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The rate of detection of thyroid nodules and carcinomas has increased with the widespread use of ultrasonography (US), which is the mainstay for the detection and risk stratification of thyroid nodules as well as for providing guidance for their biopsy and nonsurgical treatment. The Korean Society of Thyroid Radiology (KSThR) published their first recommendations for the US-based diagnosis and management of thyroid nodules in 2011. These recommendations have been used as the standard guidelines for the past several years in Korea. Lately, the application of US has been further emphasized for the personalized management of patients with thyroid nodules. The Task Force on Thyroid Nodules of the KSThR has revised the recommendations for the ultrasound diagnosis and imaging-based management of thyroid nodules. The review and recommendations in this report have been based on a comprehensive analysis of the current literature and the consensus of experts.

Abstract Introduction ElaTION is a large multicenter pragmatic randomized controlled trial, performed in 18 secondary/tertiary hospitals across England, comparing elastography ultrasound-guided fine needle aspiration cytology (EUS-FNAC) with ultrasound-guided FNAC (US-FNAC) alone in the diagnostic assessment of thyroid nodules. Secondary trial outcomes, reported here, assessed the accuracy of ultrasound alone (US) compared with US-FNAC to inform and update current practice guidelines. Methods Adults with single or multiple thyroid nodules who had not undergone previous FNAC were eligible. Radiologists assessed all thyroid nodules using US alone, thereby enabling assessment of its accuracy (sensitivity and specificity) vs US-FNAC. Results Of the 982 participants, a final definitive diagnosis was obtained in 688, who were included in the final analyses. The sensitivity of US alone was the same as US-FNAC (0.91 [95% CI, 0.85-0.97] vs 0.87 [95% CI, 0.80-0.95] P = .37). US alone had statistically significant lower specificity than US-FNAC alone (0.48 vs 0.67 respectively, P < .0001). The malignancy rate on histology in a nodule classified as benign on ultrasound (U2) was 9/263 (3.42%) and on cytology (Thy2) was 15/353 (4.25%), whereas the malignancy rate in a nodule that was benign on both (U2, Thy2) was 3/210 (1.43%). Malignancy risk for U3, U4, and U5 nodules was 68/304 (22.4%), 43/83 (51.8%), and 29/38 (76.3%), respectively (P < .0001). Yet 80/982 (8%) patients were discharged despite having U3-U5 scans with Thy1 (nondiagnostic) FNAC and no definitive diagnosis. Malignancy risk was higher in smaller nodules: < 10 mm 23/60 (38.3%), 10-20 mm 46/162 (28.4%), and >20 mm 80/466 (17.2%) (P < .0001). Nodules with indeterminate cytology with atypical features (Thy3a) carried a similar malignancy risk to those with indeterminate cytology (Thy3/3f): 27/95 (28.4%) vs 42/113 (37.2%) respectively (P = .18). Conclusion Ultrasound alone appears to be an effective diagnostic modality in thyroid nodules, confirming the recommendations of recent guidelines and the British Thyroid Association classification. However, findings also suggest caution regarding existing recommendations for conservative management of nondiagnostic (Thy1/Bethesda I) and atypical (Thy3a/Bethesda III) nodules. In those cases, ultrasound (U3-U5) features may help identify high-risk subgroups for more proactive management.

Abstract Context Radiofrequency ablation (RFA) seems to achieve a significantly larger nodule volume reduction rate (VRR) than laser ablation (LA) in benign nonfunctioning thyroid nodules (BNTNs) Objective To compare the efficacy and safety of both treatments at 12-month follow-up in patients with solid or predominantly solid BNTN. Methods This was a single-center, 12-month, randomized, superiority, open-label, parallel-group trial conducted in an outpatient clinic. Sixty patients with a solitary BNTN or dominant nodule characterized by pressure symptoms/cosmetic problems were randomly assigned (1:1 ratio) to receive either a single session of RFA or LA. Twenty-9 patients per group completed the study. The main outcome measures were VRR and proportion of nodules with more than 50% reduction (technical success rate). Results At 12 months, VRR was 70.9 ± 16.9% and 60.0 ± 19.0% in the RFA and LA groups, respectively (P = .024). This effect was confirmed in the linear regression model that was adjusted for age, sex, nodule baseline volume, and proportion of cellular components (RFA treatment: β = .390; P = .009). No significant between-group difference was observed in the technical success rate at 12 months after treatment. A statistically significant improvement was observed from the baseline to the 12-month follow-up for compression (RFA: 4.6 ± 2.6 and 1.3 ± 0.8, P < .001; and LA: 4.6 ± 2.1 and 1.6 ± 0.8, respectively, P < .001) and cosmetic (RFA: 3.4 ± 0.6 and 1.3 ± 0.5, P < .001; and LA: 3.4 ± 0.5 and 1.4 ± 0.6, P < .001) scores although the between-group differences were not significant. Conclusion RFA achieved a significantly larger nodule volume reduction at 12 months; however, the technical success rate was similar in the RFA and LA groups.

Imaging plays a key role in the diagnosis and characterization of thyroid diseases, and the information provided by imaging studies is essential for management planning. A referral guideline for imaging studies may help physicians make reasonable decisions and minimize the number of unnecessary examinations. The Korean Society of Thyroid Radiology (KSThR) developed imaging guidelines for thyroid nodules and differentiated thyroid cancer using an adaptation process through a collaboration between the National Evidence-based Healthcare Collaborating Agency and the working group of KSThR, which is composed of radiologists specializing in thyroid imaging. When evidence is either insufficient or equivocal, expert opinion may supplement the available evidence for recommending imaging. Therefore, we suggest rating the appropriateness of imaging for specific clinical situations in this guideline.

Thyroid nodules, with a prevalence of almost 25% in the general population, are a common occurrence. Their prevalence varies considerably depending on demographics such as age and sex as well as the presence of risk factors. This article provides a comprehensive overview of the prevalence, risk stratification and current management strategies for thyroid nodules, with a particular focus on changes in diagnostic and therapeutic protocols that have occurred over the past 10 years. Several sonography-based stratification systems (such as Thyroid Imaging Reporting and Data Systems (TIRADS)) might help to predict the malignancy risk of nodules, potentially eliminating the need for biopsy in many instances. However, large or suspicious nodules necessitate cytological evaluation following fine-needle aspiration biopsy for accurate classification. In the case of cytology yielding indeterminate results, additional tools, such as molecular testing, can assist in guiding the management plan. Surgery is no longer the only treatment for symptomatic or malignant nodules: active surveillance or local ablative treatments might be beneficial for appropriately selected patients. To enhance clinician–patient interactions and discussions about diagnostic options, shared decision-making tools have been developed. A personalized, risk-based protocol promotes high-quality care while minimizing costs and unnecessary testing. Thyroid nodules are common; the majority are benign and asymptomatic, and therefore the main aim of the diagnostic process is to determine their clinical significance without leading to overdiagnosis and, consequently, overtreatment, as outlined in this article. Key points Thyroid nodules are a common occurrence, with a prevalence of ~25% in the general population that varies widely according to age, sex and risk factors. The US Preventive Services Task Force recommends against screening for thyroid cancer in the general, asymptomatic adult population, as such screening would result in harms that outweigh potential benefits. If a thyroid nodule is suspected, the first step is to perform dedicated ultrasonography; ultrasonography risk stratification systems can classify and estimate the likelihood of malignancy of a nodule. If the need for further assessment is confirmed, a fine-needle aspiration biopsy is often performed; cytology results are usually classified according to a standard cytology reporting system. At the end of the initial diagnosis and risk stratification procedure, over 90% of nodules are found to be benign and asymptomatic; the patients are euthyroid and require no specific treatment. Preservation of thyroid function is of paramount importance; several non-surgical and minimally invasive techniques are available but, if surgery is needed, the minimal possible extent should be chosen.

Abstract Context Comprehensive genomic analysis of thyroid nodules for multiple classes of molecular alterations detected in a large series of fine needle aspiration (FNA) samples has not been reported. Objective To determine the prevalence of clinically relevant molecular alterations in Bethesda categories III-VI (BCIII-VI) thyroid nodules. Methods This retrospective analysis of FNA samples, tested by ThyroSeq v3 using Genomic Classifier and Cancer Risk Classifier at UPMC Molecular and Genomic Pathology laboratory, analyzed the prevalence of diagnostic, prognostic, and targetable genetic alterations in a total of 50 734 BCIII-VI nodules from 48 225 patients. Results Among 50 734 informative FNA samples, 65.3% were test-negative, 33.9% positive, 0.2% positive for medullary carcinoma, and 0.6% positive for parathyroid. The benign call rate in BCIII-IV nodules was 68%. Among test-positive samples, 73.3% had mutations, 11.3% gene fusions, and 10.8% isolated copy number alterations. Comparing BCIII-IV nodules with BCV-VI nodules revealed a shift from predominantly RAS-like alterations to BRAF V600E-like alterations and fusions involving receptor tyrosine kinases (RTK). Using ThyroSeq Cancer Risk Classifier, a high-risk profile, which typically included TERT or TP53 mutations, was found in 6% of samples, more frequently BCV-VI. RNA-Seq confirmed ThyroSeq detection of novel RTK fusions in 98.9% of cases. Conclusion In this series, 68% of BCIII-IV nodules were classified as negative by ThyroSeq, potentially preventing diagnostic surgery in this subset of patients. Specific genetic alterations were detected in most BCV-VI nodules, with a higher prevalence of BRAF and TERT mutations and targetable gene fusions compared to BCIII-IV nodules, offering prognostic and therapeutic information for patient management.

BackgroundMolecular testing can refine the risk of malignancy in cytologically indeterminate thyroid nodules and can reduce the need for diagnostic thyroidectomy. However, quality of life (QOL) in patients mananged with molecular testing is not well studied.ObjectiveWe aimed to assess the QOL of patients undergoing surveillance after a benign molecular test result, or thyroidectomy after a suspicious molecular test result.MethodsThis prospective longitudinal follow-up of the Effectiveness of Molecular Testing Techniques for Diagnosis of Indeterminate Thyroid Nodules randomized trial utilized the Thyroid-Related Patient-Reported Outcome, 39-item version (ThyPro-39) to assess the QOL of patients with indeterminate cytology on thyroid fine needle aspiration (FNA) biopsy. All patients underwent molecular testing at the time of initial FNA. A mixed-effect model was used to determine changes in QOL over time.ResultsOf 252 eligible patients, 174 completed the assessment (69% response rate). Molecular test results included 72% (n = 124) benign and 28% (n = 50) suspicious. ThyPro-39 scores of benign molecular test patients were unchanged from baseline (following initial FNA and molecular test results) to 18 months of ultrasound surveillance. Baseline symptoms of goiter, anxiety, and depression were more severe for patients with suspicious compared with benign molecular test results. At a median of 8 months after thyroidectomy, suspicious molecular test patients reported improved symptoms of goiter, anxiety, and depression.ConclusionA benign molecular test provides sustained QOL throughout ultrasound surveillance, without worsening anxiety or depression relating to the risk of malignancy. Definitive surgery results in improvement of QOL in patients with suspicious molecular tests.

The purpose of this study was to determine the positive predictive value (PPV) and false positive (FP) rate for the Afirma Gene Sequencing Classifier (GSC). The GSC was analyzed in patients with indeterminate thyroid nodules (ITN). True positive (TP), FP and PPV were determined and were correlated with pathology. From June 2023–January 2025, 75 ITN were evaluated with the GSC and it was suspicious for cancer in 21 (28 ​%); 15 patients with 16 suspicious nodules underwent thyroidectomy. There were 7 ​TP and 9 FP results for a PPV of 44 ​%. The final pathology was papillary cancer 6 and oncocytic carcinoma 1 with TP GSC and follicular/oncocytic adenoma 4, follicular nodule 2, NIFTP 2 and Hashimoto thyroiditis 1 with FP GSC. A PPV of 44 ​% for the GSC has implications for the extent of surgery and for reducing overtreatment of patients with ITN. •The positive predictive value for Afirma Gene Sequencing Classifier (GSC) suspicious Bethesda III thyroid nodules was 44 ​%.•RAS mutations were the most common genomic alteration in GSC suspicious Bethesda III nodules.•The pathology for Bethesda III nodules with a false positive GSC was most commonly a benign follicular lesion.

PurposeTo compare the value of Thyroid Imaging Reporting and Data Systems proposed by Kwak (KWAK-TIRADS) and ACR (ACR TI-RADS) and 2015 American Thyroid Association (ATA) guidelines in the diagnosis of surgically resected thyroid nodules.MethodsFrom January 2015 to December 2015, 2544 thyroid nodules in 1758 patients who underwent thyroidectomy at our center were included. The KWAK-TIRADS category, ACR TI-RADS and ultrasound (US) pattern based on ATA guidelines were assigned to each thyroid nodule. Nodules were divided into groups according to their maximal diameter further.ResultsOf all the nodules, 863 (33.9%) were benign, whereas 1681 (66.1%) were malignant. The malignancy percentage of ACR TI-RADS category 1, 2, 3, 4, and 5 were 0%, 1.3%, 9.1%, 52.5%, and 88.8%, respectively. KWAK-TIRADS and ATA guidelines showed a better diagnostic efficiency than ACR TI-RADS (P < 0.01). ACR TI-RADS demonstrated a higher specificity (79.7%, P < 0.05), whereas the ATA US pattern had a higher sensitivity (95.5%, P < 0.01). The TIRADS (KWAK-TIRADS and ACR TI-RADS) category and ATA guidelines performed better in differentiating nodules >1 cm. KWAK-TIRADS showed better diagnostic efficiency than the other methods in differentiating nodules >1 cm (AUC: 0.92, P < 0.01).ConclusionsKWAK-TIRADS and ATA guidelines provide a better diagnostic efficiency than ACR TI-RADS. The TIRADS (KWAK-TIRADS and ACR TI-RADS) category and ATA guidelines perform better in differentiating nodules >1 cm than nodules ≤1 cm. KWAK-TIRADS perform better in differentiating nodules >1 cm than other methods.

To compare single-session radiofrequency ablation (RFA) and ethanol ablation (EA) for treating predominantly cystic thyroid nodules (PCTNs). This single-blind, randomized trial was approved by the Institutional Review Board of two centers and informed consent was obtained from all patients before enrollment. Fifty patients with a single PCTN (cystic portion less than 90% and greater than 50%) were randomly assigned to be treated by either RFA (25 patients) or EA (25 patients) at two hospitals. The primary outcome was the tumor volume reduction ratio (%) at the six-month follow-up and the superiority margin was set at 13% (RFA minus EA). Analysis was performed primarily in an intention-to-treat manner. The secondary outcomes were the therapeutic success rate, improvement of symptomatic and cosmetic problems, and the number of major complications. The mean volume reduction was 87.5 ± 11.5% for RFA (n = 22) and 82.4 ± 28.6% for EA (n = 24) (p = 0.710; mean difference [95% confidence interval], 5.1% [-8.0 to 18.2]), indicating no significant difference. Regarding the secondary outcomes, therapeutic success (p = 0.490), mean symptom (p = 0.205) and cosmetic scores (p = 0.710) showed no difference. There were no major complications in either group (p > 0.99). The therapeutic efficacy of RFA is not superior to that of EA; therefore, EA might be preferable as the first-line treatment for PCTNs.