Predictors of Volume Reduction Rate Following Microwave Ablation for Benign Thyroid Nodules: A Systematic Review and Meta-Analysis.

Telomerase reverse transcriptase promoter (TERTp) mutations are associated with aggressive thyroid cancer and are most frequently found in anaplastic and poorly differentiated thyroid cancer. Pre-operative thyroid nodule molecular testing can detect TERTp, denoting a high risk of malignancy and possible aggressive clinical features such as extrathyroidal extension, regional lymph node metastases, and distant metastases. There are two described hot spot point mutations: the more common C228T and a C250T variant. Canonically, these mutations are mutually exclusive and drive monoallelic TERT expression. In this case series, we describe thyroid cancers where both the C228T and C250T variants were detected in preoperative thyroid nodule fine needle aspiration samples sent for Afirma molecular testing. All had co-mutations along with BRAFp.V600E or PIK3CAp.H1047R. Each sample was sent for kinship (relatedness between individuals) analysis to confirm the DNA and RNA samples were from the same patient and not due to sample cross contamination. All cases had confirmed thyroid carcinoma on histopathology after surgical resection. To our knowledge, this is the first report of dual TERTp mutations detected in the preoperative setting in thyroid carcinoma. Clinical correlation with future cases will be of interest, particularly if cases with monoallelic dual TERTp mutations are discovered.

Metastatic clear cell renal cell carcinoma (ccRCC) to the thyroid gland is an uncommon but significant presentation, often occurring years after primary tumor resection. We present the case of a 52-year-old female who developed a solitary thyroid metastasis 13 years after undergoing left nephrectomy for ccRCC. Initially presenting with a gradually enlarging neck mass and mild dysphagia, her thyroid nodule exhibited suspicious features on ultrasonography and computed tomography, including hypervascularity. Fine-needle aspiration cytology revealed clear-cell features, prompting a multidisciplinary discussion. Definitive diagnosis was established through right thyroid lobectomy and subsequent immunohistochemical analysis, which confirmed metastatic ccRCC (positive for PAX8, CD10, vimentin; negative for thyroglobulin, TTF-1). This case is unique for its exceptionally long disease-free interval and highlights the diagnostic challenge posed by ccRCC metastases mimicking primary thyroid neoplasms. It underscores the critical importance of a thorough medical history, even for remote malignancies, and the value of comprehensive pathological and immunohistochemical evaluation in guiding accurate diagnosis and management. The patient achieved excellent long-term disease-free survival following surgical resection, reinforcing that aggressive local therapy for solitary thyroid metastases from ccRCC can lead to favorable outcomes and impact future practice by advocating for vigilant, long-term surveillance in ccRCC patients.

Minimal access thyroidectomy can be performed using several approaches, including transaxillary, breast-axilla and transoral endoscopic thyroidectomy (ET) vestibular approach (TOETVA). These techniques are designed to minimise visible scarring and enhance cosmetic outcomes. Endoscopy allows magnification, enabling improved visualisation of the recurrent laryngeal nerve (RLN) and parathyroid glands. This retrospective study evaluates the safety, reliability and complication rates of ET and proposes criteria for selecting the optimal approach. 266 patients who underwent minimal access thyroidectomy from May 2016 to May 2025 were included. Fine-needle aspiration cytology indicated benign aetiology (Bethesda Class 2) in 171 patients, indeterminate aetiology (Bethesda Class 3 and 4) in 71 patients and 24 patients were highly suspicious or proven malignancy (Bethesda Class 5 and 6). The primary indication was a solitary thyroid nodule (STN) in 204 patients, multinodular or bilobar lesions in 62 patients and malignancy in 24 patients. TOETVA was performed in 227 patients (nodule sizes 2-6 cm, 86% <4 cm), unilateral transaxillary thyroidectomy in 31 patients (STN, 4-6 cm) and bilateral transaxillary thyroidectomy in 8 patients multinodular goitre [MNG], 4-6 cm). TOETVA had the shortest mean operative time (67.3 min), lowest blood loss and shortest post-operative hospital stay (mean 2.31 days). RLN identification was above 96% in all approaches owing to better magnification. Transaxillary approach was associated with more RLN paresis than the TOETVA approach (4.85% vs. 16.13%; P = 0.002). Parathyroid identification without adjuncts was 91.6%, 80.64% and 62.5%, respectively, with three approaches. No patients had permanent hypocalcaemia with the TOETVA approach, which was significantly better in total thyroidectomy cases than the bilateral transaxillary approach. 16.13% and 25% of patients had seroma with unilateral and bilateral transaxillary approach, respectively, despite drain placement, which accounted for longer hospital stay. ET is safe and reliable with appropriate patient selection and has a skilled endoscopic surgeon. The approach selection depends on the size of the nodule and the surgeon comfort and preference. However based on our study results and experience we recommend the following:STN/MNG <4 cm: TOETVA STN 4-6 cm: Unilateral transaxillary approach MNG 4-6 cm: Bilateral transaxillary approach.

The aims of this study were: ① to evaluate the diagnostic efficacy of six mainstream TI-RADS (Thyroid Imaging Reporting and Data System) classification systems (C-TIRADS, ACR-TIRADS, etc.) in the Northwestern Chinese population; and ② to identify risk factors for malignant thyroid nodules (TNs) using logistic regression based on clinical and ultrasound features, construct a quantifiable scoring Nomogram model, enable rapid and objective risk assessment, and assist in clinical decision-making. A total of 2,047 patients with TNs (1,433 malignant and 614 benign) were enrolled from January 2018 to January 2024 at Shaanxi Provincial People's Hospital. The nodules were divided into a training group (1,435 nodules) and a validation group (612 nodules) in a 7:3 ratio. Twelve characteristics were collected, including age, nodule size, margin, calcification, and the presence of suspicious lymph nodes. Independent risk factors were identified through univariate and multivariate logistic regression analyses to construct a Nomogram model. The model's performance was evaluated using receiver operating characteristic (ROC) curves, accuracy, and other metrics, and compared with the six traditional TI-RADS systems. Ten independent risk factors were identified, including age, nodule size, and irregular margins. In the validation group, the Nomogram model achieved an accuracy of 78.4%, a sensitivity of 81.6%, a specificity of 71.7%, and an area under the ROC curve (AUC) of 0.849. The sensitivities of the six TI-RADS systems (C-TIRADS, ACR-TIRADS, EU-TIRADS, ATA Guidelines, Kwak-TIRADS, and AACE) for distinguishing benign and malignant nodules were 86.0%, 93.2%, 96.9%, 98.3%, 84.4%, and 98.1%, respectively; specificities were 55.6%, 34.8%, 25.3%, 22.2%, 57.1%, and 21.7%, respectively; accuracies were 76.1%, 74.3%, 73.7%, 73.7%, 75.8%, and 73.4%, respectively; and AUCs were 0.752, 0.661, 0.628, 0.617, 0.757, and 0.616, respectively, with no statistically significant differences among them. The Nomogram model significantly outperformed the traditional systems in measures such as AUC, Net Reclassification Improvement (NRI), Integrated Discrimination Improvement (IDI), Positive Likelihood Ratio (PLR), and Negative Likelihood Ratio (NLR) (P < 0.001). The six traditional TI-RADS systems demonstrate similar but overall limited diagnostic efficacy in the Northwestern Chinese population. The Nomogram model, by integrating multidimensional features and applying a quantitative scoring approach, improves the accuracy and objectivity of malignancy risk assessment. Compared to traditional models, it offers better clinical utility, supports optimized decision-making, and helps reduce unnecessary invasive procedures.

Perivascular epithelioid cell tumor (PEComa) is a rare mesenchymal neoplasm, and primary involvement of the thyroid gland is exceedingly rare. TFE3-rearranged PEComas constitute a distinct molecular subset characterized by epithelioid morphology and strong nuclear TFE3 expression. Cytologic descriptions of PEComa are limited, and to date, only three cytologic cases of TFE3-rearranged PEComa or PEComa-like neoplasm have been reported in the literature, none of which involved the thyroid gland. We report a case of thyroid TFE3-rearranged PEComa-like neoplasm in a 25-year-old woman who presented with a palpable thyroid nodule. Fine-needle aspiration using liquid-based cytology revealed a hypercellular specimen composed predominantly of dispersed and loosely cohesive epithelioid cells with enlarged round to oval nuclei, fine chromatin, and frequent intranuclear pseudoinclusions, resulting in an initial interpretation suspicious for papillary thyroid carcinoma. Histologic examination demonstrated a well-circumscribed epithelioid neoplasm with pseudoalveolar architecture supported by a delicate arborizing vascular network. Immunohistochemical studies showed tumor cell positivity for TFE3, cathepsin K, desmin (patchy), and vimentin, with negativity for epithelial, thyroid-specific, melanocytic, and other smooth muscle markers, as well as PAX8, CD10, MiTF, and PAS/PAS-D stains, arguing against metastatic renal cell carcinoma and alveolar soft part sarcoma. The patient underwent surgical resection and remains disease-free after 7.5 years of follow-up. This case represents the first description of the liquid-based cytologic features of a thyroid TFE3-rearranged PEComa-like neoplasm. Awareness of this rare entity and its cytologic overlap with papillary thyroid carcinoma is essential to avoid diagnostic pitfalls in thyroid fine-needle aspiration.

Ultrasound-guided radiofrequency ablation (RFA) of benign thyroid nodules is an effective, minimally invasive alternative to surgery but has a steep learning curve and limited formal training options. Toward addressing this gap, we developed a mixed reality simulator for thyroid nodule RFA. We implemented a real-time, voxel-based heat-transfer model of a thyroid nodule that computes temperature, thermal damage, and temperature-dependent impedance within a mixed reality simulator. The model was calibrated and verified with published RFA data from a thermal property-matched thyroid phantom and validated against published ex vivo lesion volumes. The simulator provides configurable nodule size and location, renders RFA ultrasound artifacts and lesion visualization, computes quantitative ablation metrics, and includes an interactive virtual RFA generator interface. Simulated temperature-time curves matched phantom sensor readings with a root mean square error of 1.4°C. Simulated lesion volumes were within - 7.3% to + 0.9% of the ex vivo reference across 1.0-0.125 mm3 voxel volumes and lesion aspect ratios were lower by 4.7-10.5%. In a post-use survey, a single expert clinician rated visual realism, feedback fidelity, and training utility favorably. The simulator closely reproduced phantom temperature profiles and ex vivo lesion sizes. Its architecture is configurable and extensible to other organs and thermal ablation modalities. Formal educational studies are warranted to evaluate training effectiveness of the simulator.

Medical ultrasound (US) image segmentation faces significant challenges due to limited labeled data and characteristic imaging artifacts, including speckle noise and low-contrast boundaries. While semi-supervised learning (SSL) approaches have emerged to address data scarcity, existing methods suffer from suboptimal unlabeled data utilization and lack robust feature representation mechanisms. In this article, we propose Switch, a novel SSL framework with two key innovations: 1) a multiscale switch (MSS) strategy that employs hierarchical patch mixing to achieve uniform spatial coverage; and 2) a frequency-domain switch (FDS) with contrastive learning that performs amplitude switching in Fourier space for robust feature representations. Our framework integrates these components within a teacher-student architecture to effectively leverage both labeled and unlabeled data. Comprehensive evaluation across six diverse US datasets (lymph nodes, breast lesions, thyroid nodules, and prostate) demonstrates consistent superiority over state-of-the-art (SOTA) methods. At a 5% labeling ratio, Switch achieves remarkable improvements: 80.04% Dice on LN-INT, 85.52% Dice on DDTI, and 83.48% Dice on Prostate datasets, with our semi-supervised approach even exceeding fully supervised baselines. The method maintains parameter efficiency (1.8 M parameters) while delivering superior performance, validating its effectiveness for resource-constrained medical imaging applications. The source code is publicly available at https://github.com/jinggqu/Switch.

Thyroid-stimulating hormone (TSH) suppression therapy plays an important role in the postoperative management of patients with differentiated thyroid cancer (DTC). However, its role in low-risk DTC (LR-DTC) remains controversial. This article reviewed domestic and international guidelines and relevant literature on TSH suppression therapy, finding that current guidelines worldwide generally show a trend toward gradually relaxing TSH suppression targets for LR-DTC patients. The latest guidelines from the American Thyroid Association (ATA), the National Comprehensive Cancer Network Thyroid Carcinoma Guidelines, and the Japanese Guidelines for the Treatment of Thyroid Tumors advocate a more lenient TSH suppression strategy for LR-DTC patients, recommending no suppression for those with excellent response or those who have undergone lobectomy. The most recent European Society for Medical Oncology Clinical Practice Guidelines for thyroid cancer and the Chinese Guidelines for the Diagnosis and Treatment of Thyroid Nodules and Differentiated Thyroid Cancer primarily reference the 2015 ATA guidelines, currently adopting a mild suppression approach by recommending that the TSH levels be maintained at the low end of the normal range. Recent large-scale studies tend to support further relaxation of TSH suppression targets for LR-DTC patients. There has still been no consensus regarding the optimal duration of TSH suppression therapy, as well as its application during active surveillance and after thermal ablation. There is an urgent need for more large-scale, multicenter prospective studies to provide stronger evidence-based support for formulating TSH suppression strategies in LR-DTC patients.

Thyroid cancer and thyroid nodules in acromegaly: a single-center retrospective study.

Evaluation of a conversation aid for patients with thyroid nodules considering a biopsy: pilot multicenter randomized control trial.

Introduction Thermal ablation (TA) is increasingly used to treat benign thyroid nodules; however, a residual risk of occult malignancy persists despite two benign cytology results. We aimed to: (1) evaluate the proportion of non-benign histological results among patients excluded from TA during multidisciplinary team meetings (MDTMs); (2) identify clinical and ultrasonographic features suggestive of malignancy and (3) assess non-benign outcomes among patients treated with TA who subsequently underwent surgery. Methods We conducted a retrospective single-center cohort study in a tertiary referral hospital between January 2019 and December 2023. Patients referred for TA with two benign cytology results but excluded after MDTM review were analyzed. Patients treated with TA who later underwent surgery were also reviewed. The primary endpoint was the proportion of non-benign histological results among surgically treated patients excluded from TA after MDTM review. Results Among 573 patients discussed at MDTM, 131 (23%) were deemed ineligible for TA. Of these, 61 (47%) underwent surgery. Non-benign histology was identified in 6 of 61 operated patients (10%), corresponding to 4.6% of all excluded patients. Among 219 patients treated with TA, three (1.4%) required surgery during follow-up. Histology revealed one benign lesion, one noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), and one tumor of uncertain malignant potential. Conclusion Systematic MDTM evaluation in an expert center identified non-benign nodules among patients excluded from TA, while non-benign outcomes after TA were rare. These findings should be interpreted cautiously given the retrospective design and limited number of events.

Thyroid scintigraphy with 99mTc-pertechnetate is a nuclear medicine examination performed since the early 1970s that allows for functional assessment of the thyroid. Quantitative thyroid uptake expressed as a percentage of the injected dose is calculated in many centres as part of the examination. Our current normal institutional reference of 1%-4% was derived from a 1971 study. Uptake values may change with geographical location and over time, with international studies reporting updated normal reference values for local populations of 0.2%-2.0%, 0.2%-2.0%, 0.26%-1.64% and 0.4%-2.4%. To our knowledge, there have been no published reports on normal reference values for Australian populations. The aim of this study was to establish normal reference values for 99mTc-pertechnetate thyroid uptake in a Victorian, Australian patient population. A retrospective audit and prospective study of 271 consecutive patients undergoing parathyroid scans was performed between January 2017 and December 2021. Anterior thyroid images acquired following intravenous injection of 99mTc-pertechnetate were reviewed to calculate thyroid uptake. Patients with thyroid conditions, abnormal biochemical thyroid function tests and/or abnormal appearances on 99mTc-pertechnetate thyroid scans were excluded. Of the 271 patients, 151 studies met the eligibility criteria and were included for analysis. The median thyroid uptake value was 0.97% with a 95% reference range of 0.4%-2.4%. This study established a thyroid uptake reference range of 0.4%-2.4% using 99mTc-pertechnetate, which was lower than the values used in our institution. Highlighting the need for periodic evaluation of normal uptake values.

Radiofrequency ablation (RFA) has become an established minimally invasive treatment for benign thyroid nodules (BTN), offering excellent safety and efficacy. However, factors predicting treatment success and post-procedural thyroid dysfunction remain incompletely understood. This study aimed to perform a preliminary evaluation of clinical, procedural, and biochemical predictors of RFA outcomes in a real-world consecutive patient cohort. A retrospective analysis was conducted on consecutive patients who underwent ultrasound-guided RFA for cytologically benign thyroid nodules between January 2018 and March 2024 at a single tertiary medical centre. Demographic, sonographic, procedural, and biochemical variables, including thyroid-stimulating hormone (TSH), thyroglobulin (Tg), and anti-Tg antibodies, were analysed. The primary endpoint was the Volume Reduction Ratio (VRR), with ≥ 50% defined as procedural success. Sixty-two patients (mean age 52.6 years; 85.5% female) were included. The median best VRR achieved was 61.9% (IQR 46.6-74.5), with 71% of patients attaining ≥ 50% reduction. Higher pre-treatment Tg levels were significantly associated with reduced VRR (p < 0.001) and remained independently associated with procedural failure in an exploratory multivariable model (OR 0.87 per 10 ng/mL increase, p = 0.011). Pretreatment TSH levels showed a univariate positive trend but did not reach statistical significance on multivariate analysis. Two patients (3.2%) developed hypothyroidism post-RFA, both with positive anti-Tg antibodies (total 13 patients had positive anti Tg Ab). The overall complication rate was 6.5%, with no major adverse events. Our results suggest that pre-treatment thyroglobulin levels may serve as a potential biochemical predictor of RFA success in benign thyroid nodules, while antibody positivity may suggest susceptibility to post-ablation hypothyroidism. While most existing literature focuses on imaging features (e.g., sonographic features) or surgeon technique, our findings highlight the unique importance of biochemical characteristics. Incorporating biochemical profiling into pre-procedural assessment could refine patient selection and enhance individualised treatment planning. Future prospective studies are warranted to validate Tg as a biomarker of RFA response.

Mutations in RAS proto-oncogenes (NRAS, HRAS, KRAS) are common in thyroid nodules, though their prognostic significance remains unclear. This retrospective study analyzed 354 thyroid nodules from 346 patients (2018-2023) to investigate the clinical and pathological implications of isolated RAS mutations and RAS with co-occurring genetic alterations. Isolated RAS mutations were found in 41.0% (n = 145), while 54.8% (n = 194) had RAS with additional molecular alterations; NRAS was the most frequent subtype (62.1%). Among co-occurring mutations, EIF1AX (46.7%) and TERT (26.7%) were the most common, primarily in NRAS-positive cases. Surgical follow-up data from 302 cases revealed a malignancy rate of 52.3% (n = 158), with 60.1% (n = 95) being invasive encapsulated follicular variant of papillary thyroid carcinoma (IEFVPTC). NRAS mutations appeared in 64.6% of malignant cases. Isolated RAS mutations were mainly associated with benign/low-risk neoplasms (47.0%), notably follicular adenomas and encapsulated non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), or malignancies (41.0%). The malignancy rate was higher in nodules with a RAS mutation plus one concomitant molecular alteration (54.3%), and nearly 100% in those with three additional genetic alterations. Co-occurring genetic alterations with RAS mutations markedly increased the risk of malignancy compared with isolated RAS mutations (Fisher's exact test, two-tailed p = 0.0026) and were associated with more aggressive tumor phenotypes, whereas isolated RAS mutations were more common in indolent neoplasms. Comprehensive molecular profiling is essential for accurate risk stratification and management of indeterminate thyroid nodules.

Evaluation and Management of Thyroid Nodules: A Joint Consensus Statement From the British Thyroid Association (BTA), British Association of Endocrine and Thyroid Surgeons (BAETS) and Collaborating Bodies.

Decreased expression of thyroid peroxidase (TPO) is frequently observed in thyroid cancer, but the underlying regulatory mechanism remains largely unknown. This study aimed to elucidate the epigenetic basis of TPO silencing and assess its potential value for the diagnosis of thyroid cancer. DNA methylation and expression levels of TPO were analyzed using the Infinium HumanMethylation450 array and transcriptome data from The Cancer Genome Atlas thyroid cancer dataset and validated in clinical tissue samples by bisulfite sequencing polymerase chain reaction (PCR) and quantitative PCR (qPCR). Thyroid cancer cell lines MDA-T41, KTC-1, CAL62, and TTA1 were treated with the demethylating drug decitabine and subjected to DNA methylation and mRNA expression analyses. Potential regulatory proteins were identified through DNA pull-down coupled with LC-MS/MS and validated by chromatin immunoprecipitation, luciferase reporter assay, and qPCR. A pyrosequencing assay was designed to quantify the methylation level of TPO. TPO expression was markedly downregulated in thyroid cancer and showed a strong inverse correlation with DNA methylation level at TPO differentially methylated region (DMR). Treatment of thyroid cancer cells with decitabine induced significantly decreased methylation level of TPO DMR and increased expression of TPO. Mechanistic analyses demonstrated that DNA hypermethylation suppressed TPO expression by recruiting methyl-CpG binding domain protein 2 (MBD2). Moreover, a pyrosequencing-based method for quantifying TPO methylation level was developed, and a remarkable difference between malignant and benign thyroid nodules (BTNs) was observed. Two CpG sites within TPO DMR achieved diagnostic performance with areas under the receiver operating characteristic curves of 0.927 (95% confidence interval [CI]: 0.864-0.989) and 0.916 (95% CI: 0.846-0.987), respectively. DNA hypermethylation suppresses TPO transcription by recruiting MBD2 in thyroid cancer. Quantitative assessment of TPO methylation by pyrosequencing offers a promising molecular diagnostic approach to distinguish malignant cancer from BTN. Further studies are warranted to ascertain the clinical diagnostic utility of these findings.

Thyroid nodules are among the most frequently encountered endocrine abnormalities, affecting up to two-thirds of adults in iodine-sufficient regions. Although thyroid-stimulating hormone (TSH) and genetic mutations have long been implicated in their pathogenesis, emerging evidence reveals a multifactorial interplay between inflammatory, hormonal, toxic, and micronutrient influences that extend beyond the classical model. This narrative review examines the converging biological pathways that contribute to thyroid nodule formation, emphasizing the integrative roles of inflammation, estrogen signaling, environmental endocrine disruptors, and micronutrient imbalance in altering thyroid cellular homeostasis. Chronic low-grade inflammation and oxidative stress create a permissive microenvironment for thyrocyte proliferation and clonal expansion. Estrogen receptor activation-amplified by insulin and IGF-1 signaling-enhances vascular and proliferative responses within thyroid tissue, contributing to the female predominance of nodular disease. Exposure to heavy metals and xenoestrogens disrupts thyroid peroxidase activity, deiodinase regulation, and immune tolerance, while deviations in iodine, selenium, zinc, and vitamin D status further impair redox balance and DNA repair mechanisms. Together, these factors promote a spectrum of structural changes ranging from microscopic hyperplasia to clinically significant nodules. Thyroid nodules represent a visible manifestation of intersecting metabolic and environmental stressors rather than a single endocrine defect. Integrating insights from molecular endocrinology, environmental toxicology, and nutritional science may advance early detection and preventive strategies targeting the inflammatory-hormonal-toxic axis of thyroid disease.

Thyroid nodules are common, and accurate classification into benign or malignant types is essential for effective clinical management. Although high-resolution ultrasound is the primary diagnostic tool, its accuracy is limited by operator dependency. Recent advances in deep learning have shown promise for automated and objective assessment, but many existing methods lack focus on lesion-specific regions, compromising model robustness. To overcome these limitations, we propose a novel dual-branch deep learning framework that combines lesion segmentation and classification. A key feature of this framework is a nodule mask-guided feature enhancement module, which leverages probability masks from the segmentation branch to guide the classification branch toward diagnostically relevant regions while suppressing irrelevant information. Evaluated on ultrasound datasets from three medical centers, our approach demonstrates superior classification accuracy compared to baseline methods, highlighting its potential as a reliable computer-aided diagnosis tool for thyroid nodules.

Although the diagnostic performance of calcitonin (CTN) in revealing medullary thyroid carcinoma (MTC) has been widely demonstrated, to date, neck ultrasound (neck US) and FNAC remain the first-line tools in searching for malignancy in thyroid nodules. This study aims to determine which tool is more effective at suggesting MTC among preoperative CTN values and FNAC, compared with the estimated risk of malignancy at neck US according to the 5 main risk stratification systems (RSS), in a population of patients with already diagnosed MTC. We evaluated preoperative serum CTN, FNAC, and neck US data in 104 patients with sporadic MTC (2014-2020) managed at the Unit of Endocrinology of the Pisa University Hospital, Italy. According to the neck US RSS, 59.6% of patients were classified as the intermediate-low suspicion (ILS) and 40.4% as the high suspicion (HS) group. FNAC, performed according to clinical judgment in 85/104 (81.7%) cases, was diagnostic of MTC in only 45.9% of cases. Moreover, according to the guidelines, 39 (62.9%) nodules in the ILS and 14 (33.3%) in the HS group would not even be submitted for FNAC. Of note, most of these MTCs had tumor dimensions > 1cm and/or lymph node metastases. Conversely, the preoperative CTN values suggested at least a suspicion of MTC in both US risk groups and across all MTC US dimension categories, including microcarcinomas. Among patients with a confirmed diagnosis of MTC, serum CTN values were the most reliable parameter, outperforming ultrasound features and FNAC in diagnostic accuracy. Delaying or failing to diagnose MTC is undesirable if the aim is to achieve early diagnosis and effective treatment of these patients.