547542

research-article2014

UIXXXX10.1177/0161734614547542Ultrasonic ImagingÇakal et al.

Article

Elastography in the Differential Diagnosis of Thyroid Nodules

Ultrasonic Imaging 1­–7 © The Author(s) 2014 Reprints and permissions: sagepub.com/journalsPermissions.nav DOI: 10.1177/0161734614547542 ultrasonicimaging.sagepub.com

Erman Çakal1, Mustafa Şahin2, İlknur Öztürk Ünsal1, Aşkın Güngüneş1, Esra Akkaymak1, Evrim Çakır Özkaya1, Nujen Çolak Bozkurt1, Mustafa Özbek1, and Tuncay Delibaşı1

Abstract Despite the publication of a recent meta-analysis of elastography in thyroid nodules, further work is necessary on this issue in different populations. In this study, we aimed to evaluate the clinical value of elastography on nodular goiters in mild iodine-deficient regions without excluding patients according to nodule characteristics. This prospective study was conducted between April 2010 and December 2011 in Yıldırım Beyazıt Dıskapı Research Hospital Endocrinology outpatient clinic. Five hundred twenty-eight nodular goiter patients who underwent thyroid fine-needle aspiration biopsy were included in our study. Elastography scores and indexes were measured with real-time ultrasound elastography (Hitachi® EUB 7000 HV machine with 13 MHz linear transducer). There were 471 females and 57 males and their ages ranged from 45 years to 78 years. A total of 601 nodules were evaluated in these patients. The area under the curve (AUC) for the elasto score was 0.91 (p < 0.0001) and AUC for the strain index (SI) was 0.96 (p < 0.0001). We suggest that the SI reflects malignancy better than the elasto score. We conclude that elastography scores greater than 3 have 76% sensitivity and 96% specificity for diagnosing malignancy. For SI, we conclude that 3.75 (83% sensitivity and 95% specificity) is the cutoff point. Elasto score and SI measurements of thyroid nodules in our population are efficient and increase the diagnostic performance of the sonography. Keywords elastography, thyroid nodules, cancer

Introduction The most important issue in clinical nodule evaluation is to detect malignancy. Most of the thyroid nodules are benign; approximately 5% of them are likely to be malignant. Fine-needle aspiration is regarded as the most accurate method for discriminating benign thyroid nodules from malignant ones with high sensitivity and specificity.1

1Endocrinology 2Endocrinology

and Metabolism Department, Ankara Diskapi Training and Research Hospital, Turkey and Metabolism Department, Ankara University School of Medicine, Turkey

Corresponding Author: Mustafa Şahin, Associate Professor, Endocrinology and Metabolism Department, Ankara University School of Medicine, Ibni Sina Hastanesi Ek Bina M-blok Kat: 1 06100, Sihhiye/Ankara, Turkey. Email: [email protected]

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Ultrasonographic features of thyroid malignancy in thyroid nodules are hypoechogenicity, irregular margins, incomplete halo, central vascularity, microcalcifications, and taller ratherthan-wider. Sonography is useful in preoperative evaluation of thyroid nodules and in distinguishing malignant nodules from benign nodules.2 Elastography is a newly developed technique that measures the elasticity (degree of tissue distortion) of thyroid nodules using ultrasonography under the application of an external force.3 Elastography may reduce unnecessary surgeries and has been reported to be useful in the assessment of malignancy.4 Malignant nodules are harder in consistency and have a greater elastography score and strain index (SI) under elastographic evaluation.3 Despite the publication of a recent meta-analysis of elastography in thyroid nodules, further work is necessary on this issue in different populations.5 In almost all studies, patients with multiple or cystic nodules and nodules with calcification were excluded. There is a wide range of sensitivities and specificities of elastography in these studies, and patient numbers are still low even in meta-analysis.5 In this study, we aimed to evaluate the clinical value of elastography on nodular goiters in mild iodine-deficient regions without excluding patients according to nodule characteristics. We evaluated the sensitivity and specificity of elastography in diagnosing malignancy in our population. We also aimed to compare the value of strain ratio (SR) and elastography score (ES) measurements in the prediction of malignancy.

Materials and Method This prospective study was conducted between April 2010 and December 2011 in Yıldırım Beyazıt Dıskapı Research Hospital Endocrinology outpatient clinic. We included 528 nodular goiter patients who underwent thyroid fine-needle aspiration biopsy (FNAB) in our study. There were 471 females and 57 males and their ages ranged from 45 years to 78 years. A total of 601 nodules were evaluated in these patients. A local ethical committee approved the study and informed consent was collected from all patients. We did not exclude cystic nodules or nodules with calcifications. Thyroid ultrasound and elastographic examination was performed using high-resolution B-mode gray-scale ultrasonography, Power Doppler ultrasonography, and real-time ultrasound elastography (Hitachi® EUB 7000 HV machine using 13 MHz linear transducer). We evaluated the echogenicity, size, volume, margin regularity, and blood flow pattern of nodules. The presence and nature of halo signs and micro and macrocalcifications were also evaluated. Blood flow patterns were classified as type 1 if there was absence of blood flow, type 2 if there was only perinodular blood flow, and type 3 if there was marked intranodular blood flow with absent or slight perinodular flow.6 For ES measurement, according to different nodule color patterns, scoring was classified using Itoh’s elasticity score scale (Figure 1).7 We selected an area manually along the borderline of the nodule, and then we selected a similar-sized area beside the nodule in the thyroid tissue as reference. The ultrasound system software calculated the SI automatically. We took the average of three consecutive measurements (Figure 2). All measurements were made by three endocrinologists experienced in this issue.

Results The cytologic results of the nodules based on the classification proposed by the American Thyroid Association guideline 2009 were as follows: 22 (3.7%) nodules corresponded to category 1 (malignant), 23 (3.8%) nodules were included in category 2 (suspicious), 522 nodules (87%) were category 3 (benign), and 34 nodules (5.6%) were initially classified as category 6 (nondiagnostic material) and required surgery.

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Figure 1.  Elastography scores and images of lesions. (a) Ueno and Ito Elasticity Score 1 or 2 indicates higher elasticity, (b) whereas score 3 indicates lower elasticity. (c) Elasticity score 4 (Malign lesion). SI indicates relative stiffness of the lesion. Strain index (SI) = strain of thyroid tissue/strain of nodular lesion.

On definite pathologic results, 29 (4.8%) nodules corresponded to malignant lesions (25 papillary carcinomas, 4 follicular carcinomas) and 572 nodules (95.2%) were benign according to pathology or follow-up on benign cytology at 6 months.

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Figure 2.  ROC curve of strain index for distinguishing malignant from benign nodules. ROC = receiver operating characteristic. Table 1.  Distribution of Types of Nodules According to Elastosonography Scores and Final Histopathological Diagnosis. Score

Benign (%)

Malignant (%)

Total

1 2 3 4 5 Total

70 (100) 251 (99.6) 229 (97.4) 22 (51.2) 0 (0) 572

0 (0) 1 (0.04) 6 (2.64) 21 (48.8) 1 (100) 29

70 252 235 43 1 601

Table 1 shows the distribution of elastosonography scores of all the thyroid nodules and final histopathological diagnosis. The mean score or SI value for benign nodules and malignant ones was significantly different. Elastography scores 1 and 2 were assigned to 322 nodules, 321 of all were benign on final histology; score 3 was assigned to 235 nodules (6 of them were malignant); scores 4 and 5 were assigned to 44 nodules (50% were malignant) (Table 1). Also 527 nodules had a SI ≤3; among them there were 7 malignants (there was no malignancy with score 1 and only one malignancy with score 2); of 44 nodules with a SI >3, 22 were malignant. After elastographic evaluation, 76% of the malignant nodules (22/29) confirmed by cytology or histology scored 4 points or above (rigid). We did not find age, nodule echogenicity, size, volume, presence and nature of halo sign, macrocalcifications or intranodular vascularity to be a predictor of malignancy in our patient population. Male gender (p = 0.019), presence of microcalcifications (p = 0.006), presence of blurred margins (p < 0.0001), and higher elastography scores (p < 0.0001) were good predictors of malignancy in thyroid nodules. Seven nodules were found to be malignant among 49 nodules

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Figure 3.  ROC curve of elastography scores for distinguishing malignant from benign nodules. ROC = receiver operating characteristic. Table 2.  Sensitivity and Specificity of Elastosonography Scoring for distinguishing malignancy. Score

Benign

Malignant

SN (%)

SP (%)

PPV (%)

NPV (%)

1-3 4-5 Total

550 22 263

7 22 29

75.9

96.2

50.0

98.74  

SN = sensitivity; SP = specificity; PPV = positive predicted value; NPV = negative predicted value.

with microcalcifications, whereas 22 of the 577 nodules without microcalcifications were malignant. There were 13 malignant nodules among 37 nodules with blurred margins whereas only 16 of the 564 nodules that showed well-defined or regular margins were malignant. The area under the receiver operating characteristic (ROC) curve for diagnosing malignant thyroid nodules by elastosonography score was 0.91 (95% confidence interval 85.8-97.0) (Figure 3; Table 4). Elastography score value > 3 was predictive of malignancy (p < 0.0001) having a sensitivity, specificity, positive predictive value, and negative predictive value of 75.9%, 96.2%, 50%, and 98.74%, respectively (Table 2). The area under the ROC curve for diagnosing malignant thyroid nodules by SI value was 0.96 (95% confidence interval = [94.3, 98.5]) (Figure 2, Table 4). The best cutoff point for differentiating benign and malignant nodules was 3.75 with highest sensitivity and specificity (Figure 2). SI value ≥3.75 was predictive of malignancy (p < 0.0001) having a sensitivity, specificity, positive predictive value, and negative predictive value of 82.8%, 95.1%, 46.15%, and 99.1%, respectively (Table 3). There was no significant relationship between nodule size or calcification and ES score (p > 0.05 in both).

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Table 3.  Sensitivity and Specificity of Elastosonography Index for distinguishing malignancy. Index 0-3.74 3.75-81.4

Benign

Malignant

SN (%)

SP (%)

PPV (%)

NPV (%)

544 28

5 24

82.8

95.1

46.15

99.08

SN = sensitivity; SP = specificity; PPV = positive predicted value; NPV = negative predicted value.

Table 4.  AUC of Elastosonography Scoring and Index. AUC (%)

p Value

95% Confidence Interval for AUC

91.4 96.4

Elastography in the differential diagnosis of thyroid nodules.

Despite the publication of a recent meta-analysis of elastography in thyroid nodules, further work is necessary on this issue in different populations...
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