Atypia Of Undetermined Significance Or Follicular Lesion Of Undetermined Significance Research Articles

An economically efficient strategy for diagnosing atypia of undetermined significance or follicular lesion of undetermined significance thyroid nodules with ultrasound-based risk stratification systems and BRAFV600E testing.

The 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). This 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. Both 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). Incorporating 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.

Utility of Six Ultrasound-Based Risk Stratification Systems in the Diagnosis of AUS/FLUS Thyroid Nodules

To estimate the diagnostic performance of the currently usedultrasound (US)-based risk stratification systems (RSSs) (American Thyroid Association, American Association of Clinical Endocrinologists, American College of Endocrinology, and Association Medici Endocrinology Medical Guidelines for Clinical Practice for the Diagnosis and Management of Thyroid Nodules, European Thyroid Association Guidelines for Ultrasound Malignancy Risk Stratification of Thyroid Nodules in Adults [EU-TIRADS], American College of Radiology Thyroid Imaging Reporting and Data System [ACR-TIRADS], Chinese Guidelines for Ultrasound Malignancy Risk Stratification of Thyroid Nodules [C-TIRADS], and Thyroid Imaging Reporting and Data System Developed by Kwak et al [Kwak-TIRADS]) for atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS) thyroid nodules. This retrospective study included 514 consecutive AUS/FLUS nodules in 481 patients with final diagnosis. The US characteristics were reviewed and classified using the categories defined by each RSS. The diagnostic performance was evaluated and compared using a generalized estimating equation method. Of the 514 AUS/FLUS nodules, 148 (28.8%) were malignant and 366 (71.2%) were benign. The calculated malignancy rate increased from the low-risk to high-risk categories for all RSSs (all P<.001). Interobserver correlation for both US features and RSSs showed substantial to almost perfect agreement. The diagnostic efficacy of Kwak-TIRADS (AUC=0.808) and C-TIRADS (AUC=0.804) were similar (P=.721) and higher than those of other RSSs (all P<.05). The EU-TIRADS and Kwak-TIRADS exhibited similar sensitivity (86.5% vs 85.1%, P=.739) and were only higher than that of the C-TIRADS (all P<.05). The specificity of C-TIRADS and ACR-TIRADS were similar (78.1% vs 72.1%, P=.06) and were higher than those of other RSSs (all P<.05). Currently used RSSs can provide risk stratification for AUS/FLUS nodules. Kwak-TIRADS and C-TIRADS have the highest diagnostic efficacy in identifying malignant AUS/FLUS nodules. A detailed knowledge of the benefits and shortcomings of the various RSSs is essential.

Thyroid cytology during the COVID-19 pandemic: a single centre experience

Background: In our study, thyroid fine-needle aspiration biopsy (FNAB) data in the same calendar period of 1 year before and after the COVID-19 pandemic were compared.Methods: Thyroid FNAB data for the same calendar period of 1 year before and after the COVID-19 pandemic were included in the study. The patients were grouped according to age, gender and thyroid FNABs according to the Bethesda system for reporting thyroid cytopathology, and the data of both groups were compared considering the diagnoses of the patients who underwent thyroid surgery afterwards.Results: In the post-pandemic period, the number of thyroid FNABs and the number of patients over the age of 40 decreased (all p&lt;0.001). In the post-pandemic period, the rates of atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS), follicular neoplasm or suspicious for a follicular neoplasm (FN/SFN), suspicious for malignancy, and malignant cytology increased despite the decrease in the number of patients (p=0.001). Furthermore, the malignant tumour rate was 1.4% before the pandemic in patients who underwent surgical thyroidectomy and/or lobectomy; this rate was 3.5% in the post-pandemic period (p=0.045).Conclusions: We found an increase in the percentage of AUS/FLUS, FN/SFN, suspicious for malignancy, and malignant cases during the period when there were restrictions, such as pandemics, and the sampling was reduced. This finding is valuable in terms of detecting an increased malignancy rate by performing less thyroid FNAB by carefully determining the indications for thyroid aspiration biopsy regarding the latest guidelines.

Non-Invasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features Is Not a Cytological Diagnosis, but It Influences Cytological Diagnosis Outcomes: A Systematic Review and Meta-Analysis

Background: A low-risk thyroid tumour, non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) was introduced in 2016. NIFTP criteria require a thorough histological examination to rule out capsular and lymphovascular invasion, which denies the possibility of preoperative cytological diagnosis. Nevertheless, since the adoption of the new entity, the cytology of NIFTP has been a subject of interest. Objectives: The present systematic review and meta-analysis investigate the cytological diagnosis of NIFTP. Method: An online PubMed literature search was conducted between March 1, 2020, and June 30, 2020, for all original articles considering the cytology of histologically proven NIFTP. The studies including data on fine needle aspiration specimens classified by The Bethesda System for Reporting Thyroid Cytology (TBSRTC) categories, risk of malignancy (ROMs) in the TBSRTC categories, and cytomorphological features of NIFTP were included in the meta-analysis. Non-English studies and case reports were excluded. The data were tabulated and statistical analysis was performed with Open Meta-Analyst program. Results: Fifty-eight studies with a total of 2,553 NIFTP cases were included in the study. The pooled prevalence of NIFTP cases was calculated among 25,892 surgically resected cases from 20 studies and the results show that NIFTP consisted 4.4% (95% confidence interval [CI]: 3.5–5.4%) of all cases. Most of the NIFTP cases (79.0%) belonged to the intermediate categories of TBSRTC. The pooled distribution of NIFTP cases in each TBSRTC category was 1.3% (95% CI: 0.8–1.7%) in non-diagnostic (ND), 8.9% (95% CI: 6.9–10.8%) in benign, 29.2% (95% CI: 25.0–33.4%) in atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS), 24.2% (95% CI: 19.6–28.9%) in follicular neoplasm (FN), 19.5% (95% CI: 16.1–22.9%) in suspicious for malignancy (SM), and 6.9% (95% CI: 5.2–8.7%) in malignant. Compared to pre-NIFTP era, the pooled risk differences of ROM were reduced by 2.4% in ND, 2.7% in benign, 8.2% in AUS/FLUS, 8.2% in FN, 7.3% in SM, and 1.1% in the malignant category. The cytomorphological features of NIFTP were similar to follicular variant of papillary thyroid carcinoma (FVPTC) but lesser to papillary thyroid carcinoma (PTC). Conclusions: Based on our results, NIFTP remains a histological diagnosis. Although cytomorphological features cannot be used in differentiating NIFTP from FVPTC, they may guide in separating NIFTP from PTC. Features such as papillae, microfollicles, giant cells, psammoma bodies, and the amount of papillary-like nuclear features should be taken into account when suspicious of NIFTP. NIFTP should not have papillae or psammoma bodies, and giant cells were rarely observed.

Patient outcomes following surgical management of thyroid nodules classified as Bethesda category III (AUS/FLUS).

The Bethesda classification system for reporting thyroid cytopathology is the standard for interpreting fine needle aspirate (FNA). Because of its heterogeneity and inconsistent reporting, atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS), known as Bethesda category III, is the most controversial category. Thyroid nodules that fall within Bethesda categories III-IV have an overall risk of malignancy of between 15 and 40%. The aim of this study was to determine the malignancy rate in Bethesda III nodules. A retrospective study was performed for 1166 patients who underwent thyroid surgery for multinodular goitre (MNG) or solitary nodular goitre (SNG) in our institution between June 2010 and May 2020. Data retrieved included demographic characteristics of the patients, FNB cytology, thyroid function test results, type of thyroidectomy, and final histology results. During the study period, 29.5% (344/1166) of patients with an FNA categorized as AUS/FLUS underwent thyroid surgery. Of these 344 patients, 190 were diagnosed with MNG and 154 with SNG. Incidental malignancy was found in 35 of 190 cases of MNG (18.42%) and 31 of 154 cases of SNG (20.13%). The most common malignant tumour type in either category was the follicular variant of papillary thyroid carcinoma. The current study demonstrates that patients with a FNA categorized as AUS/FLUS may have a higher risk of malignancy than traditionally believed. Reconsideration may be necessary to guidelines that recommend observation or repeat FNA in this category of patients.

Patient outcomes following surgical management of thyroid nodules classified as Bethesda category III (AUS/FLUS)

Introduction: The Bethesda classification system for reporting thyroid cytopathology is the standard for interpreting fine needle aspirate (FNA). Because of its heterogeneity and inconsistent reporting, atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS), known as Bethesda category III, is the most controversial category. Thyroid nodules that fall within Bethesda categories III-IV have an overall risk of malignancy of between 15-40%. The aim of this study was to determine the malignancy rate in Bethesda III nodules.

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

To propose a diagnostic algorithm for improving the diagnosis of atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS) thyroid nodules. 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. 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). The proposed diagnostic algorithm is helpful for improving the diagnosis of AUS/FLUS nodules, which might be as a routine approach.

The role of combined BRAFV600E gene detection in the diagnosis of thyroid nodule determined as Bethesda Ⅲ by fine-needle aspiration

Objective: To analyze the malignant probability of thyroid nodules with the diagnosis of atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS) determined by fine-needle aspiration (FNA) and to explore the value of the combined application of BRAFV600E gene detection for the diagnosis of benign and malignant thyroid nodules. Methods: A total of 114 patients including 20 males and 94 females, aged 16-76 years old with thyroid nodules underwent FNA examination and surgical treatment in the Affiliated Cancer Hospital of Zhengzhou University from October 2018 to November 2019 were retrospectively analyzed. Postoperative histopathological results were used as the gold standard for the diagnosis of malignant thyroid nodules. The malignant rate of thyroid nodules with the diagnosis of AUS/FLUS was evaluated. Differential diagnostic efficacy of preoperative FNA combined with BRAFV600E gene detection for papillary thyroid carcinoma (PTC) was analyzed by McNemer test and diagnostic test evaluation method. Results: The mutation rate of BRAFV600E gene was 84.76% (89/105) in PTC. PTC accounted for 57.14% (12/21) of the patients with the diagnoses of AUS/FLUS determined by FNA. The specificity, sensitivity, positive predictive value and negative predictive value of BRAFV600E mutation examination for the diagnosis of malignant thyroid nodules determined preoperatively as AUS/FLUS were 9/9, 5/12, 5/5 and 9/16, respectively. BRAFV600E mutation examination could improve the detection rate of PTC in patients with AUS/FLUS (OR=0.438, 95%CI=0.251-0.763, P=0.016). Conclusion: FNA combined with BRAFV600E mutation examination can significantly improve the detection rate of malignant thyroid nodules diagnosed preoperatively as AUS/FLUS.

ThyroSeq v3 for Bethesda III and IV: An institutional experience.

The ThyroSeq v3 genomic classifier is a commercial molecular test that examines a wide spectrum of genomic alterations in a thyroid fine-needle aspiration (FNA) sample and reports test results as either negative or positive. The authors report their institutional experience with ThyroSeq v3. Thyroid FNA specimens diagnosed as either atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS) (Bethesda category III [Bethesda III] according to The Bethesda System for Reporting Thyroid Cytopathology) or follicular neoplasm/suspicious for follicular neoplasm (FN/SFN) (Bethesda IV) that had ThyroSeq v3 results available from December 2017 through October 2019 were retrieved for analysis. FNA diagnoses were correlated with ThyroSeq v3 results and follow-up histopathology. In total, 415 cases (AUS/FLUS, n = 251; FN/SFN, n = 164) were retrieved: 294 (71%) were reported as ThyroSeq v3-negative, and 121 (29%) were reported as ThyroSeq v3-positive. The benign call rate (BCR) of ThyroSeq v3 for AUS/FLUS (82%; 206 of 251 cases) was significantly higher (P < .001) than that for FN/SFN (BCR, 54%; 88 of 164 cases). Histopathologic follow-up was available for 127 cases (ThyroSeq v3-positive, 96; ThyroSeq v3-negative, 31), of which 57 were benign and 70 were malignant (including noninvasive follicular thyroid neoplasm with papillary-like nuclear features). The negative predictive value of ThyroSeq v3 was significantly higher for AUS/FLUS (99.5%) than for FN/SFN (95.4%; P < .0294), given malignancy rates of 10% for AUS/FLUS and 30% for FN/SFN. Forty-five unique combinations of genetic alterations were detected in the operated ThyroSeq-positive cases, and there were only 5 false-negative cases, comprised of 4 low-risk neoplasms. The high BCR of ThyroSeq v3 for AUS/FLUS prevents surgery in a majority of patients. The ThyroSeq v3 genomic classifier reveals the complexity of the genetic signature of indeterminate nodules.

Thyroid fine needle aspiration reporting rates and outcomes before and after Bethesda implementation: A single-center experience over 8 years

Aimː To evaluate data from our hospital system before and after the implementation of the Bethesda System for Reporting Thyroid Cytology (TBSRTC) and comparison of our data with the previously published studies. Methods: Seven hundred seventy-one patients with thyroid nodules who underwent fine needle aspiration biopsy (FNAB) and surgery at our institution were analyzed retrospectively. FNAB results were divided into two parts in terms of the period they related to: pre-TBSRTC (between 2005 and 2010) and TBSRTC (between 2011 and 2013). Results: 341 FNAB were applied in the period of TBSRTC. Of the 341 FNAB, 53(16%) were non diagnostic, 82(24%) were benign, 62(18%) were atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS), 28(8%) were follicular neoplasms and/or suspicion of follicular neoplasms (FN/SFN), 95(28%) were suspicion for malignancy (SuspM), and 21(6%) were malignant. Rates of malignancy reported on follow-up histopathological examination were non diagnostic in 11%, benign in 4.9%, AUS/FLUS in 23%, FN/SFN in 32%, SuspM in 44%, and malignant in 95.3%. Conclusions: In this study, the distribution of cases in TBSRTC categories and malignancy rates, differed from, recommended by TBSRTC and some studies. Implementation of TBSRTC did significantly affect our institution’s reporting rates.

An Insight into the Utility of Sub-Categorisation of Atypia of Undetermined Significance for Risk Stratification: A Retrospective Study on an Indian Cohort with Histopathological Correlation

Background: Atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS) criterion in thyroid fine-needle aspirates (FNAs) has been a heterogeneous entity with much inter-observer variation. Sub-categorisation of AUS/FLUS has been observed to play an effective role in risk stratification. We aimed to validate AUS/FLUS sub-categorisation in correlation with the spectrum of malignancy. Study Design: Subjects included patients with AUS/FLUS diagnosed between January 2015 and December 2016. AUS/FLUS cases were sub-categorised into those exhibiting (1) architectural atypia, (2) cytological atypia, (3) architectural and cytological atypia, (4) AUS with Hürthle cells, and (5) AUS not otherwise specified (AUS-NOS). Each sub-category was correlated with their corresponding incidence of malignancy in surgical resections. Result: The overall incidence of AUS/FLUS in our centre was 13% (132/1,018). On retrospective review of 117 patients with AUS/FLUS, smears with cytological atypia showed a higher incidence of malignancy (78.3%) than those with architectural atypia (75.3%). AUS/FLUS cases with both cytological and architectural atypia had a malignancy rate of 71.4%. Conclusion: AUS/FLUS cases with cytological atypia had a higher risk of malignancy than those with architectural atypia. The sub-categorisation of AUS/FLUS is diagnostically important for the proper risk stratification of patients.

Prospective Study of Bethesda Categories III and IV Thyroid Nodules: Outcomes and Predictive Value of BRAFV600E Mutation.

Introduction:Atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS) of The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) has emerged as the most controversial category because of its heterogeneity and inconsistent reporting. There is a definite paucity in data available from the Indian subcontinent about the outcome of nodules carrying Bethesda category III or Bethesda category IV diagnoses.Aims and Objectives:The primary objective of our study was to determine the malignancy rate in Bethesda categories III and IV nodules. The secondary objectives were to determine predictive value of BRAFV600E mutation analysis on indeterminate thyroid nodules, predictive value of Thyroid image reporting and data system (TI-RADS) in malignancy prediction and to study the common histological variants in indeterminate nodules.Materials and Methods:This prospective study included 176 consecutive nodules of Bethesda categories III and IV, diagnosed over a period of 2 years from August 2015 to August 2017. A part of the fine needle aspirate was used to perform the BRAFV600E mutation analysis. The malignancy risk associated with these Fine needle aspiration Cytology categories were discussed with the patients. Those with Bethesda category IV diagnosis was advised surgery, whereas those with Bethesda category III were given the options of close follow-up with repeat FNA in 3 months or immediate surgery.Results:In our prospective study, there were 176 consecutive samples of categories III (140/79.5%) and IV (36/20.5%). Seventy-five (53.6%) category III nodules and 29 (80.6%) category IV nodules underwent immediate surgical excision. Fifty-five consecutive indeterminate cytology nodules were subjected for BRAFV600E. One of the samples was found to be positive for BRAF T1799A (V600E) mutation. The second sample harboured a missense mutation at position 1819 (TCC--GCC), wherein the codon 607 (TCC) coding for serine was substituted by alanine (GCC) which is a variant of unknown significance. In our study, the malignancy rate of Bethesda categories III and IV, which were triaged for immediate surgery were 54.6% and 72.4%, respectively.Conclusion:Malignancy rate in Category III at our center was much higher than that described by ATA and by other studies published from centers around the world, including the only two studies from India. In view of the strikingly high malignancy rate in these indeterminate nodules, strong consideration to surgery should be given to patients with FNA results suggesting these two categories. BRAFV600E mutation analysis in FNA specimen has limited utility in improving the preoperative diagnostic rate for malignancy.

Bethesda Classification and Cytohistological Correlation of Thyroid Nodules in a Brazilian Thyroid Disease Center

Background: The Bethesda System has been used to classify thyroid cytology in 6 categories besides presenting malignancy rates and respective approaches. Reference centers have validated its use by comparing its proposed malignancy rates with those in in their populations. However, to the best of our knowledge, there has been no corresponding study in Brazil. Objectives: To evaluate the performance of the Bethesda classification in a Brazilian thyroid reference center and correlate the results with cytohistological reports in patients referred to surgery. Methods: Data records from 980 fine-needle aspiration (FNA) results were retrospectively analyzed, and, in patients who underwent surgery, the results were correlated with the cytohistological findings. Results: 980 FNAs and 585 patients were evaluated. The incidence of each cytological category was: 11% nondiagnostic (ND), 59.6% benign, 7.1% (atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS), 8.5% follicular neoplasm or suspicious for follicular neoplasm (FN/SFN), 5.1% suspicious for malignancy (SM), and 8.3% malignant. The surgery rate was 41.8% (245/585). The malignancy rate in each category was: 6% benign, 12% AUS/FLUS, 20.8% FN/SFN, 72.5% SM, and 97.3% malignant. For ND nodules, the malignancy rate was 25.7% (66.6% multifocal and papillary microcarcinomas), a higher rate than in the literature. In this category, surgery was performed in multinodular goiters presenting with another nodule > 3.0 cm and/or with an FN/SFN, SM, or malignant cytological result. Conclusion: The Bethesda System can be applied to the Brazilian population, since the frequency and malignancy rates of each category were similar to those described by its classification. It is noteworthy that a higher risk of malignancy was observed in the ND cytological category.

The presence of papillary features in thyroid nodules diagnosed as atypia of undetermined significance or follicular lesion of undetermined significance increases cancer risk and should influence treatment

BackgroundThe objective of this study was to evaluate the influence of papillary features on risk of malignancy (ROM) within the Atypia of Undetermined Significance or Follicular Lesion of Undetermined Significance (AUS-FLUS) Bethesda System for Reporting Thyroid Cytopathology (BSRTC) diagnostic category. MethodsA Retrospective review of cases with an AUS-FLUS diagnosis that underwent a thyroidectomy was carried out, and cases were subcategorized based upon the presence of papillary features. ResultsFor the entire study population there were 93 (22%) of 427 FNAB specimens that had an AUS-FLUS diagnosis, and a 32% associated ROM. Papillary features were identified in 44 FNAB specimens (47% of the AUS-FLUS cases or 10% of the entire study population), and when present had a 45% ROM. The 49 FNAB specimens (53%) that did not exhibit papillary features had a significantly lower ROM (20%) than those that did have papillary features (p = 0.0069). ConclusionsThe presence of papillary features in a thyroid FNAB with an AUS-FLUS diagnosis is common, and is associated with a higher ROM than is currently suggested by the BSRTC.

Impact of the modification of the diagnostic criteria in the 2017 Bethesda System for Reporting Thyroid Cytopathology: a report of a single institution in Japan.

The Bethesda System for Reporting Thyroid Cytopathology has recently been revised in 2017 (TBSRTC 2017). This study aimed to evaluate the impact of modifying the diagnostic criteria in TBSRTC 2017 at a single institute. We retrospectively reviewed cytological specimens of 10,399 thyroid nodules submitted for thyroid fine-needle aspiration cytology. Among them, 56 atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS) nodules, 16 suspicious for malignancy (SFM) nodules, and 8 malignant nodules were re-categorized into follicular neoplasm or suspicious for a follicular neoplasm (FN/SFN). The incidence of FN/SFN was increased by 0.8%, while that of AUS/FLUS, SFM, and malignant nodule was decreased by 0.5%, 0.2%, and 0.1%, respectively. In nine (60%) of the 15 nodules that were re-classified from AUS/FLUS to FN/SFN nodules and re-aspiration was performed, it was possible to judge whether they were benign or malignant. Of the 24 patients with FN/SFN nodules originally diagnosed with SFM or malignant, 16 were followed up without surgical resection. In conclusion, TBSRTC 2017 only caused minor changes in the incidence of each diagnostic category. TBSRTC 2017 was revised to avoid false positives owing to noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) that account for >10% of papillary thyroid carcinomas; however, it is not necessary in low frequency NIFTP institutes or countries. In Japan, we propose active surveillance as an accepted option for clinically managing AUS/FLUS, FN/SFN, SFM, or malignant nodules having favorable benign clinical findings or being part of the low-risk group.

Thyroid Atypia/Follicular Lesion of Undetermined Significance: Attitudes towards the Diagnosis of Bethesda System III Nodules

Objectives: To review our institutional experience and to analyze the clinical decisions made after a cytological diagnosis of atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS). Study Design: This is a retrospective review of all thyroid fine-needle aspiration (FNA) cytologies performed in the Hospital Clínico San Carlos (Madrid) between 2010 and 2014. Results: One hundred thirty thyroid FNA were categorized as AUS/FLUS (5%). One hundred six (81.5%) patients were women, and the mean age was 59 years. In 61 patients a repeated FNA was performed (46%). Fifty-five nodules were treated surgically (42.3%), with a histopathological diagnosis of nodular hyperplasia in 36 cases (65%), adenoma in 11 (20%), and carcinoma in 8 (14.5%). In the group of nonsurgical patients (n = 75), a repeated FNA was performed in 43 (57.3%) cases. We found no statistically significant association between sex or age and clinical management (p = 0.13 and p = 0.31, respectively). Conclusions: Clinical management after an AUS/FLUS FNA diagnosis is erratic and does not match standardized management protocols. The AUS/FLUS classification has not led to new diagnostic tests in a relevant percentage of patients. The implementation of consensual institutional strategies could lead to better management of these cases.

Repeat fine-needle aspiration can be performed at 6months or more after initial atypia of undetermined significance or follicular lesion of undetermined significance results for thyroid nodules 10mm or larger.

To investigate whether repeat ultrasound-guided fine-needle aspiration (US-FNA) in initial atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS) results could be performed 6months after or more. A total of 221 AUS/FLUS ≥10mm with any follow-up were grouped according to the first follow-up interval at less than 6months (group 1, n = 87) and 6months or more (group 2, n = 134). Clinical features, final assessment of ultrasound (US) or the Thyroid Imaging Reporting and Data System (TIRADS), tumour size, extrathyroidal extension and lymph node metastasis in malignancies were compared. Thirty-four (15.4%) were malignant. Age, gender, size, final assessment, TIRADS and malignancy rate were not significantly different between the two groups (p = 0.660, 0.691, 0.502, 0.237, 0.819 and 0.420). Tumour size, extrathyroidal extension and lymph node metastasis were not significantly different between the two malignancy groups (p = 0.770, 0.611 and 0.068). Two of 10 nodules with increased size were malignancies found at 7.1 and 25.0months. None of 33 nodules (14.9%) with decreased size at a median 10months were malignant. Repeat US-FNA performed on nodules ≥10mm at 6months or more after initial AUS/FLUS results can reduce unnecessary repeat US-FNAs without progression of malignancy. • Follow-up intervals of AUS/FLUS did not affect the malignancy rate • Tumour stage was not different according to the follow-up intervals • None of the nodules with decreased size were malignant • Repeat US-FNA can be performed at ≥6months after initial AUS/FLUS.

The 5-tiered categorization system for reporting cytology is sufficient for management of patients with thyroid nodules compared to the 6-tiered Bethesda system.

To analyze whether the 5-tiered categorization system without the atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS) category is sufficient compared to the 6-tiered Bethesda system. This IRB-approved retrospective study was waived informed consent. The pre-Bethesda period was from March 2008 to December 2008 and the Bethesda period was from January 2012 to January 2013. Of 4677 nodules ≥10mm with initial ultrasonography-guided fine-needle aspiration, 2553 nodules were from the pre-Bethesda period and 1754 nodules were from the Bethesda period. The utilization and malignancy rates of each category were compared between the two periods. The utilization rate of the benign category decreased from 67.7% in the pre-Bethesda period to 60.0% in the Bethesda period (p=0.001). In the pre-Bethesda period, the malignancy rates of the non-diagnostic, benign, suspicious follicular neoplasm/Hürthle cell neoplasm, suspicious for malignancy, and malignancy categories were 3.8, 1.9, 25, 78.8, and 99.7%, respectively. The malignancy rate of the benign category decreased from 1.9 to 0.3% after the Bethesda system (p<0.001). The utilization and malignancy rates of the AUS/FLUS category were 7 and 22.8%. When the AUS/FLUS category was included in the benign category, the malignancy rate became 2.6% which was not significantly different from 1.9% in the pre-Bethesda period (p=0.189). The malignancy rates of other categories were not significantly different. The 5-tiered categorization system without the AUS/FLUS category for reporting cytology was sufficient for management of patients with thyroid nodules compared to the 6-tiered categorization of the Bethesda system.

A meta-analytic review of the Bethesda System for Reporting Thyroid Cytopathology: Has the rate of malignancy in indeterminate lesions been underestimated?

The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) provides a 6-tier diagnostic framework using uniform criteria in reports of thyroid aspirates. One of the major advantages of this framework is its association with defined risks of malignancy, allowing standardized management algorithms for each diagnosis. The objective of the current meta-analysis was to demonstrate the feasibility of using TBSRTC among specimens in the atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS) and follicular neoplasm or suspicious for neoplasm (FN/SFN) categories. The authors also evaluated both the morphologic features and the risk of malignancy in the presence of Hurthle cells. A literature search was performed of the PubMed, Scopus, and Web of Science databases for English-language studies published from January 2008 to December2014. Studies were considered eligible only if they evaluated the risk of malignancy for specimens in the AUS/FLUS and/or FN/SFN categories and included surgical follow-up. In total, 51 articles were identified that used TBSRTC criteria and provided data for a total of 145,928 fine-needle aspiration (FNA) specimens. Of these, FNAs that had surgical follow-up were selected among the AUS/FLUS (N = 4475) and FN/SFN (N = 3202) specimens. The overall rate of malignancy was 27% for the AUS/FLUS category and 31% for the FN/SFN category. The AUS category was characterized by limited reported follow-up and surgical outcome. The data demonstrated that FNAs with an AUS diagnosis had a higher risk of malignancy than the risk according to published TBSRTC criteria, whereas the percentage of malignancy in FNAs with an FN/SFN diagnosis did not differ from that according to TBSRTC. Hurthle cell lesions represent a challenging category, underlying the importance of further studies to define whether they can be diagnosed in the AUS/FLUS category rather than the FN/SFN category.

Survey of cytopathologists and cytotechnologists for the clinical impact of the use of atypia or follicular lesion of undetermined significance.

Background:The cytologic diagnosis of atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS) is controversial because of variation in how it is applied in practice, as well as uncertainty about patient management. We aimed to assess the percentage of thyroid fine-needle aspiration biopsies (FNABs) with AUS/FLUS diagnoses in different North American and European practice settings (e.g. community, academic, etc.), assess whether patients were managed according to current guidelines, and determine patient outcomes.Materials and Methods:A detailed questionnaire survey was posted in secure websites used separately by cytopathologists and cytotechnologists. The questionnaire was posted from August 1 through December 31, 2013.Results:Endocrinologists and cytopathologists performed 51.7% and 37.1% of thyroid FNABs, respectively. The Bethesda reporting system for thyroid FNAB was used in 90% of practices. The rate of AUS/FLUS varied widely among institutions, with 46.1% of represented institutions reporting AUS/FLUS rates of 3–10%. The median follow-up rate of patients with an initial AUS/FLUS diagnosis was 70% (range, 10–100%). For the majority of represented institutions (86.4%), patients with initial AUS/FLUS diagnosis had follow-up with endocrinologists. Of repeat AUS/FLUS thyroid FNABs, a median of 52% was considered benign, and 18% were suspicious of or positive for malignancy (median, 10% and 7.5%, respectively).Conclusions:Reporting of the AUS/FLUS category varied widely among different institutions. The median follow-up rate was lower than published guidelines. The most common follow-up diagnosis was benign thyroid nodule. Improved standardization of cytologic criteria should be adopted to reduce such variation.