Predicting central cervical lymph node metastasis in papillary thyroid carcinoma with Hashimoto's thyroiditis: a practical nomogram based on retrospective study.

Background: In papillary thyroid carcinoma (PTC) patients with Hashimoto's thyroiditis (HT), preoperative ultrasonography frequently reveals the presence of enlarged lymph nodes in the central neck region. These nodes pose a diagnostic challenge due to their potential resemblance to metastatic lymph nodes, thereby impacting the surgical decision-making process for clinicians in terms of determining the appropriate surgical extent. Methods: Logistic regression analysis was conducted to identify independent risk factors associated with central lymph node metastasis (CLNM) in PTC patients with HT. Then a prediction model was developed and visualized using a nomogram. The stability of the model was assessed using ten-fold cross-validation. The performance of the model was further evaluated through the use of ROC curve, calibration curve, and decision curve analysis. Results: A total of 376 HT PTC patients were included in this study, comprising 162 patients with CLNM and 214 patients without CLNM. The results of the multivariate logistic regression analysis revealed that age, Tg-Ab level, tumor size, punctate echogenic foci, and blood flow grade were identified as independent risk factors associated with the development of CLNM in HT PTC. The area under the curve (AUC) of this model was 0.76 (95% CI [0.71-0.80]). The sensitivity, specificity, accuracy, and positive predictive value of the model were determined to be 88%, 51%, 67%, and 57%, respectively. Conclusions: The proposed clinic-ultrasound-based nomogram in this study demonstrated a favorable performance in predicting CLNM in HT PTCs. This predictive tool has the potential to assist clinicians in making well-informed decisions regarding the appropriate extent of surgical intervention for patients.

Risk factors for mediastinal lymph node metastasis and lung metastasis in papillary thyroid carcinoma patients: who benefits from preoperative computed tomography?

In papillary thyroid carcinoma (PTC) patients with mediastinal lymph nodes (LN) and lung metastases, adding preoperative computed tomography (CT) to ultrasound is useful for planning surgery. We identified risk factors (RFs) for mediastinal lymph node metastasis (MLNM) and lung metastasis in PTC patients. Frequencies of MLNM and lung metastases were compared in 478 patients. Relative risk (RR) was calculated based on RFs. MLNM and lung metastases were detected in 1.2% and 3.3% of patients, respectively. cT3-4, cN1, central LN metastasis, and lateral LN metastasis were RFs for MLNM in all patients (p < 0.05, p < 0.05, p < 0.05, p < 0.01) and older patients (age: ≥55 years) (p < 0.01, p < 0.05, p < 0.05, p < 0.05). cT3-4, cN1, gross extrathyroidal extension, central LN metastasis, and lateral LN metastasis were RFs for lung metastasis in all patients (p < 0.01, p < 0.05, p < 0.01, p < 0.01, p < 0.01, respectively). cN1 and gross extrathyroidal extension, central LN metastasis, and lateral LN metastasis were RFs in older patients (p < 0.01, p < 0.01, p < 0.05, p < 0.01), while lateral LN metastasis was an RF for lung metastasis in those of <55 years of age (younger patients) (p < 0.05). No MLNM was observed in cT1-2cN0 PTC patients, who accounted for 50.5% of patients included in the MLNM analysis. No lung metastasis was present in cT1-2cN0 PTC patients, who accounted for 50.5% of the patients included in the lung metastasis analysis. PTC patients with cT3-4 and cN1 have an increased risk of MLNM and lung metastasis. RFs differed between older and younger patients. Preoperative neck and chest CT are not necessary for PTC patients with ultrasound-diagnosed as cT1-2cN0.

Construction and validation of a nomogram for predicting cervical lymph node metastasis in diffuse sclerosing variant of papillary thyroid carcinoma.

OBJECTIVE: To analyze the risk factors associated with the occurrence of cervical lymph node metastasis (LNM) in patients with diffuse sclerosing variant of papillary thyroid carcinoma (DSV-PTC) and to establish a nomogram model. METHODS: Clinical data of 199 DSV-PTC patients from SEER database were obtained, and they were randomly divided into training group (n=139) and validation group (n=60). The clinicopathological characteristics were analyzed by logistic regression, including age, marital status, race, gender, tumor size(cm), T stage, M stage, bilaterality, capsular invasion, extrathyroidal extension (ETE), and multifocality. The Validation was carried out using C-index, calibration curves, and Decision Curve Analysis (DCA) in terms of differentiation and calibration of the nomogram model, respectively. RESULTS: Age, tumor size(cm), capsular invasion, and multifocality were independent risk factors for the development of LNM in patients with DSV-PTC (P<0.05). In the training and validation groups, the C-index of internal validation of the nomogram was 0.808 (95%CI: 0.733-0.755) and 0.813 (95% CI: 0.591-0.868), the calibration curves showed that the model was in good agreement, and the decision curve (DCA) indicated that the nomogram model had good clinical utility.  CONCLUSION: Age, tumor size(cm), capsular invasion, and multifocality are independent risk factors for the development of LNM in DSV-PTC. The nomogram model can predict the risk of developing LNM in DSV-PTC patients and provide clinical guidance.

Factors of Central Lymph Node Metastasis in Papillary Thyroid Cancer Based on C-TIRADS Analysis.

To study risk factors for central lymph node metastasis (CLNM) in papillary thyroid cancer (PTC) using the Chinese Thyroid Imaging Reporting and Data System (C-TIRADS). We retrospectively analysed patients who underwent PTC surgery and central lymph node dissection at First People's Hospital of Foshan City. The clinical and ultrasonic data of the patients from 1150 cases were analysed by multivariate regression to evaluate the correlation between grayscale ultrasound (US) features, C-TIRADS score, and the classification of thyroid nodules and CLNM of PTCs. The C-TIRADS score was 3.0±1.0 in the CLNM group, which was higher than that in the non-CLNM group (p<0.001). Sex (male) (OR=1.586, 95% CI 1.232-2.042, p<0.001), age (≤45 years) (OR=1.508, 95% CI 1.184-1.919, p=0.001), location of nodes (lower pole) (OR=2.193, 95% CI 1.519-3.166, p<0.001), number (multifocal) (OR=2.204, 95% CI 1.227-2.378, p<0.001), microcalcification (OR=1.610, 95% CI 2.225-4.434, p=0.002), extrathyroidal extension (OR=2.204, 95% CI 1.941-3.843, p<0.001), maximum diameter of nodule (≥20 mm) (OR=3.211, 95% CI 2.337-4.411, p<0.001), and C-TIRADS score (OR=1.356, 95% CI 1.204-1.527, p<0.001) were PTC in independent risk factors for CLNM. The C-TIRADS score of PTC combined with the location, number, size, and ultrasound features of the lesion and the patient's sex and age are important in predicting whether they present with CLNM and provide a reference basis for the clinical formulation of a reasonable surgical treatment plan.

Nomogram for preoperative estimation risk of lateral cervical lymph node metastasis in papillary thyroid carcinoma: a multicenter study.

BACKGROUND: Lateral lymph node metastasis (LLNM) is frequent in papillary thyroid carcinoma (PTC) and is associated with a poor prognosis. This study aimed to developed a clinical-ultrasound (Clin-US) nomogram to predict LLNM in patients with PTC. METHODS: In total, 2612 PTC patients from two hospitals (H1: 1732 patients in the training cohort and 578 patients in the internal testing cohort; H2: 302 patients in the external testing cohort) were retrospectively enrolled. The associations between LLNM and preoperative clinical and sonographic characteristics were evaluated by the univariable and multivariable logistic regression analysis. The Clin-US nomogram was built basing on multivariate logistic regression analysis. The predicting performance of Clin-US nomogram was evaluated by calibration, discrimination and clinical usefulness. RESULTS: The age, gender, maximum diameter of tumor (tumor size), tumor position, internal echo, microcalcification, vascularization, mulifocality, and ratio of abutment/perimeter (A/P) > 0.25 were independently associated with LLNM metastatic status. In the multivariate analysis, gender, tumor size, mulifocality, position, microcacification, and A/P > 0.25 were independent correlative factors. Comparing the Clin-US nomogram and US features, Clin-US nomogram had the highest AUC both in the training cohort and testing cohorts. The Clin­US model revealed good discrimination between PTC with LLNM and without LLNM in the training cohort (AUC = 0.813), internal testing cohort (AUC = 0.815) and external testing cohort (AUC = 0.870). CONCLUSION: Our findings suggest that the ClinUS nomogram we newly developed can effectively predict LLNM in PTC patients and could help clinicians choose appropriate surgical procedures.

Can pre-operative ultrasound elastography predict aggressive features of solitary papillary thyroid carcinoma?

OBJECTIVE: To investigate whether pre-operative ultrasound elastography (USE) can be used to predict aggressive features of solitary papillary thyroid carcinomas (PTCs). METHODS: Clinical and USE indices were retrospectively analyzed in 487 patients with surgically confirmed solitary PTCs. The patients were grouped per aggressive features on pathologic testing. Univariate and binary logistic regression analyses were performed to explore independent risk factors of aggressive features. RESULTS: Univariate analysis revealed standard deviation (SD) values of the tumor shear-wave velocity (SWV) were associated with capsular invasion (p < 0.05). Further, shear-wave elasticity and SWV ratios correlated with extrathyroidal extension (all p < 0.05). The tumor shear-wave elasticity and SWV SD values were associated with cervical lymph node metastasis (CLNM) (all p < 0.05). Binary logistic regression analysis identified location and capsule contact as independent predictive risk factors for capsular invasion (all p < 0.05); size for extrathyroidal extension (all p < 0.05); and sex, age, margin, and suspected CLNM for CLNM (all p < 0.05). However, pre-operational USE indexes were not independent predictors of aggressive features (all p > 0.05). CONCLUSION: Pre-operative USE indices were not independent risk factors of aggressive features of solitary PTCs. Thus, USE may have a limited value for predicting the aggressive features of PTC. ADVANCES IN KNOWLEDGE: Pre-operative USE indices may have a limited value for predicting the aggressive features of PTC.

Central and lateral neck involvement in papillary thyroid carcinoma patients with or without thyroid capsular invasion: A multi-center analysis.

Purposes: To quantitatively predict the probability of cervical lymph node metastasis for papillary thyroid carcinomas (PTC) patients with or without thyroid capsular invasion (TCI), to guide the decision-making of management strategies for neck regions. Methods: A total of 998 PTC patients from three medical centers were retrospectively analyzed. Results: Patients with positive TCI (TCI group) exhibited higher risks for both CLNM and LLNM than those with negative TCI (no-TCI group). Patients receiving lateral lymph node dissection showed significantly higher incidence of relatively severe postoperative complications. For no-TCI group, factors including age less than 55 years old, male, the presence of bilateral disease and multifocality, and maximum tumor diameter (MTD)>=0.5cm were confirmed to be independent risk factors for CLNM, while the presence of bilateral disease and ipsilateral nodular goiter (iNG), and maximum positive CLN diameter (MCLND)>1.0cm independent factors for LLNM. Independent risk factors of LLNM for patients within the TCI group included MCLND>1.0cm, positive CLN number>=3, and the presence of iNG. Predictive models of CLNM and LLNM were established based on the aforementioned risk factors for patients within no-TCI and TCI groups. A meticulous and comprehensive risk stratification flow chart was established for a more accurate evaluation of central neck involvement including both CLNM and LLNM risk in PTC patients. Conclusions: A meticulous and comprehensive stratification flow chart for PTC patients for quantitatively evaluating both CLNM and LLNM was constructed.

Nomogram for predicting skip metastasis in cN0 papillary thyroid cancer patients at increased risk of lymph node metastasis.

BACKGROUND: Skip lymph node metastasis (SLNM) refers to lateral lymph node metastasis (LLNM) without involving central lymph node (CLN). Some microscopic nodal positivity may be difficult to detect before surgery due to atypical imaging characteristics. These patients are misdiagnosed as having clinically node-negative (cN0) papillary thyroid cancer (PTC) even after central lymph node dissection, leading to a high risk of developing LNM after surgery. Current prediction models have limited clinical utility, as they are only applicable to predict SLNM from clinically node-positive (cN+) PTC, not cN0 PTC, and this has little impact on treatment strategies. OBJECTIVES: This study aimed to establish a nomogram for preoperatively assessing the likelihood of SLNM in cN0 PTC patients with increased risk of LNM, thus optimizing their therapeutic options. MATERIAL AND METHODS: The records of 780 PTC patients undergoing thyroidectomy along with bilateral central lymph node dissection were retrospectively reviewed. The cN0 patients with postoperative LLNM (occult SLNM) and cN+ patients without central lymph node metastasis (CLNM) (typical SLNM) were included in the SLNM group (n = 82). The CLNM-negative cN0 patients without postoperative LLNM were assigned to the non-SLNM group (n = 698). The independent correlates of SLNM constituted the nomogram for determining the likelihood of SLNM in high-risk cN0 PTC patients. RESULTS: The independent correlates of SLNM were age (hazard ratio (HR) = 1.016), tumor location (HR = 1.801), tumor size (HR = 1.528), and capsular invasion (HR = 2.941). They served as components in the development of the nomogram. This model was verified to present acceptable discrimination. It showed good calibration and a decent net benefit when the predicted probability was <60%. CONCLUSIONS: We developed a nomogram incorporating preoperative clinical data to predict the probability of SLNM development in high-risk cN0 PTC patients, which contributed to their optimized treatment options.

Predicting papillary thyroid carcinoma cervical lymph node metastases: an algorithm using the American College of Radiology Thyroid Imaging, Reporting and Data System.

BACKGROUND: It is important to predict lymph node metastasis (LNM) in papillary thyroid carcinoma (PTC) preoperatively; however, the relationship between the American College of Radiology Thyroid Imaging, Reporting and Data System (ACR TI-RADS) score and cervical LNM remains unclear. PURPOSE: To evaluate the association between the ACR TI-RADS score and cervical LNM in patients with PTC. MATERIAL AND METHODS: This retrospective study consisted of 474 patients with 548 PTCs. Cervical LNM including central LNM (CLNM) and lateral LNM (LLNM) were confirmed by pathology. Univariate and multivariate analyses were performed to investigate the risk factors of CLNM and LLNM. RESULTS: Multivariate logistic regression analyses indicated that younger age and multifocality were risk factors for CLNM in PTCs with TR5. In addition, younger age, larger tumor size, and Hashimoto's thyroiditis (HT) were risk factors for LLNM in PTCs ≥ 10 mm with TR5. In PTCs with TR4, ACR TI-RADS scores 5-6 conferred risks for LNM. In PTCs ≥ 10 mm with TR5, ACR TI-RADS scores ≥9 were risk factors for LLNM. CONCLUSION: A higher ACR TI-RADS score is a predictor for cervical LNM in PTCs with TR4 and PTCs ≥ 10 mm with TR5.

Prospective application of a prediction model for lateral lymph node metastasis in papillary thyroid cancer patients with central lymph node metastasis.

Objective: This study aimed to develop and apply a prediction model to estimate the probability of lateral lymph node metastasis (LLNM) in patients with cN0 unilateral papillary thyroid carcinoma (PTC) with central lymph node metastasis (CLNM). Setting: All study data were collected from a single tertiary hospital. Methods: Univariable and multivariable logistic regression analyses were used to explore independent predictors of LLNM in the derivation and internal validation cohorts, which were used to construct and validate a nomogram. Another 96 patients were included prospectively to evaluate the efficacy of this nomogram. Results: Maximum tumor diameter greater than 1.0 cm (OR, 2.712; 95% CI, 1.412-5.210), multifocality (OR, 2.758; 95% CI, 1.120-6.789), the number of CLNM ≥3 (OR, 2.579; 95% CI, 1.315-5.789), CLNM ratio ≥0.297 (OR, 2.905; 95% CI, 1.396-6.043), and tumors located in the upper portion (OR 2.846, 95% CI 1.151-7.039) were independent predictors associated with LLNM. The prediction model showed excellent discrimination with an AUC of 0.731 (95% CI, 0.635-0.827). Novel risk stratification for LLNM was constructed based on this nomogram. In the prospective cohort, we stratified these patients into three risk subgroups: low-, moderate-, and high-risk subgroups and we found that the probability of LLNM was positively correlated with the total points from the nomogram. Conclusion: This nomogram was applied in prospective clinical practice and distinguished PTC patients with a genuinely high risk of LLNM. Surgeons can use our nomogram to tailor the surgical plan and to credibly determine further postoperative therapy.

Meta-analysis of the effect and clinical significance of Delphian lymph node metastasis in papillary thyroid cancer.

Objective: To investigate the effect and clinical significance of Delphian lymph nodes (DLN) on the factors influencing papillary thyroid cancer (PTC) to provide individualized guidance for the surgical treatment of thyroid cancer. Methods: Relevant studies from PubMed, Web of Science, the Cochrane Library, Embase, and China National Knowledge Infrastructure databases were searched until February 13, 2023. Stringent selection parameters were used to obtain included data and homogeneous articles. Analyses were performed using Revman 5.4 and SPSS software. A P-value of < 0.05 was considered statistically significant. Results: Five studies were finally included in this study. The results revealed a higher risk of DLN metastasis (DLNM) in patients with tumor size >1cm, multifocality, and extrathyroidal extension (ETE) of the thyroid. The risk of central lymph node metastasis (CLNM) was 11.25 times higher in DLN-positive patients with PTC than in DLN-negative (OR = 11.25, 95% CI: 8.64-14.64, P < 0.05) patients. The risk of LLNM was 5.57 times higher in DLN-positive patients with PTC than in DLN-negative (OR = 5.57, 95% CI: 4.57-6.78, P < 0.001) patients. The risk of postoperative recurrence in DLN-positive patients with PTC was 3.49 times higher (OR = 3.49, 95% CI: 1.91-6.38, P < 0.001) than in DLN-negative patients with PTC. Conclusion: Patients with tumor size >1 cm in diameter, multifocality, and ETE have an increased risk for DLN development. DLN-positive patients with central and lateral cervical lymph node metastasis and postoperative recurrence are at higher risk than DLN-negative patients.

Blood immune indexes can predict lateral lymph node metastasis of thyroid papillary carcinoma.

Objective: To explore the clinical significance of blood immune indexes in predicting lateral lymph node metastasis (LLNM) of thyroid papillary carcinoma (PTC). Methods: The pathological data and preoperative blood samples of 713 patients that underwent thyroid surgery at affiliated Hangzhou First People's Hospital Zhejiang University School of Medicine from January 2013 to June 2021 were collected as the model group. The pathological data and preoperative blood samples of 177 patients that underwent thyroid surgery in the same hospital from July 2021 to October 2021 were collected as the external validation group. Univariate and multivariate logistic regression analyses were used to determine the independent risk factors of LLNM in PTC patients. A predictive model for assessing LLNM in PTC patients was established and externally validated using the external data. Results: According to univariate and multivariate logistic regression analyses, tumor diameter (P < 0.001, odds ratios (OR): 1.205, 95% confidence interval (CI): 1.162-1.249) and the preoperative systemic immune-inflammation index (SII) (P = 0.032, OR: 1.001, 95% CI: 1.000-1.002) were independent risk factors for distinguishing LLNM in PTC patients. When the Youden index was the highest, the area under the curve (AUC) was 0.860 (P < 0.001, 95% CI: 0.821-0.898). The externally validated AUC was 0.827 (P < 0.001, 95% CI: 0.724-0.929), the specificity was 86.4%, and the sensitivity was 69.6%. The calibration curve and the decision curve indicated that the model had good diagnostic value. Conclusion: Blood immune indexes can reflect the occurrence of LLNM and the biological behavior of PTC. The predictive model established in combination with SII and tumor diameter can effectively predict the occurrence of LLNM in PTC patients.

Extreme gradient boosting model to assess risk of central cervical lymph node metastasis in patients with papillary thyroid carcinoma: Individual prediction using SHapley Additive exPlanations.

BACKGROUND AND OBJECTIVES: Central cervical lymph node metastasis (CLNM) is considered a risk factor for recurrence in patients with papillary thyroid carcinoma (PTC). Traditional machine learning models suffered from "black-box" problems, which could not exactly explain the interactive effects of the risk factors. We aimed to develop an eXtreme Gradient Boosting (XGBoost) model to assess CLNM, including positive and negative effects. METHODS: 1,122 patients with PTC admitted at Tianjin First Central Hospital from 2016 to 2020 were retrospectively selected. They were randomly divided into the training and test datasets with an 8:2 ratio. 108 patients with PTC admitted at Binzhou Medical University Hospital in 2020 served as the validation dataset. The XGBoost model was used to assess CLNM. The 10-fold cross-validation was utilized for model selection, and the metric used to evaluate classification performance was the average area under the curve (AUC) of 10-fold cross-validation. Interpretation and transparency of the "black-box" problem were performed. SHapley Additive exPlanations (SHAP) and local interpretable model-agnostic explanation (LIME) were used to ensure the stability and reliability of the model. RESULTS: The XGBoost model based on ultrasound and dual-energy computed tomography images of the solitary primary lesion had an excellent performance for assessing CLNM, with average AUCs of 0.918, 0.903, and 0.881 in the training, test, and validation datasets, respectively. SHAP plots showed the influence of each parameter on the XGBoost model, including positive (i.e., capsular invasion, diameter, iodine concentration in the venous phase, and calcification) and negative (i.e., sex and age) impacts. For all cases, the capsular invasion prediction weight was the highest; for individual cases, different predictors were assigned different weights. Moreover, the performance of the XGBoost model was better than classical machine-learning models. CONCLUSIONS: This study developed and validated an XGBoost model for assessing CLNM in patients with PTC. The ability to visually interpret the positive and negative effects made the XGBoost model an effective tool for guiding clinical treatment.

Surgical treatment of pediatric and adolescent papillary thyroid cancer: a retrospective study of 54 patients in a single center.

OBJECTIVE: In 2015, American Thyroid Association (ATA) issued the first version of Management Guidelines for Children with Thyroid Nodules and Differentiated Thyroid Cancer. The purpose of this study is to evaluate whether the ATA pediatric guidelines recommended surgical approach for the patient can be applied to surgical treatment of pediatric PTC in China. METHOD: From April 2012 to December 2020, clinical data of children (≤18 years) with PTC consecutively admitted and treated with initial surgery in the study's department were retrospectively reviewed. RESULTS: The authors found that the central lymph node metastasis (CLNM) rate was significantly higher than that in the lateral neck (83.33 % vs 62.96%, χ2 = 5.704, p = 0.017) .The lymph node metastasis rate was significantly lower in cN1b (-) patients than in cN1b (+) patient (55.00% vs 100.00%, χ2 = 15.263, p = 0.000); Meanwhile, the CLNM and LLNM rates of ipsilateral were significantly higher than those of contralateral central compartment (83.33༅vs 57.41༅%, χ2 = 8.704, p = 0.003). Lymph nodes of 51 lateral lymph node dissection (LND) were analyzed, which revealed the LNM rate of cN1b (-) patients was significantly lower than that of cN1b (+) patients (55.00% vs. 100.00%, χ2 = 15.263, p = 0.000). CONCLUSION: Children and adolescents have a higher rate of lymph node metastasis at the time of diagnosis. TT should be conducted in the majority of children with PTC. CND should be routinely performed; therapeutic LND is recommended for children with cN1b (+).

Level IIb neck dissection guided by fine-needle aspiration for N1b papillary thyroid carcinoma.

BACKGROUND: The extent of neck dissection for patients with papillary thyroid carcinoma (PTC) metastasis in lateral cervical lymph nodes is still debated. Studies aiming to omit level IIb were generally based on postoperative histopathologic information. The purpose of this study was to evaluate the predictive value of fine-needle aspiration (FNA) for level II lymph nodes in identifying candidates for neck dissection sparing level IIb before surgery. METHODS: We prospectively enrolled 156 consecutive previously untreated PTC patients with lateral neck metastases who were subjected to 178 therapeutic lateral neck dissections (including level IIa, IIb, III, IV, and Vb) between June 2018 and August 2021. Ultrasound-guided FNA of suspicious lymph nodes at level II was preoperatively performed. The cytology of FNA and thyroglobulin (Tg) washout concentration with other clinical predictors was analyzed for lymph node metastases at level IIb. RESULTS: Preoperative ultrasonography revealed suspicious lymph nodes at level II in 118 cases, and fifty were positive on FNA results. Metastasis at level IIb was seen in 17 (9.6%) of the postoperative specimens. By univariate analysis, the rate of level IIb metastasis was significantly higher in patients with FNA-positive lymph nodes at level II (P<0.001, odds ratio = 16.899). The tumor sizes of the two FNA-negative level IIb metastatic lymph nodes were 0.4 mm and 3 mm. CONCLUSIONS: Level IIb lymph node dissection may be omitted in the treatment of N1b PTC patients if FNA to level II lymph nodes is negative.

Spinal metastases from thyroid cancer: Some prognostic factors.

BACKGROUND: Spinal metastases (SpMs) from thyroid cancers (TC) significantly reduce quality of life by causing pain, neurological deficits in addition to increasing mortality. Moreover, prognosis factors including surgery remain debated. METHODS: Data were stored in a prospective French national multicenter database of patients treated for SpM between January 2014 and 2017. Fifty-one consecutive patients affected by TC with 173 secondary SpM were included. RESULTS: Mean overall survival (OS) time for all patients from the diagnosis of a thyroid SpM event was 9.1 years (SD 8.7 months). The 1-year, 5-year and 10-year survival estimates were 94% (SD 3.3), 83.8.0% (SD 5.2), and 74.5% (SD 9.9). The median period of time between primary thyroid tumor diagnosis and the SpM event was 31.4 months (SD 71.6). In univariate analysis, good ECOG-PS (status 0 and 1) (p < 0.0001), ambulatory status (Frankel score) (p < 0.0001) and no epidural involvement (p = 0.01), were associated with longer survival, whereas cancer subtype (p = 0.436) and spine surgery showed no association (p = 0.937). Cox multivariate proportional hazard model only identified good ECOG-PS: 0 [HR: 0.3, 95% CI 0.1-0.941; p < 0.0001], 1 [HR: 0.8, 95% CI 0.04-2.124; p = 0.001] and ambulatory neurological status: Frankel E [HR: 0.262, 95% CI 0.048-1.443; p = 0.02] to be independent predictors of better survival. CONCLUSION: For cases presenting SpM from TC, we highlighted that the only prognostic factors were the progression of the cancer (ECOG-PS) and the clinical neurological impact of the SpM (Frankel status). Surgery should be discussed mainly for stabilization and neurological decompression.

Prevalence of cystic metastases in a consecutive cohort of surgically removed branchial cleft cysts.

BACKGROUND: Solitary cystic lesion of the neck may often be the only initial presenting symptom for branchial cleft cysts and cystic metastases. AIMS/OBJECTIVES: To analyse the malignancy rate detected in patients undergoing surgical treatment for lateral branchial cleft cyst. MATERIAL AND METHODS: The records of all patients with surgical procedure code ENB40 (Excision of lateral branchial cleft cyst- or fistula) between 2003 and 2019 were reviewed. After excluding 150 patients, 436 patients were included for final analysis. Re-evaluation of the cytology including HPV-analysis was performed in those who had a malignant cyst. RESULTS: Cystic metastases were demonstrated histologically after surgical excision in 13 patients (3%). In patients over 18 years of age, the prevalence of cystic metastasis regardless of the primary tumour type was 3.3%. CONCLUSION AND SIGNIFICANCE: When the investigation protocol for solitary cystic lesions of the neck is followed, the negative predictive value for malignancy is 97%. All adult patients with a cytologic verified diagnosis of branchial cyst should be examined with HPV-analysis of the cystic sample before excision of the cyst. Failure of predicting a malignancy is often associated with cytology of poor cellularity which may be improved by more frequent use of ultrasound guided fine-needle aspiration cytology (FNAC).

Capsular extension at ultrasound is associated with lateral lymph node metastasis in patients with papillary thyroid carcinoma: a retrospective study.

BACKGROUND: In patients with papillary thyroid cancer (PTC), cervical lymph node metastasis (LNM) must be carefully assessed to determine the extent of lymph node dissection required and patient prognosis. Few studies attempted to determine whether the ultrasound (US) appearance of the primary thyroid tumor could be used to predict cervical lymph node involvement. This study aimed to identify the US features of the tumor that could predict cervical LNM in patients with PTC. METHODS: This was a retrospective study of patients with pathologically confirmed PTC. We evaluated the following US characteristics: lobe, isthmus, and tumor size; tumor position; parenchymal echogenicity; the number of lesions (i.e., tumor multifocality); parenchymal and lesional vascularity; tumor margins and shape; calcifications; capsular extension; tumor consistency; and the lymph nodes along the carotid vessels. The patients were grouped as no LNM (NLNM), central LNM (CLNM) alone, and lateral LNM (LLNM) with/without CLNM, according to the postoperative pathological examination. RESULTS: Totally, 247 patients, there were 67 men and 180 women. Tumor size of > 10 mm was significantly more common in the CLNM (70.2%) and LLNM groups (89.6%) than in the NLNM group (45.4%). At US, capsular extension > 50% was most common in the LLNM group (35.4%). The multivariable analysis revealed that age (OR = 0.203, 95%CI: 0.095-0.431, P < 0.001) and tumor size (OR = 2.657, 95%CI: 1.144-6.168, P = 0.023) were independently associated with CLNM compared with NLNM. In addition, age (OR = 0.277, 95%CI: 0.127-0.603, P = 0.001), tumor size (OR = 6.069, 95%CI: 2.075-17.75, P = 0.001), and capsular extension (OR = 2.09, 95%CI: 1.326-3.294, P = 0.001) were independently associated with LLNM compared with NLNM. CONCLUSION: Percentage of capsular extension at ultrasound is associated with LLNM. US-guided puncture cytology and eluent thyroglobulin examination could be performed as appropriate to minimize the missed diagnosis of LNM.

Risk Factors and a Prediction Model of Lateral Lymph Node Metastasis in CN0 Papillary Thyroid Carcinoma Patients With 1-2 Central Lymph Node Metastases.

Background: Papillary thyroid cancer (PTC) in clinically lymph node-negative (cN0) patients is prone toward lymph node metastasis. As a risk factor for tumor persistence and local recurrence, lateral lymph node metastasis (LLNM) is related to the number of central lymph node metastases (CLNMs). Methods: We performed LLNM risk stratification based on the number of CLNMs for cN0 PTC patients who underwent thyroidectomy and lymph node dissection between January 2013 and December 2018. A retrospective analysis was applied to the 274 collected patients with 1-2 CLNMs. We examined the clinicopathological characteristics of the patients and constructed a LASSO model. Results: In the 1-2 CLNM group, tumors >10 mm located in the upper region and nodular goiters were independent risk factors for LLNM. Specifically, tumors >20 mm and located in the upper region contributed to metastasis risk at level II. Hashimoto's thyroiditis reduced this risk (p = 0.045, OR = 0.280). Age ≤ 30 years and calcification (microcalcification within thyroid nodules) correlated with LLNM. The LASSO model divided the population into low- (25.74%) and high-risk (57.25%) groups for LLNM, with an AUC of 0.715. Conclusions: For patients with 1-2 CLNMs, young age, calcification, nodular goiter, tumor >10 mm, and tumor in the upper region should alert clinicians to considering a higher occult LLNM burden. Close follow-up and therapy adjustment may be warranted for high-risk patients.

TFE3 Regulates the Function of the Autophagy-Lysosome Pathway to Drive the Invasion and Metastasis of Papillary Thyroid Carcinoma.

BACKGROUND: Accumulating evidence shows that autophagy plays a vital role in tumor occurrence, development, and metastasis and even determines tumor prognosis. However, little is known about its role in papillary thyroid carcinoma (PTC) or the potentially oncogenic role of TFE3 in regulating the autophagy-lysosome system. METHODS: Immunohistochemistry and quantitative real-time PCR (qRT-PCR) were used to examine the expression of TFE3, P62/SQSTM1, and LC3 in PTC and paracancerous tissues. TFE3, P62/SQSTM1, LC3, cathepsin L (CTSL), and cathepsin B (CTSB) were evaluated using Western blot analysis. After inducing TFE3 overexpression by plasmid or TFE3 downregulation by small interfering RNA (siRNA) transfection, MTT, wound healing, and cell migration and invasion assays were used to verify the effects on invasion, migration, and the levels of autophagy-lysosome system-related proteins such as P62/SQSTM1, LC3, CTSL, and CTSB. RESULTS: TFE3 was overexpressed in PTC tissues compared with paracancerous tissues. Analysis of the clinicopathological characteristics of PTC patients showed that high TFE3 expression was significantly correlated with lymph node metastasis. TFE3 overexpression in the PTC cell lines KTC-1 and BCPAP promoted proliferation, invasion, and migration, while TFE3 knockdown had the opposite effects. Furthermore, we identified a positive relationship among the expression levels of TFE3, P62/SQSTM1, LC3, CTSL, and CTSB. We found that silencing TFE3 inhibited the expression of P62/SQSTM1, LC3, CTSL, and CTSB in PTC cells. However, TFE3 overexpression had the opposite effects. CONCLUSIONS: The present study provided evidence for the underlying mechanisms by which TFE3 induces autophagy-lysosome system activity in PTC.