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      Large (≥3cm) thyroid nodules with benign cytology: Can Thyroid Imaging Reporting and Data System (TIRADS) help predict false-negative cytology?

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          Abstract

          Background

          There is controversy about the accuracy of the fine-needle aspiration (FNA) cytology results in large sized thyroid nodules. Our aim was to evaluate the false-negative rate of FNA for large thyroid nodules and the usefulness of the Thyroid Imaging Reporting and Data System (TIRADS) in predicting false-negative cytology for large thyroid nodules with benign cytology.

          Methods

          632 thyroid nodules larger than or equal to 3cm in size with subsequent benign cytology on US-guided FNA were included. US features of internal composition, echogenicity, margin, calcifications, and shape were evaluated, and nodules were classified according to TIRADS. TIRADS category 3 included nodules without any of the following suspicious features:solidity, hypoechogenicity or marked hypoechogenicity, microlobulated or irregular margins, microcalcifications, and taller-than-wide shape. Category 4a, 4b, 4c, and 5 were assigned to nodules showing one, two, three or four, or five suspicious US features, respectively. US features associated with malignancy for these lesions were analyzed and malignancy risk according to TIRADS was calculated.

          Results

          Of the 632 lesions, 23 lesions(3.6%) were malignant and 609(96.4%) were benign, suggesting a 3.6% false-negative rate for FNA cytology. Of the 23 malignant lesions, final pathology was mainly follicular carcinoma minimally invasive(65.2%, 15/23) and the follicular variant of papillary carcinoma(26.1%, 6/23). The malignancy risks of categories 3, 4a, 4b, and 4c nodules were 0.9%, 4.6%, 10.0%, and 11.8%, respectively.

          Conclusion

          Large thyroid nodules with benign cytology had a relatively high false-negative risk of 3.6% and TIRADS was helpful in predicting false-negative cytology for these lesions.

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          Most cited references31

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          Core-needle biopsy is more useful than repeat fine-needle aspiration in thyroid nodules read as nondiagnostic or atypia of undetermined significance by the Bethesda system for reporting thyroid cytopathology.

          Thyroid nodules with fine-needle aspiration (FNA) readings of nondiagnostic or atypia of undetermined significance (AUS), also referred to as follicular lesion of undetermined significance (FLUS) are problematic for their optimal management. The usefulness of performing a core-needle biopsy (CNB) to clarify whether these nodules are benign or malignant has not been established. The purpose of the present study was to determine whether CNB provides better diagnostic information than repeat FNA (rFNA) in thyroid nodules having nondiagnostic or AUS/FLUS readings. The Bethesda System for Reporting Thyroid Cytopathology was used for FNA readings and for CNB readings. The study included 225 thyroid nodules from 220 consecutive patients who previously had nondiagnostic (Group N-DIAG, n=64) or AUS/FLUS (Group AF, n=161) FNA readings. All patients simultaneously underwent rFNA and CNB of each nodule. The nondiagnostic and AUS/FLUS readings by rFNA and by CNB were compared. The diagnostic sensitivities of rFNA and CNB for malignancy in thyroid nodules were also assessed. Statistical analysis was performed using a McNemar's test. In N-DIAG Group, the nondiagnostic readings for the CNBs were lower than that those for rFNAs (1.6% vs. 28.1%, p<0.001). In the AF Group, the AUS/FLUS readings for the CNBs were lower than those for the rFNAs (23.6% vs. 39.8%, p<0.001). The inconclusive diagnoses (nondiagnostic or AUS/FLUS) for the CNBs were lower than those for the rFNAs in Group N-DIAG (12.5% vs. 45.3%, p<0.001) and Group AF (26.7% vs. 49.1%, p<0.001). The sensitivity of CNB for thyroid malignancy was higher than that of rFNA in Group N-DIAG (100% vs. 71.4%, p=0.125) and Group AF (78.5% vs. 55.4%, p<0.001). After patients have had one FNA of a thyroid nodule yielding inconclusive diagnostic results (nondiagnostic or AUS/FLUS), CNB is more useful than rFNA for reducing the frequency of inconclusive diagnostic results. CNB will improve the diagnostic performance for malignancy more than rFNA in thyroid nodules that on the first FNA had nondiagnostic or AUS/FLUS readings.
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            Interobserver and intraobserver variations in ultrasound assessment of thyroid nodules.

            Thyroid ultrasound (US) is used as the first diagnostic tool to assess the management of the disease. In spite of its importance, US is a very subjective method and highly dependent on the skill of the performer. There have been few reports evaluating thyroid US performance and even fewer reports of observer variability in US assessment. Therefore, we evaluated inter- and intraobserver variations in US assessment of thyroid nodules and diagnosis among four radiologists and estimated its diagnostic accuracy. A total of 204 thyroid nodules in 144 patients were reviewed. There were 89 benign and 115 malignant cases. Four radiologists with more than 5 years of experience independently reviewed US images twice at 6-week intervals. Echogenicity, composition, margin, shape, calcification, vascularity, and final assessment were evaluated. Inter- and intraobserver variations were determined with Cohen's kappa statistics, and accuracy was calculated. For interobserver variations, echogenicity showed slight agreement (kappa = 0.34); composition, margin, calcification, and final assessment had fair agreement (kappa = 0.59, 0.42, 0.58, and 0.54, respectively); shape and vascularity showed substantial agreement (kappa = 0.61 and 0.64, respectively). For intraobserver variability, almost all showed substantial agreement (kappa > 0.61). Overall sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for the four radiologists were 88.2%, 78.7%, 76.2%, 89.6%, and 82.8%, respectively. Experienced radiologists showed more than a moderate degree of agreement in US assessment of thyroid nodules, and their final assessments were highly accurate.
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              Value of US correlation of a thyroid nodule with initially benign cytologic results.

              To investigate the value of ultrasonographic (US) features in thyroid nodules with initially benign cytologic results. The institutional review board approved this retrospective study and required neither patient approval nor informed consent for the review of images and records. From October 2003 to February 2006, 6118 focal thyroid nodules in 6025 consecutive patients underwent US-guided fine-needle aspiration biopsy (FNAB). This study included 1343 nodules 1 cm or larger in 1302 patients that were diagnosed as benign at initial cytologic evaluation and underwent pathologic or follow-up study. We compared the risk of malignancy according to US findings and calculated the likelihoods of different subgroups having benign nodules. In total, 26 (1.9%) malignant and 1317 (98.1%) benign nodules were found according to reference standards. If initial cytologic results showed benign thyroid nodules, the likelihood of the nodule actually being benign was 98.1%. When a thyroid nodule had benign results at both initial and repeat FNAB, the likelihood increased to 100%. The likelihood of having a benign thyroid nodule with suspicious US features was lower (79.6%) than having a benign thyroid nodule with negative US features (99.4%, P<.001). In the nodule with benign features at initial US, the risk of malignancy for a thyroid nodule with an increase in size at follow-up US was slightly higher (1.4%) than that of a thyroid nodule with no interval change or decrease in size, but it was not significantly different (0.5%, P = .354). Repeat FNAB should be performed for thyroid nodules that have suspicious US features, even if the initial cytologic results indicate that it is a benign lesion.
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                Author and article information

                Contributors
                Role: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: ResourcesRole: ValidationRole: VisualizationRole: Writing – original draft
                Role: Writing – review & editing
                Role: Writing – review & editing
                Role: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: ValidationRole: Writing – original draft
                Role: InvestigationRole: Resources
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                12 October 2017
                2017
                : 12
                : 10
                : e0186242
                Affiliations
                [1 ] Department of Radiology, Severance Hospital, Research Institute of Radiological Science, Yonsei University, College of Medicine, Seoul, Korea
                [2 ] Department of Pathology, Severance Hospital, Yonsei University, College of Medicine, Seoul, Korea
                University of Toronto, CANADA
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                [¤]

                Current address: Department of Radiology, Dongtan Sacred Heart Hospital, Hallym University, College of Medicine, Hwaseong, Korea

                Author information
                http://orcid.org/0000-0002-3368-5013
                Article
                PONE-D-17-17609
                10.1371/journal.pone.0186242
                5638398
                29023564
                33392bea-eb88-4e7b-88c7-ddcb5fee97d3
                © 2017 Nam et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 10 May 2017
                : 27 September 2017
                Page count
                Figures: 3, Tables: 4, Pages: 14
                Funding
                The authors received no specific funding for this work.
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