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Differentiation of Benign and Malignant Thyroid Nodules by Using Comb-push Ultrasound Shear Elastography

Posted Oct 31, 2018 Updated Apr 10, 2023
By Adriana Gregory BS , Mahdi Bayat PhD , Viksit Kumar PhD , Max Denis PhD , Bae Hyung Kim PhD , Jeremy Webb MS , Duane D. Meixner RVT RDMS , Mabel Ryder MD , John M. Knudsen MD , Shigao Chen PhD , Mostafa Fatemi PhD , Azra Alizad MD
15 min read

Rationale and Objectives

Low specificity of traditional ultrasound in differentiating benign from malignant thyroid nodules leads to a great number of unnecessary (ie, benign) fine-needle aspiration biopsies that causes a significant financial and physical burden to the patients. Ultrasound shear wave elastography is a technology capable of providing additional information related to the stiffness of tissues. In this study, quantitative stiffness values acquired by ultrasound shear wave elastography in two different imaging planes were evaluated for the prediction of malignancy in thyroid nodules. In addition, the association of elasticity measurements with sonographic characteristics of thyroid gland and nodules is presented.

Materials and Methods

A total number of 155 patients (106 female and 49 male) (average age 57.48 ± 14.44 years) with 173 thyroid nodules (average size 24.89 ± 15.41 mm, range 5–68 mm) scheduled for fine-needle aspiration biopsy were recruited from March 2015 to May 2017. Comb-push shear elastography imaging was performed at longitudinal and transverse anatomic planes. Mean (E mean ) and maximum (E max ) elasticity values were obtained.

Results

Measurements at longitudinal view were statistically significantly higher than measurements at transverse view. Nodules with calcifications were associated with increased elasticity, and nodules with a vascular component or within an enlarged thyroid gland (goiter) were associated with a lower elasticity value. Receiver operating characteristic curve analysis was performed for E mean and E max at each imaging plane and for the average of both planes. Sensitivity of 95.45%, specificity of 86.61%, 0.58 positive predictive value, and 0.99 negative predictive value were achieved by the average of the two planes for each E mean and E max parameters, with area under the curve of 92% and 93%, and a cutoff value of 49.09 kPa and 105.61 kPa, respectively.

Conclusions

The elastic properties of thyroid nodules showed promise to be a good discriminator between malignant and benign nodules ( P < .0001). However, probe orientation and internal features such as calcifications, vascular component, and goiter may influence the final elastography measurements. A larger number of malignant nodules need to be studied to further validate our results.

Introduction

Thyroid nodules commonly grow inside the thyroid gland and are mostly benign. Only 4%–6.5% of all thyroid nodules are cancerous . The majority of individuals with thyroid nodules have no symptoms. The nodules are usually found during routine physical examination with some incidental findings seen on diagnostic imaging (eg, ultrasound [US], computed tomography, magnetic resonance imaging, or positron emission tomography) performed for other indications . The current first line of evaluation of thyroid nodules encompasses thyroid hormone and thyroid-stimulating hormone laboratory tests, and ultrasonography of the thyroid gland. Ultrasonography is noninvasive and reveals many features relevant to the pathology of nodules. For example, an increased risk of malignancy has been associated with the presence of microcalcifications, irregular or spiculated margins with no halo, marked hypoechogenicity, mostly solid composition, and taller than wider shape. Although increased intranodular vascularity itself is not useful for differentiation of malignant from benign nodules , disordered central hypervascularity is more specific to US features of malignancy . On the other hand, presence of peripheral vascularity, round shape, isoechogenicity, spongiform appearance, smooth margins, and cystic composition are associated with benignancy .

Many studies have concluded that US features alone suffer from low accuracy. As such, fine-needle aspiration (FNA) biopsy is often used to rule out cancer in thyroid nodules . Although FNA is a safe and widely used procedure, complications such as discomfort or local pain and self-limited small hematomas may occur . Approximately 60%–80% of FNAs result in benign findings .

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Materials and Methods

Study Population

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US Shear Wave Elastography

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Statistical Analysis

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Results

Pathology

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Figure 1, Recurrent Hurthle cell carcinoma. Longitudinal view of the malignant nodule on the thyroid bed. The white arrows point at the border of the nodule, and the yellow circles denote the regions of interest (ROIs) for shear wave speed calculation.

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Repeatability Analysis

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SWE Results Compared to Sonographic Pattern and FNA Cytology

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TABLE 1

Comb-push Shear Elastography Results Compared to Sonographic Pattern Classification and Bethesda Diagnostic Category for Thyroid Nodules

Classification of ThyroidNodules Based onSonographic and FNAFindings Estimated Risk of Malignancy (%) Sonographic Pattern ( N ) Benign (0) Very Low Suspicion (42) Low Suspicion (66) Intermediate Suspicion (37) High Suspicion (28) <1 <3 5–10 10–20 >70–90 E mean ± SD (kPa) Bethesda DiagnosticCategory ( N ) I (15) 1–4 — 17 ± 7 (6) 17 ± 10 (2) 25 ± 6 (2) 24 ± 12 (5) II (112) 0–3 — 29 ± 17 (32) 30 ± 18 (53) 26 ± 18 (20) 40 ± 19 (7) III (1) 5–15 — — — 12 (1) — IV (20) 15–30 — 20 ± 14 (4) 26 ± 13 (8) 19 ± 3 (4) 15 ± 4 (4) V (3) 60–75 — — 35 ± 8 (2) 63 (1) — VI (22) 97–99 — — 59 (1) 62 ± 22 (9) 73 ± 17 (12) E max ± SD (kPa) Bethesda DiagnosticCategory ( N ) I (15) 1–4 — 44 ± 31 (6) 40 ± 30 (2) 47 ± 10 (2) 60 ± 31 (5) II (112) 0–3 — 58 ± 35 (32) 60 ± 36 (53) 57 ± 54 (20) 94 ± 48 (7) III (1) 5–15 — — — 23 (1) — IV (20) 15–30 — 35 ± 24 (4) 43 ± 18 (8) 46 ± 28 (4) 27 ± 4 (4) V (3) 60–75 — — 73 ± 29 (2) 145 (1) — VI (22) 97–99 — — 114 (1) 147 ± 49 (9) 164 ± 31 (12)

( N ) indicates statistical frequency; E mean , mean elasticity; E max , maximum elasticity.

I—Nondiagnostic or Unsatisfactory.

II—Benign.

III—Atypia of Undetermined Significance or Follicular Lesion of Undetermined Significance.

IV—Follicular Neoplasm or Suspicious for a Follicular Neoplasm.

V—Suspicious for Malignancy.

VI—Malignant.

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SWE and Probe Orientation

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Figure 2, Longitudinal and transverse view of a benign thyroid nodule. The white arrows point at the border of the nodule, and the yellow circles denote the regions of interest (ROIs) for shear wave speed calculation.

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TABLE 2

Comparison of Benign and Malignant Elasticity Measurements (Mean ± Standard Deviation) at Longitudinal, Transverse, and Combination of Views

L ( N = 130) T ( N = 126) L∩T ( N = 122) L∪T ( N = 134)E mean ± SD (kPa) Benign 33.09 ± 22.28 (108) 25.41 ± 16.37 (109) 28.92 ± 17.48 (105) 29.53 ± 17.89 (112) Malignant 72.64 ± 21.81 (22) 57.94 ± 17.22 (17) 64.26 ± 16.04 (17) 67.76 ± 19.21 (22)P value <.0001 \* <.0001 \* <.0001 \* <.0001 \* E max ± SD (kPa) Benign 66.87 ± 44.37 (108) 56.01 ± 41.38 (109) 60.23 ± 37.42 (105) 62.53 ± 40.57 (112) Malignant 161.29 ± 42.08 (22) 139.05 ± 52.68 (17) 147.12 ± 39.52 (17) 155.05 ± 39.75 (22)P value <.0001 \* <.0001 \* <.0001 \* <.0001 \*

N indicates statistical frequency; E mean , mean elasticity; E max , maximum elasticity; L, longitudinal; T, transverse; L∩T, group of nodules with transverse and longitudinal measurements; L∪T, group of nodules with transverse and/or longitudinal measurements.

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Figure 3, Data comparison graph of 112 benign nodules and 22 malignant nodules. (a) Mean elasticity. Benign: lowest value = 5.33 kPa, highest value = 101.49 kPa, and median = 25.17 kPa. Malignant: lowest value = 23.07 kPa, highest value = 111.81 kPa, and median = 63.56 kPa. ( b ) Maximum elasticity. Benign: lowest value = 7.59 kPa, highest value = 195.70 kPa, and median = 50.00 kPa. Malignant: lowest value = 44.90 kPa, highest value = 224.47 kPa, and median = 148.87 kPa. (Color version of figure is available online.)

Figure 4, Longitudinal and transverse view of a benign ( a ) and a malignant ( b ) thyroid nodule. The average elasticity of the two planes resulted in E mean =20.16 kPa and E mean =111.08 kPa for the benign nodule and malignant nodule, respectively.

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Receiver Operating Characteristic Analysis

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TABLE 3

Comparison of CUSE Diagnostic Performance Respect to Elasticity Parameters and Transducer Orientation for Bethesda Category II and VI

Cutoff (kPa) AUC (95% CI) Sensitivity (95% CI) Specificity (95% CI) E mean -L 48.40 0.91 (0.851–0.955) 95.45% (77.2–99.9) 83.33% (74.9–89.8) E mean -T 40.63 0.91 (0.840–0.950) 94.12% (71.3–99.9) 84.04% (76.2–90.6) E max -L 108.48 0.92 (0.864–0.963) 95.45% (77.2–99.9) 84.04% (79.2–92.7) E max -T 82.69 0.90 (0.829–0.943) 94.12% (71.3–99.9) 78.90% (70.0–86.1) E mean -L∩T 49.09 0.92(0.857–0.962) 94.12% (71.3–99.9) 86.67% (78.6–92.5) E max -L∩T 103.72 0.93(0.864–0.966) 94.12% (71.3–99.9) 87.62% (79.8–93.2) E mean -L∪T 49.09 0.92 (0.864–0.962) 95.45% (77.2–99.9) 86.61% (78.9–92.3) E max -L∪T 105.61 0.93 (0.872–0.966) 95.45% (72.2–99.9) 86.61% (78.9–92.3)

AUC, area under the curve; CI, confidence interval; E max , maximum elasticity; E mean , mean elasticity; L, longitudinal; L∩T,: group of nodules with transverse and longitudinal measurements; L∪T, group of nodules with transverse and/or longitudinal measurements.; T, transverse.

Figure 5, Receiver operating characteristic (ROC) curve analysis of 134 nodules at longitudinal and transverse planes (L∪T) for ( a ) mean elasticity values and ( b ) maximum elasticity values. The dotted blue lines represent the 95% confidence bounds. (Color version of figure is available online.)

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Ultrasound Features

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TABLE 4

Comparison of Mean Elasticity Measurements (in kPa) With Respect to Goiter, Graves’ Disease, and Heterogeneous Thyroid Gland

Thyroid Gland Pathologies Yes (kPa)N No (kPa)N__P Value NA (kPa)N Goiter Benign 23.22 ± 13.82 (30) 31.84 ± 18.71 (82) .0125 \* — (0) Malignant 94.34 (1) 65.64 ± 19.51 (19) .1572 74.66 ± 2.46 (2) All 23.41 ± 16.89 (41) 35.39 ± 21.79 (129) .0018 \* 51.99 ± 39.29 (3) Graves’ disease Benign 31.12 ± 11.76 (3) 29.49 ± 18.06 (109) .6459 — (0) Malignant — (0) 67.07 ± 20.05 (20) — 74.66 ± 2.46 (2) All 31.12 ± 11.76 (3) 33.02 ± 21.45 (167) .8798 51.99 ± 39.29 (3) Heterogeneous thyroid gland Benign 34.22 ± 24.37 (15) 29.00 ± 16.58 (92) .2982 25.30 ± 20.80 (5) Malignant — (0) 67.07 ± 20.05 (20) — 74.66 ± 2.46 (2) All 31.23 ± 23.29 (18) 32.90 ± 21.16 (147) .7355 25.30 ± 20.80

51.99 ± 39.29 (5)

(3)

N indicates statistical frequency; NA, not apply (results excluded from t test); All includes Bethesda categories I, II, III, IV, V, and VI.

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Figure 6, Student t test comparison of elasticity values from nodules containing macrocalcifications (benign n = 18; malignant n = 5; all n = 31), microcalcifications (benign n = 9; malignant n = 4; all n = 15), and nodules without calcifications (benign n = 85; malignant n = 13; all n = 127). All includes Bethesda I, II, III, IV, V, and VI. * P < .05. (Color version of figure is available online.)

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Figure 7, Longitudinal view of a benign thyroid nodule containing a macrocalcification ( green arrow ). The white arrows point at the border of the nodule, and the yellow circle denotes the region of interest (ROI) for shear wave speed calculation. The elasticity on the nodule is 110.53 kPa.

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TABLE 5

Comparison of Mean Elasticity Measurements (in kPa) With Respect to Nodule Size, and Presence of Cystic and Vascular Components

Nodule Features <25 mm_N_ ≥25 mm_N__P_ Value Nodule size Benign 33.91 ± 19.13 (62) 24.11 ± 14.66 (50) .0035 \* Malignant 67.26 ± 20.02 (17) 69.47 ± 18.10 (5) .8278 All 37.49 ± 22.57 (103) 25.98 ± 18.40 (70) .0005 \*

Yes (kPa)N No (kPa)N__P Value Cystic component Benign 28.82 ± 18.07 (61) 30.39 ± 17.81 (51) .5338 Malignant 62.20 (1) 68.03 ± 19.64 (21) .6935 All 27.23 ± 17.99 (72) 36.83 ± 23.24 (101) .0039 \* Vascularity Benign 23.86 ± 14.55 (27) 31.33 ± 18.54 (85) .0403 \* Malignant 54.90 ± 18.89 (5) 71.55 ± 18.11 (17) .2246 All 27.12 ± 17.12 (44) 34.79 ± 22.77 (129) .0489 \*

N indicates statistical frequency; All includes Bethesda categories I, II, III, IV, V, and VI.

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Discussion

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Conclusions

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Acknowledgments

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Academic Radiology, Volume 25, Issue 11
Journals General Radiology
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