Thyroid Nodules with Indeterminate Cytology: Utility of the American Thyroid Association Sonographic Patterns for Cancer Risk Stratification

The fine needle aspiration (FNA) cytology is the gold standard for the preoperative diagnosis of thyroid cancer. However, up to 30% of FNA examinations yield nondiagnostic or indeterminate results and this complicates patient management. Clinical features and ultrasound (US) patterns, including US risk stratification systems, could be useful in the preoperative diagnostic workup and prediction of malignancy, but the evidences are not univocal. Methods: 400 consecutive patients subjected to thyroid surgery were retrospectively enrolled at our institution in Calabria, Southern Italy. Preoperative US and FNA cytological descriptions, formulated according to the “Italian consensus for reporting thyroid fine-needle aspiration cytology” (ICCRTC) classification and three US risk stratification systems (those developed by the American Association of Clinical Endocrinologists, American College of Endocrinology and Associazione Medici Endocrinologi (AACE/ACE/AME), American Thyroid Association (ATA), and American College of Radiology (ACR-TIRADS)), were collected, along with histological results. Results: 147 thyroid cancer cases, in large majority papillary carcinomas, were detected on final histological examination. Almost two-thirds of patients subjected to thyroid surgery for either benign or malignant lesions were female. Patient’s age ≤20 years and between 21–30 years were clinical features associated with increased risk of thyroid cancer in logistic regression analyses. US features associated with thyroid cancer included irregular margins, solid composition, microcalcifications, and marked hypoechogenicity. The AACE/ACE/AME, ATA, and ACR-TIRADS risk categories, corresponding to specific US patterns, were strong predictors of malignancy in both genders, but not in nodules with indeterminate cytology. A measured difference between the longitudinal (L) and the anteroposterior (AP) diameter >5 mm, a proxy for a parallel-oriented oval shape of a nodule, emerged as a robust protective factor against thyroid cancer (OR 0.288 (95%CI 0.817–0.443); p < 0.001), regardless of cytological risk. Conclusions: Some, but not all, well-established predictors of TC have been confirmed in this study. Controversy surrounds the diagnostic performance of US risk stratification systems for the detection of thyroid cancer in the subgroup of nodules with indeterminate cytology, suggesting their use only to set the thresholds for FNA. A measured difference between L and AP diameters >5 mm may represent an additional and practical tool for ruling out malignancy in thyroid nodules, with the potential to reduce unnecessary surgical procedures.

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ACR TI-RADS and ATA US scores are helpful for the management of thyroid nodules with indeterminate cytology

BMC Endocrine Disorders ◽

10.1186/s12902-019-0429-5 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 11

Author(s):

Thayse Lozovoy Madsen Barbosa ◽

Cleo Otaviano Mesa Junior ◽

Hans Graf ◽

Teresa Cavalvanti ◽

Marcus Adriano Trippia ◽

...

Keyword(s):

Thyroid Nodules ◽

Clinical Decision Making ◽

Clinical Decision ◽

Needle Aspiration ◽

Molecular Testing ◽

American Thyroid Association ◽

Institutional Review ◽

The Us ◽

Risk Of Malignancy ◽

Indeterminate Cytology

Abstract Background Cytologically indeterminate thyroid nodules currently present a challenge for clinical decision-making. The main aim of our study was to determine whether the classifications, American College of Radiology (ACR) TI-RADS and 2015 American Thyroid Association (ATA) guidelines, in association with The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC), could be used to stratify the malignancy risk of indeterminate thyroid nodules and guide their clinical management. Methods The institutional review board approved this retrospective study of a cohort of 140 thyroid nodules in 139 patients who were referred to ultrasound-guided fine-needle aspiration cytology (FNAC) from January 2012 to June 2016 with indeterminate cytological results (44 Bethesda III, 52 Bethesda IV and 44 Bethesda V) and in whom pre-FNAC thyroid US images and histological results after surgery were available. Each included nodule was classified by one radiologist blinded to the cytological and histological diagnoses according to the ACR TIRADS scores and the US patterns as recommended in the 2015 ATA guidelines. The risk of malignancy was estimated for Bethesda, TI-RADS scores, ATA US patterns and their combination. Results Of the 140 indeterminate thyroid nodules examined, 74 (52.9%) were histologically benign. A different rate of malignancy (p < 0.001) among Bethesda III, IV and V was observed. The rate of malignancy increased according to the US suspicion categories (p < 0.001) in both US classifications (TI-RADS and ATA). Thyroid nodules classified as Bethesda III and the lowest risk US categories (very low, low and intermediate suspicion by ATA and 2, 3 and 4a by TI-RADS) displayed a sensitivity of 95.3% for both classifications and a negative predictive value of 94.3 and 94.1%, respectively. The highest risk US categories (high suspicion by ATA and 4b,4c and 5 by TI-RADS) were significantly associated with cancer (odds ratios [ORs] 14.7 and 9.8, respectively). Conclusions Ultrasound classifications, ACR TI-RADS and ATA guidelines, may help guide the management of indeterminate thyroid nodules, suggesting a conservative approach to nodules with low-risk US suspicion and Bethesda III, while molecular testing and surgery should be considered for nodules with high-risk US suspicion and Bethesda IV or V.

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Ultrasound characterization for thyroid nodules with indeterminate cytology: inter-observer agreement and impact of combining pattern-based and scoring-based classifications in risk stratification

Endocrine ◽

10.1007/s12020-019-02000-0 ◽

2019 ◽

Vol 66 (2) ◽

pp. 278-287 ◽

Cited By ~ 4

Author(s):

Cesar A. Lam ◽

Melissa J. McGettigan ◽

Zachary J. Thompson ◽

Laila Khazai ◽

Christine H. Chung ◽

...

Keyword(s):

Risk Stratification ◽

Thyroid Nodules ◽

Observer Agreement ◽

Indeterminate Cytology

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Ultrasonography Classification of the American Thyroid Association for Predicting Malignancy in Thyroid Nodules >1cm with Indeterminate Cytology: A Prospective Study

Hormone and Metabolic Research ◽

10.1055/a-0655-3016 ◽

2018 ◽

Vol 50 (08) ◽

pp. 597-601 ◽

Cited By ~ 8

Author(s):

Tiara Rocha ◽

Pedro Rosario ◽

Alexandre Silva ◽

Maurício Nunes ◽

Tulio Silva ◽

...

Keyword(s):

Prospective Study ◽

Thyroid Nodules ◽

Thyroid Neoplasms ◽

Needle Aspiration ◽

American Thyroid Association ◽

Molecular Tests ◽

Indeterminate Cytology ◽

A Prospective Study ◽

Doppler Analysis

AbstractThe objective of this prospective study was to evaluate the ultrasonography classification of the American Thyroid Association (ATA) for predicting malignancy in thyroid nodules >1 cm with indication for fine-needle aspiration (FNA) whose cytology was indeterminate. Additionally, the combination of the ATA classification with Doppler analysis was evaluated. All patients with thyroid nodules >1 cm were eligible. Each nodule was assigned to one of the ATA categories. Exclusively or predominantly intranodular vascularity was considered suspicious. One hundred and thirty-seven patients with 143 nodules underwent FNA and those with indeterminate cytology (Bethesda category III or IV) were selected. All patients were referred for surgery. Among the 143 nodules evaluated, 92 were benign, 33 were malignant, 13 were noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP), and 5 were tumors of uncertain malignant potential (TUMP). The rate of malignancy, including NIFTP and TUMP in this definition, was 80%, 42.8%, 13%, 10%, and 23% for nodules with a high suspicion, intermediate suspicion, low suspicion, very low suspicion, and undefined ultrasonographic pattern, respectively. Considering NIFPT and TUMP as benign, these rates were 72%, 22.4%, 4.3%, 0%, and 15.4%, respectively. The addition of Doppler analysis did not significantly improve the prediction of malignancy obtained with the ATA classification alone. The results of this prospective study show the usefulness of the ATA ultrasonographic classification for predicting malignancy specifically in thyroid nodules >1 cm with indeterminate cytology. The ATA category of the nodule should influence the decision for follow-up, molecular tests, or surgery.

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Reducing the Number of Unnecessary Thyroid Biopsies While Improving Diagnostic Accuracy: Toward the “Right” TIRADS

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2018-01674 ◽

2018 ◽

Vol 104 (1) ◽

pp. 95-102 ◽

Cited By ~ 41

Author(s):

Giorgio Grani ◽

Livia Lamartina ◽

Valeria Ascoli ◽

Daniela Bosco ◽

Marco Biffoni ◽

...

Keyword(s):

Risk Stratification ◽

Thyroid Nodules ◽

False Negative ◽

False Negative Rate ◽

Needle Aspiration ◽

Classification Systems ◽

American Thyroid Association ◽

Predictive Values ◽

Korean Society ◽

The Right

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%.

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Taller-Than-Wide Shape: A New Definition Improves the Specificity of TIRADS Systems

European Thyroid Journal ◽

10.1159/000504219 ◽

2019 ◽

Vol 9 (2) ◽

pp. 85-91 ◽

Cited By ~ 6

Author(s):

Giorgio Grani ◽

Livia Lamartina ◽

Valeria Ramundo ◽

Rosa Falcone ◽

Cristiano Lomonaco ◽

...

Keyword(s):

Risk Stratification ◽

Diagnostic Performance ◽

Thyroid Nodules ◽

Negative Impact ◽

Lower Sensitivity ◽

Intraobserver Variability ◽

Transverse Diameter ◽

American Thyroid Association ◽

Alternative Definition ◽

The Impact

Introduction: A taller-than-wide (TTW) shape is a suspicious feature of thyroid nodules commonly defined as an anteroposterior/transverse diameter (AP/T) ratio >1. An intraobserver variability of up to 18% in AP diameter evaluations has been described, which may lead to overreporting of this feature. To potentially improve the reliability of the TTW definition, we propose an arbitrary ratio of ≥1.2. Objective: The aim of this study was to estimate the impact of this definition on diagnostic performance. Methods: We prospectively analyzed 553 thyroid nodules referred for cytology evaluation at an academic center. Before fine-needle aspiration, two examiners jointly defined all sonographic features considered in risk stratification systems developed by the American Thyroid Association (ATA), the American Association of Clinical Endocrinologists (AACE), the American College of Radiology (ACR TIRADS), the European Thyroid Association (EU-TIRADS), and the Korean Society of Thyroid Radiology (K-TIRADS). TTW was defined according to the current definition (AP/T diameter ratio >1) and an arbitrary alternative definition (AP/T ratio >1.2). Results: The alternative definition classified fewer nodules as TTW (28, 5.1% vs. 94, 17%). The current and proposed definitions have a sensitivity of 26.2 and 11.9% (p = 0.03) and a specificity of 83.8 and 95.5% (p < 0.001). Thus, as a single feature, the arbitrary definition has a lower sensitivity and a higher specificity. When applied to sonographic risk stratification systems, however, the proposed definition would increase the number of avoided biopsies (up to 58.2% for ACR TIRADS) and the specificity of all systems, without negative impact on sensitivity or diagnostic odds ratio. Conclusions: Re-defining TTW nodules as those with an AP/T ratio ≥1.2 improves this marker’s specificity for malignancy. Using this definition in risk stratification systems will increase their specificity, reducing the number of suggested biopsies without significantly diminishing their overall diagnostic performance.

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Risk Stratification in Patients With Follicular Neoplasm on Cytology: Use of Quantitative Characteristics and Sonographic Patterns

Frontiers in Endocrinology ◽

10.3389/fendo.2021.614630 ◽

2021 ◽

Vol 12 ◽

Author(s):

Ming-Hsun Wu ◽

Kuen-Yuan Chen ◽

Min-Shu Hsieh ◽

Argon Chen ◽

Chiung-Nien Chen

Keyword(s):

Risk Stratification ◽

Thyroid Nodules ◽

Region Of Interest ◽

Diagnostic Value ◽

Follicular Neoplasm ◽

American Thyroid Association ◽

Cad System ◽

Hospital Patients ◽

Risk Of Malignancy ◽

Us Findings

ObjectivesDifferentiating thyroid nodules with a cytological diagnosis of follicular neoplasm remains an issue. The goal of this study was to determine whether ultrasonographic (US) findings obtained preoperatively from the computer-aided detection (CAD) system are sufficient to further stratify the risk of malignancy for this diagnostic cytological category.MethodsFrom September 2016 to September 2018 in our hospital, patients diagnosed with Bethesda category IV (follicular neoplasm or suspicion of follicular neoplasm) thyroid nodules and underwent surgical excisions were include in the study. Quantification and analysis of tumor features were performed using CAD software. The US findings of the region of interest, including index of composition, margin, echogenicity, texture, echogenic dots indicative of calcifications, tall and wide orientation, and margin were calculated into computerized values. The nodules were further classified into American Thyroid Association (ATA) and American College of Radiology Thyroid Imaging Reporting & Data System (TI-RADS) categories.Results92 (10.1%) of 913 patients were diagnosed with Bethesda category IV thyroid nodules. In 65 patients, the histological type of the nodule was identified. The quantitative features between patients with benign and malignant conditions differed significantly. The presence of heterogeneous echotexture, blurred margins, or irregular margins was shown to have the highest diagnostic value. The risks of malignancy for nodules classified as having very low to intermediate suspicion ATA, non-ATA, and high suspicion ATA patterns were 9%, 35.7%, and 51.7%, respectively. Meanwhile, the risks of malignancy were 12.5%, 26.1%, and 53.8% for nodules classified as TIRADS 3, 4, and 5, respectively. When compared to human observers, among whom poor agreement was noticeable, the CAD software has shown a higher average accuracy.ConclusionsFor patients with nodules diagnosed as Bethesda category IV, the software-based characterizations of US features, along with the associated ATA patterns and TIRADS system, were shown helpful in the risk stratification of malignancy.

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Ultrasonography and the American Thyroid Association Ultrasound-Based Risk Stratification Tool: Utility in Pediatric and Adolescent Thyroid Nodules

Hormone Research in Paediatrics ◽

10.1159/000490468 ◽

2018 ◽

Vol 90 (2) ◽

pp. 93-101 ◽

Cited By ~ 8

Author(s):

Ana Creo ◽

Fares Alahdab ◽

Alaa Al Nofal ◽

Kristen Thomas ◽

Amy Kolbe ◽

...

Keyword(s):

Risk Stratification ◽

Thyroid Nodules ◽

Pediatric Patients ◽

Needle Aspiration ◽

American Thyroid Association ◽

Multiple Features ◽

Pediatric Malignancy ◽

Fine Needle ◽

Risk Stratification Tool ◽

Increased Blood Flow

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.

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ACR TI-RADS and ATA ultrasound classifications are helpful for the management of thyroid nodules located in the isthmus

Clinical Hemorheology and Microcirculation ◽

10.3233/ch-211304 ◽

2021 ◽

pp. 1-9

Author(s):

Jianhui Cao ◽

Weiwei Huang ◽

Pintong Huang ◽

Yunlin Huang

Keyword(s):

Risk Stratification ◽

Operating Characteristic ◽

Thyroid Nodules ◽

False Negative ◽

Roc Curves ◽

Needle Aspiration ◽

Maximum Diameter ◽

American Thyroid Association ◽

Management Recommendations ◽

Diagnostic Capabilities

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.

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