Exploring near-infrared autofluorescence properties in parathyroid tissue: an analysis of fresh and paraffin-embedded thyroidectomy specimens.

Significance: Near-infrared autofluorescence (NIRAF) utilizes the natural autofluorescence of parathyroid glands (PGs) to improve their identification during thyroid surgeries, reducing the risk of inadvertent removal and subsequent complications such as hypoparathyroidism. This study evaluates NIRAF's effectiveness in real-world surgical settings, highlighting its potential to enhance surgical outcomes and patient safety. Aim: We evaluate the effectiveness of NIRAF in detecting PGs during thyroidectomy and central neck dissection and investigate autofluorescence characteristics in both fresh and paraffin-embedded tissues. Approach: We included 101 patients diagnosed with papillary thyroid cancer who underwent surgeries in 2022 and 2023. We assessed NIRAF's ability to locate PGs, confirmed via parathyroid hormone assays, and involved both junior and senior surgeons. We measured the accuracy, speed, and agreement levels of each method and analyzed autofluorescence persistence and variation over 10 years, alongside the expression of calcium-sensing receptor (CaSR) and vitamin D. Results: NIRAF demonstrated a sensitivity of 89.5% and a negative predictive value of 89.1%. However, its specificity and positive predictive value (PPV) were 61.2% and 62.3%, respectively, which are considered lower. The kappa statistic indicated moderate to substantial agreement (kappa = 0.478; P < 0.001 ). Senior surgeons achieved high specificity (86.2%) and PPV (85.3%), with substantial agreement (kappa = 0.847; P < 0.001 ). In contrast, junior surgeons displayed the lowest kappa statistic among the groups, indicating minimal agreement (kappa = 0.381; P < 0.001 ). Common errors in NIRAF included interference from brown fat and eschar. In addition, paraffin-embedded samples retained stable autofluorescence over 10 years, showing no significant correlation with CaSR and vitamin D levels. Conclusions: NIRAF is useful for PG identification in thyroid and neck surgeries, enhancing efficiency and reducing inadvertent PG removals. The stability of autofluorescence in paraffin samples suggests its long-term viability, with false positives providing insights for further improvements in NIRAF technology.

Clinicopathological features affecting the efficacy in 131I ablation therapy of papillary thyroid carcinoma with lymph node metastasis.

Background: Lymph node metastasis is the major cause of increased recurrence and death in patients with papillary thyroid carcinoma (PTC). We evaluate the clinicopathologic factors affecting excellent response (ER) in patients with PTC with lymph node metastasis following operation and 131I ablation therapy. Methods: A total of 423 patients with PTC with lymph node metastasis who underwent thyroidectomy and postoperative 131I ablation therapy were enrolled. The relationship between clinicopathological factors affecting ER achievement was analyzed. Results: Multivariate analysis showed that the foci diameter (≤1 cm), unifocal, combination with Hashimoto's thyroiditis (HT), lymph node metastases rate (LR) (≤40%), no postoperative lymph node metastasis, low preablative stimulated thyroglobulin (ps-Tg) level (≤3.87 ng/mL), and the time of 131I ablation therapy (one time) were positively correlated with the ER achievement [odds ratio (OR): 1.744, 3.114, 3.920, 4.018, 2.074, 9.767, and 49.491, respectively; all p < 0.05]. The receiver operating characteristic (ROC) curves showed that the cutoff values of ps-Tg and LR were 4.625 ng/mL and 50.50%, respectively. The AUC of ROC of ps-Tg and LR for predicting ER achievement was 0.821 and 0.746, respectively. The Tg and the cumulative risk of non-ER elevated with the increase of LR, especially for the high-level ps-Tg (>4.625 ng/mL) group. Conclusion: The foci diameter and number, combination with HT, LR, and ps-Tg level are independent factors for ER. Ps-Tg level and LR are valid predictive factors for the efficacy of 131I therapy in patients with PTC. The predictive value of the cumulative risk of non-ER can be improved by the combination of ps-Tg and LR.

Mitochondrial DNA copy number and risk of papillary thyroid carcinoma.

BACKGROUND: Mitochondrial DNA (mtDNA) copy number is associated with tumor activity and carcinogenesis. This study was undertaken to investigate mtDNA copy number in papillary thyroid cancer (PTC) tissues and to evaluate the risk of PTC development. The clinicopathological features of patients and mtDNA copy number were correlated. The value of mtDNA copy number was evaluated as a biomarker for PTC. METHOD: DNA was extracted from 105 PTC tissues and 67 control thyroid tissues, and mtDNA copy number mtDNA oxidative damage were determined using qPCR techniques. RESULTS: Overall, the relative mtDNA copy number was significantly higher in PTC patients (p < 0.001). The risk of developing PTC increased significantly across the tertiles of mtDNA copy number (p trend < 0.001). The higher the mtDNA copy number tertile, the greater the risk of developing PTC. Patients with follicular variants had an odds ratio of 2.09 (95% CI: 1.78-2.44) compared to those with classical variants (p < 0.001). The level of mtDNA oxidative damage in PTC was significantly elevated compared to controls (p < 0.001). The ROC analysis of mtDNA copy number indicated an area under the curve (AUC) of 77.7% (95% CI: 0.71 to 0.85, p < 0.001) for the ability of mtDNA copy number z-scores in differentiate between PTC and controls. CONCLUSION: Our results indicated that the augmentation of mtDNA content plays a significant role during the initiation of thyroid cancer, and it might represent a potential biomarker for predicting the risk of PTC.

Application of color doppler ultrasound and US shear wave elastography with connective tissue growth factor in the risk assessment of papillary thyroid carcinoma.

BACKGROUND: This study aims to investigate the role of shear wave elastography (SWE) and connective tissue growth factor (CTGF) in the assessment of papillary thyroid carcinoma (PTC) prognosis. METHODS: CTGF expression was detected with immunohistochemistry. Clinical and pathological data were collected. Parameters of conventional ultrasound combined with SWE were also collected. The relationship among CTGF expression, ultrasound indicators, the elastic modulus and the clinicopathological parameters were analyzed. RESULTS: Univariate analysis showed that patients with high risk of PTC were characterized with male, Uygur ethnicity, increased expression of CTGF, convex lesions, calcified, incomplete capsule, intranodular blood flow, rear echo attenuation, cervical lymph node metastasis, lesions larger than 1 cm, psammoma bodies, advanced clinical stage, increased TSH and high value in the shear modulus (P < 0.05). Multivariate analysis demonstrated that the risk factors of high expression of CTGF according to contribution size order were irregular shape, aspect ratio ≥ 1, and increased TSH. The logistic regression model equation was Logit (P) = 1.153 + 1.055 × 1 + 0.926 × 2 + 1.190 × 3 and the Area Under Curve value of the logistic regression was calculated to be 0.850, with a 95% confidence interval of 0.817 to 0.883. CONCLUSION: SWE and CTGF are of great value in the risk assessment of PTC. The degree of fibrosis of PTC is closely related to the prognosis. The hardness of PTC lesions and the expression level of CTGF are correlated with the main indexes of conventional ultrasound differentiating benign or malignant nodules. Irregular shape, aspect ratio ≥ 1, and increased TSH are independent factors of CTGF.

Prediction of the Aggressive Clinical Course of Papillary Thyroid Carcinoma Based on Fine Needle Aspiration Biopsy Molecular Testing.

Molecular genetic events are among the numerous factors affecting the clinical course of papillary thyroid carcinoma (PTC). Recent studies have demonstrated that aberrant expression of miRNA, as well as different thyroid-related genes, correlate with the aggressive clinical course of PTC and unfavorable treatment outcomes, which opens up new avenues for using them in the personalization of the treatment strategy for patients with PTC. In the present work, our goal was to assess the applicability of molecular markers in the preoperative diagnosis of aggressive variants of papillary thyroid cancer. The molecular genetic profile (expression levels of 34 different markers and BRAF mutations) was studied for 108 cytology specimens collected by fine-needle aspiration biopsy in patients with PTC having different clinical manifestations. Statistically significant differences with adjustment for multiple comparisons (p < 0.0015) for clinically aggressive variants of PTC were obtained for four markers: miRNA-146b, miRNA-221, fibronectin 1 (FN1), and cyclin-dependent kinase inhibitor 2A (CDKN2A) genes. A weak statistical correlation (0.0015 < p < 0.05) was observed for miRNA-31, -375, -551b, -148b, -125b, mtDNA, CITED1, TPO, HMGA2, CLU, NIS, SERPINA1, TFF3, and TMPRSS4. The recurrence risk of papillary thyroid carcinoma can be preoperatively predicted using miRNA-221, FN1, and CDKN2A genes.

An age-and sex-matched postoperative therapy should be required in thyroid papillary carcinoma.

Background and purpose: Thyroid papillary carcinoma (PTC) had a high possibility of recurrence after surgery, and thyroid stimulating hormone (TSH) suppression and radioactive iodine (131I) were used for postoperative therapy. This study explored the potential mechanism of lymph node metastasis (LNM) and aimed to develop differentiated treatments for PTC. Method: This study explored the risk factors of lymph node metastasis in PTC by analyzing the clinical information of 2073 cases. The Cancer Genome Atlas Thyroid Cancer (TCGA-THCA) and the Gene Expression Omnibus (GEO) databases of gene expression were analyzed to identify the interrelationships between gene expression to phenotype. Results: Analyzing clinical data, we found that male gender, younger age, larger tumor size, and extra-thyroidal extension (ETE) were risk significant risk factors for lymph node metastasis(P<0.05). Conversely, thyroid function parameters such as TSH, FT3, FT4, TSH/FT3, and TSH/FT4 didn't correlate with LNM(P>0.05), and TSH levels were observed to be higher in females(P<0.05). Gene expression analysis revealed that SLC5A5 was down-regulated in males, younger individuals, and those with lymph node metastasis, and a lower level of SLC5A5 was associated with a worse disease-free survival(P<0.05). Additionally, our examination of single-cell RNA sequencing (scRNA-seq) data indicated that SLC5A5 expression was reduced in tumors and lymph node metastasis samples, correlating positively with the expression of TSHR. Conclusion: The impact of TSH on PTC behavior remained unclear, while the capacity for absorbing 131I in dependence on SLC5A5 showed variations across different genders and ages. We conclude that postoperative treatment of PTC should take into account the differences caused by gender and age.

The neurotransmitter calcitonin gene-related peptide shapes an immunosuppressive microenvironment in medullary thyroid cancer.

Neurotransmitters are key modulators in neuro-immune circuits and have been linked to tumor progression. Medullary thyroid cancer (MTC), an aggressive neuroendocrine tumor, expresses neurotransmitter calcitonin gene-related peptide (CGRP), is insensitive to chemo- and radiotherapies, and the effectiveness of immunotherapies remains unknown. Thus, a comprehensive analysis of the tumor microenvironment would facilitate effective therapies and provide evidence on CGRP's function outside the nervous system. Here, we compare the single-cell landscape of MTC and papillary thyroid cancer (PTC) and find that expression of CGRP in MTC is associated with dendritic cell (DC) abnormal development characterized by activation of cAMP related pathways and high levels of Kruppel Like Factor 2 (KLF2), correlated with an impaired activity of tumor infiltrating T cells. A CGRP receptor antagonist could offset CGRP detrimental impact on DC development in vitro. Our study provides insights of the MTC immunosuppressive microenvironment, and proposes CGRP receptor as a potential therapeutic target.

Ultrasound-based nomogram to predict the recurrence in papillary thyroid carcinoma using machine learning.

BACKGROUND AND AIMS: The recurrence of papillary thyroid carcinoma (PTC) is not unusual and associated with risk of death. This study is aimed to construct a nomogram that combines clinicopathological characteristics and ultrasound radiomics signatures to predict the recurrence in PTC. METHODS: A total of 554 patients with PTC who underwent ultrasound imaging before total thyroidectomy were included. Among them, 79 experienced at least one recurrence. Then 388 were divided into the training cohort and 166 into the validation cohort. The radiomics features were extracted from the region of interest (ROI) we manually drew on the tumor image. The feature selection was conducted using Cox regression and least absolute shrinkage and selection operator (LASSO) analysis. And multivariate Cox regression analysis was used to build the combined nomogram using radiomics signatures and significant clinicopathological characteristics. The efficiency of the nomogram was evaluated by receiver operating characteristic (ROC) curves, calibration curves and decision curve analysis (DCA). Kaplan-Meier analysis was used to analyze the recurrence-free survival (RFS) in different radiomics scores (Rad-scores) and risk scores. RESULTS: The combined nomogram demonstrated the best performance and achieved an area under the curve (AUC) of 0.851 (95% CI: 0.788 to 0.913) in comparison to that of the radiomics signature and the clinical model in the training cohort at 3 years. In the validation cohort, the combined nomogram (AUC = 0.885, 95% CI: 0.805 to 0.930) also performed better. The calibration curves and DCA verified the clinical usefulness of combined nomogram. And the Kaplan-Meier analysis showed that in the training cohort, the cumulative RFS in patients with higher Rad-score was significantly lower than that in patients with lower Rad-score (92.0% vs. 71.9%, log rank P < 0.001), and the cumulative RFS in patients with higher risk score was significantly lower than that in patients with lower risk score (97.5% vs. 73.5%, log rank P < 0.001). In the validation cohort, patients with a higher Rad-score and a higher risk score also had a significantly lower RFS. CONCLUSION: We proposed a nomogram combining clinicopathological variables and ultrasound radiomics signatures with excellent performance for recurrence prediction in PTC patients.

Risk factors for cervical lymph node metastasis of papillary thyroid cancer in elderly patients aged 65 and older.

Objective: To assess the risk factors of cervical lymph node metastasis in elderly patients aged 65 years and older diagnosed with papillary thyroid cancer (PTC). Design and method: In this retrospective analysis, we included a total of 328 elderly patients aged 65 years and older diagnosed with PTC. We thoroughly examined clinical features from these patients. Utilizing univariate and multivariate logistic regression analyses, we aimed to identify factors contributing to the risk of central and lateral lymph node metastasis (CLNM/LLNM) in this specific population of PTC patients aged 65 years and older. Results: In the univariate analysis, CLNM was significantly associated with tumor size, multifocality, bilaterality, and microcalcification, while only tumor size ≥ 1cm (OR = 0.530, P = 0.019, 95% CI = 0.311 - 0.900) and multifocality (OR = 0.291, P < 0.001, 95% CI = 0.148 - 0.574) remained as risk factors in the multivariate analysis. LLNM was confirmed to be associated with male (OR = 0.454, P < 0.020, 95% CI = 0.233 - 0.884), tumor size ≥ 1cm (OR = 0.471, P = 0.030, 95% CI = 0.239 - 0.928), age ≥ 70 (OR = 0.489, P = 0.032, 95% CI = 0.254 - 0.941), and microcalcification (OR = 0.384, P = 0.008, 95% CI = 0.189 - 0.781) in the multivariate analysis. In elderly PTC patients with CLNM, male gender (OR = 0.350, P = 0.021, 95% CI = 0.143 - 0.855), age ≥ 70 (OR = 0.339, P = 0.015, 95% CI = 0.142 - 0.810), and bilaterality (OR = 0.320, P = 0.012, 95% CI = 0.131 - 0.779) were closely associated with concomitant LLNM in both univariate and multivariate analyses. Conclusion: For elderly PTC patients aged 65 and older, tumor size ≥ 1cm and multifocality are significant risk factors for CLNM. Meanwhile, male, tumor size ≥ 1cm, age ≥ 70, and microcalcification are crucial predictors for LLNM. In patients already diagnosed with CLNM, male, age ≥ 70, and bilaterality increase the risk of LLNM.

METTL3 regulates thyroid cancer differentiation and chemosensitivity by modulating PAX8.

Background: Thyroid cancer (TC) is a common endocrine cancer with a favourable prognosis. However, poor patient prognosis due to TC dedifferentiation is becoming an urgent challenge. Recently, methyltransferase-like 3 (METTL3)-mediated N6 -methyladenosine (m6A) modification has been demonstrated to play an important role in the occurrence and progression of various cancers and a tumour suppressor role in TC. However, the mechanism of METTL3 in TC remains unclear. Methods: The correlation between METTL3 and prognosis in TC patients was evaluated by immunohistochemistry. Mettl3fl/flBrafV600ETPO-cre TC mouse models and RNA-seq were used to investigate the underlying molecular mechanism, which was further validated by in vitro experiments. The target gene of METTL3 was identified, and the complete m6A modification process was described. The phenomenon of low expression of METTL3 in TC was explained by identifying miRNAs that regulate METTL3. Results: We observed that METTL3 expression was negatively associated with tumour progression and poor prognosis in TC. Mechanistically, silencing METTL3 promoted the progression and dedifferentiation of papillary thyroid carcinoma (PTC) both in vivo and in vitro. Moreover, overexpressing METTL3 promoted the sensitivity of PTC and anaplastic thyroid cancer (ATC) cells to chemotherapeutic drugs and iodine-131 (131I) administration. Overall, the METTL3/PAX8/YTHDC1 axis has been revealed to play a pivotal role in repressing tumour occurrence, and is antagonized by miR-493-5p.

Histiocytic lesion masquerading as papillary carcinoma thyroid-A case report.

ABSTRACT: Langerhans cell histiocytosis (LCH) is a rare clonal neoplasm derived from Langerhans-type cells that express CD 1a, langerin, and S 100 on immunohistochemistry. LCH usually involves multiple sites and multiple systems or multiple sites in a single system. Solitary LCH commonly involves the bones (especially the skull), lymph nodes, skin, and lungs. Solitary LCH of the thyroid is an extremely rare disease with a few reported cases in the indexed literature and poses a diagnostic dilemma for both the clinician and pathologist. Histopathology along with ancillary tests forms the gold standard for diagnosis. Surgical resection alone offers a good prognosis once multisystemic involvement has been ruled out. Herein is reported one such case of solitary LCH in a young male patient who remains disease-free after 2 years of follow-up.

Predictors of response to Radioactive Iodine Therapy in Intermediate and high risk patients with papillary thyroid carcinoma.

BACKGROUND: Radioactive iodine (RAI) therapy is the standard treatment approach after total thyroidectomy in patients with papillary thyroid carcinoma (PTC). We aimed to identify predictive factors of response to the treatment in intermediate and high-risk patients with PTC. In addition, the impact of multiple RAI treatments was explored. METHODS: In a 3-year retrospective study, data from intermediate and high-risk patients with PTC who received RAI therapy following total thyroidectomy, were analyzed by the end of year-one and year-three. Demographic data, tumor size, capsular/vascular invasion, extrathyroidal extension, local or distant metastasis, initial dose and cumulative dose of RAI, serum thyroglobulin(Tg), antithyroglobulin antibody(TgAb), and imaging findings were investigated. Patients with an excellent response to a single dose of RAI treatment, after three years of follow-up were classified as the "Responder group". Excellent response was defined as stimulated serum Tg less than 1 ng/ml, or unstimulated serum Tg less than 0.2 ng/ml in TgAb-negative patients with negative imaging scans. RESULTS: 333 patient records with a complete data set were analyzed in this study. After three years of initial treatment, 271 patients were non-responders (NR) and 62 were responders (R). At baseline, the median pre-ablation serum Tg level was 5.7 ng/ml in the NR group, and 1.25 ng/ml in the R group (P < 0.001). TSH-Stimulated serum Tg greater than 15.7 ng/ml, was associated with response failure even after multiple RAI therapy, AUC: 0.717(0.660-0.774), sensitivity: 52.5%, specificity: 89.47%, P < 0.001. On the other hand, multiple RAI therapy was associated with excellent response in 16.2% of the patients. The chance of ER was decreased by 74% if initial post-operation ultrasound imaging confirmed the presence of locoregional involvement, OR 0.26, (95% CI: 0.12-0.55), P < 0.001. CONCLUSION: Stimulated serum Tg and locoregional involvement after total thyroidectomy are predictive factors of non-response to RAI therapy in intermediate and high-risk patients with PTC. In addition, a minority of patients achieve excellent response after multiple RAI therapy.

[circ_BACH2 affects the malignant biological behavior of papillary thyroid cancer by regulating miR-370-3p].

Objective: To investigate the influence of circ_BACH2 on the malignant biological behavior of papillary thyroid cancer and its molecular mechanism. Methods: Cancer tissues and paracancer tissues of 51 patients with papillary thyroid carcinoma from the Fourth Central Hospital of Tianjin between 2017 and 2019 were collected. Reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) was used to detect the expressions of circ_BACH2, miR-370-3p and G protein coupled receptor kinase interacting factor 1 (GIT1) mRNA in tissues and cells; flow cytometry to detect cell apoptosis and cell cycle; plate clone formation experiment to detect the number of cell clones; cell counting kit 8 (CCK-8) to detect cell proliferation; Transwell array to detect cell migration and invasion; western blot to detect protein expressions; dual luciferase report experiment to detect the targeting relationship between circ_BACH2, miR-370-3p and GIT1; the nude mouse tumor formation experiment to detect the effect of circ_BACH2 on tumors in mice. Results: Compared with adjacent tissues, the expressions of circ_BACH2 and GIT1 in papillary thyroid cancer tissues was increased, while the expression of miR-370-3p was decreased. Compared with Nthy-ori3-1 cells, the expressions of circ_BACH2 in papillary thyroid cancer cells TPC-1 and SW579 were increased, the mRNA and protein levels of GIT1 were increased, miR-370-3p expression was decreased. The expression level of GIT1 mRNA was negatively correlated with that of miR-370-3p (r=-0.634), and the expression level of circ_BACH2 was positively correlated with that of GIT1 (r=0.635). The expression level of circ_BACH2 was negatively correlated with that of miR-370-3p (r=-0.394, P＜0.05). Circ_BACH2 and miR-370-3p has a binding site at the 3' UTR of GIT1. After knocking down circ_BACH2, the proportion of G0/G1 cells in papillary thyroid cancer cells TPC-1 and SW579 was increased, the proportion of S-phase cells was decreased and the proportion of G2/M-phase cells did not change significantly. The cell absorbance value was lower than that in si-NC group. The number of cell clone formation was decreased (43±5 vs 100±6, 54±8 vs 100±9); the cell apoptosis rate was increased [(19.60±2.40)% vs (4.30±0.20)%, (18.10±2.10)% vs (5.10±0.23)%]; cell migration number was decreased (61±7 vs 134±15, 58±6 vs 112±11), the invasion number was also decreased (45±6 vs 113±11, 47±4 vs 92±9); the expressions of Snail and Twist1 were decreased, and the expression of E-cadherin was increased (P＜0.000). Inhibition of miR-370-3p expression reversed the effect of circ_BACH2 knockdown on proliferation, migration, invasion and apoptosis of thyroid papillary cancer cells. Overexpression of GIT1 reversed the effects of overexpression of miR-370-3p on proliferation, migration, invasion and apoptosis of thyroid papillary cancer cells. Mice injected with TPC-1 cells stably transfected with sh-circ_BACH2 showed a reduction in tumor volume [(535±91) mm3 vs (857±114) mm3] after 35 days of culture; tumor weight was decreased [(0.62±0.13) mg vs (1.06±0.15) mg, P＜0.05]; the expressions of circ_BACH2 and GIT1 were decreased, and the expression of miR-370-3p was increased in nude mouse tumor tissue. Conclusion: Silencing circ_BACH2 may inhibit the proliferation, migration and invasion of papillary thyroid cancer cells in vitro, promote cell apoptosis, and inhibit tumor growth in vivo through targeted regulation of miR-370-3p/GIT1.

Predictive value of an ultrasound-based radiomics model for central lymph node metastasis of papillary thyroid carcinoma.

Purpose: We aimed to explore the predictive value of an ultrasound-based radiomics model for the central lymph node metastasis of papillary thyroid carcinoma. Methods: A total of 126 patients with papillary thyroid carcinoma treated between February 2021 and February 2023 were retrospectively enrolled and assigned into metastasis group (n=59, with cervical central lymph node metastasis) or non-metastasis group (n=67, without metastasis) based on surgical and pathological findings. Intergroup comparisons were conducted on the results of contrast-enhanced ultrasonography, preoperative conventional ultrasonography, as well as real-time shear wave elastography. Results: The maximum lesion diameter, echo, margin, capsule invasion, calcification, average elasticity modulus (Eavg), rising time (RT), and peak intensity (PI) had diagnostic value for papillary thyroid carcinoma, and their combination exhibited higher diagnostic value (area under the curve: 0.817). The logistic regression model was built, and the maximum lesion diameter, hypoechoic/extremely hypoechoic, lobulated or irregular margin (95% confidence interval: 1.451-6.755), capsule invasion, microcalcification/macrocalcification or peripheral calcification, high-level Eavg, low-level RT and high-level PI served as risk elements affecting papillary thyroid carcinoma from the aspect of central lymph node metastasis (odds ratio>1, P<0.05). According to the logistic regression model, the model was reliable and stable (area under the curve: 0.889, P<0.05). Conclusion: The established ultrasound-based radiomics model can be utilized for early identifying the central lymph node metastasis of papillary thyroid carcinoma.

Case report: An adolescent female with anosmic hypogonadotropic hypogonadism, intellectual disability, and papillary thyroid carcinoma: heterozygous deletion of TCF12.

Background: Isolated hypogonadotropic hypogonadism is a heterogeneous clinical entity. There is a growing list of molecular defects that are associated with hypogonadotropic hypogonadism (HH). TCF12, a recently identified molecular defect, causes craniosynostosis and is suggested to be used as a biomarker for prognosis in various cancer types. Recently, TCF12 variants were shown in a cohort with HH. Case presentation: A 15.3 years old female patient was referred to the endocrinology clinic for obesity. She had been gaining weight from mid-childhood. She had her first epileptic seizure at the age of 15.1 years and mildly elevated thyroid autoantibodies were detected during evaluation for etiology of seizures. She had not experienced menarche yet. She was operated for left strabismus at the age of 7 years. School performance was poor and she was receiving special education. Tanner stage of breast was 1 and pubic hair was 3. The endocrine workup revealed hypogonadotropic hypogonadism. Also, the Sniffin' Sticks test detected anosmia. Thyroid ultrasonography was performed due to the mildly elevated thyroid autoantibodies, and thyroid nodules with punctate calcifications were detected. Total thyroidectomy and central lymph node dissection were performed regarding the cytological findings of the nodules and multicentric papillary thyroid carcinoma with no lymph node metastasis was detected on pathology specimens. Regarding the phenotypic features of the patients, whole exome sequencing was performed and heterozygous deletion of exon 1 and exon 6-8 in TCF12 was detected. Conclusion: Haploinsufficiency of TCF12 causes anosmic HH. Probably due to the incomplete penetrance and variable expressivity of the disease, patients could display variable phenotypic features such as intellectual disability, developmental delay, and craniosynostosis. Further description of new cases with TCF12 variations could enhance our understanding of craniosynostosis and its potential link to Kallmann syndrome associated with this gene.

Transoral endoscopic thyroidectomy submental vestibular approach for early-stage papillary thyroid carcinoma: a systematic review and meta-analysis.

PURPOSE: Our study aimed to compare the effectiveness and complications of the transoral endoscopic thyroidectomy submental vestibular approach (TOETSMVA) versus the transoral endoscopic thyroidectomy vestibular approach (TOETVA) or conventional open thyroidectomy (COT) in patients with early-stage papillary thyroid carcinoma (PTC). METHODS: We searched online databases up to January 2024. The outcomes were analyzed using RevMan 5.4 and inverse variance. RESULTS: Seven studies (two RCTs and five retrospective cohort studies) were included. We established higher significance differences for TOETSMVA in comparison with TOETVA in terms of all primary outcomes; operation time, hospital stay, number of resected lymph nodes [MD -21.05, 95% CI= -30.98, -11.12; p < 0.0001], [MD -1.76, 95% CI= -2.21, -1.32, p < 0.00001], [MD -2.99, 95% CI= -19.75, 13.76, p < 0.73], [MD -0.83, 95% CI = -1.19 to -0.47; p < 0.00001], respectively, except the drainage volume, it showed no difference [MD -2.99, 95% CI= -19.75, 13.76, p < 0.73]. In secondary outcomes, it was favored only in mandibular numbness and return to normal diet outcomes. Additionally, TOETSMVA compared with COT showed a significant difference in drainage volume, pain, cosmetic effect, and satisfaction score. CONCLUSIONS: TOETSMVA showed a significant improvement compared to the TOETVA in operation time, hospital stay, number of resected lymph nodes, mandibular numbness, and return to normal diet but did not show a difference in drainage volume. However, TOETSMVA was better in cosmetic effect, drainage volume, satisfaction, and pain scores compared with COT. Further RCTs with larger sample size, multicentral, and longer follow-up are necessary to evaluate the limitations.

Tumor deposits in thyroid carcinomas.

Tumor deposits (TDs) are defined as discontinuous neoplastic masses within the lymphatic drainage pathway of the primary tumor. The poor prognostic implication of these masses have been demonstrated in various cancers. The aim of this study is to investigate the incidence of TDs in our thyroid carcinoma cases, which has not been studied so far to the best of our knowledge, and to determine the prognostic value of their existence. In this retrospective cohort study, 194 thyroid carcinoma cases with cervical lymph node sampling and/or dissection were reevaluated for TDs. The case series consisted of 176 thyroid papillary carcinoma (TPC) and 18 thyroid medullary carcinoma (TMC) patients. TDs were detected in 54 (27.8%) patients. TMC cases (55.6%) had significantly more TDs compared to TPCs (25.0%; P = .006). TDs were more common in women (P = .045), and in multifocal tumors (P = .017). In addition, cases with TDs had larger tumor size (P = .002), more lymphatic invasion (P = .009), extrathyroidal extension (P < .001), and distant metastasis (P < .001). The mean follow-up period of the patients was 120.1 months (range, 4-341 months). Locoregional recurrence detected in 17 patients (8.8%) was more common in TMC (33.3%) than TPC cases (6.3%; P = .002). Distant metastasis was identified in 27 patients (13.9%). Ten-year recurrence free survival (RFS) and overall survival (OS) for all patients were 89.0% and 92.4%, respectively. Mean estimated OS time for TD negative and TD positive cases were: 281.9 (±17.2), 325.6 (±6.2) and 217.6 (±27.4) months, respectively (P = .002). Sex (P = .001), tumor type (P = .002), pT classification of the tumor (P < .001), perineural invasion (P = .002) and TDs (P = .002) were significantly associated with OS. In TPC cases individually, extrathyroidal extension (P = .001) and TDs (P = .002) were significantly correlated with distant metastasis. In multivariate analysis, only tumor size was detected as an independent prognostic marker in TPC cases (P = .005). Our results demonstrate the existence of TDs in thyroid carcinoma cases, and indicate a more aggressive behavior pattern of TDs in these tumors.

Relationship between recurrence and age in the diffuse sclerosing variant of papillary thyroid carcinoma: clinical significance in pediatric patients.

Background: The diffuse sclerosing variant (DSV) is among the aggressive variants of papillary thyroid carcinoma (PTC) and is more prevalent in pediatric patients than in adult patients. Few studies have assessed its characteristics owing to its low incidence. We aimed to evaluate the relationship between recurrence and age in the DSV of PTC. Methods: We retrospectively reviewed patients diagnosed with the DSV or conventional PTC (cPTC) after surgery at a medical center between May 1988 and January 2019. We compared the clinico-pathological characteristics and surgical outcomes of the DSV and cPTC groups and between adult and pediatric patients with DSV. Results: Among the 24,626 patients, 202 had the DSV, and 24,424 were diagnosed with cPTC. The recurrence rate was significantly higher in the DSV group than in the cPTC group. In the DSV group, the recurrence rate was significantly higher in the pediatric patient group than in the adult patient group. Moreover, the association between recurrence and age group showed different patterns between the DSV and cPTC groups with restricted cubic splines (RCS). While both RCS curves showed a U-shaped distribution, the RCS curve tended to be located within the younger age group. Conclusions: This study demonstrated that pediatric patients with DSV are at a greater risk for recurrence compared with adult patients; moreover, the pattern of recurrence risk according to age is different from that of cPTC.

Minimally Invasive Open Bilateral Total Thyroidectomy Using Unilateral Neck Incision in Thyroid Cancer: Preliminary Surgical and Quality of Life Outcomes.

PURPOSE: Thyroid cancer incidence has increased in recent decades, and thyroid surgery is continuously evolving in response to demands for postoperative comfort and cosmesis. This study aimed to introduce a new surgical method for minimally invasive open bilateral total thyroidectomy (MI-BTT) using a unilateral 2.5-3.0 cm neck incision. Furthermore, we reported the surgical outcomes and postoperative quality of life (QoL) using a validated Korean translated Dermatology Life Quality Index (DLQI) questionnaire. MATERIALS AND METHODS: We retrospectively evaluated 41 Asian patients who underwent MI-BTT for low-risk papillary thyroid cancer by a single surgeon from March 2019 to December 2021. RESULTS: A total of 4 male and 37 female patients were included. The mean age and body mass index were 46.2±10.1 years and 23.3±3.3 kg/m², respectively. The average tumor size was 1.1±0.6 cm, and 36 patients (87.8%) had bilateral cancer. Twenty-three (56.1%) patients had occult central lymph node (CLN) metastasis in the final pathologic report, with the mean number of dissected CLNs being 7.2±6.5. Gross capsular extension was found in 6 patients (14.6%). Moreover, 28 patients (68.3%) received additional treatment after surgery with low or high doses of radioactive iodine. The average serum-stimulated thyroglobulin value identified during treatment was 1.57±2.30 ng/mL. The mean operation time was 78.0±13.9 minutes, and postoperative complications included transient hypocalcemia (36.6%), transient hoarseness (24.4%), and seroma (2.4%). The mean total DLQI score was 2.73±0.78, indicating a small effect on QoL. CONCLUSION: MI-BTT is a novel, safe, and feasible technique to improve patient satisfaction for surgical scars and QoL.