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Search Results (478)

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15 pages, 3133 KB  
Article
Correlation Between Thyroid Nodule Size and Risk of Thyroid Cancer: A Retrospective Cohort Study at a Tertiary Care Center
by Osama Zeidan, Talal Sarhan, Zeid Alkhairi, Omar Abusedera, Qaswar Sudani, Hasan Kadhem, Jenan Obaid and Alexandra E. Butler
Diagnostics 2026, 16(10), 1505; https://doi.org/10.3390/diagnostics16101505 - 15 May 2026
Abstract
Background: Thyroid nodules are common, yet only a small proportion are malignant. The independent role of nodule size in malignancy risk remains debated, particularly after adjustment for clinical, biochemical, and sonographic features. Methods: A retrospective cohort study was conducted on adult patients with [...] Read more.
Background: Thyroid nodules are common, yet only a small proportion are malignant. The independent role of nodule size in malignancy risk remains debated, particularly after adjustment for clinical, biochemical, and sonographic features. Methods: A retrospective cohort study was conducted on adult patients with thyroid nodules evaluated between 2018 and 2025 at a tertiary care center. Clinical, laboratory, ultrasound, cytology, and histopathology data were extracted. Thyroid-stimulating hormone (TSH), free thyroxine (free T4), and sonographic characteristics were analyzed. Univariable and multivariable logistic regression were performed. Missing ultrasound data were addressed using multiple imputation (m = 20), with pooled estimates derived using Rubin’s rules. The final multivariable model included 446 patients. Results: A total of 446 patients were included, of whom 91 (20.4%) had thyroid malignancy. Malignant nodules were significantly larger than benign nodules (2.30 [1.80] cm vs. 1.80 [1.13] cm; p = 0.015). In univariable analysis, TSH, free T4, and multiple ultrasound features were associated with malignancy. In multivariable analysis, nodule size remained the strongest independent predictor of malignancy (adjusted odds ratio [aOR] 1.51; p < 0.001). Hypoechogenicity (aOR 2.07; p = 0.020) and microcalcifications (aOR 1.86; p = 0.047) also remained independently significant, whereas thyroid function parameters were not associated with malignancy after adjustment. Conclusions: Thyroid nodule size is the strongest independent predictor of malignancy, with select ultrasound features retaining additional predictive value. These findings support incorporating nodule size more prominently into thyroid cancer risk stratification while maintaining key sonographic features. Full article
(This article belongs to the Section Clinical Diagnosis and Prognosis)
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11 pages, 241 KB  
Article
Risk Stratification of Indeterminate Thyroid Nodules (TIR3A vs. TIR3B): Impact of NIFTP Reclassification in a Surgical Cohort
by Pietro De Luca, Giulia Chiappino, Luca de Campora, Anna Sambito, Angelo Camaioni and Claudio Viti
Cancers 2026, 18(9), 1481; https://doi.org/10.3390/cancers18091481 - 5 May 2026
Viewed by 555
Abstract
Background: Indeterminate thyroid nodules classified as TIR3 according to the SIAPEC-IAP classification represent a heterogeneous group with variable malignancy risk, complicating clinical management. The reclassification of non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) has further influenced risk estimates. Methods: We conducted [...] Read more.
Background: Indeterminate thyroid nodules classified as TIR3 according to the SIAPEC-IAP classification represent a heterogeneous group with variable malignancy risk, complicating clinical management. The reclassification of non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) has further influenced risk estimates. Methods: We conducted a retrospective single-center study including adult patients who underwent ultrasound-guided fine-needle aspiration cytology followed by thyroid surgery between January 2016 and September 2025. Cytological diagnoses were classified according to the SIAPEC-IAP system and correlated with final histology. Ultrasound risk stratification was performed according to EU-TIRADS criteria. Risk of malignancy (ROM) and cytology–histology concordance were assessed, including the impact of NIFTP reclassification. Results: A total of 228 patients were included, with an overall malignancy rate of 27.6%. TIR3A nodules showed a significantly lower ROM than TIR3B (15.6% vs. 48.7%), decreasing to 12.5% and 41.4%, respectively, after exclusion of NIFTP. Cytology–histology agreement was substantial (κ = 0.72). Ultrasound features associated with malignancy included microcalcifications, irregular margins, taller-than-wide shape, and EU-TIRADS ≥4. The BRAF V600E mutation was significantly associated with malignant histology. Conclusions: TIR3A and TIR3B nodules exhibit markedly different malignant potential and should not be managed as a homogeneous group. NIFTP significantly modifies malignancy risk estimates and represents an important source of potential overtreatment. Integration of cytological subclassification with ultrasound and molecular findings improves preoperative risk stratification and supports personalized management of indeterminate thyroid nodules. Full article
(This article belongs to the Special Issue Targeted Therapy in Head and Neck Cancer)
17 pages, 3221 KB  
Article
Doppler–Scintigraphy Combination with Thyroxine Profiling Enhances Diagnostic Accuracy of Thyroid Lesions: A 144-Patient Cross-Sectional Study
by Reham Mohamed Taha, Moawia Gameraddin, Yasir Hassan Elhassan, Awadia Gareeballah, Osama Musa, Fatimah Ahmed Daghas, Ali Ibrahim Aamry, Nisreen Haj, Tasneem S. A. Elmahdi, Sahar A. Mustafa, Abdullah Fahad A. Alshamrani, Amel F. H Alzain and Awatif M. Omer
J. Clin. Med. 2026, 15(9), 3364; https://doi.org/10.3390/jcm15093364 - 28 Apr 2026
Viewed by 294
Abstract
Background: The characterization of thyroid lesions is essential in clinical practice. Recent advances in imaging modalities, including nuclear imaging (NM), color Doppler ultrasonography, and sonography, have markedly improved the diagnostic accuracy for thyroid nodules. Objective: To assess thyroid diseases using Doppler [...] Read more.
Background: The characterization of thyroid lesions is essential in clinical practice. Recent advances in imaging modalities, including nuclear imaging (NM), color Doppler ultrasonography, and sonography, have markedly improved the diagnostic accuracy for thyroid nodules. Objective: To assess thyroid diseases using Doppler ultrasound, nuclear scintigraphy, and sonography. Results: In this cross-sectional single-center study, 144 patients were examined to determine their thyroid structure and function using a multimodal imaging approach. Fine-needle aspiration cytology (FNAC) indicated that most thyroid nodules were benign (62.5%), with 37.5% being malignant. Doppler vascularity demonstrated a sensitivity of 70.4% and a specificity of 40% (AUC = 0.514) for malignancy detection, while scintigraphy uptake in hypofunctioning nodules (nodules with decreased radionuclide uptake) showed a sensitivity of 37% and a specificity of 54.4% (AUC = 0.388). Thyroxine hormone levels showed a sensitivity of 57.4% and a specificity of 45.6% (AUC = 0.503) for detecting malignant thyroid nodules. In multivariate logistic regression, increased Doppler vascularity remained an independent predictor of malignancy (OR = 2.39; 95% CI: 1.15–4.96; p = 0.019), whereas decreased scintigraphic uptake showed a borderline effect (OR = 1.82; p = 0.069); high T4 level and increased uptake were not significant predictors. The combined Doppler ultrasound, scintigraphy, and thyroxine level model yielded an AUC of 0.72 (95% CI: 0.63–0.81), markedly higher than any single parameter. At the optimal Youden threshold (0.43), the model achieved 79.6% sensitivity, 68.2% specificity, and 72.4% accuracy, highlighting the superior diagnostic performance of the integrated approach for pre-FNAC stratification of thyroid malignancies. There was a strong, significant linear association between thyroxine levels and thyroid scintigraphy uptake (p-value < 0.001). Most patients with normal thyroxine levels exhibited decreased uptake (66.1%), whereas a minority (6.5%) demonstrated elevated uptake levels. This study found a strong correlation between mixed-echogenicity nodules and thyroid scintigraphy uptake (p-value = 0.019). Mixed-echogenicity nodules were most often associated with reduced uptake (57.8%), and hypoechoic nodules often had normal uptake (57.1%). Conclusions: The complementary integration of color Doppler vascularity, Tc-99m thyroid scintigraphy, and serum thyroxine levels yields superior Doppler–scintigraphy uptake correlation, increases the overall diagnostic accuracy, and offers a practical, non-invasive algorithm for differentiating benign from malignant thyroid nodules prior to FNAC or surgery. Full article
(This article belongs to the Section Nuclear Medicine & Radiology)
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22 pages, 5208 KB  
Review
Interventional Radiology in the Management of Parathyroid Disorders: Current Diagnostic and Therapeutic Approaches
by Onur Taydas, Erbil Arik, Mehmet Ali Durmus, Volkan Tasci, Omer Faruk Topaloglu, Mustafa Ozdemir, Yusuf Ozturk, Mahmud Islam, Zulfu Bayhan and Mehmet Halil Ozturk
J. Clin. Med. 2026, 15(9), 3360; https://doi.org/10.3390/jcm15093360 - 28 Apr 2026
Viewed by 358
Abstract
This narrative review evaluates the current role of interventional radiology in the diagnosis and treatment of parathyroid disorders. In patients with biochemically confirmed hyperparathyroidism but inconclusive or discordant preoperative localization imaging, image-guided interventions can help establish a diagnosis that can alter management. This [...] Read more.
This narrative review evaluates the current role of interventional radiology in the diagnosis and treatment of parathyroid disorders. In patients with biochemically confirmed hyperparathyroidism but inconclusive or discordant preoperative localization imaging, image-guided interventions can help establish a diagnosis that can alter management. This review outlines the current diagnostic and therapeutic modalities for the study of parathyroid pathology from the interventional radiologist’s perspective, highlighting novel techniques and their growing clinical adoption. The combination of ultrasound-guided fine-needle aspiration biopsy and measurement of parathyroid hormone (PTH) in the needle washout fluid can improve diagnostic specificity by providing biochemical evidence of parathyroid tissue. This is particularly useful for lesions that are difficult to differentiate from thyroid nodules or cervical lymph nodes based solely on imaging characteristics. Despite this, no widely accepted cut-off washout PTH level has yet been established. Due to the differences in assay techniques and laboratory procedures, results should be interpreted in conjunction with clinical findings and concomitant biochemical parameters. Ultrasound-guided thermal ablation techniques, especially radiofrequency and microwave ablation, have recently been reported as minimally invasive alternatives or adjuvants to surgery in appropriately selected patients. Evidence supporting parathyroid embolization is limited, but it may be considered a potential salvage option for persistent or recurrent disease. Given that most of the current evidence is derived from retrospective case series, multicenter prospective studies for technical standardization and long-term outcomes evaluation are clearly needed. Full article
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12 pages, 780 KB  
Article
Disease-Relevant Preoperative Serum miRNA Levels in Papillary Thyroid Cancer
by Olga Bourogianni, Eliza Tsitoura, Konstantinos Sifakis, Nikolaos Kapsoritakis, Alexander Karatzanis, Maria Doulaptsi, Katerina Antoniou, Sophia Koukouraki and Emmanuel Prokopakis
Biology 2026, 15(8), 626; https://doi.org/10.3390/biology15080626 - 16 Apr 2026
Viewed by 376
Abstract
Background: Papillary thyroid cancer (PTC) is the most common form of thyroid malignancy, with an incidence that has been steadily rising globally. Early and accurate diagnosis remains crucial for effective treatment and improved outcomes. MicroRNAs (miRNAs), small non-coding RNA molecules that regulate gene [...] Read more.
Background: Papillary thyroid cancer (PTC) is the most common form of thyroid malignancy, with an incidence that has been steadily rising globally. Early and accurate diagnosis remains crucial for effective treatment and improved outcomes. MicroRNAs (miRNAs), small non-coding RNA molecules that regulate gene expression, have emerged as promising biomarkers in cancer research due to their stability and accessibility in serum. In this pilot study we compared the expression of 84 consistently reported, malignancy-associated serum miRNAs in patients with PTC (PTC group) and benign thyroid disease (Control group) as potential PTC markers. Methods: A focused panel containing primer assays for 84 human miRNAs that are consistently reported in the literature as being detectable and differentially expressed in serum in various organ-specific cancers was used to measure miRNA levels in serum samples from PTC (n = 8) and benign thyroid disease (n = 6) patients prior to thyroidectomy. Results: Among the 84 miRNAs analyzed, a panel of ten miRNAs showed numerical trends of differential expression between the two groups, including three upregulated (hsa-miR-150-5p, hsa-miR-21-5p, hsa-miR-23a-3p) and seven downregulated miRNAs (hsa-miR-17-5p, hsa-miR-17-3p, hsa-miR-200c-3p, hsa-miR-296-5p, hsa-miR-574-3p, hsa-miR-885-5p, hsa-miR-130-3p). The serum expression levels of hsa-miR-23a-3p were markedly elevated in patients with malignant nodules compared with those with benign lesions, while hsa-miR-574-3p was significantly downregulated in the PTC group. Conclusions: These findings warrant further investigation of hsa-miR-23a-3p and hsa-miR-574-3p in larger cohorts of patients with PTC to validate their potential clinical relevance. Full article
(This article belongs to the Special Issue Signalling Pathways in Cancer and Disease)
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22 pages, 2097 KB  
Article
Thyroid-Originating Extracellular Vesicles Harbor Thyroid-Specific Biomarkers with Potential Relevance for Thyroid Cancer Recurrence Detection
by Nevena Bobar, Ninoslav Mitić, Maja Kosanović, Sonja Šelemetjev, Tijana Išić Denčić, Katarina Taušanović and Jelena Janković Miljuš
Int. J. Mol. Sci. 2026, 27(8), 3510; https://doi.org/10.3390/ijms27083510 - 14 Apr 2026
Viewed by 382
Abstract
Thyroid cancer (TC) is the most common endocrine malignancy, and challenges persist in preoperative diagnosis of indeterminate nodules and postoperative monitoring when thyroglobulin (Tg) assays are compromised by interfering anti-Tg antibodies (Tg-Ab). Extracellular vesicles (EVs) carry molecular cargo reflective of cells of origin [...] Read more.
Thyroid cancer (TC) is the most common endocrine malignancy, and challenges persist in preoperative diagnosis of indeterminate nodules and postoperative monitoring when thyroglobulin (Tg) assays are compromised by interfering anti-Tg antibodies (Tg-Ab). Extracellular vesicles (EVs) carry molecular cargo reflective of cells of origin and are increasingly explored as biomarker sources. In this study, we investigated whether thyroid-derived EVs retain the expression of thyroid-specific thyrotropin-receptor (TSHR), a suitable target in immunoaffinity-based EV isolation, and explored the presence of Tg in EV cargo as potential surrogate for serum Tg. EVs from thyroid cell lines (Nthy-Ori 3-1, TPC-1, OCUT2) and plasma of patients with benign, malignant tumors and recurrent TC were isolated by differential ultracentrifugation and characterized via nanoparticle tracking and Dot and Western blot analyses. EVs derived from Nthy-Ori 3-1 and TPC-1 cell lines were positive for surface TSHR and vesicular Tg, but not OCUT2. All plasma-derived EVs were positive for TSHR and Tg, while their electrophoretic profiles from vesicles differed compared to tissue lysate. Tg was detectable in EVs isolated from recurrent TC samples, even in Tg-Ab positive cases. Together, these results support the use of TSHR for targeted EV isolation and point to vesicular Tg as a potential recurrence marker. Full article
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17 pages, 1520 KB  
Article
Clinical Value of Core Needle Biopsy as a Second-Line Approach After Non-Conclusive Fine-Needle Aspiration in Thyroid Nodules: A Paired Analysis
by Vladan Markovic, Slobodanka Mitrovic, Tijana Maksic, Irfan Corovic, Marija Sekulic, Mladen Maksic and Vesna Grbovic
Diagnostics 2026, 16(7), 1104; https://doi.org/10.3390/diagnostics16071104 - 7 Apr 2026
Viewed by 442
Abstract
Background: Fine-needle aspiration biopsy (FNAB) is the standard initial diagnostic procedure for thyroid nodules; however, a considerable proportion of results are non-diagnostic or indeterminate, often requiring repeat procedures and delaying management. Core needle biopsy (CNB) has been proposed as a second-line option. This [...] Read more.
Background: Fine-needle aspiration biopsy (FNAB) is the standard initial diagnostic procedure for thyroid nodules; however, a considerable proportion of results are non-diagnostic or indeterminate, often requiring repeat procedures and delaying management. Core needle biopsy (CNB) has been proposed as a second-line option. This study evaluated the frequency of non-conclusive FNAB and CNB results and assessed the diagnostic contribution of CNB in nodules with initially non-conclusive FNAB findings. Methods: A retrospective–prospective study was conducted between 2019 and 2025 at a tertiary referral center, including 434 thyroid nodules. Ultrasound risk stratification followed ACR TI-RADS criteria. FNAB was performed in 430 nodules, and CNB in 85 nodules, including 82 evaluated by both methods. Biopsy results were classified according to the Bethesda system as conclusive or non-conclusive. Paired comparisons were analyzed using the McNemar test, and associations with ultrasound risk were assessed. Results: FNAB produced non-conclusive results in 56.5% of cases, compared with 23.5% for CNB. In paired analysis, 53.7% of nodules with non-conclusive FNAB were reclassified as conclusive after CNB (p < 0.001). CNB significantly distinguished benign from malignant lesions, unlike FNAB. Hypoechogenicity, irregular margins, and punctate echogenic foci were independent predictors of malignancy. Minor complications were more frequent after CNB, while major complications were rare in both groups. Conclusions: CNB improves diagnostic yield when used as a second-line procedure in nodules with non-conclusive FNAB findings. Selective use in higher-risk nodules may reduce repeat procedures and facilitate more structured clinical management. Full article
(This article belongs to the Section Pathology and Molecular Diagnostics)
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9 pages, 218 KB  
Opinion
Thyroid Artery Embolization for Benign Thyroid Hyperplasia
by Alan A. Sag, Saim Yilmaz, Nariman Nezami, Gary Tse, Shamar J. Young, Tim Huber, Ravi N. Srinivasa, Juan C. Camacho, Nassir Rostambeigi, Venkatesh P. Krishnasamy, Erik N. K. Cressman, Marc Sapoval and Jafar Golzarian
J. Clin. Med. 2026, 15(7), 2664; https://doi.org/10.3390/jcm15072664 - 1 Apr 2026
Viewed by 706
Abstract
Thyroid artery embolization (TAE) is emerging as a potential minimally invasive therapy for benign thyroid hyperplasia (BTH), including multinodular goiter and Graves’ disease, particularly for patients who are poor surgical candidates or who decline surgery. This review summarizes contemporary evidence, technical practices, and [...] Read more.
Thyroid artery embolization (TAE) is emerging as a potential minimally invasive therapy for benign thyroid hyperplasia (BTH), including multinodular goiter and Graves’ disease, particularly for patients who are poor surgical candidates or who decline surgery. This review summarizes contemporary evidence, technical practices, and areas of consensus and heterogeneity in this technique. Full article
(This article belongs to the Special Issue New Insights into Clinical Application of Embolization Techniques)
10 pages, 1624 KB  
Article
Ultrasonographic Microcalcifications in Metastatic Lymph Nodes of Papillary Thyroid Carcinoma: A Sonopathological Study
by Adile Begüm Bahçecioğlu, Meliha Merve Ekelik Özyılmaz, Muhammed Şamil Özlü, Serpil Dizbay Sak, Sevim Güllü and Murat Faik Erdoğan
Diagnostics 2026, 16(7), 1048; https://doi.org/10.3390/diagnostics16071048 - 31 Mar 2026
Viewed by 429
Abstract
Background/Objectives: Ultrasonographic microcalcifications are highly specific imaging features of malignancy in both thyroid nodules and metastatic cervical lymph nodes in papillary thyroid carcinoma (PTC). However, although their histopathological correlates in thyroid nodules have been extensively investigated, the pathological substrates underlying microcalcifications in [...] Read more.
Background/Objectives: Ultrasonographic microcalcifications are highly specific imaging features of malignancy in both thyroid nodules and metastatic cervical lymph nodes in papillary thyroid carcinoma (PTC). However, although their histopathological correlates in thyroid nodules have been extensively investigated, the pathological substrates underlying microcalcifications in metastatic lymph nodes remain poorly defined, particularly for ultrasound-based diagnostic interpretation. Methods: This retrospective sonopathological cohort study included 32 patients with PTC, contributing 70 metastatic cervical lymph nodes. Lymph nodes were classified based on the presence or absence of microcalcifications detected by ultrasonography. Histopathological features—psammoma bodies, hyalinization, stromal calcification, cystic degeneration, and papillary formation—were systematically re-evaluated by pathologists blinded to ultrasonographic findings using a predefined semi-quantitative grading protocol. Microcalcification-positive metastatic lymph nodes were additionally compared with a reference cohort of microcalcification-positive thyroid nodules (n = 30). Results: Ultrasonographic microcalcifications were identified in 30 of 70 metastatic lymph nodes (42.9%). Microcalcification-positive lymph nodes demonstrated significantly higher frequencies of psammoma bodies (56.7% vs. 17.5%, p = 0.001), moderate-to-extensive psammoma bodies (40.0% vs. 12.5%, p = 0.003), stromal calcification (30.0% vs. 0.0%, p < 0.001), and cystic degeneration (80.0% vs. 12.5%, p < 0.001) compared with microcalcification-negative nodes. Notably, 43.3% of microcalcification-positive nodes lacked moderate-to-extensive psammoma bodies, indicating heterogeneous pathological correlates. Comparative analysis revealed no significant differences between microcalcification-positive nodes and thyroid nodules in the prevalence or extent of psammoma bodies or stromal calcification; however, hyalinization was significantly more frequent and extensive in thyroid nodules (both p < 0.001). Conclusions: Ultrasonographic microcalcifications in metastatic lymph nodes of PTC reflect heterogeneous histopathological correlates beyond psammoma bodies alone. These findings highlight the importance of anatomically informed, context-specific interpretation of microcalcifications in ultrasound-based diagnostic practice. Full article
(This article belongs to the Section Pathology and Molecular Diagnostics)
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34 pages, 6554 KB  
Article
Syncretic Grad-CAM Integrated ViT-CNN Hybrids with Inherent Explainability for Early Thyroid Cancer Diagnosis from Ultrasound
by Ahmed Y. Alhafdhi, Gibrael Abosamra and Abdulrhman M. Alshareef
Diagnostics 2026, 16(7), 999; https://doi.org/10.3390/diagnostics16070999 - 26 Mar 2026
Viewed by 442
Abstract
Background/Objectives: Accurate detection of thyroid cancer using ultrasound remains a challenge, as malignant nodules can be microscopic and heterogeneous, easily confused with point clusters and borderline-featured tissues. Current studies in deep learning demonstrate good performance with convolutional neural networks (CNNs) and clustering; however, [...] Read more.
Background/Objectives: Accurate detection of thyroid cancer using ultrasound remains a challenge, as malignant nodules can be microscopic and heterogeneous, easily confused with point clusters and borderline-featured tissues. Current studies in deep learning demonstrate good performance with convolutional neural networks (CNNs) and clustering; however, many approaches focus on local tissue and provide limited, non-quantitative interpretation, reducing clinical confidence. This study proposes an integrated framework combining enhanced convolutional feature encoders (DenseNet169 and VGG19) with an enhanced vision transformer (ViT-E) to integrate local feature and global relational context during learning, rather than delayed integration. Methods: The proposed framework integrates enhanced convolutional feature encoders (DenseNet169 and VGG19) with an enhanced vision transformer (ViT-E), enabling simultaneous learning of local feature representations and global relational context. This design allows feature fusion during the learning stage instead of delayed integration, aiming to improve diagnostic performance and interpretability in thyroid ultrasound image analysis. Results: The best-performing model, ViT-E–DenseNet169, achieved 98.5% accuracy, 98.9% sensitivity, 99.15% specificity, and 97.35% AUC, surpassing the robust basic hybrid model (CNN–XGBoost/ANN) and existing systems. A second contribution is improved interpretability, moving from mere illustration to validation. Gradient-weighted class activation mapping (Grad-CAM) maps demonstrated distinct and clinically understandable concentration patterns across various thyroid cancers: precise intralesional concentration for high-confidence malignancies (PTC = 0.968), edge/interface concentration for capsule risk patterns (PTC = 0.957), and broader-field activation consistent with infiltration concerns (PTC = 0.984), while benign scans showed low and diffuse activation (PTC = 0.002). Spatial audits reinforced this behavior (IoU/PAP: 0.72/91%, 0.65/78%, 0.58/62%). Conclusions: The integrated ViT-E–DenseNet169 framework provides highly accurate thyroid cancer detection while offering clinically meaningful interpretability through Grad-CAM-based spatial validation, supporting improved confidence in AI-assisted ultrasound diagnosis. Full article
(This article belongs to the Special Issue Deep Learning Techniques for Medical Image Analysis)
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16 pages, 1895 KB  
Article
The Value of Multimodal Ultrasound in Differentiating Benign from Malignant Cytologically Indeterminate Thyroid Nodules
by Rong Yang, Yanfang Wang, Guo Chen, Xiaorong Lv, Yuanqing Zhang and Fang Nie
Cancers 2026, 18(7), 1071; https://doi.org/10.3390/cancers18071071 - 25 Mar 2026
Viewed by 520
Abstract
Aim: To evaluate the diagnostic value of conventional ultrasound (CUS) and contrast-enhanced ultrasound (CEUS) features in differentiating benign from malignant Bethesda III/IV thyroid nodules, and to identify independent predictors of malignancy. Methods: We retrospectively analyzed 164 surgically confirmed Bethesda III/IV thyroid nodules. CUS [...] Read more.
Aim: To evaluate the diagnostic value of conventional ultrasound (CUS) and contrast-enhanced ultrasound (CEUS) features in differentiating benign from malignant Bethesda III/IV thyroid nodules, and to identify independent predictors of malignancy. Methods: We retrospectively analyzed 164 surgically confirmed Bethesda III/IV thyroid nodules. CUS and CEUS features were evaluated by two experienced radiologists blinded to pathological outcomes. Univariate analysis compared features between benign and malignant groups. Multivariate logistic regression was used to identify independent predictors. Diagnostic models were constructed based on CUS alone, CEUS alone, and their combination, with performance evaluated using receiver operating characteristic (ROC) curve analysis. The area under the curve (AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for each model. Results: The malignancy rate was 48.8% (80/164). Multivariate analysis identified microcalcifications (OR = 4.815, p < 0.001), aspect ratio >1 (OR = 2.499, p = 0.028), and irregular shape (OR = 2.465, p = 0.035) as independent risk factors, while older age (OR = 0.926 per year, p < 0.001) was protective. The CUS model achieved an AUC of 0.815 with high sensitivity (91.3%) and NPV (87.7%). The CEUS model performed poorly (AUC = 0.609). The combined model (AUC = 0.823) showed no significant improvement over CUS alone (p > 0.05). Physician subjective diagnosis based on CEUS TI-RADS yielded an AUC of 0.775. Conclusions: Conventional ultrasound features provide good diagnostic value for Bethesda III/IV nodules, with high sensitivity and NPV suitable for clinical screening. The addition of CEUS offered limited incremental benefit in this specific population, suggesting that the diagnostic value of CEUS for differentiating benign from malignant cytologically indeterminate thyroid nodules (ITNs) may be limited. Full article
(This article belongs to the Special Issue Application of Ultrasound in Cancer Diagnosis and Treatment)
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14 pages, 4768 KB  
Article
Prospective Optimization of Malignancy Risk Prediction in Indeterminate Thyroid Nodules: Diagnostic Synergy of ACR TI-RADS and the 2023 Bethesda System
by Ozlem Aydin, Bulent Colakoglu, Cavit Kerem Kayhan, Mehmet Güven Günver, Mariana Simplício, Joana Pinto Schmitt and Sule Canberk
Endocrines 2026, 7(1), 12; https://doi.org/10.3390/endocrines7010012 - 19 Mar 2026
Cited by 2 | Viewed by 637
Abstract
Background: Risk stratification of indeterminate thyroid nodules (Bethesda III–IV) remains difficult and often triggers unnecessary procedures. Ultrasound-based ACR TI-RADS and the 2023 Bethesda System are widely used, but the incremental value of combining them and the role of size thresholds needs prospective validation. [...] Read more.
Background: Risk stratification of indeterminate thyroid nodules (Bethesda III–IV) remains difficult and often triggers unnecessary procedures. Ultrasound-based ACR TI-RADS and the 2023 Bethesda System are widely used, but the incremental value of combining them and the role of size thresholds needs prospective validation. Objective: The objective of this study was to prospectively compare the diagnostic performance of ACR TI-RADS and the 2023 Bethesda System, alone and in combination, for predicting malignancy in thyroid nodules, with dedicated analyses of indeterminate lesions (Bethesda categories III–IV), including subtypes of Bethesda III (nuclear atypia vs. other atypia), and the impact of nodule size. Methods: Histopathology was available for 131 nodules. Diagnostic metrics (sensitivity, specificity, PPV, NPV), ROC curves (DeLong comparison), and Youden indices were calculated for individual and combined thresholds; a 16 mm size cut-off was explored. Results: Malignancy was confirmed in 105/131 nodules (80.2%). Bethesda outperformed TI-RADS (AUC 0.87 vs. 0.69; DeLong p = 0.041). Malignancy rates rose with higher categories (e.g., TI-RADS 5: 93.6%; Bethesda category V: 100%; Bethesda category VI: 100%) and were markedly elevated in the histologically confirmed subset for Bethesda category III (32/41; 78.0%) and IV (6/8; 75.0%). The combined requirement of TI-RADS ≥ 4 and Bethesda ≥ 4 maximized specificity (96.2%) and PPV (98.4%) with a high Youden J (0.552), supporting a rule-in strategy in category IV of Bethesda. Size alone was a weak discriminator (AUC 0.66); within Bethesda III–IV nodules, malignancy did not differ significantly by the 16 mm threshold (p = 1.00). ROC using continuous tumor size yielded AUC = 0.66; the ROC-derived optimal cut-off was 16 mm. Applying this split produced sensitivity 0.80 and specificity 0.50. Conclusions: Integrating ACR TI-RADS with Bethesda cytology significantly improves specificity and PPV for indeterminate thyroid nodules, supporting a morphology-driven approach over traditional size-based thresholds. Incorporation of combined sonographic–cytologic criteria into management algorithms may reduce unnecessary interventions and optimize patient care. Full article
(This article belongs to the Section Thyroid Endocrinology)
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13 pages, 1091 KB  
Article
Thyroid Nodule Detection and Classification on Small Datasets: An Ensemble Deep Learning Approach with Attention Mechanism and Focal Loss
by Wei-Chen Hung, Yi-Kai Chang, Chih-Ming Chang, Po-Wen Cheng, Wu-Chia Lo, Ping-Chia Cheng and Li-Jen Liao
Diagnostics 2026, 16(6), 825; https://doi.org/10.3390/diagnostics16060825 - 10 Mar 2026
Viewed by 709
Abstract
Background: Thyroid nodule classification on ultrasound remains challenging due to limited labeled data and marked class imbalance. This study proposes an integrated deep learning framework combining YOLO-based region-of-interest detection with an enhanced ResNet18 classifier. Methods: A total of 522 thyroid ultrasound [...] Read more.
Background: Thyroid nodule classification on ultrasound remains challenging due to limited labeled data and marked class imbalance. This study proposes an integrated deep learning framework combining YOLO-based region-of-interest detection with an enhanced ResNet18 classifier. Methods: A total of 522 thyroid ultrasound images from 522 patients examined between July 2020 and June 2024 were included. The dataset comprised 467 images for training (399 benign, 68 malignant), 41 for independent testing (19 benign, 22 malignant), and 14 for internal validation (4 benign, 10 malignant). An external validation set of 36 images (22 benign, 14 malignant) was collected from online sources. ResNet18 with a convolutional block attention module was used to enhance feature extraction. To address small sample size and class imbalance, the training pipeline incorporated focal loss, weighted random sampling, mixup augmentation, cosine annealing learning rate scheduling, and a 5-fold cross-validation ensemble. Results: The ensemble model achieved 85.4% accuracy (95% CI: 74.5–96.2%), 86.4% sensitivity (95% CI: 72.0–100%), and 84.2% specificity (95% CI: 67.8–100%) on the independent test set. Internal validation yielded 85.7% accuracy, 90.0% sensitivity, and 75.0% specificity, while external validation demonstrated 77.8% accuracy, 78.6% sensitivity, and 77.3% specificity. These findings suggest that advanced regularization combined with ensemble learning improves generalizability despite limited data. Conclusions: This study demonstrates that a lightweight ResNet18 architecture with strategic optimization outperforms deeper networks on small medical datasets. The proposed framework demonstrated good diagnostic performance across multiple validation cohorts, offering a promising computer-aided diagnosis tool for thyroid nodule assessment. Full article
(This article belongs to the Section Medical Imaging and Theranostics)
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15 pages, 1228 KB  
Article
Relationship Between Thyroid Hormonal Function and Ultrasound TI-RADS Stratification in a Saudi Cohort
by Ali H. Alghamdi, Ashwag A. Albalawi, Shahad S. Aljuhani, Ahmed Alghamdi, Mansuor A. Alanazi, Arwa Baeshen, Adnan Alahmadi and Njoud Aldusary
Metabolites 2026, 16(3), 165; https://doi.org/10.3390/metabo16030165 - 28 Feb 2026
Viewed by 532
Abstract
Introduction: Thyroid disorders are among the most prevalent endocrine diseases worldwide, with rising incidence linked to aging, lifestyle, and environmental factors. Early identification of both functional and structural abnormalities is essential to prevent complications. This study aimed to investigate the coherence between thyroid [...] Read more.
Introduction: Thyroid disorders are among the most prevalent endocrine diseases worldwide, with rising incidence linked to aging, lifestyle, and environmental factors. Early identification of both functional and structural abnormalities is essential to prevent complications. This study aimed to investigate the coherence between thyroid function as measured by thyroid-stimulating hormone (TSH) and free thyroxine (FT4) tests and ultrasound-based thyroid classification according to the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS). Methods: This retrospective cross-sectional study included patients in Tabuk, Saudi Arabia, who underwent thyroid ultrasound alongside TSH and FT4 tests within two weeks. Thyroid nodules were classified using TI-RADS. Demographic, clinical, and laboratory data were extracted from electronic records, and statistical analyses examined associations between hormone levels, ultrasound findings, and clinical variables (p < 0.05). Results: A total of 102 patient records were included in the study. Most participants were female and overweight, with a mean body mass index (BMI) of 30.2 ± 4.6 kg/m2. The majority were euthyroid (58.3%) or subclinical hypothyroid (27.8%); most nodules were benign (TI-RADS 2–3). BMI showed a moderate positive correlation with TSH (ρ = 0.20, p = 0.041) and a negative correlation with FT4 (ρ = –0.20, p = 0.040). No significant relationship was observed between TI-RADS classification and thyroid hormone levels (p > 0.05). Conclusions: Structural thyroid changes identified by ultrasound appeared largely independent of hormonal status. Meanwhile, BMI demonstrated a modest physiological association with thyroid function reflected in TSH and/or FT4 levels. These findings emphasize the need for integrated biochemical and imaging evaluation to enhance diagnostic precision in the assessment of thyroid disease. Full article
(This article belongs to the Section Endocrinology and Clinical Metabolic Research)
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12 pages, 239 KB  
Article
Papillary Thyroid Carcinoma in Patients with Carotid Body Tumors: Prevalence and Management in a Retrospective Surgical Series from Two Tertiary Centers
by Mohammed Alshahrani, Sharif Almatrafi, Alanoud Alshathri, Manar Alzahrani, Mohammed Alessa, Saleh Aldhahri, Majed Albarrak, Mohammed Almayouf and Khalid AlQahtani
J. Clin. Med. 2026, 15(5), 1864; https://doi.org/10.3390/jcm15051864 - 28 Feb 2026
Viewed by 387
Abstract
Background/Objectives: The co-occurrence of a carotid body tumor (CBT) and papillary thyroid carcinoma (PTC) is a rare clinical event. The frequency of this dual pathology in recent reports has sparked a debate on whether it represents a true pathophysiological association or an artifact [...] Read more.
Background/Objectives: The co-occurrence of a carotid body tumor (CBT) and papillary thyroid carcinoma (PTC) is a rare clinical event. The frequency of this dual pathology in recent reports has sparked a debate on whether it represents a true pathophysiological association or an artifact of increased diagnostic surveillance. This study aims to report the prevalence, clinicopathological characteristics, management, and outcomes of concurrent CBT and PTC in a contemporary cohort. Methods: We conducted a retrospective review of patients who underwent CBT resection at two tertiary centers between 2014 and 2024. Data on patient demographics, tumor characteristics, preoperative imaging, surgical management (single stage vs. staged), final histopathology, and clinical outcomes were collected and analyzed. Results: Overall, 32 patients with surgically resected CBTs were included. Eleven patients (34.4%) had thyroid nodules identified on preoperative imaging. The mean age of the participants was 57.2 ± 16.3 years. Females represented the majority of the population (n = 27, 84.4%). Nine patients underwent thyroid surgery with subsequent pathological confirmation. Management involved resection at two different time intervals in five cases (55.6%) and a single-stage operation in four (44.4%). On final pathology, PTC was confirmed in eight patients (25.0%). During the follow-up period, no recurrences of either tumor type were observed. Conclusions: The prevalence of concurrent PTC in patients with CBTs is significantly higher than previously reported, reaching 25% in our cohort. This incidental finding raises the possibility of surveillance bias or underlying genetic mechanisms. Management with either a single-stage or staged surgical approach was not associated with major complications. The prognosis for patients with this dual pathology is excellent and appears to be dictated by the independent characteristics of each tumor. Full article
(This article belongs to the Section Otolaryngology)
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