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Purpose: This study compared the diagnostic performance of the modified Korean Thyroid Imaging Reporting and Data System (K-TIRADS) for thyroid malignancy with three international guidelines.Methods: From June to September 2015, 5,708 thyroid nodules (≥1.0 cm) in 5,081 consecutive patients who underwent thyroid ultrasound (US) at 26 institutions were evaluated. The US features of the thyroid nodules were retrospectively reviewed and classified according to all four guidelines. In the modified K-TIRADS, the biopsy size threshold was changed to 2.0 cm for K-TIRADS 3 and 1.0 or 1.5 cm for K-TIRADS 4 (K-TIRADS1.0cm and K-TIRADS1.5cm, respectively). We compared the diagnostic performance and unnecessary fine-needle aspiration biopsy (FNAB) rates for thyroid malignancy between the modified K-TIRADS and three international guidelines.Results: Of the 5,708 thyroid nodules, 4,597 (80.5%) were benign and 1,111 (19.5%) were malignant. The overall sensitivity was highest for the modified K-TIRADS1.0cm (91.0%), followed by the European (EU)-TIRADS (84.6%), American Association of Clinical Endocrinologists/American College of Endocrinology/Associazione Medici Endocrinologi (AACE/ACE/AME) (80.5%), American College of Radiology (ACR)-TIRADS (76.1%), and modified K-TIRADS1.5cm (76.1%). For large nodules (>2.0 cm), the sensitivity increased to 98.0% in both the modified K-TIRADS1.0cm and K-TIRADS1.5cm. For small nodules (≤2.0 cm), the unnecessary FNAB rate was lowest with the modified K-TIRADS1.5cm (17.6%), followed by the ACR-TIRADS (18.6%), AACE/ACE/AME (19.3%), EU-TIRADS (28.1%), and modified K-TIRADS1.0cm (31.2%).Conclusion: The modified K-TIRADS1.5cm can reduce the unnecessary FNAB rate for small nodules (1.0-2.0 cm), while maintaining high sensitivity for detecting malignancies >2.0 cm.

Background Stepwise surgical approach with hemithyroidectomy and completion thyroidectomy was used to solve the dilemma of definite characterization of follicular thyroid carcinoma (FTC). However, which patients will be candidates for completion thyroidectomy has been controversial. The aim of this study is to clarify the selection criteria for completion thyroidectomy using TERT promoter mutation. Methods A total of 87 FTC patients who had information about TERT promoter mutation from August 1995 to November 2020 were investigated. The cumulative risk of initial distant metastasis, disease recurrence, and cancer-specific death according to primary tumor size in each of the WHO 2017 classifications were calculated. Results Of the 87 patients, 8 patients (9.2%) had initial distant metastasis, and 15 patients (17.2%) had persistent disease or developed structural recurrence. Threshold diameter for initial distant metastasis, disease recurrence, and cancer-specific death was 2cm in minimally invasive FTC (MI-FTC) with mutant TERT (M-TERT) and in encapsulated angioinvasive FTC (EA-FTC) with M-TERT, while in MI-FTC with wild-type TERT (WT-TERT) and EA-FTC with WT-TERT it was 4cm. Cumulative risk of initial distant metastasis, disease recurrence, and cancer-specific death according to primary tumor size in each WHO 2017 classification were significantly different only in patients with WT-TERT (P = 0. 001, P = 0. 019, and P = 0. 005, respectively). Conclusions The data suggested that 2 cm may be a critical threshold diameter for deciding completion thyroidectomy in MI-FTC with M-TERT and EA-FTC with M-TERT. TERT promoter mutational status can be a game changer for selecting candidates for completion thyroidectomy. Presentation: No date and time listed

Objective The purpose of this study was to evaluate a novel radiofrequency ablation (RFA) application utilizing an adjustable electrode for treatment of benign thyroid nodules. Materials and methods From April 2011 to December 2018, 21 patients underwent RFA treatment on 21 thyroid nodules, utilizing an 18-gauge internally cooled electrode equipped with a size adjustable active tip. The peripheral nodule portions were ablated with the moving-shot technique and a shorter active tip, and the nodule centers were ablated with the fixed technique and a longer active tip. We assessed parameters including characteristics of the treated nodules, use of variablesized active tips, volume reduction rate, therapeutic success rate, and post-procedural complications. The therapeutic success rate was defined as a > 50% volume reduction of the initial nodule volume at the 6- or 12-month follow-up. Results The treated thyroid nodules were large enough to cause symptoms (mean volume, 29.6 mL). Two types of active tips per session were used for all nodules. The mean volume reduction rate at the last follow-up was 68.3 ± 4.4% and our therapeutic success rate was 90.5%. Both symptoms and cosmetic scores decreased significantly. Minor complications in three patients were recorded during and after the procedure. Conclusion This initial study demonstrated that an adjustable electrode for RFA of benign thyroid nodules effectively and safely resulted in volume reduction.

We previously reported that high thyroid-stimulating hormone (TSH) levels are associated with papillary thyroid microcarcinoma (PTMC) progression during active surveillance. However, validation with multicenter, long-term data, and identification of appropriate age or TSH levels are needed. This multicenter retrospective study enrolled PTMC patients under active surveillance with TSH measurements and ultrasonography. The primary outcome was PTMC progression (volume increase ≥50%, size increase ≥3 mm, or new lymph node (LN) metastasis). PTMC progression according to time-weighted average of TSH (TW-TSH) groups was compared using survival analyses in overall patients and each age subgroups (P = 0.006), but the impact was significant only in patients aged P = 0.004), 2.55 (1.00–6.47; P = 0.049)). For patients aged P for trend = 0.034). In young PTMC patients (

Incidental thyroid nodules are commonly detected on ultrasonography (US). This has contributed to the rapidly rising incidence of low-risk papillary thyroid carcinoma over the last 20 years. The appropriate diagnosis and management of these patients is based on the risk factors related to the patients as well as the thyroid nodules. The Korean Society of Thyroid Radiology (KSThR) published consensus recommendations for US-based management of thyroid nodules in 2011 and revised them in 2016. These guidelines have been used as the standard guidelines in Korea. However, recent advances in the diagnosis and management of thyroid nodules have necessitated the revision of the original recommendations. The task force of the KSThR has revised the Korean Thyroid Imaging Reporting and Data System and recommendations for US lexicon, biopsy criteria, US criteria of extrathyroidal extension, optimal thyroid computed tomography protocol, and US follow-up of thyroid nodules before and after biopsy. The biopsy criteria were revised to reduce unnecessary biopsies for benign nodules while maintaining an appropriate sensitivity for the detection of malignant tumors in small (1-2 cm) thyroid nodules. The goal of these recommendations is to provide the optimal scientific evidence and expert opinion consensus regarding US-based diagnosis and management of thyroid nodules.

This study evaluated how to manage Bethesda category III (Bethesda III) (atypia of undetermined significance/follicular lesion of undetermined significance [AUS/FLUS]) thyroid nodules according to the Korean Thyroid Imaging Reporting and Data System (K-TIRADS) to reduce unnecessary surgeries. A total of 161 thyroid nodules diagnosed as Bethesda III underwent surgery from 2016 to 2019. Ultrasonography-guided fine-needle aspiration (US-FNA) or core needle biopsy (CNB) was used for repeat examination. K-TIRADS category was assigned to the thyroid nodules. The proportion of malignancy in Bethesda III nodules confirmed by surgery were significantly increased in proportion relative to K-TIRADS with 60.0% low suspicion, 88.2% intermediate suspicion, and 100% high suspicion nodules (p < 0.001). The proportion of malignancy in AUS and FLUS were significantly different (94.2% vs. 40.0% p = 0.003). The proportion of malignancy in AUS increased with K-TIRADS categories, but there was no difference in FLUS. All K-TIRADS high suspicion nodules were AUS as papillary carcinomas (99%), while 80% of FLUS nodules and 50% of follicular carcinomas showed K-TIRADS low suspicion. In 116 nodules with repeat FNA or CNB after initial Bethesda III results, the conclusive result rate was significantly increased in proportion to K-TIRADS with 58.3% low suspicion, 83.3% intermediate suspicion, and 88.8% high suspicion nodules (p = 0.015). K-TIRADS low suspicion nodules of Bethesda III nodules should be managed after risk-benefit consideration rather than immediate surgery or repeat examination. K-TIRADS for Bethesda III nodules can predict papillary carcinoma well, but not follicular carcinoma.

The role of telomerase reverse transcriptase (TERT) promoter mutations as an independent poor prognostic factor in differentiated thyroid cancer (DTC) patients is well known, but there is no prognostic system that combines the TERT promoter mutation status with tumor-node-metastasis (TNM) stage to predict cancer-specific survival (CSS). A total of 393 patients with pathologically confirmed DTC after thyroidectomy were enrolled. After incorporating wild-type TERT and mutant TERT with stages I, II, and III/IV of the AJCC TNM system 8th edition (TNM-8), we generated six combinations and calculated 10-year and 15-year CSS and adjusted hazard ratios (HRs) for cancer-related death using Cox regression. Then, a new mortality prediction model termed TNM-8T was derived based on the CSS and HR of each combination in the four groups. Of the 393 patients, there were 27 (6.9%) thyroid cancer-related deaths during a median follow-up of 14 years. Patients with a more advanced stage had a lower survival rate (10-year CSS for TNM-8T stage 1, 2, 3, and 4: 98.7%, 93.5%, 77.3%, and 63.0%, respectively, p &lt, 0.001). TNM-8T showed a better spread of CSS (p &lt, 0.001) than TNM-8 (p = 0.002) in the adjusted survival curves. The C-index for mortality risk predictability was 0.880 (95% CI, 0.665–0.957) in TNM-8T and 0.827 (95% CI, 0.622–0.930) in TNM-8 (p &lt, 0.001). TNM-8T, a new prognostic system that incorporates the TERT mutational status into TNM-8, showed superior predictability to TNM-8 in the long-term survival of DTC patients.

Objective To retrospectively compare the diagnostic performances of two different ultrasound (US)-guided core needle biopsy (CNB) techniques for intermediate or low suspicion thyroid nodules. Materials and methods Between August 2015 and December 2016, two different biopsy techniques were alternatively applied for 248 consecutive thyroid nodules, of which, 140 intermediate or low suspicion thyroid nodules were included in this study. In the first technique, two specimens included nodular tissue, nodular margin, and surrounding normal parenchyma (i.e., marginal target). In the second technique, two specimens were obtained from two different target areas, one for the marginal target and another for the intranodular target. The diagnostic performances of the two techniques to predict neoplasm and malignancy were compared. Results CNB was performed on 80 intermediate or low suspicion nodules (57.1%) using the first technique and on 60 (42.9%) using the second technique. The accuracy of the first technique for predicting neoplasm or malignancy was significantly higher than that of the second technique (100% vs. 93.3%, p = 0.032 for predicting neoplasm; 88.8% vs. 75.0%, p = 0.033 for predicting malignancy). The negative predictive value of the first technique for predicting malignancy was also significantly higher than that of the second technique (87.5% vs. 72.7%, p = 0.035). Conclusion For intermediate or low suspicion thyroid nodules, US-guided CNB to obtain two specimens with marginal targets is more effective for diagnosing neoplasm or malignancy than is CNB for respective marginal and intranodular targets.

Background: The current American Thyroid Association risk-stratification system for papillary thyroid carcinoma (PTC) incorporates the number and size of positive lymph nodes (LNs) but places less ...

Background Indications for computed tomography (CT) in preoperative patients with thyroid cancer are still controversial. Purpose To determine the value of CT and ultrasonography (US) in preoperative lymph node assessment of patients with papillary thyroid carcinoma (PTC) according to primary tumor size. Material and Methods A total 453 patients with surgically proven PTC who underwent US and CT for preoperative evaluation in 2010 at our tertiary referral center were included. The diagnostic sensitivity, specificity, and accuracy of US, CT, and the combination of US and CT (US/CT) in the preoperative nodal assessment were compared. We performed subgroup analysis to compare the findings according to primary tumor size. Results In overall tumors, adding CT to US had greater sensitivity, lower specificity, and greater accuracy in predicting central lymph node metastasis (LNM) but lower accuracy in prediction of lateral LNM. In smaller cancers (≤1 cm), US alone had greater specificity and accuracy than CT alone or US/CT in predicting lateral LNM. In larger cancers (>1 cm), CT had greater sensitivity and accuracy than US in predicting central LNM, while US had greater specificity and accuracy than CT in predicting lateral LNM. There were no patients with smaller tumors who showed retropharyngeal and superior mediastinal LNM diagnosed by CT alone. Conclusion CT is superior to US for detecting central LNM in preoperative patients with PTCs > 1 cm. However, there are no benefits to adding CT to US to predict lateral LNM in small cancers (≤1 cm).

We compared American Thyroid Association (ATA) guidelines, Korean (K)-Thyroid Imaging, Reporting and Data Systems (TIRADS), EU-TIRADS, and American College of Radiology (ACR) TIRADS in diagnosing malignancy for thyroid nodules with nondiagnostic/unsatisfactory cytology. Among 1143 nondiagnostic/unsatisfactory aspirations from April 2011 to March 2016, malignancy was detected in 39 of 89 excised nodules. The minimum malignancy rate was 7.82% in EU-TIRADS 5 and 1.87–3.00% in EU-TIRADS 3–4. In the other systems, the minimum malignancy rate was 14.29–16.19% in category 5 and ≤3% in the remaining categories. Although the EU-TIRADS category ≥ 5 exhibited the highest positive likelihood ratio (LR) of only 2.214, category ≥ 5 in the other systems yielded the highest positive LR of &gt, 5. Receiver operating characteristic (ROC) curves of all systems to predict malignancy were located statistically above the diagonal nondiscrimination line (P for ROC curve: EU-TIRADS, 0.0022, all others, 0.0001). The areas under the ROC curve (AUCs) were not significantly different among the four systems. The ATA guidelines, K-TIRADS, and ACR TIRADS may be useful to guide management for nondiagnostic/unsatisfactory nodules. The EU-TIRADS, although also useful, exhibited inferior performance in predicting malignancy for nondiagnostic/unsatisfactory nodules in Korea, an iodine-sufficient area.

The neutrophil–lymphocyte ratio (NLR) is a marker of systemic inflammation, and its elevation has recently been associated with poor survival in many solid cancers. Leukocyte elevation and lymphocyte reduction are associated with a poor response to radiotherapy (RT). This study aimed to assess the prognostic value of NLR before and after RT for anaplastic thyroid carcinoma (ATC). This retrospective study analyzed 40 patients with ATC who received RT with available complete blood cell count data from November 1995 through May 2020 at Samsung Medical Center (Seoul, Korea). Patients were classified into two groups according to the NLR before and after RT. The median overall survival (OS) was 8.9 months (range, 3.5–18.2) in the low NLR group (&lt, 3.47) and 5.2 months (range, 2.7–7.5) months in the high NLR group (≥3.47). The association between NLR and OS was also observed in multivariable Cox regression analysis (hazard ratio, 3.18, 95% confidence interval, 1.15–8.85, p = 0.026). The OS curves differed significantly according to post-RT NLR (p = 0.036). A high NLR before and after RT may be significantly associated with poor OS in patients with ATC who receive RT.

Our research group has previously shown that the presence of TERT promoter mutations is an independent prognostic factor, by applying the TERT mutation status to the variables of the AJCC 7th edition. This study aimed to determine if TERT mutations could be independent predictors of thyroid cancer-specific mortality based on the AJCC TNM 8th edition, with long-term follow-up. This was a retrospective study of 393 patients with pathologically confirmed differentiated thyroid carcinoma (DTC) after thyroidectomy at a tertiary Korean hospital from 1994 to 2004. The thyroid cancer-specific mortality rate was 6.9% (5.2% for papillary and 15.2% for follicular cancers). TERT promoter mutations were identified in 10.9% (43/393) of DTC cases (9.8% of papillary and 16.7% of follicular cancer) and were associated with older age (p &lt, 0.001), the presence of extrathyroidal invasion (p &lt, 0.001), distant metastasis (p = 0.001), and advanced stage at diagnosis (p &lt, 0.001). The 10-year survival rate in mutant TERT was 67.4% for DTC patients (vs. 98% for wild-type, adjusted hazard ratio (HR) of 9.93, (95% CI: 3.67–26.90)) and 75% for patients with papillary cancer (vs. 99%, 18.55 (4.83–71.18)). In addition, TERT promoter mutations were related to poor prognosis regardless of histologic type (p &lt, 0.001 for both papillary and follicular cancer) or initial stage (p &lt, 0.001, p = 0.004, and p = 0.086 for stages I, II, and III and IV, respectively). TERT promoter mutations comprise an independent poor prognostic factor after adjusting for the clinicopathological risk factors of the AJCC TNM 8th edition, histologic type, and each stage at diagnosis, which could increase prognostic predictability for patients with DTC.

The optimal initial surgical extent for medullary thyroid carcinoma (MTC) remains controversial. Previous studies on serum calcitonin are limited to reporting the calcitonin threshold according to anatomical disease burden. Here, we evaluated whether preoperative calcitonin levels can be used to predict optimal surgical extent. We retrospectively reviewed the 170 patients with MTC at a tertiary Korean hospital from 1994 to 2019. We extracted data on preoperative calcitonin level, primary tumor size and the number and location of lymph node metastases (LNMs). To evaluate disease extent, we divided the patients into five groups: no LNM, central LNM, ipsilateral lateral LNM, contralateral lateral LNM, and distant metastasis. We calculated the positive and negative likelihood ratios (LRs) for multiple categories of preoperative calcitonin levels. Preoperative calcitonin level positively correlated with primary tumor size (rho = 0.744, p &lt, 0.001) and LNM number (rho = 0.537, p &lt, 0.001). Preoperative calcitonin thresholds of 20, 200, and 500 pg/mL were associated with the presence of ipsilateral lateral LNM, contralateral lateral LNM, and distant metastasis, respectively. The negative LRs were 0.1 at a preoperative calcitonin cut-off of 100 pg/mL in the central LNM, 0.18 at a cut-off of 300 pg/mL in the ipsilateral lateral LNM, and 0 at a cut-off of 300 pg/mL in the contralateral lateral LNM. The preoperative calcitonin level correlates with disease extent and has diagnostic value for predicting LNM extent. Our results suggest that the preoperative calcitonin level can be used to determine optimal initial surgical extent.

The purpose of this study was to evaluate and compare the diagnostic performances of the deep convolutional neural network (CNN) and expert radiologists for differentiating thyroid nodules on ultrasonography (US), and to validate the results in multicenter data sets. This multicenter retrospective study collected 15,375 US images of thyroid nodules for algorithm development (n = 13,560, Severance Hospital, SH training set), the internal test (n = 634, SH test set), and the external test (n = 781, Samsung Medical Center, SMC set; n = 200, CHA Bundang Medical Center, CBMC set; n = 200, Kyung Hee University Hospital, KUH set). Two individual CNNs and two classification ensembles (CNNE1 and CNNE2) were tested to differentiate malignant and benign thyroid nodules. CNNs demonstrated high area under the curves (AUCs) to diagnose malignant thyroid nodules (0.898–0.937 for the internal test set and 0.821–0.885 for the external test sets). AUC was significantly higher for CNNE2 than radiologists in the SH test set (0.932 vs. 0.840, P P = 0.113, 0.126, and 0.690). CNN showed diagnostic performances comparable to expert radiologists for differentiating thyroid nodules on US in both the internal and external test sets.

Background Few studies have categorized ultrasound (US) findings of various sized medullary thyroid carcinomas (MTCs) according to updated guidelines. Purpose To evaluate and compare the differences in US findings of MTC according to nodule size, using the Korean Thyroid Imaging Reporting and Data System (K-TIRADS) and American Thyroid Association (ATA) guidelines. Material and Methods The study included 119 patients with 129 MTC nodules, which were surgically confirmed at our institution between March 1999 and September 2017. Nodules were divided into large (≥1.0 cm) and small (Results Of 129 MTC nodules, 84 (65.1%) were large nodules and 45 (34.9%) were small nodules. According to the nodule size, small MTC nodules were classified more commonly as high suspicion by K-TIRADS and ATA (95.6% and 93.3%, respectively) ( P Conclusion Most small MTC nodules are classified as high suspicion on US, whereas large MTC nodules are diagnosed more frequently as low or intermediate suspicion by K-TIRADS and ATA.

Imaging plays a key role in the diagnosis and characterization of thyroid diseases, and the information provided by imaging studies is essential for management planning. A referral guideline for imaging studies may help physicians make reasonable decisions and minimize the number of unnecessary examinations. The Korean Society of Thyroid Radiology (KSThR) developed imaging guidelines for thyroid nodules and differentiated thyroid cancer using an adaptation process through a collaboration between the National Evidence-based Healthcare Collaborating Agency and the working group of KSThR, which is composed of radiologists specializing in thyroid imaging. When evidence is either insufficient or equivocal, expert opinion may supplement the available evidence for recommending imaging. Therefore, we suggest rating the appropriateness of imaging for specific clinical situations in this guideline.

BACKGROUND AND PURPOSE: It is not known how radiomics using ultrasound images contribute to the detection of BRAF mutation. This study aimed to evaluate whether a radiomics study of gray-scale ultrasound can predict the presence or absence of B-Raf proto-oncogene, serine/threonine kinase (BRAF) mutation in papillary thyroid cancer. MATERIALS AND METHODS: The study retrospectively included 96 thyroid nodules that were surgically confirmed papillary thyroid cancers between January 2012 and June 2013. BRAF mutation was positive in 48 nodules and negative in 48 nodules. For analysis, ROIs from the nodules were demarcated manually on both longitudinal and transverse sonographic images. We extracted a total of 86 radiomics features derived from histogram parameters, gray-level co-occurrence matrix, intensity size zone matrix, and shape features. These features were used to build 3 different classifier models, including logistic regression, support vector machine, and random forest using 5-fold cross-validation. The performance including accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and area under the receiver operating characteristic curve, of the different models was evaluated. RESULTS: The incidence of high-suspicion nodules diagnosed on ultrasound was higher in the BRAF mutation–positive group than in the mutation–negative group (P = .004). The radiomics approach demonstrated that all classification models showed moderate performance for predicting the presence of BRAF mutation in papillary thyroid cancers with an area under the curve value of 0.651, accuracy of 64.3%, sensitivity of 66.8%, and specificity of 61.8%, on average, for the 3 models. CONCLUSIONS: Radiomics study using thyroid sonography is limited in predicting the BRAF mutation status of papillary thyroid carcinoma. Further studies will be needed to validate our results using various diagnostic methods.

The incidence of thyroid cancer (TC) has been increasing in many countries and concerns about overdiagnosis are also widely shared. However, early detection may be helpful in some high-risk TC patients, such as those with initial distant metastasis. We conducted this study to evaluate the usefulness of early detection in TC patients with initial distant metastasis. We retrospectively reviewed the clinical data of 13,249 TC patients, and found 127 patients with initial distant metastasis. Enrolled patients were divided into two groups according to the diagnostic periods; before and after 2004, when the early detection of TC by ultrasonography began in earnest in Korea. Patients were also divided into two groups according to the presence of symptoms. Prior to 2004, 33 patients (1.7% of TC patients) were diagnosed with TC with initial distant metastasis and 16 (48.5%) of them died. After 2004, 94 patients (0.8% of TC patients) were diagnosed with TC with initial distant metastasis and 29 (30.9%) of them died. Prior to 2004, the disease-specific death rates were similar between the asymptomatic and symptomatic groups (46.2% vs. 50.0%, P = 0.566). Conversely, after 2004, the asymptomatic group showed a significantly lower disease-specific death rate as compared with that of the symptomatic groups (17.2% vs. 60.0%; P

Objective To evaluate the ultrasonography (US) features and clinical characteristics of columnar cell variant of papillary thyroid carcinoma (CCV-PTC) that can predict disease progression. Materials and Methods Six cases of CCV-PTC were identified via surgical pathology analysis at our institution from 1994 to 2016. The histological, architectural, and cytological features met the diagnostic criteria of CCV-PTC. We reviewed the US features and clinicopathological findings in the six cases. Results An indolent clinical course was observed in four young female patients aged 27-34 years (median: 32 years), while two older patients aged 55 years or 70 years had an aggressive clinical course. All patients underwent total thyroidectomy and radioiodine therapy. The indolent group included patients with T1 and nodal metastasis, where the disease was not observed during the follow-up period (range: 8-17 years). On the other hand, a larger tumor size (1.8 cm and 6.0 cm), gross extrathyroidal extension to the muscle and lymph node, and distant metastasis were observed in the aggressive group. In one male patient, recurrence occurred immediately after operation, and this patient died 4 years after the diagnosis of thyroid cancer. Based on US, the individuals from the indolent group had a smooth margin, except for one. Both cases in the aggressive group had a microlobulated margin. Conclusion Favorable prognosis in CCV-PTC is observed in young patients with T1 staging and demonstrates a smooth margin at US. These US findings might help exclude the same treatment as the aggressive type in the indolent type of CCV-PTC.

BACKGROUND The purpose of this study was to construct a web-based predictive model using ultrasound characteristics and subcategorized biopsy results for thyroid nodules of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) to stratify the risk of malignancy. METHODS Data included 672 thyroid nodules from 656 patients from a historical cohort. We analyzed ultrasound images of thyroid nodules and biopsy results according to nuclear atypia and architectural atypia. Multivariate logistic regression analysis was performed to predict whether nodules were diagnosed as malignant or benign. RESULTS The ultrasound features, including spiculated margin, marked hypoechogenicity, calcifications, biopsy results, and cytologic atypia, showed significant differences between groups. A 13-point risk scoring system was developed, and the area under the curve (AUC) of the receiver operating characteristic (ROC) curve of the development and validation sets were 0.837 and 0.830, respectively (http://www.gap.kr/thyroidnodule_b3.php). CONCLUSION We devised a web-based predictive model using the combined information of ultrasound characteristics and biopsy results for AUS/FLUS thyroid nodules to stratify the malignant risk.

In the eighth edition, TNM staging system omits location of nodal metastasis as a criterion for staging patients with papillary thyroid cancer (PTC). Accordingly, all of non-metastatic N1b PTC patients are classified as stage I or II solely according to an age-cutoff of 55 years. We hypothesized that incorporating other lymph node (LN) factors into TNM staging system would better predict cancer-specific mortality (CSM) in N1b patients.We enrolled 745 N1b PTC patients without distant metastasis. Alternative prognostic LN factors and cut-off points were assessed using Cox regression and time-dependent ROC analysis. Alternative prognostic groupings were derived based on minimal hazard differences for CSM among groups stratified by LN risk and age. We assessed accuracy of CSM prediction.Lateral LN ratio (LNR)0.3 and largest LN size3 cm were prognostic factors for CSM. Stage II patients (eighth edition) with LN risk (lateral LNR0.3 or largest LN size3 cm) had a much higher CSM rate (20.9%) than those in the same stage without LN risk (3.2%). Alternative prognostic grouping (Group 1,55 years without LN risk; Group 2,55 years with LN risk or ≥55 years without LN risk; and Group 3, ≥55 with LN risk) achieved higher proportions of variance explained (PVEs) for predicting CSM (10.7%) than those of the eighth edition TNM staging system (4.8%).The proposed grouping for N1b patients using LN risk can distinguish patients with poor prognosis from those with good prognosis better than the eighth edition TNM staging system.

SummaryAim Noninvasive encapsulated follicular variant of papillary thyroid carcinoma (FVPTC) has been managed as low-risk malignancy. Recently, a proposal was made to reclassify this tumor type as a premalignant lesion and rename it noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). However, a comprehensive study on molecular genotype-phenotype correlations of encapsulated FVPTC is lacking. Methods and results This study consisted of 177 consecutive FVPTCs from January 2014 to April 2016. These were classified into noninvasive (n=74), invasive (n=51) encapsulated FVPTC, and infiltrative FVPTC (n=52) according to standard criteria by two independent pathologists. Genetic alterations and other clinicopathologic information were compared. A BRAFV600E mutation was found in 12.2% (noninvasive) and 11.8% (invasive) of encapsulated FVPTCs and 34.6% of infiltrative FVPTCs (P=0.001). Mutation in encapsulated FVPTCs was limited to cases with rare or abortive papillae. RET/PTC1 and RET/PTC3 rearrangements were present (11.5%) only in infiltrative FVPTC. In contrast, N-, H-, and KRAS mutations were observed predominantly in encapsulated FVPTCs (48.6% in noninvasive and 66.7% in invasive) compared to infiltrative FVPTCs (15.4%) (P

Follicular variant of papillary thyroid carcinoma (FVPTC) is traditionally divided into infiltrative and encapsulated types. Adding to this classification, noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) represents a reclassification of a subset of cases (encapsulated tumors without lymphovascular or capsular invasion). The purpose of this study was to assess the role of ultrasound (US) in predicting tumor invasiveness in FVPTC.From January 2014 to May 2016, preoperative US examinations were performed on 151 patients with 152 FVPTCs who underwent surgery. Based on a pathologic analysis, the FVPTCs were categorized into three groups: NIFTP, invasive encapsulated FVPTC (iE-FVPTC), or infiltrative FVPTC (I-FVPTC). Each nodule was categorized based on the US pattern according to the Korean Thyroid Imaging Reporting and Data System (K-TIRADS) and the American Thyroid Association (ATA) guidelines. The correlation between tumor invasiveness and the K-TIRADS or ATA category was investigated using Spearman's rank correlation coefficient.Among the 152 FVPTCs, there were 48 (31.6%) NIFTPs, 60 (39.5%) iE-FVPTCs, and 44 (28.9%) I-FVPTCs. US characteristics of the FVPTCs differed significantly according to tumor invasiveness (p ≤ 0.030). Tumor invasiveness showed a significant positive correlation with K-TIRADS (tumors of all sizes: r = 0.591, p 0.001; tumors ≥1.0 cm: r = 0.427, p 0.001) and ATA categories (tumors of all sizes: r = 0.532, p 0.001; tumors ≥1.0 cm: r = 0.466, p 0.001). According to both K-TIRADS and ATA guidelines for all-sized tumors, the most common subtype was NIFTP in low-suspicion nodules (52.6% and 51.6%), iE-FVPTC in intermediate-suspicion nodules (52.7% and 54.2%), and I-FVPTC in high-suspicion nodules (82.5% and 69.4%). After surgery, lymph node metastases were confirmed in two (4.2%) NIFTP cases, three (5.0%) iE-FVPTC cases, and eight (18.2%) I-FVPTC cases (p = 0.001). The results of the BRAF mutation analysis were not significantly different between the groups (p = 0.507).Increasing tumor invasiveness from NIFTP to iE-FVPTC to I-FVPTC is positively correlated with the level of suspicion on US using both K-TIRADS and ATA guidelines.

The current 7th TNM staging stratifies N1b papillary thyroid cancer (PTC) patients without distant metastasis into either stage I or stage IV merely by an age threshold (45 years). To date, no studies have adequately quantified the mortality risk of PTC patients with N1b disease. We hypothesized that incorporating lymph node (LN) factors into the staging system would better predict cancer‐specific mortality (CSM). A total of 745 nonmetastatic PTC patients with N1b disease were enrolled. We identified factors related to LNs and cut‐points using Cox regression and time‐dependent ROC analysis. New prognostic groupings were derived based on minimal hazard differences for CSM among the groups stratified by LN risk and age, and prediction of CSM was assessed. Lateral lymph node ratio (LNR) and largest LN size were significant prognostic LN factors at cut‐points of 0.3 and 3 cm. Without LN risk (lateral LNR >0.3 or largest LN size >3 cm), stage IV patients had prognosis [adjusted HR 1.10 (98% CI 0.19–6.20); P = 0.906] similar to stage I patients with LN risk. Patients were restratified into three prognostic groups: Group 1

PD-L1 expression is being considered a potential biomarker for response of anti-PD-1 or anti-PD-L1 agents in various tumors. The reported frequency of PD-L1 positivity varies in thyroid carcinomas, and multiple factors may contribute to the variability in PD-L1 positivity. We evaluated the PD-L1 expression in various thyroid cancers on a large scale. A total of 407 primary thyroid cancers with a median 13.7-year of follow-up were included. We evaluated the frequency of PD-L1 expression using a rabbit monoclonal antibody (clone SP142). In addition, we analyzed the relationships between PD-L1 expression and clinicopathologic factors, includingTERTpromoter, BRAFstatus and disease progression. Tumoral PD-L1 was expressed in 6.1% of papillary thyroid carcinomas, 7.6% of follicular thyroid carcinomas and 22.2% of anaplastic thyroid carcinomas. The distribution of PD-L1 positivity was different according to cancer histology types (P