Search Results (278)

Thyroid cancer is the most common endocrine malignancy, and preoperative distinction between benign and malignant nodules remains challenging, especially in cytologically indeterminate cases. Circulating microRNAs (miRNAs) have gained interest as non-invasive biomarkers due to their stability and involvement in tumorigenesis. This study aimed to assess the preoperative diagnostic value of circulating miR-146a and miR-221 in patients undergoing thyroidectomy. A total of 56 patients were included, of whom 24 had malignant and 32 had benign thyroid lesions confirmed by histopathology. Preoperative plasma levels of miR-146a and miR-221 were quantified using qRT-PCR, and relative expression was calculated with the 2^−ΔΔCt method. miR-221 expression was significantly higher in malignant cases, with an area under the ROC curve of 1.00, achieving 100% sensitivity and specificity at the optimal threshold. miR-146a showed no significant discriminatory ability. Weak correlations were observed between miRNA expression and clinical parameters such as age, TIRADS score, or thyroid volume. Logistic regression including miR-221 led to perfect separation, indicating strong predictive capacity but precluding multivariate modeling. These findings suggest that circulating miR-221 may serve as a highly accurate biomarker for thyroid malignancy and warrant further validation in larger, prospective cohorts. 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

Background: Medullary thyroid carcinoma (MTC) has a high rate of local and distant metastases. In particular, the RET protooncogene appears to be the predominant driver mutation for oncogenesis. The German S3 thyroid carcinoma guidelines recommend molecular genetic analysis of the tumour without specifying the site of the tissue sampling. Whether there is difference in RET protooncogene between the primary tumour, lymph node, and distant metastasis has not yet been investigated. However, differences could be important with regard to biopsy localization, and also, thus, the choice of single- or multi-tyrosine-kinase-inhibitor therapy. Methods: In a case of sporadic MTC, Cancer Hotspot panel diagnostics were performed on the primary tumour, lymph node metastasis, and distant metastasis. Mutations were classified using different gene databases, and the different stages of metastasis were compared. Results: RET protooncogene (chr10:43609933, c.1886_1891delTGTGCG, p.Leu629_Asp631delinsHis) was found to be present in the MTC tissue of the primary tumour, lymph node, and distant metastasis in the Cancer Hotspot Panel diagnostic, while the other investigated therapy-relevant mutational profiles were not consistently found. Conclusions: Further longitudinal studies in larger patient cohorts are required to elucidate the role of the RET protooncogene in the metastatic progression of MTC and to determine its impact on the selection of biopsy sites and the subsequent decision-making regarding single- versus multi-tyrosine kinase inhibitor therapy. 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

The discovery of proteomic biomarkers in cancer research can be effectively performed in situ by exploiting Matrix-Assisted Laser Desorption Ionization (MALDI) Mass Spectrometry Imaging (MSI). However, due to experimental limitations, the spectra extracted by MALDI-MSI can be noisy, so pre-processing steps are generally needed to reduce the instrumental and analytical variability. Thus far, the importance and the effect of standard pre-processing methods, as well as their combinations and parameter settings, have not been extensively investigated in proteomics applications. In this work, we present a systematic study of 15 combinations of pre-processing steps—including baseline, smoothing, normalization, and peak alignment—for a real-data classification task on MALDI-MSI data measured from fine-needle aspirates biopsies of thyroid nodules. The influence of each combination was assessed by analyzing the feature extraction, pixel-by-pixel classification probabilities, and LASSO classification performance. Our results highlight the necessity of fine-tuning a pre-processing pipeline, especially for the reliable transfer of molecular diagnostic signatures in clinical practice. We outline some recommendations on the selection of pre-processing steps, together with filter levels and alignment methods, according to the mass-to-charge range and heterogeneity of data. Full article

We present a case with unusual findings on nuclear imaging after mild SARS-CoV-2 infection. During evaluation for an incidentaloma, 18F-Fluorodeoxyglucose Positron Emission Tomography–Computed Tomography imaging showed activity in the thyroid gland, in the lower thoracic spinal column, in portal lymph nodes, and in the terminal ileum and surrounding lymph nodes, all suspicious for metastatic cancer. The patient underwent extensive invasive and non-invasive diagnostic procedures, including biopsies of all the suspicious foci, only showing a small low-grade thyroid cancer that would often be followed and not immediately operated on. Three months later, the findings had either disappeared or were considered reactive. The patient later recalled having had mild COVID-19 seven days prior to the PET/CT. 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

Background/Objectives: Cowden syndrome (or PTEN hamartoma tumor syndrome) (CS/PHTS) belongs to a group of inherited disorders associated with the development of multiple hamartomas. The clinical presentation of patients may include dysmorphic facial features, macrocephaly, developmental delay, and multiple benign and malignant tumors of various localizations. At the same time, only thyroid cancer is thought to have an increased risk in childhood. Skin lesions in CS/PHTS occur in 90–100% of patients and include multiple tricholemmoma, papilloma, acral keratosis, pigmentation changes, as well as rarer forms like vascular malformations, fibromas, neuromas, melanoma, and basal cell carcinoma. Methods: Next-generation sequencing and Sanger sequencing were used to search for PTEN genetic variants. A histological and immunohistochemical examination of tumor biopsies and skin lesions was performed. Results: A total of 13 patients from six families with CS/PHTS, including 10 children, were described. Seven pediatric patients belonged to families with paternal transmission of the PTEN pathogenic variants, while three others were de novo cases. Atypical manifestations in CS/PHTS were diffuse large B-cell lymphoma in one adult, a renal cell carcinoma, three germ cell tumors, and a linear epidermal nevus in pediatric patients. A literature review of the identified pathogenic variants in the PTEN gene was performed, assessing their clinical significance and analyzing the traditional and modified diagnostic criteria as applied to the pediatric population. Conclusions: Taking into account the low incidence of CS/PHTS, the data presented significantly expand our current understanding of this disease and guide physicians to consider a wider range of possible malignant neoplasms in pediatric patients with CS/PHTS. Full article

Background and Objectives: Many diagnostic methods exist for identifying thyroid malignancy, but most of them resemble an odyssey, as the journey from palpating a nodule to receiving a definitive diagnose is often long and costly. The aim of the present study is to investigate the role of Sestamibi scintigraphy in the characterization of cytological indeterminate thyroid nodules. Materials and Methods: A focused literature review was conducted, emphasizing the comparison between Fine Needle Aspiration Biopsy (FNAB), the main diagnostic method for thyroid cancer, and Sestamibi. Results: It is widely accepted that Sestamibi is the primary alternative for patients with non-diagnostic FNAB. As shown in the literature, Sestamibi has a high negative predictive value in excluding thyroid malignancy. Conclusions: Much like Odysseus’ adventurous 10-year journey returning to Ithaca, the path to diagnosing thyroid cancer is not straightforward. Molecular imaging with 99mTc-Sestamibi may serve as a valuable adjunct in evaluating thyroid nodules with inconclusive cytological findings. Full article

Background: A novel and highly effective strategy for tumor immunotherapy involves enhancing host immune responses against tumors through the blockade of checkpoint molecules. The most common toxicities associated with checkpoint blockade therapies include autoimmune damage to various organs. Purpose: This study aims to investigate hematological markers derived from complete blood counts (CBCs)—including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), derived neutrophil-to-lymphocyte ratio (dNLR), white blood cell-to-hemoglobin ratio (WHR), neutrophils, lymphocytes, platelets, hemoglobin, red blood cell (RBC) count, neutrophil-to-RBC ratio (NRR), and neutrophil-to-hemoglobin ratio (NHR)—as potential prognostic biomarkers for the early identification of hypothyroidism in patients receiving PD-1 or PD-1/CTLA-4 immune checkpoint inhibitors. Materials and Methods: A prospective observational study was conducted on 44 patients with stage III-IV solid tumors treated with immune checkpoint (PD-1 or PD-1/CTLA-4) inhibitors. Thyroid function tests and CBC-derived biomarkers were collected at baseline, before immunotherapy. In the immunotherapy cohort, 15 of the 44 patients developed immune-related hypothyroidism, defined as overt autoimmune thyroiditis (TSH > 4.0, FT4 < 12, and anti-TPO antibodies > 30 IU/mL and/or anti-TG antibodies > 95 IU/mL) (Group 1). In comparison, 29 patients maintained normal thyroid function (Group 2). The control group comprised 14 age- and sex-matched healthy volunteers (Group 3). Statistical analyses were performed using analysis of variance (ANOVA) to compare blood parameters among the three groups (Group 1, Group 2, and Group 3) before treatment, with statistical significance set at a p-value < 0.05. Receiver operating characteristic (ROC) curve analysis was conducted to evaluate the diagnostic power of the potential prognostic biomarkers areas. The area under the curve (AUC), sensitivity, and specificity were calculated for the 44 immunotherapy patients. Results: The PLR was significantly higher (262.25 ± 162.95), while WBCs-neutrophils, the WHR, the NRR, the NHR, WBCs, neutrophils, and lymphocytes were lower (2.07 ± 0.66, 0.54 ± 0.19, 0.96 ± 0.28, 0.36 ± 0.14, 6.36 ± 2.07, 4.29 ± 1.55, and 1.23 ± 0.41, respectively) at baseline in Group 1 in comparison to Group 2. ROC curve analysis revealed that the areas under the curve (AUC) for WBCs, neutrophils, lymphocytes, WBCs-neutrophils, the PLR, the WHR, the NRR, and the NHR were 0.9, 0.87, 0.83, 0.85, 0.84, 0.92, 0.89, and 0.87, respectively. These values exceeded the threshold, indicating the high prognostic potential of each marker. Conclusions: Lower baseline levels of WBCs-neutrophils, the WHR, the NRR, the NHR, WBCs, neutrophils, and lymphocytes, along with a higher PLR, were associated with an increased risk of hypothyroidism in patients receiving PD-1 or PD-1/CTLA-4 inhibitors. These CBC-derived biomarkers represent simple, accessible, and potentially useful tools for predicting hypothyroidism in cancer patients undergoing immunotherapy. Further studies in bigger cohorts are needed to validate our findings. 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

Background: Parathyroid neoplasia is a heterogeneous group of tumors, including parathyroid adenoma (PA), atypical parathyroid tumors (aPTs), and parathyroid carcinoma (PC). Differential diagnosis, especially preoperatively, between parathyroid carcinoma and the other two entities is challenging. The purposes of this study were to highlight the main differences between different parathyroid tumors and to evaluate how combined PC suspicion and intraoperative adjuncts can influence surgical decision-making and outcome-related issues. Methods: We performed a retrospective study of a database of patients diagnosed with parathyroid tumors who underwent surgical treatment at our endocrine surgery referral center between June 2019 and July 2024. Demographic, clinical, biochemical, imaging, intraoperative, immunohistochemical, and follow-up data were analyzed. Results: A total of 83 cases were included in our study, divided for analysis into PA (n = 67), aPT (n = 9) and PC (n = 7) subgroups. The clinical profile of the cohort showed a significant difference (p < 0.05) between the PA, aPT, and PC subgroups regarding the presence of palpable tumors (0% vs. 11.11% vs. 14.29%), both bone and kidney involvement (14.93% vs. 44.44% vs. 85.71%), and extensive disease beyond bone and kidney involvement (4.48% vs. 44.44% vs. 71.43%). PTH levels over five times the normal value were present at significantly different rates (p < 0.001), with higher rates in the aPT and PC subgroups (55.56% and 85.71%, respectively) compared with the PA subgroup (7.46%). Also, a significant difference (p < 0.001) was observed when analyzing extreme albumin-corrected serum calcium elevations over 14 mg/dL, with much higher rates in the PC subgroup (71.43%) compared to PA (1.49%) and aPT (33.33%). On preoperative ultrasonography, a significantly higher number of PCs presented diameters ≥ 3 cm (p < 0.001), depth-to-width ratios (D/W) ≥ 1 (p = 0.003), suspicious delineation (p < 0.001), and suspicious echotexture features (p < 0.001), compared to PAs. On preoperative US performed by the surgeon, suspicious features for thyroid cancer were identified in five more patients compared to the four identified by the initial US evaluation, and all (10.84% of all patients) were confirmed on final histopathology as papillary thyroid cancers. Intraoperatively, a significant difference (p < 0.001) regarding parathyroid macroscopic suspicious features, including adhesions to the thyroid gland, was seen between subgroups. When analyzing only cases with en bloc resection, we found that, in all PC cases, a combined preoperative suspicion was present, and in five cases an intraoperative suspicion was raised. Immunohistochemical data showed significantly different median Ki-67 indices between subgroups (1, 2, and 5; p = 0.008) and a different parafibromin staining profile between PC and aPT. Regarding intraoperative neuromonitoring use, a significantly lower incidence of voice changes related to the external branch of the superior laryngeal nerve was observed in the monitoring vs. non-monitoring group (57.14% vs. 12.5%, p = 0.019). Conclusions: Our findings confirm that, in a multimodal and combined diagnostic approach, early pre- and intraoperative PC suspicion can be raised in order to optimize surgical treatment and, thus, favorably influence the outcome. Utilizing all resources available, including intraoperative parathormone determination, laryngeal nerve neuromonitoring, and immunohistochemistry staining, can bring extra benefit to the management of these challenging cases. Full article

Objectives: The current standard of care for endocrine tumors includes a personalized diagnostic and therapeutic approach aimed at the early detection of tumor recurrence after radical surgery. Assessment of tumor-associated biological factors in serum may be useful in patient management. The aim of this study is to determine whether any of the selected growth factors (VEGF, FGF), lectins (Galectin-1, Galectin-3), proteins (Fascin), or TNF-α measured in serum may serve as a potential marker of recurrence. Methods: A total of 68 cases, including 43 patients with disseminated endocrine neoplasm (neuroendocrine tumor (NET) 30 cases, medullary thyroid cancer (MTC) 6 cases, adrenal neoplasm 7 cases) and 25 healthy participants, were included in the analysis. Serum concentrations of TNF-α, Fascin, VEGF, Galectin-1, Galectin-3, and FGF were determined in all cases. The results were compared between groups. Results: A comparison between all patients and controls revealed differences in TNF-α concentrations (2.88 vs. 0.93 (ng/mL), p = 0.008). When comparing the concentrations of the measured factors between the subgroups (classified by tumor type) and the control group, differences were found for TNF-α (p = 0.007) and Fascin (p = 0.035). In the case of Fascin, differences were found for MTC and adrenal neoplasm patients (0.52 vs. 5.28 (ng/mL), p = 0.048), as well as MTC and NET patients (0.52 vs. 5.59 (ng/mL), p = 0.007), while the differences between NET patients and controls were close to significance (5.59 vs. 3.67 (ng/mL), p = 0.076). For TNF-α, significant differences were found between NET patients and controls (2.88 vs. 0.03 (ng/mL), p = 0.005) as well as between MTC patients and controls (2.77 vs. 0.93 (ng/mL), p = 0.004). Conclusions: Serum concentrations of selected proteins and growth factors (Fascin, TNF-α) are significantly higher in those with disseminated endocrine tumors compared to healthy controls. More studies are needed to determine the role of these selected proteins and growth factors in the early detection of NET/MTC recurrence. Full article

Thyroid ultrasonography (US) usage has risen significantly over the past two decades, with annual increases of up to 21% in some healthcare systems. This review examines patterns in thyroid US usage, factors driving potential misuse, and strategies to mitigate overuse. While thyroid US provides valuable information on thyroid morphology and structure without radiation exposure, inappropriate use—estimated at 10–50% of exams—leads to adverse consequences, including patient anxiety, unnecessary procedures, and potential overdiagnosis of thyroid cancer. The widespread adoption of US has coincided with increased thyroid cancer diagnoses, yet mortality rates remain unchanged, suggesting overdiagnosis rather than actual disease increase. Clinical guidelines consistently recommend selective US use not for routine evaluation of thyroid dysfunction (hyper/hypothyroidism) without palpable abnormalities, but for the anatomical assessment of palpable nodules. For thyroid incidentalomas (ITNs), evidence suggests negligible malignancy risk for nodules < 1 cm, arguing against further investigation. The paper proposes a rational approach to thyroid US, emphasizing that patients with thyroid dysfunction without palpable abnormalities, euthyroid patients without palpable nodules, and patients with subcentimetric ITNs should not undergo thyroid US. Addressing this overutilization requires a better understanding of contributing factors and targeted interventions. By restricting US to appropriate clinical scenarios, healthcare resources can be optimized without compromising patient outcomes, ensuring that rare cases of clinically significant thyroid cancer receive proper diagnosis and treatment. Full article