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Malignancy Risk and Related Factors of Atypia of Undetermined Significance/Follicular Lesion of Undetermined Significance in Thyroid Fine Needle Aspiration.

ABSTRACT: Atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) in thyroid fine needle aspiration (FNA) is a challenging category. The malignancy risk is different by multiple factors and subsequent management strategy is inconclusive. Therefore, we analyzed the malignancy risk of AUS/FLUS according to radiological and clinical features. A total of 687 nodules that had been initially diagnosed as AUS/FLUS were retrospectively reviewed from 6365 thyroid FNAs between 2011 and 2014. The ultrasonographic (US) features were categorized using the Korean Thyroid Imaging Reporting and Data System. Radiological and clinical features were compared according to the second FNA results or histologically confirmed results from surgery. Repeat FNA was performed on 248 (36%) nodules, and 49 (7%) nodules underwent immediate surgery. Among the 248 nodules subjected to repeated FNA, 49 (20%) nodules were diagnosed again as AUS/FLUS, 123 (50%) were found to be benign, and 47 (19%) were diagnosed as follicular neoplasm, suspicious for malignancy or malignant. Among histologically confirmed nodules, the US features were more unfavorable in malignant nodules, and hypo- or anechogenicity was associated with a higher risk of malignancy after adjusting for age, size, and other US features (P < 0.01). In conclusion, we observed that malignant nodules tended to show unfavorable US features, especially hypo- or anechogenicity. Age, sex, and thyroid function were not significantly associated with malignancy risk. We also found out that malignancy risk was not different between the group which underwent immediate operation following the AUS/FLUS diagnosis and the group which underwent repeated FNA after the initial diagnosis.

SUBMITTER: Hong SH

PROVIDER: S-EPMC6091291 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Malignancy Risk and Related Factors of Atypia of Undetermined Significance/Follicular Lesion of Undetermined Significance in Thyroid Fine Needle Aspiration.

Hong So-Hyeon SH Lee Hyejin H Cho Min-Sun MS Lee Jee Eun JE Sung Yeon-Ah YA Hong Young Sun YS

International journal of endocrinology 20180730

Atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) in thyroid fine needle aspiration (FNA) is a challenging category. The malignancy risk is different by multiple factors and subsequent management strategy is inconclusive. Therefore, we analyzed the malignancy risk of AUS/FLUS according to radiological and clinical features. A total of 687 nodules that had been initially diagnosed as AUS/FLUS were retrospectively reviewed from 6365 thyroid FNAs between ...[more]

PMID: 30154840

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Project description:BackgroundMicroRNA (miR) expression signatures are proposed to be able to differentiate thyroid cancer from benign thyroid lesions. We selected eight miRs (miR-146b, -221, -187, -197, -346, -30d, -138, and -302c) to examine the potential use of miRs to supplement diagnostic cytology in cases designated as "atypia of undetermined significance."MethodsmiR expression was measured in thyroid fine needle aspiration (FNA) specimens by quantitative polymerase chain reaction. Gene expression analyses and linear discriminant analysis (LDA) were performed in a training sample set (n=60) to obtain a classification rule to predict FNA cases as benign or malignant. The predictions were cross-validated by comparing with the corresponding histological diagnoses. A validation sample set (n=68) was further tested with the established four-miR LDA classification rule.ResultsA set of four miRs (miR-146b, -221, -187, and -30d) was identified that could differentiate malignant from benign lesions. A four-miR LDA classification rule was obtained and used to predict FNA cases as benign or malignant. For the training sample set, we obtained a diagnostic accuracy of 93.3%, sensitivity of 93.2%, specificity of 93.8%, positive predictive value (PPV) of 0.98, and negative predictive value (NPV) of 0.83. For the validation sample set, we obtained a diagnostic accuracy of 85.3%, sensitivity of 88.9%, specificity of 78.3%, PPV of 0.89, and NPV of 0.78. For the 30 atypia cases in the validation sample set, we obtained a diagnostic accuracy of 73.3%, sensitivity of 63.6%, specificity of 78.9%, PPV of 0.64, and NPV of 0.79. Based on the miR predictions, we classified the atypia cases predicted as "malignant" into "high risk" and those predicted as "benign" into "low risk" categories. While thyroid carcinomas, particularly papillary thyroid carcinomas (PTCs), were relatively enriched in the high-risk category, this particular miR panel is subject to inaccurate results in follicular neoplasias in atypia cases.ConclusionsWe demonstrate that miR amplification from FNA samples is feasible and that the particular four miR profile in this study can identify PTCs. However, further refinement is required for application to FNA cytology of "atypia of undetermined significance" cases due to low accuracy in classifying follicular neoplasias.

Project description:BackgroundThe management of thyroid nodules classified as atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS) has been a subject of ongoing debate. Therefore, the aim of this study was to investigate a cost-effective approach for managing these nodules by combining BRAFV600E mutation analysis with the guidelines provided by the American Thyroid Association (ATA) or the American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TIRADS).MethodsThis study included 762 AUS/FLUS nodules in 551 patients with a postoperative pathology. A preoperative BRAFV600E gene test and an evaluation using the ATA guidelines and ACR-TIRADS were performed. Two combined diagnostic approaches were employed: In method 1, all nodules underwent BRAFV600E gene testing, and nodules testing positive for BRAFV600E or for risk stratification systems (RSSs) were diagnosed as malignant, while those with negative results in both tests were considered benign. In method 2 (modified combination method), nodules were reclassified into low-risk (category 2 and 3 in the ATA guidelines and ACR-TIRADS), medium-risk (category 4), and high-risk (category 5) groups based on the malignancy rate of the RSSs. BRAFV600E gene testing was applied only with the medium-risk group. Nodules with positive BRAFV600E mutation were upgraded to the high-risk group, while negative cases remained in the medium-risk group.ResultsBoth malignancy rates and positive BRAFV600E mutation rates increased with the increase in RSS category (P<0.001). The combination of ACR with BRAFV600E gene testing significantly improved the area under the curve (AUC) compared to the use of ACR or BRAFV600E alone (the AUCs for ACR combined with BRAFV600E, modified ACR combined with BRAFV600E, ACR alone, and BRAFV600E alone were 0.875, 0.878, 0.832, and 0.839, respectively; P<0.05 for both combinations vs. ACR or BRAFV600E alone). Similarly, ATA combined with BRAFV600E showed significant improvements in AUC compared to ATA alone (the AUCs for ATA combined with BRAFV600E, modified ATA combined with BRAFV600E, and ATA alone were 0.851, 0.846, 0.809, respectively; P<0.001 for both combination methods vs. ATA alone), but there was no significant difference observed compared to using BRAFV600E alone (P=0.450 and P=0.680 for both combination methods vs. BRAFV600E). Notably, the AUC of ACR combined with BRAFV600E was greater than that of ATA combined with BRAFV600E (P=0.047 and P=0.007 for both combination methods, respectively). There were no significant differences in diagnostic performance between the two combination approaches (P=0.428 for ACR combined with BRAFV600E and P=0.314 for ATA combined with BRAFV600E). Performing BRAFV600E gene testing only on the medium-risk groups (modified combination method) significantly reduced the rate of BRAFV600E gene testing (P<0.001) without increasing the false-negative rate (P=0.818 and P=0.394 for ACR and ATA, respectively).ConclusionsIncorporating the BRAFV600E gene test exclusively for nodules in the medium-risk group significantly improved diagnostic efficacy, reduced the utilization of gene tests, and maintained a consistent false-negative rate.

Project description:BackgroundFine-needle aspiration biopsy (FNAB) is a recognized technique for the basic, preoperative cytological diagnosis of thyroid nodules.Aim of the studyTo analyze the accuracy of FNAB in the diagnosis of thyroid cancer in patients with solitary and multiple thyroid nodules and to compare the demographic, clinical and pathological characteristics of patients with thyroid carcinoma in solitary and multiple tumors.Materials and methodsThe case records of 2,403 patients with solitary and multiple thyroid tumors treated consecutively between 2008 and 2013 were analyzed retrospectively. We selected 1,645 for further analysis. A solitary thyroid nodule was observed in 493 patients, and multiple nodules were detected in 1,152 patients. Further classification of the patients in these two groups was performed on the basis of the FNAB results, type of surgery performed and histopathology. TC was histopathologically confirmed in 166 patients, and benign disease was found in 1,479. The TC patients were assigned to the study group, and those with benign thyroid disease were placed into the control group. The study group was divided into two subgroups according to the presence of cancer in a single thyroid nodule or in multiple nodules. Malignancy in a solitary thyroid nodule was diagnosed in 98 (59.0%) patients, and cancer in multiple nodules was diagnosed in 68 (41.0%). Comparative analyses of the demographic, clinical and histopathological characteristics were performed for both subgroups. The following statistical analyses were performed: comparative characteristic of subgroups, ROC analysis for study group and subgroup of patients, and multivariable logistic regression analysis for study group.ResultsThe rate of prediction of TC by FNAB was three times higher in the patients with a solitary thyroid nodule compared with those with multiple thyroid nodules and it was statistically significant (p<0.001). The rate of total thyroid resection and lack of necessity for reoperation were also significantly higher in the TC patients with a solitary nodule. The histopathological results showed that significantly more patients with a solitary nodule had advanced-stage TC (stage III or IV) and tumor progression (pT3 or pT4) (p = 0.002 for both). ROC analysis demonstrated that the overall accuracy of FNAB as a predictor of thyroid cancer presence was high, especially for the subgroup of patients with a solitary thyroid nodule (AUC = 0.958, p<0.0001). Multivariable logistic regression analysis confirmed that a positive FNAB result was the sole predictor of the performance of total resection in the TC study group (p<0.0001), while a negative FNAB result and the presence of a papillary cancer type were independent predictors of the risk of reoperation (p<0.0001 and p = 0.002, respectively).ConclusionsFNAB often produces false-negative results in patients with multiple malignant thyroid tumors, which results in reoperation in many cases. False-negative FNAB results are rare in patients with a solitary tumor. Because of the low predictive capacity of FNAB for thyroid cancer in patients with multiple thyroid tumors, total thyroid excision should be considered in most cases despite a "negative" (no malignant) FNAB result.

Dataset Information

Malignancy Risk and Related Factors of Atypia of Undetermined Significance/Follicular Lesion of Undetermined Significance in Thyroid Fine Needle Aspiration.

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Malignancy Risk and Related Factors of Atypia of Undetermined Significance/Follicular Lesion of Undetermined Significance in Thyroid Fine Needle Aspiration.

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