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.

Functional analysis of ESM1 by shRNA-mediated knockdown of its expression in papillary thyroid cancer cells.

OBJECTIVE: Endothelial specific molecule-1 (ESM1) is implicated as an oncogene in multiple human cancers. However, the function of ESM1 in papillary thyroid cancer (PTC) is not well understood. The current study aimed to investigate the effect of ESM1 on the growth, migration, and invasion of PTC to provide a novel perspective for PTC treatment. METHODS: The expression levels of ESM1 in PTC tissues form 53 tumor tissue samples and 59 matching adjacent normal tissue samples were detected by immunohistochemical analysis. Knockdown of ESM1 expression in TPC-1 and SW579 cell lines was established to investigate its role in PTC. Moreover, cell proliferation, apoptosis, wound healing, and transwell assays were conducted in vitro to assess cell proliferation, migration and invasion. RESULTS: The findings revealed that ESM1 expression was significantly higher in PTC tissues than that found in paraneoplastic tissues (P<0.0001). Knockdown of ESM1 expression inhibited the proliferation, migration, and invasion of TPC-1 and SW579 cells in vitro. Compared with the control group, the mRNA and protein levels of ESM1 in PTC cells were significantly reduced following knockdown of its expression (P<0.01). In addition, ESM1-knockdown cells indicated decreased proliferation and decreased migratory and invasive activities (P<0.01, P<0.01, P<0.001, respectively). CONCLUSIONS: ESM1 was identified as a major gene in the occurrence and progression of PTC, which could increase the proliferation, migration, and invasion of PTC cells. It may be a promising diagnostic and therapeutic target gene.

[Expert consensus on thermal ablation of papillary thyroid cancer (2024 edition)].

Ultrasound-guided thermal ablation of papillary thyroid cancer (PTC) has been promoted in clinical practice over the past few years. Thermal ablation has the advantages of being minimally invasive, effective, and safe. However, current guidelines and consensus only focus on low-risk papillary thyroid microcarcinoma. With growing clinical application and accumulating scientific research in thermal ablation for PTC, there is considerable evidence to demonstrate that thermal ablation can treat larger PTC tumors and benefit more patients with PTC. To expand the indications and standardize the technical details and perioperative patient management for PTC ablation, experts from the Society of Tumor Ablation Therapy of the Chinese Anti-Cancer Association, the Ablation Expert Committee of the Chinese Society of Clinical Oncology (CSCO), Chinese Medical Doctor Association College of Interventionalists Tumor Ablation Committee, and Chinese Bethune Spirit Research Association Endocrinology and Diabetes Branch Interventional Endocrine Committee discussed and developed a consensus on thermal ablation of PTC based on the latest research results. This consensus aims to promote the rapid development of thermal ablation for PTC in the clinic.

Clinical features combined with ultrasound characteristics to predict TERT promoter mutations in papillary thyroid carcinoma: a single-center study over the past 5 years.

Purpose: Telomerase reverse transcriptase (TERT) has been reported in papillary thyroid carcinoma (PTC). This study aimed to investigate the correlation of TERT promoter mutations with clinical and ultrasound (US) features in PTC and to develop a model to predict TERT promoter mutations. Methods: Preoperative US images, postoperative pathological features, and TERT promoter mutation information were evaluated in 365 PTC patients confirmed by surgery. Univariate and multivariate factor analyses were performed to identify risk factors for TERT promoter mutations. A predictive model was established to assess the clinical predictive value. Results: Of the 365 patients with PTC (498 nodules), the number of those with TERT promoter mutations was 67 cases (75 nodules), and the number of those without mutations was 298 cases (423 nodules). The median age was 40 years in the wild-type group and 60 years in the mutant group. Male patients made up 35.82% of the mutant group and 22.82% of the wild-type group. Multivariate analysis revealed that the independent risk factors associated with the occurrence of TERT promoter mutation in PTC were as follows: older age (odds ratio (OR) = 1.07; p = 0.002), maximum diameter of ≥ 10 mm (OR = 3.94; p < 0.0001), unilateral (OR = 4.15; p < 0.0001), multifocal (OR = 7.69; p < 0.0001), adjacent to the thyroid capsule (OR = 1.94; p = 0.044), and accompanied by other benign nodules (OR = 1.94, p = 0.039). A predictive model was established, and the area under the curve (AUC) of the receiver operating characteristic was 0.839. TERT promoter mutations were associated with high-risk US and clinical features compared with the wild-type group. Conclusion: TERT promoter mutations were associated with older ages. They were also found to be multifocal, with a maximum diameter of ≥ 10 mm, unilateral, adjacent to the thyroid capsule, and accompanied by other benign nodules. The predictive model was of high diagnostic value.

Predicting central cervical lymph node metastasis in papillary thyroid microcarcinoma using deep learning.

Background: The aim of this study is to design a deep learning (DL) model to preoperatively predict the occurrence of central lymph node metastasis (CLNM) in patients with papillary thyroid microcarcinoma (PTMC). Methods: This research collected preoperative ultrasound (US) images and clinical factors of 611 PTMC patients. The clinical factors were analyzed using multivariate regression. Then, a DL model based on US images and clinical factors was developed to preoperatively predict CLNM. The model's efficacy was evaluated using the receiver operating characteristic (ROC) curve, along with accuracy, sensitivity, specificity, and the F1 score. Results: The multivariate analysis indicated an independent correlation factors including age ≥55 (OR = 0.309, p < 0.001), tumor diameter (OR = 2.551, p = 0.010), macrocalcifications (OR = 1.832, p = 0.002), and capsular invasion (OR = 1.977, p = 0.005). The suggested DL model utilized US images achieved an average area under the curve (AUC) of 0.65, slightly outperforming the model that employed traditional clinical factors (AUC = 0.64). Nevertheless, the model that incorporated both of them did not enhance prediction accuracy (AUC = 0.63). Conclusions: The suggested approach offers a reference for the treatment and supervision of PTMC. Among three models used in this study, the deep model relied generally more on image modalities than the data modality of clinic records when making the predictions.

Dihydrotanshinone I exhibits antitumor effects via ß-catenin downregulation in papillary thyroid cancer cell lines.

Thyroid cancer is the most common endocrine carcinoma and, among its different subtypes, the papillary subtype (PTC) is the most frequent. Generally, PTCs are well differentiated, but a minor percentage of PTCs are characterized by a worse prognosis and more aggressive behavior. Phytochemicals, naturally found in plant products, represent a heterogeneous group of bioactive compounds that can interfere with cell proliferation and the regulation of the cell cycle, taking part in multiple signaling pathways that are often disrupted in tumor initiation, proliferation, and progression. In this work, we focused on 15,16-dihydrotanshinone I (DHT), a tanshinone isolated from Salvia miltiorrhiza Bunge (Danshen). We first evaluated DHT biological effect on PTC cells regarding cell viability, colony formation ability, and migration capacity. All of these parameters were downregulated by DHT treatment. We then investigated gene expression changes after DHT treatment by performing RNA-seq. The analysis revealed that DHT significantly reduced the Wnt signaling pathway, which plays a role in various diseases, including cancer. Finally, we demonstrate that DHT treatment decreases protein levels of ß-catenin, a final effector of canonical Wnt signaling pathway. Overall, our data suggest a possible use of this nutraceutical as an adjuvant in the treatment of aggressive papillary thyroid carcinoma.

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.

Trends of the prevalence rate of central lymph node metastasis and multifocality in patients with low-risk papillary thyroid carcinoma after delayed thyroid surgery.

Background: Active surveillance has been an option for patients with low-risk papillary thyroid carcinoma (PTC). However, whether delayed surgery leads to an increased risk of local tumor metastasis remain unclear. We sought to investigate the impact of observation time on central lymph node metastasis (CLNM) and multifocal disease in patients with low-risk PTC. Methods: Patients who were diagnosed with asymptomatic low-risk PTC, and with a pathological maximum tumor size ≤1.5 cm by were included. The patients were classified into observation group and immediate surgery group, and subgroup analyses were conducted by observation time period. The prevalence of CLNM, lymph node (LN) involved >5, multifocal PTC and bilateral multifocal PTC were considered as outcome variables. The changing trend and risk ratio of prevalence over observation time were evaluated by Mann-Kendall trend test and Logistics regression. Results: Overall, 3,427 and 1,860 patients were classified to the observation group and immediate surgery group, respectively. Trend tests showed that decreasing trends both on the prevalence of CLNM and LN involved >5 over the observation time, but the difference was not statistically significant, and the prevalence of multifocal PTC and bilateral multifocal PTC showed the significant decreasing trends. After adjustment, multivariate analysis showed no statistically significant difference between observed and immediate surgery groups in the four outcome variables. Conclusion: In patients with subclinical asymptomatic low-risk PTC, observation did not result in an increased incidence of local metastatic disease, nor did the increased surgery extent in patients with delayed surgery compared to immediate surgery. These findings can strengthen the confidence in the active surveillance management for both doctors and patients.

Diagnostic value of high-frequency ultrasound combined with fine needle aspiration cytology and BRAF gene for papillary thyroid microcarcinoma.

We attempted to evaluate clinical application value of high-frequency ultrasound (HFUS), fine needle aspiration cytology (FNAC), BRAF gene, and combination of HFUS, FNAC, and BRAF gene in diagnosing papillary thyroid microcarcinoma (PTMC). The 150 patients with thyroid minimal lesions who underwent HFUS, FNAC and BRAF gene testing before surgery in our hospital from June 2020 to December 2021 were selected as research subjects. Patients were divided into two groups based on postoperative pathological results. The consistency of diagnostic results of HFUS, FNAC, and BRAF gene and their combination with those of pathological examination, diagnostic efficacy of HFUS, FNAC and BRAF gene combined detection and individual detection for PTMC lymph node metastasis, and diagnostic value of HFUS, FNAC and BRAF gene combined detection and individual detection for PTMC lymph node metastasis received analysis and comparison. The consistency of diagnostic results of combined detection with pathological examination exhibited elevation relative to that of HFUS, FNAC and BRAF gene detection alone (P < 0.05). The negative predictive value, sensitivity and accuracy of combined detection exhibited elevation relative to individual detection (P < 0.05). The AUC of combined detection in diagnosing PTMC lymph node metastasis exhibited elevation relative to that of HFUS and BRAF gene alone (P < 0.05). HFUS combined with FNAC and BRAF genes possesses high diagnostic value, with high diagnostic sensitivity, specificity, and accuracy. Thus, combined detection for PTMC before surgery can accurately determine whether lymph node metastasis occurs, reduce occurrence of missed diagnosis and misdiagnosis, and thus improve diagnostic precision.

Intraluminal extension of papillary thyroid carcinoma into the Internal Jugular Vein; a case report.

BACKGROUND: Papillary thyroid carcinoma (PTC), being the most common thyroid malignancy, is a slow-growing tumor and is usually limited to the thyroid. Extra thyroid extension is uncommon; besides, invasion to the vasculature seems to be extremely rare and usually indicates aggressive nature of the disease. CASE PRESENTATION: We present a case of a 40-year-old lady who referred with a palpable neck mass a month after total thyroidectomy which its histopathologic examination revealed follicular variant of PTC; the same variant as prior thyroidectomy. Preoperative ultrasonography failed to comment on the intravascular component of the mass. Surgical procedure confirmed a mass attaching and infiltrating to the internal jugular vein, which turned out to be persistent disease. CONCLUSIONS: Awareness of this entity is important for surgeons, oncologists and radiologist as it can influence patient management.

Impact of age on central lymph nodes involvement in papillary thyroid cancer.

BACKGROUND: Total thyroidectomy is the main line of treatment for papillary thyroid cancer. Central lymph node dissection (CLND) is still debatable. In this study, we aimed to correlate the central lymph node status with the age of patients. METHODS: This is a retrospective study including patients with papillary thyroid cancer (PTC) who underwent total thyroidectomy and CLND at a tertiary cancer center during the period from January 2012 to September 2022. Patients were subdivided into 3groups: patients younger than 20 years old, patients between 20 and 40 years old, and patients older than 40 years old. Correlation between central lymph node status, lateral lymph node status, and harvest count with each other and between age groups was done. RESULTS: 315 patients were included. The younger the age group the higher the possibility of harboring positive central nodes, however, the positivity of lateral nodes was similar. Neither central nodal harvest nor positive central node count significantly differed between groups. The lateral nodal harvest was significantly higher in the < 20 years group with no affection to the number of positive nodes retrieved. The younger the age group the longer the disease-free survival (DFS). CONCLUSION: We can conclude that patients younger than twenty years had a higher probability of harboring malignancy in central nodes and higher lateral node harvest on dissection. In contrast, they do have a lower incidence of recurrence.

Tumor growth manifested in two-fifths of low-risk papillary thyroid microcarcinoma patients during active surveillance: data from a tertiary center in China.

Purpose: To assess tumor growth using tumor doubling rate (TDR) during active surveillance (AS) in China. Methods: Between January 2016 and June 2020, a total of 219 patients with low-risk papillary thyroid microcarcinoma (PTMC) (aged 23-75 years) were consecutively enrolled in the AS program. Results: Four sections of TDR, >0.5, 0.1~0.5, -0.1~0.1 and <-0.1, corresponded with four categories of tumor volume kinetics: rapid growth, slow growth, stable, and decreased size. We found that 10.5% of PTMCs exhibited rapid growth, 33.33% exhibited slow growth, 26.48% were stable, and 29.68% decreased in size. Tumor growth was associated with two factors: age and volume of PTMC at diagnosis. 85.72% of elderly patients (≥ 61 years old) had tumors that remained stable or even shrank and rapidly growing tumors were not found in them. When the volume was small (≤14.13 mm3), the proportion of rapid growth was high (41.67%), whereas when the volume was large (> 179.5 mm3), the proportion of non-growth was 68.75%. Conclusion: TDR may be a better metric for evaluating tumor growth in observational PTMCs. A certain proportion of PTMCs grow during the period of AS and tumor growth was associated with age and volume of PTMC at initial diagnosis. Therefore, how to block tumor growth during the AS period, especially for young patients and patients with early-stage PTMC (size ≤ 5 mm), will be a new challenge.

Correlation between genetic alterations and clinicopathological features of papillary thyroid carcinomas.

OBJECTIVE: To investigate the correlations between multigene alterations and clinicopathological features in papillary thyroid carcinoma (PTC) samples. METHODS: In this retrospective study, 111 cytological specimens of thyroid nodules, including 74 PTC samples and 37 benign samples, were analyzed using a 22-gene mutation assay employing next-generation sequencing. Clinicopathological information was retrospectively collected and analyzed. RESULTS: Gene alterations were associated with a higher rate of lymph node metastasis (LNM) and thyroid capsular invasion, a lower rate of coexisting Hashimoto's thyroiditis, the classical PTC subtype, and younger age (<45 years). Among the 22 genes tested, the BRAF mutation rates showed a significant difference between the PTC and benign groups. In the subgroup analysis, younger age (odds ratio = 12.512, 95% confidence interval: 3.126-50.087) was an independent risk factor for LNM. In further analyses, BRAF mutation was significantly associated with LNM in the older subgroup (age ≥ 45 years), suggesting that the BRAF mutation test has greater value for determining PTC prognosis in the older age group. CONCLUSIONS: Our findings will provide a more comprehensive understanding of the relationship between gene mutations and PTC and may contribute to improved PTC management.

Two lymphoma histotypes and papillary thyroid carcinoma coexisting on Hashimoto ground: a case report and review of the literature.

BACKGROUND: Papillary carcinoma is the most frequent type of thyroid carcinoma, while primary thyroid lymphoma is uncommon disease. The coexistence of these entities has already been described, and the common risk factor is considered Hashimoto thyroiditis. The two most frequent histotypes of primary thyroid lymphoma are diffuse large B-cell and mucosa-associated lymphoid tissue lymphoma, but the coexistence of both with papillary carcinoma is rarely reported. METHODS: We present a case of a previously healthy 57-years old male with rapidly growing lump on the right side of the neck. Ultrasonography revealed nodules in both thyroid lobes. Fine needle aspiration cytology and pertechnetate scintigraphy were performed. Due to the Bethesda T-5 in the "cold" nodule of the right lobe, surgery with histopathological and immunohistochemistry analysis was indicated. RESULTS: Histopathological and immunohistochemistry methods confirmed concomitant malignancies in the thyroid gland: diffuse large B-cell lymphoma and papillary carcinoma in the right, and mucosa-associated lymphoid tissue lymphoma in the left lobe with Hashimoto thyroiditis in the remaining tissue. Patient underwent therapy procedures and was without signs of local recurrence or metastatic spread on subsequent follow-up. CONCLUSIONS: Sudden appearance of the neck mass in patients with Hashimoto thyroiditis should raise suspicion on primary thyroid lymphoma and be promptly taken in the diagnostic workup, including fine needle aspiration cytology. Pathology with immunohistochemistry is crucial for further clinical decision making. Since the standardized protocol in management of these complex patients is missing, personal approach and close collaboration between cytologist, pathologist, surgeon, haematologist and nuclear medicine specialist is essential.

Accurate preoperative prediction of nodal metastasis in papillary thyroid microcarcinoma: Towards optimal management of patients.

OBJECTIVE: To enhance the accuracy in predicting lymph node metastasis (LNM) preoperatively in patients with papillary thyroid microcarcinoma (PTMC), refining the "low-risk" classification for tailored treatment strategies. METHODS: This study involves the development and validation of a predictive model using a cohort of 1004 patients with PTMC undergoing thyroidectomy along with central neck dissection. The data was divided into a training cohort (n = 702) and a validation cohort (n = 302). Multivariate logistic regression identified independent LNM predictors in PTMC, leading to the construction of a predictive nomogram model. The model's performance was assessed through ROC analysis, calibration curve analysis, and decision curve analysis. RESULTS: Identified LNM predictors in PTMC included age, tumor maximum diameter, nodule-capsule distance, capsular contact length, bilateral suspicious lesions, absence of the lymphatic hilum, microcalcification, and sex. Especially, tumors larger than 7 mm, nodules closer to the capsule (less than 3 mm), and longer capsular contact lengths (more than 1 mm) showed higher LNM rates. The model exhibited AUCs of 0.733 and 0.771 in the training and validation cohorts respectively, alongside superior calibration and clinical utility. CONCLUSION: This study proposes and substantiates a preoperative predictive model for LNM in patients with PTMC, honing the precision of "low-risk" categorization. This model furnishes clinicians with an invaluable tool for individualized treatment approach, ensuring better management of patients who might be proposed observation or ablative options in the absence of such predictive information.

Feasibility of active surveillance in patients with clinically T1b papillary thyroid carcinoma ≤1.5 cm in preoperative ultrasonography: MASTER study.

Objective: Active surveillance (AS) is generally accepted as an alternative to immediate surgery for papillary thyroid carcinoma (PTC) measuring ≤1.0 cm (cT1a) without risk factors. This study investigated the clinicopathologic characteristics of PTCs measuring ≤2.0 cm without cervical lymph node metastasis (cT1N0) by tumor size group to assess the feasibility of AS for PTCs between 1.0 cm and 1.5 cm (cT1b≤1.5). Design: This study enrolled clinically T1N0 patients with preoperative ultrasonography information (n= 935) from a cohort of 1259 patients who underwent lobectomy and were finally diagnosed with PTC from June 2020 to March 2022. Results: The cT1b≤1.5 group (n = 171; 18.3 %) exhibited more lymphatic invasion and occult central lymph node (LN) metastasis with a higher metastatic LN ratio than the cT1a group (n = 719; 76.9 %). However, among patients aged 55 years or older, there were no significant differences in occult central LN metastasis and metastatic LN ratio between the cT1a, cT1b≤1.5, and cT1b>1.5 groups. Multivariate regression analyses revealed that occult central LN metastasis was associated with age, sex, tumor size, extrathyroidal extension, and lymphatic invasion in patients under 55, while in those aged 55 or older, it was associated only with age and lymphatic invasion. Conclusion: For PTC patients aged 55 years or older with cT1b≤1.5, AS could be a viable option due to the absence of a significant relationship between tumor size and occult central LN.

Progress in long non-coding RNAs as prognostic factors of papillary thyroid carcinoma.

Papillary thyroid carcinoma (PTC) is generally recognized as a slow-growing tumor. However, a small subset of patients may still experience relapse or metastasis shortly after therapy, leading to a poor prognosis and raising concerns about excessive medical treatment. One major challenge lies in the inadequacy of effective biomarkers for accurate risk stratification. Long non-coding RNAs (lncRNAs), which are closely related to malignant characteristics and poor prognosis, play a significant role in the genesis and development of PTC through various pathways. The objective of this review is to provide a comprehensive summary of the biological functions of lncRNAs in PTC, identify prognosis-relevant lncRNAs, and explore their potential mechanisms in drug resistance to BRAF kinase inhibitors, tumor dedifferentiation, and lymph node metastasis. By doing so, this review aims to offer valuable references for both basic research and the prediction of PTC prognosis.

Adiponectin Inhibits the Progression of Obesity-Associated Papillary Thyroid Carcinoma Through Autophagy.

CONTEXT: Obesity is a risk factor for the development of papillary thyroid cancer (PTC). However, the molecular mechanisms by which obesity promotes PTC are unclear. OBJECTIVE: This study aims to identify adipokines that are linked to PTC progression. METHODS: An adipokine antibody array was used to determine the serum levels of 40 adipokines in normal-weight and obese PTC patients. Enzyme-linked immunosorbent assay was used to determine the serum levels of adiponectin. Recombinant human adiponectin was produced by human adipose-derived stem cells and used to treat PTC cells. Cell proliferation and migration were evaluated using the CCK8 and Transwell assays. Bioinformatics analysis was used to predict mechanisms by which adiponectin affects PTC. RESULTS: Adipokines differentially expressed between normal-weight and obese patients showed a gender-dependent pattern. Obese PTC patients had a significantly lower serum adiponectin level than normal-weight patients, especially in female individuals. Adiponectin levels were negatively correlated with aggressive features of PTC, including tumor diameter > 1 cm, extrathyroidal extension, and lymph node metastasis. Recombinant human adiponectin inhibited the proliferation and migration of human PTC cells in vitro. Bioinformatics analysis identified adiponectin receptor 2 (ADIPOR2) and the autophagy pathway as possible mediators of adiponectin function in TC. In vitro experiments confirmed that adiponectin activated autophagy in PTC cells. These findings shed new lights into the role and mechanisms of adiponectin in TC pathogenesis. CONCLUSION: Adiponectin is involved in development of obesity-related PTC. Adiponectin can directly inhibit thyroid cancer growth and metastasis through the autophagy pathway.

Cyto-Histological Profile of MicroRNAs as Diagnostic Biomarkers in Differentiated Thyroid Carcinomas.

INTRODUCTION: The repertoire of microRNAs (miRNAs) in thyroid carcinomas starts to be elucidated. Among differentiated thyroid carcinomas (DTCs), papillary thyroid carcinoma (PTC) is the most frequent. The assessment of miRNAs expression may contribute to refine the pre-surgical diagnosis in order to obtain a personalized and more effective treatment for patients. AIMS: This study aims to evaluate (1) the miRNAs in a series of DTCs, and their association with the presence of selected genetic mutations in order to improve diagnosis and predict the biologic behavior of DTC/PTC. (2) The reliability of molecular tests in Ultrasound-guided Fine Needle Aspiration Cytology (US-FNAC) for a more precise preoperative diagnosis. MATERIAL AND METHODS: This series includes 176 samples (98 cytology and 78 histology samples) obtained from 106 patients submitted to surgery, including 13 benign lesions (controls) and 93 DTCs (cases). The microRNA expression was assessed for miR-146b, miR-221, miR-222, and miR-15a through quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). The results were analyzed by the 2-ΔΔCT method, using miR16 as an endogenous control. Regarding PTC diagnosis, the discriminative ability of miRNAs expression was assessed by the area under the Receiver Operating Characteristic Curve (AUC). In PTCs, the association of miRNAs expression, clinicopathological features, and genetic mutations (BRAF, RAS, and TERTp) was evaluated. RESULTS/DISCUSSION: All the analyzed miRNAs presented a tendency to be overexpressed in DTCs/PTCs when compared with benign lesions, both in cytology and histology samples. In cytology, miRNAs expression levels were higher in malignant tumors than in benign tumors. In histology, the discriminative abilities regarding PTC diagnosis were as follows: miR-146b (AUC 0.94, 95% CI 0.87-1), miR-221 (AUC 0.79, 95% CI 0.68-0.9), miR-222 (AUC 0.76, 95% CI 0.63-0.89), and miR-15a (AUC 0.85, 95% CI 0.74-0.97). miR-146b showed 89% sensitivity (se) and 87% specificity (sp); miR-221 se = 68.4, sp = 90; miR-222 se = 73, sp = 70; and mi-R15a se = 72, sp = 80. MicroRNAs were associated with worst-prognosis clinicopathological characteristics in PTCs (p < 0.05), particularly for miR-222. Our data reveal a significant association between higher expression levels of miR-146b, miR-221, and miR-222 in the presence of the BRAF mutation (p < 0.001) and miR-146b (p = 0.016) and miR-221 (p = 0.010) with the RAS mutation, suggesting an interplay of these mutations with miRNAs expression. Despite this study having a relatively small sample size, overexpression of miRNAs in cytology may contribute to a more precise preoperative diagnosis. The miRNAs presented a good discriminative ability in PTC diagnosis. The association between the miRNAs expression profile and genetic alterations can be advantageous for an accurate diagnosis of DTCs/PTCs in FNAC.

Frequency of Thyroid Microcarcinoma in Patients Who Underwent Total Thyroidectomy with Benign Indication-A 5-Year Retrospective Review.

Background and Objectives: Incidental thyroid cancers (ITCs) are often microcarcinomas. The most frequent histologic type is a papillary microcarcinoma. Papillary thyroid microcarcinomas are defined as papillary thyroid tumours measuring less than 10 mm at their greatest diameter. They are clinically occult and frequently diagnosed incidentally in histopathology reports after a thyroidectomy. The aim of this study is to evaluate the rate of papillary thyroid microcarcinomas (PTMC) in patients who were thyroidectomised with indications of benign disease. Materials and Methods: We retrospectively evaluated the histological incidence of PTMC in 431 consecutive patients who, in a 5 year period, underwent a thyroidectomy with benign indications. Patients with benign histology and with known or suspected malignancy were excluded. Results: Histopathology reports from 540 patients who underwent a total thyroidectomy in our department between 2016 and 2021 were reviewed. A total of 431 patients were thyroidectomised for presumed benign thyroid disease. A total of 395 patients had confirmed benign thyroid disease in the final histopathology, while 36 patients had incidental malignant lesions (33 PTMC-7.67%, one multifocal PTC without microcarcinomas-0.23%, two follicular thyroid carcinoma-0.46%). Out of the PTMC patients, 29 were female and four were male (7.2:1 female-male ratio). The mean age was 54.2 years old. A total of 24 out of 33 patients had multifocal lesions, 11 of which co-existed with macro PTC. Nine patients had unifocal lesions. A total of 21 of these patients were initially operated on for multinodular goitre (64%), while 13 were operated on for Hashimoto/Lymphocytic thyroiditis (36%). Conclusions: PTMC-often multifocal-is not an uncommon, incidental finding after thyroidectomy for benign thyroid lesions (7.67% in our series) and often co-exists with other incidental malignant lesions (8.35% in our series). The possibility of an underlying papillary microcarcinoma should be taken into account in the management of patients with benign-especially nodular-thyroid disease, and total thyroidectomy should be considered.