Outcomes Following Negative Screening MRI Results in Korean Women with a Personal History of Breast Cancer: Implications for the Next MRI Interval.

Background There are limited data on outcomes following screening breast MRI in women with a personal history of breast cancer (PHBC). Purpose To investigate outcomes and factors associated with subsequent cancers following a negative screening MRI study in women with a PHBC. Materials and Methods Consecutive women with a PHBC and a negative prevalence screening breast MRI result between August 2014 and December 2016 were retrospectively identified. Inclusion criteria were prevalence screening MRI performed as part of routine surveillance protocol (1-3 years after treatment) and follow-up data for at least 12 months. The incidence and characteristics of subsequent cancers were reviewed. Logistic regression analysis was used to investigate associations between clinical-pathologic characteristics and subsequent cancers. Performance metrics were compared among screening MRI, mammography, and US. Results A total of 993 women (mean age ± standard deviation, 53 years ± 10) were evaluated. Ten second in-breast cancers (ie, ipsilateral or contralateral) occurred at a median interval of 31.8 months (range, 13.3-44.8 months) after MRI, of which eight (80%) were ductal carcinoma in situ (DCIS) or node-negative T1 cancers. Only one node-negative T1mi (tumor ≤1 mm) second in-breast cancer visible on a mammogram was detected within 24 months of MRI. Of second in-breast cancers, 40% (four of 10) were detected only at subsequent screening MRI, which was performed a median of 30.5 months after negative prevalence screening MRI. Ten local-regional recurrences occurred at a median interval of 16.9 months (range, 6-35 months). Previous treatment for DCIS was associated with second in-breast cancers (odds ratio, 3.73; 95% CI: 1.04, 13.38; P = .04). In 1048 women who underwent prevalence screening MRI (including all Breast Imaging Reporting and Data System categories), MRI showed a lower abnormal interpretation rate and higher specificity than mammography or US (P < .001 for all). Conclusion After a negative screening MRI result, 90% of subsequent cancers were detected at intervals longer than 24 months and there was a low second in-breast cancer rate (1%). © RSNA, 2021 Supplemental material is available for this article. See also the editorial by Chang in this issue.

Combining radiomics with ultrasound-based risk stratification systems for thyroid nodules: an approach for improving performance.

OBJECTIVES: To develop a radiomics score using ultrasound images to predict thyroid malignancy and to investigate its potential as a complementary tool to improve the performance of risk stratification systems. METHODS: We retrospectively included consecutive patients who underwent fine-needle aspiration (FNA) for thyroid nodules that were cytopathologically diagnosed as benign or malignant. Nodules were randomly assigned to a training and test set (8:2 ratio). A radiomics score was developed from the training set, and cutoff values based on the maximum Youden index (Rad_maxY) and for 5%, 10%, and 20% predicted malignancy risk (Rad_5%, Rad_10%, Rad_20%, respectively) were applied to the test set. The performances of the American College of Radiology (ACR) and the American Thyroid Association (ATA) guidelines were compared with the combined performances of the guidelines and radiomics score with interpretations from expert and nonexpert readers. RESULTS: A total of 1624 thyroid nodules from 1609 patients (mean age, 50.1 years [range, 18-90 years]) were included. The radiomics score yielded an AUC of 0.85 (95% CI: 0.83, 0.87) in the training set and 0.75 (95% CI: 0.69, 0.81) in the test set (Rad_maxY). When the radiomics score was combined with the ACR or ATA guidelines (Rad_5%), all readers showed increased specificity, accuracy, and PPV and decreased unnecessary FNA rates (all p < .05), with no difference in sensitivity (p > .05). CONCLUSION: Radiomics help predict thyroid malignancy and improve specificity, accuracy, PPV, and unnecessary FNA rate while maintaining the sensitivity of the ACR and ATA guidelines for both expert and nonexpert readers. KEY POINTS: • The radiomics score yielded an AUC of 0.85 and 0.75 in the training and test set, respectively. • For all readers, combining a 5% predicted malignancy risk cutoff for the radiomics score with the ACR and ATA guidelines significantly increased specificity, accuracy, and PPV and decreased unnecessary FNA rates, with no decrease in sensitivity. • Radiomics can help predict malignancy in thyroid nodules in combination with risk stratification systems, by improving specificity, accuracy, and PPV and unnecessary FNA rates while maintaining sensitivity for both expert and nonexpert readers.

Validation of the 2015 American Thyroid Association Management Guidelines for Thyroid Nodules With Benign Cytologic Findings in the Era of the Bethesda System.

OBJECTIVE: The purpose of this study is to investigate follow-up strategies for cytologically benign thyroid nodules according to size and ultrasound (US) pattern according to the 2015 American Thyroid Association (ATA) guidelines in the era of the Bethesda system. MATERIALS AND METHODS: This retrospective study included 1208 patients with 1230 nodules that were cytologically benign at initial fine-needle aspiration performed from June 2012 to December 2014. False-negative rates (FNRs) were calculated by considering nodule size and US pattern according to the 2015 ATA guidelines and were compared between nodules with the high-suspicion US pattern and nodules with the high- or intermediate-suspicion US patterns according to size. RESULTS: Twenty-five of the 1230 nodules (2.0%) were malignant. The FNRs were 5.1% (8/158) for nodules with the high-suspicion US pattern and 1.6% (17/1072) for nodules with other US patterns. With regard to nodule size, the FNRs were 3.2% (9/277) for nodules 3 cm or larger and 5.2% (6/115) for nodules 4 cm or larger. The FNRs of nodules with the high-suspicion pattern were not significantly higher than those of nodules with the high- or intermediate-suspicion patterns among nodules 2 cm or larger (2.5% vs 1.9%; p = 0.208), 3 cm or larger (3.4% vs 2.9%; p = 0.498), and 4 cm or larger (5.4% vs 3.8%; p = 0.353). CONCLUSION: Thyroid nodules with initial benign cytologic findings had a low malignancy rate in the era of the Bethesda system, regardless of US pattern and size. Therefore, any immediate diagnostic intervention may be discouraged in cytologically benign nodules.

Qualitative and Semiquantitative Elastography for the Diagnosis of Intermediate Suspicious Thyroid Nodules Based on the 2015 American Thyroid Association Guidelines.

OBJECTIVES: To evaluate qualitative and semiquantitative elastography for the diagnosis of intermediate suspicious thyroid nodules based on the 2015 American Thyroid Association (ATA) guidelines. METHODS: Through a retrospective search of our institutional database, 746 solid thyroid nodules found on grayscale ultrasonography, strain elastography, and ultrasound-guided fine-needle aspiration between June and November 2009 were collected. Among them, 80 nodules from 80 patients with an intermediate suspicion of malignancy based on the 2015 ATA guidelines that were 10 mm or larger were recruited as the final study nodules. Elastographic findings were categorized according to the criteria of Rago et al (J Clin Endocrinol Metab 2007; 92:2917-2922) and Asteria et al (Thyroid 2008; 18:523-531), and strain ratio values were calculated and recorded. The independent 2-sample t test and χ2 test (or Fisher exact test) were used to evaluate differences in clinical parameters between benign and malignant thyroid nodules. All variables were compared by univariate and multivariate logistic regression analyses, and odds ratios with 95% confidence intervals were calculated. RESULTS: Of the 80 nodules, 6 (7.5%) were malignant, and 74 (92.5%) were benign. No significant differences were observed in age, sex, nodule size, elasticity score, and strain ratio between benign and malignant nodules. No variables significantly predicted thyroid malignancy on the univariate analysis. On the multivariate logistic regression analysis, there were no independent variables associated with thyroid malignancy, including the elasticity score and strain ratio (all P > .05). CONCLUSIONS: Elastographic analysis using the elasticity score and strain ratio has limited ability to characterize the benignity or malignancy of thyroid nodules with an intermediate suspicion of malignancy based on the 2015 ATA guidelines.

Dynamic enhancement pattern of HCC smaller than 3 cm in diameter on gadoxetic acid-enhanced MRI: comparison with multiphasic MDCT.

BACKGROUND & AIMS: The dynamic enhancement pattern of HCCs smaller than 3 cm in diameter on gadoxetic acid-enhanced magnetic resonance imaging (MRI) have not been extensively investigated. We aimed to evaluate the dynamic enhancement patterns of small HCCs (≤3 cm) on gadoxetic acid-enhanced magnetic resonance imaging (MRI) and compare enhancement patterns with multiphasic multidetector computed tomography (MDCT) based on tumour cellular differentiation and size. METHODS: We retrospectively included 55 patients with 67 surgically confirmed small HCCs (≤3 cm) who underwent multiphasic MDCT and gadoxetic acid-enhanced MRI. Dynamic enhancement patterns were analysed according to tumour cellular differentiation and size. Hepatobiliary phase images were also analysed to assess their additional value. RESULTS: The proportion of small HCCs demonstrating the typical enhancement pattern differed depending on tumour cellular differentiation on both MRI (P = 0.001) and MDCT (P = 0.001), but differed depending on tumour size only on CT (P = 0.008). Gadoxetic acid-enhanced MRI more sensitively depicted the typical enhancement pattern than CT for all tumours (P = 0.001), for moderately or poorly differentiated HCCs (P = 0.021) and for HCCs ≤2 cm (P = 0.001). 80% of tumours with atypical enhancement could be diagnosed as HCC based on tumour size and hepatobiliary phase images. CONCLUSIONS: On both gadoxetic acid-enhanced MRI and multiphasic CT, the dynamic enhancement patterns of small HCCs (≤3 cm) differed according to tumour cellular differentiation. Gadoxetic acid-enhanced MRI more frequently demonstrated the typical HCC enhancement pattern than CT in small HCCs.

Preoperative Magnetic Resonance Imaging Features Associated with Positive Resection Margins in Patients with Invasive Lobular Carcinoma.

OBJECTIVE: To investigate preoperative magnetic resonance imaging (MRI) findings associated with resection margin status in patients with invasive lobular carcinoma (ILC) who underwent breast-conserving surgery. MATERIALS AND METHODS: One hundred and one patients with ILC who underwent preoperative MRI were included. MRI (tumor size, multifocality, type of enhancing lesion, distribution of non-mass enhancement [NME], and degree of background parenchymal enhancement) and clinicopathological features (age, pathologic tumor size, presence of ductal carcinoma in situ [DCIS] or lobular carcinoma in situ, presence of lymph node metastases, and estrogen receptor/progesterone receptor/human epidermal growth factor receptor type 2 status) were analyzed. A positive resection margin was defined as the presence of invasive cancer or DCIS at the inked surface. Logistic regression analysis was performed to determine pre- and postoperative variables associated with positive resection margins. RESULTS: Among the 101 patients, 21 (20.8%) showed positive resection margins. In the univariable analysis, NME, multifocality, axillary lymph node metastasis, and pathologic tumor size were associated with positive resection margins. With respect to preoperative MRI findings, multifocality (odds ratio [OR] = 3.977, p = 0.009) and NME (OR = 2.741, p = 0.063) were associated with positive resection margins in the multivariable analysis, although NME showed borderline significance. CONCLUSION: In patients with ILC, multifocality and the presence of NME on preoperative breast MRI were associated with positive resection margins.

Intranodular Vascularity May Be Useful in Predicting Malignancy in Thyroid Nodules with the Intermediate Suspicion Pattern of the 2015 American Thyroid Association Guidelines.

The aim of the study described here was to determine whether vascularity patterns on Doppler ultrasonography (US) differentiate benign and malignant thyroid nodules with the intermediate suspicion pattern based on the 2015 American Thyroid Association guidelines. A total of 411 benign or malignant thyroid nodules from 406 patients with intermediate-suspicion US features were retrospectively collected. Univariate and multivariate logistic regression analyses with the generalized estimating equation were used to identify factors predicting malignancy, and odds ratios with 95% confidence intervals were calculated. The vascularity patterns significantly differed between the benign (353 of 411, 85.9%) and malignant (58 of 411, 14.1%) nodules (p = 0.005). Only intranodular vascularity was significantly associated with malignancy on univariate analysis (p = 0.006) and was an independent predictor of malignancy on multivariate analysis (p = 0.004). In conclusion, intranodular vascularity on Doppler US may be useful for predicting malignancy in thyroid nodules with the intermediate-suspicion pattern.

Radiomics signature for prediction of lateral lymph node metastasis in conventional papillary thyroid carcinoma.

PURPOSE: Preoperative neck ultrasound (US) for lateral cervical lymph nodes is recommended for all patients undergoing thyroidectomy for thyroid malignancy, but it is operator dependent. We aimed to develop a radiomics signature using US images of the primary tumor to preoperatively predict lateral lymph node metastasis (LNM) in patients with conventional papillary thyroid carcinoma (cPTC). METHODS: Four hundred consecutive cPTC patients from January 2004 to February 2006 were enrolled as the training cohort, and 368 consecutive cPTC patients from March 2006 to February 2007 served as the validation cohort. A radiomics signature, which consisted of 14 selected features, was generated by the least absolute shrinkage and selection operator (LASSO) regression model in the training cohort. The discriminating performance of the radiomics signature was assessed in the validation cohort with the area under the receiver operating characteristic curve (AUC). RESULTS: The radiomics signature was significantly associated with lateral cervical lymph node status (p < 0.001). The AUC of its performance in discriminating metastatic and non-metastatic lateral cervical lymph nodes was 0.710 (95% CI: 0.649-0.770) in the training cohort and was 0.621 (95% CI: 0.560-0.682) in the validation cohort. CONCLUSIONS: The present study showed that US radiomic features of the primary tumor were associated with lateral cervical lymph node status. Although their discriminatory performance was slightly lower in the validation cohort, our study shows that US radiomic features of the primary tumor alone have the potential to predict lateral LNM.

Association Between Radiomics Signature and Disease-Free Survival in Conventional Papillary Thyroid Carcinoma.

Patients with papillary thyroid carcinoma (PTC) would benefit from risk stratification tools that can aid in planning personalized treatment and follow-up. The aim of this study was to develop a conventional ultrasound (US)-based radiomics signature to estimate disease-free survival (DFS) in patients with conventional PTC. Imaging features were extracted from the pretreatment US images of 768 patients with conventional PTC who were treated between January 2004 and February 2006. The median follow-up period was 117.3 months, with 85 (11.1%) events. A radiomics signature (Rad-score) was generated by using the least absolute shrinkage and selection operator (LASSO) method in Cox regression. The Rad-score was significantly associated with DFS (hazard ratio [HR], 3.087; P < 0.001), independent of clinicopathologic risk factors. A radiomics model which incorporated the Rad-score demonstrated better performance in the estimation of DFS (C-index: 0.777; 95% confidence interval [CI]: 0.735, 0.829) than the clinicopathologic model (C-index: 0.721; 95% CI: 0.675, 0.780). In conclusion, radiomics features from pretreatment US may be potential imaging biomarkers for risk stratification in patients with conventional PTC.

Diagnosis of Thyroid Nodules: Performance of a Deep Learning Convolutional Neural Network Model vs. Radiologists.

Computer-aided diagnosis (CAD) systems hold potential to improve the diagnostic accuracy of thyroid ultrasound (US). We aimed to develop a deep learning-based US CAD system (dCAD) for the diagnosis of thyroid nodules and compare its performance with those of a support vector machine (SVM)-based US CAD system (sCAD) and radiologists. dCAD was developed by using US images of 4919 thyroid nodules from three institutions. Its diagnostic performance was prospectively evaluated between June 2016 and February 2017 in 286 nodules, and was compared with those of sCAD and radiologists, using logistic regression with the generalized estimating equation. Subgroup analyses were performed according to experience level and separately for small thyroid nodules 1-2 cm. There was no difference in overall sensitivity, specificity, positive predictive value (PPV), negative predictive value and accuracy (all p > 0.05) between radiologists and dCAD. Radiologists and dCAD showed higher specificity, PPV, and accuracy than sCAD (all p < 0.001). In small nodules, experienced radiologists showed higher specificity, PPV and accuracy than sCAD (all p < 0.05). In conclusion, dCAD showed overall comparable diagnostic performance with radiologists and assessed thyroid nodules more effectively than sCAD, without loss of sensitivity.

Deep convolutional neural network for the diagnosis of thyroid nodules on ultrasound.

BACKGROUND: We designed a deep convolutional neural network (CNN) to diagnose thyroid malignancy on ultrasound (US) and compared the diagnostic performance of CNN with that of experienced radiologists. METHODS: Between May 2012 and February 2015, 589 thyroid nodules in 519 patients were diagnosed as benign or malignant by surgical excision. Experienced radiologists retrospectively reviewed the US of the thyroid nodules in a test set. CNNs were trained and tested using retrospective data of 439 and 150 US images, respectively. Diagnostic performances were compared between the two groups. RESULTS: Of the 589 thyroid nodules, 396 were malignant and 193 were benign. The area under the curve (AUC) for diagnosing thyroid malignancy was 0.805-0.860 for radiologists. The AUCs for diagnosing thyroid malignancy for the three CNNs were 0.845, 0.835, and 0.850. There was no significant difference in AUC between radiologists and CNNs. CONCLUSIONS: CNNs showed comparable diagnostic performance compared to experienced radiologists in differentiating thyroid malignancy on US.

High suspicion US pattern on the ATA guidelines, not cytologic diagnosis, may be a predicting marker of lymph node metastasis in patients with classical papillary thyroid carcinoma.

BACKGROUND: To evaluate the utility of ultrasound (US) patterns based on the 2015 American Thyroid Association (ATA) guidelines and cytologic diagnosis of the Bethesda System for Reporting Thyroid Cytopathology as predicting markers for lymph node metastasis (LNM) in classical papillary thyroid carcinoma (PTC). METHODS: A retrospective analysis of 657 patients with classical PTC who underwent ultrasound-guided fine-needle aspiration (US-FNA) and surgery were included in this study. The associations between LNM and the US features or the Bethesda System for Reporting Thyroid Cytopathology were evaluated. RESULTS: Multivariate logistic regression analysis showed that the high suspicion US pattern was independently associated with LNM (odds ratio = 3.081; 95% confidence interval = 1.515-6.262; P = .002). And the Bethesda category was not significantly associated with LNM (P = .056). CONCLUSIONS: The high suspicion US pattern of the 2015 ATA guidelines, not cytologic diagnosis, could be a predicting marker of LNM in patients with classical PTC.

Ultrasound-guided fine needle aspiration versus core needle biopsy: comparison of post-biopsy hematoma rates and risk factors.

PURPOSE: To compare post-biopsy hematoma rates between ultrasound guided-fine needle aspiration and ultrasound guided-core needle biopsy, and to investigate risk factors for post-biopsy hematoma. METHODS: A total of 5304 thyroid nodules which underwent ultrasound guided biopsy were included in this retrospective study. We compared clinical and US features between patients with and without post-biopsy hematoma. Associations between these features and post-biopsy hematoma were analyzed. RESULTS: Post-biopsy hematoma rate was 0.8% (43/5121) for ultrasound guided-fine needle aspiration and 4.9% (9/183) for ultrasound guided-core needle biopsy (P < 0.001). For ultrasound guided-fine needle aspiration, gender, age, size, presence of vascularity, and suspicious US features were not associated with post-biopsy hematoma according to experience level. Post-biopsy hematoma occurred significantly more with ultrasound guided-core needle biopsy (9/179, 5.0%) than with ultrasound guided-fine needle aspiration (9/1138, 0.8%) (P < 0.001) in experienced performers and ultrasound guided-core needle biopsy was the only significant risk factor for post-biopsy hematoma (adjusted Odds Ratio, 6.458, P < 0.001). CONCLUSION: Post-biopsy hematoma occurred significantly more in ultrasound guided-core needle biopsy than in ultrasound guided-fine needle aspiration and ultrasound guided-core needle biopsy was the only independent factor of post-biopsy hematoma in thyroid nodules.

Clinical Significance of Histogram Parameters on Elastography in Patients With Papillary Thyroid Microcarcinomas.

OBJECTIVE: The purpose of our study was to determine objective histogram parameters on elastography that could predict poor prognosis factors of conventional papillary thyroid microcarcinomas (PTMCs). METHODS: From September to November in 2012, 79 patients with a diagnosis of PTMCs were included. Mean values of clinicopathologic variables and histogram parameters on elastography were compared between groups with or without poor prognostic factors using the Student t test, χ test, or Fisher exact test. Multivariate logistic regression analysis adjusted for age, gender, and size was performed to investigate independent elastography parameters predicting extrathyroidal extension, lymph node metastasis, and high TNM stage (III-IV). RESULTS: Of 79 patients with PTMCs, 32 (40.5%) had extrathyroidal extension, 14 (17.7%) had lymph node metastasis, and 18 (22.8%) received a diagnosis with a high TNM stage. None of the histogram parameters on elastography had significant associations with any of the poor prognostic factors. CONCLUSIONS: There were no significant associations between all histogram parameters on elastography and known poor prognostic factors such as extrathyroidal extension, lymph node metastasis, and high TNM stage in patients with PTMCs.

Risk Stratification of Thyroid Nodules With Atypia of Undetermined Significance/Follicular Lesion of Undetermined Significance (AUS/FLUS) Cytology Using Ultrasonography Patterns Defined by the 2015 ATA Guidelines.

PURPOSE: The purpose of this study was to evaluate the predictive value of ultrasonography (US) patterns based on the 2015 American Thyroid Association (ATA) guidelines for malignancy in atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS) nodules. METHODS: From January 2014 to August 2015, 133 thyroid nodules that were initially diagnosed as AUS/FLUS on fine needle aspiration (FNA) were included in this study. Each nodule was assigned a category with US patterns defined by the ATA guidelines. Clinical characteristics and US patterns were compared between the benign and malignant nodules, and malignancy rates were calculated according to the ATA guidelines. RESULTS: The malignancy rate in the very low suspicion group was 0.0% in AUS/FLUS nodules. When applying the ATA guidelines, significant differences existed for US patterns between the benign and malignant nodules in the AUS group ( P = .032) but not the FLUS group ( P = .168). CONCLUSIONS: Ultrasonography patterns by the 2015 ATA guidelines can provide risk stratification for nodules with AUS cytology but not for ones with FLUS cytology. For nodules with AUS/FLUS cytology with the very low suspicion pattern of the ATA guidelines, follow-up US might be recommended instead of repeat FNA.

Validation of the modified 4-tiered categorization system through comparison with the 5-tiered categorization system of the 2015 American Thyroid Association guidelines for classifying small thyroid nodules on ultrasound.

BACKGROUND: The purpose of this study was to validate the modified 4-tiered categorization system and to compare stratification of malignancy risk in small thyroid nodules with the 2015 American Thyroid Association (ATA) management guidelines. METHODS: From January 2015 to December 2015, 737 thyroid nodules measured ≥ 1 cm and <2 cm were included in this study. Each nodule was assigned a category with the ultrasonographic patterns described by the 2015 ATA guidelines. RESULTS: On univariate analysis, there was no difference of malignancy risk between low suspicion and very low suspicion nodules (P = .584). Therefore, we suggested a modified 4-tiered categorization, which combines very low suspicion and low suspicion nodules into the "revised low suspicion" category. Specificity, positive predictive value (PPV) and accuracy were higher with the modified 4-tiered categorization system (P < .001 for all). CONCLUSION: The modified 4-tiered categorization system allows more efficient management with better diagnostic performance than the 2015 ATA categorization system in small thyroid nodules.

Clinical Parameter for Deciding the BRAFV600E Mutation Test in Atypia of Undetermined Significance/Follicular Lesion of Undetermined Significance Thyroid Nodules: US Features According to TIRADS.

This study aimed to investigate the usefulness of a thyroid imaging reporting and data system (TIRADS) to select thyroid nodules with atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) cytology for additional BRAF mutation testing. Three hundred three thyroid nodules were included. Statistical analysis was performed at both patient and nodule levels according to BRAF mutation positivity and clinical factors. Univariate and multivariate logistic regression analyses were performed to assess independent associations between BRAF mutation positivity and clinical factors. Of 303 AUS/FLUS nodules, 16 (5.3%) of 303 nodules had the BRAF mutation. The frequency of the BRAF mutation according to the TIRADS was 35.7% for category 5, 10.8% for category 4c, 2.5% for category 4b, 1.1% for category 4a, and 0% for category 3 nodules (P < 0.001). On multivariate analysis, BRAF mutation positivity was significantly associated with high suspicion on the TIRADS (odds ratio, 15.247; P < 0.001). In conclusion, the ultrasonography patterns of the TIRADS can be used as a clinical parameter for deciding the BRAF mutation test in thyroid nodules with AUS/FLUS cytology.

The thyroid imaging reporting and data system on US, but not the BRAFV600E mutation in fine-needle aspirates, is associated with lateral lymph node metastasis in PTC.

The majority of patients with papillary thyroid carcinoma (PTC) have an excellent prognosis, but some show poorer outcomes and would benefit from adjunctive prognostic tools. The B-Raf proto-oncogene, serine/threonine kinase (BRAF) mutation, either based on both its presence or its quantitative measurement, and ultrasound (US) features may serve as a prognostic marker. The aim of this study was to investigate (1) the association between clinical-pathologic prognostic factors and the BRAF mutation found in fine-needle aspirates, based on both its presence and its corresponding cycle threshold (Ct) value, and (2) the association between prognostic factors and suspicious US features classified by the thyroid imaging reporting and data system (TIRADS) in PTC.Two-hundred fifty-eight consecutive patients with PTC > 1 cm and who underwent preoperative US-guided fine-needle aspiration were included in this retrospective study. Clinical-pathologic variables were compared between patients with and without the BRAF mutation. Multivariate analyses were performed to investigate (1) the association between clinical-pathologic prognostic factors and the BRAF mutation found in fine-needle aspirates, based on both its presence and corresponding Ct values, and (2) the association between prognostic factors and suspicious TIRADS US features.BRAF-positive patients had a higher proportion of multiple tumors (P = 0.017). The number of suspicious US features classified by the TIRADS was an independent factor for predicting lateral lymph node metastasis, both in all 258 patients (odds ratio [OR] = 1.902, P = 0.005) and in 214 BRAF-positive patients (OR = 1.686, P = 0.037). The BRAF mutation status or BRAFCt values were not associated with any of the clinical-pathologic prognostic factors.In conclusion, a higher number of suspicious US features classified by the TIRADS, but not the BRAF mutation, are associated with lateral lymph node metastasis in patients with PTC, and can aid in the preoperative identification of patients at increased risk of lateral lymph node metastasis.

Real-Time PCR Cycle Threshold Values for the BRAFV600E Mutation in Papillary Thyroid Microcarcinoma May Be Associated With Central Lymph Node Metastasis: A Retrospective Study.

Papillary thyroid microcarcinoma (PTMC) usually has excellent prognosis, but a small subset shows aggressive behavior. Although the B-Raf proto-oncogene, serine/threonine kinase (BRAF)V600E mutation is the most common oncogenic alteration in PTMCs, it is frequently heterogeneously distributed within tumors. The aim of this study was to investigate the association of the BRAFV600E mutation found in fine needle aspirates from PTMCs with known clinicopathologic prognostic factors, based on both its presence and a quantitative approach that uses cycle threshold (Ct) values obtained by a real-time PCR technique. The 460 PTMC patients were included, with 367 patients having the BRAFV600E mutation. Clinicopathologic variables were compared between patients with and without the BRAFV600E mutation. BRAFV600E Ct values were compared according to clinicopathologic prognostic factors. Multivariate analyses were performed to evaluate factors predicting extrathyroidal extension and central and lateral lymph node metastasis (LNM). Each analysis used either the BRAFV600E mutation status or the Ct value as an independent variable for all the study patients and the 367 BRAFV600E-positive patients. Receiver-operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic performance of BRAFV600E Ct values in predicting central and lateral LNM. The BRAFV600E mutation status was not associated with clinicopathologic prognostic factors among the 460 PTMC patients. Of the 367 BRAFV600E-positive patients, Ct values were significantly lower in patients with central and lateral LNM (P < 0.001, P = 0.007). The Ct value was the only independent factor to predict central LNM (OR 0.918, P = 0.025). The area under the ROC curve (AUC) for diagnosing central LNM was 0.623 (sensitivity, 50.0%; specificity, 71.9%) and for diagnosing lateral LNM, it was 0.796 (sensitivity, 71.4%; specificity, 94.7%). In conclusion, real-time PCR Ct values for the BRAFV600E mutation obtained from fine needle aspirates can be associated with central LNM in PTMC patients. Although BRAFV600E Ct values did not reach statistical significance for predicting lateral LNM in our study, further validation through larger studies can be used to overcome any possible type-II errors. With further studies, Ct values for the BRAFV600E mutation obtained from fine needle aspirates may have important implications for predicting both central and lateral LNM in patients with PTMCs.