Special thanks to Dr. Gustavo Alonzo Correa, Prof. Ricardo Daniel Alp¨ªzar Cruz, Dra. M¨®nica Chapa Ibarg¨¹engoitia, Dra. Ver¨®nica Espinosa Cruz - Instituto Nacional de Ciencias M¨¦dicas y Nutrici¨®n "Salvador Zubir¨¢n" M¨¦xico, for sharing these cases.

Case?Introduction

Thyroid nodules are a common finding in the population, and their detection rate is increasing with the widespread use of different imaging modalities. ^[1] In clinical practice, ultrasound often represents the first diagnostic step in its evaluation. ^[2] A prevalence of ultrasound-detected thyroid nodules of up to 50% has been reported in the general population, with a malignancy rate of 5-15%. ^[3] The primary objective of ultrasonographic evaluation is to exclude the possibility of thyroid cancer by differentiating benign from malignant nodules. However, no feature by itself is sufficiently sensitive or specific to exclude or confirm malignancy. ^{[3, 4]} Fine needle aspiration biopsy (FNA) is considered the gold standard for confirming the nature of thyroid nodules. ^[5] However, not all nodules require FNA and/or surgery. ^[4] Therefore, new ultrasonographic techniques, such as?Contrast-Enhanced Ultrasound (CEUS) and elastography, have been developed in recent years to increase the specificity and diagnostic accuracy for the detection of thyroid malignancies. ^[5]

Case Report

A previously healthy 36-year-old female who reported an increase in volume in the left cervical region secondary to a small palpable mass, subsequently presented asthenia, adinamia and lack of appetite, in addition to loss of 8 kg in approximately 6 months.

?

During the diagnostic process, thyroid ultrasound was performed using the Mindray Resona I9 system. A solid, hypoechoic nodule was observed on the left side which was wider than high and had apparent extrathyroid extension and punctate echogenic foci. Additionally, internal vascularity was observed upon application of color Doppler. This nodule was evaluated as ACR TI-RADS 5 based on the findings (Fig. 1). Similarly, the Smart Thyroid AI of Resona i9 ultrasound system program was used to measure and analysy malignant signs and yielded comparable findings, except for the extrathyroidal extension which was assessed as having lobed/irregular borders. However, it also garnered an ACR TI-RADS 5 score (Fig. 2). The elastography examination indicated a heterogeneous appearance with an Emax stiffness of 40.53 kPa . Finally, the CEUS revealed that the lesion was heterogeneously iso-enhanced in comparison with thyroid parenchyma that showed early washout at 45 seconds (Fig. 3). The central portion of the nodule achieved peak intensity of 26.7 dB at 26.8 seconds, correspondingly; while the peripheral portion achieved peak intensity of 29.1 dB at 22.3 seconds (Fig. 4 ). The patient underwent Fine Needle Aspiration (FNA), which yielded a histopathological report of category VI of the Bethesda system, indicating papillary thyroid carcinoma. Additionally, confirmation of invasion in the prethyroid muscles was obtained during the surgical procedure.

Discussion

In recent years there has been an increase in the prevalence of thyroid nodules. High-resolution ultrasound is the most important imaging modality for the evaluation of a thyroid nodule. ^[3] However, initial ultrasound alone is not always effective in achieving characterization. That is why, especially in recent years, it has become increasingly necessary to develop other imaging modalities to limit the use of FNA or even diagnostic thyroidectomy as much as possible. ^[2]?Contrast-Enhanced Ultrasound (CEUS) is considered an effective technique for assessing the microvasculature, estimating the sequence and intensity of vascular perfusion, as well as hemodynamics in the thyroid nodule, providing real-time characterization of the nodule, and is considered a valuable new approach in the differentiation of benign versus malignant nodules. ^{[1, 3]} Several studies have shown that there are certain characteristics of CEUS that suggest malignancy, including late filling, heterogeneous enhancement, poorly defined enhancement edges, and rapid wash rate. ^[3] However, no statistically significant differences in absolute values of time to peak and peak intensity have been observed between malignant and benign nodules. ^[5] In our case, the nodule presented a heterogeneous enhancement with early wash-out, being highly suggestive characteristics of malignancy. Most malignant nodules contain areas of fibrosis, calcification, or focal necrosis, which may explain the tendency to heterogeneous enhancement. Some published studies have shown that early washout could be due to shrinkage of microvasculature in carcinomas as a result of necrosis. ^[1] Regarding elastography, there is no established parameter on the behavior of malignant thyroid nodules. In some studies, there has been a trend towards increased stiffness, although the findings have not yielded a specific quantitative value. ^[1] In our case, we observed similar behavior, with a heterogeneous appearance and areas of increased stiffness.

Conclusion

Conventional ultrasound continues to be the cornerstone in thyroid nodule evaluation, however, the advent of artificial intelligence as well as non-invasive imaging techniques such as CEUS and elastography have shown reliable performance in detecting or excluding thyroid cancer. In our case, they showed good performance in detecting malignancy characteristics subsequently confirmed by histopathology. However, more studies are required to standardize the technique, define indications, and quantitative and qualitative parameters to confirm its usefulness in daily practice.

References:

[1] Jia Zhan, Hong Ding. Application of contrast-enhanced ultrasound for evaluation of thyroid nodules. Ultrasonography 2018;37:288-297. doi:https://doi.org/10.14366/usg.18019.

[2] Salvatore Sorrenti, Vincenzo Dolcetti, Daniele Fresilli, Giovanni Del Gaudio, Patrizia Pacini, Pintong Huang, Chiara Camponovo, Andrea Leoncini, Vito D¡¯Andrea, Daniele Pironi, Fabrizio Frattaroli, Pierpaolo Trimboli, Maija Radzina and Vito Cantisani. The Role of CEUS in the Evaluation of Thyroid Cancer: From Diagnosis to Local Staging. Clin. Med. 2021, 10, 4559. doi: https://doi.org/10.3390/jcm10194559.

[3] Radzina M, Ratniece M, Putrins DS, Saule L, Cantisani V. Performance of Contrast-Enhanced Ultrasound in Thyroid Nodules: Review of Current State and Future Perspectives. Cancers (Basel). 2021 Oct 30;13(21):5469. doi: 10.3390/cancers13215469.

[4] Jingliang Ruan, Xiaolin Xu, Yan Cai, Hongyan Zeng, Man Luo, Wenyue Zhang, Rongbin Liu, Peiliang Lin, Yangming Xu, Qiong Ye, Bing Ou, Baoming Luo. A Practical CEUS Thyroid Reporting System for Thyroid Nodules. Radiology 2022; 305:149¨C159. doi: https://doi.org/10.1148/radiol.212319.

[5] Petrasova H, Slaisova R, Rohan T, Stary K, Kyclova J, Pavlik T, Kovalcikova P, Kazda T, Valek V. Contrast-Enhanced Ultrasonography for Differential Diagnosis of Benign and Malignant Thyroid Lesions: Single-Institutional Prospective Study of Qualitative and Quantitative CEUS Characteristics. Contrast Media Mol Imaging. 2022 Apr 23;2022:8229445. doi: 10.1155/2022/8229445.