Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Jun 29:11:592927.
doi: 10.3389/fonc.2021.592927. eCollection 2021.

Establishment of an Ultrasound Malignancy Risk Stratification Model for Thyroid Nodules Larger Than 4 cm

Xuehua Xi  1 , Ying Wang  2 , Luying Gao  2 , Yuxin Jiang  2 , Zhiyong Liang  3 , Xinyu Ren  3 , Qing Gao  2 , Xingjian Lai  2 , Xiao Yang  2 , Shenling Zhu  2 , Ruina Zhao  2 , Xiaoyan Zhang  2 , Bo Zhang  1
Affiliations

Establishment of an Ultrasound Malignancy Risk Stratification Model for Thyroid Nodules Larger Than 4 cm

Xuehua Xi et al. Front Oncol. .

Abstract

Background: The incidence and mortality of thyroid cancer, including thyroid nodules > 4 cm, have been increasing in recent years. The current evaluation methods are based mostly on studies of patients with thyroid nodules < 4 cm. The aim of the current study was to establish a risk stratification model to predict risk of malignancy in thyroid nodules > 4 cm.

Methods: A total of 279 thyroid nodules > 4 cm in 267 patients were retrospectively analyzed. Nodules were randomly assigned to a training dataset (n = 140) and a validation dataset (n = 139). Multivariable logistic regression analysis was applied to establish a nomogram. The risk stratification of thyroid nodules > 4 cm was established according to the nomogram. The diagnostic performance of the model was evaluated and compared with the American College Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS), Kwak TI-RADS and 2015 ATA guidelines using the area under the receiver operating characteristic curve (AUC).

Results: The analysis included 279 nodules (267 patients, 50.6 ± 13.2 years): 229 were benign and 50 were malignant. Multivariate regression revealed microcalcification, solid mass, ill-defined border and hypoechogenicity as independent risk factors. Based on the four factors, a risk stratified clinical model was developed for evaluating nodules > 4 cm, which includes three categories: high risk (risk value = 0.8-0.9, with more than 3 factors), intermediate risk (risk value = 0.3-0.7, with 2 factors or microcalcification) and low risk (risk value = 0.1-0.2, with 1 factor except microcalcification). In the validation dataset, the malignancy rate of thyroid nodules > 4 cm that were classified as high risk was 88.9%; as intermediate risk, 35.7%; and as low risk, 6.9%. The new model showed greater AUC than ACR TI-RADS (0.897 vs. 0.855, p = 0.040), but similar sensitivity (61.9% vs. 57.1%, p = 0.480) and specificity (91.5% vs. 93.2%, p = 0.680).

Conclusion: Microcalcification, solid mass, ill-defined border and hypoechogenicity on ultrasound may be signs of malignancy in thyroid nodules > 4 cm. A risk stratification model for nodules > 4 cm may show better diagnostic performance than ACR TI-RADS, which may lead to better preoperative decision-making.

Keywords: risk stratification; size; thyroid cancer; thyroid nodules; ultrasound.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
The study protocol.
Figure 2
Figure 2
Risk stratification nomogram to predict the probability of malignancy of thyroid nodules > 4 cm. For example, a solid hypoechogenic thyroid nodule > 4 cm that shows the ultrasound feature of microcalcification, but not ill-defined border receives 221 points and a malignancy risk of 0.88 (high risk).
Figure 3
Figure 3
Receiver operating characteristic curve in the training dataset (A) and validation dataset (C). Calibration curve showing nomogram-predicted malignancy compared with the actual malignancy in the training dataset (B) and validation dataset (D).
See this image and copyright information in PMC

References

    1. Guth S, Theune U, Aberle J, Galach A, Bamberger CM. Very High Prevalence of Thyroid Nodules Detected by High Frequency (13 MHz) Ultrasound Examination. Eur J Clin Invest (2019) 39(8):699–706. 10.1111/j.1365-2362.2009.02162.x - DOI - PubMed
    1. Cooper DS, Doherty GM, Haugen BR, Kloos RT, Lee SL, Mandel SJ, et al. . Revised American Thyroid Association Management Guidelines for Patients With Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid (2009) 19(11):1167–214. 10.1089/thy.2009.0110 - DOI - PubMed
    1. Lim H, Devesa SS, Sosa JA, Check D, Kitahara CM. Trends in Thyroid Cancer Incidence and Mortality in the United States, 1974-2013. JAMA (2017) 317(13):1338–48. 10.1001/jama.2017.2719 - DOI - PMC - PubMed
    1. Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, et al. . 2015 American Thyroid Association Management Guidelines for Adult Patients With Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid (2016) 26(1):1–133. 10.1089/thy.2015.0020 - DOI - PMC - PubMed
    1. Perrier ND, Brierley JD, Tuttle RM. Differentiated and Anaplastic Thyroid Carcinoma: Major Changes in the American Joint Committee on Cancer Eighth Edition Cancer Staging Manual. CA Cancer J Clin (2018) 68(1):55–63. 10.3322/caac.21439 - DOI - PMC - PubMed