The Reliability of Ultrasound Diagnosis in Differentiating Malignant from Benign Thyroid Nodules Using TI-RADS Selection Followed by FNA

Context: Diagnostic imaging has increased the rate of thyroid nodules detection and improved utilization of fine-needle aspiration (FNA). Objective: This study aims to demonstrate the effects of the most reliable non-invasive technique on thyroid nodules. Methods: Between 2016 and 2020, 190 patients with 214 nodules visiting King Khalid University Hospital were randomly selected and retrospectively reviewed. Following the ACR TI-RADS recommendations for FNA and correlating cytology reports. Two expert radiologists with ultrasonographic imaging experience re-evaluated and reviewed the images. 88 nodules (41%) in 79 patients were excluded because the nodule size was smaller than the FNA recommended size. Results: Following the ACR TI-RADS for FNA recommended selection, 27 nodules (21.4%) out of the recommended 126 nodules were consistent with malignancy in cytology, with overall mean sensitivities, specificities, accuracies, precisions, and negative predictive values (NPV) of 96.4%, 40.7%, 48.7%, 28.4%, and 98.6% respectively. The nodules were subdivided into the TI-RADS 3, 4, and 5. Conclusion: In conclusion, ACR TI-RADS is feasible,


Introduction
Thyroid nodular disease is a common healthcare problem, prevalent among 20% -50% of the population [1]. However, thyroid malignancies are uncommon, only account for approximately 2% -7% of all thyroid nodules [1] [2] [3]. Thyroid cancer incidence has increased in the last few decades, without a significant change in the disease mortality. Diagnostic imaging has increased the rate of thyroid nodules detection and improved utilization of fine-needle aspiration (FNA) [4]. Ultrasound (US) guided FNA using the Bethesda [5] pathological evaluation system is the gold standard for thyroid nodules evaluation because of its cost-effectiveness and accurate detection rate [6]- [11]. Early assessment of thyroid nodules using the US has become the most valuable noninvasive diagnostic tool [12]. American College of Radiology (ACR) provides an easy-to-apply method for radiologists and physicians for proper management and increasing consistency across ultrasound practices. Thyroid Imaging Reporting and Data System (TI-RADS) [13], using the classification system, offers reliable, feasible, practical, and non-invasiveness techniques to eliminate 26% -53% of FNA cases [14] [15]. The aim of this study is to determine if using Ultrasound using TI-RADS selection can differentiate malignant from benign thyroid nodules confirmed by FNA. This will eliminate unnecessary invasive procedures for diagnostic purpose only in the management of thyroid nodules, thus avoiding unnecessary patients' morbidities, reflecting positively over the net cost.

Patients
Using the ACR TI-RADS, we randomly selected and retrospectively evaluated nodules in 190 patients visiting King Khalid University Hospital (KKUH) from 2016 to 2020, for thyroid US and FNA. A total of 126 nodules were evaluated in 111 patients; the outcome showed the absence of primary malignancy. Approximately 88 nodules in 79 patients were evaluated. Exclusion criteria were: 1) nodules without FNA recommendation according to the ACR TI-RADS, either because of size and/or grade (69 nodules). 2) Nodules with indefinite cytology, including any BETHESDA that scores more than 2 or 6 (19 nodules). No other exclusion criteria were applied. Table 1 provides a summary of all the evaluated nodules.

Imaging and TI-RADS Scoring
Two expert radiologists with ultrasonographic imaging experience re-evaluated and reviewed the images using the ACR TI-RADS protocols. To eliminate evalu- were summed to determine the FNA recommendation and malignancy risk levels of each nodule, from TI-RADS 1 (lowest risk) to TI-RADS 5 (highest risk) [13]. Figure 1 provides the ACR-TI-RADS assessment categories. To confirm all the selected nodules, we validated the corresponding US-guided FNA procedure images and reviewed its correlated pathological report.

FNA Technique and Cytology
Well-trained and experienced interventional radiology consultants conducted all FNA procedures using local anesthesia. The US scan and guided biopsy images were reviewed to confirm the biopsied nodules. All the cytological samples were evaluated using the BETHESDA scoring system; with 1 unsatisfactory, 2 benign, 3 typical cells, 4 follicular neoplasms, 5 suspicious for malignancy, and 6 malignancy [5].

Results
Microsoft Excel was used to collect data. Afterward, we used SPSS version 22.0 for the analysis. The sensitivity, specificity, accuracy, precision, and negative predictive value (with a confidence interval of 95%) were conducted to determine the ACR TI-RADS reliability and differentiate benign from malignant thyroid nodules. A p-value < 0.05 was considered a significant level. respectively. The nodules were subdivided into the TI-RADS 3, 4, and 5. Table 4 summarizes the results of the ACR TI-RADS for malignancy detection, and

Discussion
While excluding thyroid malignancy using FNA is a gold standard for suspicious thyroid nodules evaluation, it is proven to be user-dependent based on the 20% years of experience in diagnostic ultrasound to complete a blind review of the corresponding cytology reports. We reevaluated all the cases without further se- lection. Yet, cases in the lower ACR TI-RADS subcategories (TR-1 and TR-2) were minimal and could not be properly evaluated. However, the ACR and many recent studies concluded that the malignancy risk in TR-1 and TR-2 subcategories never exceeded 2% in the ACR partial analysis [13] and 0% of studies conducted by Warinthorn Phuttharak et al. [15] and Hoang et al. [17].
Our TI-RADS evaluation results were in agreement with the ACR TI-RADS paper that focused on malignancy risk stratification: Less than 5% in TR-3 (1.2%), from 5% to 20% in TR-4 (14.1%), and more than 20% in TR-5 (60%) [13]. Figure 3 and Figure  Although this nodule fails to receive an FNA recommendation used in the ACR TI-RADS due to its small size, this nodule is categorized as a TI-RADS 4 nodule, and it measures 1 × 0.8 cm diameter. Hence, follow-up is not dismissed. Nonetheless, 62 patients went through a stressful procedure without proper imaging or medical justification, wasting medical and financial resources. In addition, the procedure is without standardized, clear diagnostic methods, and guidelines subjecting to many incorrect user-dependent judgmental discrepancies and resource misuse.

Conclusion
In conclusion, ACR TI-RADS is feasible, reliable, and well structured, easily applicable in thyroid nodules reporting. ACR TI-RADS can eliminate many unnecessary FNAs, providing a decline in costs and complications. We recommend the ACR TI-RADS in our radiology department to eliminate reporting discre-Open Journal of Radiology pancies and cut costs, thereby standardizing the reports, improving intra-user agreements, and improving overall patients' health care. Our future research topic is to find ancillary non-invasive modality to enhance the accuracy in differentiating malignant from benign thyroid nodules.

Disclosure
This work was not supported or funded by any drug or machine company.