Management Of Thyroid Nodules Research Articles

Deciphering the progression of fine-needle aspiration: A bibliometric analysis of thyroid nodule research.

This study aims to dissect the evolution and pivotal shifts in Fine-Needle Aspiration (FNA) research for thyroid nodules over the past 2 decades, focusing on delineating key technological advancements and their impact on clinical practice. A comprehensive bibliometric analysis was conducted on 5418 publications from the Web of Science Core Collection database (2000-2023). Publications were rigorously selected based on their contributions to the advancement of FNA techniques and their influence on thyroid nodule management practices. Our analysis uncovered significant breakthroughs, most notably the incorporation of ultrasound and molecular diagnostics in FNA, which have markedly elevated diagnostic accuracy. A pivotal shift was identified towards minimally invasive post-FNA treatments, such as Radiofrequency Ablation, attributable to these diagnostic advancements. Additionally, the emergence of AI-assisted cytology represents a frontier in precision diagnostics, promising enhanced disease identification. The geographical analysis pinpointed the United States, Italy, and China as key contributors, with the United States leading in both publication volume and citation impact. This bibliometric analysis sheds light on the transformative progression in FNA practices for thyroid nodules, characterized by innovative diagnostic technologies and a trend towards patient-centric treatment approaches. The findings underscore the need for further research into AI integration and global practice standardization. Future explorations should focus on the practical application of these advancements in diverse healthcare settings and their implications for global thyroid nodule management.

Management of thyroid nodule in pregnancy

Management of thyroid nodule in pregnancy

Management of hot thyroid nodules: experience of our department

Management of hot thyroid nodules: experience of our department

Diagnostic accuracy of Afirma Gene Expression Classifier, Afirma Gene Sequencing Classifier, ThyroSeq v2 and ThyroSeq v3 for indeterminate (Bethesda III and IV) thyroid nodules: a meta-analysis.

The management of thyroid nodules with indeterminate cytology (ITN) is still a challenge. To evaluate the performance of commercial molecular tests for ITN, we performed this comprehensive meta-analysis. We performed an electronic search using PubMed/Medline, Embase and the Cochrane Library. Studies assessing the diagnostic accuracy of Afirma Gene Expression Classifier (GEC), Afirma Gene Sequencing Classifier (GSC), ThyroSeq v2 (TSv2) or ThyroSeq v3 (TSv3) in patients with ITN (only Bethesda category III or IV) were selected; Statistical analyses were performed by using Stata. 71 samples (GEC, n=38; GSC, n=16; TSv2, n=9; TSv3, n=8) in 53 studies, involving 6,490 fine needle aspirations (FNA) with ITN cytology with molecular diagnostics (GEC, GSC, TSv2 or TSv3) were included in the study. Meta-analysis showed the following pooled estimates: sensitivity 0.95 (95% CI, 0.94-0.97), specificity 0.35 (0.28-0.43), Positive Likelihood Ratio (LR+) 1.5 (1.3-1.6), and Negative Likelihood Ratio (LR-) 0.13 (0.09-0.19), with the best performance for TSv3 (area under the ROC curve 0.95 (0.93-0.96), followed by TSv2 (0.90 (0.87-0.92)), GSC (0.86 (0.82-0.88)) and GEC (0.82 (0.78-0.85)); with the best rule-out property for GSC (LR-, 0.07 (0.02-0.19)), followed by TSv3 (0.11 (0.05-0.24)) and GEC (0.16 (0.10-0.28); with the best rule-in for TSv2 (LR+, 2,9 (1.4-4.6)), followed by GSC (1.9 (1.6-2.4)). Meta-regression analysis revealed that study design, Bethesda category, and type of molecular test were independent factors. We showed that in patients with ITN, TSv3 has the best molecular diagnostic performance, followed by TSv2, GSC, and GEC. For rule-out malignancy, GSC, and for rule-in, TSV2 is superior to other tests.

Evolutionary analysis of indeterminate cytology and risk of malignancy in a thyroid nodule unit.

The objective of this study was to analyze the evolution in the diagnosis and management of indeterminate thyroid nodules over three time periods. 3020 patients with thyroid nodules underwent cytological evaluation during three periods (2006-2008, 2012-2014, 2017-2019). Distribution of diagnostic cytologies, risk of malignancy, diagnostic performance indices of FNA, and cytologic-histologic correlation in indeterminate cytologies were analyzed. only 2.2% of cytology tests were insufficient for a diagnosis. 86.9% cytologies were benign, 1.7% malignant, and 11.4% indeterminate. Indeterminate cytology rates were 15.9% (2006-2008), 10.1% (2012-2014), and 10% (2017-2019). Surgery was performed in 13% of benign cytology, result-ing in malignant histology in 2.7%. All malignant and suspicious cytologies underwent surgery: malig-nancy confirmed in 98% and 77% of cases, respectively. All 'indeterminate with atypia' cytologies (2006-2008) and Bethesda IV (2012-2014; 2017-2019) un-derwent surgery, with malignancy confirmed in 19.6%, 43.8%, and 25.7%, respectively. In the 'inde-terminate without atypia' category (2006-2008) and Bethesda III (2012-2014; 2017-2019), diagnostic surgery was performed in 57.7%, 78.6%, and 59.4%, respectively, with malignancy confirmed in 3.3%, 20.5%, and 31.6%. The FNA sensitivity was 91.6% with a negative predictive value greater than 96% in all periods. The specificity exceeded 75% in the last two periods. Bethesda system reduces indeterminate cytologies and improves the accuracy of FNA diagnosis. We reported a higher proportion of malignancy than expected in Bethesda III, underscoring the importance of having institution-specific data to guide decision-making. However, there is a need for risk stratification tools that allow for conservative management in low-risk cases.

Diagnostic performance of artificial intelligence in interpreting thyroid nodules on ultrasound images: a multicenter retrospective study.

Thyroid nodules are commonly identified through ultrasound imaging, which plays a crucial role in the early detection of malignancy. The diagnostic accuracy, however, is significantly influenced by the expertise of radiologists, the quality of equipment, and image acquisition techniques. This variability underscores the critical need for computational tools that support diagnosis. This retrospective study evaluates an artificial intelligence (AI)-driven system for thyroid nodule assessment, integrating clinical practices from multiple prominent Thai medical centers. We included patients who underwent thyroid ultrasonography complemented by ultrasound-guided fine needle aspiration (FNA) between January 2015 and March 2021. Participants formed a consecutive series, enhancing the study's validity. A comparative analysis was conducted between the AI model's diagnostic performance and that of both an experienced radiologist and a third-year radiology resident, using a dataset of 600 ultrasound images from three distinguished Thai medical institutions, each verified with cytological findings. The AI system demonstrated superior diagnostic performance, with an overall sensitivity of 80% [95% confidence interval (CI): 59.3-93.2%] and specificity of 71.4% (95% CI: 53.7-85.4%). At Siriraj Hospital, the AI achieved a sensitivity of 90.0% (95% CI: 55.5-99.8%), specificity of 100.0% (95% CI: 69.2-100%), positive prediction value (PPV) of 100.0%, negative prediction value (NPV) of 90.9%, and an overall accuracy of 95.0%, indicating the benefits of AI's extensive training across diverse datasets. The experienced radiologist's sensitivity was 40.0% (95% CI: 21.1-61.3%), while the specificity was 80.0% (95% CIs: 63.6-91.6%), respectively, showing that the AI significantly outperformed the radiologist in terms of sensitivity (P=0.043) while maintaining comparable specificity. The inter-observer variability analysis indicated a moderate agreement (K=0.53) between the radiologist and the resident, contrasting with fair agreement (K=0.37/0.33) when each was compared with the AI system. Notably, 95% CIs for these diagnostic indexes highlight the AI system's consistent performance across different settings. The findings advocate for the integration of AI into clinical settings to enhance the diagnostic accuracy of radiologists in assessing thyroid nodules. The AI system, designed as a supportive tool rather than a replacement, promises to revolutionize thyroid nodule diagnosis and management by providing a high level of diagnostic precision.

A Study to Evaluate TIRADS Scoring in the Management of Thyroid Nodules

A Study to Evaluate TIRADS Scoring in the Management of Thyroid Nodules

Overweight as a biomarker for concomitant thyroid cancer in patients with Graves' disease.

The incidence of concomitant thyroid cancer in Graves' disease varies and Graves' disease can make the diagnosis and management of thyroid nodules more challenging. Since the majority of Graves' disease patients primarily received non-surgical treatment, identifying biomarkers for concomitant thyroid cancer in patients with Graves' disease may facilitate planning the surgery. The aim of this study is to identify the biomarkers for concurrent thyroid cancer in Graves' disease patients and evaluate the impact of being overweight on cancer risk. This retrospective cohort study analyzed 122 patients with Graves' disease who underwent thyroid surgery at Seoul St. Mary's Hospital (Seoul, Korea) from May 2010 to December 2022. Body mass index (BMI), preoperative thyroid function test, and thyroid stimulating hormone receptor antibody (TR-Ab) were measured. Overweight was defined as a BMI of 25 kg/m² or higher according to the World Health Organization (WHO). Most patients (88.5%) underwent total or near-total thyroidectomy. Multivariate analysis revealed that patients who were overweight had a higher risk of malignancy (Odds ratios, 3.108; 95% confidence intervals, 1.196-8.831; p = 0.021). Lower gland weight and lower preoperative TR-Ab were also biomarkers for malignancy in Graves' disease. Overweight patients with Graves' disease had a higher risk of thyroid cancer than non-overweight patients. A comprehensive assessment of overweight patients with Graves' disease is imperative for identifying concomitant thyroid cancer.

Preference Phenotypes in Thyroid Nodule Management: A Patient Segmentation Approach.

Patient preferences regarding thyroid nodules are poorly understood. Our objective is to (1) employ a discrete choice experiment (DCE) to explore risk tradeoffs in thyroid nodule management, and (2) segment respondents into preference phenotypes. DCE. Thyroid surgery clinic, online survey. A DCE including 5 attributes (cancer risk, voice concerns, incision/scar, medication requirement, follow-up frequency) was refined with qualitative patient and physician input. A final DCE including 8 choice tasks, demographics, history, and risk tolerance was administered to participants with and without thyroid disease. Analysis was performed with multinomial logit modeling and latent class analysis (LCA) for preference phenotyping. A total of 1026 respondents were included; 480 had thyroid disease. Risk aversion was associated with increasing age (P < .001), female gender (P < .001), and limited education (P = .038), but not previous thyroid disease. Cancer risk most significantly impacted decision-making. Of the total possible utility change from thyroid nodule decision-making, 47.8% was attributable to variations in cancer risk; 20.0% from medication management; 14.9% from voice changes; 12.7% from incision/scar; and 4.6% from follow-up concerns. LCA demonstrated 3 classes with distinct preference phenotypes: the largest group (64.2%) made decisions primarily based on cancer risk; another group (18.2%) chose based on aversion to medication; the smallest group (17.7%) factored in medication and cancer risk evenly. Cancer risk and the need to take medication after thyroid surgery factor into patient decision-making most heavily when treating thyroid nodules. Distinct preference phenotypes were demonstrated, reinforcing the need for individual preference assessment before the treatment of thyroid disorders.

Cost-Effectiveness of the ACR TIRADS Compared to the ATA 2015 Risk Stratification Systems in the Evaluation of Incidental Thyroid Nodules

Rationale and ObjectivesThyroid nodules are a common incidental imaging finding and prone to overdiagnosis. Several risk stratification systems have been developed to reduce unnecessary work-up, with two of the most utilized including the American Thyroid Association 2015 (ATA2015) and the newer American College of Radiology Thyroid Imaging, Reporting and Data System (TIRADS) guidelines. The purpose of this study is to evaluate the cost effectiveness of the ATA2015 versus the TIRADS guidelines in the management of incidental thyroid nodules. MethodsA cost-utility analysis was conducted using decision tree modeling, evaluating adult patients with incidental thyroid nodules <4 cm. Model inputs were populated using published literature, observational data, and expert opinion. Single-payer perspective, Canadian dollar currency, 5-year time horizon, willingness to pay (WTP) threshold of $50,000, and discount rate of 1.5% per annum were utilized. Scenario, deterministic and probabilistic sensitivity analyses were performed. The primary outcome was the incremental cost effectiveness ratio (ICER) expressed as incremental cost per quality-adjusted life year (QALY) gained. ResultsFor the base case scenario, TIRADS dominated the ATA2015 strategy by a slim margin, producing 0.005 more QALYs at $25 less cost. Results were sensitive to the malignancy rate of biopsy and the utilities of a patient with a benign nodule/subclinical malignancy or under surveillance. Probabilistic sensitivity analysis showed that TIRADS was the more cost effective option 79.7% of the time. ConclusionThe TIRADS guidelines may be the more cost-effective strategy by a small margin compared to ATA2015 in most scenarios when used to risk stratify incidental thyroid nodules.

Cytological Grading of Lymphocytic Thyroiditis and Its Correlation With Biochemical Parameters: An Experience From a Tertiary Care Center in North India.

Chronic lymphocytic thyroiditis is the most common cause of acquired hypothyroidism. The clinical management of thyroid nodules, with or without chronic lymphocytic thyroiditis, mainly depends on clinical data, ultrasonography, and fine-needle aspiration cytology (FNAC), the latter being the gold standard for the pre-surgical diagnosis of thyroidal nodules. The grading of chronic lymphocytic thyroiditis can be divided into three categories. The spectrum of the thyroid profile can be correlated to the cytological diagnosis of chronic lymphocytic thyroiditis. This study aims to study the cytomorphology of various grades of chronic lymphocytic thyroiditis and its correlation with the hormonal profile. In this study, 44 patients with a diagnosis of lymphocytic thyroiditis on FNAC were included. The cases of lymphocytic thyroiditis were graded cytomorphologically, and correlation with the thyroid hormone profile was done. The majority of the patients were between 16 and 30 years age group, with a female predominance. The majority of the patients presented with diffuse enlargement of the thyroid gland. The maximum number of cases was graded in the grade II cytological category (70.46%). A hypothyroid profile was present in 63% of patients, followed by an euthyroid profile. The majority of patients with grade II thyroiditis also had a hypothyroid profile. However, no significant association was found between cytological grading and hormonal status. Cytological grading is a clear, easy-to-use diagnostic tool for confirmation of lymphocytic thyroiditis. However, the cytological grades show no statistically significant correlation with thyroid hormonal status. Lymphocytic thyroiditis should be diagnosed with a multidisciplinary approach, as clinical features and hormonal profile when used alone may result in a missed diagnosis.

2023 Update of the Korean Thyroid Association Guidelines for the Management of Thyroid Nodules

2023 Update of the Korean Thyroid Association Guidelines for the Management of Thyroid Nodules

Assessment of ChatGPT's adherence to ETA-thyroid nodule management guideline over two different time intervals 14 days apart: in binary and multiple-choice queries.

Artificial intelligence (AI) has significant potential in healthcare, particularly in providing decision-support in specialized domains like thyroid nodule management. This study assesses the effectiveness of ChatGPT-v4, an advanced AI model, in aligning with the European Thyroid Association (ETA) - 2023 guidelines. The study utilized a structured questionnaire comprising 100 questions, divided into true/false and multiple-choice formats, reflecting real-world clinical scenarios in thyroid nodule management. These questions encompassed diagnostic criteria, treatment options, follow-up protocols, and patient counseling. ChatGPT response was evaluated for accuracy, consistency, and comprehensiveness using a six-point Likert scale. The assessment occurred initially and was repeated after 14 days. In the binary queries, the AI model showed an ability to correct some initially incorrect responses. However, there was a noticeable regression in certain responses. 8 of the 11 previously non-compliant responses remained unchanged, while 3 non-compliant responses were rectified. Conversely, 6 initially compliant answers transitioned to non-compliance after 14 days. In multiple-choice queries, the AI's performance was more consistent. A majority of the responses, 43 (86% of the total), were initially correct and maintained their correctness upon re-assessment. However, 4 responses that were initially incorrect remained unchanged, and 3 correct responses shifted to non-compliance over time. ChatGPT exhibited improving potential as a clinical support tool in thyroid nodule management altgouh it showed varied performance for binary and multiple-choice questions. N/A.

A Cytohistologic Correlation Study of Thyroid Lesions: Evaluation of Diagnostic Accuracy and Pitfalls of Fine Needle Aspiration Cytology.

Background Only about 5% of palpable thyroid nodules are malignant; the rest are entirely benign. In order to reduce the number of unnecessary treatments and properly identify situations that need surgical intervention, it is essential to distinguish between benign and malignant lesions prior to surgery. There exists a "grey zone" in thyroid cytology characterized by a significant decrease in diagnostic accuracy, making it difficult to precisely classify the lesion and leading to discrepancies. Aims and objectives The study aims to accomplish the following objectives: (1) assess the prevalence of thyroid lesions according to age and sex; (2) evaluate the accuracy of the fine needle aspiration cytology (FNAC) in diagnosing thyroid conditions; and (3) investigate the causes of cytohistological discordance within the context of this study. Materials and methods In our five-year study of thyroid lesions, 125 cases were studied for cytohistological correlation. Discrepant and likened FNAs were classified according to the diagnostic findings. A review of the cytological smears and histological sections was conducted. Results The cytological diagnoses were correlated with histopathology in 109 cases (90.83%). A total of 11 cases (09.16%) were discrepant. There were no false positives (FPs). The causes of false negative (FN) diagnoses in our study can be attributed to geographic misses and failure to recognize dual pathologies. Conclusion FNA is a very precise and time-saving technique for the diagnosis and subsequent management of palpable thyroid nodules. Patients having thyroidectomies have a much higher malignant yield, and the frequency of procedures performed on the thyroid is decreased. When FNA interpretation based on strict specimen sufficiency standards is considered along with clinical and imaging findings, the occurrence of FN and FP diagnoses is expected to decrease.

Assessment of the risk of malignancy in Bethesda III thyroid nodules: a comprehensive review.

The increasing prevalence of thyroid cancer emphasizes the need for a thorough assessment of risk of malignancy in Bethesda III nodules. Various methods ranging commercial platforms of molecular genetic testing (including Afirma® GEC, Afirma® GSC, ThyroSeq® V3, RosettaGX®, ThyGeNEXT®/ThyraMIR®, ThyroidPRINT®) to radionuclide scans and ultrasonography have been investigated to provide a more nuanced comprehension of risk estimation. The integration of molecular studies and imaging techniques into clinical practice may provide clinicians with improved and personalized risk assessment. This integrated approach we feel may enable clinicians to carefully tailor interventions, thereby minimizing the likelihood of unnecessary thyroid surgeries and overall crafting the optimal treatment. By aligning with the evolving landscape of personalized healthcare, this comprehensive strategy ensures a patient-centric approach to thyroid nodule and thyroid cancer management.

Poorly differentiated papillary thyroid carcinoma in a 5-year-old girl: a case report

BackgroundThe incidence of thyroid cancer has been increasing among the population less than 20 years of age, especially during the second decade of life. Differentiated papillary thyroid cancer is the most common pathology in children. It usually presents with thyroid nodules with or without cervical lymphadenopathy. Thyroid nodules carry a considerable risk of malignancy in children.Case presentationWe herein report a 5-year-old girl with poorly differentiated papillary thyroid cancer which is an extremely rare finding at this age. The patient underwent right thyroid lobectomy followed by left hemi thyroidectomy and right central and lateral neck dissection. Pathologic examination revealed a poorly differentiated papillary thyroid carcinoma with nodal deposits.ConclusionIt is essential to raise awareness of proper evaluation and management of thyroid nodules at such an age.

A Narrative Review of the 2023 Korean Thyroid Association Management Guideline for Patients with Thyroid Nodules.

The 2023 Korean Thyroid Association (KTA) Management Guideline for Patients with Thyroid Nodules constitute an update of the 2016 KTA guideline for thyroid nodules and cancers that focuses specifically on nodules. The 2023 guideline aim to offer updated guidance based on new evidence that reflects the changes in clinical practice since the 2016 KTA guideline. To update the 2023 guideline, a comprehensive literature search was conducted from January 2022 to May 2022. The literature search included studies, reviews, and other evidence involving human subjects that were published in English in MEDLINE (PubMed), Embase, and other relevant databases. Additional significant clinical trials and research studies published up to April 2023 were also reviewed. The limitations of the current evidence are discussed, and suggestions for areas in need of further research are identified. The purpose of this review is to provide a summary of the 2023 KTA guideline for the management of thyroid nodules released in May 2023 and to give a balanced insight with comparison of recent guidelines from other societies.

Thyroid Ethanol and Radiofrequency Ablation: A Call for Patient-Friendly Online Resources

Introduction: The multiple treatment options available to patients with thyroid nodules can generate uncertainty and confusion. Radiofrequency ablation (RFA) and ethanol ablation (EA) are two alternative modalities to manage thyroid nodules. As patients more frequently utilize online resources to guide their decision-making, the quality of such resources must be evaluated. The goal of this study was to assess the quality of online patient materials relating to RFA and EA compared to standard thyroidectomy. Methods: The terms “thyroidectomy,” “thyroid radiofrequency ablation,” and “thyroid ethanol ablation” were searched on Google. Flesch Reading Ease (FRE), Flesch-Kincaid Grade Level (FKGL), Simple Measure of Gobbledygook (SMOG), and Patient Education Materials Assessment Tool (PEMAT) understandability and actionability were calculated for each website. Statistical analysis was conducted on SPSS Statistics. Google trends were used to determine search interest for each term (May 2016 – May 2021). Results: Of the 77 websites that met our inclusion criteria (30 thyroidectomy sites, 30 RFA sites, and 17 EA sites), the average FRE, FKGL, and SMOG scores of the RFA websites were significantly worse than those of the thyroidectomy websites (p < 0.05). The FKGL and SMOG scores of the EA websites were significantly worse than those of the thyroidectomy websites (p < 0.05). The average understandability and actionability scores for thyroidectomy websites were significantly higher than those of RFA and EA websites (p < 0.05). Conclusion: Ablation websites have lower search interest, readability, validity, understandability, and actionability scores in comparison to traditional thyroidectomy websites. Our findings emphasize the need to consider readability and PEMAT scores when developing online educational resources for ablative alternatives to thyroidectomy to allow for greater patient accessibility.

The value of quantitative and a new qualitative color pattern shear wave elastography for the differentiation of ACR TI-RADS 4 or 5 category thyroid nodules measuring ≤10 mm.

This study aims to evaluate the diagnostic performance of quantitative shear wave elastography (SWE) and a new qualitative color pattern SWE for the differentiation of benign and malignant American College of Radiology Thyroid Imaging, Reporting, and Data System (ACR TI-RADS) 4 or 5 category thyroid nodules measuring ≤10 mm. From May 2020 to July 2022, a total of 237 patients with 270 thyroid nodules were enrolled, and conventional ultrasound and SWE examinations were performed for each patient. Each ACR TI-RADS 4 or 5 category thyroid nodule measuring ≤10 mm was evaluated by quantitative SWE and a new qualitative color pattern SWE. The diagnostic performance of quantitative SWE parameters, the new qualitative color pattern SWE, and the combination of SWE with ACR TI-RADS, respectively, for the differentiation of benign and malignant ACR TI-RADS 4 or 5 category thyroid nodules measuring ≤10 mm was evaluated and compared. Among 270 thyroid nodules in 237 patients, 72 (26.67%) thyroid nodules were benign and 198 (73.33%) thyroid nodules were malignant. The qualitative color pattern SWE showed better diagnostic performance than the quantitative SWE parameters. When combining the qualitative color pattern SWE with ACR TI-RADS scores, with the optimal cutoff value of the total points ≥8, the thyroid nodules were considered malignant. The sensitivity, specificity, accuracy, and AUC were 89.90%, 56.94%, 81.11%, and 0.820 (95% CI: 0.768-0.864), respectively. Compared with using qualitative color pattern SWE alone, the combination of qualitative color pattern SWE and ACR TI-RADS had better diagnostic performance, which was significantly different (p < 0.05). The combination of qualitative SWE color patterns and ACR TI-RADS had high sensitivity and accuracy, which might be a convenient and useful method to differentiate benign and malignant ACR TI-RADS 4 or 5 category thyroid nodules measuring ≤10 mm. It would be helpful for the management of thyroid nodules and improving prognosis.

Molecular Profiling for Bethesda III to VI Nodules: Results of a Multicenter International Retrospective Study

ObjectiveMolecular testing is a well-established tool that assists in the management of thyroid nodules. We describe our experience using molecular testing of thyroid nodules with Bethesda III to VI cytology. MethodsThis is a retrospective multicenter, multinational study of thyroid nodules that underwent preoperative molecular profiling with ThyGenX/ThyGeNEXT or ThyroSeq V3 between 2015 and 2022. The clinical characteristics and mutational profiles of tumors were compared. Collected data included demographics, cytology results, surgical pathology, and molecular alterations. Molecular alterations were categorized into 3 main phenotypes: BRAF-like, RAS-like, and non-BRAF-non-RAS (NBNR). ResultsOverall, 784 patients who had surgery were included, of which 603 (76.2%) were females. The most common histologic type was papillary thyroid cancer (PTC) with 727 (91.9%) cases. In total, 205 (28.2%) cases showed an aggressive subtype of PTC (eg, tall cell and hobnail). BRAF-like alterations were most likely to be found in Bethesda V and VI nodules and show extrathyroidal extension (ETE), nodal disease, and/or aggressive subtypes of PTC (P < .001 for all). RAS-like alterations were more commonly found in Bethesda III and IV nodules and were less likely to show ETE, nodal disease, and/or aggressive histology (P < .001 for all). NBNR alterations were more commonly found in Bethesda III and IV nodules and were less likely to show ETE, nodal disease, and/or aggressive subtypes of PTC. However, they were rarely but significantly associated with poorly differentiated thyroid cancer (P < .005). ConclusionMolecular testing of thyroid nodules can help determine the likelihood of malignancy and classify nodules into several tumor phenotypes, predicting their behaviors and potentially allowing for a more tailored treatment. NBNR alterations should be managed with caution.