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Keywords = microcarcinoma

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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
Viewed by 256
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
Viewed by 292
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
Viewed by 608
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
Viewed by 752
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
Viewed by 1095
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 539
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
Viewed by 691
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
Viewed by 597
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 1 | Viewed by 1490
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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12 pages, 1596 KB  
Article
Validation of the Updated Porto Proposal in Papillary Thyroid Microtumors: Analysis of Cases at a University Hospital in Catalonia, Spain
by Karmele Saez de Gordoa, Elias Tasso, Alexandre Rei, Martin Ramonda, Belinda Salinas, Sandra Cobo-Lopez, Aida Orois, Amparo Cobo, Marti Manyalich-Blasi, Teresa Ramón y Cajal, Mireia Mora, Felicia Hanzu, Oscar Vidal Pérez and Maria Teresa Rodrigo-Calvo
Cancers 2025, 17(12), 2021; https://doi.org/10.3390/cancers17122021 - 17 Jun 2025
Viewed by 531
Abstract
Background/Objectives: Given the high incidence and generally favorable prognosis of papillary thyroid microcarcinomas (PTMs), the Porto Proposal aims to refine the management of these tumors. It designates tumors lacking certain risk factors as papillary microtumors (PMTs) to avoid overtreatment and reduce patient [...] Read more.
Background/Objectives: Given the high incidence and generally favorable prognosis of papillary thyroid microcarcinomas (PTMs), the Porto Proposal aims to refine the management of these tumors. It designates tumors lacking certain risk factors as papillary microtumors (PMTs) to avoid overtreatment and reduce patient stress. The updated Porto Proposal (uPp) suggests criteria for reclassifying incidental PTMs as PMTs. This study seeks to validate these criteria using data from a university hospital in Catalonia, Spain, and assess the clinical and pathological characteristics of PTMs. Methods: This retrospective study analyzed patients diagnosed with PTM (≤1 cm) at a university hospital from 2000 to 2024. The study examined variables, including lymph node positivity, incidental diagnosis, tumor location, histological type, treatment, multifocality, age at diagnosis, tumor size, and survival. The uPp criteria were applied to reclassify PTMs into PMTs or PMCs (true papillary microcarcinomas). Student’s t-test and chi-square tests were used to evaluate the associations between these variables and the uPp classification. Results: The cohort comprised 107 patients, with 77 (72%) women and 30 men. The mean age at diagnosis was 54.5 years. Out of the total, 77 (72%) cases were reclassified as PMTs and 30 (28%) as PMCs according to the uPp criteria. PMC tumors were larger (mean size 4.5 mm vs. 3.3 mm for PMT, p = 0.014) and were significantly associated with multifocality (52.2%; p = 0.004). Most lymph node-positive cases were classified as PMCs (69.2%; p < 0.001) and were multifocal and bilateral more commonly. However, no significant differences in outcomes between PMCs and PMTs were found (p = 0.188). Follicular histology was significantly more common in PMTs (87.0%, p < 0.001) and rarely had lymph node metastases (4.6%; p = 0.047). Conclusions: The updated Porto Proposal (uPp) effectively identifies PTMs with minimal malignant potential, distinguishing between PMT and PMC. The findings support the protocol’s use in reducing unnecessary treatments and psychological stress for patients. The study highlights significant clinical and pathological differences between PTM subtypes, reinforcing the protocol’s applicability in daily pathological practice. Full article
(This article belongs to the Special Issue Thyroid Cancer: New Advances from Diagnosis to Therapy: 2nd Edition)
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20 pages, 1733 KB  
Article
Risk Stratification for Thyroid Malignancies in Chronic Lymphocytic Thyroiditis
by Anna Krzentowska, Aleksander Konturek, Filip Gołkowski, Anna Merklinger-Gruchała and Marcin Barczyński
Cancers 2025, 17(12), 1964; https://doi.org/10.3390/cancers17121964 - 12 Jun 2025
Cited by 1 | Viewed by 760
Abstract
Background: Our study investigated the association between chronic lymphocytic thyroiditis (CLT) and thyroid cancer (TC). Methods: A retrospective review of 1670 patients who underwent thyroid surgery between October 2022 to February 2025 was performed. The clinicopathological characteristics of patients with TC [...] Read more.
Background: Our study investigated the association between chronic lymphocytic thyroiditis (CLT) and thyroid cancer (TC). Methods: A retrospective review of 1670 patients who underwent thyroid surgery between October 2022 to February 2025 was performed. The clinicopathological characteristics of patients with TC and CLT were collected. CLT was diagnosed histopathologically. Results: Patients with a positive CLT result (60.39%) compared to a negative CLT result (34.12%) had more frequently TC (p < 0.001), predominantly PTC. In univariate analysis, patients with malignancy + CLT-positive compared to malignancy + CLT-negative were found to be younger in age (p < 0.001), female gender (p < 0.001), smaller tumours focus (p = 0. 013), smaller mass of thyroid removed (p < 0.001) and more often Bethesda category V and VI (p = 0.019), true positive fine needle aspiration biopsy (FNAB) for PTC (p = 0.009), and microcarcinoma (p = 0.021). There were no differences in multifocality, the presence of LNM, or the number of LNMs. The location of metastases at neck lymph nodes was at the borderline of significance (p = 0.065). In multivariate analysis, after accounting for Bethesda and age, CLT+ was found to increase the risk of TC by 73% (OR = 1.73; 95%CI, 1.15-2.29), while the risk of PTC increased more than 2-fold (OR = 2.12; 95% CI, 1.45–3.11). CLT had no statistically significant effect on the presence of LNM. Conclusions: We found that CLT is a risk factor for TC. One should be vigilant concerning the coexistence of these two diseases. We suggest that total thyroidectomy should be considered in patients referred for thyroid nodules and suspected CLT. However, this issue requires further research. Full article
(This article belongs to the Special Issue Thyroid Cancer: New Advances from Diagnosis to Therapy: 2nd Edition)
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19 pages, 2515 KB  
Article
Descriptive Analysis of Common Fusion Mutations in Papillary Thyroid Carcinoma in Hungary
by Richard Armos, Bence Bojtor, Janos Podani, Ildiko Illyes, Bernadett Balla, Zsuzsanna Putz, Andras Kiss, Andrea Kohanka, Erika Toth, Istvan Takacs, Janos P. Kosa and Peter Lakatos
Int. J. Mol. Sci. 2024, 25(19), 10787; https://doi.org/10.3390/ijms251910787 - 8 Oct 2024
Cited by 5 | Viewed by 2403
Abstract
Thyroid cancer is the most common type of endocrine malignancy. Papillary thyroid carcinoma (PTC) is its predominant subtype, which is responsible for the vast majority of cases. It is true that PTC is a malignant tumor with a very good prognosis due to [...] Read more.
Thyroid cancer is the most common type of endocrine malignancy. Papillary thyroid carcinoma (PTC) is its predominant subtype, which is responsible for the vast majority of cases. It is true that PTC is a malignant tumor with a very good prognosis due to effective primary therapeutic approaches such as thyroidectomy and radioiodine (RAI) therapy. However, we are often required to indicate second-line treatments to eradicate the tumor properly. In these scenarios, molecular therapies are promising alternatives, especially if specifically targetable mutations are present. Many of these targetable gene alterations originate from gene fusions, which can be found using molecular diagnostics like next-generation sequencing (NGS). Nonetheless, molecular profiling is far from being a routine procedure in the initial phase of PTC diagnostics. As a result, the mutation status, except for BRAF V600E mutation, is not included in risk classification algorithms either. This study aims to provide a comprehensive analysis of fusion mutations in PTC and their associations with clinicopathological variables in order to underscore certain clinical settings when molecular diagnostics should be considered earlier, and to demonstrate yet unknown molecular–clinicopathological connections. We conducted a retrospective fusion mutation screening in formalin-fixed paraffin-embedded (FFPE) PTC tissue samples of 100 patients. After quality evaluation by an expert pathologist, RNA isolation was performed, and then NGS was applied to detect 23 relevant gene fusions in the tumor samples. Clinicopathological data were collected from medical and histological records. To obtain the most associations from the multivariate dataset, we used the d-correlation method for our principal component analysis (PCA). Further statistical analyses, including Chi-square tests and logistic regressions, were performed to identify additional significant correlations within certain subsets of the data. Fusion mutations were identified in 27% of the PTC samples, involving nine distinct genes: RET, NTRK3, CCDC6, ETV6, MET, ALK, NCOA4, EML4, and SQSTM1. RET and CCDC6 fusions were associated with type of thyroidectomy, RAI therapy, smaller tumor size, and history of Hashimoto’s disease. NCOA4 fusion correlated with sex, multifocality, microcarcinoma character, history of goiter, and obstructive pulmonary disease. EML4 fusion was also linked with surgical procedure type and smaller tumor size, as well as the history of hypothyroidism. SQSTM1 fusion was associated with multifocality and a medical history of thyroid/parathyroid adenoma. NTRK3 and ETV6 fusions showed significant associations with Hashimoto’s disease, and ETV6, also with endometriosis. Moreover, fusion mutations were linked to younger age at the time of diagnosis, particularly the fusion of ETV6. The frequent occurrence of fusion mutations and their associations with certain clinicopathological metrics highlight the importance of integrating molecular profiling into routine PTC management. Early detection of fusion mutations can inform surgical decisions and therapeutic strategies, potentially improving clinical outcomes. Full article
(This article belongs to the Special Issue Current Research on Cancer Biology and Therapeutics: 2nd Edition)
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11 pages, 688 KB  
Article
Interstitial Fibrosis as a Common Counterpart of Histopathological Risk Factors in Papillary Thyroid Microcarcinoma: A Retrospective Analysis
by Can Sahin, Mehmet Arda Inan, Banu Bilezikci, Hasan Bostanci, Ferit Taneri and Ramazan Kozan
Diagnostics 2024, 14(15), 1624; https://doi.org/10.3390/diagnostics14151624 - 27 Jul 2024
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Abstract
Purpose. Interstitial fibrosis in papillary thyroid microcarcinoma is a subject which is under-investigated. The aim of this study is to determine the relationship between interstitial fibrosis, the subtypes of papillary microcarcinoma, and the established prognostic factors. Material and Methods. A total of 75 [...] Read more.
Purpose. Interstitial fibrosis in papillary thyroid microcarcinoma is a subject which is under-investigated. The aim of this study is to determine the relationship between interstitial fibrosis, the subtypes of papillary microcarcinoma, and the established prognostic factors. Material and Methods. A total of 75 patients diagnosed with papillary microcarcinoma of the thyroid from January 2011 to December 2020 have been evaluated retrospectively, using demographic features, tumor size, subtype of the tumor, surgical margin status, unifocality, lymphovascular invasion, extracapsular spread and lymph node metastasis as parameters. Hematoxylin and eosin slides were reviewed for interstitial fibrosis. Results. The study includes 13 males and 62 females, in a total of 75 patients. There were 51 patients (68%) with interstitial fibrosis and 24 (32%) patients without interstitial fibrosis. Among them, 45 (60%) were classic, 27 (36%) were follicular variant and 3 (4%) were other subtypes. Interstitial fibrosis is significantly associated with bilaterality (p = 0.023), multifocality (p = 0.004), capsule invasion (p < 0.001) and lymph node metastasis (p = 0.043). Evaluation of tumor sub groups showed significant increased risk of lymphovascular invasion in the follicular variant (p = 0.019). Conclusion. Although the relationship of interstitial fibrosis and prognosis of other cancer types has been discussed, there are few studies in the literature regarding its effect on the prognosis of papillary microcarcinoma. Our results show that interstitial fibrosis can be used as a risk factor. However, new studies are needed to clearly reveal the physiopathology of interstitial fibrosis and its effect on tumorigenesis. Full article
(This article belongs to the Section Pathology and Molecular Diagnostics)
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21 pages, 26366 KB  
Article
BRAF Detection in FNAC Combined with Semi-Quantitative 99mTc-MIBI Technique and AI Model, an Economic and Efficient Predicting Tool for Malignancy in Thyroid Nodules
by Laura Teodoriu, Maria-Christina Ungureanu, Mioara Matei, Irena Grierosu, Alexandra Iuliana Saviuc, Jalloul Wael, Iuliu Ivanov, Loredana Dragos, Radu Danila, Velicescu Cristian, Mihai-Andrei Costandache, Adrian Iftene, Cristina Preda and Cipriana Stefanescu
Diagnostics 2024, 14(13), 1398; https://doi.org/10.3390/diagnostics14131398 - 30 Jun 2024
Viewed by 1826
Abstract
Background: Technology allows us to predict a histopathological diagnosis, but the high costs prevent the large-scale use of these possibilities. The current liberal indication for surgery in benign thyroid conditions led to a rising frequency of incidental thyroid carcinoma, especially low-risk papillary micro-carcinomas. [...] Read more.
Background: Technology allows us to predict a histopathological diagnosis, but the high costs prevent the large-scale use of these possibilities. The current liberal indication for surgery in benign thyroid conditions led to a rising frequency of incidental thyroid carcinoma, especially low-risk papillary micro-carcinomas. Methods: We selected a cohort of 148 patients with thyroid nodules by ultrasound characteristics and investigated them by fine needle aspiration cytology (FNAC)and prospective BRAF collection for 70 patients. Also, we selected 44 patients with thyroid nodules using semi-quantitative functional imaging with an oncological, 99mTc-methoxy-isobutyl-isonitrile (99mTc-MIBI) radiotracer. Results: Following a correlation with final histopathological reports in patients who underwent thyroidectomy, we introduced the results in a machine learning program (AI) in order to obtain a pattern. For semi-quantitative functional visual pattern imaging, we found a sensitivity of 33%, a specificity of 66.67%, an accuracy of 60% and a negative predicting value (NPV) of 88.6%. For the wash-out index (WOind), we found a sensitivity of 57.14%, a specificity of 50%, an accuracy of 70% and an NPV of 90.06%.The results of BRAF in FNAC included 87.50% sensitivity, 75.00% specificity, 83.33% accuracy, 75.00% NPV and 87.50% PPV. The prevalence of malignancy in our small cohort was 11.4%. Conclusions: We intend to continue combining preoperative investigations such as molecular detection in FNAC, 99mTc-MIBI scanning and AI training with the obtained results on a larger cohort. The combination of these investigations may generate an efficient and cost-effective diagnostic tool, but confirmation of the results on a larger scale is necessary. Full article
(This article belongs to the Special Issue Pathology and Diagnosis of Thyroid Disease)
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12 pages, 606 KB  
Article
The European Thyroid Imaging and Reporting Data System as a Remedy for the Overdiagnosis and Overtreatment of Thyroid Cancer: Results from the EUROCRINE Surgical Registry
by Andrzej Rafał Hellmann, Piotr Wiśniewski, Maciej Śledziński, Marco Raffaelli, Jarosław Kobiela and Marcin Barczyński
Cancers 2024, 16(12), 2237; https://doi.org/10.3390/cancers16122237 - 17 Jun 2024
Viewed by 3029
Abstract
Background: The European Thyroid Imaging and Reporting Data System (EU-TIRADS) aims to reduce the overdiagnosis of thyroid cancer (TC) by guiding the selection of nodules for fine-needle aspiration biopsy (FNAB). This study sought to validate EU-TIRADS nodule selection criteria using data from EUROCRINE, [...] Read more.
Background: The European Thyroid Imaging and Reporting Data System (EU-TIRADS) aims to reduce the overdiagnosis of thyroid cancer (TC) by guiding the selection of nodules for fine-needle aspiration biopsy (FNAB). This study sought to validate EU-TIRADS nodule selection criteria using data from EUROCRINE, an extensive international endocrine surgery registry. Method: We reviewed indications for FNAB among patients with TC compared to those with benign disease who underwent surgery between March 2020 and March 2022, considering preoperative EU-TIRADS scores and dominant nodule size (FNAB is recommended in Category 5 (˃10 mm or ˂10 mm with suspicious lymph nodes), 4 (˃15 mm), and 3 (˃20 mm)). Patients were categorized into three risk groups: minimal risk (patients with papillary microcarcinoma), high risk (patients with pT3b stage or higher, pN1b, or pM1), and low–moderate risk (all other patients). We conducted a Receiver Operating Characteristic (ROC) analysis to assess the diagnostic accuracy of the EU-TIRADS. Results: We analyzed 32,008 operations. Approximately 68% of the surgical records included EU-TIRADS classifications. The EU-TIRADS exhibited diagnostic accuracy across high-volume sites, with a median ROC Area Under the ROC Curve (AUC) of 0.752, indicating its effectiveness in identifying malignancy. Among the cases, 7907 patients had TC. Notably, 55% of patients with TC underwent FNAB despite not initially meeting the EU-TIRADS criteria. These patients were distributed across the minimal- (58%), low–moderate- (36%), and high-risk (5.8%) categories. Of the patients with TC recommended for FNAB, 78% were deemed low–moderate risk, 21% high risk, and only 0.7% minimal risk. Conclusion: The EU-TIRADS offers effective preoperative malignancy risk stratification. Promoting the proper use of the EU-TIRADS in clinical practice is essential to mitigate the overdiagnosis and overtreatment of low-risk TC. Full article
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