follow-up of 81 months) than in the retrospectively studied group. Among all the patients with nodules, significantly more females developed cancer than males (p < 0.04).ConclusionsEarly treatment for hypothyroidism and ultrasound evaluation of the parenchyma are needed to limit nodule onset and growth.