Search Results (674)

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

(1) Background: Sertoli–Leydig cell tumors (SLCTs) are rare ovarian neoplasms that account for less than 0.5% of all ovarian tumors. They usually affect young women and often present with androgenic symptoms. We report a unique case of a 40-year-old woman diagnosed with both SLCT and clear cell papillary renal cell carcinoma (CCP-RCC), a rare tumor association with unclear pathogenesis. (2) Methods: Both tumors were treated surgically. The diagnostic workup included hormonal testing, imaging studies, and extensive genetic testing, including DICER1 mutation analysis and multiplex ligation-dependent probe amplification (MLPA), as well as the examination of a next-generation sequencing (NGS) panel covering ~280 cancer-related genes. (3) Results: Histopathologic examination confirmed a well-differentiated SLCT and CCP-RCC. No pathogenic variants in DICER1 were identified by WES or MLPA. No clinically relevant changes were found in the extended NGS panel either, so a known hereditary predisposition could be ruled out. The synchronous occurrence of both tumors without genomic alterations could indicate a sporadic event or as yet unidentified mechanisms. (4) Conclusions: This case highlights the importance of a multidisciplinary approach in the management of rare tumor compounds. The exclusion of DICER1 mutations and the absence of genetic findings adds new evidence to the limited literature and underscores the importance of long-term surveillance and further research into potential shared oncogenic pathways. Full article

Background: In patients with familial adenomatous polyposis (FAP), the duodenum is another high-risk region for malignancy after the large bowel. However, endoscopic and surgical management differs for papillary lesions and adenomas located in other parts of the duodenum. The aim of the study was to present the principles of the endoscopic surveillance of extrapapillary polyps based on a single-center 14-year observational study. Methods: The retrospective analysis was carried out in 2010–24 on a group of 45 people enrolled in endoscopic surveillance of the upper gastrointestinal tract due to FAP. The evaluation was aimed at detecting the malignant transformation of extrapapillary duodenal adenomas, with a radical removal of high-risk lesions. The severity of polyposis in the subsequent years of observation as well as the effectiveness of routine polypectomy on downstaging according to the Spiegelmann score were also assessed. Results: Invasive duodenal cancer was not detected in any case; however, high-grade dysplasia (HGD) was confirmed in five patients. The severity of polyposis and the number of polyps with HGD increased in following examinations, but routine polypectomy performed mainly during the 4th and 5th endoscopies allowed for a transient decrease in the Spiegelman score. Finally, progression of duodenal polyposis was observed in 18 patients, another 4 experienced regression (downstaging) and in 23 cases the stage of severity did not change. In addition, five patients were diagnosed with LST-G lesions, which were removed without recurrence. Conclusions: The patient’s age correlates with the severity of polyposis and the risk of malignancy, but routine endoscopic resections eliminate potentially invasive lesions and contribute to disease regression expressed by the Spiegelmann score. The radical endoscopic therapy of extrapapillary duodenal lesions limits the indications for surgical procedures. Full article

Thyroid cancer (TC) is the most common endocrine malignancy, with a rising global incidence. In Ecuador, TC rates are among the highest worldwide. Generally, fine-needle aspiration (FNA) remains the standard diagnostic tool; however, due to its limitations, alternative or complementary approaches are required. In this context, liquid biopsy, particularly circulating tumor DNA (ctDNA), offers a promising, minimally invasive option for tumor genotyping. Objective: This study evaluated the concordance between genetic variants identified in ctDNA and tumor tissue. Thirty-six women with papillary thyroid cancer were included. Tumor tissue and blood samples were collected, and DNA was extracted. Next-Generation Sequencing (NGS) using the TruSight Tumor 15 panel identified genetic variants in both ctDNA and tumor DNA. Variant pathogenicity was assessed following ACMG guidelines. Genetic ancestry was determined using Ancestry Informative Markers (AIMs). A total of 71 cancer-associated variants were detected, with 81.69% concordance between tumor DNA and ctDNA. TP53 was the most frequently mutated gene. While most pathogenic variants were found in tumor tissue, some variants appeared exclusively in ctDNA samples on specific patients, suggesting tumor heterogeneity. Ancestry analysis revealed a predominant Native American component (62.4%). Liquid biopsy demonstrates high concordance with tumor tissue analysis and holds potential as a complementary diagnostic tool for thyroid cancer. However, challenges such as low ctDNA yield and underrepresentation in genetic databases highlight the need for improved protocols and increased inclusion of admixed populations in genomic studies. 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/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 and Objectives: This study reports an association between nasolacrimal duct obstruction (NLDO) and perinasal uptake on radioactive iodine (RAI) whole-body scan. Materials and Methods: This is a retrospective study of 37 patients from May to November 2017 who underwent thyroidectomy and I-131 ablation for papillary thyroid cancer (PTC) and had a follow-up I-123 diagnostic WBS and dacryoscintigraphy. Ophthalmic examinations assessed punctal stenosis, NLDO, tear film break-up time, Schirmer’s test, punctate keratopathy, tear meniscus height, epiphora, and ocular dryness. Perinasal and nasal uptake on whole-body scans (WBSs) were assessed as negative (no uptake) or positive (focal uptake). The associations between perinasal uptake on WBS, dacryoscintigraphy findings, and ophthalmic assessments were assessed. Results: Nasal uptake on I-131 post-ablation WBS were observed in 60 eyes (81%); perinasal uptake was observed in 8 eyes (11%). Nasal uptake on I-123 post-ablation WBS were observed in all eyes; perinasal uptake was observed in 15 eyes (20%). Perinasal and nasal uptake on I-131 post-ablation WBS were significantly associated with delayed excretion on dacryoscintigraphy (p < 0.001 and p = 0.03, respectively). Perinasal uptake on I-123 WBS was associated with both abnormal dacryoscintigraphy findings and ocular dryness (p < 0.001 and p = 0.02, respectively). Conclusions: Perinasal uptake on I-131 post-ablation and I-123 diagnostic WBS was significantly associated with delayed excretion on dacryoscintigraphy, suggesting NLDO. 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

Thyroid carcinogenesis has multiple hallmarks, including evasion of tumor suppressors. Reactivation of wild-type p53 function is the ultimate goal in cancer therapy, which requires an understanding of the p53 suppression mechanism specific to the cancer type. MiR-7-5p and IPO7 are implicated in the pathogenesis of several human diseases. This work aims to investigate the role of miR-7-5p and IPO7 in p53 regulation in papillary thyroid cancer (PTC) cells. Primary cultured thyroid cells and FFPE thyroid tissues from PTC and benign cases were used. Functional experiments were performed by transfection with IPO7 siRNA or miR-7-5p mimic/inhibitor, followed by apoptosis and luciferase reporter assays, immunoblot assays, and RT-PCR. The expression and subcellular localization of IPO7, p53, MDM2, and ribosomal proteins (RPL11 and RPL5) were studied by immunofluorescence staining and confocal microscopy. The results show that IPO7 is overexpressed in PTC and regulated by miR-7-5p. Modulation of IPO7 expression in cultured thyroid cells altered the nucleocytoplasmic shuttling of p53, MDM2, RPL11, and RPL5, in addition to the p53 protein level and activity. The expression pattern of IPO7, p53, and MDM2 in cultured thyroid cells and clinical thyroid tissue specimens confirmed the association between IPO7 overexpression and reduced p53 stability in PTC. In conclusion, the data here show that p53 level and activity are differentially controlled in malignant and benign thyroid cells through miR-7-5P/IPO7-mediated regulation of RP-MDM2-p53 nucleocytoplasmic trafficking. In PTC, downregulation of miR-7-5p with consequent overexpression of IPO7 might be a protective mechanism used by cancer cells to evade p53 growth suppression during carcinogenesis. Full article

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

Accurate tumor classification is essential for guiding treatment, yet histology alone may overlook key molecular differences or result in misclassification. We present a multimodal strategy that integrates gene expression (mRNA) and DNA methylation data to improve classification accuracy and detect misclassified tumors. Using 6216 samples from The Cancer Genome Atlas (TCGA), we applied Support Vector Machines (SVMs) and hierarchical clustering to evaluate classification accuracy across single and integrated platforms. mRNA and methylation data alone achieved accuracies of 97% and 95.4%, respectively. Their integration further reduced false positives and improved the identification of outliers, including histologically misclassified cases such as papillary renal cell carcinoma samples clustering with bladder cancer. The integrated approach also revealed molecular subtypes correlated with somatic mutations and patient survival, offering clinically relevant insights. Our findings highlight the value of combining genetic and epigenetic profiles to refine cancer diagnostics. This framework enhances diagnostic precision, supports treatment decisions, and provides a scalable quality control tool for molecular oncology. 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