Search Results (410)

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

Organoid and spheroid technologies have rapidly become pivotal in thyroid cancer research, offering models that are more physiologically relevant than traditional two-dimensional culture. In the study of papillary and anaplastic thyroid carcinomas, two subtypes that differ both histologically and clinically, three-dimensional (3D) models offer unparalleled insights into tumor biology, therapeutic vulnerabilities, and resistance mechanisms. These models maintain essential tumor characteristics such as cellular diversity, spatial structure, and interactions with the microenvironment, making them extremely valuable for disease modeling and drug testing. This review emphasizes recent progress in the development and use of thyroid cancer organoids and spheroids, focusing on their role in replicating disease features, evaluating targeted therapies, and investigating epithelial–mesenchymal transition (EMT), cancer stem cell behavior, and treatment resistance. Patient-derived organoids have shown potential in capturing individualized drug responses, supporting precision oncology strategies for both differentiated and aggressive subtypes. Additionally, new platforms, such as thyroid organoid-on-a-chip systems, provide dynamic, high-fidelity models for functional studies and assessments of endocrine disruption. Despite ongoing challenges, such as standardization, limited inclusion of immune and stromal components, and culture reproducibility, advancements in microfluidics, biomaterials, and machine learning have enhanced the clinical and translational potential of these systems. Organoids and spheroids are expected to become essential in the future of thyroid cancer research, particularly in bridging the gap between laboratory discoveries and patient-focused therapies. Full article

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

Thyroid cancer, the most frequently occurring endocrine neoplasm, comprises a heterogeneous group of histological subtypes, spanning from the indolent papillary thyroid carcinoma (PTC) to the rapidly progressive and lethal anaplastic thyroid carcinoma (ATC). Although conventional therapies, such as surgery and radioactive iodine (RAI), are effective for differentiated thyroid cancers, treatment resistance and poor prognosis remain major challenges in advanced and undifferentiated forms. In current times, growing attention has been directed toward the potential of Natural Killer (NK) cells as a promising immunotherapeutic avenue. These innate immune cells are capable of direct cytotoxicity against tumor cells, but their efficiency is frequently compromised by the immunosuppressive tumor microenvironment (TME), which inhibits NK cell activation, infiltration, and persistence. This review explores the dynamic interaction between NK cells and the TME in thyroid cancer, detailing key mechanisms of immune evasion, including the impact of suppressive cytokines, altered chemokine landscapes, and inhibitory ligand expression. We further discuss latest advancements in NK cell-based immunotherapies, including strategies for ex vivo expansion, genetic modification, and combinatorial approaches with checkpoint inhibitors or cytokines. Additionally, emerging modalities, such as NK cell-derived extracellular vesicles, are addressed. By combining mechanistic insights with advancing therapeutic techniques, this review provides a comprehensive perspective on NK cell-based interventions and their future potential in improving outcomes for patients with thyroid cancer. Full article

Background and Objectives: Thyroid nodules are a common endocrine disorder, with 10–15% exhibiting malignancy. Accurate differentiation of malignant and benign nodules is crucial for optimizing treatment outcomes. Current diagnostic tools, such as the Bethesda classification and fine-needle aspiration biopsy (FNAB), are limited in sensitivity and specificity, particularly in indeterminate cases. Tumor-infiltrating immune cells (TIICs) in the tumor microenvironment (TME) play a significant role in thyroid cancer progression. CD66b⁺ neutrophil-like monocytes constitute a novel subset of myeloid cells that are implicated in the modulation of anti-tumor immune responses, but their role in thyroid cancer remains unclear. Materials and Methods: Peripheral blood and thyroid nodule tissue samples were obtained from 24 patients with papillary thyroid carcinoma, and from 10 patients who underwent surgery for symptoms of tracheal compression due to benign thyroid nodules. Myeloid cell populations were assayed by flow cytometric immunophenotyping with CD45, HLA-DR, CD14, and CD66b. The data were statistically analyzed with the clinical properties of the patients. Results: The neutrophil-like monocytes, which were determined as HLA-DR⁺CD14⁺CD66b⁺ cells, found in the circulation (11.9 ± 2.4% of total mononuclear immune cells) of the patients with papillary thyroid carcinoma, were significantly elevated (p < 0.001). Accordingly, these cells were more frequently detected in tumor tissues (21.1 ± 2.1% of total tumor-infiltrating immune cells) compared to non-tumor thyroid tissues (p = 0.0231). The infiltration levels of neutrophil-like monocytes were significantly higher in malignant nodules as well as in the peripheral blood of the papillary thyroid carcinoma patients compared to the samples obtained from the patients with benign nodules. The tumor tissues exhibited increased immune cell infiltration and harbored CD66b-expressing neutrophil-like HLA-DR⁺CD14⁺ monocytic cells, which indicates an inflammatory milieu in malignant thyroid cancer. Conclusions: This study identifies neutrophil-like monocytes as a potential biomarker for differentiating malignant and benign thyroid nodules. Elevated levels of this novel subtype of immune cells in malignant tissues suggest their role in tumor progression and their utility in enhancing diagnostic accuracy. Incorporating these findings into clinical practice may refine surgical decision-making and improve outcomes through personalized diagnostic and therapeutic strategies, particularly for radioiodine-refractory thyroid cancer. Full article

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

Background/Objectives: Differentiated Thyroid Cancer (DTC), comprising papillary and follicular carcinomas, is the most common type of thyroid cancer. This is highly infectious and increasing at a higher rate. Some patients experience recurrence even after undergoing successful treatment. Early signs of recurrence can be hard to identify, and the existing health care system cannot always identify it on time. Therefore, predicting its recurrence accurately and in its early stage is a significant clinical challenge. Numerous advanced technologies, such as machine learning, are being used to overcome this clinical challenge. Thus, this study presents a novel approach for predicting the recurrence of DTC. The key objective is to improve the prediction accuracy through hyperparameter optimization. Methods: In order to achieve this, we have used a metaheuristic algorithm, the whale optimization algorithm (WOA) and its modified version. The modifications that we introduced in the original WOA algorithm are a piecewise linear chaotic map for population initialization and inertia weight. Both of our algorithms optimize the hyperparameters of the Extreme Gradient Boosting (XGBoost) model to increase the overall performance. The proposed algorithms were applied to the dataset collected from the University of California, Irvine (UCI), Machine Learning Repository to predict the chances of recurrence for DTC. This dataset consists of 383 samples with a total of 16 features. Each feature captures the critical medical and demographic information. Results: The model has shown an accuracy of 99% when optimized with WOA and 97% accuracy when optimized with the modified WOA. Conclusions: Furthermore, we have compared our work with other innovative works and validated the performance of our model for the prediction of DTC recurrence. Full article

Background/Objectives: Papillary thyroid carcinoma (PTC) is the most common malignancy of the endocrine system, characterized by various molecular alterations. This study evaluates the relationship between p16 promoter methylation status, BRAFV600E mutation presence, and ETS1 (E26 transformation-specific) expression, aiming to better understand their clinical significance and to enhance the risk stratification of PTC patients. Methods: p16 promoter methylation was analyzed by methylation-specific PCR (MSP), BRAFV600E by mutant allele-specific PCR amplification (MASA), ETS1 mRNA expression by quantitative PCR (qPCR), ETS1 protein expression by immunohistochemistry (IHC), and Western blot. All tested factors were further associated with the occurrence of unfavorable clinicopathological data of the patients. Results: While p16 methylation did not correlate with adverse clinical parameters or BRAFV600E mutation presence, it was significantly associated with the increased ETS1 mRNA levels. Combined p16 methylation with high ETS1 protein levels was significantly associated with advanced pT and pTNM stages. BRAFV600E-mutated PTC cases with p16 methylation showed increased mRNA and protein ETS1 expression. Conclusions: Therefore, although p16 methylation could not be used as a standalone prognostic marker, its association with elevated ETS1 levels points to its potential involvement in tumor progression and adverse clinical outcomes, particularly in BRAFV600E-mutated PTCs. Deeper insights into these interactions may enhance PTC prognosis and the selection of high-risk patients. Full article

Background and Objectives: Thyroid cancer is the prevailing endocrine malignancy, with incidence growing over the last decades in the world. The current diagnostic techniques often yield inconclusive results, emphasizing the need for more effective diagnostic approaches. Molecular profiling emerges as a promising avenue for carcinoma differentiation, offering precise insights to guide patient selection for surgical intervention. This study aimed to identify molecular markers in thyroid cancer through the expression analysis of genes within the MAPK pathway, aiming to enhance the sensitivity and specificity of carcinoma diagnosis. Methods: Through a comparative analysis of malignant and benign thyroid samples, we identified 46 genes of the MAPK pathway that exhibited differential expression by PCR array analysis. Results: Validation through RT-qPCR and in silico analysis using TCGA confirmed significant results for CCNA1, CDKN1C, CREB1, FOS, HSPA5, JUN, MAP2K6, and SFN genes identified in our cohort, reinforcing the relevance of these biomarkers. Specifically, noteworthy are our findings regarding the potential diagnostic value of CCNA1 and SFN genes in papillary thyroid carcinoma, while the reduced expression of CDKN1C, FOS, and JUN genes in follicular carcinoma suggests their value in distinguishing the thyroid pathologies. Conclusions: This study identifies promising diagnostic markers, namely CCNA1, CDKN1C, FOS, JUN, and SFN genes, which have the potential to enhance clinical decision-making in thyroid cancer. Full article

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

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

Background/Objectives: Papillary thyroid carcinoma (PTC) accounts for the majority of thyroid cancers, with lymph node metastasis, including skip metastasis (SM), playing a crucial role in guiding prognosis and therapeutic planning. SM, characterized by lateral lymph node spread in the absence of central compartment involvement, has been observed in PTC with a wide range of reported frequencies. The identification of risk factors for SM is crucial for preoperative evaluation and surgical planning. This research aims to explore the clinicopathological features and potential risk factors linked to SM in patients with PTC, while also offering valuable insights for preoperative risk evaluation. Methods: A retrospective cohort study was conducted on 81 PTC patients who underwent central and lateral cervical lymph node dissection (LND) in our center. Clinical, demographic, and pathological data, including age, sex, tumor size, location, subtype, extrathyroidal extension, lymphovascular invasion, and the number of lymph node metastases were analyzed. Clinicopathological characteristics were analyzed between SM-positive and SM-negative patient groups using suitable statistical methods. Additionally, a regression analysis was performed to identify the risk factors for SM. Results: Of the 81 patients, 17.3% (n = 14) were diagnosed with skip metastasis (SM). The SM-positive group had a significantly higher age (p = 0.006), smaller tumor size (p < 0.001), and higher rates of extrathyroidal extension (p = 0.006). The proportion of female patients was elevated in the SM-positive group, but this observation did not achieve statistical significance (p = 0.128). Tumors located in the upper pole were more common in the SM-positive group (p = 0.016). Multivariate analysis revealed that female sex, older age, and tumor location in the upper pole were significant risk factors for SM (p = 0.031, p = 0.004, and p = 0.017, respectively), while a lower number of lateral lymph node metastases was significantly associated with SM (p = 0.010). Additionally, an age over 43.5 years predicted SM with a sensitivity of 78.6% and a specificity of 72.7%. Conclusions: Skip metastasis is not uncommon in PTC and may be associated with older age, female sex, upper pole tumor location, and fewer lateral lymph node metastases. Recognizing these factors during preoperative assessment may aid in anticipating atypical lymphatic spread patterns and optimizing surgical strategies. Full article

Background/Objective: Radiotherapy for leukemia, the most common childhood malignancy, often exposes patients to radiation, increasing the risk of second malignancies, including thyroid cancer. To assess the incidence and survival outcomes of thyroid cancer after childhood acute lymphoblastic leukemia (ALL). Methods: We systematically reviewed articles reporting the incidence of thyroid cancer in childhood leukemia survivors (age at diagnosis < 18 years) published between 2000–2024 in Science Direct, PubMed, Google Scholar, CENTRAL, and EMBASE. The Newcastle Ottawa Scale was utilized to appraise the methodological quality of the included studies. Descriptive statistics and calculations of incidence were performed using Microsoft Excel. Results: The literature search yielded 1265 articles, of which 18 met the inclusion criteria. Data from 135,861 childhood cancer survivors, among whom 102,070 had a confirmed diagnosis of childhood leukemia, including ALL. The crude incidence of secondary malignancies after childhood leukemia was 10.1 per 1000 patients. Among these, 1.5 per 1000 patients developed second thyroid carcinomas. Overall, 14.6% of the second malignancies in childhood leukemia survivors were thyroid carcinomas, mostly of the papillary type. Survival rates after second thyroid cancer were 100% in all 11/18 studies reporting this outcome. Radiotherapy had been used as part of ALL treatments in 17/18 studies. The use of radiotherapy, female sex, and younger age at the diagnosis of primary ALL emerged as important risk factors for thyroid cancer. Conclusions: Thyroid carcinomas account for ~15% of secondary malignancies after childhood leukemia, with radiation remaining a significant risk factor despite its overall reduced use for the treatment of ALL in the last few decades. Importantly, survival rates remain high. Further research is warranted to determine the incidence and outcomes of thyroid cancer in childhood ALL survivors Full article

Papillary thyroid carcinoma (PTC) frequently involves cervical lymph node (LN) metastases and is a major determinant of prognosis and recurrence. However, cytology alone has limitations. Fine-needle aspiration thyroglobulin (FNA-Tg) has emerged as a promising diagnostic marker, although its cutoff value remains controversial, particularly in patients with thyroglobulin antibodies (TgAbs). We retrospectively analyzed 63 LNs of 60 patients with PTC at a single medical center. Patients underwent FNA-Tg measurements and concurrent cytological evaluation. Diagnostic performance metrics, including sensitivity, specificity, positive and negative predictive value, and overall accuracy, were evaluated; the cutoff value was determined; and the potential influence of factors such as TgAb on FNA-Tg levels was investigated. A cutoff value of 4.23 ng/mL for FNA-Tg achieved 100% sensitivity and 90.2% specificity, with an overall accuracy of 93.6%. TgAb positivity did not significantly affect the diagnostic performance in patients with FNA-Tg. FNA-Tg might be useful for detecting local LN recurrence and providing valuable diagnostic insights, particularly in patients with residual thyroid tissue or positive TgAbs. Full article

Thyroid cancer (TC) invariably remains the most prevalent endocrine cancer in the world. Major histological forms of TC include papillary (PTC), follicular (FTC), medullary (MTC), and anaplastic thyroid carcinoma (ATC), each of which has a unique clinical and molecular profile. The incidence rate of TC is higher in females, and unfortunately, it has tended to increase over the last several years. Yet the treatment of advanced or aggressive TC forms has improved recently because of developments in immunotherapy and targeted medicines, including PD-1 inhibitors and tyrosine kinase inhibitors (e.g., lenvatinib, sorafenib). Imaging, fine-needle aspiration biopsies, and molecular testing are implemented in the diagnostic process, e.g., in search of mutations that might affect prognosis and provide the most successful treatment option. Chemotherapy, immunotherapy, radioactive iodine therapy (RAI), surgery (such as a total thyroidectomy), and molecularly targeted therapies are currently standard treatment modalities in TC. Optimizing patient outcomes requires better diagnostic precision and individualized treatment regimens based on the genetic profile and tumor subtype. To improve survival and quality of life, it is critical to comprehend the complex etiology of TC and the changing therapeutic landscape. Full article