Polymorphism Pro64His within galectin-3 has functional consequences at proteome level in thyroid cells.

Introduction: The single nucleotide polymorphism (SNP) rs4644 at codon 64 of galectin-3 (gal-3, gene name: LGALS3), specifying the variant proline (P64) to histidine (H64), is known to affect the protein's functions and has been associated with the risk of several types of cancer, including differentiated thyroid carcinoma (DTC). Materials and methods: To deepen our understanding of the biological effects of this SNP, we analyzed the proteome of two isogenic cell lines (NC-P64 vs. NA-H64) derived from the immortalized non-malignant thyrocyte cell line Nthy-Ori, generated through the CRISPR-Cas9 technique to differ by rs4644 genotype. We compared the proteome of these cells to detect differentially expressed proteins and studied their proteome in relation to their transcriptome. Results: Firstly, we found, consistently with previous studies, that gal-3-H64 could be detected as a monomer, homodimer, and heterodimer composed of one cleaved and one uncleaved monomer, whereas gal-3-P64 could be found only as a monomer or uncleaved homodimer. Moreover, results indicate that rs4644 influences the expression of several proteins, predominantly upregulated in NA-H64 cells. Overall, the differential protein expression could be attributed to the altered mRNA expression, suggesting that rs4644 shapes the function of gal-3 as a transcriptional co-regulator. However, this SNP also appeared to affect post-transcriptional regulatory mechanisms for proteins whose expression was oppositely regulated compared to mRNA expression. It is conceivable that the rs4644-dependent activities of gal-3 could be ascribed to the different modalities of self-dimerization. Conclusion: Our study provided further evidence that rs4644 could affect the gal-3 functions through several routes, which could be at the base of differential susceptibility to diseases, as reported in case-control association studies.

Deep convolutional neural network model ResNeSt for discrimination of papillary thyroid carcinomas and benign nodules in thyroid nodules diagnosed as atypia of undetermined significance.

Background: A deep convolutional neural network (DCNN) model was employed for the differentiation of thyroid nodules diagnosed as atypia of undetermined significance (AUS) according to the 2023 Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). The aim of this study was to investigate the efficiency of ResNeSt in improving the diagnostic accuracy of fine-needle aspiration (FNA) biopsy. Methods: Fragmented images were used to train and test DCNN models. A training dataset was built from 1,330 samples diagnosed as papillary thyroid carcinoma (PTC) or benign nodules, and a test dataset was built from 173 samples diagnosed as AUS. ResNeSt was trained and tested to provide a differentiation. With regard to AUS samples, the characteristics of the cell nuclei were compared using the Wilcoxon test. Results: The ResNeSt model achieved an accuracy of 92.49% (160/173) on fragmented images and 84.78% (39/46) from a patient wise viewpoint in discrimination of PTC and benign nodules in AUS nodules. The sensitivity and specificity of ResNeSt model were 95.79% and 88.46%. The κ value between ResNeSt and the pathological results was 0.847 (P<0.001). With regard to the cell nuclei of AUS nodules, both area and perimeter of malignant nodules were larger than those of benign ones, which were 2,340.00 (1,769.00, 2,807.00) vs. 1,941.00 (1,567.50, 2,455.75), P<0.001 and 190.46 (167.64, 208.46) vs. 171.71 (154.95, 193.65), P<0.001, respectively. The grayscale (0 for black, 255 for white) of malignant lesions was lower than that of benign ones, which was 37.52 (31.41, 46.67) vs. 45.84 (31.88, 57.36), P <0.001, indicating nuclear staining of malignant lesions were deeper than benign ones. Conclusions: In summary, the DCNN model ResNeSt showed great potential in discriminating thyroid nodules diagnosed as AUS. Among those nodules, malignant nodules showed larger and more deeply stained nuclei than benign nodules.

Synchronous papillary and follicular thyroid carcinomas: the first retrospective cohort study and literature review.

Background: Papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC) contribute to more than 95% of thyroid malignancies. However, synchronous PTC and FTC are less common; it is most commonly discovered incidentally as synchronous malignancies during operation, which adds difficulties to intraoperative decision-making and postoperative treatment. Therefore, we analyzed the clinicopathological characteristics and prognosis of patients with PTC and FTC in our center. Methods: We conducted a search of single PTC, single FTC, and synchronous PTC/FTC patients who received initial surgery treatment at Fudan University Shanghai Cancer Center from 2006 to 2018 and collected paraffin-embedded samples of synchronous patients. Clinicopathological characteristics were collected from the electronic medical record system. Follow-up was performed through telephone contact or medical records. Exome sequencing was performed by ThyroLead panel. Results: Total of 42 synchronous PTC/FTC patients, 244 single FTC patients, and 2,959 single PTC patients were included. It showed a similarity between the clinicopathological features of synchronous thyroid cancer patients and single PTC patients, with a greater proportion of females, higher probabilities of lymph node metastasis, and higher rate of concurrence of Hashimoto's disease. The disease-free survival (DFS) curve indicated a worse prognosis of the synchronous group and single PTC group compared to the single FTC group, who had a propensity for neck lymph node recurrence; however, logistic multivariate regression analysis did not find any factor related to recurrence in the synchronous group. After re-checking pathology, DNA extraction, and quality control, genetic alteration information of 62 samples including primary tumors and metastatic lymph nodes from 35 synchronous cancer patients was displayed. In total, 81 mutations and 1 fusion gene were identified, including mutations related to outcomes and targeted therapy. Besides, some rare mutations in thyroid cancer were found in these patients. Conclusions: To conclude, synchronous PTC/FTC tend to be incidentally discovered during or after operation, behaving more like single PTC. The prognosis of synchronous patients is worse than that of single FTC patients and supplemental cervical lymph node dissection, total thyroidectomy, and postoperative radioiodine therapy should be taken into consideration after diagnosis. The next-generation sequencing (NGS) showed a unique molecular feature of synchronous patients with some rare mutations.

The coexistence of papillary thyroid carcinoma, anaplastic thyroid carcinoma (squamous cell carcinoma subtype) and poorly differentiated thyroid carcinoma: a case report.

Background: Papillary thyroid carcinoma (PTC) accounts for about 60% of adult thyroid carcinoma and generally has an excellent prognosis. Primary squamous cell carcinoma of thyroid (PSCCT) is a rare thyroid tumor with high malignancy and poor prognosis. In 2022, the 5th edition of World Health Organization (WHO) has classified it as a subtype of anaplastic thyroid carcinoma (ATC), abbreviated as ATC-squamous cell carcinoma (SCC) subtype. Poorly differentiated thyroid carcinoma (PDTC) is a kind of follicular-derived malignancy, which is prone to recurrence and distant metastasis. Here, we report a rare case of the coexistence of PTC, ATC-SCC subtype and PDTC. Case Description: We herein report a case of 69-year-old female who initially presented with a history of left neck mass for one month. Comprehensive auxiliary examinations and postoperative pathology confirmed the diagnosis of PTC combined with ATC-SCC subtype, and PDTC. Total thyroidectomy with radical left cervical lymph node dissection was performed, followed by thyroid-stimulating hormone (TSH) suppressive therapy, 131I, radiotherapy and chemotherapy. The patient showed no tumor recurrence or metastasis after a 5-month postoperative follow-up. Conclusions: The simultaneous occurrence of PTC, ATC-SCC subtype, and PDTC is extremely rare in clinical terms or literature reports. The treatment has not been standardized, and early radical surgery is the first choice. In addition, the combination of adjuvant therapies such as TSH suppressive therapy, radiotherapy, chemotherapy and 131I may further improve the prognosis of the patient.

Analysis of risk factors for lateral lymph node metastasis in T1 stage papillary thyroid carcinoma: a retrospective cohort study.

Background: The occurrence of cervical lymph node metastasis in T1 stage papillary thyroid carcinoma (PTC) is frequently observed. Notably, lateral lymph node metastasis (LLNM) emerges as a critical risk factor adversely affecting prognostic outcomes in PTC. The primary aim of this investigation was to delineate the risk factors associated with LLNM in the initial stages of PTC. Methods: This retrospective analysis encompassed 3,332 patients diagnosed with T1 stage PTC without evident LLNM at the time of diagnosis. These individuals underwent primary surgical intervention at West China Hospital, Sichuan University between June 2017 and February 2023. The cohort was divided into two groups: patients manifesting LLNM and those without metastasis at the time of surgery. Additionally, T1 stage PTC patients were subdivided into T1a and T1b categories. Factors influencing LLNM were scrutinized through both univariate and multivariate analyses. Results: The incidence of LLNM was observed in 6.2% of the cohort (206 out of 3,332 patients). Univariate analysis revealed significant correlations between LLNM and male gender (P<0.001), tumor localization in the upper lobe (P<0.001), maximal volume of the primary tumor (P<0.001), largest tumor diameter (P<0.001), multifocality (P<0.001), and bilaterality (P<0.001), with the exception of age (P=0.788) and duration of active surveillance (AS) (P=0.978). Multivariate logistic regression analysis identified male gender (P<0.001), upper lobe tumor location (P<0.001), maximal primary tumor volume (P<0.001), and multifocality (P<0.001) as independent predictors of LLNM. However, age categories (≤55, >55 years), maximum tumor diameter, bilaterality, and surveillance duration did not exhibit a significant impact. Comparative analyses between T1a and T1b subgroups showed congruent univariate results but revealed differences in multivariate outcomes. In the T1a subgroup, gender, tumor location, and multifocality (all P<0.05) were associated with elevated LLNM risk. Conversely, in the T1b subgroup, tumor location, dimensions, and multifocality (all P<0.05) were significant predictors of LLNM risk, whereas gender (P=0.097) exerted a marginal influence. Conclusions: The investigation highlights several key risk factors for LLNM in T1 stage PTC patients, including gender, upper lobe tumor location, larger tumor size, and multifocality. Conversely, prolonged AS and younger age did not significantly elevate LLNM risk, suggesting the viability of AS as a strategic option in selected cases.

Multi-modal ultrasound multistage classification of PTC cervical lymph node metastasis via DualSwinThyroid.

Objective: This study aims to predict cervical lymph node metastasis in papillary thyroid carcinoma (PTC) patients with high accuracy. To achieve this, we introduce a novel deep learning model, DualSwinThyroid, leveraging multi-modal ultrasound imaging data for prediction. Materials and methods: We assembled a substantial dataset consisting of 3652 multi-modal ultrasound images from 299 PTC patients in this retrospective study. The newly developed DualSwinThyroid model integrates various ultrasound modalities and clinical data. Following its creation, we rigorously assessed the model's performance against a separate testing set, comparing it with established machine learning models and previous deep learning approaches. Results: Demonstrating remarkable precision, DualSwinThyroid achieved an AUC of 0.924 and an 96.3% accuracy on the test set. The model efficiently processed multi-modal data, pinpointing features indicative of lymph node metastasis in thyroid nodule ultrasound images. It offers a three-tier classification that aligns each level with a specific surgical strategy for PTC treatment. Conclusion: DualSwinThyroid, a deep learning model designed with multi-modal ultrasound radiomics, effectively estimates the degree of cervical lymph node metastasis in PTC patients. In addition, it also provides early, precise identification and facilitation of interventions for high-risk groups, thereby enhancing the strategic selection of surgical approaches in managing PTC patients.

Risk factors and nomogram to predict skip metastasis in papillary thyroid carcinoma.

Background: Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy. Skip metastases of PTCs are easily misdiagnosed before surgery, and it could lead to re-operation and affect the prognosis. Although there are a few studies about nomograms for predicting central lymph node metastases (CLNM) or lateral lymph node metastases (LLNM) of PTCs, there are few studies about nomograms for skip metastases. Based on the clinical and ultrasonographic characteristics of patients with PTCs, the aim of our study was to investigate the risk factors and establish a nomogram for predicting the risk of skip metastases in PTCs. Methods: This study enrolled 218 PTCs patients with lateral cervical lymph node metastases and their data were analyzed retrospectively. According to the postoperative pathological results, the patients were divided into skip-positive group and skip-negative group. In order to establish the nomogram, univariate and multivariate analyses were used to estimate risk factors of skip metastases. The receiver operating characteristic (ROC) curve, internal calibration plot and decision curve analysis (DCA) were used to evaluate the nomogram model's efficacy. Results: There were statistical differences between skip-positive group and skip-negative group in tumor location, the maximum diameter (D) and capsule invasion (P<0.05). No statistical differences were observed in sex, age, Hashimoto's thyroiditis, multifocality, anteroposterior diameter/transverse diameter (A/T) ratio, shape, margin, microcalcification, intra-nodular vascularity and preoperative serum thyroglobulin (Tg) (P≥0.05). The risk factors of skip metastases in PTCs were D ≤10 mm, location in the upper portion and capsule invasion. The area under the curve (AUC) of nomogram was 0.877, the accuracy was 85.32%, the sensitivity was 60.98%, and the specificity was 90.96%. The calibration curve and the Hosmer-Lemeshow goodness of fit test showed that the consistency between the nomogram and the actual observation was good. The DCA showed that most PTC patients might benefit from the predictive nomogram model. Conclusions: A nomogram for predicting skip metastases in PTCs may be useful in clinical diagnosis and treatment.

Prediction of bilateral thyroid carcinoma and lateral cervical lymph node metastasis in PTC patients with suspicious thyroid nodules.

PURPOSE: This study aimed to evaluate the factors associated with bilateral papillary thyroid carcinoma (PTC) and lateral cervical lymph node metastasis (LLNM) in patients with suspicious unilateral PTC. METHODS: This study analyzed patients with suspicious unilateral PTC who were enrolled in a university hospital between 2016 and 2019 in Zhejiang, China. Using logistic regression, the study examined the factors associated with bilateral PTC and LLNM in demographic data, anthropometric measurements, lifestyle factors, medical history, preoperative diagnostic tests, and histopathological factors. RESULTS: A total of 256 patients, with a mean age of 49 years, were enrolled. Bilateral PTC was associated with multifocality (aOR: 5.069, 95% CI: 2.440-10.529, P < 0.001), and contralateral nodule in the upper (aOR: 9.073, 95% CI: 2.111-38.985, P = 0.003) and middle (aOR: 9.926, 95% CI: 2.683-36.717, P < 0.001). LLNM was positively associated with bilateral PTC (aOR, 4.283, 95% CI: 1.378-13.308, p = 0.012), male (aOR, 3.377, 95% CI: 1.205-9.461, P = 0.021), upper location of carcinoma (aOR, 3.311, 95% CI: 1.091-10.053, p = 0.035), and punctate echogenic foci (aOR, 3.309, 95% CI: 1.165-9.394, P = 0.025). Contralateral maximal nodule in the upper (aOR: 0.098, 95% CI: 0.015-0.628, p = 0.014), middle (aOR: 0.114, 95% CI: 0.033-0.522, p < 0.001), and lower (aOR, 0.028, 95% CI: 0.003-0.276, P = 0.002) location were inversely associated with LLNM. CONCLUSION: Upper and middle location of contralateral nodule and tumor multifocality predicted the risk bilateral PTC. Bilateral PTC, male, upper tumor location, punctate echogenic foci and contralateral nodule location in the entire lobes were independent predictors for LLNM.

Are Higher Body Mass Index and Worse Metabolic Parameters Associated with More Aggressive Differentiated Thyroid Cancer? A Retrospective Cohort Study.

Obesity is a risk factor for differentiated thyroid cancer (DTC), but the association with DTC aggressiveness is controversial. To evaluate the association between preoperative body mass index (BMI)/other metabolic parameters and DTC aggressiveness in our surgical cohort, we retrospectively evaluated patients following thyroid surgery who were diagnosed with DTC between December 2013 and January 2021. Baseline characteristics, histopathological features, treatment modalities, and follow-up data were studied. We conducted logistic regression to analyze the association between BMI/other metabolic parameters and adverse DTC features. The final study cohort included 211 patients (79.6% women; mean age± standard deviation 48.7 ± 15.9 years): 66 (31.3%) with normal weight, 81 (38.4%) with overweight, and 64 (30.3%) with obesity. The median follow-up was 51 months (range 7-93). Complete versus partial thyroidectomy was more common among patients living with overweight or obesity than in normal weight patients (79.7% versus 61.7%, p = 0.017, respectively). Logistic regression demonstrated that higher BMI was associated with mildly increased risk for lymph nodes metastases (odds ratio [OR] 1.077, 95% CI: 1.013-1.145), and higher triglycerides/high-density lipoprotein-cholesterol (TG/HDL-C) ratio was associated with aggressive histological variants of DTC (OR 1.269, 95% CI 1.001-1.61). To conclude, specific adverse clinical and histopathological DTC features were indeed associated with higher BMI and higher TG/HDL-C ratio.

Detection of thyroglobulin for diagnosis of metastatic lateral cervical lymph nodes in papillary thyroid carcinoma: accuracy and application in clinical practice.

Background: Accurate assessment of lateral cervical lymph node metastasis (LLNM) involvement is important for treating papillary thyroid carcinoma (PTC). Thyroglobulin is associated with LLNM, but there may be differences in the diagnostic value of serum thyroglobulin (sTg) and fine needle aspiration washout fluid thyroglobulin (FNA-Tg). Herein, we investigated the optimal cutoff value (OCV) of sTg and FNA-Tg and their diagnostic performance. Methods: We enrolled 116 PTC patients who underwent radical resection of thyroid carcinoma with lateral cervical lymph node dissection at the Affiliated Hospital of Zunyi Medical University from June 2018 to July 2022. We used the receiver operating characteristic (ROC) curve analysis to determine the OCV for sTg and FNA-Tg to diagnose LLNM in PTC patients. We also evaluated the performance of FNA-Tg, sTg, fine needle aspiration cytology (FNAC), and their combinations for diagnosis. Pathological results were the gold standard. Results: We performed 125 lymph node dissections, 106 had metastasis, and 19 did not. The OCV for sTg was 17.31 ng/mL [area under the curve (AUC) =0.760, sensitivity =78.30%, specificity =73.68%, and accuracy =77.60%]. Meanwhile, the OCV for FNA-Tg was 4.565 ng/mL (AUC =0.948, sensitivity =89.62%, specificity =100%, and accuracy =91.20%). The combination of FNAC and FNA-Tg presented the greatest diagnostic performance for LLNM detection in PTC patients. Moreover, serum antithyroglobulin antibody (TgAb) was not correlated with sTg or FNA-Tg levels. Conclusions: The cutoff value for the diagnosis of LLNM in PTC are sTg >17.31 ng/mL or FNA-Tg >4.565 ng/mL. The combination method of FNA-Tg and FNAC is the most optimal choice for the diagnosis of LLNM and is highly recommended for further clinical application.

Interaction of BANCR in the relationship between Hashimoto's thyroiditis and papillary thyroid carcinoma expression patterns and possible molecular mechanisms.

BACKGROUND: Previous studies have established a connection between Hashimoto's thyroiditis (HT) and an increased risk of papillary thyroid carcinoma (PTC). However, the molecular mechanisms driving this association are not well understood. The long non-coding RNA (lncRNA) BRAF-activated non-coding RNA (BANCR) has been implicated in various cancers, suggesting a potential role in the HT-PTC linkage. METHODS: This study investigated the expression levels of BANCR in PTC and HT samples, compared to control tissues. We also examined the association between BANCR expression and clinicopathological features, including lymph node metastasis. Furthermore, we explored the molecular mechanisms of BANCR in PTC pathogenesis and its potential as a therapeutic target. RESULTS: BANCR expression was significantly lower in PTC samples than in controls, while it was moderately increased in HT samples. In PTC cases with concurrent HT, BANCR expression was markedly reduced compared to normal tissues. Our analysis revealed BANCR's role as an oncogene in PTC, influencing various cancer-related signaling pathways. Interestingly, no significant correlation was found between BANCR expression and lymph node metastasis. CONCLUSION: Our findings underscore the involvement of BANCR in the connection between HT and PTC. The distinct expression patterns of BANCR in PTC and HT, especially in PTC with concurrent HT, provide new insights into the molecular interplay between these conditions. This study opens avenues for the development of innovative diagnostic and therapeutic strategies targeting BANCR in PTC and HT.

Impact of radioiodine therapy on recurrence and survival outcomes in intermediate-risk papillary thyroid carcinoma -A systematic review and meta-analysis.

OBJECTIVE: The utility of radioiodine (RAI) therapy in intermediate-risk papillary thyroid carcinoma (PTC) remains a topic of ongoing discussion. This systematic review and meta-analysis aimed to consolidate existing evidence on the impact of postoperative RAI therapy on recurrence and survival outcomes in intermediate-risk PTC. METHODS: A literature search was performed using relevant keywords in PubMed, Scopus, and EMBASE. Articles from January 2008 to March 2023 were included. Odds ratios (ORs) and hazard ratios (HRs) were extracted from the individual articles, and pooled estimates were generated using meta-analysis. RESULTS: Eleven articles comprising 56,266 intermediate-risk PTC patients were included. 41,530 (73.8%) patients underwent postoperative RAI therapy, while 14,736 (26.2%) patients were kept on no-RAI (NOI) follow-up. No significant reduction in rates of structural disease recurrence was noted with RAI therapy in comparison to NOI follow-up (pooled univariate OR, 0.73, 95% confidence interval [CI], 0.29-1.87, I2 = 75%). RAI therapy was not a significant predictor of better recurrence-free survival (pooled multivariate HR, 0.21; 95% CI, 0.01-3.74, I2 = 94%). Interestingly, RAI therapy was associated with an overall survival benefit compared to NOI follow-up (pooled multivariate HR, 0.63; 95% CI, 0.48-0.82, I2 = 79%). CONCLUSIONS: This meta-analysis did not establish a conclusive benefit of RAI therapy in preventing structural disease recurrence or improving recurrence-free survival in intermediate-risk PTC. However, these results need to be interpreted with caution owing to significant heterogeneity in the existing literature. A prospective, randomised clinical trial is the need of the hour to better understand the effect of RAI therapy on long-term outcomes.

A diagnostic model based on DNA methylation haplotype block characteristics for identifying papillary thyroid carcinoma from thyroid adenoma.

Papillary thyroid carcinoma (PTC) is the most prevalent form of thyroid cancer. Methylation of some genes plays a crucial role in the tendency to malignancy as well as poor prognosis of thyroid cancer, suggesting that methylation features can serve as complementary markers for molecular diagnosis. In this study, we aimed to develop and validate a diagnostic model for PTC based on DNA methylation markers. A total of 142 thyroid nodule tissue samples containing 84 cases of PTC and 58 cases of thyroid adenoma (TA) were collected for reduced representation bisulfite sequencing (RRBS) and subsequent analysis. The diagnostic model was constructed by the logistic regression (LR) method followed by 5-cross validation and based on 94 tissue methylation haplotype block (MHB) markers. The model achieved an area under the receiver operating characteristic curve (AUROC) of 0.974 (95% CI, 0.964-0.981) on 108 training samples and 0.917 (95% CI, 0.864-0.973) on 27 independent testing samples. The diagnostic model scores showed significantly high in males (P = 0.0016), age ≤ 45 years (P = 0.026), high body mass index (BMI) (P = 0.040), lymph node metastasis (P = 0.00052) and larger nodules (P = 0.0017) in the PTC group, and the risk score of this diagnostic model showed significantly high in recurrent PTC group (P = 0.0005). These results suggest that the diagnostic model can be expected to be a powerful tool for PTC diagnosis and there are more potential clinical applications of methylation markers to be excavated.

BRAF V600E mutation co-existing with oncogenic mutations is associated with aggressive clinicopathologic features and poor prognosis in papillary thyroid carcinoma.

BACKGROUND: The aim of this study was to evaluate the correlation among mutations in cancer-related genes, clinicopathologic features, and clinical outcome in classical papillary thyroid carcinoma (PTC). PATIENTS AND METHODS: A total of 130 patients with classical PTC who underwent curative surgery between April 2012 and June 2023 at Hokuto Hospital were included. Mutations in targeted regions of 160 cancer-related genes were detected by next-generation sequencing (NGS)-based cancer panel testing. RESULTS: The BRAF V600E mutation was detected in 108 (83.1%) of 130 PTC patients. Among the 108 patients with the BRAF V600E mutation, other co-existing oncogenic mutations were found in 12 (9.2%) patients. When we divided into 3 groups of no mutations, BRAF V600E mutation alone, and BRAF V600E and other oncogenic mutations, significant differences were observed in terms of tracheal invasion (P = 0.0024), and bilateral neck lymph node metastasis (P = 0.0047). Kaplan-Meier analysis of overall survival (OS) revealed patients with BRAF V600E and other oncogenic mutations had significantly poorer survival than those with BRAF V600E mutation alone (P = 0.0026). Multivariate cox proportional hazard analysis revealed BRAF V600E and other oncogenic mutations was an independent prognostic factor for OS (HR: 10.559; 95%CI: 1.007-110.656, P = 0.0493). CONCLUSIONS: The BRAF V600E mutation co-existing with other oncogenic mutations but not the BRAF V600E mutation alone was associated with aggressive clinicopathologic features, resulting in poor prognosis in patients with classical PTC. Detection of oncogenic mutations using NGS-based cancer panel testing could enhance understanding of the clinical features of classical PTC.

Central lymph nodes in frozen sections can effectively guide extended lymph node resection for papillary thyroid carcinoma.

OBJECTIVES: The scope of lateral neck lymph node dissection (LND) in papillary thyroid carcinoma (PTC) remains controversial. Our research aimed to explore the value of central lymph node metastasis (CLNM) in frozen sections for predicting neck lateral lymph node metastasis (NLLNM) and to guide clinical surgeons in performing surgical lymph node dissection. PATIENTS: A total of 275 patients with PTC with suspected 'Cervical lymph node metastasis (LNM, including CLNM and NLLNM)' underwent unilateral or bilateral thyroidectomy and an intraoperative frozen diagnosis of central lymph nodes (LNs), as well as central and neck lateral LND. Validity indices and consistency of central LNs in frozen sections were calculated. In total, 216 patients then met the inclusion criteria and were enrolled in the follow-up study. The clinical and pathological data of the patients were retrospectively analyzed. The relationship between the number, metastatic diameter, and the ratio of CLNM to NLLNM was investigated. RESULTS: CLNM in frozen and paraffin-embedded sections was associated with NLLNM. Univariate and multivariate analyses revealed the following risk factors for NLLNM metastasis: maximum diameter, total number, and ratio of metastatic LNs. A significant result was obtained when a cut-off value of 2.050 mm for the maximum metastatic diameter, 5.5 in the total number, and 0.5342 for the CLNM ratio level was used. Interaction term analyses showed that the association between the number of CLNM and NLLNM differed according to maximum diameter. CONCLUSION: Central LNs in frozen sections accurately predicted NLLNM. In patients with PTC with >5 CLNMs, ≥2 and ≤5 CLNMs and maximum metastatic diameter > 2 mm, neck lateral LND should be considered. Our findings will facilitate the identification of patients who are likely to benefit from extended lateral neck LND.

Total thyroidectomy versus less-than-total thyroidectomy for papillary thyroid carcinoma of isthmus: a systematic review and meta-analysis.

Background: Papillary thyroid carcinoma of isthmus (PTCI) has a more aggressive nature, a higher rate of lymph node metastasis and tumor recurrence. Clinicians have different preferences for the surgical approach to PTCI, but there are no definitive guidelines. The purpose of this article is to compare the oncologic outcomes and complications of total thyroidectomy and less-than-total thyroidectomy for PTCI using meta-analysis. Methods: We searched PubMed, Embase, Cochrane Library, and Web of Science databases for articles that met the inclusion criteria, with an unlimited start date and an end date of February 19, 2023. Exclusion criteria were applied to filter out articles for further analysis. Ultimately, seven articles were used for analysis, all of which were retrospective studies. The MINORS scale was adopted to evaluate the quality of the included literature, and Review Manager 5.4 was used for data analysis. Results: A total of 814 patients were included in the seven articles, including 401 in the less-than-total thyroidectomy group (trial group) and 413 in the total thyroidectomy group (control group). The results of the meta-analysis showed that there was no significant difference in the tumor recurrence rate between the two groups after total thyroidectomy or less-than-thyroidectomy for PTCI (odds ratio, 1.51; 95% confidence interval: 0.49, 4.65; P=0.47), and there was no statistical difference in the incidence of all postoperative complications between the two groups. Conclusions: There may be some limitations in this analysis, such as publication bias and the fact that the included articles were all retrospective studies with a certain degree of heterogeneity. PTCI patients with early staging and no significant lymph node metastases may be able to choose a more conservative surgical approach, which is less-than-total thyroidectomy. Patients with relatively late staging and significant preoperative lymph node metastases or extra thyroidal extension may opt for total thyroidectomy plus lymph node dissection in the central region and, if necessary, lymph node dissection in the lateral cervical region.

A model for predicting lymph node metastasis of thyroid carcinoma: a multimodality convolutional neural network study.

Background: Early preoperative evaluation of cervical lymph node metastasis (LNM) in papillary thyroid carcinoma (PTC) is critical for further surgical treatment. However, insufficient accuracy in predicting LNM status for PTC based on ultrasound images is a problem that needs to be urgently resolved. This study aimed to clarify the role of convolutional neural networks (CNNs) in predicting LNM for PTC based on multimodality ultrasound. Methods: In this study, the data of 308 patients who were clinically diagnosed with PTC and had confirmed LNM status via postoperative pathology at Beijing Tiantan Hospital, Capital Medical University, from August 2018 to April 2022 were incorporated into CNN algorithm development and evaluation. Of these patients, 80% were randomly included into the training set and 20% into the test set. The ultrasound examination of cervical LNM was performed to assess possible metastasis. Residual network 50 (Resnet50) was employed for feature extraction from the B-mode and contrast-enhanced ultrasound (CEUS) images. For each case, all of features were extracted from B-mode ultrasound images and CEUS images separately, and the ultrasound examination data of cervical LNM information were concatenated together to produce a final multimodality LNM prediction. Sensitivity, specificity, accuracy, and area under the receiver operating characteristic curve (AUC) were used to evaluate the performance of the predictive model. Heatmaps were further developed for visualizing the attention region of the images of the best-working model. Results: Of the 308 patients with PTC included in the analysis, 158 (51.3%) were diagnosed as LNM and 150 (48.7%) as non-LNM. In the test set, when a triple-modality method (i.e., B-mode image, CEUS image, and ultrasound examination of cervical LNM) was used, accuracy was maximized at 80.65% (AUC =0.831; sensitivity =80.65%; specificity =82.26%), which showed an expected increased performance over B-mode alone (accuracy =69.00%; AUC =0.720; sensitivity =70.00%; specificity =73.00%) and a dual-modality method (B-mode image plus CEUS image: accuracy =75.81%; AUC =0.742; sensitivity =74.19%; specificity =77.42%). The heatmaps of our triple-modality model demonstrated a possible focus area and revealed the model's flaws. Conclusions: The PTC lymph node prediction model based on the triple-modality features significantly outperformed all the other feature configurations. This deep learning model mimics the workflow of a human expert and leverages multimodal data from patients with PTC, thus further supporting clinical decision-making.

An unusual case of three concomitant primary solid cancers with unique histopathological characteristics.

INTRODUCTION AND IMPORTANCE: Struma Ovarii is a rare type of monodermal teratoma with at least 50 % of its mass being thyroid tissue. They make up <1 % of all ovarian tumours and 3 to 5 % of all ovarian teratomas. These tumours are usually benign but malignant transformation is seen in <5 % of cases. CASE PRESENTATION: We present the case of a 45-year-old lady with three synchronous primary cancers on a background of Struma Ovarii; primary lung adenocarcinoma, papillary thyroid carcinoma and ovarian teratoma. Over the course of 18 months, this lady underwent full pelvic clearance of malignant Struma Ovarii and lymph nodes, total thyroidectomy, and an anatomical lung resection. CLINICAL DISCUSSION: This case represents an incredibly rare condition of Struma Ovarii for which there is no firm management consensus. Furthermore, the uniqueness of three separate primaries has to the best of our knowledge not previously been reported in the literature. CONCLUSION: This reinforces the notion that in select patients, radical management with curative intent is entirely possible but requires complete multi-disciplinary and multi-modal sub-specialty collaboration.

Lenvatinib and selpercatinib successfully treated RET fusion gene-positive papillary thyroid carcinoma cardiac metastases: a case report.

Background: Cardiac metastasis from thyroid cancer is rare and has an extremely poor prognosis. Although some patients who undergo heart surgery survive, the therapeutic effectiveness of systemic therapy is limited. Case Description: A 53-year-old woman with a history of papillary thyroid carcinoma (PTC) presented with cough and right chest discomfort. She underwent total thyroidectomy, followed by three rounds of radioactive iodine therapy, to treat pulmonary metastasis. Metastases to the lung, chest wall, liver, heart, and lymph nodes were observed on computed tomography. Core needle biopsy of the tumor in the right chest wall revealed the recurrence of PTC. Cardiac metastasis was discovered by echocardiography and cardiac magnetic resonance imaging, and blood test indicated a thyroglobulin level of 851 ng/mL. Based on the presence of cardiac metastasis and strong clinical symptoms, the condition was assumed to be fatal, and lenvatinib was started right away. Three weeks after starting lenvatinib, every metastatic lesion shrank. Once the ERC1-RET fusion gene was identified, we switched to selpercatinib therapy. Ten weeks after starting selpercatinib, every tumor shrank and blood thyroglobulin dropped to 68.1 ng/mL. Initial symptoms such as cough and right chest pain improved. Lenvatinib- and selpercatinib-related adverse effects can be managed with supportive care. Conclusions: To the best of our knowledge, this is the first case of successful systemic therapy for cardiac metastasis from PTC. Conventionally, cardiac surgery is the main treatment for cardiac metastasis, but now systemic therapy is also an important alternative.

Correlation research between preoperative ultrasonographic features and postoperative recurrence of papillary thyroid carcinoma: a retrospective study.

OBJECTIVE: This study sought to evaluate the risk factors for recurrent papillary thyroid carcinoma by preoperative ultrasonography. METHODS: A retrospective study enrolled a total of 146 patients with thyroid papillary carcinoma confirmed by postoperative pathology, and divided into a recurrence group (n = 35) and a non-recurrence group (n = 111) to study their preoperative ultrasound report examination, including the presence of thyroiditis, tumor location, the maximum diameter of the primary tumor, tumor number, the presence of focal strong echogenicity within the lesion, the presence of abnormal lymph nodes, the presence of ultrasound imaging manifestations of thyroid invasion, and to explore the risk factors associated with recurrent papillary thyroid cancer. Moreover, the consistency of ultrasound examination and postoperative pathological findings was explored. RESULTS: There were significant differences in the maximum diameter of the primary tumor and thyroid invasion between the recurrent and non-recurrent papillary thyroid carcinoma groups (P < 0.05), and the preoperative tumor diameter diagnostic cutoff value is 13.750 mm. At the same time, ultrasound and pathology have good consistency in the number of papillary thyroid carcinoma tumors, moderate consistency in lymph node metastasis, and excellent consistency in the presence or absence of thyroid invasion. CONCLUSIONS: The maximum diameter of the primary tumor and thyroid invasion can be used as indicators to evaluate the risk of recurrence of thyroid papillary carcinoma by ultrasonic examination. In addition, the number of tumors and the presence of thyroid invasion in ultrasonic and pathological diagnosis showed good consistency.