Characterization Of Thyroid Nodules Research Articles

Frontiers in Thyroid Cancer: December 2009

Frontiers in Thyroid Cancer: December 2009

Real-time Elastography and Contrast-Enhanced Ultrasound for the Assessment of Thyroid Nodules

Work-up of thyroid nodules remains challenging. Recent technologies enable determination of tissue elasticity and perfusion using ultrasound devices. The aim of the present study was to evaluate real-time elastography (RTE) and contrast-enhanced ultrasound with Sonovue (CEUS) for the differentiation of benign and malignant thyroid nodules. Inclusion criteria were: nodules ≥1 cm, non-functioning or hypo-functioning on radionuclide scanning, and cytological/histological assessment. All patients received conventional ultrasound, RTE and CEUS. RTE was classified as: Elasticity-Score (ES)1 = soft, ES2 = predominantly soft, ES3 = predominantly hard, ES4 = hard nodule. CEUS-video clips were digitally recorded and analyzed using time-intensity-curves within selected regions-of-interest. Fifty-three nodules in 50 patients were available for analysis. Forty-six nodules were benign on cytology/histology, 6 nodules were papillary carcinoma and one nodule was a follicular carcinoma. Nodule margin irregularity was the ultrasound pattern most predictive of malignancy with sensitivity 57% (95% confidence interval: 18-90%) and specificity 85% (71-94% p<0.05). When using ES3&4 for the diagnosis of malignant nodules sensitivity and specificity were 86% (42-99.7%) and 87% (75-95%), respectively (p = 0.0003). The only malignant nodule missed with RTE was a follicular carcinoma. Sensitivity for the diagnosis of papillary carcinoma therefore was 100%. No specific CEUS pattern could be identified to differentiate between benign and malignant nodules. RTE seems to be a useful tool in the work-up of thyroid nodules to exclude papillary thyroid cancer. However, follicular carcinoma remains a challenging problem. CEUS did not improve the characterization of thyroid nodules in this preliminary study.

99mTc-MIBI Imaging in the Presurgical Characterization of Thyroid Follicular Neoplasms: Relationship to Multidrug Resistance Protein Expression

Recently, thyroid (99m)Tc-methoxyisobutylisonitrile ((99m)Tc-MIBI) scintiscanning has been proposed in an attempt to preoperatively identify thyroid malignancies, but discrepant results have been reported for oncocytic lesions. The aim of this study was to investigate the usefulness of visual and semiquantitative analyses of (99m)Tc-MIBI scintigraphy for preoperatively characterizing thyroid nodules with indeterminate cytologic diagnoses, segregating in advance nononcocytic variants from those that are oncocytic. This study also aimed to analyze the relationship between (99m)Tc-MIBI images and P-glycoprotein (P-gp)/multidrug resistance-associated protein-1 (MRP1) immunohistochemical expression. Fifty-one consecutive patients with cold thyroid nodules cytologically diagnosed as nononcocytic or oncocytic follicular neoplasm were prospectively studied. Visual and semiquantitative (99m)Tc-MIBI scanning was performed and the diagnoses of the lesions were histologically proven by subsequent thyroidectomy. Immunohistochemical evaluation of P-gp and MRP1 was also performed on surgical samples. Visual and semiquantitative (99m)Tc-MIBI scintiscans showed a low specificity in preoperatively discriminating malignant oncocytic lesions. In nononcocytic nodules, the semiquantitative method was more accurate than the visual (94.44% and 77.78%, respectively). P-gp protein expression was negative in all thyroid lesions, whereas apical plasma membrane MRP1 expression was found in 78% of the lesions with a negative (99m)Tc-MIBI retention index, compared with 11% of lesions with a positive retention index, correlating most strongly with a negative (99m)Tc-MIBI RI in those cases with strong MRP1 apical expression. Semiquantitative (99m)Tc-MIBI scintigraphy is an adjunctive method to predict preoperatively the malignant behavior of nononcocytic follicular thyroid nodules indeterminate at fine-needle aspiration biopsy, with a potential impact on the definition of their clinical management. Moreover, the good correlation found between immunohistochemical apical expression of MRP1 and the scintigraphic findings supports the (99m)Tc-MIBI results and provides tissue information on the molecular mechanisms responsible for (99m)Tc-MIBI images in thyroid lesions.

Do tumor characteristics predict risk of malignancy in thyroid nodules with indeterminate cytology?

The use of ultrasonography-guided, fine-needle aspiration cytology (FNAC) has enhanced the preoperative characterization of thyroid nodules and reduced the need for diagnostic surgeries. However, complete preoperative characterization is not yet possible for patients with an indeterminate FNAC result. Here, results are discussed from a retrospective study by Banks et al. that aimed to refine preoperative risk assessment of thyroid cancer in patients with indeterminate FNAC results. The authors found that patients' age, nodule size and specific cytological diagnoses were all associated with thyroid malignancy. These variables were used to construct a diagnostic predictor model. The study by Banks et al. provides general guidance for clinicians who need to estimate thyroid cancer risk for patients with indeterminate FNAC results. Refinements in risk assessment for thyroid malignancy might help to individualize care of these patients; however, the results also underscore the need for enhanced diagnostic methods.

Ultrasound examination using contrast agent and elastosonography in the evaluation of single thyroid nodules: Preliminary results

Aim To evaluate the usefulness of ultrasound (US) using contrast agent and elastosonography in the characterization of thyroid nodules. Materials and methods From November 2006 to July 2007, 23 patients with single thyroid nodules underwent B-mode US and power Doppler, US examination using contrast agent, elastosonography and fine needle aspiration cytology (FNAC). Sixteen patients underwent thyroidectomy. Results The 23 nodules included 14 benign and 9 malignant lesions. Analysis of time/intensity curves showed that wash-in (8.8 ± 1.3 vs 12.1 ± 2.6 s; p = 0.002, t-test) and peak enhancement (15.3 ± 4.6 vs 22.2 ± 3.9 s; p = 0.001, t-test) occurred significantly earlier in the malignant nodules than in the benign nodules. Wash-out was monophasic in 70% of benign nodules, but in none of the malignant nodules; polyphasic in 30% of benign nodules and in 100% of malignant nodules. Polyphasic wash-out showed a statistically significant association with malignancy ( p = 0.0007, χ 2). Polyphasic wash-out yielded a sensitivity of 100%, specificity of 71%, positive predictive value (PPV) of 69%, negative predictive value (NPV) of 100% and diagnostic accuracy of 83%. In 78% of the benign nodules (11/14) elastosonographic patterns was 1–2 (elevated elasticity); in 88% of the malignant nodules (8/9) elastosonographic patterns was 3–4 (reduced elasticity). Elastosonography yielded a sensitivity of 88%, specificity of 78%, PPV of 72%, NPV of 91% and diagnostic accuracy of 82%. Elastosonographic patterns 3–4 is associated with malignancy ( p = 0.001, χ 2). Conclusion US using contrast agent and elastosonography can be a useful diagnostic tool in the evaluation of single thyroid nodules, particularly when FNAC result is non-diagnostic or suggests a follicular lesion, and in nodules <1 cm.

Élastographie ultrasonore des lésionsthyroïdiennes

While ultrasound is the imaging modality of choice for diagnosis of thyroid lesions, characterization remains limited and tissue diagnosis frequently is required for management. The availability of additional tools such as elastography may improve lesion characterization and direct management. A total of 96 patients (11 males and 85 females; 58+/-24 years) referred for fine needle aspiration (FNA) of mainly solid thyroid nodules 9-32 mm in diameter underwent conventional US and elastosonography. Results on elastography were correlated with histological results from FNA and classified as follows: suspected malignant lesion, suspected benign lesion, suspicious, indeterminate. The nodules were classified as follows: 95 nodules were soft (classes I and II) and 13 nodules were hard (classes III and IV). No cancers were detected in class and II lesions and 6 cancers were detected in class III and IV lesions. FNA provided insufficient cellular material for diagnosis in 5 class I-II nodules and 2 class III-IV nodules. Real-time elastosonography may be a useful adjunct to conventional US in the evaluation and characterization of thyroid nodules allowing identification of patients at high risk of malignancy for whom tissue diagnosis and/or close follow-up is required.

Initial Clinical Experience Imaging Scatterer Size and Strain in Thyroid Nodules

This article describes a new research ultrasound scanner that can be programmed to produce elastograms and backscatter parametric images in real time. Its performance was evaluated in a clinical setting. Radio frequency data were acquired from 13 patients with thyroid nodules and from 4 normal thyroids, along with reference phantom data. Scatterer size was deduced by measuring the backscatter versus frequency and fitting data to a model. Strain was obtained by a cross-correlation method, comparing precompression and postcompression radio frequency signals. Scatterer size contrast was defined as the observed contrast between the "normal" and "abnormal" tissue in the same gland or, when considering diffuse conditions, by comparing with normal values. Strain contrast was estimated if abnormal and normal tissue was captured in the same palpation, that is, excluding diffuse disease, which was the case for 9 subjects. On scatterer size images, 4 nodules exhibited positive contrast versus the adjacent normal parenchyma, indicating larger scatterers. Five nodules were isoechoic, and 4 had negative contrast. Four nodules exhibited positive strain contrast, indicating that they were softer than the normal parenchyma. Two nodules had the same brightness, and 3 were darker than the background thyroid tissue on strain images. Contrast was observed between nodules and thyroid parenchymal tissue for both types of parametric images. Further work is needed to determine whether the diagnostic importance of these parameters in characterizing thyroid nodules might be worthwhile. Both modes must be of a sufficient frame rate to provide real-time feedback to operators, which will require further work.

Large needle aspiration biopsy and galectin-3 determination in selected thyroid nodules with indeterminate FNA-cytology

Thyroid fine-needle aspiration biopsy (FNA)-cytology is widely used for the preoperative characterisation of thyroid nodules but this task is difficult for follicular lesions, which often remain undefined. We propose a strategy for improving the preoperative characterisation of selected follicular thyroid proliferations, which is based on large needle aspiration biopsy (LNAB) and galectin-3 expression analysis. Eighty-five thyroid specimens were obtained by LNAB (20-gauge needles) from thyroid nodules with indeterminate follicular FNA-cytology. Aspirated material was processed as a tissue microbiopsy to obtain cell blocks for both cyto/histo-morphological evaluation and galectin-3 expression analysis, by using a purified monoclonal antibody to galectin-3 and a biotin-free immunoperoxidase staining method. Preoperative diagnosis was compared to the final histology. LNAB and cell-block technique allow a preliminary distinction between nodules with a homogeneous microfollicular/trabecular structure, as frequently observed in tumours, and lesions with mixed normo–micro–macrofollicular architecture, as observed in goitre. Furthermore, LNAB provides optimal substrates for galectin-3 expression analysis. Among 85 cases tested, 14 galectin-3-positive cases were discovered preoperatively (11 thyroid cancers and three adenomas confirmed at the final histology), whereas galectin-3-negative cases were 71 (one carcinoma and 70 benign proliferations at the final histology). Sensitivity, specificity and diagnostic accuracy of this integrated morphologic and phenotypic diagnostic approach were 91.6, 97.2 and 95.3%, respectively. In conclusion, LNAB plus galectin-3 expression analysis when applied preoperatively to selected thyroid nodules candidate to surgery can potentially reduce unnecessary thyroid resections.

Qualitative and quantitative evaluation of solitary thyroid nodules with contrast-enhanced ultrasound: initial results

To assess the feasibility of contrast-enhanced ultrasound (CEUS) of the thyroid gland and to evaluate the potential of this method for characterising solitary thyroid nodules.18 patients affected by solitary thyroid nodules (size range: 0.6 to 3.6 cm; mean: 1.8 cm) confirmed by surgery (nine papillary carcinomas, four follicular carcinomas, three hyperplasias, one follicular adenoma and one Plummer's adenoma) underwent pulse inversion US at low M.I. (0.06 to 0.08) after i.v. injection of a 2.4-mL bolus of SonoVue. Baseline echogenicity and the dynamic enhancement pattern of each nodule, in comparison with adjacent thyroid parenchyma, were assessed. Signal intensity values on grey-scale images were also calculated at baseline, 30 s, 60 s and 120 s after SonoVue administration. Following administration of SonoVue, malignant nodules showed absent (4 out of 13), faint dotted (4 out of 13) and diffuse (5 out of 13) contrast enhancement, in this last case inhomogeneous (4 out of 5 cases) or homogeneous (1 out of 5). Benign nodules showed diffuse contrast enhancement, both homogeneous (3 out of 5) and heterogeneous (2 out of 5). Quantitative data have confirmed subjective findings, but CEUS never modified precontrast analysis. CEUS of thyroid gland is a feasible technique, but overlapping findings seem to limit the potential of this technique in the characterization of thyroid nodules.

3543: Role of contrast enhanced ultrasound with SonoVue® in characterization of thyroid nodules in comparison with color-power Doppler and fine needle aspiration biopsy

3543: Role of contrast enhanced ultrasound with SonoVue® in characterization of thyroid nodules in comparison with color-power Doppler and fine needle aspiration biopsy

From the bench to the bedside. Galectin-3 immunodetection for improving the preoperative diagnosis of the follicular thyroid nodules

The authors discuss the principal aspects concerning the preoperative characterization of thyroid nodules, in particular those with follicular histology, and illustrate the potential clinical impact of a new diagnostic test-method, named “galectin-3 thyrotest”, which is based on the immunodetection of galectin-3 molecule in cytological specimens derived from thyroid nodular lesions. This diagnostic test method, which consistently improves the accuracy of conventional cytology, has been recently validated in a large international multicenter study and is going to impact hardly the clinical management of patients bearing thyroid nodular diseases. The rationale of this new diagnostic approach, the possibility to improve its performance in selected cases by using large needle aspiration biopsy (LNAB) together with technical and operative details are presented and discussed.

Grey scale thyroid ultrasonography in the evaluation of patients with Graves' disease.

Graves’ disease is a genetically induced autoimmune disorder characterized by hyperthyroidism due to circulating thyroid stimulating hormone (TSH) receptor autoantibodies (TRAb) with thyroid stimulating activity (1). Graves’ disease is the most common cause of hyperthyroidism, which has an estimated prevalence in iodine sufficient areas of 20/1000 females and 2.3/ 1000 males (2). It is most common in females between the ages of 20 and 50 years, but it may occur at any age. The laboratory diagnosis of Graves’ disease is based on the finding of high serum thyroid hormone and undetectable serum TSH concentrations associated with circulating thyroglobulin and thyroperoxidase antibodies. TRAb is detectable in almost 90% of patients, but usually it is not needed for the diagnosis. Radioisotope scan of the thyroid shows a diffuse and homogeneous radionuclide uptake. Treatment strategies for Graves’ hyperthyroidism include medical therapy with antithyroid drugs (ATD) or thyroid ablation with 131 I or surgery. ATD, mainly thionamides, inhibit thyroid hormone synthesis by blocking iodine organification catalysed by thyroid peroxidase. Treatment of Graves’ disease with thionamides is mainly performed in Europe and in Japan, while in the USA and Canada radioiodine is commonly preferred as the first choice treatment (3). Many studies have been undertaken to find parameters which help predict the clinical outcome of Graves’ hyperthyroidism after ATD withdrawal. Among them, TRAb measurement at the end of an ATD course was found to be the most predictive (4, 5). After its introduction into clinical practice in the late sixties, thyroid ultrasonography (US) proved to be very effective in the diagnostic approach to thyroid diseases, the anatomical location of the gland being advantageous for this technique. The most widely used application of thyroid US is identification and characterization of thyroid nodules (6). Rapid improvements in the development of US equipment have made available real-time high frequency transducers (7.5‐ 10 MHz) with high resolution, which allow a more precise definition of the echostructure of the thyroid tissue. In addition, recently developed color Doppler technology allows determination of the blood flow through the gland, offering the possibility of recording objective measurements, such as the peak systolic velocity of the blood flow at the level of thyroid arterial vessels (i.e. inferior thyroid artery). Using these techniques, thyroid blood flow has been shown to be correlated with the thyroid status in patients with Graves’ disease, being markedly increased in 17/18 patients with untreated active hyperthyroidism and less clearly increased in treated patients. In patients with Hashimoto’s thyroiditis, the thyroid blood flow was not correlated to thyroid status or treatment and was never markedly increased (7). Color Doppler sonography was also shown to be useful in distinguishing cases of destructive thyrotoxicosis by amiodarone (i.e. amiodarone thyrotoxicosis type 2), characterized by a low thyroid blood flow, from cases in which thyroid hyperfunction also occurs (i.e. amiodarone thyrotoxicosis type 1), characterized by an increased thyroid

Power Doppler Improves the Diagnostic Accuracy of Color Doppler Ultrasonography in Cold Thyroid Nodules: Follow-Up Results

The usefulness of a recent color Doppler (CD) ultrasonography technique, named power Doppler (PD), was evaluated in the diagnosis of thyroid nodules showing low or absent uptake of ^99mTc-pertechnetate, in order to investigate the possibility to improve the diagnostic accuracy of ultrasonography. The rationale was the evidence that at PD the color map displays the total integrated Doppler power in color, while CD generally displays an estimate of the mean Doppler shift. The vascular patterns recorded at PD and CD evaluation of 322 thyroid nodules were compared to the results of cytology and/or histology, when surgery was performed. In respect to the results of cytology, PD has a higher sensitivity (100 vs. 91%) and specificity (95.1 vs. 86.2%) than CD. A similar result was found when PD and CD were compared to the results of histology, sensitivity being 100 vs. 89% and specificity 98.1 vs. 93.7%, respectively. During the follow-up the 2 nodules considered false positive at PD resulted to be tumoral lesions. On this basis, the final specificity of PD in our series was 100%. In conclusion, in the current series including 322 thyroid nodules characterized by a low or absent uptake of ^99mTc-pertechnetate, PD seems to provide a better characterization of thyroid nodules, possibly allowing a more accurate selection of the patients to subject to fine-needle biopsy.