Diagnostic performance of the ACR TI-RADS classification in identifying and excluding thyroid malignancy: A multi-correlative retrospective study in a South African tertiary hospital

Diagnostic performance of the ACR TI-RADS classification in identifying and excluding thyroid malignancy: A multi-correlative retrospective study in a South African tertiary hospital | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Diagnostic performance of the ACR TI-RADS classification in identifying and excluding thyroid malignancy: A multi-correlative retrospective study in a South African tertiary hospital Neelam Bagratee, Tanusha Sewchuran This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7465890/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 03 Dec, 2025 Read the published version in Egyptian Journal of Radiology and Nuclear Medicine → Version 1 posted You are reading this latest preprint version Abstract BACKGROUND Nodular thyroid disease is becoming increasingly prevalent worldwide, with the primary aim of evaluation being to exclude malignancy. The ACR TI-RADS classification was designed to stratify the risk of malignancy in thyroid nodules based on sonographic features, thereby guiding biopsy decisions with the aim of reducing the number of unnecessary invasive procedures performed. Fine-needle aspiration cytology remains the preferred diagnostic tool for evaluating thyroid nodules due to its safety profile and cost-effectiveness. However, it can yield non-diagnostic or indeterminate results, resulting in repeat biopsies, which in resource-limited settings precipates poor patient follow-up or missed malignancy. Core needle biopsy, with histological evaluation, has become increasingly recognized as the gold standard for definitive diagnosis, reducing the need for repeat sampling. The aim of this study was to retrospectively assess the diagnostic accuracy of the reported ACR TI-RADS classification in identifying and excluding malignant thyroid lesions using histology as the gold standard of reference, with further secondary correlation with cytology, biochemistry, and nuclear medicine studies where available, at our local setting in Grey’s Hospital, Pietermaritzburg. RESULTS The study group consisted of 68 patients with a mean age of 52.6 years (range, 27–82 years), female predominance and a 16.2% thyroid malignancy rate. For ease of analysis, ACR TI-RADS categories 1–3 were grouped as benign, and categories 4–5 as malignant. Comparison of ACR TI-RADS with histology showed a sensitivity of 63.6%, specificity of 38.6%, positive predictive value of 16.7%, and negative predictive value of 84.6%. Receiver operating characteristic curve analysis showed an area under the curve of 0.51. Among the sonographic features evaluated, the presence of intralesional vascularity was significantly associated with malignancy (p < 0.05), advocating its inclusion into a modified ACR-TIRADS score. CONCLUSION ACR TI-RADS is a valuable tool for thyroid nodule risk stratification, but it demonstrates limitations in sensitivity and specificity within our setting. Discrepancies between the ACR TI-RADS scoring and histology highlights potential over- or under-estimation of malignancy risk, influenced by inter-operator variability and inconsistent reporting. Standardized reporting protocols, ongoing training, and the incorporation of additional sonographic features, such as vascularity assessment, may improve diagnostic performance, thereby reducing patient morbidity and mortality. Thyroid nodule Thyroid malignancy TI-RADS Ultrasound Histology Core needle biopsy Intralesional vascularity Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 Figure 13 BACKGROUND The evaluation of thyroid nodules is imperative to exclude thyroid malignancy. A system, the ACR TI-RADS ultrasound classification, has been developed to classify thyroid nodules according to malignancy risk, based on several imaging characteristics. This has assisted in risk stratification of thyroid nodules, thereby significantly reducing the number of invasive confirmatory tests performed. Many studies have been conducted globally in both developing and developed countries, correlating the use of the ACR TI-RADS ultrasound classification to assist in differentiating benign from malignant thyroid nodules, thereby guiding further management. A thyroid nodule is defined by the American Thyroid Association as “discrete lesions within the thyroid gland, radiologically distinct from surrounding thyroid parenchyma” ( 1 ). Nodular thyroid disease is common globally, with the incidence rising dramatically over the past few decades due to higher detection rates from increased use of thyroid ultrasonography ( 2 – 5 ). The global prevalence of thyroid nodules ranges from 4–7% by palpation, 19–68% by ultrasound, and 8–65% at autopsy by pathologic examination ( 3 , 6 , 7 ). The majority of thyroid nodules are asymptomatic and discovered incidentally during imaging investigations, such as ultrasound, computed tomography, magnetic resonance imaging, and 18F-fluorodeoxyglucose positron emission tomography for other conditions, and are termed thyroid incidentalomas ( 2 , 4 , 8 ). A study performed by Moifo et al. ( 8 ) demonstrated a prevalence of thyroid incidentalomas of 28.3% at a hospital in Yaounde, Cameroon, in sub-Saharan Africa. There is a greater prevalence of thyroid nodules in areas with iodine deficiency, among females, and in individuals exposed to neck irradiation ( 2 , 9 ). Thyroid nodules are classified as either benign or malignant ( 7 ). The principal goal in the clinical evaluation of thyroid nodules is to identify potentially malignant nodules ( 2 , 10 – 12 ). Benign thyroid nodule disorders include adenoma, multinodular goitres, localized thyroiditis, including autoimmune disease, and cysts ( 3 ). Globally, thyroid cancer accounts for 1–2% of all malignancies. In a surgical series in Africa, thyroid cancer was the most common endocrine malignancy with a prevalence ranging from 7.3–15% ( 13 ). The diagnostic assessment of a thyroid nodule includes a detailed history, physical examination, laboratory studies, thyroid ultrasonography, thyroid scintigraphy, fine needle aspirate cytology (FNAC) of the nodule, and/or biopsy of the nodule for histopathology ( 2 ). A thorough history taking and physical examination includes assessing for signs and symptoms of hyperthyroidism and compression such as dysphagia, dysphonia, and Horner syndrome ( 2 , 9 ). Assessment of concomitant risk factors associated with an increased risk of malignancy includes male sex, age below 20 years or above 60 years, prior neck irradiation, and a family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2 (MEN2) ( 9 ). Features associated with an increased risk of malignancy include thyroid nodules with a firm and hard consistency, rapid growth of the nodule, and the presence of suspicious, enlarged cervical lymph nodes ( 2 , 9 ). Thyroid function tests, including serum thyrotropin (TSH) level, total or free thyroxine (T4), and total triiodothyronine (T3), are useful for establishing the functional status of a thyroid nodule ( 2 , 14 ). High-resolution thyroid ultrasonography is the primary imaging modality of choice for screening and detecting thyroid nodules ( 1 , 5 ). The advantages of thyroid ultrasound include its cost-effectiveness, non-invasiveness, favourable safety profile with no radiation or radioisotopes involved, and superior spatial resolution compared to computed tomography, magnetic resonance imaging, and thyroid scintigraphy ( 4 , 5 , 15 ). The main limitation is the poor reproducibility of ultrasound, due to inter- and intra-operator variability, as well as the utilization of equipment with different settings and performance. In our setting, this is further compounded by the lack of a standardized thyroid ultrasound report ( 9 ), to unify reporting capabilities. The aim of thyroid ultrasonography is to differentiate benign nodules that can be managed conservatively from malignant thyroid nodules requiring further workup and management ( 7 , 16 ). Horvath et al. ( 10 ) proposed the Thyroid Image Reporting and Data Systems (TIRADS) in 2009, a classification system that correlates sonographic features with cytological classification. The foundation of the TIRADS classification is based on the American College of Radiology (ACR) Breast Imaging Reporting and Data System (BI-RADS) ( 17 ). The TIRADS classification assigns levels of malignancy risk to specific ultrasound features, which allows for a streamlined selection of thyroid nodules designated to undergo FNAC ( 9 , 10 ). This risk stratification system aims to prevent unnecessary invasive procedures and facilitates effective communication between radiologists and endocrinologists worldwide ( 10 ). Numerous risk stratification systems for assessing thyroid nodules have been developed, including the ACR-TIRADS by the American College of Radiology, EU-TIRADS by the European Thyroid Association, K-TIRADS by the Korean Society of Thyroid Radiology, and Chinese-TIRADS by the Chinese professional society ( 9 ). The ACR-TIRADS demonstrated the best sensitivity (96.9%) and lowest specificity (52.9%) in a study conducted by Xu et al. ( 18 ). Ultrasound-guided fine needle aspiration cytology is the diagnostic tool of choice for detecting malignancy in thyroid nodules, as cytology results determine treatment protocols ( 9 ). FNAC is a cost-effective and safe procedure that shows “superior diagnostic reliability over thyroid ultrasound and scintigraphy” ( 19 ). Non-diagnostic results, which occur in up to 29% of ultrasound-guided fine-needle aspiration cytology specimens, are a known limitation of this technique ( 6 ). This can be due to various factors such as thyroid nodule size, vascularity, and consistency, as well as operator experience and the cytopathologist’s threshold of adequacy ( 6 ). Improved diagnostic yield and accuracy of cytology were noted when FNAC was performed under ultrasound guidance ( 2 ). Supervised training and rapid on-site evaluation (ROSE) of the cytologic aspirate to determine its adequacy has improved specimen yields by 83–92% and reduced the rate of non-diagnostic specimens by 44% ( 6 ). Core needle biopsy (CNB), with corresponding histology, is increasingly being used in the evaluation of thyroid nodules, particularly after a non-diagnostic or indeterminate result from fine-needle aspiration (FNA) cytology. CNB offers several advantages, including significantly lower rates of non-diagnostic (5.5%) and inconclusive results (8%), compared to FNA cytology, which reports rates of 22.6% and 40.2%, respectively. Technological advancements, such as the use of higher-gauge automated biopsy devices and ultrasound guidance, have further improved the accuracy of CNB. These innovations have led to reduced false-negative rates (1–3%) and a low complication rate ranging from 0–4.1% ( 20 ). Although FNAC remains the globally recognized first-line procedure for evaluating incidental thyroid nodules, its use is particularly challenging in low-resource settings, such as our own. Many patients rely on public or hospital transport, often traveling long distances to tertiary centres at significant personal cost. Additionally, FNAC can yield non-diagnostic or indeterminate results, necessitating repeat FNAC or confirmatory CNB. This creates logistical barriers, and many patients are lost to follow-up, leaving potential thyroid malignancies undiagnosed until they present at more advanced stages. In contrast, CNB offers a higher likelihood of a definitive diagnosis at initial presentation, with a favourable safety profile, making it the preferred first-line diagnostic tool in developing countries for evaluating suspicious thyroid nodules. The aim of this study was to retrospectively assess the diagnostic accuracy of the reported ACR TI-RADS classification in identifying and excluding malignant thyroid lesions using histology as the gold standard of reference, with further secondary correlation with cytology, biochemistry, and nuclear medicine studies where available, at our local setting in Grey’s Hospital, Pietermaritzburg. This study will further add to the pre-existing body of knowledge, documenting the current scope of practice and its efficacy at Grey’s Hospital, a teaching hospital in Pietermaritzburg, South Africa, in assessing the sensitivity (identifying malignant lesions) and specificity (excluding malignant lesions/confirmed benign lesions) of the ACR TI-RADS scoring system utilized in practice. MATERIALS AND METHODS Study setting, design, and participants This retrospective, descriptive audit was conducted in the Radiology department at Grey’s Hospital, a tertiary-level hospital in Pietermaritzburg, KwaZulu-Natal, South Africa. Adult patients above 18 years of age who had an ultrasound evaluation of the thyroid gland, with an ACR TI-RADS score documented, and had subsequent histology results available from either an ultrasound-guided core needle biopsy of a thyroid nodule and/or partial/complete thyroidectomy between January 2020 and May 2024 were included in the study. Additional data, including thyroid biochemistry, cytology, and nuclear medicine imaging, were evaluated, where available. Excluded patients had an incomplete or missing ultrasound report. Ultrasound assessment Thyroid ultrasound examinations were performed using an Aloka Prosound Alpha 7 and a Canon Aplio 500 ultrasound machine, both equipped with high-frequency linear array transducers ranging from 4 to 13 MHz and 5 to 14 MHz, respectively. Ultrasound images were acquired and interpreted by experienced sonographers as well as registrars or medical officers in training. Thyroid nodules were assessed and classified according to the ACR TI-RADS scoring system. The ACR-TIRADS classifies ultrasound features into five categories: Composition, echogenicity, shape, margin, and echogenic foci ( 1 , 7 ). The total points determine the thyroid nodule’s risk level, which ranges from TI-RADS 1 (TR1) (Benign) to TI-RADS 5 (TR5) (Highly suspicious) ( 7 ). ACR TI-RADS 1 refers to a benign thyroid nodule, ACR TI-RADS 2 refers to a not suspicious thyroid nodule (0% malignancy risk), ACR TI-RADS 3 refers to a mildly suspicious thyroid nodule ( 80% malignancy risk) ( 15 , 17 ). While individual ultrasound features required for ACR TI-RADS classification were not consistently documented, all reports included a final ACR TI-RADS score for each thyroid nodule. The most suspicious thyroid nodule in each location (isthmus, right, and left thyroid lobes), with the highest ACR TI-RADS category, was documented in the final assessment. Histologic and cytologic examination ACR TI-RADS 3,4, or 5 thyroid nodules are managed with either an ultrasound-guided core needle biopsy, ultrasound-guided FNAC, or ultrasound surveillance, depending on their size ( 1 ). Demographic details of patients undergoing a partial/complete thyroidectomy and/or ultrasound-guided core needle biopsy of a thyroid nodule were collected retrospectively from theatre and interventional radiology suite records. Histology results were then traced on the National Health Laboratory Service (NHLS) TrakCare website and were classified as benign or malignant. In each patient undergoing an ultrasound-guided core needle biopsy, the most suspicious thyroid nodule, with the highest ACR TI-RADS category, was targeted for sampling. A subgroup of patients in our study cohort underwent concurrent ultrasound-guided fine needle aspiration cytology (FNAC) of their thyroid nodules. These results were collected retrospectively from the interventional radiology suite records. A universal standardized reporting format was developed in 2007 in Maryland, USA, in the form of the Bethesda System for Reporting Thyroid Cytopathology ( 5 , 19 ). This system classifies the cytology results into six diagnostic categories, which stratify the associated malignancy risk: 1. Non-diagnostic or unsatisfactory (1–4%), 2. Benign (0–3%), 3. Atypia of undetermined significance (AUS) or follicular lesion of undetermined significance (FLUS) (5–15%), 4. Follicular neoplasm or suspicious for a follicular neoplasm (15–30%), 5. Suspicious for malignancy (60–75%), 6. Malignant (97–99%) ( 5 ). Data collection Demographic data and thyroid ultrasound reports were obtained from the hospital's Carestream picture archiving and communication system (PACS). Thyroid biochemical tests, histology, and cytology were collected from the patients’ NHLS records. Thyroid function biochemistry was recorded as euthyroidism, hyperthyroidism, or hypothyroidism. Thyroid scintigraphy reports were obtained from patients’ hospital files and categorized as normal, increased, or decreased uptake. Thyroid scintigraphy is a form of radioisotope scanning which determines whether a thyroid nodule is normal functioning (warm nodule) which accounts for 10–15% of thyroid nodules, non-functioning (cold nodule) which accounts for 80–85% of thyroid nodules or hyperfunctioning (hot nodule) which accounts for 5% of thyroid nodules ( 2 ). After data collection, the data was anonymised and captured on a Microsoft Excel spreadsheet. Statistical analysis The data was analysed using IBM SPSS version 30. Descriptive statistics present the patients' demographic and clinical profiles in terms of frequencies and percentages (categorical variables) and means with standard deviations (numeric variables). Associations between ACR TI-RADS categories and histology results were examined using the Pearson chi-square test and Fisher’s exact test. The diagnostic sensitivity, specificity, positive predictive value, and negative predictive value of the ACR TI-RADS scoring method were calculated using a 2 × 2 cross tabulation, where the histology results served as the gold standard. A receiver-operating characteristic (ROC) curve plot provided visualisation of the ACR TI-RADS scoring method’s benign and malignant lesion classification accuracy. A p-value < 0.05 indicated statistical significance. Ethical considerations Ethical approval was obtained from the Biomedical Research Ethics Committee of the University of KwaZulu-Natal (BREC/00007428/2024). Hospital site approval was obtained from the medical manager and chief executive officer of Grey’s Hospital. Informed consent was waived due to the retrospective nature of the study. RESULTS Patient demographics and histology findings In the final study population of 68 patients, 59 (86.8%) were female and 9 (13.2%) were male, with ages ranging from 27 to 82 years, and a mean age of 52.6 years. 57 patients (83.8%) had benign thyroid nodules and 11 patients (16.2%) had malignant thyroid nodules. Correlation of histology with demographics There were no statistically significant differences in sex or age between the histological benign group (mean age = 51.9 years, standard deviation = 14.1 years) and the histological malignant group (mean age = 56.4 years, standard deviation = 13.0 years), p = 0.338 for age and p = 0.631 for sex. Correlation of ACR TI-RADS score on ultrasound with histopathology Of the 68 patients, 2 patients (2.9%), 7 patients (10.3%), 17 patients (25%), 32 patients (47.1%) and 10 patients (14.7%) had thyroid nodules classified as ACR TI-RADS 1 (Benign), 2 (Not suspicious), 3 (Mildly suspicious), 4 (Moderately suspicious) and 5 (Highly suspicious) respectively. In ACR TI-RADS 1 (Benign), 2 patients had histologically confirmed benign thyroid nodules. There were no patients with malignant thyroid nodules. In ACR TI-RADS 2 (Not suspicious), 6 out of 7 patients had histologically confirmed benign thyroid nodules, whilst 1 out of 7 patients had a histologically confirmed malignant thyroid nodule. In ACR TI-RADS 3 (Mildly suspicious), 14 out of 17 patients had histologically confirmed benign thyroid nodules, whilst 3 out of 17 patients had histologically confirmed malignant thyroid nodules. In ACR TI-RADS 4 (Moderately suspicious), 26 out of 32 patients had histologically confirmed benign thyroid nodules, whilst 6 out of 32 patients had histologically confirmed malignant thyroid nodules. In ACR TI-RADS 5 (Highly suspicious), 9 out of 10 patients had histologically confirmed benign thyroid nodules, whilst 1 out of 10 patients had a histologically confirmed malignant thyroid nodule. No statistical significance is demonstrated between histology status (benign or malignant) and the ACR TI-RADS score. A marked discrepancy is noted when correlating the ACR TI-RADS category with the histology results. For ease of analysis and to perform statistical tests of diagnostic accuracy, ACR TI-RADS 1, 2, and 3 were combined to approximate benign results, and ACR TI-RADS 4 and 5 were combined to approximate malignant results. The level of agreement between the Thyroid Ultrasound Results (ACR TI-RADS score) and the histology results was then computed in a 2x2 cross-tabulation in which the histology results were treated as the gold standard. The results show that the Thyroid Ultrasound Results (ACR TI-RADS) scoring method had a sensitivity of 63.6% (95% confidence interval (CI): 30.8% − 89.1%), a specificity of 38.6% (95% CI: 26.0% − 52.4%), a positive predictive value of 16.7% (95% CI: 10.9% − 24.6%), and a negative predictive value of 84.6% (95% CI: 70.3% − 92.8%). ROC curve analysis on the same data yields an area under the curve (AUC) value of 0.51 (95% CI: 0.39–0.63), indicating that the ACR TI-RADS scoring method failed to discriminate between benign and malignant lesions in our setting when histology results are used as the gold standard. Correlation of specific ultrasound features of the ACR TI-RADS score with histopathology COMPOSITION Of the 68 patients, 60 had their thyroid nodule composition documented on ultrasound, with the majority having mixed solid-cystic thyroid nodules (38.3%), followed by solid (36.7%), spongiform (16.7%), and cystic (8.3%) thyroid nodules. In the malignant histology group, the majority of thyroid nodules (5 out of 10 nodules) demonstrated a mixed solid-cystic composition (50%). In the benign histology group, the majority of thyroid nodules (20 out of 50 nodules each) demonstrated a solid composition (40%). ECHOGENICITY Of the 68 patients, 46 had thyroid nodule echogenicity documented on ultrasound, with the majority being hypoechoic (54.3%), followed by hyper- or isoechoic (39.1%), and anechoic (6.5%). In the malignant histology group, there were no anechoic thyroid nodules; instead, hyper- or isoechoic and hypoechoic nodules (3 out of 6 nodules each) contributed 50% each. In the benign histology group, the majority of thyroid nodules (22 out of 40 nodules) demonstrated hypoechogenicity (55%). SHAPE Of the 68 patients, 38 had their thyroid nodule shape documented on ultrasound, with 73.7% of thyroid nodules exhibiting a wider-than-tall shape and 26.3% demonstrating a taller-than-wide shape. In the malignant histology group, the majority of thyroid nodules (7 out of 8 nodules) demonstrated a wider-than-tall shape (87.5%). In the benign histology group, the majority of thyroid nodules (20 out of 30 nodules) demonstrated a wider-than-tall shape as well (70%). MARGIN Of the 68 patients, 42 had thyroid nodule margins documented on ultrasound, with the majority having thyroid nodules with smooth margins (52.4%), followed by those with lobulated or irregular margins (16.7%), ill-defined margins (16.7%), and extra-thyroidal extension (14.3%). In the malignant histology group, the majority of thyroid nodules (7 out of 9 nodules) had a smooth margin (77.8%). In the benign histology group, the majority of thyroid nodules (15 out of 33 nodules) had a smooth margin as well (45.5%). ECHOGENIC FOCI Of the 68 patients, 44 had thyroid nodule echogenic foci documented on ultrasound, with the majority of thyroid nodules containing no echogenic foci (59.1%), followed by thyroid nodules containing punctate echogenic foci (29.5%), peripheral (rim) calcifications (9.1%), and macrocalcifications (2.3%). In the malignant histology group, the majority of thyroid nodules (5 out of 8 nodules) had no echogenic foci (62.5%). In the benign histology group, the majority of thyroid nodules (21 out of 36 nodules) also had no echogenic foci (58.3%). No statistical significance is demonstrated between histology status (benign or malignant) and each of the specific ultrasound features of the ACR TI-RADS score. Correlation of intralesional vascularity on ultrasound with histopathology Of the 68 thyroid nodules, 24 nodules demonstrated the presence of intralesional vascularity on ultrasound (35.3%). Of the 11 patients with histologically confirmed malignant thyroid nodules, 7 (63.6%) demonstrated intralesional vascularity on ultrasound, while 4 (36.4%) did not. Among patients with benign thyroid nodules, intralesional vascularity was absent in 39 cases (69.7%) and present in 17 cases (30.3%), as documented on ultrasound. The prevalence of intralesional vascularity in malignant lesions was significantly higher compared to those without intralesional vascularity, p = 0.046. Correlation of histology with cytology Out of the 68 patients, 22 had available cytology results. Initial FNAC was performed, followed by histology results from core needle biopsy (CNB) or partial thyroidectomy, most likely due to initial cytology being non-diagnostic and/or discrepant with the sonographic findings. 13 patients (59.1%) had non-diagnostic/Bethesda Diagnostic Category I thyroid nodules, 8 patients (36.4%) had benign/Bethesda Diagnostic Category II thyroid nodules, and 1 patient (4.5%) had a suspicious for malignancy/Bethesda Diagnostic Category V thyroid nodule. 13 of the 22 patients (59%) had non-diagnostic cytology (Bethesda Diagnostic Category I), which corresponded to histologically confirmed benign thyroid nodules. 6 of the 22 patients (27%) had benign cytology (Bethesda Diagnostic Category II), which corresponded to histologically confirmed benign thyroid nodules. 2 of the 22 patients (9.1%) had benign cytology (Bethesda Diagnostic Category II) which corresponded to histologically confirmed malignant thyroid nodules. 1 of the 22 patients (4.5%) had suspicious for malignancy cytology (Bethesda Diagnostic Category V), which corresponded to a histologically confirmed malignant thyroid nodule, resulting in statistical significance (p = 0.010). Correlation of thyroid function tests and histopathology 6 out of the 11 patients (54.5%) with histologically proven malignant thyroid nodules had a thyroid function test demonstrating subclinical hypothyroidism, followed by 4 patients (36.3%) having euthyroidism and 1 patient (9.1%) having hypothyroidism. In contrast, the majority of patients with histologically proven benign thyroid nodules, 37 out of 57 patients (64.9%), had a thyroid function test demonstrating euthyroidism, subclinical hypothyroidism was found in 11 patients (19.3%), subclinical hyperthyroidism in 5 patients (8.8%), hyperthyroidism in 3 patients (5.3%) and hypothyroidism in 1 patient (1.8%). No statistical significance is demonstrated between histology (benign or malignant) and serum thyroid function test results, p = 0.060 Correlation of thyroid scintigraphy and histopathology Of the 68 patients, a small subgroup of 6 patients had nuclear medicine thyroid scintigraphy results available. 1 patient (16.7%) had normal uptake, and 5 patients (83.3%) demonstrated increased uptake. Increased uptake was seen in 3 patients with histologically confirmed benign thyroid nodules and 2 patients with histologically confirmed malignant thyroid nodules. Normal uptake was seen in 1 patient with a histologically confirmed malignant thyroid nodule. No statistical significance is demonstrated between histology status (benign or malignant) and thyroid scintigraphy results (p = 1.000). DISCUSSION Demographic Profile In this study, the majority of the cohort with thyroid nodular disease and histologically proven malignant thyroid nodules were female (86.8% and 81.8% respectively). The mean ages were 51.9 years and 56.4 years in the benign and malignant thyroid nodule groups, respectively. No statistically significant differences were demonstrated in age or sex between the benign and malignant groups. This was in keeping with global and local literature. A meta-analysis comprising 52 studies revealed an increased prevalence of thyroid nodular disease in females and in patients over 40 years old. A study by Chagi et al. ( 13 ) conducted in a tertiary South African hospital demonstrated an increased incidence of thyroid carcinoma in patients between 20 and 55 years of age. The higher incidence of thyroid nodules in females, which is four times greater than in males, can be explained by the hormonal influence of progesterone and oestrogen, as the development of new nodules and the increase in size of pre-existing nodules are thought to be related to pregnancy and multiparity ( 10 , 21 , 22 ). Histopathology Profile 83.8% of the study population had histologically confirmed benign thyroid nodules, which were mainly composed of multinodular goiters, followed by benign follicular adenomas and Hashimoto’s thyroiditis. This finding is not in keeping with the global prevalence of 90–95% and the prevalence in Africa of 89% ( 4 , 7 ). This is likely due to the small sample size of the study cohort. The large proportion of benign thyroid nodular disease is thought to be due to the increased incidence of multinodular goiters in iodine-deficient regions of developing countries, such as South Africa ( 4 , 6 , 9 ). 16.2% of the study cohort had histologically confirmed malignant thyroid nodules made mainly of papillary, followed by follicular thyroid carcinoma (54.5% and 45.4% respectively). This is in line with the prevalence of thyroid malignancy in the literature, which ranges from 0.9–20.5% globally. A study conducted by Chagi et al. ( 13 ) in Johannesburg, South Africa, also demonstrated a greater prevalence of papillary thyroid cancer as the predominant thyroid carcinoma type ( 3 , 7 ). Most CNB procedures for histology were performed on ACR TI-RADS category 4 lesions (47.1%), followed by categories 3 and 5 (25% and 14.7%, respectively), in accordance with literature on the established guidelines for lesions requiring biopsy ( 1 ). Concordance of ACR TI-RADS score on ultrasound with histopathology In this study, ACR TI-RADS 1, 2, 3, 4, and 5 had malignancy risks of 0%, 14.3%, 17.6%, 18.8%, and 10%, respectively. The risk of malignancy in this study for ACR TI-RADS 1 and 4 compares to the literature, which reports 0% and 5–80%, respectively. There is discordance between the malignancy risk in ACR TI-RADS 2, 3, and 5 and the literature, which reports 0%, 80% ( 1 , 10 , 15 , 17 ). The high incidence of benign thyroid lesions classified under the ACR TI-RADS 4 and 5 categories, which are associated with a high likelihood of malignancy, suggests that junior staff may be over-estimating the malignancy risk of these lesions. Conversely, the presence of malignant thyroid lesions categorized as benign (ACR TI-RADS 2 and 3) indicates the under-estimation of lesion malignancy risk. These discrepancies in our setting can be attributed to the absence of standardized thyroid ultrasound reporting protocols, as well as inter-user variability resulting from the frequent rotation of inexperienced junior staff, which is typical of institutions with ongoing medical training. A study conducted by Rago et al. ( 9 ) in Pisa, Italy, demonstrated the main limitations of ultrasound, including poor reproducibility due to inter- and intra-operator variability, the use of equipment with different settings and performance, and the lack of a standardized ultrasound report. This highlights the need for further training and the development of a standardized reporting template to improve diagnostic accuracy. For the assessment of diagnostic accuracy, ACR TI-RADS 1, 2, and 3 were combined to approximate benign results, and ACR TI-RADS 4 and 5 were combined to represent malignant results. In this study, the ACR TI-RADS scoring system had a sensitivity of 63.6%, specificity of 38.6%, positive predictive value of 16.7%, negative predictive value of 84.6% and accuracy of 42.6% which is discordant with the literature, thus failing to discriminate between benign and malignant lesions when histology results are used as the gold standard. A study by Schenke et al. ( 23 ) in Germany compared three TI-RADS scoring systems for assessing small thyroid nodules and found that the ACR TI-RADS had a positive predictive value of 65%, a negative predictive value of 100%, and an accuracy of 71.7%. Several risk stratification systems have been developed to assess thyroid nodules, with the ACR-TIRADS showing the highest sensitivity (96.9%) but the lowest specificity (52.9%) ( 18 ). Correlation of specific ultrasound features of the ACR TI-RADS score with histopathology The most common individual ultrasound features exhibited in malignant thyroid nodules in this study were a mixed solid-cystic composition, hyper- or isoechoic and hypoechoic echogenicity, a wider-than-tall shape, smooth margins, and no echogenic foci. The most common individual ultrasound features exhibited in benign thyroid nodules were solid composition, hypoechoic echogenicity, a wider-than-tall shape, smooth margins, and no echogenic foci. These findings are discordant with the literature, which proposes that sonographic features suspicious for thyroid nodule malignancy include a solid component, hypoechogenicity, a taller-than-wide shape, microcalcifications, and microlobulated or irregular margins ( 11 ). There are a few reasons to explain this in our setting: Firstly, with regard to each component of the ACR TI-RADS scoring system, only 88.2%, 67.6%, 55.9%, 61.8% and 64.7% of ultrasound reports recorded composition, echogenicity, shape, margin, and the presence of echogenic foci, respectively. This is likely due to a lack of a standardized reporting template for thyroid ultrasounds in our setting, as junior staff are reporting on only selected components of the scoring system. Thus many malignant features may be unaccounted for in the thyroid ultrasound report, further highlighting inexperience with thorough assessment of each of the ACR TI-RADS components on ultrasound. Secondly, inconsistencies in measuring a nodule may result in inaccurate values, particularly when accounting for lesion shape, specifically those that are “taller than wider”. There are also confounding factors that we need to be aware of, which can overestimate the malignancy risk of a benign thyroid nodule, resulting in a higher ACR TI-RADS classification. Chen et al. ( 24 ) found that 9.4% of histologically confirmed benign thyroid nodules were misdiagnosed as suspicious ACR TI-RADS 4–5 lesions based on solid composition (98%), hypoechogenicity (89.4%) and punctate echogenic foci (42.7%) due to features of fibrosis and calcification associated with follicular epithelial hyperplasia, thyroid adenoma and nodular goitres. This study also found that benign thyroid nodules can have a taller-than-wide shape due to the nodule being pulled up and down during the fibrosis and degenerative stages, which could explain why 30% of benign thyroid lesions in our setting demonstrated a taller-than-wide shape, a characteristic more commonly associated with malignancy. A contradictory study conducted in Germany by Schenke et al. ( 23 ) found that the majority of malignant thyroid nodules (55%) displayed a wider-than-tall shape, in keeping with the majority shape of malignant thyroid nodules in our study. Most ACR TI-RADS individual ultrasound features have low sensitivities on their own, apart from hypoechogenicity (87.2% sensitivity) ( 22 ). A taller-than-wide shape has a 93% specificity for diagnosing malignancy, with a spiculated margin, marked hypoechogenicity, and microcalcifications, which are further features highly suggestive of malignancy, with specificities of 92%, 92–94%, and 86–95%, respectively ( 9 ). No single ultrasound feature can be used to differentiate between benign and malignant thyroid nodules in isolation ( 7 , 10 , 22 ). A meta-analysis by Remonti et al. ( 22 ) reported that combining suspicious ultrasound features enhanced the accuracy in predicting the likelihood and potential for malignant disease. Correlation of intralesional vascularity on ultrasound with histopathology 63.6% of the study cohort with histologically confirmed malignant thyroid nodules demonstrated intralesional vascularity on ultrasound, with a sensitivity of 63.64% and specificity of 69.64%, aligning with the available literature. The prevalence of malignant lesions was significantly higher among patients with documented intralesional vascularity compared to those without, with a statistical significance of p = 0.046. A review by Rago et al. ( 9 ) reported that intranodular vascularization has good sensitivity and can be observed in 69–74% of thyroid malignancies; however, it has low specificity. The study also raises concerns about misinterpreting vascularity as intra-nodal, as opposed to peri-nodal vascularity, in smaller thyroid nodules (< 5mm). Remonti et al. ( 22 ) conducted a meta-analysis involving 52 studies, which validated that central vascularization in a thyroid nodule was one of four individual features with good specificity (78%) but lower sensitivity (45.9%) in determining the risk of malignancy. A further meta-analysis by Khadra et al . ( 25 ) evaluated whether vascular flow served as a predictor of a malignancy in thyroid nodules and found that the majority of malignant thyroid nodules had internal and peripheral vascular flow (50% and 17% respectively), however, no difference in the intralesional vascularity was found between benign and malignant thyroid nodules. These findings suggest that intralesional vascularity alone is not diagnostic of malignancy, but may indicate an increased risk when observed in conjunction with other suspicious sonographic features. Correlation of cytology with histopathology 22 patients in our study had cytology results available, with 13 patients (59%) having non-diagnostic results that corresponded to benign pathology on subsequent histology. There was good concordance between Bethesda Diagnostic Category II (Benign) cytology and histologically benign nodules. Furthermore, the Bethesda Diagnostic Category V (Suspicious for malignancy) cytology also corresponded to a histologically confirmed malignant thyroid nodule with a statistically significant p-value of 0.010; however, this is not an entirely representative result, with only 1 patient in this category V. Two patients with Bethesda diagnostic category II (benign) cytology had discordant malignant histology results. The sensitivity was 33.3% and the specificity was 100%, in line with the literature, which reports that FNAC has variable sensitivity (38–98%) and specificity (72–99%) ( 26 ). The low sensitivity in our study is likely due to the small sample size of available cytology results. Non-diagnostic results, which occur in up to 29% of ultrasound-guided fine-needle aspiration biopsies, are a limitation of this technique ( 6 ). This can be due to various factors such as thyroid nodule size, vascularity, and consistency, as well as operator experience and the cytopathologist’s threshold of adequacy ( 6 ). Improved diagnostic yield was noted when FNAC was performed under ultrasound guidance ( 2 ). Supervised training and rapid on-site evaluation (ROSE) of the aspirate, by a cytopathologist, to determine its adequacy has improved specimen yields by 83–92% and reduced the rate of non-diagnostic specimens by 44%. Despite our FNAC being performed under ultrasound guidance, we unfortunately do not have ROSE available at our institution, which would possibly account for the higher non-diagnostic results rate compared to the literature. The implementation of the ACR TI-RADS classification system has proven valuable in stratifying the risk of thyroid nodules, particularly in distinguishing between benign and malignant lesions. This has important clinical implications, as it facilitates more cautious use of fine-needle aspiration cytology (FNAC), potentially reducing the number of unnecessary procedures performed on nodules with low suspicion for malignancy ( 1 ). Correlation of thyroid function tests and histopathology Thyroid function tests, including serum thyrotropin (TSH) level, total or free thyroxine (T4), and total triiodothyronine (T3), are useful for establishing the functional status of the thyroid nodule ( 2 , 14 ). The majority of patients in this study (60.3%) had a thyroid function test demonstrating euthyroidism, whilst 54.5% of patients with thyroid malignancy had subclinical hypothyroidism. This aligns with the literature, which indicates that most thyroid nodules are non-functioning/euthyroid, with normal or elevated TSH levels ( 2 , 12 ). On the contrary, 14% of the study cohort with benign thyroid nodules had biochemistry consistent with subclinical and overt hyperthyroidism, again consistent with the literature, which states that 10% of solitary thyroid nodules are benign hyperfunctioning adenomas ( 2 ). There were no patients in the malignant ( 1 , 3 ) nodule category with biochemical features of hyperthyroidism, which is in accordance with the literature, as hyperfunctioning thyroid nodules are less likely to be of a malignant nature ( 1 , 3 , 12 ). Several studies have attempted to establish a link between TSH levels and their ability to predict the risk of malignancy. A study by Naidu et al. ( 4 ) conducted in Johannesburg, South Africa, found no association between TSH and the risk of thyroid malignancy. A study by Khider et al. ( 14 ) conducted in Saudi Arabia on a cohort of 222 patients demonstrated that the level of TSH increases exponentially in individuals with malignant thyroid nodules as opposed to those with mildly suspicious or benign nodules. Furthermore, this study found low levels of T3 and T4 in malignant thyroid nodules. This makes biochemistry a valuable tool in low-resource environments, in combination with sonographic findings, for safely identifying a subset of hyperthyroid/hyperfunctioning thyroid nodules that do not require biopsy or surgical intervention. Correlation of thyroid scintigraphy and histopathology Thyroid scintigraphy is indicated when TSH levels are low or suppressed, suggesting a diagnosis of primary hyperthyroidism ( 12 ). However, in our study, only a subset of 6 patients with mixed biochemistry results proceeded to have thyroid uptake scans and biopsies. Three patients had subclinical and overt hyperthyroidism with histologically confirmed benign thyroid nodules, and 3 patients had subclinical hypothyroidism and euthyroidism with histologically confirmed malignant thyroid nodules, concordant with the literature that suggests hyperfunctioning/hyperthyroid nodules have a low risk of malignancy ( 12 ). Increased uptake was demonstrated in 5 patients, 2 of whom had thyroid malignancy and 1 patient with a benign nodule who was diagnosed with Graves' disease. 1 patient had a normal uptake scan and a histologically confirmed malignant thyroid nodule. A study by Kant et al. ( 12 ) reported that a local increase in uptake in the thyroid nodule on thyroid scintigraphy is consistent with a hyperfunctioning or “hot” nodule. Hyperfunctioning thyroid nodules do not require FNAC as they are unlikely to be malignant. Non-functioning or “cold” thyroid nodules may have a normal or elevated TSH level and are further evaluated with FNAC if they meet clinical or ultrasound criteria ( 12 ). There is no role for radioisotope scanning in the initial evaluation of a thyroid nodule, as its sensitivity for diagnosing malignancy ranges from 89–93% with a specificity of 5% ( 2 ). There is, however, a role for thyroid scintigraphy in identifying hyperfunctioning or “hot” thyroid nodules to avoid unnecessary biopsies of these nodules ( 2 ). LIMITATIONS While this study provides valuable insights into the diagnostic accuracy of the ACR TI-RADS classification in a local resource-restricted setting, several recognized limitations exist. The small sample size and the single-centre study design limit the generalizability of the findings. Further studies with a larger multi-centre cohort would provide more varied data, allowing for more definitive conclusions. Due to the retrospective nature of the study, the accuracy of the data collected depends on good record-keeping, and missing histology records could have led to a sizable portion of the study population being excluded. Patients with only thyroid nodule cytology results, with no corresponding histology, were not included in the study, as histology was recognized as the gold standard, resulting in a smaller sample size. The absence of a standardized thyroid ultrasound reporting template in our setting may have contributed to incomplete or inconsistent assessment of important characteristics, such as nodule shape, echogenicity, and margin. This could lead to underreporting of suspicious imaging features, resulting in reduced diagnostic accuracy and discrepant ACR TI-RADS classification. One of the major limitations identified in this study, in addition to the lack of a standardized ultrasound reporting protocols, was the presence of inter- and intra-operator variability. Given that the study setting included inexperienced junior staff, variability in interpreting the ultrasound features of thyroid nodules could have contributed to misclassification or over- or under-estimation of malignancy risk. The use of thyroid scintigraphy in our study was inconsistent, as it is not available on-site and was not routinely performed on all patients. The role of nuclear medicine in evaluating thyroid nodules may have provided additional insights into the functionality of the nodules and contributed to a more thorough evaluation of malignancy risk. CONCLUSION This study offers a valuable assessment of the diagnostic accuracy of the ACR TI-RADS classification in distinguishing between benign and malignant thyroid nodules, using histology as the gold standard. The results suggest that the ACR TI-RADS scoring system, although widely used, has limitations in sensitivity and specificity in our local setting. Notably, there were marked discrepancies between the ultrasound features of certain nodules and the histopathology results, suggesting over- or under-estimation of malignancy risk. These findings underline the challenges of relying solely on ultrasound features in diagnosing thyroid cancer, particularly where inter-operator variability and inconsistent reporting are key factors. Despite these limitations, the study reinforces the importance of ongoing education and training for junior staff, as well as the development of standardized reporting templates to enhance diagnostic accuracy. Furthermore, our study emphasized the additional value of assessing sonographic intralesional vascularity in thyroid nodules, as a potential important predictor of malignancy despite controversy in the literature, and one not routinely included in ACR-TIRADS classification. The study also highlights the value of integrating ultrasound findings with cytology, biochemistry, and nuclear medicine results to achieve a more comprehensive evaluation of thyroid nodules. RECOMMENDATIONS Our primary recommendation is integrating the use of a standardized thyroid ultrasound reporting template into daily practice in our setting (Appendix A). This would ensure that all relevant features of the ACR TI-RADS classification system, such as nodule composition, echogenicity, shape, margin, and echogenic foci, are consistently documented, with the aim of reducing inter-operator variability, improving diagnostic accuracy, and accurately assigning an ACR TI-RADS score. Incorporating lesion vascularity is a further recommended addition to the ACR-TIRADS classification. Regular workshops and supervised in-service training sessions are crucial for enhancing the reproducibility and accuracy of ultrasound assessments. A multidisciplinary approach involving radiologists, endocrinologists, pathologists, and nuclear medicine specialists should also be encouraged to help integrate findings from various diagnostic modalities, such as ultrasound, histology, cytology, biochemistry, and scintigraphy, thereby more reliably differentiating benign from malignant lesions. Future studies targeting larger sample sizes and those involving multiple centers could help validate the diagnostic performance of ACR TI-RADS across diverse patient populations in Sub-Saharan Africa. This study found a significant proportion of non-diagnostic cytology results, which limits the ability to definitively classify nodules. To address this, future studies could explore methods to enhance cytology diagnostic yield, such as standardizing ROSE, which could improve the specimen adequacy and diagnostic accuracy. Thyroid scintigraphy should be more consistently used in patients with biochemistry suggestive of hyperthyroidism to identify "hot" or hyperfunctioning nodules, which are unlikely to be malignant. This could help in avoiding unnecessary invasive procedures, thereby reducing healthcare costs and patient burden. Regular audits of ultrasound reports and histology results, with feedback to clinicians, could help identify areas for improvement in thyroid nodule assessment. Audits would also provide an opportunity to refine diagnostic criteria and protocols over time, ultimately enhancing patient care and reducing morbidity and mortality. Abbreviations ACR American College of Radiology AUC Area under the curve AUS Atypia of undetermined significance CI Confidence interval CNB Core needle biopsy FLUS Follicular lesion of undetermined significance FNAC Fine needle aspiration cytology NHLS National Health Laboratory Service ROC Receiver-operating characteristic ROSE Rapid on-site evaluation T3 Total triiodothyronine T4 Total or free thyroxine TI-RADS Thyroid Imaging Reporting and Data System TSH Serum thyrotropin Declarations Ethics approval and consent to participate : Ethical approval was obtained from the Biomedical Research Ethics Committee of the University of KwaZulu-Natal (BREC/00007428/2024). Hospital site approval was obtained from the medical manager and chief executive officer of Grey’s Hospital. Consent for publication : Informed consent was waived due to the retrospective nature of the study. Availability of data and material : Data sharing is not applicable to this article as no new data were created or analysed in this study. Competing interests : The authors declare that they have no competing interests. Funding : None. Authors’ contributions : N.B. was responsible for the research protocol, data collection and compilation of the article. T.S. was the principal supervisor and assisted with all components. Both authors read and approved the final manuscript. Acknowledgements : We thank Mrs. Heshika Singh for her contribution to data collection. We are grateful to Mr. Promise Khumbula for statistical assistance. Authors’ information : Mentioned above. References Huang EYF, Kao NH, Lin SY, Jang IJH, Kiong KL, See A, et al. (2023) Concordance of the ACR TI-RADS Classification With Bethesda Scoring and Histopathology Risk Stratification of Thyroid Nodules. JAMA Netw Open 6(9):e2331612. doi:10.1001/jamanetworkopen.2023.31612 Ahmad F (2020) Diagnostic accuracy of ultrasound-guided fine needle aspiration cytology of thyroid nodules at Universitas Academic Hospital, Bloemfontein. Dissertation, University of the Free State. Bhuiyan MM, Machowski A (2015) Nodular thyroid disease and thyroid malignancy: Experience at Polokwane Mankweng Hospital Complex, Limpopo Province, South Africa. S Afr Med J. 105(7):570-2. Naidu K, Saksenberg V, Mahyoodeen NG (2023) Clinical and ultrasound characteristics distinguishing benign and malignant thyroid nodules in Johannesburg, South Africa. Journal of Endocrinology, Metabolism and Diabetes in South Africa 28(2):62-8. Nicolaou MA, Jacobs K, Bhana S, Naidu K, Nicolaou V (2019) A retrospective study correlating sonographic features of thyroid nodules with fine-needle aspiration cytology in a South African setting. SA J Radiol 23(1):1749. Conradie W, Du Plessis A, Edge J, Baatjes K, Ruiters A, Razack R (2022) Impact of a multidisciplinary approach to ultrasound-guided thyroid fine-needle aspiration biopsy at Tygerberg Hospital, Cape Town, South Africa: A retrospective audit. S Afr Med J 112(1):13521. Isse HM, Lukande R, Sereke SG, Odubu FJ, Nassanga R, Bugeza S (2023) Correlation of the ultrasound thyroid imaging reporting and data system with cytology findings among patients in Uganda. Thyroid Res 16(1):26. Moifo B, Moulion Tapouh JR, Dongmo Fomekong S, Djomou F, Manka'a Wankie E (2017) Ultrasonographic prevalence and characteristics of non-palpable thyroid incidentalomas in a hospital-based population in a sub-Saharan country. BMC Med Imaging 17(1):21. Rago T, Vitti P (2022) Risk Stratification of Thyroid Nodules: From Ultrasound Features to TIRADS. Cancers (Basel) 14(3). Periakaruppan G, Seshadri KG, Vignesh Krishna GM, Mandava R, Sai VPM, Rajendiran S (2018) Correlation between Ultrasound-based TIRADS and Bethesda System for Reporting Thyroid-cytopathology: 2-year Experience at a Tertiary Care Center in India. Indian J Endocrinol Metab 22(5):651-5. Baldini E, Sorrenti S, Tartaglia F, Catania A, Palmieri A, Pironi D, et al. (2017) New perspectives in the diagnosis of thyroid follicular lesions. Int J Surg 41 Suppl 1:S7-S12. Kant R, Davis A, Verma V (2020) Thyroid Nodules: Advances in Evaluation and Management. Am Fam Physician 102(5):298-304. Chagi N, Bombil I, Mannell A (2019) The profile of thyroid cancer in patients undergoing thyroidectomy at Chris Hani Baragwanath Academic Hospital. S Afr J Surg 57(3):55. Khider MO, Ayad C, Suliman AG, Alshoabi SA, Gameraddin M, Elzaki M, et al. (2022) Can Thyrotropin, Tri-Iodothyronine, and Thyroxine Hormones be Predictors of Cancer in Thyroid Lesions? Cureus 14(12):e32422. Classens S (2017) Quality Assessment of Thyroid Ultrasound and Implementation of a Standard Reporting Template to Be Used in Training Hospitals. Dissertation, University of the Witwatersrand. Matimati B (2022) Diagnostic yield of ultrasound-guided fine needle aspiration biopsy (US-guided FNAB) and post-surgical histopathological correlation of thyroid nodules in the Department of Radiology, Groote Schuur Hospital, Cape Town, South Africa over a two-year period. Dissertation, University of Cape Town. Botha M, Kisansa M, Greeff W (2020) American College of Radiology Thyroid Imaging Reporting and Data System standardises reporting of thyroid ultrasounds. SA J Radiol 24(1):1804. Kallepalli VSD, Nelson T, Sanniyasi S (2023) Analysis of Thyroid Imaging Reporting and Data System Criteria and Its Correlation With the Pathological Results. Cureus 15(6):e40117. Kilani L (2023) Thyroidectomies at an academic hospital in Johannesburg-correlation between pre-operative cytology findings and post-operative histology results. Dissertation, University of the Witwatersrand. Jung CK, Baek JH (2017) Recent Advances in Core Needle Biopsy for Thyroid Nodules. Endocrinol Metab (Seoul) 32(4):407-12. Chetty M, Mbatha B, Fru P (2023) The association between cytology and histopathology in thyroid nodules over a 6-year period in an urban hospital in South Africa. S Afr Med J 113(8):58-62. Remonti LR, Kramer CK, Leitao CB, Pinto LC, Gross JL (2015) Thyroid ultrasound features and risk of carcinoma: a systematic review and meta-analysis of observational studies. Thyroid 25(5):538-50. Schenke S, Klett R, Seifert P, Kreissl MC, Gorges R, Zimny M (2020) Diagnostic Performance of Different Thyroid Imaging Reporting and Data Systems (Kwak-TIRADS, EU-TIRADS and ACR TI-RADS) for Risk Stratification of Small Thyroid Nodules (</=10 mm). J Clin Med 9(1). Chen J, Ye D, Lv S, Li X, Ye F, Huang Y, et al (2024) Benign thyroid nodules classified as ACR TI-RADS 4 or 5: Imaging and histological features. Eur J Radiol 175:111261. Khadra H, Bakeer M, Hauch A, Hu T, Kandil E (2016) Is vascular flow a predictor of malignant thyroid nodules? A meta-analysis. Gland Surg 5(6):576-82. Bukasa-Kakamba J, Bayauli P, Sabbah N, Bidingija J, Atoot A, Mbunga B, et al (2022) Ultrasound performance using the EU-TIRADS score in the diagnosis of thyroid cancer in Congolese hospitals. Sci Rep 12(1):18442. Additional Declarations No competing interests reported. Supplementary Files AppendixA.docx Cite Share Download PDF Status: Published Journal Publication published 03 Dec, 2025 Read the published version in Egyptian Journal of Radiology and Nuclear Medicine → Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7465890","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":510331751,"identity":"27503780-02c7-436e-adf9-413c1b4ceca8","order_by":0,"name":"Neelam Bagratee","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABBklEQVRIiWNgGAWjYHACxgMMDAdgHBuQQOMBXGphAKaFsYGBIQ1Mk6TlMEwENzBnbz5w4GfOHXn56MPPH3yoOG+3tv0w0JYam2hcWix7jiUc7N32zHDjuTTDxhlnbidvO5MI1HIsLbcBhxaDGzkGB3i3HWbc2MNg2MzbdjvZ7ABQC2PDYdxa7r//cPDvtsP2G3vYPzb//Xcu2ez8QwJabvAwHAbakjifh8ewGRhWdmY3CNlyJs3gsOy2Z8kbeHgKZ/YcS04wuwG0JQGfX44ffvjw7bY7tvN72Dd8+FFjZ292Pv3hgw81Nji1IPQegNCJYJUJhJSDgDzUUHtiFI+CUTAKRsHIAgAL3HNzpjn5fQAAAABJRU5ErkJggg==","orcid":"","institution":"University of KwaZulu-Natal","correspondingAuthor":true,"prefix":"","firstName":"Neelam","middleName":"","lastName":"Bagratee","suffix":""},{"id":510331752,"identity":"db385cd5-b363-48cc-ac33-67cc88b39bb0","order_by":1,"name":"Tanusha Sewchuran","email":"","orcid":"","institution":"University of KwaZulu-Natal","correspondingAuthor":false,"prefix":"","firstName":"Tanusha","middleName":"","lastName":"Sewchuran","suffix":""}],"badges":[],"createdAt":"2025-08-26 19:53:18","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7465890/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7465890/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s43055-025-01648-1","type":"published","date":"2025-12-03T15:58:03+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":90882003,"identity":"69331756-3791-4f43-ba78-a20917303d39","added_by":"auto","created_at":"2025-09-09 09:51:33","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":775834,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7465890/v1/ddff677da6059bed00dbc51d.png"},{"id":90882008,"identity":"dc476475-1702-4cbc-9590-5174f17c8dc0","added_by":"auto","created_at":"2025-09-09 09:51:33","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":304641,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-7465890/v1/3d6334d2cd67b3b3ced8b0f6.png"},{"id":90885487,"identity":"7fc54208-ffef-4a05-9da2-cbf056a1269f","added_by":"auto","created_at":"2025-09-09 10:07:33","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":523669,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-7465890/v1/2524f43438585374be548b0b.png"},{"id":90884189,"identity":"8ade741c-6c6e-46d0-a0ab-04c1678c92b8","added_by":"auto","created_at":"2025-09-09 09:59:33","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":516288,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-7465890/v1/bb435c9a03f960f0d68d14e7.png"},{"id":90886831,"identity":"b8685c58-01a9-4859-bb60-ed5fc20143df","added_by":"auto","created_at":"2025-09-09 10:15:33","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":363671,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-7465890/v1/5e88f1d908d741f564672d68.png"},{"id":90882015,"identity":"c9d42f9e-dca6-4f07-a8bb-52778c7fc768","added_by":"auto","created_at":"2025-09-09 09:51:33","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":519821,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend\u003c/p\u003e","description":"","filename":"6.png","url":"https://assets-eu.researchsquare.com/files/rs-7465890/v1/95d5b6bb0687b75fb2939722.png"},{"id":90886833,"identity":"d8813633-78f7-410b-8f3b-ef7ee1754f24","added_by":"auto","created_at":"2025-09-09 10:15:34","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":419872,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend\u003c/p\u003e","description":"","filename":"7.png","url":"https://assets-eu.researchsquare.com/files/rs-7465890/v1/f4fe2acc86b60a5eb7cc3d69.png"},{"id":90882026,"identity":"6fff17f5-32e2-4325-8dee-670c46f401fc","added_by":"auto","created_at":"2025-09-09 09:51:34","extension":"png","order_by":8,"title":"Figure 8","display":"","copyAsset":false,"role":"figure","size":397336,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend\u003c/p\u003e","description":"","filename":"8.png","url":"https://assets-eu.researchsquare.com/files/rs-7465890/v1/bfd5e604ba4dd0b223f07a1b.png"},{"id":90887550,"identity":"664fec50-f2a7-431f-9b96-4436234d98da","added_by":"auto","created_at":"2025-09-09 10:23:33","extension":"png","order_by":9,"title":"Figure 9","display":"","copyAsset":false,"role":"figure","size":480860,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend\u003c/p\u003e","description":"","filename":"9.png","url":"https://assets-eu.researchsquare.com/files/rs-7465890/v1/daecb18b097166a565fa9d07.png"},{"id":90882025,"identity":"ebf3ed93-f853-48b1-bfb9-89ca9cbdd6ee","added_by":"auto","created_at":"2025-09-09 09:51:34","extension":"png","order_by":10,"title":"Figure 10","display":"","copyAsset":false,"role":"figure","size":418318,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend\u003c/p\u003e","description":"","filename":"10.png","url":"https://assets-eu.researchsquare.com/files/rs-7465890/v1/d7012a7facc73457c9211e6e.png"},{"id":90882033,"identity":"6e08f033-0985-4cd8-a7a1-8bc7a5139d0d","added_by":"auto","created_at":"2025-09-09 09:51:34","extension":"png","order_by":11,"title":"Figure 11","display":"","copyAsset":false,"role":"figure","size":488683,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend\u003c/p\u003e","description":"","filename":"11.png","url":"https://assets-eu.researchsquare.com/files/rs-7465890/v1/b3411255c384a05e395bf933.png"},{"id":90882023,"identity":"68d57449-77d2-4822-9231-70033d7806c8","added_by":"auto","created_at":"2025-09-09 09:51:34","extension":"png","order_by":12,"title":"Figure 12","display":"","copyAsset":false,"role":"figure","size":516154,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend\u003c/p\u003e","description":"","filename":"12.png","url":"https://assets-eu.researchsquare.com/files/rs-7465890/v1/972478b7147140d12f3d1093.png"},{"id":90884191,"identity":"d05fdb1a-a79c-4aad-a23f-df127d9b0e5e","added_by":"auto","created_at":"2025-09-09 09:59:34","extension":"png","order_by":13,"title":"Figure 13","display":"","copyAsset":false,"role":"figure","size":721483,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend\u003c/p\u003e","description":"","filename":"13.png","url":"https://assets-eu.researchsquare.com/files/rs-7465890/v1/8372b4e5f555531e5a291540.png"},{"id":97723921,"identity":"632e725a-e88a-44bb-98aa-e42c1026e3c8","added_by":"auto","created_at":"2025-12-08 16:09:47","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":10542857,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7465890/v1/94da6200-fca9-4a22-b1da-290e7bbee3f1.pdf"},{"id":90882001,"identity":"c88f2395-3561-423a-8225-386d0c4f8328","added_by":"auto","created_at":"2025-09-09 09:51:33","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":301896,"visible":true,"origin":"","legend":"","description":"","filename":"AppendixA.docx","url":"https://assets-eu.researchsquare.com/files/rs-7465890/v1/cd4ed14cabace957875f5419.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Diagnostic performance of the ACR TI-RADS classification in identifying and excluding thyroid malignancy: A multi-correlative retrospective study in a South African tertiary hospital","fulltext":[{"header":"BACKGROUND","content":"\u003cp\u003eThe evaluation of thyroid nodules is imperative to exclude thyroid malignancy. A system, the ACR TI-RADS ultrasound classification, has been developed to classify thyroid nodules according to malignancy risk, based on several imaging characteristics. This has assisted in risk stratification of thyroid nodules, thereby significantly reducing the number of invasive confirmatory tests performed. Many studies have been conducted globally in both developing and developed countries, correlating the use of the ACR TI-RADS ultrasound classification to assist in differentiating benign from malignant thyroid nodules, thereby guiding further management.\u003c/p\u003e\u003cp\u003eA thyroid nodule is defined by the American Thyroid Association as \u0026ldquo;discrete lesions within the thyroid gland, radiologically distinct from surrounding thyroid parenchyma\u0026rdquo; (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). Nodular thyroid disease is common globally, with the incidence rising dramatically over the past few decades due to higher detection rates from increased use of thyroid ultrasonography (\u003cspan additionalcitationids=\"CR3 CR4\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). The global prevalence of thyroid nodules ranges from 4\u0026ndash;7% by palpation, 19\u0026ndash;68% by ultrasound, and 8\u0026ndash;65% at autopsy by pathologic examination (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). The majority of thyroid nodules are asymptomatic and discovered incidentally during imaging investigations, such as ultrasound, computed tomography, magnetic resonance imaging, and 18F-fluorodeoxyglucose positron emission tomography for other conditions, and are termed thyroid incidentalomas (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). A study performed by Moifo \u003cem\u003eet al.\u003c/em\u003e (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e) demonstrated a prevalence of thyroid incidentalomas of 28.3% at a hospital in Yaounde, Cameroon, in sub-Saharan Africa. There is a greater prevalence of thyroid nodules in areas with iodine deficiency, among females, and in individuals exposed to neck irradiation (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eThyroid nodules are classified as either benign or malignant (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). The principal goal in the clinical evaluation of thyroid nodules is to identify potentially malignant nodules (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan additionalcitationids=\"CR11\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). Benign thyroid nodule disorders include adenoma, multinodular goitres, localized thyroiditis, including autoimmune disease, and cysts (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). Globally, thyroid cancer accounts for 1\u0026ndash;2% of all malignancies. In a surgical series in Africa, thyroid cancer was the most common endocrine malignancy with a prevalence ranging from 7.3\u0026ndash;15% (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eThe diagnostic assessment of a thyroid nodule includes a detailed history, physical examination, laboratory studies, thyroid ultrasonography, thyroid scintigraphy, fine needle aspirate cytology (FNAC) of the nodule, and/or biopsy of the nodule for histopathology (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eA thorough history taking and physical examination includes assessing for signs and symptoms of hyperthyroidism and compression such as dysphagia, dysphonia, and Horner syndrome (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). Assessment of concomitant risk factors associated with an increased risk of malignancy includes male sex, age below 20 years or above 60 years, prior neck irradiation, and a family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2 (MEN2) (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). Features associated with an increased risk of malignancy include thyroid nodules with a firm and hard consistency, rapid growth of the nodule, and the presence of suspicious, enlarged cervical lymph nodes (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eThyroid function tests, including serum thyrotropin (TSH) level, total or free thyroxine (T4), and total triiodothyronine (T3), are useful for establishing the functional status of a thyroid nodule (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eHigh-resolution thyroid ultrasonography is the primary imaging modality of choice for screening and detecting thyroid nodules (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). The advantages of thyroid ultrasound include its cost-effectiveness, non-invasiveness, favourable safety profile with no radiation or radioisotopes involved, and superior spatial resolution compared to computed tomography, magnetic resonance imaging, and thyroid scintigraphy (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). The main limitation is the poor reproducibility of ultrasound, due to inter- and intra-operator variability, as well as the utilization of equipment with different settings and performance. In our setting, this is further compounded by the lack of a standardized thyroid ultrasound report (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e), to unify reporting capabilities.\u003c/p\u003e\u003cp\u003eThe aim of thyroid ultrasonography is to differentiate benign nodules that can be managed conservatively from malignant thyroid nodules requiring further workup and management (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). Horvath \u003cem\u003eet al.\u003c/em\u003e (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e) proposed the Thyroid Image Reporting and Data Systems (TIRADS) in 2009, a classification system that correlates sonographic features with cytological classification. The foundation of the TIRADS classification is based on the American College of Radiology (ACR) Breast Imaging Reporting and Data System (BI-RADS) (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). The TIRADS classification assigns levels of malignancy risk to specific ultrasound features, which allows for a streamlined selection of thyroid nodules designated to undergo FNAC (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). This risk stratification system aims to prevent unnecessary invasive procedures and facilitates effective communication between radiologists and endocrinologists worldwide (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). Numerous risk stratification systems for assessing thyroid nodules have been developed, including the ACR-TIRADS by the American College of Radiology, EU-TIRADS by the European Thyroid Association, K-TIRADS by the Korean Society of Thyroid Radiology, and Chinese-TIRADS by the Chinese professional society (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). The ACR-TIRADS demonstrated the best sensitivity (96.9%) and lowest specificity (52.9%) in a study conducted by Xu \u003cem\u003eet al.\u003c/em\u003e (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eUltrasound-guided fine needle aspiration cytology is the diagnostic tool of choice for detecting malignancy in thyroid nodules, as cytology results determine treatment protocols (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). FNAC is a cost-effective and safe procedure that shows \u0026ldquo;superior diagnostic reliability over thyroid ultrasound and scintigraphy\u0026rdquo; (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eNon-diagnostic results, which occur in up to 29% of ultrasound-guided fine-needle aspiration cytology specimens, are a known limitation of this technique (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). This can be due to various factors such as thyroid nodule size, vascularity, and consistency, as well as operator experience and the cytopathologist\u0026rsquo;s threshold of adequacy (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). Improved diagnostic yield and accuracy of cytology were noted when FNAC was performed under ultrasound guidance (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Supervised training and rapid on-site evaluation (ROSE) of the cytologic aspirate to determine its adequacy has improved specimen yields by 83\u0026ndash;92% and reduced the rate of non-diagnostic specimens by 44% (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eCore needle biopsy (CNB), with corresponding histology, is increasingly being used in the evaluation of thyroid nodules, particularly after a non-diagnostic or indeterminate result from fine-needle aspiration (FNA) cytology. CNB offers several advantages, including significantly lower rates of non-diagnostic (5.5%) and inconclusive results (8%), compared to FNA cytology, which reports rates of 22.6% and 40.2%, respectively. Technological advancements, such as the use of higher-gauge automated biopsy devices and ultrasound guidance, have further improved the accuracy of CNB. These innovations have led to reduced false-negative rates (1\u0026ndash;3%) and a low complication rate ranging from 0\u0026ndash;4.1% (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eAlthough FNAC remains the globally recognized first-line procedure for evaluating incidental thyroid nodules, its use is particularly challenging in low-resource settings, such as our own. Many patients rely on public or hospital transport, often traveling long distances to tertiary centres at significant personal cost. Additionally, FNAC can yield non-diagnostic or indeterminate results, necessitating repeat FNAC or confirmatory CNB. This creates logistical barriers, and many patients are lost to follow-up, leaving potential thyroid malignancies undiagnosed until they present at more advanced stages. In contrast, CNB offers a higher likelihood of a definitive diagnosis at initial presentation, with a favourable safety profile, making it the preferred first-line diagnostic tool in developing countries for evaluating suspicious thyroid nodules.\u003c/p\u003e\u003cp\u003eThe aim of this study was to retrospectively assess the diagnostic accuracy of the reported ACR TI-RADS classification in identifying and excluding malignant thyroid lesions using histology as the gold standard of reference, with further secondary correlation with cytology, biochemistry, and nuclear medicine studies where available, at our local setting in Grey\u0026rsquo;s Hospital, Pietermaritzburg. This study will further add to the pre-existing body of knowledge, documenting the current scope of practice and its efficacy at Grey\u0026rsquo;s Hospital, a teaching hospital in Pietermaritzburg, South Africa, in assessing the sensitivity (identifying malignant lesions) and specificity (excluding malignant lesions/confirmed benign lesions) of the ACR TI-RADS scoring system utilized in practice.\u003c/p\u003e"},{"header":"MATERIALS AND METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStudy setting, design, and participants\u003c/h2\u003e\u003cp\u003eThis retrospective, descriptive audit was conducted in the Radiology department at Grey\u0026rsquo;s Hospital, a tertiary-level hospital in Pietermaritzburg, KwaZulu-Natal, South Africa. Adult patients above 18 years of age who had an ultrasound evaluation of the thyroid gland, with an ACR TI-RADS score documented, and had subsequent histology results available from either an ultrasound-guided core needle biopsy of a thyroid nodule and/or partial/complete thyroidectomy between January 2020 and May 2024 were included in the study. Additional data, including thyroid biochemistry, cytology, and nuclear medicine imaging, were evaluated, where available. Excluded patients had an incomplete or missing ultrasound report.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eUltrasound assessment\u003c/h3\u003e\n\u003cp\u003eThyroid ultrasound examinations were performed using an Aloka Prosound Alpha 7 and a Canon Aplio 500 ultrasound machine, both equipped with high-frequency linear array transducers ranging from 4 to 13 MHz and 5 to 14 MHz, respectively. Ultrasound images were acquired and interpreted by experienced sonographers as well as registrars or medical officers in training. Thyroid nodules were assessed and classified according to the ACR TI-RADS scoring system. The ACR-TIRADS classifies ultrasound features into five categories: Composition, echogenicity, shape, margin, and echogenic foci (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). The total points determine the thyroid nodule\u0026rsquo;s risk level, which ranges from TI-RADS 1 (TR1) (Benign) to TI-RADS 5 (TR5) (Highly suspicious) (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). ACR TI-RADS 1 refers to a benign thyroid nodule, ACR TI-RADS 2 refers to a not suspicious thyroid nodule (0% malignancy risk), ACR TI-RADS 3 refers to a mildly suspicious thyroid nodule (\u0026lt;\u0026thinsp;5% malignancy risk), ACR TI-RADS 4 refers to a moderately suspicious thyroid nodule (5\u0026ndash;80% malignancy risk) and ACR TI-RADS 5 refers to a highly suspicious thyroid nodule (\u0026gt;\u0026thinsp;80% malignancy risk) (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). While individual ultrasound features required for ACR TI-RADS classification were not consistently documented, all reports included a final ACR TI-RADS score for each thyroid nodule. The most suspicious thyroid nodule in each location (isthmus, right, and left thyroid lobes), with the highest ACR TI-RADS category, was documented in the final assessment.\u003c/p\u003e\n\u003ch3\u003eHistologic and cytologic examination\u003c/h3\u003e\n\u003cp\u003eACR TI-RADS 3,4, or 5 thyroid nodules are managed with either an ultrasound-guided core needle biopsy, ultrasound-guided FNAC, or ultrasound surveillance, depending on their size (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eDemographic details of patients undergoing a partial/complete thyroidectomy and/or ultrasound-guided core needle biopsy of a thyroid nodule were collected retrospectively from theatre and interventional radiology suite records. Histology results were then traced on the National Health Laboratory Service (NHLS) TrakCare website and were classified as benign or malignant. In each patient undergoing an ultrasound-guided core needle biopsy, the most suspicious thyroid nodule, with the highest ACR TI-RADS category, was targeted for sampling.\u003c/p\u003e\u003cp\u003eA subgroup of patients in our study cohort underwent concurrent ultrasound-guided fine needle aspiration cytology (FNAC) of their thyroid nodules. These results were collected retrospectively from the interventional radiology suite records. A universal standardized reporting format was developed in 2007 in Maryland, USA, in the form of the Bethesda System for Reporting Thyroid Cytopathology (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). This system classifies the cytology results into six diagnostic categories, which stratify the associated malignancy risk: 1. Non-diagnostic or unsatisfactory (1\u0026ndash;4%), 2. Benign (0\u0026ndash;3%), 3. Atypia of undetermined significance (AUS) or follicular lesion of undetermined significance (FLUS) (5\u0026ndash;15%), 4. Follicular neoplasm or suspicious for a follicular neoplasm (15\u0026ndash;30%), 5. Suspicious for malignancy (60\u0026ndash;75%), 6. Malignant (97\u0026ndash;99%) (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e\n\u003ch3\u003eData collection\u003c/h3\u003e\n\u003cp\u003eDemographic data and thyroid ultrasound reports were obtained from the hospital's Carestream picture archiving and communication system (PACS). Thyroid biochemical tests, histology, and cytology were collected from the patients\u0026rsquo; NHLS records. Thyroid function biochemistry was recorded as euthyroidism, hyperthyroidism, or hypothyroidism. Thyroid scintigraphy reports were obtained from patients\u0026rsquo; hospital files and categorized as normal, increased, or decreased uptake. Thyroid scintigraphy is a form of radioisotope scanning which determines whether a thyroid nodule is normal functioning (warm nodule) which accounts for 10\u0026ndash;15% of thyroid nodules, non-functioning (cold nodule) which accounts for 80\u0026ndash;85% of thyroid nodules or hyperfunctioning (hot nodule) which accounts for 5% of thyroid nodules (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). After data collection, the data was anonymised and captured on a Microsoft Excel spreadsheet.\u003c/p\u003e\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\u003ch2\u003eStatistical analysis\u003c/h2\u003e\u003cp\u003eThe data was analysed using IBM SPSS version 30. Descriptive statistics present the patients' demographic and clinical profiles in terms of frequencies and percentages (categorical variables) and means with standard deviations (numeric variables). Associations between ACR TI-RADS categories and histology results were examined using the Pearson chi-square test and Fisher\u0026rsquo;s exact test. The diagnostic sensitivity, specificity, positive predictive value, and negative predictive value of the ACR TI-RADS scoring method were calculated using a 2 \u0026times; 2 cross tabulation, where the histology results served as the gold standard. A receiver-operating characteristic (ROC) curve plot provided visualisation of the ACR TI-RADS scoring method\u0026rsquo;s benign and malignant lesion classification accuracy. A p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 indicated statistical significance.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003eEthical considerations\u003c/h2\u003e\u003cp\u003eEthical approval was obtained from the Biomedical Research Ethics Committee of the University of KwaZulu-Natal (BREC/00007428/2024). Hospital site approval was obtained from the medical manager and chief executive officer of Grey\u0026rsquo;s Hospital. Informed consent was waived due to the retrospective nature of the study.\u003c/p\u003e\u003c/p\u003e\u003c/div\u003e"},{"header":"RESULTS","content":"\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e\u003ch2\u003ePatient demographics and histology findings\u003c/h2\u003e\u003cp\u003eIn the final study population of 68 patients, 59 (86.8%) were female and 9 (13.2%) were male, with ages ranging from 27 to 82 years, and a mean age of 52.6 years.\u003c/p\u003e\u003cp\u003e57 patients (83.8%) had benign thyroid nodules and 11 patients (16.2%) had malignant thyroid nodules.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003eCorrelation of histology with demographics\u003c/h2\u003e\u003cp\u003eThere were no statistically significant differences in sex or age between the histological benign group (mean age\u0026thinsp;=\u0026thinsp;51.9 years, standard deviation\u0026thinsp;=\u0026thinsp;14.1 years) and the histological malignant group (mean age\u0026thinsp;=\u0026thinsp;56.4 years, standard deviation\u0026thinsp;=\u0026thinsp;13.0 years), p\u0026thinsp;=\u0026thinsp;0.338 for age and p\u0026thinsp;=\u0026thinsp;0.631 for sex.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003eCorrelation of ACR TI-RADS score on ultrasound with histopathology\u003c/h2\u003e\u003cp\u003eOf the 68 patients, 2 patients (2.9%), 7 patients (10.3%), 17 patients (25%), 32 patients (47.1%) and 10 patients (14.7%) had thyroid nodules classified as ACR TI-RADS 1 (Benign), 2 (Not suspicious), 3 (Mildly suspicious), 4 (Moderately suspicious) and 5 (Highly suspicious) respectively.\u003c/p\u003e\u003cp\u003eIn ACR TI-RADS 1 (Benign), 2 patients had histologically confirmed benign thyroid nodules. There were no patients with malignant thyroid nodules.\u003c/p\u003e\u003cp\u003eIn ACR TI-RADS 2 (Not suspicious), 6 out of 7 patients had histologically confirmed benign thyroid nodules, whilst 1 out of 7 patients had a histologically confirmed malignant thyroid nodule.\u003c/p\u003e\u003cp\u003eIn ACR TI-RADS 3 (Mildly suspicious), 14 out of 17 patients had histologically confirmed benign thyroid nodules, whilst 3 out of 17 patients had histologically confirmed malignant thyroid nodules.\u003c/p\u003e\u003cp\u003eIn ACR TI-RADS 4 (Moderately suspicious), 26 out of 32 patients had histologically confirmed benign thyroid nodules, whilst 6 out of 32 patients had histologically confirmed malignant thyroid nodules.\u003c/p\u003e\u003cp\u003eIn ACR TI-RADS 5 (Highly suspicious), 9 out of 10 patients had histologically confirmed benign thyroid nodules, whilst 1 out of 10 patients had a histologically confirmed malignant thyroid nodule.\u003c/p\u003e\u003cp\u003eNo statistical significance is demonstrated between histology status (benign or malignant) and the ACR TI-RADS score. A marked discrepancy is noted when correlating the ACR TI-RADS category with the histology results.\u003c/p\u003e\u003cp\u003eFor ease of analysis and to perform statistical tests of diagnostic accuracy, ACR TI-RADS 1, 2, and 3 were combined to approximate benign results, and ACR TI-RADS 4 and 5 were combined to approximate malignant results. The level of agreement between the Thyroid Ultrasound Results (ACR TI-RADS score) and the histology results was then computed in a 2x2 cross-tabulation in which the histology results were treated as the gold standard. The results show that the Thyroid Ultrasound Results (ACR TI-RADS) scoring method had a sensitivity of 63.6% (95% confidence interval (CI): 30.8% \u0026minus;\u0026thinsp;89.1%), a specificity of 38.6% (95% CI: 26.0% \u0026minus;\u0026thinsp;52.4%), a positive predictive value of 16.7% (95% CI: 10.9% \u0026minus;\u0026thinsp;24.6%), and a negative predictive value of 84.6% (95% CI: 70.3% \u0026minus;\u0026thinsp;92.8%). ROC curve analysis on the same data yields an area under the curve (AUC) value of 0.51 (95% CI: 0.39\u0026ndash;0.63), indicating that the ACR TI-RADS scoring method failed to discriminate between benign and malignant lesions in our setting when histology results are used as the gold standard.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\u003ch2\u003eCorrelation of specific ultrasound features of the ACR TI-RADS score with histopathology\u003c/h2\u003e\u003cdiv id=\"Sec14\" class=\"Section3\"\u003e\u003ch2\u003eCOMPOSITION\u003c/h2\u003e\u003cp\u003eOf the 68 patients, 60 had their thyroid nodule composition documented on ultrasound, with the majority having mixed solid-cystic thyroid nodules (38.3%), followed by solid (36.7%), spongiform (16.7%), and cystic (8.3%) thyroid nodules.\u003c/p\u003e\u003cp\u003eIn the malignant histology group, the majority of thyroid nodules (5 out of 10 nodules) demonstrated a mixed solid-cystic composition (50%).\u003c/p\u003e\u003cp\u003eIn the benign histology group, the majority of thyroid nodules (20 out of 50 nodules each) demonstrated a solid composition (40%).\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv id=\"Sec15\" class=\"Section2\"\u003e\u003ch2\u003eECHOGENICITY\u003c/h2\u003e\u003cp\u003eOf the 68 patients, 46 had thyroid nodule echogenicity documented on ultrasound, with the majority being hypoechoic (54.3%), followed by hyper- or isoechoic (39.1%), and anechoic (6.5%).\u003c/p\u003e\u003cp\u003eIn the malignant histology group, there were no anechoic thyroid nodules; instead, hyper- or isoechoic and hypoechoic nodules (3 out of 6 nodules each) contributed 50% each.\u003c/p\u003e\u003cp\u003eIn the benign histology group, the majority of thyroid nodules (22 out of 40 nodules) demonstrated hypoechogenicity (55%).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec16\" class=\"Section2\"\u003e\u003ch2\u003eSHAPE\u003c/h2\u003e\u003cp\u003eOf the 68 patients, 38 had their thyroid nodule shape documented on ultrasound, with 73.7% of thyroid nodules exhibiting a wider-than-tall shape and 26.3% demonstrating a taller-than-wide shape.\u003c/p\u003e\u003cp\u003eIn the malignant histology group, the majority of thyroid nodules (7 out of 8 nodules) demonstrated a wider-than-tall shape (87.5%).\u003c/p\u003e\u003cp\u003eIn the benign histology group, the majority of thyroid nodules (20 out of 30 nodules) demonstrated a wider-than-tall shape as well (70%).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec17\" class=\"Section2\"\u003e\u003ch2\u003eMARGIN\u003c/h2\u003e\u003cp\u003eOf the 68 patients, 42 had thyroid nodule margins documented on ultrasound, with the majority having thyroid nodules with smooth margins (52.4%), followed by those with lobulated or irregular margins (16.7%), ill-defined margins (16.7%), and extra-thyroidal extension (14.3%).\u003c/p\u003e\u003cp\u003eIn the malignant histology group, the majority of thyroid nodules (7 out of 9 nodules) had a smooth margin (77.8%).\u003c/p\u003e\u003cp\u003eIn the benign histology group, the majority of thyroid nodules (15 out of 33 nodules) had a smooth margin as well (45.5%).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec18\" class=\"Section2\"\u003e\u003ch2\u003eECHOGENIC FOCI\u003c/h2\u003e\u003cp\u003eOf the 68 patients, 44 had thyroid nodule echogenic foci documented on ultrasound, with the majority of thyroid nodules containing no echogenic foci (59.1%), followed by thyroid nodules containing punctate echogenic foci (29.5%), peripheral (rim) calcifications (9.1%), and macrocalcifications (2.3%).\u003c/p\u003e\u003cp\u003eIn the malignant histology group, the majority of thyroid nodules (5 out of 8 nodules) had no echogenic foci (62.5%).\u003c/p\u003e\u003cp\u003eIn the benign histology group, the majority of thyroid nodules (21 out of 36 nodules) also had no echogenic foci (58.3%).\u003c/p\u003e\u003cp\u003eNo statistical significance is demonstrated between histology status (benign or malignant) and each of the specific ultrasound features of the ACR TI-RADS score.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec19\" class=\"Section2\"\u003e\u003ch2\u003eCorrelation of intralesional vascularity on ultrasound with histopathology\u003c/h2\u003e\u003cp\u003eOf the 68 thyroid nodules, 24 nodules demonstrated the presence of intralesional vascularity on ultrasound (35.3%).\u003c/p\u003e\u003cp\u003eOf the 11 patients with histologically confirmed malignant thyroid nodules, 7 (63.6%) demonstrated intralesional vascularity on ultrasound, while 4 (36.4%) did not.\u003c/p\u003e\u003cp\u003eAmong patients with benign thyroid nodules, intralesional vascularity was absent in 39 cases (69.7%) and present in 17 cases (30.3%), as documented on ultrasound.\u003c/p\u003e\u003cp\u003eThe prevalence of intralesional vascularity in malignant lesions was significantly higher compared to those without intralesional vascularity, p\u0026thinsp;=\u0026thinsp;0.046.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec20\" class=\"Section2\"\u003e\u003ch2\u003eCorrelation of histology with cytology\u003c/h2\u003e\u003cp\u003eOut of the 68 patients, 22 had available cytology results. Initial FNAC was performed, followed by histology results from core needle biopsy (CNB) or partial thyroidectomy, most likely due to initial cytology being non-diagnostic and/or discrepant with the sonographic findings.\u003c/p\u003e\u003cp\u003e13 patients (59.1%) had non-diagnostic/Bethesda Diagnostic Category I thyroid nodules, 8 patients (36.4%) had benign/Bethesda Diagnostic Category II thyroid nodules, and 1 patient (4.5%) had a suspicious for malignancy/Bethesda Diagnostic Category V thyroid nodule.\u003c/p\u003e\u003cp\u003e13 of the 22 patients (59%) had non-diagnostic cytology (Bethesda Diagnostic Category I), which corresponded to histologically confirmed benign thyroid nodules.\u003c/p\u003e\u003cp\u003e6 of the 22 patients (27%) had benign cytology (Bethesda Diagnostic Category II), which corresponded to histologically confirmed benign thyroid nodules.\u003c/p\u003e\u003cp\u003e2 of the 22 patients (9.1%) had benign cytology (Bethesda Diagnostic Category II)\u003c/p\u003e\u003cp\u003ewhich corresponded to histologically confirmed malignant thyroid nodules.\u003c/p\u003e\u003cp\u003e1 of the 22 patients (4.5%) had suspicious for malignancy cytology (Bethesda Diagnostic Category V), which corresponded to a histologically confirmed malignant thyroid nodule, resulting in statistical significance (p\u0026thinsp;=\u0026thinsp;0.010).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec21\" class=\"Section2\"\u003e\u003ch2\u003eCorrelation of thyroid function tests and histopathology\u003c/h2\u003e\u003cp\u003e6 out of the 11 patients (54.5%) with histologically proven malignant thyroid nodules had a thyroid function test demonstrating subclinical hypothyroidism, followed by 4 patients (36.3%) having euthyroidism and 1 patient (9.1%) having hypothyroidism.\u003c/p\u003e\u003cp\u003eIn contrast, the majority of patients with histologically proven benign thyroid nodules, 37 out of 57 patients (64.9%), had a thyroid function test demonstrating euthyroidism, subclinical hypothyroidism was found in 11 patients (19.3%), subclinical hyperthyroidism in 5 patients (8.8%), hyperthyroidism in 3 patients (5.3%) and hypothyroidism in 1 patient (1.8%).\u003c/p\u003e\u003cp\u003eNo statistical significance is demonstrated between histology (benign or malignant) and serum thyroid function test results, p\u0026thinsp;=\u0026thinsp;0.060\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec22\" class=\"Section2\"\u003e\u003ch2\u003eCorrelation of thyroid scintigraphy and histopathology\u003c/h2\u003e\u003cp\u003eOf the 68 patients, a small subgroup of 6 patients had nuclear medicine thyroid scintigraphy results available. 1 patient (16.7%) had normal uptake, and 5 patients (83.3%) demonstrated increased uptake.\u003c/p\u003e\u003cp\u003eIncreased uptake was seen in 3 patients with histologically confirmed benign thyroid nodules and 2 patients with histologically confirmed malignant thyroid nodules. Normal uptake was seen in 1 patient with a histologically confirmed malignant thyroid nodule.\u003c/p\u003e\u003cp\u003eNo statistical significance is demonstrated between histology status (benign or malignant) and thyroid scintigraphy results (p\u0026thinsp;=\u0026thinsp;1.000).\u003c/p\u003e\u003c/div\u003e"},{"header":"DISCUSSION","content":"\u003cdiv id=\"Sec24\" class=\"Section2\"\u003e\u003ch2\u003eDemographic Profile\u003c/h2\u003e\u003cp\u003eIn this study, the majority of the cohort with thyroid nodular disease and histologically proven malignant thyroid nodules were female (86.8% and 81.8% respectively). The mean ages were 51.9 years and 56.4 years in the benign and malignant thyroid nodule groups, respectively. No statistically significant differences were demonstrated in age or sex between the benign and malignant groups. This was in keeping with global and local literature. A meta-analysis comprising 52 studies revealed an increased prevalence of thyroid nodular disease in females and in patients over 40 years old. A study by Chagi \u003cem\u003eet al.\u003c/em\u003e (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e) conducted in a tertiary South African hospital demonstrated an increased incidence of thyroid carcinoma in patients between 20 and 55 years of age. The higher incidence of thyroid nodules in females, which is four times greater than in males, can be explained by the hormonal influence of progesterone and oestrogen, as the development of new nodules and the increase in size of pre-existing nodules are thought to be related to pregnancy and multiparity (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e).\u003c/p\u003e\u003cdiv id=\"Sec25\" class=\"Section3\"\u003e\n \u003ch2\u003eHistopathology Profile\u003c/h2\u003e\n \u003cp\u003e\u003cspan\u003e83.8% of the study population had histologically confirmed benign thyroid nodules, which were mainly composed of multinodular goiters, followed by benign follicular adenomas and Hashimoto\u0026rsquo;s thyroiditis. This finding is not in keeping with the global prevalence of 90\u0026ndash;95% and the prevalence in Africa of 89% (\u003cspan class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e7\u003c/span\u003e). This is likely due to the small sample size of the study cohort. The large proportion of benign thyroid nodular disease is thought to be due to the increased incidence of multinodular goiters in iodine-deficient regions of developing countries, such as South Africa (\u003cspan class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e6\u003c/span\u003e,\u0026nbsp;\u003cspan class=\"CitationRef\"\u003e9\u003c/span\u003e).\u003cbr\u003e\u003c/span\u003e\u003cspan\u003e16.2% of the study cohort had histologically confirmed malignant thyroid nodules made mainly of papillary, followed by follicular thyroid carcinoma (54.5% and 45.4% respectively). This is in line with the prevalence of thyroid malignancy in the literature, which ranges from 0.9\u0026ndash;20.5% globally. A study conducted by Chagi \u003cem\u003eet al.\u003c/em\u003e(\u003cspan class=\"CitationRef\"\u003e13\u003c/span\u003e) in Johannesburg, South Africa, also demonstrated a greater prevalence of papillary thyroid cancer as the predominant thyroid carcinoma type (\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e,\u0026nbsp;\u003cspan class=\"CitationRef\"\u003e7\u003c/span\u003e).\u003cbr\u003e\u003c/span\u003e\u003c/p\u003e\n\n\u003c/div\u003e\u003cp\u003eMost CNB procedures for histology were performed on ACR TI-RADS category 4 lesions (47.1%), followed by categories 3 and 5 (25% and 14.7%, respectively), in accordance with literature on the established guidelines for lesions requiring biopsy (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec26\" class=\"Section3\"\u003e\u003ch2\u003eConcordance of ACR TI-RADS score on ultrasound with histopathology\u003c/h2\u003e\u003cp\u003eIn this study, ACR TI-RADS 1, 2, 3, 4, and 5 had malignancy risks of 0%, 14.3%, 17.6%, 18.8%, and 10%, respectively. The risk of malignancy in this study for ACR TI-RADS 1 and 4 compares to the literature, which reports 0% and 5\u0026ndash;80%, respectively. There is discordance between the malignancy risk in ACR TI-RADS 2, 3, and 5 and the literature, which reports 0%, \u0026lt;\u0026thinsp;5%, and \u0026gt;\u0026thinsp;80% (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). The high incidence of benign thyroid lesions classified under the ACR TI-RADS 4 and 5 categories, which are associated with a high likelihood of malignancy, suggests that junior staff may be over-estimating the malignancy risk of these lesions. Conversely, the presence of malignant thyroid lesions categorized as benign (ACR TI-RADS 2 and 3) indicates the under-estimation of lesion malignancy risk.\u003c/p\u003e\u003cp\u003eThese discrepancies in our setting can be attributed to the absence of standardized thyroid ultrasound reporting protocols, as well as inter-user variability resulting from the frequent rotation of inexperienced junior staff, which is typical of institutions with ongoing medical training. A study conducted by Rago \u003cem\u003eet al.\u003c/em\u003e (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e) in Pisa, Italy, demonstrated the main limitations of ultrasound, including poor reproducibility due to inter- and intra-operator variability, the use of equipment with different settings and performance, and the lack of a standardized ultrasound report. This highlights the need for further training and the development of a standardized reporting template to improve diagnostic accuracy.\u003c/p\u003e\u003cp\u003eFor the assessment of diagnostic accuracy, ACR TI-RADS 1, 2, and 3 were combined to approximate benign results, and ACR TI-RADS 4 and 5 were combined to represent malignant results. In this study, the ACR TI-RADS scoring system had a sensitivity of 63.6%, specificity of 38.6%, positive predictive value of 16.7%, negative predictive value of 84.6% and accuracy of 42.6% which is discordant with the literature, thus failing to discriminate between benign and malignant lesions when histology results are used as the gold standard. A study by Schenke \u003cem\u003eet al.\u003c/em\u003e (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e) in Germany compared three TI-RADS scoring systems for assessing small thyroid nodules and found that the ACR TI-RADS had a positive predictive value of 65%, a negative predictive value of 100%, and an accuracy of 71.7%. Several risk stratification systems have been developed to assess thyroid nodules, with the ACR-TIRADS showing the highest sensitivity (96.9%) but the lowest specificity (52.9%) (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec27\" class=\"Section3\"\u003e\u003ch2\u003eCorrelation of specific ultrasound features of the ACR TI-RADS score with histopathology\u003c/h2\u003e\u003cp\u003eThe most common individual ultrasound features exhibited in malignant thyroid nodules in this study were a mixed solid-cystic composition, hyper- or isoechoic and hypoechoic echogenicity, a wider-than-tall shape, smooth margins, and no echogenic foci.\u003c/p\u003e\u003cp\u003eThe most common individual ultrasound features exhibited in benign thyroid nodules were solid composition, hypoechoic echogenicity, a wider-than-tall shape, smooth margins, and no echogenic foci.\u003c/p\u003e\u003cp\u003eThese findings are discordant with the literature, which proposes that sonographic features suspicious for thyroid nodule malignancy include a solid component, hypoechogenicity, a taller-than-wide shape, microcalcifications, and microlobulated or irregular margins (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eThere are a few reasons to explain this in our setting: Firstly, with regard to each component of the ACR TI-RADS scoring system, only 88.2%, 67.6%, 55.9%, 61.8% and 64.7% of ultrasound reports recorded composition, echogenicity, shape, margin, and the presence of echogenic foci, respectively. This is likely due to a lack of a standardized reporting template for thyroid ultrasounds in our setting, as junior staff are reporting on only selected components of the scoring system. Thus many malignant features may be unaccounted for in the thyroid ultrasound report, further highlighting inexperience with thorough assessment of each of the ACR TI-RADS components on ultrasound. Secondly, inconsistencies in measuring a nodule may result in inaccurate values, particularly when accounting for lesion shape, specifically those that are \u0026ldquo;taller than wider\u0026rdquo;.\u003c/p\u003e\u003cp\u003eThere are also confounding factors that we need to be aware of, which can overestimate the malignancy risk of a benign thyroid nodule, resulting in a higher ACR TI-RADS classification. Chen \u003cem\u003eet al.\u003c/em\u003e (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e) found that 9.4% of histologically confirmed benign thyroid nodules were misdiagnosed as suspicious ACR TI-RADS 4\u0026ndash;5 lesions based on solid composition (98%), hypoechogenicity (89.4%) and punctate echogenic foci (42.7%) due to features of fibrosis and calcification associated with follicular epithelial hyperplasia, thyroid adenoma and nodular goitres. This study also found that benign thyroid nodules can have a taller-than-wide shape due to the nodule being pulled up and down during the fibrosis and degenerative stages, which could explain why 30% of benign thyroid lesions in our setting demonstrated a taller-than-wide shape, a characteristic more commonly associated with malignancy. A contradictory study conducted in Germany by Schenke \u003cem\u003eet al.\u003c/em\u003e (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e) found that the majority of malignant thyroid nodules (55%) displayed a wider-than-tall shape, in keeping with the majority shape of malignant thyroid nodules in our study.\u003c/p\u003e\u003cp\u003eMost ACR TI-RADS individual ultrasound features have low sensitivities on their own, apart from hypoechogenicity (87.2% sensitivity) (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). A taller-than-wide shape has a 93% specificity for diagnosing malignancy, with a spiculated margin, marked hypoechogenicity, and microcalcifications, which are further features highly suggestive of malignancy, with specificities of 92%, 92\u0026ndash;94%, and 86\u0026ndash;95%, respectively (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). No single ultrasound feature can be used to differentiate between benign and malignant thyroid nodules in isolation (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). A meta-analysis by Remonti \u003cem\u003eet al.\u003c/em\u003e (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e) reported that combining suspicious ultrasound features enhanced the accuracy in predicting the likelihood and potential for malignant disease.\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv id=\"Sec28\" class=\"Section2\"\u003e\u003ch2\u003eCorrelation of intralesional vascularity on ultrasound with histopathology\u003c/h2\u003e\u003cp\u003e63.6% of the study cohort with histologically confirmed malignant thyroid nodules demonstrated intralesional vascularity on ultrasound, with a sensitivity of 63.64% and specificity of 69.64%, aligning with the available literature. The prevalence of malignant lesions was significantly higher among patients with documented intralesional vascularity compared to those without, with a statistical significance of p\u0026thinsp;=\u0026thinsp;0.046.\u003c/p\u003e\u003cp\u003eA review by Rago \u003cem\u003eet al.\u003c/em\u003e (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e) reported that intranodular vascularization has good sensitivity and can be observed in 69\u0026ndash;74% of thyroid malignancies; however, it has low specificity. The study also raises concerns about misinterpreting vascularity as intra-nodal, as opposed to peri-nodal vascularity, in smaller thyroid nodules (\u0026lt;\u0026thinsp;5mm). Remonti \u003cem\u003eet al.\u003c/em\u003e (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e) conducted a meta-analysis involving 52 studies, which validated that central vascularization in a thyroid nodule was one of four individual features with good specificity (78%) but lower sensitivity (45.9%) in determining the risk of malignancy. A further meta-analysis by Khadra \u003cem\u003eet al\u003c/em\u003e. (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e) evaluated whether vascular flow served as a predictor of a malignancy in thyroid nodules and found that the majority of malignant thyroid nodules had internal and peripheral vascular flow (50% and 17% respectively), however, no difference in the intralesional vascularity was found between benign and malignant thyroid nodules. These findings suggest that intralesional vascularity alone is not diagnostic of malignancy, but may indicate an increased risk when observed in conjunction with other suspicious sonographic features.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec29\" class=\"Section2\"\u003e\u003ch2\u003eCorrelation of cytology with histopathology\u003c/h2\u003e\u003cp\u003e22 patients in our study had cytology results available, with 13 patients (59%) having non-diagnostic results that corresponded to benign pathology on subsequent histology. There was good concordance between Bethesda Diagnostic Category II (Benign) cytology and histologically benign nodules. Furthermore, the Bethesda Diagnostic Category V (Suspicious for malignancy) cytology also corresponded to a histologically confirmed malignant thyroid nodule with a statistically significant p-value of 0.010; however, this is not an entirely representative result, with only 1 patient in this category V. Two patients with Bethesda diagnostic category II (benign) cytology had discordant malignant histology results. The sensitivity was 33.3% and the specificity was 100%, in line with the literature, which reports that FNAC has variable sensitivity (38\u0026ndash;98%) and specificity (72\u0026ndash;99%) (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e). The low sensitivity in our study is likely due to the small sample size of available cytology results. Non-diagnostic results, which occur in up to 29% of ultrasound-guided fine-needle aspiration biopsies, are a limitation of this technique (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). This can be due to various factors such as thyroid nodule size, vascularity, and consistency, as well as operator experience and the cytopathologist\u0026rsquo;s threshold of adequacy (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). Improved diagnostic yield was noted when FNAC was performed under ultrasound guidance (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Supervised training and rapid on-site evaluation (ROSE) of the aspirate, by a cytopathologist, to determine its adequacy has improved specimen yields by 83\u0026ndash;92% and reduced the rate of non-diagnostic specimens by 44%. Despite our FNAC being performed under ultrasound guidance, we unfortunately do not have ROSE available at our institution, which would possibly account for the higher non-diagnostic results rate compared to the literature.\u003c/p\u003e\u003cp\u003eThe implementation of the ACR TI-RADS classification system has proven valuable in stratifying the risk of thyroid nodules, particularly in distinguishing between benign and malignant lesions. This has important clinical implications, as it facilitates more cautious use of fine-needle aspiration cytology (FNAC), potentially reducing the number of unnecessary procedures performed on nodules with low suspicion for malignancy (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eCorrelation of thyroid function tests and histopathology\u003c/h3\u003e\n\u003cp\u003eThyroid function tests, including serum thyrotropin (TSH) level, total or free thyroxine (T4), and total triiodothyronine (T3), are useful for establishing the functional status of the thyroid nodule (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eThe majority of patients in this study (60.3%) had a thyroid function test demonstrating euthyroidism, whilst 54.5% of patients with thyroid malignancy had subclinical hypothyroidism. This aligns with the literature, which indicates that most thyroid nodules are non-functioning/euthyroid, with normal or elevated TSH levels (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). On the contrary, 14% of the study cohort with benign thyroid nodules had biochemistry consistent with subclinical and overt hyperthyroidism, again consistent with the literature, which states that 10% of solitary thyroid nodules are benign hyperfunctioning adenomas (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). There were no patients in the malignant (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) nodule category with biochemical features of hyperthyroidism, which is in accordance with the literature, as hyperfunctioning thyroid nodules are less likely to be of a malignant nature (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). Several studies have attempted to establish a link between TSH levels and their ability to predict the risk of malignancy. A study by Naidu \u003cem\u003eet al.\u003c/em\u003e (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e) conducted in Johannesburg, South Africa, found no association between TSH and the risk of thyroid malignancy. A study by Khider \u003cem\u003eet al.\u003c/em\u003e (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e) conducted in Saudi Arabia on a cohort of 222 patients demonstrated that the level of TSH increases exponentially in individuals with malignant thyroid nodules as opposed to those with mildly suspicious or benign nodules. Furthermore, this study found low levels of T3 and T4 in malignant thyroid nodules. This makes biochemistry a valuable tool in low-resource environments, in combination with sonographic findings, for safely identifying a subset of hyperthyroid/hyperfunctioning thyroid nodules that do not require biopsy or surgical intervention.\u003c/p\u003e\u003cdiv id=\"Sec31\" class=\"Section2\"\u003e\u003ch2\u003eCorrelation of thyroid scintigraphy and histopathology\u003c/h2\u003e\u003cp\u003eThyroid scintigraphy is indicated when TSH levels are low or suppressed, suggesting a diagnosis of primary hyperthyroidism (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). However, in our study, only a subset of 6 patients with mixed biochemistry results proceeded to have thyroid uptake scans and biopsies. Three patients had subclinical and overt hyperthyroidism with histologically confirmed benign thyroid nodules, and 3 patients had subclinical hypothyroidism and euthyroidism with histologically confirmed malignant thyroid nodules, concordant with the literature that suggests hyperfunctioning/hyperthyroid nodules have a low risk of malignancy (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). Increased uptake was demonstrated in 5 patients, 2 of whom had thyroid malignancy and 1 patient with a benign nodule who was diagnosed with Graves' disease. 1 patient had a normal uptake scan and a histologically confirmed malignant thyroid nodule.\u003c/p\u003e\u003cp\u003eA study by Kant \u003cem\u003eet al.\u003c/em\u003e (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e) reported that a local increase in uptake in the thyroid nodule on thyroid scintigraphy is consistent with a hyperfunctioning or \u0026ldquo;hot\u0026rdquo; nodule. Hyperfunctioning thyroid nodules do not require FNAC as they are unlikely to be malignant. Non-functioning or \u0026ldquo;cold\u0026rdquo; thyroid nodules may have a normal or elevated TSH level and are further evaluated with FNAC if they meet clinical or ultrasound criteria (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eThere is no role for radioisotope scanning in the initial evaluation of a thyroid nodule, as its sensitivity for diagnosing malignancy ranges from 89\u0026ndash;93% with a specificity of 5% (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). There is, however, a role for thyroid scintigraphy in identifying hyperfunctioning or \u0026ldquo;hot\u0026rdquo; thyroid nodules to avoid unnecessary biopsies of these nodules (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec32\" class=\"Section2\"\u003e\u003ch2\u003eLIMITATIONS\u003c/h2\u003e\u003cp\u003eWhile this study provides valuable insights into the diagnostic accuracy of the ACR TI-RADS classification in a local resource-restricted setting, several recognized limitations exist. The small sample size and the single-centre study design limit the generalizability of the findings. Further studies with a larger multi-centre cohort would provide more varied data, allowing for more definitive conclusions. Due to the retrospective nature of the study, the accuracy of the data collected depends on good record-keeping, and missing histology records could have led to a sizable portion of the study population being excluded.\u003c/p\u003e\u003cp\u003ePatients with only thyroid nodule cytology results, with no corresponding histology, were not included in the study, as histology was recognized as the gold standard, resulting in a smaller sample size. The absence of a standardized thyroid ultrasound reporting template in our setting may have contributed to incomplete or inconsistent assessment of important characteristics, such as nodule shape, echogenicity, and margin. This could lead to underreporting of suspicious imaging features, resulting in reduced diagnostic accuracy and discrepant ACR TI-RADS classification. One of the major limitations identified in this study, in addition to the lack of a standardized ultrasound reporting protocols, was the presence of inter- and intra-operator variability. Given that the study setting included inexperienced junior staff, variability in interpreting the ultrasound features of thyroid nodules could have contributed to misclassification or over- or under-estimation of malignancy risk. The use of thyroid scintigraphy in our study was inconsistent, as it is not available on-site and was not routinely performed on all patients. The role of nuclear medicine in evaluating thyroid nodules may have provided additional insights into the functionality of the nodules and contributed to a more thorough evaluation of malignancy risk.\u003c/p\u003e\u003c/div\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eThis study offers a valuable assessment of the diagnostic accuracy of the ACR TI-RADS classification in distinguishing between benign and malignant thyroid nodules, using histology as the gold standard. The results suggest that the ACR TI-RADS scoring system, although widely used, has limitations in sensitivity and specificity in our local setting. Notably, there were marked discrepancies between the ultrasound features of certain nodules and the histopathology results, suggesting over- or under-estimation of malignancy risk. These findings underline the challenges of relying solely on ultrasound features in diagnosing thyroid cancer, particularly where inter-operator variability and inconsistent reporting are key factors. Despite these limitations, the study reinforces the importance of ongoing education and training for junior staff, as well as the development of standardized reporting templates to enhance diagnostic accuracy. Furthermore, our study emphasized the additional value of assessing sonographic intralesional vascularity in thyroid nodules, as a potential important predictor of malignancy despite controversy in the literature, and one not routinely included in ACR-TIRADS classification. The study also highlights the value of integrating ultrasound findings with cytology, biochemistry, and nuclear medicine results to achieve a more comprehensive evaluation of thyroid nodules.\u003c/p\u003e\u003cdiv id=\"Sec34\" class=\"Section2\"\u003e\u003ch2\u003eRECOMMENDATIONS\u003c/h2\u003e\u003cp\u003eOur primary recommendation is integrating the use of a standardized thyroid ultrasound reporting template into daily practice in our setting (Appendix A). This would ensure that all relevant features of the ACR TI-RADS classification system, such as nodule composition, echogenicity, shape, margin, and echogenic foci, are consistently documented, with the aim of reducing inter-operator variability, improving diagnostic accuracy, and accurately assigning an ACR TI-RADS score. Incorporating lesion vascularity is a further recommended addition to the ACR-TIRADS classification. Regular workshops and supervised in-service training sessions are crucial for enhancing the reproducibility and accuracy of ultrasound assessments. A multidisciplinary approach involving radiologists, endocrinologists, pathologists, and nuclear medicine specialists should also be encouraged to help integrate findings from various diagnostic modalities, such as ultrasound, histology, cytology, biochemistry, and scintigraphy, thereby more reliably differentiating benign from malignant lesions.\u003c/p\u003e\u003cp\u003eFuture studies targeting larger sample sizes and those involving multiple centers could help validate the diagnostic performance of ACR TI-RADS across diverse patient populations in Sub-Saharan Africa. This study found a significant proportion of non-diagnostic cytology results, which limits the ability to definitively classify nodules. To address this, future studies could explore methods to enhance cytology diagnostic yield, such as standardizing ROSE, which could improve the specimen adequacy and diagnostic accuracy. Thyroid scintigraphy should be more consistently used in patients with biochemistry suggestive of hyperthyroidism to identify \"hot\" or hyperfunctioning nodules, which are unlikely to be malignant. This could help in avoiding unnecessary invasive procedures, thereby reducing healthcare costs and patient burden. Regular audits of ultrasound reports and histology results, with feedback to clinicians, could help identify areas for improvement in thyroid nodule assessment. Audits would also provide an opportunity to refine diagnostic criteria and protocols over time, ultimately enhancing patient care and reducing morbidity and mortality.\u003c/p\u003e\u003c/div\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eACR American College of Radiology\u003c/p\u003e\n\u003cp\u003eAUC Area under the curve\u003c/p\u003e\n\u003cp\u003eAUS Atypia of undetermined significance\u003c/p\u003e\n\u003cp\u003eCI Confidence interval\u003c/p\u003e\n\u003cp\u003eCNB Core needle biopsy\u003c/p\u003e\n\u003cp\u003eFLUS Follicular lesion of undetermined significance \u003c/p\u003e\n\u003cp\u003eFNAC Fine needle aspiration cytology\u003c/p\u003e\n\u003cp\u003eNHLS National Health Laboratory Service\u003c/p\u003e\n\u003cp\u003eROC Receiver-operating characteristic\u003c/p\u003e\n\u003cp\u003eROSE Rapid on-site evaluation\u003c/p\u003e\n\u003cp\u003eT3 Total triiodothyronine\u003c/p\u003e\n\u003cp\u003eT4 Total or free thyroxine\u003c/p\u003e\n\u003cp\u003eTI-RADS Thyroid Imaging Reporting and Data System\u003c/p\u003e\n\u003cp\u003eTSH Serum thyrotropin\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cu\u003eEthics approval and consent to participate\u003c/u\u003e: Ethical approval was obtained from the Biomedical Research Ethics Committee of the University of KwaZulu-Natal (BREC/00007428/2024). Hospital site approval was obtained from the medical manager and chief executive officer of Grey\u0026rsquo;s Hospital.\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eConsent for publication\u003c/u\u003e: Informed consent was waived due to the retrospective nature of the study.\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eAvailability of data and material\u003c/u\u003e: Data sharing is not applicable to this article as no new data were created or analysed in this study.\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eCompeting interests\u003c/u\u003e: The authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eFunding\u003c/u\u003e: None.\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eAuthors\u0026rsquo; contributions\u003c/u\u003e: N.B. was responsible for the research protocol, data collection and compilation of the article. T.S. was the principal supervisor and assisted with all components. Both authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eAcknowledgements\u003c/u\u003e: We thank Mrs. Heshika Singh for her contribution to data collection. We are grateful to Mr. Promise Khumbula for statistical assistance.\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eAuthors\u0026rsquo; information\u003c/u\u003e: Mentioned above.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eHuang EYF, Kao NH, Lin SY, Jang IJH, Kiong KL, See A, et al. (2023) Concordance of the ACR TI-RADS Classification With Bethesda Scoring and Histopathology Risk Stratification of Thyroid Nodules. JAMA Netw Open 6(9):e2331612. doi:10.1001/jamanetworkopen.2023.31612\u003c/li\u003e\n\u003cli\u003eAhmad F (2020) Diagnostic accuracy of ultrasound-guided fine needle aspiration cytology of thyroid nodules at Universitas Academic Hospital, Bloemfontein. Dissertation, University of the Free State.\u003c/li\u003e\n\u003cli\u003eBhuiyan MM, Machowski A (2015) Nodular thyroid disease and thyroid malignancy: Experience at Polokwane Mankweng Hospital Complex, Limpopo Province, South Africa. S Afr Med J. 105(7):570-2.\u003c/li\u003e\n\u003cli\u003eNaidu K, Saksenberg V, Mahyoodeen NG (2023) Clinical and ultrasound characteristics distinguishing benign and malignant thyroid nodules in Johannesburg, South Africa. Journal of Endocrinology, Metabolism and Diabetes in South Africa 28(2):62-8.\u003c/li\u003e\n\u003cli\u003eNicolaou MA, Jacobs K, Bhana S, Naidu K, Nicolaou V (2019) A retrospective study correlating sonographic features of thyroid nodules with fine-needle aspiration cytology in a South African setting. SA J Radiol 23(1):1749.\u003c/li\u003e\n\u003cli\u003eConradie W, Du Plessis A, Edge J, Baatjes K, Ruiters A, Razack R (2022) Impact of a multidisciplinary approach to ultrasound-guided thyroid fine-needle aspiration biopsy at Tygerberg Hospital, Cape Town, South Africa: A retrospective audit. S Afr Med J 112(1):13521.\u003c/li\u003e\n\u003cli\u003eIsse HM, Lukande R, Sereke SG, Odubu FJ, Nassanga R, Bugeza S (2023) Correlation of the ultrasound thyroid imaging reporting and data system with cytology findings among patients in Uganda. Thyroid Res 16(1):26.\u003c/li\u003e\n\u003cli\u003eMoifo B, Moulion Tapouh JR, Dongmo Fomekong S, Djomou F, Manka\u0026apos;a Wankie E (2017) Ultrasonographic prevalence and characteristics of non-palpable thyroid incidentalomas in a hospital-based population in a sub-Saharan country. BMC Med Imaging 17(1):21.\u003c/li\u003e\n\u003cli\u003eRago T, Vitti P (2022) Risk Stratification of Thyroid Nodules: From Ultrasound Features to TIRADS. Cancers (Basel) 14(3).\u003c/li\u003e\n\u003cli\u003ePeriakaruppan G, Seshadri KG, Vignesh Krishna GM, Mandava R, Sai VPM, Rajendiran S (2018) Correlation between Ultrasound-based TIRADS and Bethesda System for Reporting Thyroid-cytopathology: 2-year Experience at a Tertiary Care Center in India. Indian J Endocrinol Metab 22(5):651-5.\u003c/li\u003e\n\u003cli\u003eBaldini E, Sorrenti S, Tartaglia F, Catania A, Palmieri A, Pironi D, et al. (2017) New perspectives in the diagnosis of thyroid follicular lesions. Int J Surg 41 Suppl 1:S7-S12.\u003c/li\u003e\n\u003cli\u003eKant R, Davis A, Verma V (2020) Thyroid Nodules: Advances in Evaluation and Management. Am Fam Physician 102(5):298-304.\u003c/li\u003e\n\u003cli\u003eChagi N, Bombil I, Mannell A (2019) The profile of thyroid cancer in patients undergoing thyroidectomy at Chris Hani Baragwanath Academic Hospital. S Afr J Surg 57(3):55.\u003c/li\u003e\n\u003cli\u003eKhider MO, Ayad C, Suliman AG, Alshoabi SA, Gameraddin M, Elzaki M, et al. (2022) Can Thyrotropin, Tri-Iodothyronine, and Thyroxine Hormones be Predictors of Cancer in Thyroid Lesions? Cureus 14(12):e32422.\u003c/li\u003e\n\u003cli\u003eClassens S (2017) Quality Assessment of Thyroid Ultrasound and Implementation of a Standard Reporting Template to Be Used in Training Hospitals. Dissertation, University of the Witwatersrand.\u003c/li\u003e\n\u003cli\u003eMatimati B (2022) Diagnostic yield of ultrasound-guided fine needle aspiration biopsy (US-guided FNAB) and post-surgical histopathological correlation of thyroid nodules in the Department of Radiology, Groote Schuur Hospital, Cape Town, South Africa over a two-year period. Dissertation, University of Cape Town.\u003c/li\u003e\n\u003cli\u003eBotha M, Kisansa M, Greeff W (2020) American College of Radiology Thyroid Imaging Reporting and Data System standardises reporting of thyroid ultrasounds. SA J Radiol 24(1):1804.\u003c/li\u003e\n\u003cli\u003eKallepalli VSD, Nelson T, Sanniyasi S (2023) Analysis of Thyroid Imaging Reporting and Data System Criteria and Its Correlation With the Pathological Results. Cureus 15(6):e40117.\u003c/li\u003e\n\u003cli\u003eKilani L (2023) Thyroidectomies at an academic hospital in Johannesburg-correlation between pre-operative cytology findings and post-operative histology results. Dissertation, University of the Witwatersrand.\u003c/li\u003e\n\u003cli\u003eJung CK, Baek JH (2017) Recent Advances in Core Needle Biopsy for Thyroid Nodules. Endocrinol Metab (Seoul) 32(4):407-12.\u003c/li\u003e\n\u003cli\u003eChetty M, Mbatha B, Fru P (2023) The association between cytology and histopathology in thyroid nodules over a 6-year period in an urban hospital in South Africa. S Afr Med J 113(8):58-62.\u003c/li\u003e\n\u003cli\u003eRemonti LR, Kramer CK, Leitao CB, Pinto LC, Gross JL (2015) Thyroid ultrasound features and risk of carcinoma: a systematic review and meta-analysis of observational studies. Thyroid 25(5):538-50.\u003c/li\u003e\n\u003cli\u003eSchenke S, Klett R, Seifert P, Kreissl MC, Gorges R, Zimny M (2020) Diagnostic Performance of Different Thyroid Imaging Reporting and Data Systems (Kwak-TIRADS, EU-TIRADS and ACR TI-RADS) for Risk Stratification of Small Thyroid Nodules (\u0026lt;/=10 mm). J Clin Med 9(1).\u003c/li\u003e\n\u003cli\u003eChen J, Ye D, Lv S, Li X, Ye F, Huang Y, et al (2024) Benign thyroid nodules classified as ACR TI-RADS 4 or 5: Imaging and histological features. Eur J Radiol 175:111261.\u003c/li\u003e\n\u003cli\u003eKhadra H, Bakeer M, Hauch A, Hu T, Kandil E (2016) Is vascular flow a predictor of malignant thyroid nodules? A meta-analysis. Gland Surg 5(6):576-82.\u003c/li\u003e\n\u003cli\u003eBukasa-Kakamba J, Bayauli P, Sabbah N, Bidingija J, Atoot A, Mbunga B, et al (2022) Ultrasound performance using the EU-TIRADS score in the diagnosis of thyroid cancer in Congolese hospitals. Sci Rep 12(1):18442.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Thyroid nodule, Thyroid malignancy, TI-RADS, Ultrasound, Histology, Core needle biopsy, Intralesional vascularity","lastPublishedDoi":"10.21203/rs.3.rs-7465890/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7465890/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cb\u003eBACKGROUND\u003c/b\u003e\u003c/p\u003e\u003cp\u003eNodular thyroid disease is becoming increasingly prevalent worldwide, with the primary aim of evaluation being to exclude malignancy. The ACR TI-RADS classification was designed to stratify the risk of malignancy in thyroid nodules based on sonographic features, thereby guiding biopsy decisions with the aim of reducing the number of unnecessary invasive procedures performed. Fine-needle aspiration cytology remains the preferred diagnostic tool for evaluating thyroid nodules due to its safety profile and cost-effectiveness. However, it can yield non-diagnostic or indeterminate results, resulting in repeat biopsies, which in resource-limited settings precipates poor patient follow-up or missed malignancy. Core needle biopsy, with histological evaluation, has become increasingly recognized as the gold standard for definitive diagnosis, reducing the need for repeat sampling. The aim of this study was to retrospectively assess the diagnostic accuracy of the reported ACR TI-RADS classification in identifying and excluding malignant thyroid lesions using histology as the gold standard of reference, with further secondary correlation with cytology, biochemistry, and nuclear medicine studies where available, at our local setting in Grey\u0026rsquo;s Hospital, Pietermaritzburg.\u003c/p\u003e\u003cp\u003e\u003cb\u003eRESULTS\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThe study group consisted of 68 patients with a mean age of 52.6 years (range, 27\u0026ndash;82 years), female predominance and a 16.2% thyroid malignancy rate. For ease of analysis, ACR TI-RADS categories 1\u0026ndash;3 were grouped as benign, and categories 4\u0026ndash;5 as malignant. Comparison of ACR TI-RADS with histology showed a sensitivity of 63.6%, specificity of 38.6%, positive predictive value of 16.7%, and negative predictive value of 84.6%. Receiver operating characteristic curve analysis showed an area under the curve of 0.51. Among the sonographic features evaluated, the presence of intralesional vascularity was significantly associated with malignancy (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05), advocating its inclusion into a modified ACR-TIRADS score.\u003c/p\u003e\u003cp\u003e\u003cb\u003eCONCLUSION\u003c/b\u003e\u003c/p\u003e\u003cp\u003eACR TI-RADS is a valuable tool for thyroid nodule risk stratification, but it demonstrates limitations in sensitivity and specificity within our setting. Discrepancies between the ACR TI-RADS scoring and histology highlights potential over- or under-estimation of malignancy risk, influenced by inter-operator variability and inconsistent reporting. Standardized reporting protocols, ongoing training, and the incorporation of additional sonographic features, such as vascularity assessment, may improve diagnostic performance, thereby reducing patient morbidity and mortality.\u003c/p\u003e","manuscriptTitle":"Diagnostic performance of the ACR TI-RADS classification in identifying and excluding thyroid malignancy: A multi-correlative retrospective study in a South African tertiary hospital","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-09 09:51:28","doi":"10.21203/rs.3.rs-7465890/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"50af5c70-4bcf-45d3-8727-ab0083ab9781","owner":[],"postedDate":"September 9th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-12-08T16:03:02+00:00","versionOfRecord":{"articleIdentity":"rs-7465890","link":"https://doi.org/10.1186/s43055-025-01648-1","journal":{"identity":"egyptian-journal-of-radiology-and-nuclear-medicine","isVorOnly":false,"title":"Egyptian Journal of Radiology and Nuclear Medicine"},"publishedOn":"2025-12-03 15:58:03","publishedOnDateReadable":"December 3rd, 2025"},"versionCreatedAt":"2025-09-09 09:51:28","video":"","vorDoi":"10.1186/s43055-025-01648-1","vorDoiUrl":"https://doi.org/10.1186/s43055-025-01648-1","workflowStages":[]},"version":"v1","identity":"rs-7465890","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7465890","identity":"rs-7465890","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}