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Keywords = microcarcinoma

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10 pages, 522 KB  
Article
The Role of Preoperative Radiological, Cytological, and Systemic Inflammatory Markers in Predicting Incidental Papillary Microcarcinoma in Patients with Multinodular Goiter: A Retrospective Single-Center Study
by Yavuz Selim Kahraman, Fatma Gün, İbrahim Kurtoğlu, Yasin Alper Yıldız, Ezgi Kartal and Adem Şentürk
J. Clin. Med. 2026, 15(11), 4343; https://doi.org/10.3390/jcm15114343 - 4 Jun 2026
Viewed by 310
Abstract
Objective: Preoperative prediction of incidental papillary thyroid microcarcinoma (PTMC) in patients undergoing surgery for multinodular goiter (MNG) is a clinically significant challenge. This study aimed to evaluate the association of preoperative radiological (TI-RADS), cytological (Bethesda), and systemic inflammatory markers (neutrophil/lymphocyte ratio [NLR] [...] Read more.
Objective: Preoperative prediction of incidental papillary thyroid microcarcinoma (PTMC) in patients undergoing surgery for multinodular goiter (MNG) is a clinically significant challenge. This study aimed to evaluate the association of preoperative radiological (TI-RADS), cytological (Bethesda), and systemic inflammatory markers (neutrophil/lymphocyte ratio [NLR] and systemic immune-inflammation index [SII]) with incidental PTMC. Methods: This retrospective study included patients who underwent total thyroidectomy due to multinodular goiter. Preoperative ultrasonography findings (TI-RADS), fine needle aspiration biopsy results (Bethesda), and inflammatory markers (NLR and SII) were analyzed. Patients were grouped according to the presence of PTMC based on postoperative pathology results. Independent associations with PTMC were evaluated using multivariable binary logistic regression analysis with TI-RADS and Bethesda classifications entered as categorical variables. Results: A total of 283 patients who underwent total thyroidectomy for multinodular goiter were included in the study. The mean age was 52.75 ± 11.39 years, and 78.1% of the patients were female. Postoperative histopathological examination revealed incidental papillary thyroid microcarcinoma (PTMC) in 67 patients (23.6%). PTMC was detected in 67 patients (23.6%). In multivariable binary logistic regression analysis, high-risk TI-RADS categories (TR4–5 vs. TR1–3) and Bethesda III–IV categories (vs. Bethesda I–II) were independently associated with PTMC, whereas NLR and SII were not independently significant. Conclusions: High-risk TI-RADS and Bethesda categories were independently associated with incidental PTMC in patients with multinodular goiter, whereas inflammatory markers including NLR and SII were not independent predictors. Radiological and cytological evaluation appear to remain the primary components of preoperative assessment in incidental PTMC. Full article
(This article belongs to the Section General Surgery)
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18 pages, 695 KB  
Article
Prognostic Factors and Recurrence in Papillary Thyroid Microcarcinoma
by Aydan Farzaliyeva, Feride Pınar Altay, Ozlem Turhan Iyidir and Neslihan Bascil Tutuncu
Medicina 2026, 62(5), 981; https://doi.org/10.3390/medicina62050981 - 17 May 2026
Viewed by 422
Abstract
Background and Objectives: Papillary thyroid microcarcinoma (PTMC) is generally indolent; however, a subset exhibits aggressive features, reflecting biological heterogeneity. In the era of treatment de-escalation and active surveillance, accurate risk stratification is essential. We aimed to evaluate recurrence, identify factors associated with [...] Read more.
Background and Objectives: Papillary thyroid microcarcinoma (PTMC) is generally indolent; however, a subset exhibits aggressive features, reflecting biological heterogeneity. In the era of treatment de-escalation and active surveillance, accurate risk stratification is essential. We aimed to evaluate recurrence, identify factors associated with recurrence, determine predictors of lymph node metastasis (LNM) at diagnosis, and assess management strategies at our center. Materials and Methods: This retrospective study included 302 patients with PTMC. Associations between clinicopathological variables and outcomes were evaluated using chi-square test, Spearman correlation, and univariate and multivariate logistic regression analyses. Results: The cohort included 240 females (79.5%) and 62 males (20.5%), with a median age of 47 years. Total thyroidectomy was performed in 97.7%, and radioactive iodine (RAI) in 64.2%. LNM was identified in 26 patients (8.6%). Recurrence occurred in 4 patients (1.3%), and 98.0% were alive at last follow-up. Recurrence was associated with LNM at diagnosis, higher ATA risk categories, and positive surgical margins (p < 0.005). Younger age, larger tumor size, and vascular invasion independently predicted LNM (all p < 0.05), while autoimmune thyroiditis was associated with a reduced risk (p = 0.020). Conclusions: PTMC demonstrates clinically relevant heterogeneity, particularly in patients with LNM. However, given the limited number of recurrence events, recurrence-related findings should be interpreted cautiously and considered exploratory. These findings support risk-adapted management and careful patient selection in the era of treatment de-escalation. Full article
(This article belongs to the Section Endocrinology)
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28 pages, 755 KB  
Article
Exploratory Statistical Analyses of Clinical and Biochemical Factors for Differentiated Thyroid Cancer from a Romanian Cohort
by Alexandru Dima, Irina-Oana Lixandru-Petre, Denis Iorga, Gratiela Gradisteanu Pircalabioru, Dana Cristina Terzea, Andrei Goldstein, Florina Silvia Iliescu, Mihai Dascalu, Madalina Musat and Ciprian Iliescu
Cancers 2026, 18(6), 1036; https://doi.org/10.3390/cancers18061036 - 23 Mar 2026
Viewed by 784
Abstract
Background/Objectives: Thyroid cancer (TC) is among the most common endocrine malignancies, with incidence rates increasing worldwide. However, careful inferential analysis based on refined data is needed to provide a sharper clinical and epidemiological description of this serious condition in a biologically and technologically [...] Read more.
Background/Objectives: Thyroid cancer (TC) is among the most common endocrine malignancies, with incidence rates increasing worldwide. However, careful inferential analysis based on refined data is needed to provide a sharper clinical and epidemiological description of this serious condition in a biologically and technologically evolving society. This study presents an exploratory statistical analysis of data from 1470 patients who underwent thyroid surgery for differentiated TC. Methods: The analysis combines bivariate exploration of associations between variables with univariate and multivariate analyses stratified by histological subtype. We examined pathological characteristics (tumor location, nodal metastases, distant metastases, margin involvement, lymphovascular invasion, vascular invasion, and perineural invasion), clinical characteristics (clinical stage), biochemical markers (thyroglobulin, anti-thyroglobulin antibodies, and thyroid-stimulating hormone), and demographic variables (sex assigned at birth and age). In addition, exploratory multivariable models were used to investigate factors associated with lymph node metastasis and margin involvement in papillary microcarcinoma, the diffuse sclerosing variant, and the classical variant of papillary thyroid carcinoma. Results: Notably, moderate to high effect size correlations highlight the interdependence of invasive histopathological features in thyroid cancer and their collective link to adverse surgical outcomes and prognosis. Conclusions: This study provides an analysis of associations between the variables and subtype-specific descriptive estimates, serving as a foundation for future work in tailoring personalized medicine. Full article
(This article belongs to the Special Issue Advances in Cancer Data and Statistics: 2nd Edition)
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12 pages, 546 KB  
Article
Clinical Impact of Multifocality and Bilaterality on Lymph Node Metastasis in Papillary Thyroid Microcarcinoma
by Merima Goran, Marko Buta, Srdjan Nikolic, Nada Santrac, Nikola Jeftic, Nevena Savkovic, Jovan Raketic, Zoran Kozomara, Natasa Medic-Milijic, Ana Cvetkovic, Saska Pavlovic and Ivan Markovic
Diagnostics 2026, 16(2), 208; https://doi.org/10.3390/diagnostics16020208 - 9 Jan 2026
Viewed by 665
Abstract
Objective: Papillary thyroid microcarcinoma (PTMC) often presents with multifocality and bilaterality, but the clinical significance of these features and their association with cervical lymph node metastases (LNMs) remain debated. The aim of this study was to investigate the patterns of multifocality and bilaterality [...] Read more.
Objective: Papillary thyroid microcarcinoma (PTMC) often presents with multifocality and bilaterality, but the clinical significance of these features and their association with cervical lymph node metastases (LNMs) remain debated. The aim of this study was to investigate the patterns of multifocality and bilaterality in PTMC and their association with central and lateral neck lymph node metastases. Methods: This retrospective study analyzed 254 patients with histologically confirmed PTMC treated at the Institute for Oncology and Radiology of Serbia between 2004 and 2016. All patients underwent total thyroidectomy with central and, when indicated, lateral neck dissection. Associations between multifocality, bilaterality, and cervical LNM were evaluated using appropriate statistical tests. A p-value < 0.05 was considered statistically significant. Results: Multifocal tumors were present in 40.55% of patients, with bilateral involvement in 27.17%. Cervical LNM occurred in 33.07% of patients, with 26.77% showing central and 20.08% lateral metastases. Patients with multifocal tumors were associated with significantly higher proportions of male patients (p = 0.0283), higher rates of capsular invasion (p = 0.0002), larger tumor size (p = 0.0134), and increased incidence of LNM (p = 0.0152). Bilateral tumors were associated with larger tumor size (p = 0.0004) and more frequent capsular invasion (p = 0.0248), but not with a statistically significant increase in LNM. The number of tumor foci was strongly associated with both central and lateral LNM (p < 0.001). Conclusions: Multifocality, particularly with a higher number of tumor foci, is significantly associated with more aggressive tumor features and higher rates of cervical lymph node metastases in PTMC. While bilaterality also reflects a more aggressive phenotype, it was not independently predictive of LNM. These findings underscore the importance of careful risk stratification in PTMC and suggest that multifocality should inform surgical and follow-up strategies. Full article
(This article belongs to the Special Issue Innovations in Thyroid Nodule and Cancer Diagnostics)
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14 pages, 1864 KB  
Article
Evolving Practices in Low-Risk Papillary Thyroid Cancer: Impact of the 2015 ATA Guidelines
by Benard Gjeloshi, Leonardo Rossi, Carlo Enrico Ambrosini, Chiara Becucci, Piermarco Papini, Andrea De Palma, Luigi De Napoli, Marco Puccini and Gabriele Materazzi
Curr. Oncol. 2026, 33(1), 26; https://doi.org/10.3390/curroncol33010026 - 2 Jan 2026
Cited by 1 | Viewed by 1865
Abstract
Background/Objectives: The extent of initial surgical resection for low-risk papillary thyroid carcinoma (PTC) remains debated. Traditionally, total thyroidectomy (TT) has been the standard approach, although the 2015 American Thyroid Association (ATA) guidelines endorsed a more conservative strategy. The real-world adoption of these [...] Read more.
Background/Objectives: The extent of initial surgical resection for low-risk papillary thyroid carcinoma (PTC) remains debated. Traditionally, total thyroidectomy (TT) has been the standard approach, although the 2015 American Thyroid Association (ATA) guidelines endorsed a more conservative strategy. The real-world adoption of these recommendations, however, is unclear. This study evaluated changes in the surgical management of low-risk PTC in a high-volume center following the implementation of the ATA guidelines and analyzed the impact on postoperative outcomes. Methods: We conducted a retrospective study of 1644 patients who underwent surgery for localized low-risk PTC < 4 cm between 2014 and 2023. Temporal trends in the initial surgical procedure (TT vs. thyroid lobectomy [TL]) were analyzed overall and by tumor size and patient demographics. The need for completion thyroidectomy after TL and postoperative outcomes were also assessed. Results: The use of TL increased from 0% in 2014 to 59.4% in 2023 (p < 0.001). For microcarcinomas, TL rose from 17.5% in 2016 to 78% in 2023, with similar but less pronounced trends for 1–2 cm tumors. TT remained predominant for nodules > 2 cm. The completion thyroidectomy rate declined from 32% in 2016 to 4% in 2022. Patients undergoing TT experienced higher rates of postoperative complications (12.4% vs. 3.0%), particularly transient hypoparathyroidism (8.9% vs. 0%), and permanent hypoparathyroidism (1.8% vs. 0%), as well as longer operative time and hospital stay (all p < 0.001). The incidence of hypoparathyroidism decreased over time as TL use increased. Conclusions: Adoption of the 2015 ATA guidelines has progressively increased the use of TL in the management of low-risk PTC. This shift in surgical practice is associated with a reduction in the overall postoperative complication burden at the population level, largely driven by decreased hypoparathyroidism. Although guideline uptake has been gradual, current trends suggest increasing acceptance of less aggressive surgical strategies in routine clinical practice. Full article
(This article belongs to the Special Issue Advancements in Thyroid Cancer Management)
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15 pages, 2760 KB  
Case Report
Medullary Thyroid Carcinoma Without Calcitonin: A Case Linking Ultimobranchial Bodies to Tumor Evolution
by Ion Prisneac, Abigail I. Wald, Chelsea Bragg and John A. Ozolek
Pathophysiology 2025, 32(4), 56; https://doi.org/10.3390/pathophysiology32040056 - 23 Oct 2025
Viewed by 1701
Abstract
Medullary thyroid carcinoma (MTC) is a thyroid tumor with neuroendocrine properties purportedly derived from C-cells. The biochemical activity of medullary thyroid carcinoma includes the production of calcitonin and carcinoembryonic antigen, which are sensitive tumor markers, facilitating diagnosis, follow-up, and prognostication. Calcitonin-negative medullary thyroid [...] Read more.
Medullary thyroid carcinoma (MTC) is a thyroid tumor with neuroendocrine properties purportedly derived from C-cells. The biochemical activity of medullary thyroid carcinoma includes the production of calcitonin and carcinoembryonic antigen, which are sensitive tumor markers, facilitating diagnosis, follow-up, and prognostication. Calcitonin-negative medullary thyroid carcinoma is a rare, poorly understood primary neuroendocrine carcinoma of the thyroid characterized by classic medullary thyroid carcinoma morphology without raised serum calcitonin and with or without the expression of calcitonin detected by immunohistochemistry. Previous studies reported that C-cells were derived from the neural crest; however, more recently, C-cells have been indisputably shown to be derived from the pharyngeal endoderm and ultimobranchial bodies. Ultimobranchial body (UBB) remnants can persist in the thyroid and express p63, but their function is poorly understood. Some have postulated that ultimobranchial bodies may be the “stem” cell of the thyroid and may be precursors for thyroid tumors, particularly mixed tumors with follicular and medullary components. We present a unique case of calcitonin-negative MTC in a 58-year-old male arising in an inflamed and fibrotic thyroid with numerous scattered ultimobranchial body remnants and concomitant C-cell hyperplasia/medullary microcarcinoma (CCH/MMC). The ultimobranchial body remnants, C-cell hyperplasia, and medullary thyroid carcinoma were MTC classifier positive according to ThyroSeq®. The areas representing CCH/MMC expressed calcitonin by IHC while the main MTC tumor was negative. An additional unique feature was an area demonstrating a “mixed” C-cell/thyroid follicular epithelial phenotype. In this review we review the possible etiologies of calcitonin-negative MTC, the possibility of a neoplastic sequential progression from ultimobranchial bodies to CCH/MMC to medullary thyroid carcinoma with the individual elements (UBB, CCH/MMC, MTC) demonstrated in this thyroid, and previous postulations that ultimobranchial bodies may be the source of some follicular thyroid cancers, medullary thyroid cancers, and mixed tumors of medullary and follicular epithelial types. Full article
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14 pages, 529 KB  
Article
Predictive Factors of Lymph Node Metastasis in Papillary Thyroid Microcarcinoma (PTMC)
by Odysseas Violetis, Maria Sfakiotaki, Ariadni Spyroglou, Evangelia Pissadaki, Konstantinos Iliakopoulos, Eleni-Konstantina Syntzanaki, Panagiota Konstantakou, Eleni Chouliara, Constantinos Nastos, Nikolaos Dafnios, George Simeakis, Konstantinos Bramis, Despoina Myoteri, George Mastorakos, Paraskevi Xekouki and Krystallenia I. Alexandraki
Medicina 2025, 61(10), 1800; https://doi.org/10.3390/medicina61101800 - 6 Oct 2025
Cited by 2 | Viewed by 2286
Abstract
Background and Objectives: The incidence of papillary thyroid microcarcinoma (PTMC) has increased. Some patients present with lymph node metastases (LNM), while risk factors remain unclear. This study aims to examine clinicopathological markers predictive of LNM in PTMC. Materials and Methods: We retrospectively [...] Read more.
Background and Objectives: The incidence of papillary thyroid microcarcinoma (PTMC) has increased. Some patients present with lymph node metastases (LNM), while risk factors remain unclear. This study aims to examine clinicopathological markers predictive of LNM in PTMC. Materials and Methods: We retrospectively analyzed 170 patients with a histological diagnosis of PTMC. The patients were grouped based on the presence of LNM. Results: Our cohort consisted of 133 females and 37 males, aged 47.14 ± 12.81 years. Twenty-seven (15.9%) individuals had LNM. Median tumor size was 5 mm (4.25, 0.15–10), and multifocality was present in 37.1% of patients. Thyroid capsular invasion (TCI) was observed in 22.9% of patients. Extrathyroidal extension (ETE) and aggressive variants were present in 12.9% and 8.8% of patients, respectively. Forty-four patients had a history of autoimmune thyroid disease. From univariate analysis, age < 55 years (OR: 6.317; p = 0.015), TCI (OR: 2.824; p = 0.020), and ETE (OR: 2.987; p = 0.034) were independent predictors of LNM. Multivariate analysis showed that younger patients are at a significantly increased risk of LNM in PTMC (OR: 6.30910; p = 0.016). Conclusions: The findings of this study highlight the need for greater attention to PTMC in younger patients with ultrasonographic features of TCI and ETE, as they may require a more thorough evaluation of LNM, strict follow-up, and may benefit from a surgical decision of lymphadenectomy. Full article
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15 pages, 3399 KB  
Article
Predictive Value of Arterial Enhancement Fraction Derived from Dual-Layer Spectral Computed Tomography for Thyroid Microcarcinoma
by Yuwei Chen, Jiayi Yu, Liang Lv, Zuhua Song, Jie Huang, Bi Zhou, Xinghong Zou, Ya Zou and Dan Zhang
Diagnostics 2025, 15(19), 2427; https://doi.org/10.3390/diagnostics15192427 - 23 Sep 2025
Cited by 1 | Viewed by 1116
Abstract
Background/Objectives: Accurately distinguishing malignancy in thyroid micronodules (≤10 mm) is crucial for clinical management, yet it is challenging due to the limitations of conventional ultrasonography-guided biopsy. This study aims to evaluate the predictive value of dual-layer spectral computed tomography (DSCT)-derived arterial enhancement fraction [...] Read more.
Background/Objectives: Accurately distinguishing malignancy in thyroid micronodules (≤10 mm) is crucial for clinical management, yet it is challenging due to the limitations of conventional ultrasonography-guided biopsy. This study aims to evaluate the predictive value of dual-layer spectral computed tomography (DSCT)-derived arterial enhancement fraction (AEF) in diagnosing thyroid microcarcinomas. Methods: In the study, 321 pathologically confirmed thyroid micronodules (benign = 131, malignant = 190) from Chongqing General Hospital underwent preoperative DSCT. Quantitative parameters of DSCT, including the normalized iodine concentration (NIC), normalized effective atomic number (NZeff), and slope of the spectral Hounsfield unit curve (λHU(40–100)), were assessed. Both single-energy CT (SECT)-derived AEF (AEFS) and DSCT-derived AEF (AEFD) were calculated. Conventional image features included microcalcifications and enhancement blurring. Correlation between AEFD and AEFS was determined using Spearman’s correlation coefficient. Diagnostic performance was evaluated by calculating the area under the curve (AUC) using receiver operating characteristic (ROC) analysis. Results: Malignant micronodules exhibited significantly lower AEFD (0.958 vs. 1.259, p < 0.001) and AEFS (0.964 vs. 1.436, p < 0.001) versus benign nodules. Arterial phase parameters—APλHU(40–100), APNIC, APNZeff—differed significantly between groups (all p < 0.001), whereas venous phase parameters (VPλHU(40–100), VPNIC, VPNZeff) showed no differences (all p > 0.05). Multivariate analysis revealed that λHU(40–100) as an independent predictor of malignancy, with an odds ratio (OR) of 0.600 (95% confidence interval (CI): 0.437–0.823; p = 0.002) and an AUC of 0.752 (95% CI: 0.698–0.806). A significant positive correlation was identified between AEFD and AEFS (r = 0.710; p < 0.001). For diagnosing malignancy, AEFD demonstrated superior overall performance (AUC: 0.794; sensitivity: 70.5%; specificity: 81.7%; accuracy: 75.1%) to AEFS (0.753; 71.1%; 74.0%; 72.3%), APλHU(40–100) (0.752; 68.9%; 75.6%; 71.7%), and calcification (0.573; 21.6%; 92.4%; 50.5%). Clinically, AEFD reduced the unnecessary biopsy rate to 18.3%, preventing 107 procedures in our cohort. Conclusions: AEFD and AEFS demonstrated strong correlation and comparable diagnostic performance in the evaluation of thyroid micronodules. Furthermore, AEFD showed favorable diagnostic efficacy compared to both spectral parameters and conventional imaging feature. More importantly, the application of AEFD significantly reduced unnecessary biopsy rates, highlighting its clinical value in optimizing patient management. Full article
(This article belongs to the Special Issue Thyroid Cancer: Types, Symptoms, Diagnosis and Management)
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14 pages, 1870 KB  
Article
Analysis of Risk Factors for High-Risk Lymph Node Metastasis in Papillary Thyroid Microcarcinoma
by Yi-Hsiang Chiu, Shu-Ting Wu, Yung-Nien Chen, Wen-Chieh Chen, Lay-San Lim, Yvonne Ee Wern Chiew, Ping-Chen Kuo, Ya-Chen Yang, Shun-Yu Chi and Chen-Kai Chou
Cancers 2025, 17(15), 2585; https://doi.org/10.3390/cancers17152585 - 6 Aug 2025
Cited by 1 | Viewed by 2085
Abstract
Background: Papillary thyroid microcarcinoma (PTMC) is associated with certain features that carry an increased risk of local recurrence, underscoring the importance of preoperative risk assessment. This study investigated the clinicopathological factors associated with high-risk lymph node metastasis (HRLNM) and patient outcomes. HRLNM is [...] Read more.
Background: Papillary thyroid microcarcinoma (PTMC) is associated with certain features that carry an increased risk of local recurrence, underscoring the importance of preoperative risk assessment. This study investigated the clinicopathological factors associated with high-risk lymph node metastasis (HRLNM) and patient outcomes. HRLNM is defined as ≥5 metastatic lymph nodes and/or lateral neck metastasis. Methods: We conducted a retrospective review of 985 patients with PTMC who underwent thyroidectomy at the Kaohsiung Chang Gung Memorial Hospital from 2013 to 2022. Results: Among the 985 patients, 100 (10.2%) had lymph node metastasis (LNM), and 27% of these were classified as having HRLNM. Male sex (OR 3.61, p = 0.04) and extranodal extension (OR 3.76, p = 0.043) were independent predictors of HRLNM. Patients with LNM exhibited lower rates of excellent treatment response (75% vs. 87%, p = 0.001), higher recurrence rates (9.0% vs. 0.6%, p = 0.001), and an increased risk of distant metastasis (2.0% vs. 0%). Recurrence-free survival (RFS) was significantly shorter in patients with LNM (120.9 vs. 198.6 months, p < 0.001). Although HRLNM showed a trend toward reduced RFS (113.5 vs. 124.6 months, p = 0.177), its impact on long-term survival remains uncertain. Conclusions: Male sex and extranodal extension were significant risk factors for HRLNM in patients with PTMC. These findings highlight the need for individualized risk stratification to guide treatment strategies and improve patient outcomes. Full article
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12 pages, 463 KB  
Article
Association Between BRAF V600E Allele Frequency and Aggressive Behavior in Papillary Thyroid Microcarcinoma
by Luiza Tatar, Saruchi Bandargal, Marc P. Pusztaszeri, Véronique-Isabelle Forest, Michael P. Hier, Jasmine Kouz, Raisa Chowdhury and Richard J. Payne
Cancers 2025, 17(15), 2553; https://doi.org/10.3390/cancers17152553 - 1 Aug 2025
Cited by 2 | Viewed by 1906
Abstract
Background/Objectives: Papillary thyroid microcarcinoma (MPTC), a subset of papillary thyroid carcinoma (PTC), is increasingly detected with advanced imaging. While most MPTCs are indolent, some exhibit aggressive behavior, complicating clinical management. The BRAF V600E mutation, common in PTC, is linked to aggressive features, [...] Read more.
Background/Objectives: Papillary thyroid microcarcinoma (MPTC), a subset of papillary thyroid carcinoma (PTC), is increasingly detected with advanced imaging. While most MPTCs are indolent, some exhibit aggressive behavior, complicating clinical management. The BRAF V600E mutation, common in PTC, is linked to aggressive features, and its allele frequency (AF) may serve as a biomarker for tumor aggressiveness. This study explored the association between BRAF V600E AF and aggressive histopathological features in MPTC. Methods: Data from 1 January 2016 to 23 December 2023 were retrieved from two McGill University teaching hospitals. Inclusion criteria comprised patients aged ≥ 18 years with thyroid nodules ≤ 1 cm, documented BRAF V600E mutation and AF results, and available surgical pathology reports. Tumor aggressiveness was defined as the presence of lymph node metastasis, aggressive histological subtype (tall cell, hobnail, columnar, solid/trabecular or diffuse sclerosing), extra thyroidal extension, or extensive lymphovascular extension. Associations were explored using t-tests. Results: Among 1564 records, 34 met the inclusion criteria and were included in analyses. The mean BRAF V600E AF was significantly higher in aggressive tumors (23.58) compared to non-aggressive tumors (13.73) (95% CI: −18.53 to −1.16, p = 0.03). Although not statistically significant, trends were observed for higher BRAF V600E AF in tumors with lymph node metastasis (mean AF: 25.4) compared to those without (mean AF: 16.67, p = 0.08). No significant difference was noted in BRAF V600E AF by histological subtype (mean AF for aggressive: 19.57; non-aggressive: 19.15, p = 0.94). Conclusions: Elevated BRAF V600E AF is associated with aggressive behavior in MPTC, highlighting its potential as a biomarker to inform treatment strategies. Larger studies are warranted to validate these findings and enhance clinical management of MPTC patients. Full article
(This article belongs to the Special Issue Thyroid Cancer: Diagnosis, Prognosis and Treatment (2nd Edition))
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9 pages, 213 KB  
Article
Total Thyroidectomy vs. Lobectomy in Papillary Thyroid Microcarcinoma: A Contested Gold Standard
by Enrico Battistella, Luca Pomba, Riccardo Toniato, Andrea Piotto and Antonio Toniato
J. Pers. Med. 2025, 15(7), 324; https://doi.org/10.3390/jpm15070324 - 18 Jul 2025
Cited by 2 | Viewed by 3932
Abstract
Background: Papillary thyroid microcarcinoma (PTMC), a subtype of papillary thyroid carcinoma ≤ 1 cm in diameter, has shown a marked increase in incidence in recent decades, largely due to the widespread use of neck ultrasonography and fine needle aspiration cytology. Despite its [...] Read more.
Background: Papillary thyroid microcarcinoma (PTMC), a subtype of papillary thyroid carcinoma ≤ 1 cm in diameter, has shown a marked increase in incidence in recent decades, largely due to the widespread use of neck ultrasonography and fine needle aspiration cytology. Despite its generally indolent course, optimal management of PTMC remains controversial, with treatment strategies ranging from active surveillance to total thyroidectomy. Methods: This retrospective study analyzes five years of experience at a single tertiary care center, including 130 patients diagnosed with PTMC following thyroid surgery between July 2018 and December 2023. Clinical, cytological, and pathological data were collected and analyzed to identify factors influencing surgical decision-making and postoperative outcomes. Patients underwent either total thyroidectomy or hemithyroidectomy, with central and lateral lymph node dissection performed as indicated. Follow-up included clinical and biochemical surveillance for a mean duration of 3 years. Results: Total thyroidectomy was performed in 89.3% of patients, while hemithyroidectomy was limited to 10.7%. Multifocality was observed in 26.1% of cases, with bilateral involvement in 17.7%. Occult lymph node metastases were found in 14.6% (central compartment) and 3.8% (lateral neck). Postoperative radioactive iodine therapy was administered in 23.8% of patients. At final follow-up, 90.7% were disease-free. No significant predictors of recurrence or adverse outcomes were identified, though multifocality and lymph node involvement influenced surgical planning. Conclusions: Our findings support a risk-adapted surgical approach to PTMC, favoring total thyroidectomy in patients with suspicious or multifocal disease to avoid reoperation. While active surveillance and minimally invasive techniques are emerging, total thyroidectomy remains a safe and effective strategy in selected cases. Prospective, multicenter studies are needed to further refine management guidelines for this increasingly common thyroid malignancy. Full article
(This article belongs to the Section Evidence Based Medicine)
9 pages, 216 KB  
Article
Higher Body Mass Index Shows No Evidence of Association with Histopathologic Markers of Aggressiveness in Early-Stage Papillary Thyroid Carcinoma
by Aliki Economides, Demetris Lamnisos, Paris Vogazianos, Konstantinos Giannakou, Savvas Frangos, Vasilis Constantinides, Panagiotis Papageorgis and Panayiotis A. Economides
Biomedicines 2025, 13(7), 1681; https://doi.org/10.3390/biomedicines13071681 - 9 Jul 2025
Viewed by 1151
Abstract
Background: Obesity has been implicated in the pathogenesis and progression of several malignancies, including papillary thyroid carcinoma (PTC), but its role in tumor aggressiveness remains controversial. This study aimed to investigate the association between adiposity, as measured by body mass index (BMI), and [...] Read more.
Background: Obesity has been implicated in the pathogenesis and progression of several malignancies, including papillary thyroid carcinoma (PTC), but its role in tumor aggressiveness remains controversial. This study aimed to investigate the association between adiposity, as measured by body mass index (BMI), and histopathological features of aggressiveness in patients with PTC. Methods: This single-center retrospective study included 298 consecutive adult patients diagnosed with PTC between 2016 and 2021 at an endocrine referral center. Patients were stratified based on BMI into normal weight (<25 kg/m2) and overweight/obese (≥25 kg/m2) groups. Clinical, metabolic, and histopathological data were compared between the two groups. Results: Overweight/obese patients had significantly higher rates of hypertension, type 2 diabetes, fasting glucose, and triglycerides, as well as lower high-density lipoprotein cholesterol (all p < 0.01). Tumor size was similar between groups, with over 85% of tumors measuring ≤ 1 cm (microcarcinomas) and no significant difference in the proportion of tumors > 1 cm (p = 0.582). There were no significant differences in multifocality (p = 0.269) or extrathyroidal extension (ETE) (p = 0.826). Lymph node metastases occurred in 34% of normal weight and 28% of overweight/obese patients, without a statistically significant difference (p = 0.402). Lymph node compartment involvement did not significantly differ between groups (p = 0.160). Conclusions: Despite being associated with adverse metabolic profiles, higher BMI was not linked to tumor aggressiveness in patients with predominantly early-stage PTC. As the incidence of obesity and PTC continues to rise, these findings highlight the need for further research into early-stage PTC biology and more precise risk measures of adiposity beyond BMI alone. Full article
(This article belongs to the Special Issue Advanced Research in Thyroid and Parathyroid Diseases)
11 pages, 417 KB  
Communication
Predicting the Metastatic Potential of Papillary Thyroid Microcarcinoma Based on the Molecular Profile of Preoperative Cytology Specimens
by Sergei A. Lukyanov, Sergei E. Titov, Aria V. Dzodzaeva, Vladimir E. Vanushko, Dmitry G. Beltsevich, Yuliya A. Veryaskina, Semyon V. Kupriyanov, Ekaterina V. Bondarenko, Ekaterina A. Troshina, Liliya S. Urusova and Sergei V. Sergiyko
Int. J. Mol. Sci. 2025, 26(13), 6418; https://doi.org/10.3390/ijms26136418 - 3 Jul 2025
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Abstract
The strategy of active surveillance for papillary thyroid microcarcinoma (PTMC) is becoming increasingly popular within the global medical community. A key criterion for selecting this strategy is the absence of any signs of lymphogenic or distant metastases. The present study assessed the diagnostic [...] Read more.
The strategy of active surveillance for papillary thyroid microcarcinoma (PTMC) is becoming increasingly popular within the global medical community. A key criterion for selecting this strategy is the absence of any signs of lymphogenic or distant metastases. The present study assessed the diagnostic accuracy of molecular genetic markers for predicting the metastatic potential of patients with PTMC. We evaluated the expression levels of 33 molecular genetic markers in cytology samples from 92 patients with PTMC and confirmed histological diagnosis. Among these patients, 32 had metastases to regional cervical lymph nodes. Our findings revealed the upregulated expression of the HMGA2, TIMP1, and FN1 genes, as well as microRNA-146b, in patients with metastatic PTMC. Conversely, we found the downregulated expression of miRNA-7 and -148b in metastatic tumors. In metastatic tumors, significant reductions were observed in DIO1 activity (11-fold), TFF3 gene expression (8-fold), TPO expression (4-fold), and SLC26A7 expression (2.6-fold). All the markers exhibited high sensitivity (84.5–90.6%) in detecting metastatic PTMC, although the specificity proved to be low. The use of molecular markers to predict lymphogenic metastatic spread in patients with PTMC could enhance existing risk grading systems. Such assessments can already be applicable at the preoperative stage. Full article
(This article belongs to the Special Issue Editorial Board Members’ Collection Series: Cancer Metastasis)
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20 pages, 3082 KB  
Article
Diagnosis and Evaluation of Aggressiveness Using Circulating Plasma miRNAs in Papillary Thyroid Microcarcinoma
by Jiwon Jang, Ji Min Kim, Sung-Chan Shin, Yong-il Cheon, Bo Hyun Kim, Mijin Kim, Sang Soo Kim and Byung-Joo Lee
Cancers 2025, 17(13), 2079; https://doi.org/10.3390/cancers17132079 - 21 Jun 2025
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Abstract
Background/Objectives: MicroRNAs are emerging as valuable diagnostic markers for various diseases, including papillary thyroid carcinoma (PTC). However, there is limited research on circulating miRNA expression in papillary thyroid microcarcinoma (PTMC). Therefore, we conducted a study to explore whether plasma-derived miRNAs can distinguish PTMC [...] Read more.
Background/Objectives: MicroRNAs are emerging as valuable diagnostic markers for various diseases, including papillary thyroid carcinoma (PTC). However, there is limited research on circulating miRNA expression in papillary thyroid microcarcinoma (PTMC). Therefore, we conducted a study to explore whether plasma-derived miRNAs can distinguish PTMC from benign nodules or predict aggressiveness. Methods: A total of 150 patients who underwent thyroidectomy from January 2013 to July 2021 were enrolled in this study. Patients were divided into three groups: benign, low-risk PTMC, and advanced PTMC. Nine patients from each group were selected for microarray analysis for plasma miRNAs. Six miRNAs were selected for comparison of expression levels using TaqMan assay. The ROC curve was utilized to evaluate the diagnostic and aggressiveness value of the miRNAs. Results: From the microarray analysis, miR-455-3p and miR-548ac were identified as miRNAs that can significantly differentiate between benign nodules and PTMC. A combination of six miRNAs (miR-455-3p, miR-548ac., miR-221, miR-222, miR-146a. miR-146b) rather than individual miRNAs had the highest AUC (0.857), sensitivity (0.867), and specificity (0.800) in differentiating benign and PTMC. In microarray analysis, no significant miRNAs were observed to distinguish between low-risk group and aggressive PTMC. However, in the six-miRNA combination, it was possible to distinguish low-risk PTMC from aggressive PTMC with an AUC of 0.763, sensitivity of 0.739, and the specificity of 0.727. Conclusions: A combination of six miRNAs presents the possibility of distinguishing between benign and PTMC and low-risk and aggressive PTMC with an acceptable AUC, sensitivity, and specificity. Full article
(This article belongs to the Section Cancer Causes, Screening and Diagnosis)
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17 pages, 1378 KB  
Article
Papillary Thyroid Microcarcinoma in Thyroid Surgical Practice: Incidental vs. Non-Incidental: A Ten-Year Comparative Study
by Amani A. Bashir, Mohamed M. El-Zaheri, Ahmad A. Bashir, Luma Fayyad, Aiman H. Obed, Dima Alkam and Abdalla Y. Bashir
Cancers 2025, 17(12), 2029; https://doi.org/10.3390/cancers17122029 - 18 Jun 2025
Cited by 5 | Viewed by 3877
Abstract
Background/Objectives: With evolving guidelines favoring de-escalation in the management of papillary thyroid microcarcinoma (PTMC), options such as active surveillance and minimally invasive procedures are now considered for patients with low-risk disease. However, a subset of PTMCs—particularly non-incidental cases—may exhibit aggressive behavior. This study [...] Read more.
Background/Objectives: With evolving guidelines favoring de-escalation in the management of papillary thyroid microcarcinoma (PTMC), options such as active surveillance and minimally invasive procedures are now considered for patients with low-risk disease. However, a subset of PTMCs—particularly non-incidental cases—may exhibit aggressive behavior. This study compares disease characteristics and outcomes between incidental and non-incidental PTMCs over a 10-year period. Methods: This is a single-center retrospective comparative analysis utilizing a prospectively collected database of patients referred for thyroid surgery. Results: Papillary thyroid carcinoma accounted for 86.7% of thyroid malignancies, with PTMC comprising 36.2% (137 patients). Incidental PTMC represented 109 out of 1012 patients undergoing surgery for benign thyroid disease (10.8%). Non-incidental PTMC (NIPTMC), diagnosed preoperatively and presenting clinically without coexisting thyroid disease, was identified in 28 patients (20.4%). NIPTMCs were more frequently associated with high-risk features (75% vs. 10.1%, p = 0.004), including extrathyroidal extension (21.43% vs. 7.3% p = 0.0015), positive central lymph nodes (21.43% vs. 2.8%, p = 0.0291), positive lateral lymph nodes (28.6% vs. 0% p = 0.012), and lymphovascular invasion (3.6% vs. 0%). Multifocal PTMC was seen in 37 patients (27%), of which 27 had bilobar disease. Multifocal tumors had a higher likelihood of high-risk features (48.6% vs. 14%, p = 0.007). NIPTMC was a significant predictor of multifocality (p = 0.0098). All patients underwent surgery, none opted for active surveillance. Conclusions: NIPTMC is more often associated with high-risk features and multifocality, necessitating more extensive surgery. These findings emphasize the need for careful preoperative risk stratification to guide individualized management. Full article
(This article belongs to the Section Cancer Metastasis)
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