Extrathyroidal Extension In Papillary Thyroid Carcinoma Research Articles

Can texture analysis of T2-weighted MRI be used to predict extrathyroidal extension in papillary thyroid carcinoma?

Determining the presence of extrathyroidal extension (ETE) is important for established of different surgical protocol and postoperative patient management in patients with papillary thyroid carcinoma (PTC). The correlation relationship between texture features from T2-weighted imaging (T2WI) and ETE has not been explored extensively. This study aimed to explore the value of T2-weighted magnetic resonance imaging - based whole tumor texture analysis in predict extrathyroidal extension with PTC. In this retrospectively study, 76 patients with pathologically proven PTC were recruited, who received surgical resection and underwent preoperative thyroid magnetic resonance imaging. Based on histo-pathologically findings, patients were classified into ETE and no ETE groups. ETE group was further divided into 2 subgroups (minimal ETE and extensive ETE). Whole-tumor texture analysis was independently performed by 2 radiologists on axial T2WI images. Nine histogram and gray-level co-occurrence matrix (GLCM) texture features were automatically extracted. Univariate and multivariate analysis were performed to determine risk factors associated with ETE. Predictive performance was evaluated by receiver operating characteristic (ROC) analysis. Interobserver agreement, confirmed by intraclass correlation coefficients (ICCs) ranging from 0.78 to 0.89, was excellent for texture analysis between 2 radiologists. T2WI image derived entropy, standard deviation, energy and correlation have significant difference between PTC with and without ETE (all P < .05). Among these, entropy showed the best diagnostic efficiency with the area under ROC curve of 0.837, diagnostic threshold of 5.86, diagnostic sensitivity and specificity of 81.5% and 75.6%, respectively. Additionally, the multivariate analysis revealed that high entropy was an independent risk factor of ETE (odds ratio, OR = 19.348; 95%CI, 4.578-81.760; P = .001). The findings indicate a significant association between texture features of the primary tumor based on T2WI and the presence of ETE in PTC. These results have the potential to help predict ETE preoperatively in patients with PTC, offering valuable insights for clinical decision-making.

Predicting Extrathyroidal Extension in Papillary Thyroid Carcinoma Using a Clinical-Radiomics Nomogram Based on B-Mode and Contrast-Enhanced Ultrasound.

Papillary thyroid carcinoma (PTC) is the most common pathological type of thyroid cancer. PTC patients with extrathyroidal extension (ETE) are associated with poor prognoses. The preoperative accurate prediction of ETE is crucial for helping the surgeon decide on the surgical plan. This study aimed to establish a novel clinical-radiomics nomogram based on B-mode ultrasound (BMUS) and contrast-enhanced ultrasound (CEUS) for the prediction of ETE in PTC. A total of 216 patients with PTC between January 2018 and June 2020 were collected and divided into the training set (n = 152) and the validation set (n = 64). The least absolute shrinkage and selection operator (LASSO) algorithm was applied for radiomics feature selection. Univariate analysis was performed to find clinical risk factors for predicting ETE. The BMUS Radscore, CEUS Radscore, clinical model, and clinical-radiomics model were established using multivariate backward stepwise logistic regression (LR) based on BMUS radiomics features, CEUS radiomics features, clinical risk factors, and the combination of those features, respectively. The diagnostic efficacy of the models was assessed using receiver operating characteristic (ROC) curves and the DeLong test. The model with the best performance was then selected to develop a nomogram. The results show that the clinical-radiomics model, which is constructed by age, CEUS-reported ETE, BMUS Radscore, and CEUS Radscore, showed the best diagnostic efficiency in both the training set (AUC = 0.843) and validation set (AUC = 0.792). Moreover, a clinical-radiomics nomogram was established for easier clinical practices. The Hosmer-Lemeshow test and the calibration curves demonstrated satisfactory calibration. The decision curve analysis (DCA) showed that the clinical-radiomics nomogram had substantial clinical benefits. The clinical-radiomics nomogram constructed from the dual-modal ultrasound can be exploited as a promising tool for the pre-operative prediction of ETE in PTC.

Optimal Cutoff Values of the Contact Angle of Tumor on Sonography System for Predicting Extrathyroidal Extension of Papillary Thyroid Carcinoma by Tumor Location.

Extrathyroidal extension (ETE) significantly affects the treatment strategy for thyroid cancer. We present a new method to predict ETE of papillary thyroid carcinoma (PTC). We enrolled 1 481 patients with PTCs. The ETE was classified into minimal and gross ETE. Using the novel "contact angle of the tumor on sonography" (CATS) system, we calculated optimal cutoffs for predicting ETE according to tumor location and compared the diagnostic performance to that of previous methods. The optimal cutoff angles for predicting anterior minimal and gross ETE were 41.5° and 49.4°, respectively, while those for posterior ETE were 39.8° and 54.6°, respectively. The optimal cutoff angle predicting tracheal ETE was 88.0°. The diagnostic performance was comparable to that of previous methods. The CATS method for predicting ETE is a valuable alternative.

A pilot study of radiomics signature based on biparametric MRI for preoperative prediction of extrathyroidal extension in papillary thyroid carcinoma.

To investigate efficiency of radiomics signature to preoperatively predict histological features of aggressive extrathyroidal extension (ETE) in papillary thyroid carcinoma (PTC) with biparametric magnetic resonance imaging findings. Sixty PTC patients with preoperative MR including T2WI and T2WI-fat-suppression (T2WI-FS) were retrospectively analyzed. Among them, 35 had ETE and 25 did not. Pre-contrast T2WI and T2WI-FS images depicting the largest section of tumor were selected. Tumor regions were manually segmented using ITK-SNAP software and 107 radiomics features were computed from the segmented regions using the open Pyradiomics package. Then, a random forest model was built to do classification in which the datasets were partitioned randomly 10 times to do training and testing with ratio of 1:1. Furthermore, forward greedy feature selection based on feature importance was adopted to reduce model overfitting. Classification accuracy was estimated on the test set using area under ROC curve (AUC). The model using T2WI-FS image features yields much higher performance than the model using T2WI features (AUC = 0.906 vs. 0.760 using 107 features). Among the top 10 important features of T2WI and T2WI-FS, there are 5 common features. After feature selection, the models trained using top 2 features of T2WI and the top 6 features of T2WI-FS achieve AUC 0.845 and 0.928, respectively. Combining features computed from T2WI and T2WI-FS, model performance decreases slightly (AUC = 0.882 based on all features and AUC = 0.913 based on top features after feature selection). Adjusting hyper parameters of the random forest model have negligible influence on the model performance with mean AUC = 0.907 for T2WI-FS images. Radiomics features based on pre-contrast T2WI and T2WI-FS is helpful to predict aggressive ETE in PTC. Particularly, the model trained using the optimally selected T2WI-FS image features yields the best classification performance. The most important features relate to lesion size and the texture heterogeneity of the tumor region.

Can Diffusion-Weighted MR Imaging Be Used as a Tool to Predict Extrathyroidal Extension in Papillary Thyroid Carcinoma?

To evaluate whether quantitative diffusion-weighted MR imaging (DWI) with multi-b values can be used as a tool to predict the aggressiveness by using the histological feature of extrathyroidal extension (ETE) in papillary thyroid carcinoma (PTC). 238 patients were pathologically confirmed as PTCs underwent preoperative multi-b value DWI (300, 500, and 800 s/mm2) between January 2015 and December 2017. The patients were divided into three groups according to the degree of ETE: without ETE, minimal ETE, and extensive ETE. The apparent diffusion coefficients (ADCs) were evaluated for three different b values (b = 300 s/mm2, b = 500 s/mm2, and b = 800 s/mm2). The ADC values of the groups with and without ETE, minimal and extensive ETE were compared. The diagnostic relevance of the ADC values in terms of predicting ETE was compared using a receiver operating characteristic analysis. Differences between the areas under the curves (AUCs) were compared by using a Delong test. PTCs with ETE had significantly lower ADC300, ADC500 and ADC800 values than PTCs without ETE (p = 0.001, p < 0.001, and p < 0.001, respectively). The AUC of the mean ADC500 value (0.905) was higher than that of the ADC300 and ADC800 values (0.607 and 0.770, respectively) in differentiating ETE from without ETE (p < 0.001). The cut-off value of ADC500 to discriminate PTCs with and without ETE was determined at 1.407 × 10-3 mm2/s, with sensitivity of 80.7%, specificity of 86.7%, and an AUC of 0.905. The ADC value can be demonstrated an effective tool for evaluating the aggressiveness with the histological feature of ETE in PTC. In particular, ADC value at b = 500 s/mm2 showed the best performance for noninvasive preoperative evaluation of ETE.

Transcriptomic signature associated with carcinogenesis and aggressiveness of papillary thyroid carcinoma.

Papillary thyroid carcinoma (PTC) is the fastest-growing disease caused by numerous molecular alterations in addition to previously reported DNA mutations. There is a compelling need to identify novel transcriptomic alterations that are associated with the pathogenesis of PTC with potential diagnostic and prognostic implications.Methods: We gathered and compared 242 expression profiles between paired PTC and adjacent normal tissues and identified and validated the coding and long non-coding RNAs (lncRNAs) associated with the extrathyroidal extension (ETE) of 655 PTC patients in two independent cohorts, followed by predicting their interactions with drugs. Co-expression, RNA interaction, Kaplan-Meier survival and multivariate Cox proportional regression analyses were performed to identify dysregulated lncRNAs and genes that correlated with clinical outcomes of PTC. Alternative splicing (AS), RNA circularization, and editing were also compared between transcriptomes to expand the repertoire of molecular alterations in PTC.Results: Numerous genes related to cellular microenvironment and steroid hormone response were associated with the ETE of PTC. Drug susceptibility predictions of the expression signature revealed two highly ranked compounds, 6-bromoindirubin-3'-oxime and lovastatin. Co-expression and RNA interaction analysis revealed the essential role of lncRNAs in PTC pathogenesis by modulating extracellular matrix and cell adhesion. Eight genes and two novel lncRNAs were identified that correlated with the aggressive nature and disease-free survival of PTC. Furthermore, this study provided the transcriptome-wide landscape of circRNAs in PTC and uncovered dissimilar expression profiles among circRNAs originating from the same host gene, suggesting the functional complexity of circRNAs in PTC carcinogenesis. The newly identified AS events in the SERPINA1 and FN1 genes may improve the sensitivity and specificity of these diagnostic biomarkers.Conclusions: Our study uncovered a comprehensive transcriptomic signature associated with the carcinogenesis and aggressive behavior of PTC, as well as presents a catalog of 10 potential biomarkers, which would facilitate PTC prognosis and development of new therapeutic strategies for this cancer.

Relationship between BRAF V600E mutation, cervical lymph node metastases and extrathyroidal extension in papillary thyroid carcinoma

Objective To explore the relationship between BRAF V600E mutation status as well as cervical lymph node metastases(CLNM) and clinical pathological features of papillary thyroid carcinoma (PTC). Methods The clinicopathologic data of 262 PTC patients who underwent thyroidectomy from January 2012 to December 2014 were retrospectively analyzed. All patients were performed ipsilateral cervical central compartment lymph node dissection and BRAF V600E mutation testing. Results Either BRAF V600E or CLNM positive status was associated with extra thyroidal extension of PTC, as compared with that in corresponding negative patients, respectively [BRAF V600E: 30.6% (45/147) vs. 10.4% (12/115), P<0.001; CLNM: 30.8% (37/120) vs. 14.1% (20/142), P=0.001]. Logistic regression analysis showed that PTC with BRAF V600E or CLNM was more prone to develop extra thyroidal extension, respectively (BRAF V600E: OR=5.02, 95% CI=1.56-16.13, P=0.007; CLNM: OR=3.94, 95% CI=1.07-14.46, P=0.039). The combined effect of BRAF V600E and CLNM for PTC was found to be more susceptible to extra thyroidal extension (OR=11.09, 95% CI=3.54-34.74, P<0.001). Conclusions Both BRAF V600E mutation and CLNM are significantly associated with extra thyroidal extension of PTC. PTC with BRAF V600E and CLNM has increased the risk of extra thyroidal extension. Key words: Papillary thyroid carcinoma; BRAF V600E; Cervical lymph node metastases; Extra thyroidal extension

Do Helper T Cell Subtypes in Lymphocytic Thyroiditis Play a Role in the Antitumor Effect?

BackgroundPapillary thyroid carcinoma (PTC) is frequently accompanied by lymphocytic thyroiditis (LT). Some reports claim that Hashimoto’s thyroiditis (the clinical form of LT) enhances the likelihood of PTC; however, others suggest that LT has antitumor activity. This study was aimed to find out the relationship between the patterns of helper T cell (Th) cytokines in thyroid tissue of PTC with or without LT and the clinicopathological manifestation of PTC. MethodsFresh surgical samples of PTC with (13 cases) or without (10 cases) LT were used. The prognostic parameters (tumor size, extra-thyroidal extension of PTC, and lymph node metastasis) were analyzed. The mRNA levels of two subtypes of Th cytokines, Th1 (tumor necrosis factor α [TNF-α], interferon γ [IFN-γ ], and interleukin [IL] 2) and Th2 (IL-4 and IL-10), were analyzed. Because most PTC cases were microcarcinomas and recent cases without clinical follow-up, negative or faint p27 immunoreactivity was used as a surrogate marker for lymph node metastasis. ResultsPTC with LT cases showed significantly higher expression of TNF-α (p = .043), IFN-γ (p < .010), IL-4 (p = .015) than those without LT cases. Although the data were not statistically significant, all analyzed cytokines (except for IL-4) were highly expressed in the cases with higher expression of p27 surrogate marker. ConclusionsThese results indicate that mixed Th1 (TNF-α, IFN-γ , and IL-2) and Th2 (IL-10) immunity might play a role in the antitumor effect in terms of lymph node metastasis.

Potential relationship between Hashimoto's thyroiditis and BRAF(V600E) mutation status in papillary thyroid cancer.

The purpose of this study was to evaluate the potential relationship between Hashimoto's thyroiditis and BRAF(V600E) mutation status in patients with papillary thyroid carcinoma (PTC). A total of 619 patients with PTC who underwent total thyroidectomy with lymph node dissection were enrolled in this study. Univariable and multivariate analyses were used. Hashimoto's thyroiditis was present in 35.9% (222 of 619) of PTCs. Multivariate logistic regressions showed that BRAF(V600E) mutation, sex, extrathyroidal extension, and lymph node metastasis were independent factors for Hashimoto's thyroiditis. Female sex, more frequent extrathyroidal extension, and a higher incidence of lymph node metastasis were significantly associated with PTCs accompanied by BRAF(V600E) mutation without Hashimoto's thyroiditis compared with PTCs accompanied by BRAF(V600E) mutation with Hashimoto's thyroiditis. Hashimoto's thyroiditis was negatively associated with BRAF(V600E) mutation, extrathyroidal extension, and lymph node metastasis. In addition, Hashimoto's thyroiditis was related to less lymph node metastasis and extrathyroidal extension in PTCs with BRAF(V600E) mutation. Therefore, Hashimoto's thyroiditis is a potentially protective factor in PTC. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1019-E1025, 2016.

Characteristics and significance of minimal and maximal extrathyroidal extension in papillary thyroid carcinoma

Maximal extrathyroidal extension (ETE) is known to be an important prognostic factor in papillary thyroid carcinoma (PTC). However, the significance of minimal ETE is controversial. The aim of this study was to investigate the clinicopathologic characteristics and prognostic significance of minimal vs maximal ETE in PTC. A group of 967 patients who underwent thyroidectomy for PTC in a tertiary hospital between January 2000 and December 2011 were studied retrospectively. Patients were classified into three groups: absence of ETE, and minimal and maximal ETE. The minimal ETE group was further categorized into two subgroups according to invasion of strap muscles or no invasion (STI+ and STI-). Gender did not differ between the three groups of patients. The mean age of the patients with maximal ETE was significantly higher than in those belonging to the other groups. Tumor size, bilaterality, lymph node metastasis and stage increased significantly according to the degree of ETE. Recurrence and survival rates did not differ between the absence and minimal ETE groups, or between the STI- and STI+ subgroups of minimal ETE. However, the maximal ETE group had significantly higher recurrence and lower survival rates than the other groups (P<0.001). Maximal ETE is a significant factor for poor prognosis. However, minimal ETE is not associated with increased recurrence or decreased survival in patients with PTC.