Malignancy Risk Stratification of Thyroid Nodules According to Echotexture and Degree of Hypoechogenicity: A Multicenter Validation Study

Abstract

Purpose Various risk stratification systems show some discrepancies in the ultrasound (US) lexicon of nodule echotexture and hypoechogenicity. This study aimed to determine the malignancy risk of thyroid nodules according to their echotexture and degree of hypoechogenicity in a multicenter dataset.

Methods From June to September 2015, 5,601 thyroid nodules (≥ 1.0 cm) in 4,989 consecutive patients who underwent thyroid US and with a final diagnoses from 26 institutions were evaluated. Thyroid nodules were stratified according to the US echotexture (homogeneous vs. heterogeneous) and degree of hypoechogenicity (mild, moderate, or marked). We then calculated malignancy risk and compared four subgroups stratified with nodule composition and presence of suspicious features.

Results Heterogeneous hypoechoic nodules showed a significantly higher malignancy risk than heterogeneous isoechoic nodules (P ≤ 0.017) except in partially cystic nodules. There was no significant difference in malignancy risk between homogeneous vs. heterogeneous hypoechoic nodules (P ≥ 0.086) and between homogeneous vs. heterogeneous iso- or hyperechoic nodules (P ≥ 0.05) except in partially cystic nodules without suspicious features. The malignancy risks of both homogeneous and heterogeneous iso- or hyperechoic nodules were low to intermediate, depending on the presence of suspicious features. Regarding the degree of hypoechogenicity, there was no significant difference in malignancy risk between markedly and moderately hypoechoic nodules in all subgroups (P ≥ 0.48). Marked or moderately hypoechoic nodules showed a significantly higher risk than mild hypoechoic (P ≤ 0.016) and iso- or hyperechoic (P < .001) nodules.

Conclusions The predominant echogenicity effectively stratifies the malignancy risk of nodules with heterogeneous echotexture. For malignancy risk stratification, the degree of nodules’ hypoechogenicity could be grouped as mild vs. moderate to marked hypoechogenicity.  

Introduction

The echogenicity of a thyroid nodule on ultrasonography (US) is an important descriptor for distinguishing malignancy from benign nodules [1–4]. Previous studies have consistently reported that the malignancy risk of hypoechoic nodules was higher than that of iso- or hyperechoic nodules [1, 3–5]. Marked hypoechogenicity is related to increased malignancy risk of thyroid nodules [1, 5–8] and has been adopted in several risk stratification systems (RSS) [9–12].

Despite of its importance, the US definition of nodule echogenicity shows discrepancies across risk stratification systems (RSS) [13]. For nodules with heterogeneous echogenicity, guidelines adopt different strategies; the Korean Thyroid Imaging Reporting and Data System (K-TIRADS) and American College of Radiology (ACR) TIRADS classified them based on the predominant echogenicity [11, 14], but the European Thyroid Imaging Reporting and Data System (EU-TIRADS) classified heterogeneous nodules as mildly hypoechoic nodules when they had any hypoechoic portion [10]. While the American Association of Clinical Endocrinologists/American College of Endocrinology/Associazione Medici Endocrinologi [9], ACR [11], EU-TIRADS [10], and the Chinese Thyroid Imaging Reporting and Data System (C-TIRADS) [12] distinguished between marked and mild hypoechogenicity, the American Thyroid Association [15] and K-TIRADS [14] did not discriminate between marked versus mild hypoechogenicity regarding nodule risk stratification. In these RSSs, nodules with similar echogenicity to the anterior neck muscles (i.e., moderate hypoechogenicity) were grouped with nodules with mild hypoechogenicity [9–12, 14, 15].

A recent study demonstrated that nodule hypoechogenicity could be stratified as mild versus moderate to marked, and nodules with heterogeneous echogenicity are stratified by the predominant echogenicity of the solid portion [7]. According to the results of this study, the 2021 K-TIRADS revised the definition of marked hypoechogenicity as hypoechoic or similar echogenicity relative to the anterior neck muscles [16]. However, insufficient evidence supports this take on hypoechoic nodules’ stratification because the previous study was a single-center study [7]. We designed a multicenter study to validate if this revised definition of nodule hypoechogenicity could effectively stratify the malignancy risk of thyroid nodules. The purpose of this study was to validate thyroid nodules’ malignancy risk according to their echotexture and degree of hypoechogenicity in a multicenter cohort.

Materials And Methods

The institutional review boards of the 26 participating centers approved this study. The informed consent requirement was waived for this retrospective review.

Results

Discussion

Our study demonstrated no significant difference in malignancy risks between homogeneous vs. heterogeneous hypoechoic nodules in all subgroups and in homogenous vs. heterogeneous iso- or hyperechoic nodules in all subgroups except partially cystic nodules without suspicious features. Meanwhile, heterogeneous hypoechoic nodules showed significantly higher malignancy risk than heterogeneous isoechoic nodules in all subgroups except partially cystic nodules. Our study validated the concept of classifying nodules by their predominant echogenicity as a reasonable form of risk stratification. Regarding the degree of hypoechogenicity, nodules with moderate hypoechogenicity showed similar malignancy risks compared to markedly hypoechoic nodules. In contrast, moderately hypoechoic nodules showed significantly higher malignancy risks than mild hypoechoic nodules in all subgroups except partially cystic nodules without suspicious features. Based on our results, moderately hypoechoic nodules should be grouped with marked hypoechoic nodules for risk stratification.

For nodules with heterogeneous echogenicity, the EU-TIRADS suggested that nodules with any hypoechoic component should be regarded as hypoechoic nodules and classified as intermediate risk [10]. However, in our study, the malignancy risks of heterogeneous isoechoic nodules were not significantly different from their homogeneous counterparts except in the partially cystic nodules without suspicious features subgroup; this result aligned with the findings of our previous study [7]. Although the malignancy risks of heterogeneous isoechoic nodules were higher than homogeneous isoechoic nodules in overall nodules, the malignancy risks of heterogeneous isoechoic nodules were ranged within the low to intermediate risk categories, depending on concurrent suspicious US features. Therefore, our study’s results support the strategy provided by K-TIRADS and ACR TIRADS when assessing nodules with heterogeneous echogenicity.

In the EU-TIRADS [10] and ACR-TIRADS [11], moderate hypoechogenicity was classified as similar risk with mild hypochogenicity; however in this study, moderate hypochogenicity showed a similar malignancy risk to marked hypochogenicity. The results of this study suggest that the previous definition of marked hypoechogenicity should be revised as hypoechoic or similar echogenicity relative to the anterior neck muscles. The result of this study confirmed the validity of the revised definition of marked hypoechogenicity by 2021 K-TIRADS.

The results of our study are in line with those of our previous study in that the malignancy risks of moderately hypoechoic nodules are similar to that of markedly hypoechoic nodules [7]. However, the results in overall nodules were somewhat discrepant from the previous study [7], demonstrating that the malignancy risks of marked hypoechoic nodules were higher than that of moderately hypoechoic nodules [6]. In this cohort, concurrent suspicious US features occurred more frequently in marked hypoechoic nodules than moderately hypoechoic nodules (marked hypoechoic, 72.4% vs. moderate hypoechoic, 52.5%, P <.001). The higher prevalence of suspicious features in marked hypoechoic nodules might have caused confounding effects in the malignancy risks between these two groups.

In the partially cystic nodules without suspicious features subgroup, the malignancy risks of most nodules ranged within the low risk category, regardless of their predominant echogenicity. This contrasts partially cystic nodules with suspicious features’ risks, which fell within the intermediate risk category in most nodules. In contrast to solid nodules, partially cystic nodules without suspicious features showed no significant difference in malignancy risk between marked/moderate versus mild hypoechoic nodules, and the difference between various degrees of hypoechogenicity was diminished. Additionally, in partially cystic nodules, most partially cystic hypoechoic nodules showed mild hypoechogenicity (68.7-85.0%) and the incidence of marked hypoechogenicity was very rare. Based on our results, we assume that in partially cystic nodules, malignancy risk is mainly determined by the presence of suspicious features and the degree of hypoechogenicity had little impact.

Our study has several limitations. First, the reference standards for benign and malignant diagnoses were based on FNA results as well as surgical histology findings, which may inevitably cause false-negative or false-positive results, although the effect may have been small. Second, we retrospectively assessed the nodules’ US features. However, we believe our large sample size across a multicenter setting mitigated this shortcoming. Third, this study did not consider the interobserver agreement for US features described by different radiologists, possibly resulting in discrepant interpretations. However, we performed training sessions prior to formal analysis to mitigate for interobserver variability. Although a previous study demonstrated that this proposed classification of echogenicity showed improved reproducibility than the previous lexicon [7], future in-depth studies are needed to validate the reproducibility of this US lexicon in multiple readers.

In conclusion, the malignancy risk of nodules with heterogeneous echotexture can be stratified based on predominant echogenicity. Additionally, nodule hypoechogenicity can be classified as mild vs. moderate to marked hypoechogenicity for malignancy risk stratification.

Declarations

Funding This research was supported by research fund from the Korean Society of Radiology through Radiology Imaging Network of Korea for Clinical Research (RINK-CR).

Conflict of Interest The authors declare no competing interest.

Author contributions Conceptualization: J.Y. Lee, C.Y. Lee, D.G. Na; Data Curation: all authors; Methodology: J.Y. Lee, C.Y. Lee, D. G. Na; Project administration: J.Y.Lee, C.Y. Lee, J-h. Kim, D.G. Na; Formal analysis: all authors; Investigation: all authors; Resources: J.Y. Lee, C.Y. Lee, J-h. Kim, D.G. Na; Supervision: all authors; Writing—original draft preparation: J.Y. Lee.; Writing—review and editing: D. G. Na; Funding acquisition: D. G. Na, J-h. Kim

Ethics approval This retrospective study was approved by the institutional review boards of 26 participating centers.

Consent to participate/Consent to publish The requirement for patient informed consent was waived

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