Anaplastic and poorly differentiated thyroid carcinomas: genetic evidence of high-grade transformation from differentiated thyroid carcinoma.

Anaplastic thyroid carcinoma (ATC) is the most advanced and aggressive thyroid cancer, and poorly differentiated thyroid carcinoma (PDTC) lacks anaplastic histology but has lost architectural and cytologic differentiation. Only a few studies have focused on the genetic relationship between the two advanced carcinomas and coexisting differentiated thyroid carcinomas (DTCs). In the present study, we investigated clinicopathologic features and genetic profiles in 57 ATC and PDTC samples, among which 33 cases had concomitant DTC components or DTC history. We performed immunohistochemistry for BRAF V600E, p53, and PD-L1 expression, Sanger sequencing for TERT promoter and RAS mutations, and fluorescence in situ hybridization for ALK and RET rearrangements. We found that ATCs and PDTCs shared similar gene alterations to their coexisting DTCs, and most DTCs were aggressive subtypes harboring frequent TERT promoter mutations. A significantly higher proportion of ATCs expressed p53 and PD-L1, and a lower proportion expressed PAX-8 and TTF-1, than the coexisting DTCs. Our findings provide more reliable evidence that ATCs and PDTCs are derived from DTCs.

Standard Radio-Iodine Labeling Protocols Impaired the Functional Integrity of Mesenchymal Stem/Stromal Cell Exosomes.

Mesenchymal stem/stromal cells (MSCs) are an extensively studied cell type in clinical trials due to their easy availability, substantial ex vivo proliferative capacity, and therapeutic efficacy in numerous pre-clinical animal models of disease. The prevailing understanding suggests that their therapeutic impact is mediated by the secretion of exosomes. Notably, MSC exosomes present several advantages over MSCs as therapeutic agents, due to their non-living nature and smaller size. However, despite their promising therapeutic potential, the clinical translation of MSC exosomes is hindered by an incomplete understanding of their biodistribution after administration. A primary obstacle to this lies in the lack of robust labels that are highly sensitive, capable of directly and easily tagging exosomes with minimal non-specific labeling artifacts, and sensitive traceability with minimal background noise. One potential candidate to address this issue is radioactive iodine. Protocols for iodinating exosomes and tracking radioactive iodine in live imaging are well-established, and their application in determining the biodistribution of exosomes has been reported. Nevertheless, the effects of iodination on the structural or functional activities of exosomes have never been thoroughly examined. In this study, we investigate these effects and report that these iodination methods abrogate CD73 enzymatic activity on MSC exosomes. Consequently, the biodistribution of iodinated exosomes may reflect the biodistribution of denatured exosomes rather than functionally intact ones.

Association between Consumption of Iodine-Rich Foods and Thyroid Cancer Prevalence: Findings from a Large Population-Based Study.

The influence of iodine-rich foods on thyroid cancer (TC) risk remains inadequately understood. Therefore, we aimed to comprehensively investigate the relationship between three iodine-rich food groups and TC prevalence using extensive data from a large Korean population. We assessed the dietary intake of 169,057 participants in the Korean Genome and Epidemiology Study (2004-2013) using a food frequency questionnaire. The top-three iodine-rich food groups (including egg, seaweed, and dairy) were selected based on Korean dietary reference intakes and categorized by weekly consumption frequency. We conducted multiple logistic regression models to examine the relationship between food consumption and TC prevalence. After adjusting for confounding factors, higher seaweed consumption (>5 times/week) was significantly associated with lower TC prevalence (odds ratio [OR], 95% confidence interval [CI] = 0.42, 0.32-0.56, p-value < 0.001). In contrast, compared with moderate dairy consumption (3-4 times/week), lower dairy product intake (<1 time/week) was associated with higher TC prevalence (OR, 95% CI = 1.32, 1.05-1.67, p-value = 0.017). Our findings suggest that sufficient seaweed consumption may offer protection against TC, and incorporating dairy products into the diet may lower TC incidence in the Korean population. The most significant limitations of our study are the absence of 24 h urine samples for iodine status assessment and the lack of clinical data on the diagnosis of thyroid cancer.

Unraveling the Significance of DGCR8 and miRNAs in Thyroid Carcinoma.

MicroRNAs (miRNAs) act as negative regulators for protein-coding gene expression impacting cell proliferation, differentiation, and survival. These miRNAs are frequently dysregulated in cancer and constitute classes of blood-based biomarkers useful for cancer detection and prognosis definition. In thyroid cancer (TC), the miRNA biogenesis pathway plays a pivotal role in thyroid gland formation, ensuring proper follicle development and hormone production. Several alterations in the miRNA biogenesis genes are reported as a causality for miRNA dysregulation. Mutations in microprocessor component genes are linked to an increased risk of developing TC; in particular, a recurrent mutation affecting DGCR8, the E518K. In this review, we explore these novel findings and resume the current state-of-the-art in miRNAs in thyroid carcinomas.

Genetic alterations and allele frequency of BRAF V600E and TERT mutation in papillary thyroid carcinoma with intermediate-to-high recurrence risk: a retrospective study.

The predictive value of allele frequency (AF) of BRAF V600E and TERT mutations in papillary thyroid carcinoma (PTC) remains controversial. We aimed to investigate the AF of BRAF V600E and TERT mutations in intermediate-to-high risk PTC and their association between tumor invasiveness, prognosis, and other mutations. Probe hybridization capture and high-throughput sequencing were used to quantitatively test 40 gene loci in 94 intermediate-to-high recurrence risk PTC patients, combined with clinical characteristics and follow-up for retrospective analysis. BRAF V600E mutation AF was linked to a increased risk of thyroid capsule penetration, recurrence, and concurrent mutations. Concurrent mutations could lead to a worse prognosis and increased invasiveness. TERT promoter mutation frequently accompanied other mutations and resulted in a poorer prognosis. However, there was no clear association between the TERT mutation AF and tumor invasiveness or recurrence. The sensitivity and specificity of predicting recurrence in intermediate-to-high risk PTC with BRAF V600E mutation AF > 28.2% were 60 and 80%. Although genetic alterations in PTC can differ among different ethnicities, the AF of BRAF V600E and TERT mutations may be similar. The AF of BRAF V600E has the potential to be a novel indicator in predicting PTC invasiveness and prognosis.

THYROID CANCER AS A PUBLIC HEALTH CHALLENGE IN GEORGIA.

Thyroid cancer (TC) is the most common endocrine cancer. The increase in thyroid cancer incidence has been observed in both developed and developing countries in different Geographical and climate areas The share of thyroid cancer drastically increased during the last decades in Georgia and ranked as the second most prevalent cause of cancer among women. Although for addressing the burden of cancer, important steps were taken by the State during the last decades, the burden of this disease is still significant. The presented paper aims to provide an overview of the current burden of thyroid cancer in Georgia, delving into its risk factors. To explore the opinion of key stakeholders about the factors causing the increased trend of thyroid cancer in Georgia in-depth interviews were used. The study was conducted from March to August 2023 in the capital of Georgia - Tbilisi. Women and men who had thyroid cancer and survived, women and men who are suffering from thyroid cancer along with healthcare providers, policymakers, and national professional bodies were the respondents in this study. The guides for the in-depth interviews were prepared based on the literature review. Stakeholders agreed that the number of thyroid cancer cases has increased during the last decades. The concern that the prevalence and incidence of thyroid cancer is the highest in the world in Georgia and it is the second leading cause of cancer among women was also expressed by respondents. According to study findings, new diagnostic methods revealed more cases of thyroid cancer. Other respondents stated that the development of the cancer registry, and the improvement of the reporting system existing cases of this disease. The issue of over-diagnosis was also mentioned by the stakeholders, Almost all study participant patients are challenged by the post-operational period. Some of them had not gotten information on how to deal with this period. Several patients mentioned financial problems due to fee-for-service or co-payments. According to the study participants, the recent sharp increase in the incidence and prevalence of thyroid cancer cases might be associated with overdiagnosis and the lack of monitoring and unified diagnostic and treatment methods.

Integrated proteogenomic and metabolomic characterization of papillary thyroid cancer with different recurrence risks.

Although papillary thyroid cancer (PTC) has a good prognosis, its recurrence rate is high and remains a core concern in the clinic. Molecular factors contributing to different recurrence risks (RRs) remain poorly defined. Here, we perform an integrative proteogenomic and metabolomic characterization of 102 Chinese PTC patients with different RRs. Genomic profiling reveals that mutations in MUC16 and TERT promoter as well as multiple gene fusions like NCOA4-RET are enriched by the high RR. Integrative multi-omics analyses further describe the multi-dimensional characteristics of PTC, especially in metabolism pathways, and delineate dominated molecular patterns of different RRs. Moreover, the PTC patients are clustered into four subtypes (CS1: low RR and BRAF-like; CS2: high RR and metabolism type, worst prognosis; CS3: high RR and immune type, better prognosis; CS4: high RR and BRAF-like) based on the omics data. Notably, the subtypes display significant differences considering BRAF and TERT promoter mutations, metabolism and immune pathway profiles, epithelial cell compositions, and various clinical factors (especially RRs and prognosis) as well as druggable targets. This study can provide insights into the complex molecular characteristics of PTC recurrences and help promote early diagnosis and precision treatment of recurrent PTC.

Cervical lymph node metastasis prediction from papillary thyroid carcinoma US videos: a prospective multicenter study.

BACKGROUND: Prediction of lymph node metastasis (LNM) is critical for individualized management of papillary thyroid carcinoma (PTC) patients to avoid unnecessary overtreatment as well as undesired under-treatment. Artificial intelligence (AI) trained by thyroid ultrasound (US) may improve prediction performance. METHODS: From September 2017 to December 2018, patients with suspicious PTC from the first medical center of the Chinese PLA general hospital were retrospectively enrolled to pre-train the multi-scale, multi-frame, and dual-direction deep learning (MMD-DL) model. From January 2019 to July 2021, PTC patients from four different centers were prospectively enrolled to fine-tune and independently validate MMD-DL. Its diagnostic performance and auxiliary effect on radiologists were analyzed in terms of receiver operating characteristic (ROC) curves, areas under the ROC curve (AUC), accuracy, sensitivity, and specificity. RESULTS: In total, 488 PTC patients were enrolled in the pre-training cohort, and 218 PTC patients were included for model fine-tuning (n = 109), internal test (n = 39), and external validation (n = 70). Diagnostic performances of MMD-DL achieved AUCs of 0.85 (95% CI: 0.73, 0.97) and 0.81 (95% CI: 0.73, 0.89) in the test and validation cohorts, respectively, and US radiologists significantly improved their average diagnostic accuracy (57% vs. 60%, P = 0.001) and sensitivity (62% vs. 65%, P < 0.001) by using the AI model for assistance. CONCLUSIONS: The AI model using US videos can provide accurate and reproducible prediction of cervical lymph node metastasis in papillary thyroid carcinoma patients preoperatively, and it can be used as an effective assisting tool to improve diagnostic performance of US radiologists. TRIAL REGISTRATION: We registered on the Chinese Clinical Trial Registry website with the number ChiCTR1900025592.

A Pyroglutamate Aminopeptidase 1 Responsive Fluorescence Imaging Probe for Real-Time Rapid Differentiation between Thyroiditis and Thyroid Cancer.

Current diagnostic methods for thyroid diseases, including blood tests, ultrasound, and biopsy, always have difficulty diagnosing thyroiditis accurately, occasionally mistaking it for thyroid cancer. To address this clinical challenge, we developed Ox-PGP1, a novel fluorescent probe realizing rapid, noninvasive, and real-time diagnostic techniques. This is the first imaging tool capable of noninvasively distinguishing between thyroiditis and thyroid cancer. Ox-PGP1 was introduced as a fluorescent probe custom-built for the specific detection and quantification of pyroglutamate aminopeptidase 1 (PGP-1), a known pivotal biomarker of inflammation. Ox-PGP1 overcame the disadvantages of traditional enzyme-responsive fluorescent probes that relied on the intramolecular charge transfer (ICT) mechanism, including the issue of high background fluorescence, while offering exceptional photostability under laser irradiation. The spectral properties of Ox-PGP1 were meticulously optimized to enhance its biocompatibility. Furthermore, the low limit of detection (LOD) of Ox-PGP1 was determined to be 0.09 µg/mL, which demonstrated its remarkable sensitivity and precision. Both cellular and in vivo experiments validated the capacity of Ox-PGP1 for accurate differentiation between normal, inflammatory, and cancerous thyroid cells. Furthermore, Ox-PGP1 showed the potential to rapidly and sensitively differentiate between autoimmune thyroiditis and anaplastic thyroid carcinoma in a mouse model, achieving results in just 5 min. The successful design and application of Ox-PGP1 represent a substantial advancement in technology over traditional diagnostic approaches, potentially enabling earlier interventions for thyroid diseases.

Stimulated Raman Scattering Microscopy Reveals Aberrant Triglyceride Accumulation in Lymphatic Metastasis of Papillary Thyroid Carcinoma.

Lipid metabolic alterations are known to play a crucial role in cancer metastasis. As a key hub in lipid metabolism, intracellular neutral lipid accumulation in lipid droplets (LDs) has become a signature of aggressive human cancers. Nevertheless, it remains unclear whether lipid accumulation displays distinctive features in metastatic lesions compared to the primary ones. Here, we integrated multicolor stimulated Raman scattering (SRS) imaging with confocal Raman spectroscopy on the same platform to quantitatively analyze the amount and composition of LDs in intact human thyroid tissues in situ without any processing or labeling. Inspiringly, we found aberrant accumulation of triglycerides (TGs) in lymphatic metastases but not in normal thyroid, primary papillary thyroid carcinoma (PTC), or normal lymph node. In addition, the unsaturation degree of unsaturated TGs was significantly higher in the lymphatic metastases from patients diagnosed with late-stage (T3/T4) PTC compared to those of patients diagnosed with early-stage (T1/T2) PTC. Furthermore, both public sequencing data analysis and our RNA-seq transcriptomic experiment showed significantly higher expression of alcohol dehydrogenase-1B (ADH1B), which is critical to lipid uptake and transport, in lymphatic metastases relative to the primary ones. In summary, these findings unravel the lipid accumulation as a novel marker and therapeutic target for PTC lymphatic metastasis that has a poor response to the regular radioactive iodine therapy.

Diagnostic value of contrast-enhanced ultrasound in the diagnosis of papillary thyroid microcarcinoma: A systematic review and meta-analysis.

BACKGROUND: Using meta-analysis to evaluate the diagnostic value of contrast-enhanced ultrasound (CEUS) in the diagnosis of papillary thyroid microcarcinoma (PTMC). METHODS: For this systematic review and meta-analysis, we searched PubMed, Cochrane Library, Web of Science, WanFang Data, VPCS Data, and China National Knowledge Infrastructure electronic databases for diagnostic studies on PTMC by CEUS from January 2013 to November 2022. Data were not available or incomplete such as case reports, nonhuman studies, etc, were excluded. Random-effects meta-analyses were used to evaluate the diagnostic accuracy of CEUS in diagnosing PTMC. The quality of the evidence was assessed with the QUADAS-2 scale. This study is registered on PROSPERO, number CRD42023409417. RESULTS: Of 1064 records identified, 33 were eligible. The results showed that the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio of CEUS in diagnosing PTMC were 0.84 (95% confidence interval [CI] = 0.83-0.86), 0.82 (95% CI = 0.80-0.83), 3.90 (95% CI = 3.23-4.72), 0.21 (95% CI = 0.18-0.25), and 20.01 (95% CI = 14.97-26.74), respectively, and the area under the summary receiver operating characteristic curve was 0.8930 (the Q index was 0.8239). The Deek funnel plot indicated publication bias (P ˂.01). CONCLUSION: This meta-analysis provides an overview of diagnostic accuracy of CEUS in diagnosing PTMC which indicates CEUS has a good diagnostic value for PTMC. The limitations of this study are publication bias and strong geographical bias.

A Novel TSHR Gene Mutation in a Family with Non-autoimmune Hyperthyroidism.

Background: Familial non-autoimmune hyperthyroidism is a rare disorder characterized by the absence of thyroid autoimmunity, particularly TSH receptor antibody [TRAb]. Objective: The aim of this study was to describe a novel TSHR mutation identified in a family of two siblings and their father. Methods: Two siblings presented for endocrine assessment at ages 7 and 14 years with mild T3 toxicosis, and the father presented at 30 years of age with non-autoimmune thyrotoxicosis. Both siblings were treated with oral antithyroid therapy to achieve reasonable symptom control and thyroid function normalization. The father was treated with oral antithyroid therapy, radioactive iodine, thyroidectomy, and thyroid replacement therapy. Peripheral blood DNA was extracted from both affected siblings and father. Mutation analysis of TSHR was carried out by PCR and Sanger sequencing of both strands of the extracted DNA. Results: Both siblings and their father were heterozygous for the missense TSHR variant c.1855G>C, p.[Asp619His], in exon 10. Conclusions: This novel TSHR variant is associated with T3 toxicosis during childhood. Therefore, early identification and treatment may improve patient outcomes.

Comparison of ultrasound risk stratification systems for pediatric thyroid nodules.

Background: There is currently insufficient data to validate adult-based US risk stratification systems (RSSs) for the identification of malignant thyroid nodules in a pediatric population. Methods: From October 2016 and May 2023, 173 thyroid nodules of pediatric patients (age ≤ 18 years) with definitive pathology results and ultrasound (US) examination within 1 month before surgery or fine-needle aspiration (FNA) biopsy in our institution were enrolled in this study. The clinical and US characteristics of these nodules were retrospectively reviewed and categorized according to the ACR-TIRADS, C-TIRADS, and ATA guidelines. The diagnostic performance of US-based FNA criteria (original and simulating) of the three guidelines in thyroid cancer detection was estimated. Results: The three RSSs had similar AUC according to the categories(0.849-0.852, all P > 0.05). When combined with the original FNA criteria of the three RSSs to manage the nodules, the FNA rate of ACR-TIRADS and C-TIRADS were significantly less than ATA guidelines (53.18% vs. 64.63%, P < 0.05, and 52.60% vs. 64.63%, P < 0.05). The missed malignancy rate (MMR) and unnecessary FNA rate (UFR) of ATA guidelines (50.00%, 35.85%) was highest among the three RSSs, followed by the C-TIRADS (37.80%, 19.57%) and the ACR-TIRADS (37.04%, 19.57%). When nodules < 1 cm with the highest category in each RSS biopsied, that is when using the simulating FNA thresholds, the MMR was reduced overall (all P < 0.001), without a change in the UFR (all P > 0.05). All the three RSSs showed a substantial improvement in accuracy and malignant detection rate (all P < 0.05). Conclusion: The ACR-TIRADS, C-TIRADS, and ATA guidelines showed high missed malignancy rates when using their original recommended FNA criteria. When nodules < 1 cm with the highest category in each RSS biopsied, the missed malignancy rate of each RSS was decreased. Decreasing the FNA thresholds for highly suspicious malignant nodules may therefore be an effective means of managing malignant thyroid nodules in pediatric patients.

Development and validation of a nomogram model for predicting distant metastasis of aged ≥50 patients with thyroid carcinoma: a SEER database analysis.

OBJECTIVE: This work aimed to construct and validate a model for predicting distant metastasis (DM) in thyroid carcinoma (TC) patients aged≥50. PATIENTS AND METHODS: The research data were collected from the Surveillance, Epidemiology, and End Results (SEER) program databases via SEER*Stat software (https://seer.cancer.gov/). Logistics regression was used to screen the independent risk factors for TC patients. The nomogram was constructed and validated based on the logistics regression results for predicting DM occurrence in TC patients. Moreover, the characteristic curves (ROC) were used to assess the predictive performance. The decision analysis curve (DCA) and the calibration curve were used to test this nomogram's accuracy and discrimination. Additionally, we analyzed survival and risk scores in TC patients with metastasis using the Kaplan-Meier (KM) method. RESULTS: A total of 11,166 TC patients were divided into a training set and a validation set. The results showed that topography (T), lymph node metastasis (N), and (grade) G were crucial risk factors for predicting DM. ROC analysis showed that the model had a good discriminative ability both in the training and validation set. The DCA curve showed greater net benefits across a range of DM risks for the nomogram in the training and validation set. Survival analyses showed that the metastasis cases with low-risk scores have shown a poorer prognosis in this study, both in the training and validation set. CONCLUSIONS: The nomogram model had excellent predictive performance and net benefit for predicting DM of TC patients aged ≥50. The model can help doctors develop treatment plans for their patients.

Microwave Ablation versus Surgical Resection for US-detected Multifocal T1N0M0 Papillary Thyroid Carcinoma: A 10-Center Study.

Background Microwave ablation (MWA) is currently under preliminary investigation for the treatment of multifocal papillary thyroid carcinoma (PTC) and has shown promising treatment efficacy. Compared with surgical resection (SR), MWA is minimally invasive and could preserve thyroid function. However, a comparative analysis between MWA and SR is warranted to draw definitive conclusions. Purpose To compare MWA and SR for preoperative US-detected T1N0M0 multifocal PTC in terms of overall and 1-, 3-, and 5-year progression-free survival rates and complication rates. Materials and Methods In this retrospective study, 775 patients with preoperative US-detected T1N0M0 multifocal PTC treated with MWA or SR across 10 centers between May 2015 and December 2021 were included. Propensity score matching (PSM) was performed for patients in the MWA and SR groups, followed by comparisons between the two groups. The primary outcomes were overall and 1-, 3-, and 5-year progression-free survival (PFS) rates and complication rates. Results After PSM, 229 patients (median age, 44 years [IQR 36.5-50.5 years]; 179 female) in the MWA group and 453 patients (median age, 45 years [IQR 37-53 years]; 367 female) in the SR group were observed for a median of 20 months (range, 12-74 months) and 26 months (range, 12-64 months), respectively. MWA resulted in less blood loss, shorter incision length, and shorter procedure and hospitalization durations (all P < .001). There was no evidence of differences in overall and 1-, 3-, or 5-year PFS rates (all P > .05) between MWA and SR (5-year rate, 77.2% vs 83.1%; P = .36) groups. Permanent hoarseness (2.2%, P = .05) and hypoparathyroidism (4.0%, P = .005) were encountered only in the SR group. Conclusion There was no evidence of a significant difference in PFS rates between MWA and SR for US-detected multifocal T1N0M0 PTC, and MWA resulted in fewer complications. Therefore, MWA is a feasible option for selected patients with multifocal T1N0M0 PTC. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Georgiades in this issue.

Negative regulation of thyroid adenoma-associated protein (THADA) in the cardiac glycoside-induced anti-cancer effect.

Cardiac glycosides, known as inhibitors of Na+,K+-ATPase, have anti-cancer effects such as suppression of cancer cell proliferation and induction of cancer cell death. Here, we examined the signaling pathway elicited by cardiac glycosides in the human hepatocellular carcinoma HepG2 cells and human epidermoid carcinoma KB cells. Three kinds of cardiac glycosides (ouabain, oleandrin, and digoxin) inhibited the cancer cell proliferation and decreased the expression level of thyroid adenoma-associated protein (THADA). Interestingly, the knockdown of THADA inhibited cancer cell proliferation, and the proliferation was significantly rescued by re-expression of THADA in the THADA-knockdown cells. In addition, the THADA-knockdown markedly decreased the expression level of L-type amino acid transporter LAT1. Cardiac glycosides also reduced the LAT1 expression. The LAT1 inhibitor, JPH203, significantly weakened the cancer cell proliferation. These results suggest that the binding of cardiac glycosides to Na+,K+-ATPase negatively regulates the THADA-LAT1 pathway, exerting the anti-proliferative effect in cancer cells.

Blood leukocytes as a non-invasive diagnostic tool for thyroid nodules: a prospective cohort study.

BACKGROUND: Thyroid nodule (TN) patients in China are subject to overdiagnosis and overtreatment. The implementation of existing technologies such as thyroid ultrasonography has indeed contributed to the improved diagnostic accuracy of TNs. However, a significant issue persists, where many patients undergo unnecessary biopsies, and patients with malignant thyroid nodules (MTNs) are advised to undergo surgery therapy. METHODS: This study included a total of 293 patients diagnosed with TNs. Differential methylation haplotype blocks (MHBs) in blood leukocytes between MTNs and benign thyroid nodules (BTNs) were detected using reduced representation bisulfite sequencing (RRBS). Subsequently, an artificial intelligence blood leukocyte DNA methylation (BLDM) model was designed to optimize the management and treatment of patients with TNs for more effective outcomes. RESULTS: The DNA methylation profiles of peripheral blood leukocytes exhibited distinctions between MTNs and BTNs. The BLDM model we developed for diagnosing TNs achieved an area under the curve (AUC) of 0.858 in the validation cohort and 0.863 in the independent test cohort. Its specificity reached 90.91% and 88.68% in the validation and independent test cohorts, respectively, outperforming the specificity of ultrasonography (43.64% in the validation cohort and 47.17% in the independent test cohort), albeit with a slightly lower sensitivity (83.33% in the validation cohort and 82.86% in the independent test cohort) compared to ultrasonography (97.62% in the validation cohort and 100.00% in the independent test cohort). The BLDM model could correctly identify 89.83% patients whose nodules were suspected malignant by ultrasonography but finally histological benign. In micronodules, the model displayed higher specificity (93.33% in the validation cohort and 92.00% in the independent test cohort) and accuracy (88.24% in the validation cohort and 87.50% in the independent test cohort) for diagnosing TNs. This performance surpassed the specificity and accuracy observed with ultrasonography. A TN diagnostic and treatment framework that prioritizes patients is provided, with fine-needle aspiration (FNA) biopsy performed only on patients with indications of MTNs in both BLDM and ultrasonography results, thus avoiding unnecessary biopsies. CONCLUSIONS: This is the first study to demonstrate the potential of non-invasive blood leukocytes in diagnosing TNs, thereby making TN diagnosis and treatment more efficient in China.

Correlation of 18F-sodium fluoride uptake and radiodensity in extraosseous metastases of medullary thyroid carcinoma.

Objective: Although 18F-sodium fluoride (18F-NaF) uptake is frequently observed in extraosseous metastases of medullary thyroid carcinoma (MTC) with calcification, itcan also occur in metastatic sites without visible calcium deposition, leading to the hypothesis that visually undetectable calcium accumulation may be responsible for this uptake. The aim of this study was to indirectly support this hypothesis by analyzing the correlation between the degree of 18F-NaF uptake and radiodensity in extraosseous MTC metastases, since calcium deposition can increase attenuation even when not visually detectable. Subjects and methods: Extraosseous metastatic lesions of 15 patients with MTC were evaluated using 18F-NaF positron-emission tomography (PET)/computed tomography (CT)and segmented by levels of standardized uptake value (SUV). The correlation between mean SUV and mean Hounsfield unit (HU) values was assessed for the entire group of segments and for two subgroups with different mean HU values. Results: Very high correlations were observed between mean SUV and mean HU values for both the entire group of segments and the subgroup with a mean HU value greater than 130 (p = 0.92 and p = 0.95, respectively; p < 0.01). High correlation (p = 0.71) was also observed in the subgroup with mean HU values ranging from 20 to 130 (p < 0.01). Conclusion: The findings of the present study suggest that there is an association between 18F-NaF uptake and calcium deposition in extraosseous metastasesof MTC, supporting the hypothesis that visually undetectable calcium accumulation may be responsible for 18F-NaF uptake in regions without visible calcium deposition.