Corrigendum: The Risk Stratification of Papillary Thyroid Cancer With Bethesda Category III (Atypia of Undetermined Significance/Follicular Lesion of Undetermined Significance) by Thyroid Fine-Needle Aspiration Could Be Assisted by Tumor Size for Precision Treatment.

[This corrects the article DOI: 10.3389/fendo.2022.822423.].

Predictors of Malignancy in Thyroid Nodules Classified as Bethesda Category III.

OBJECTIVE: To determine predictors of malignancy in surgically treated Bethesda category III nodules. METHODS: Patients with surgically treated thyroid nodules classified as Bethesda category III were retrospectively enrolled. The association between clinical/sonographic features and postoperative pathology was evaluated using univariate and multivariate analyses. RESULTS: A total of 188 nodules from 184 patients were included. The overall malignancy rate was 54.3%. In univariate analysis, male sex, aspect ratio >1, microcalcification, unclear boundary, BRAFV600E mutation, and nuclear atypia were significantly associated with malignant disease in Bethesda category III nodules. Multivariate analysis confirmed that male sex, aspect ratio >1, microcalcification, and BRAFV600E mutation were independent predictors of malignant disease. CONCLUSIONS: Malignant disease was common in Bethesda category III nodules, and surgical treatment was strongly indicated in the presence of male sex, aspect ratio>1, microcalcification, and BRAFV600E mutation.

The Risk Stratification of Papillary Thyroid Cancer With Bethesda Category III (Atypia of Undetermined Significance/Follicular Lesion of Undetermined Significance) by Thyroid Fine-Needle Aspiration Could Be Assisted by Tumor Size for Precision Treatment.

Purpose: To investigate the clinical characteristics of papillary thyroid cancer (PTC) classified as Bethesda category III [atypia of undetermined significance (AUS)/follicular lesion of undetermined significance (FLUS)] by fine-needle aspiration (FNA) for precision treatment. Methods: A total of 1,739 patients diagnosed with Bethesda category III (AUS/FLUS) by FNA were investigated, and 290 patients diagnosed with PTC were analyzed. Results: The rate of papillary thyroid microcarcinoma (PTMC) was 82.1% (238/290). The rates of lymph node metastases were 44.9% (22/49) and 25.2% (56/222) for PTC and PTMC, respectively (p = 0.006). The rates of extra-thyroid extension were 46.2% (24/52) and 19.8% (47/237) (p < 0.001). Compared with PTMC, PTC had significantly higher odds ratios (ORs) of 3.41 (1.81-6.44, p < 0.001), 2.19 (1.16-4.13, p = 0.016), and 2.51 (1.29-4.88, p = 0.007) for extra-thyroid extension, multifocality, and lymph node metastases, respectively, after adjustment for age and gender. The larger size and BRAF V600E mutation had a robust synergistic effect for invasive features. The rates of lymph node metastases, multifocality, and extra-thyroid extension were significantly increased with larger sizes harboring BRAF V600E mutation. Compared with PTMC harboring wild type (WT)-BRAF, PTC harboring BRAF V600E mutation had adjusted higher ORs of 3.01 (1.26-8.68, p = 0.015), 3.20 (1.22-8.42, p = 0.018), and 5.62 (2.25-14.01, p < 0.001) for lymph node metastases, multifocality, and extra-thyroid extension, respectively. Conclusions: In this study, risk stratification was recommended for patients with Bethesda category III (AUS/FLUS) nodules with a size under 1 cm harboring WT-BRAF being regarded as low risk and should be recommended for active surveillance. Nodules with a size over 1 cm harboring WT-BRAF or those under 1 cm harboring BRAF V600E mutation could be regarded as moderate risk, and molecular testing should be recommended. However, those with a size over 1 cm harboring BRAF V600E mutation should be regarded as high risk, and a diagnostic surgery should be recommended.

Malignancy rates in thyroid nodules classified as Bethesda categories III and IV; a subcontinent perspective.

BACKGROUND: Bethesda category III and IV thyroid nodules fall in the indeterminate risk of malignancy category. These nodules have been a relatively elusive entity to manage as previous studies have shown a wide variation in malignancy rates in different regions and institutions across the world. However, data from the subcontinent with regards to this is scarce. AIM AND OBJECTIVE: This study aimed to determine the characteristics and malignancy rates of cytology proven Bethesda Category III and IV thyroid nodules and its association with clinical, histopathological and laboratory variables, in the regional population. METHOD: A retrospective search was performed on all patients with thyroid nodules who presented to this hospital, from January 2011 to September 2018. Patients who had cytology proven Bethesda category III and IV thyroid nodules that underwent surgery were included in the study. RESULTS: Malignancy in Bethesda Category III and Bethesda Category IV thyroid nodules was 29.6% and 47.1%, respectively. There was no significant association determined between malignancy rate and various clinical, histopathological, and radiological characteristics. CONCLUSION: The malignancy rates in Bethesda category III and IV thyroid nodules in this study are significantly higher than that initially suggested by the Bethesda consensus publication but is comparable to international data present.

Cytological Sub-Classification of Atypia of Undetermined Significance May Predict Malignancy Risk in Thyroid Nodules.

BACKGROUND: Atypia/follicular lesion of undetermined significance (AUS/FLUS) carries a malignancy risk reaching up to 50%. Based on the reported malignancy rate in a given population, the clinical practice towards such a category varies. We hereby identify clinical parameters for risk stratification to aid in decision-making for either surgical referral or a clinical follow-up. Our aim is to identify clinical parameters that guided both clinicians and patients at our institutions to reach a clinical decision including atypia types. METHODS: A retrospective review of patients with Bethesda III category thyroid nodules from tertiary centres in the Emirate of Abu Dhabi during January 2011 through December 2015 was carried out. Malignancy risk in Bethesda category III nodules and repeat FNA utility were calculated. Parameters that guided both clinicians and patients for appropriate referral to surgery were studied. RESULTS: Two hundred and two cases were included in the study. Of these, 101 cases underwent surgery initially following the first FNA and 10 cases following FNA repeat. Histology confirmed malignancy in (41%) of cases that went initially to surgery and in (40%) of cases that underwent a repeat FNA. Repeat FNA resulted in 17 (44.74%) cases being re-classified into benign category, 10 (26.3%) being AUS/FLUS category, 6 (15.7%) being both suspicious and malignant, and 5 (13.16%) being unsatisfactory. Repeating FNA resulted in a definitive diagnostic utility in 50% of the cases. Eighty percent of malignant cases demonstrated nuclear atypia. CONCLUSION: The relatively high malignancy rate in our institutions, the suspicious radiographic features, the atypia groups, and the repeat FNA predictive value stratified Bethesda III category nodules for proper malignancy prediction and appropriate management.

Atypia of undetermined significance/follicular lesions of undetermined significance: What radiologists need to know.

Atypia of undetermined significance/follicular lesions of undetermined significance (AUS/FLUS) refers to an intermediate histologic category of thyroid nodules in The Bethesda System for Reporting Thyroid Cytopathology. Although the risk of malignancy in this category was originally cited as 5-15%, recent literature has suggested higher rates of related malignancy ranging from 38% to 55%. Malignant nodules warrant surgery with total thyroidectomy or thyroid lobectomy, whereas benign nodules can be observed or followed with serial ultrasounds (US) based on their imaging characteristics. The management of nodules with a cytopathologic diagnosis of AUS/FLUS can be difficult because theses nodules lie between the extremes of benign and malignant. The management options for such nodules include observation, repeat fine-needle aspiration, and surgery. The use of molecular genetics, the identification of suspicious US characteristics, and the recognition of additional clinical factors are all important in the development of an appropriate, tailored management approach. Institutional factors also play a crucial role.

Risk stratification of thyroid nodules with Bethesda category III results on fine-needle aspiration cytology: The additional value of acoustic radiation force impulse elastography.

To assess the value of conventional ultrasound, conventional strain elastography (CSE) and acoustic radiation force impulse (ARFI) elastography in differentiating likelihood of malignancy for Bethesda category III thyroid nodules. 103 thyroid nodules with Bethesda category III results on fine-needle aspiration cytology (FNAC) in 103 patients were included and all were pathologically confirmed after surgery. Conventional ultrasound, CSE and ARFI elastography including ARFI imaging and point shear wave speed (SWS) measurement were performed. Univariate and multivariate analyses were performed to identify the independent factors associated with malignancy. Area under the receiver operating characteristic curve (Az) was calculated to assess the diagnostic performance. Pathologically, 65 nodules were benign and 38 were malignant. Significant differences were found between benign and malignant nodules in ARFI. The cut-off points were ARFI imaging grade ≥ 4, SWS > 2.94 m/s and SWS ratio > 1.09, respectively. ARFI imaging (Az: 0.861) had the highest diagnostic performance to differentiate malignant from benign nodules, following by conventional ultrasound (Az: 0.606 - 0.744), CSE (Az: 0.660) and point SWS measurement (Az: 0.725 - 0.735). Multivariate logistic regression analysis showed that ARFI imaging grade ≥ 4 was the most significant independent predictor. The combination of ARFI imaging with point SWS measurement significantly improved the specificity (100% vs. 80.0%) and positive predictive value (100 % vs. 72.9%) in comparison with ARFI imaging alone. ARFI elastography is a useful tool in differentiating malignant from benign thyroid nodules with Bethesda category III results on FNAC.

Thyroid imaging reporting and data system in assessment of cytological Bethesda Category III thyroid nodules.

OBJECTIVE: To assess the usefulness of thyroid imaging reporting and data system (TI-RADS) for cytological Bethesda Category III thyroid nodules (TNs). METHODS: This retrospective study included 121 patients with 121 TNs classified as Bethesda Category III at fine needle aspiration (FNA) cytology and thereafter underwent surgery. The TNs were classified according to US TI-RADS category and the malignancy risk of each category was calculated. RESULTS: Surgical pathology confirmed 43 (35.5%) malignant and 78 (64.5%) benign TNs. The malignancy risks of categories 3, 4a, 4b, 4c, and 5 TNs were 0%, 4.0%, 12.5%, 62.2%, and 100%, respectively. For those >10 mm (n = 55), the malignancy risks were 0%, 6.2%, 12.5%, 73.3%, and 100%, respectively, whereas for those ≤10 mm (n = 66), the risks were 0%, 0%, 12.5%, 56.7%, and 100%, respectively. CONCLUSION: Bethesda Category III TNs without suspicious US features or those ≤10 mm with only one suspicious US feature can be followed up with US.

Malignancy rate associated with Bethesda category III (AUS/FLUS) with and without repeat fine needle aspiration biopsy.

BACKGROUND: Selection of nodules for surgery diagnosed as Bethesda category III [atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) category] is important. It was aimed to define the malignancy rates associated with and without repeat fine needle aspiration biopsy (FNAB) and to define the contribution of repeat FNAB to triage to surgery or observation in nodules with AUS/FLUS FNAB. METHODS: The records of all patients with nodules who underwent FNAB and classified by Bethesda reporting system as AUS/FLUS at their institution were reviewed. Malignancy rates for patients with AUS/FLUS FNAB with and without repeat FNAB were calculated. RESULTS: Of the 582 patients who were classified as AUS/FLUS on initial FNAB, 179 underwent surgery with an associated malignancy rate of 22.9% (upper boundary). Risk of malignancy among all patients with AUS/FLUS nodules was 7% (lower boundary). The upper and lower boundaries of the malignancy rates with and without repeat FNAB were 38.6% and 15.6% for resected patients, and 13% and 4.6% for all patients, respectively. Reclassification rate with repeat FNAB was 56%. CONCLUSION: The findings showed that repeat FNAB for initial AUS/FLUS category was associated with a significantly increased malignancy rate compared with those without repeat FNAB. Repeat FNAB could help selection of patients with AUS/FLUS to triage to surgery. Therefore, repeat FNAB for nodules with AUS/FLUS on initial FNAB was suggested.

Atypia of undetermined significance and follicular lesions of undetermined significance: sonographic assessment for prediction of the final diagnosis.

OBJECTIVES: To determine whether radiologic assessment of thyroid nodules can potentially help guide clinical management after a cytologic diagnosis of atypia of undetermined significance or a follicular lesion of undetermined significance. METHODS: We identified 41 patients with 41 thyroid nodules initially diagnosed as atypia or follicular lesions of undetermined significance on fine-needle aspiration that were subsequently definitively diagnosed by either surgical resection or repeated fine-needle aspiration. All sonograms of nodules were reviewed by 2 blinded board-certifiedradiologists. Lesions were assessed in 3 ways: (1) Mayo pattern classification as benign, indeterminate, or worrisome for malignancy (Ultrasound Q 2005; 21:157-165); (2) thyroid imaging reporting and data system scores (scale of 1-5) based on 2 different previously published scoring criteria (Park et al [Thyroid 2009; 19:1257-1264] and Kwak et al [Radiology 2011; 260:892-899]); and (3) binary classification as benign or malignant. RESULTS: Of the 41 nodules, 25 had benign histologic findings, and 16 were malignant. Mayo pattern classification was 100% accurate for the benign score. Lesions with a Mayo score of indeterminate were malignant in 21% of cases (6 of 28) and benign in 79% (22 of 28). Lesions with a Mayo score of malignant were malignant in 91% of cases (10 of 11) and benign in 9% (1 of 11). Thyroid imaging reporting and data system scores had area under the receiver operating characteristic curve values of 0.827 for Park scores and 0.822 for Kwak scores. Radiologist binary classification of thyroid nodules showed 88% overall accuracy. CONCLUSIONS: Radiologist assessment of thyroid nodules in cases of atypia of undetermined significance or follicular lesions of undetermined significance is highly predictive of the final diagnosis and can help guide management of thyroid nodules of these pathologic types.