Improving the diagnosis of AUS/FLUS thyroid nodules using an algorithm with combination of BRAFV600E mutation analysis and ultrasound pattern-based risk stratification

Author(s):  
Ya-Fang Zhou ◽  
Yi-Feng Zhang ◽  
Hui-Jun Fu ◽  
Wei-Ping Yang ◽  
Chong-Ke Zhao ◽  
...  

Purpose: To propose a diagnostic algorithm for improving the diagnosis of atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS) thyroid nodules. Methods: This study retrospectively enrolled 77 consecutive patients with 81 AUS/FLUS nodules who underwent preoperative BRAFV600E mutation analysis. A new diagnostic algorithm was proposed that BRAFV600E mutation analysis for the Fine-needle aspiration cytology specimen was firstly carried out, in which positive BRAFV600E mutation indicated malignancy and classification of the nodules with negative BRAFV600E mutation was further performed based on ultrasound pattern-based risk stratification of American Thyroid Association Guidelines. The diagnostic performance of the new diagnostic algorithm was evaluated. Results: The sensitivity, specificity, positive predictive value, negative predictive value, accuracy and area under the receiver operating characteristic curve (AUROC) of new diagnostic algorithm were 94.6%, 84.0%, 91.4%, 86.9%, 90.1%, and 0.893, respectively. The proposed diagnostic algorithm significantly increased the diagnostic performances (AUROC: 0.893 vs. 0.837 and 0.795), sensitivity (94.6% vs. 71.4% and 75.0%), and accuracy (90.1% vs. 79.0% and 77.8%) compared with BRAFV600E mutation analysis alone and ultrasound pattern-based risk stratification alone (all P <  0.05). Conclusion: The proposed diagnostic algorithm is helpful for improving the diagnosis of AUS/FLUS nodules, which might be as a routine approach.

2017 ◽  
Vol 126 (9) ◽  
pp. 625-633 ◽  
Author(s):  
Ji Hye Lee ◽  
Kyunghwa Han ◽  
Eun-Kyung Kim ◽  
Hee Jung Moon ◽  
Jung Hyun Yoon ◽  
...  

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.


2018 ◽  
Vol 104 (1) ◽  
pp. 95-102 ◽  
Author(s):  
Giorgio Grani ◽  
Livia Lamartina ◽  
Valeria Ascoli ◽  
Daniela Bosco ◽  
Marco Biffoni ◽  
...  

Abstract Context The prevalence of thyroid nodules in the general population is increasingly high, and at least half of those biopsied prove to be benign. Sonographic risk-stratification systems are being proposed as “rule-out” tests that can identify nodules that do not require fine-needle aspiration (FNA) cytology. Objective To comparatively assess the performances of five internationally endorsed sonographic classification systems [those of the American Thyroid Association, the American Association of Clinical Endocrinologists, the American College of Radiology (ACR), the European Thyroid Association, and the Korean Society of Thyroid Radiology] in identifying nodules whose FNAs can be safely deferred and to estimate their negative predictive values (NPVs). Design Prospective study of thyroid nodules referred for FNA. Setting Single academic referral center. Patients Four hundred seventy-seven patients (358 females, 75.2%); mean (SD) age, 55.9 (13.9) years. Main Outcome Measures Number of biopsies classified as unnecessary, false-negative rate (FNR), sensitivity, specificity, predictive values, and diagnostic ORs for each system. Results Application of the systems’ FNA criteria would have reduced the number of biopsies performed by 17.1% to 53.4%. The ACR Thyroid Imaging Reporting and Data System (TIRADS) allowed the largest reduction (268 of 502) with the lowest FNR (NPV, 97.8%; 95% CI, 95.2% to 99.2%). Except for the Korean Society of Thyroid Radiology TIRADS, all other systems exhibited significant discriminatory performance but produced significantly smaller reductions in the number of procedures. Conclusions Internationally endorsed sonographic risk stratification systems vary widely in their ability to reduce the number of unnecessary thyroid nodule FNAs. The ACR TIRADS outperformed the others, classifying more than half the biopsies as unnecessary with a FNR of 2.2%.


2016 ◽  
Vol 60 (3) ◽  
pp. 205-210 ◽  
Author(s):  
Shweta Chaudhary ◽  
Yanjun Hou ◽  
Rulong Shen ◽  
Shveta Hooda ◽  
Zaibo Li

Objective: The Afirma gene expression classifier (GEC) is a molecular test to further classify indeterminate fine-needle aspiration (FNA) as benign or suspicious for malignancy. Study Design: A total of 158 FNAs with Bethesda category III/IV cytology were sent for an Afirma GEC test. We correlated the Afirma GEC results with surgical outcome and also compared the data after Afirma's implementation with the data before. Results: Among the 158 FNAs, the Afirma result was benign in 63 (40%), suspicious in 85 (54%) and unsatisfactory in 10 (6%). In total, 73 (86%) suspicious Afirma cases had surgery and 28 (38%) showed carcinoma. In contrast, only 8 (13%) benign Afirma cases had surgery and all of them were benign. The sensitivity, specificity, negative predictive value and positive predictive value (PPV) of Afirma were 100, 15, 100 and 38%, respectively. The PPV was 20% in cases with follicular lesion of undetermined significance, but was 50% in cases suspicious for follicular neoplasm (SFN). The surgical excisional rate was significantly decreased in SFN cases after the Afirma test. Conclusions: The Afirma GEC is useful for further risk stratifying SFN cases.


2020 ◽  
Vol 93 (4) ◽  
pp. 239-244
Author(s):  
Shruthi Arora ◽  
Jane Khoury ◽  
Andrew T. Trout ◽  
Janet Chuang

<b><i>Introduction:</i></b> The standard workup of thyroid nodules concerning for malignancy includes fine-needle aspiration (FNA). In 2015, the American Thyroid Association (ATA) guidelines for the management of pediatric thyroid nodules recommended that all nodules with a Bethesda III cytology undergo surgical resection. <b><i>Objectives:</i></b> To correlate a Bethesda III cytology with histologic and clinical outcomes to determine the relevance of the ATA recommendations, and to evaluate whether Thyroid Imaging Reporting and Data System (TI-RADS) scoring could identify Bethesda III nodules at a lower risk of malignancy. <b><i>Methods:</i></b> A retrospective chart review of patients who had undergone thyroid nodule FNA from 2008 to 2018 was performed. Malignancy rates were determined for each Bethesda category. The reference standard was histopathology or 2-year follow-up of imaging outcomes for nonoperative cases. Ultrasound exams of Bethesda III nodules were reviewed and TI-RADS scores assigned. <b><i>Results:</i></b> A total of 143 FNA samples from 128 patients were identified. The mean age was 14.9 years (range 7–22). Twenty-two (15%) of the FNA samples were Bethesda III; the malignancy rate was 38%. A TI-RADS score was assigned in 20 of the 22 Bethesda III nodules. ROC analysis found an optimal cut-off for malignancy prediction of ≥7 points (risk category TR5). The negative predictive value was 85.7% (95% CI 35.9–99.6) and the positive predictive value was 83.3% (95% CI 57.2–98.2). <b><i>Conclusion:</i></b> Although, at baseline, thyroid nodules with a Bethesda III classification carry a moderate risk of malignancy in the pediatric population, TI-RADS scoring can identify nodules with a lower risk within this group. If validated by larger studies, this can inform decision making and reduce unneeded surgery.


2018 ◽  
Vol 90 (2) ◽  
pp. 93-101 ◽  
Author(s):  
Ana Creo ◽  
Fares Alahdab ◽  
Alaa Al Nofal ◽  
Kristen Thomas ◽  
Amy Kolbe ◽  
...  

Background: Pediatric thyroid nodules are more likely to be malignant compared to those in adults and may have different concerning ultrasound (US) features. Recent adult guidelines stratify malignancy risk by US features. Our aim is to (1) describe and confirm US features that predict pediatric malignancy, and (2) apply the Adult American Thyroid Association (ATA) Risk Stratification Guidelines to a large pediatric cohort. Methods: We identified 112 children with 145 thyroid nodules from 1996 to 2015. Two blinded pediatric radiologists independently read all US images, described multiple features, and reported their overall impression: benign, indeterminate, or malignant. Each nodule was assigned an ATA risk stratification category. Radiologists’ impressions and ATA risk stratification were compared to histology and cytology results. Results: Multiple US features including a solid composition, presence of microcalcifications, irregular margins, increased blood flow, and hypoechogenicity were associated with increased odds of malignancy. ATA risk stratification correlated with the radiologists’ overall impression (p < 0.001). The sensitivity for detecting malignancy was comparable between both ATA stratification (91%) and the radiologists’ overall impression (90%). The specificity of the radiologists’ malignant overall impression (80%) was better compared to the ATA high risk stratification (54%). Conclusions: At our institution, pediatric radiologists’ overall impressions had similar sensitivity but better specificity for detecting malignancy than the ATA risk stratification tool by our convention. However, neither US-based methods perfectly discriminated benign from malignant nodules, supporting the continued need for fine needle aspiration for suspicious nodules. Further work is needed to develop an US-based scoring system specific to pediatric patients.


Author(s):  
Jianhui Cao ◽  
Weiwei Huang ◽  
Pintong Huang ◽  
Yunlin Huang

PURPOSE: To compare the application value of the American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS) and the American Thyroid Association (ATA) guidelines in the risk stratification of thyroid isthmic nodules. METHODS: A total of 315 patients with thyroid isthmic nodules (315 nodules) confirmed by surgical pathology or fine-needle aspiration biopsy (FNAB) were selected in this retrospective study. The nodules were evaluated and classified according to ACR TI-RADS and the ATA guidelines. Taking pathological results as the reference, receiver operating characteristic (ROC) curves were drawn to evaluate the diagnostic capabilities of the ACR TI-RADS and the ATA guidelines for the risk stratification of thyroid isthmic nodules. The unnecessary biopsy rates and false-negative rates were compared. RESULTS: Multivariate analysis of ultrasonographic features of suspicious malignancies showed that an aspect ratio >  1 was not an independent risk factor for malignant thyroid nodules located in the isthmus (odds ratio: 3.193, 95%confidence interval: 0.882–11.552) (P = 0.077). The area under the ROC curves for diagnosing malignant thyroid nodules located in the isthmus in by the ACR TI-RADS and the ATA guidelines were 0.853 and 0.835, respectively. Under the management recommendations of the ACR TI-RADS and ATA guidelines, the false-negative rates of malignant thyroid nodules were 66.2%(ATA intermediate suspicion), 62.3%(ACR TR 4), 81.8%(ATA high suspicion) and 86.5%(ACR TR 5). CONCLUSION: Both the ACR TI-RADS and the ATA guidelines have high diagnostic capabilities for the risk stratification of thyroid isthmic nodules. For ACR TR 4 and 5 and ATA intermediate- and high-suspicion thyroid isthmic nodules with a maximum diameter <  1 cm, the criteria for puncture should be lowered, and FNAB should be done to clarify their diagnosis.


2020 ◽  
Vol 26 (9) ◽  
pp. 945-952 ◽  
Author(s):  
Wei Yang ◽  
Ghaneh Fananapazir ◽  
Jennifer LaRoy ◽  
Machelle Wilson ◽  
Michael J. Campbell

Objective: Management of thyroid nodules with Bethesda category III and IV cytology on fine needle aspiration (FNA) is challenging as they cannot be adequately classified as benign or malignant. Ultrasound (US) patterns have demonstrated the utility in evaluating the risk of malignancy (ROM) of Bethesda category III nodules. This study aims to evaluate the value of 3 well-established US grading systems (American Thyroid Association [ATA], Korean Thyroid Imaging Reporting and Data System [Korean-TIRADS], and The American College of Radiology Thyroid Imaging Reporting and Data System [ACR-TIRADS]) in determining ROM in Bethesda category IV nodules. Methods: Ninety-two patients with 92 surgically resected thyroid nodules who had Bethesda category IV cytology on FNA were identified. Nodule images were retrospectively graded using the 3 systems in a blinded manner. Associations between US risk category and malignant pathology for each system were analyzed. Results: Of the 92 nodules, 56 (61%) were benign and 36 (39%) were malignant. Forty-seven per cent of ATA high risk nodules, 53% of K-TIRADS category 5 nodules, and 50% of ACR-TIRADS category 5 nodules were malignant. The ATA high-risk category had 25% sensitivity, 82% specificity, 47% positive predictive value (PPV) for malignancy. K-TIRADS category 5 had 25% sensitivity, 85% specificity, 53% PPV for malignancy. ACR-TIRADS category 5 had 25% sensitivity, 84% specificity, 50% PPV for malignancy. None of the 3 grading systems yielded a statistically significant correlation between US risk category and the ROM ( P = .30, .72, .28). Conclusion: The ATA, Korean-TIRADS, and ACR-TIRADS classification systems are not helpful in stratifying ROM in patients with Bethesda category IV nodules. Clinicians should be cautious of using ultra-sound alone when deciding between therapeutic options for patients with Bethesda category IV thyroid nodules. Abbreviations: ACR-TIRADS = The American College of Radiology Thyroid Imaging Reporting and Data System; ATA NSP = American Thyroid Association nodule sonographic patterns and risk of malignancy classification system; FN = follicular neoplasm; FNA = fine needle aspiration; FTC = follicular thyroid carcinoma; FVPTC = follicular variant of papillary thyroid carcinoma; HCC = Hurthle cell carcinoma; HCN = Hurthle cell neoplasm; K-TIRADS = Korean Thyroid Imaging Reporting and Data System; NIFTP = noninvasive follicular thyroid neoplasm with papillary-like nuclear features; NPV = negative predictive value; PPV = positive predictive value; ROM = risk of malignancy; US = ultrasound


2018 ◽  
Vol 33 (1) ◽  
pp. 1
Author(s):  
Hae Won Lee ◽  
So Young Ock ◽  
Bu Kyoung Kim ◽  
Su Kyoung Kwon ◽  
Young Sik Choi ◽  
...  

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