Atypia Of Undetermined Significance/follicular Lesion Of Undetermined Significance Research Articles

Is the nodule location a predictive risk factor for cancer in AUS/FLUS thyroid nodules? A retrospective cohort study

Atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) is a heterogeneous category of thyroid nodules with uncertain cytology and controversial management. This study aimed to assess the association between nodule location and malignancy risk and whether the location can be used as a predictive risk factor for cancer in AUS/FLUS nodules. A cohort of 102 patients (79 [77.5%] women, 23 [22.5%] men) was retrospectively analyzed. Only patients with a final histopathology of benign or well-differentiated thyroid cancer and an available nodule location were included. Sociodemographic, histopathological, and sonographic data were statistically evaluated and correlated. Based on pathology findings, 54 (52.9%) and 48 (47.1%) nodules were benign and malignant, respectively. Most nodules were right-sided (54.9%). Considering the nodule location, 41.2% of nodules occupied the whole lobe, 20.6% only the lower pole, 15.7% only the upper pole, and 2.9% the isthmus. Cases with nodules occupying only the upper, middle, or lower pole showed significant associations with cancer risk (odds ratio, [95% confidence interval]: 2.6, [1.1-5.7]; 2.0, [1.0-4.7]; and 1.9, [1.0-3.9], respectively). Male sex and the presence of a peripheral halo were significantly associated with malignancy risk (3.3, [1.2-9.1], P=0.014; and 2.7, [1.0-9.5], P=0.049, respectively). Isthmic nodules had the highest malignancy level (66.7%). Nodule location is a promising predictor of malignancy in AUS/FLUS nodules. Furthermore, isthmic nodules had the highest malignancy level, emphasizing the significance of careful evaluation of these nodules. Further large prospective studies are required to confirm these findings.

Thyroid fine-needle aspiration cytology: malignancy rate in the category of indeterminate significant atypia/indeterminate significant follicular lesion.

Fine needle aspiration cytology (FNAC) is a standard preoperative diagnostic modality for thyroid nodules. The Bethesda Thyroid Cytopathology Reporting System (TBSRTC) defines the FNAC atypia group as atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS). Determine the risk of malignancy after surgical resection in patients with AUS/FLUS. Retrospective. Pathology department of a tertiary care center. All thyroid FNACs between 2015 and 2023 that were diagnosed as AUS/FLUS in Turkey. Patient demographics, preoperative ultrasonographic features, and follow-up data were collected. Relationship between AUS/FLUS diagnosis and final histopathological diagnosis. 562. In total, 562 thyroid nodules were diagnosed as AUS/FLUS, and 267 (47.5%) were surgically excised. A malignant histopathological diagnosis was given in 28 cases (10.4%). Malignancy risk sensitivity of AUS/FLUS diagnosis was 75.68% (95% CI=58.80-88.23%), specificity was 55.24% (95% CI=50.91-59.52%), positive predictive value was 10.49% (95% CI=8.71-12.58%), and negative predictive value was 97.04% (95% CI=94.86-98.31%). In the ultrasonographic data, having symptomatic nodules, nodule calcification, and irregular nodule borders were all statistically significant signs of cancer in a one-variable analysis (P<.01). The presence of a family history emerged as a statistically significant prognostic marker for malignancy (P=.012). Although not statistically significant, the malignancy rate for nodules with nuclear atypia was 11.9%, significantly higher than the rate of 8.3% for nodules with architectural atypia only (P=0.32). The diagnosis of AUS/FLUS has a high rate of predicting the risk of malignancy and should continue to be offered. In addition to cytopathological features, ultrasound data and family history should be taken into consideration when evaluating the case. Retrospective design and no molecular studies.

[Diagnostic Value of American Thyroid Association Guidelines,American College of Radiology Thyroid Imaging Reporting and Data System,and Chinese Thyroid Imaging Reporting and Data System Alone and Combined With BRAFV600E Mutation in Atypia of Undetermined Significance/Follicular Lesion of Undetermined Significance].

Objective To explore the diagnostic efficacy of American Thyroid Association(ATA)guidelines,American College of Radiology Thyroid Imaging Report and Data System(ACR-TIRADS),and Chinese Thyroid Imaging Reporting and Data System(C-TIRADS)alone and combined with BRAFV600E mutation in atypia of undetermined significance/follicular lesion of undetermined significance(AUS/FLUS).Methods A total of 138 patients who underwent ultrasound-guided fine needle aspiration(FNA)in the Chinese PLA General Hospital from January 2020 to May 2023 were selected.The clinicopathological and ultrasound characteristics were retrospectively analyzed for each nodule.Each nodule underwent preoperative BRAFV600E mutation testing and was diagnosed according to the ATA guidelines,ACR-TIRADS,and C-TIRADS.The diagnostic efficacy of ATA guidelines,ACR-TIRADS,and C-TIRADS alone and combined with BRAFV600E mutation was assessed based on the results of histopathological diagnosis.Results The 138 AUS/FLUS thyroid nodules included 45(32.6%)benign ones and 93(67.4%)malignant ones.The patient age(t=1.444,P=0.151),gender(χ2=0.259,P=0.611),and location of nodules(χ2=2.055,P=0.358)had no statistical significance for the differentiation between benign and malignant nodules,while nodule size(Z=2.500,P=0.012),echo(χ2=14.693,P<0.001),composition(χ2=17.075,P<0.001),aspect ratio ≥1(χ2=9.477,P=0.002),and microcalcification(χ2=6.892,P=0.009)were of significance for the differentiation.When applied alone,BRAFV600E mutation showed high specificity(95.56%)and positive predictive value(95.65%).Among the three ultrasound grading systems,ACR-TIRADS had the highest sensitivity(χ2=37.923,P<0.001;χ2=40.462,P<0.001)and accuracy(χ2=81.595,P<0.001;χ2=76.912,P<0.001),while C-TIRADS had the highest specificity(χ2=11.746,P<0.001;χ2=21.235,P<0.001).However,the three systems showed no statistically significant difference in the diagnostic efficiency when applied alone(Z=1.177,P=0.239;Z=0.213,P=0.831;Z=1.016,P=0.310).The combination of BRAFV600E mutation with ACR-TIRADS or C-TIRADS improved the diagnostic efficacy of BRAFV600E mutation in distinguishing the benign and malignant AUS/FLUS nodules(Z=2.107,P=0.035;Z=2.752,P=0.006).The combination of ATA guidelines with BRAFV600E mutation increased the diagnostic accuracy of BRAFV600E mutation(χ2=20.679,P<0.001),while it had no statistically significant difference in distinguishing the benign and malignant AUS/FLUS nodules(Z=1.321,P=0.186).The combination of ATA guidelines,ACR-TIRADS,or C-TIRADS with BRAFV600E mutation improved the diagnostic efficacy of ultrasound grading systems for AUS/FLUS nodules(Z=2.770,P=0.006;Z=2.770,P=0.006;Z=2.890,P=0.004).Specifically,ACR-TIRADS combined with BRAFV600E mutation showed the highest sensitivity(χ2=4.712,P=0.030;χ2=4.712,P=0.030),while C-TIRADS combined with BRAFV600E mutation showed the highest accuracy(χ2=77.627,P<0.001;χ2=85.827,P<0.001).However,there were no statistically significant differences in diagnostic performance between the combinations(Z=1.276,P=0.202;Z=0.808,P=0.419;Z=1.615,P=0.106).Conclusion ATA guidelines,ACR-TIRADS,and C-TIRADS combined with BRAFV600E mutation can improve the diagnostic efficacy of BRAFV600E mutation or ultrasound grading system alone in AUS/FLUS nodules,which can facilitate the further management and treatment of such patients.

EphB3 protein is a potential ancillary diagnostic biomarker for thyroid cancers

ObjectiveTo investigate the expression of ephrin type B receptor 3 (EphB3) in thyroid tumors and its usage as an ancillary diagnostic biomarker for thyroid tumors. MethodsFormalin-fixed and paraffin-embedded (FFPE) tissue samples (78 cases) and FNAC samples (57 cases) were assessed with the EphB3 antibody using immunohistochemistry. PTC and other thyroid follicular tumors were compared regarding their EphB3 expression. Sanger sequencing was used to assess for the presence of a BRAF V600E mutation. ResultsEphB3 was positive in 81.8 % (27/33) of papillary thyroid carcinoma (PTC), 83.3 % (5/6) of medullary thyroid carcinoma (MTC), 25 % (1/4) of hyperplastic/adenomatoid nodule (HN), 14.3 % (1/7) of follicular adenoma (FA), and negative in follicular tumors of uncertain malignant potential (FT-UMP) (0/13), noninvasive follicular neoplasm with papillary-like nuclear features (NIFTP) (0/7), thyroid follicular carcinoma (TFC) (0/4), Hashimoto's thyroiditis (0/4), and normal thyroid follicular tissues (0/33). In cellular blocks, EphB3 was positive in 87.1 % (20/23) of PTC, 75 % (3/4) of MTC, 20 % (2/10) of HN, and negative in atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) (0/20) and normal thyroid follicular cells (0/10). ConclusionEphB3 is expressed in the majority of PTC, but less so in benign follicular nodules. EphB3 expression in fine needle aspiration cytology (FNAC) specimens can be used as a diagnostic tool to differentiate thyroid cancer from other follicular lesions in its differential diagnosis, especially AUS/FLUS and PTC.

Malignancy in Thyroid Nodules with Bethesda III Category on Repeat Fine Needle Aspiration Biopsy.

This study aimed to evaluate the risk of malignancy for nodules repeatedly classified as Bethesda category III on fine needle aspiration biopsy (FNAB). A chart review on a series of 59 patients seen with thyroid nodules who underwent both initial and repeat FNAB at the Diabetes, Thyroid and Endocrine Center of St. Luke's Medical Center, Quezon City was conducted. The Thyroid Registry was utilized to collect each patient's demographic and clinical characteristics, ultrasonographic features of thyroid nodules along with the cytopathologic and histopathologic results. The subclassification of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) were retrieved from the cytopathology reports using the institution's electronic Healthcare-Results Management System. A total of 59 adult patients with thyroid nodules were included. Nodules which were initially AUS/FLUS turned out to be malignant on repeat FNAB in 38 patients with a prevalence of 64.41% (95% CI: 50.87-76.45%). There was no significant difference with regards to clinical, ultrasonographic and cytopathologic features of malignancy between benign and malignant nodules. Findings of this study support surgical intervention as a reasonable option after a repeat Bethesda III classification on FNAB. However, the small sample size warrants confirmation in future studies with a representative sample of patients.

Multi-class classification of thyroid nodules from automatic segmented ultrasound images: Hybrid ResNet based UNet convolutional neural network approach

Background and objectivesEarly detection and diagnosis of thyroid nodule types are important because they can be treated more effectively in their early stages. The types of thyroid nodules are generally stated as atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS), benign follicular, and papillary follicular. The risk of malignancy for AUS/FLUS is typically stated to be between 5 and 15 %, while some studies indicate a risk as high as 25 %. Without complete histology, it is difficult to classify nodules and these diagnostic operations are pricey and risky. To minimize laborious workload and misdiagnosis, recently various AI-based decision support systems have been developed. MethodsIn this study, a novel AI-based decision support system has been developed for the automated segmentation and classification of the types of thyroid nodules. This system is based on a hybrid deep-learning procedure that makes both an automatic thyroid nodule segmentation and classification tasks, respectively. In this framework, the segmentation is executed with some U-Net architectures such as ResUNet and ResUNet++ integrating with the feature extraction and upsampling with dropout operations to prevent overfitting. The nodule classification task is achieved by various deep nets architecture such as VGG-16, DenseNet121, ResNet-50, and Inception ResNet-v2 considering some accurate classification criteria such as Intersection over Union (IOU), Dice coefficient, accuracy, precision, and recall. ResultsIn analysis, a total of 880 patients with ages ranging from 10 to 90 years were included by taking the ultrasound images and demographics. The experimental evaluations showed that ResUNet++ demonstrated excellent segmentation outcomes, attaining remarkable evaluation scores including a dice coefficient of 92.4 % and a mean IOU of 89.7 %. ResNet-50 and Inception ResNet-v2 trained over the images segmented with UNets have shown better performance in terms of achieving high evaluation scores for the classification accuracy such as 96.6 % and 95.0 %, respectively. In addition, ResNet-50 and Inception ResNet-v2 classified AUS/FLUS from the images segmented with UNets with AUC=97.0 % and 96.0 %, respectively. ConclusionsThe proposed AI-based decision support system improves the automatic segmentation performance of AUS/FLUS and it has shown better performance than available approaches in the literature with respect to ACC, Jaccard and DICE losses. This system has great potential for clinical use by both radiologists and surgeons as well.

SAT454 Repetition Of Fine Needle Aspiration Cytology After An Initial Nondiagnostic Result: Does An Optimal Timing Exist?

Abstract Disclosure: I. Cosme: None. E.L. Nobre: None. M.J. Bugalho: None. Background: The optimal time to repeat a fine-needle aspiration cytology (FNAC) of a thyroid nodule, after a nondiagnostic (ND) result, is not established. It has been proposed to wait at least 3 months for a 2nd FNAC, in order to mitigate the possible inflammatory cytological changes induced by a previous FNAC. This study aimed to evaluate whether the time between 2 consecutive FNACs, influences the final cytological result. We analysed the occurrence of ND or atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) in the 2nd FNAC, in different repetition time intervals. Methods: Retrospective study (2017-2020) including thyroid nodules with a first ND FNAC, submitted to a 2nd FNAC. All FNACs were ultrasound-guided. Demographic data, time interval between FNACs and their results were collected. The 2nd FNAC results were analysed according to FNACs´ repetition interval. We considered 2 intervals: ≤ vs &amp;gt; 3 months and ≤ vs &amp;gt;6 months after the initial FNAC. The 2nd FNAC results were classified as ND, AUS/FLUS or diagnostic (including the other Bethesda FNAC categories). Results: Included 190 nodules (190 patients, 82.1% women, mean age 60±13.7 years) with a 1st ND FNAC submitted to a 2nd FNAC. The 2nd FNAC result remained ND in 63 cases, was AUS/FLUS in 9 and diagnostic in 118 (benign in 116 cases, follicular neoplasm/suspicious follicular neoplasm in 1 and malignant in 1 case). There were no statistical differences in 2nd FNAC result performed ≤3 months (13 ND, 2 AUS/FLUS, 19 diagnostic) vs &amp;gt;3 months (50 ND, 7 AUS/FLUS, 99 diagnostic) - p=0.71. Considering a wider time interval between FNACs, there were also no statistical differences in the 2nd FNAC result: ≤ 6 months (32 ND, 3 AUS/FLUS, 59 diagnostic) vs &amp;gt;6 months (31 ND, 6 AUS/FLUS, 59 diagnostic) - p=0.61. Conclusions: The time interval between FNACs was not relevant to the final cytological result. Early FNAC repetition did not increase the cases of ND or AUS/FLUS. Presentation: Saturday, June 17, 2023

The role of inflammatory parameters in the management of cases with atypia of undetermined significance/follicular lesions of undetermined significance

AIM: This study aimed to evaluate the potential of hematologic parameters and markers such as neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), monocyte-lymphocyte ratio (MLR), systemic immune-inflammation index (SII), and systemic inflammation response index (SIRI) to predict the risk of malignancy in patients whose biopsy results were classified as Atypia of Undetermined Significance/Follicular Lesion of Undetermined Significance (AUS/FLUS).&#x0D; MATERIAL AND METHOD: A total of 188 patients who underwent thyroidectomy at a General Surgery clinic were included in the study. Hematological parameters, including neutrophil count, platelet count, lymphocyte count, monocyte count, and mean platelet volume (MPV) were collected from the hospital database. NLR, PLR, MLR, SII, and SIRI were calculated. Statistical analyses were performed using SPSS v25. &#x0D; RESULTS: 38 patient (20.21%) were male and 150 patients (79.79 %) were female. The mean age was 48.6 (range 23-79, standard deviation (SD) ± 12.41years). Histopathological examination of the thyroidectomy specimens revealed benign findings in 102 patients (54.3%) and malignant findings in 86 patients (45.7%). The mean age of the malignant group was 45.6, while that of the benign group was 51.1 (p = 0.02). The median tumor size was 17 mm in the malignant group and 21 mm in the benign group (p =0.042). Mean neutrophil count were 4.29 ± 1.0 × 109/L in the benign group and 4.69 ± 1.9 × 109/L in malignant group, respectively (p = 0.031). NLR values were calculated as 1.89 for the benign group and 1.99 for the malignant group (p = 0.045). SII values were higher in the malignant group, with a median value of 584.11× 109/L in the malignant group, median value were 504.63× 109/L in the benign group (p=0.037). &#x0D; Multivariate logistic regression analysis revealed that both age (odds ratio (OR) = 0.964; 95% confidence interval (CI)= (0.939 – 0.989); p = 0.05) and neutrophil count (odds ratio (OR) = 1.598; 95% confidence interval (CI)= (1.118 – 2.285); p = 0.01) had a significant impact on the differentiation between benign and malignant thyroid nodules.&#x0D; CONCLUSION: Age and neutrophil count were identified as independent risk factors for malignant thyroid nodules. Among patients with Bethesda Category III thyroid nodules, those under 59.5 years of age and with a neutrophil count above 4.16 x 10^9/L have an increased risk for thyroid malignancy.&#x0D; Platelet count, monocyte count, MPV and inflammatory parameters, such as PLR, MLR, and SIRI, were insufficient for detecting malignancy in Bethesda III nodules. In this group, young age, small nodule size, high neutrophil count, NLR, and SII were identified as risk factors for malignancy. The Thyroid Imaging Reporting and Data System (TI-RADS) characteristics of nodules should also be considered in the management of these patients.

The risk of malignancy in the atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) category subgroups: a Thai institute experience

This study investigated the rate of reporting and the risk of malignancy (ROM) for atypia of undetermined significance (AUS) subgroups in a Thai population. AUS, which is category III of the Bethesda System for Reporting Thyroid Cytopathology, is a problematic diagnosis for thyroid nodule management because the risks of malignancy are diverse. Patients who underwent thyroid fine needle aspirations between January 2015 and December 2019 were included in this retrospective study. Gender, age, and nodule features were described, and all slides were re-evaluated and categorized into 2 subgroups: AUS-Nuclear (including cytology atypia and cytologic and architectural atypia) and AUS-Other (including architectural atypia, oncocytic atypia, and atypia not otherwise specified). The lower and upper limits of ROM were calculated for each subgroup. Of total, 258 out of 2995 fine needle aspirations (8.6%) were diagnosed as AUS. The patients were predominantly female (88.9%), with a mean age of 54.1 years. The average nodule size was 2.5 cm. Of the 258 AUS patients, 81 (38.9%) had histological correlations. The ROM for the AUS category was 9.1% to 23.5%. The ROM of the AUS-Nuclear and AUS-Other were 11.1% to 27.3% and 2.2% to 6.7%, respectively. Features of pseudonuclear inclusions had the highest ROM (33.3%-42.9%), followed by pale chromatin (28.57%-47.06%). Less than ten percent of our interpretations were AUS, which is acceptable in our practice. Cytological atypia harbored the highest ROM. Studies of associations between cytology and histology may aid in improving diagnostic criteria for this population.

Weighty Matters: The Obesity-Thyroid Nodule Connection Unveiling the Impact of Obesity on Thyroid Cancer Risk.

Background and Objectives: The effect of obesity on the development/progression of thyroid nodules with uncertain cytology is unknown. Therefore, our objective was to assess the role of body mass index (BMI) in predicting malignancy in patients with atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) nodules. Materials and Methods: We retrospectively analyzed 113 patients with available BMI data and final histopathology of benign or differentiated thyroid cancer. Patients were classified into four groups based on BMI: <18.5 (underweight), 18.5-24.9 (normal weight), 25-29.9 (overweight), and ≥30 (obesity) kg/m2. The association between risk of malignancy and BMI was examined for all data and subgroups based on nodule size, sex, and age. Results: Overall, 44.2% were obese, 36.3% were ≥45 years, and 75.4% were women. Final pathological results showed malignant nodules in 52 patients (46%) and benign nodules in 61 patients (54%) (mean age: 41 ± 11.6 vs. 39.9 ± 11.7 years; p = 0.62). Men had more malignant nodules than benign nodules (32.7% vs. 16.4%, p < 0.05). Overall, no significant correlation was identified between the risk of thyroid cancer and BMI, and the risk of malignancy was not significantly different between obese men and women (p = 0.4). However, in individuals with BMI < 30 kg/m2 (non-obese group), malignant nodules were more frequent in men than in women (71% vs. 41%, p = 0.04). No significant difference was observed in mean nodule size between the benign and malignant groups. Furthermore, BMI was not related to increased risk of malignancy in multiple logistic regression models using all data, even after controlling for confounding variables (odds ratio, 0.99, 95% confidence interval: 0.93-1.06, p = 0.87) or when stratifying by sex. Conclusions: Our study showed no correlation between obesity and thyroid cancer in patients with AUS/FLUS. Moreover, men had more malignant nodules than benign nodules. Further well-designed prospective studies are required to confirm our findings.

Evaluation of Thyroid Nodules in Patients With Fine-Needle Aspiration Biopsy.

The incidence of thyroid nodules has increased in the last 50 years due to the widespread use of imaging methods and incidental detection of small thyroid nodules. Thyroid fine-needle aspiration biopsy (FNAB) is the most accurate, reliable, and cost-effective test to evaluate thyroid nodules. In this research, we aimed to elucidate thyroid fine-needle aspiration cytology (FNAC) to understand how suspicious cases predict malignancy. Within this research's scope, 411 patients over 16 years old who were evaluated in IzmirKatipCelebi University, Ataturk Training and Research Hospital Internal Medicine (Izmir, Turkey) outpatient clinic for thyroid nodules between2018 and 2022and underwent thyroid FNAC followed by thyroid surgery were analyzed retrospectively. The age, gender, thyroid FNAC, operation type, and histopathology of all the patients were reviewed. Individuals with a history of head and neck cancer were excluded from the analysis. No statistically significant relationship between the pathology results and demographic characteristics was found. A statistically significant correlation existed between the pathology and FNAB results (p<0.05). Although 84.5% of the patients were diagnosed as benign, 14.7% as suspicious, and 0.8% as malignant in FNAC, all of these cases were diagnosed as benign in final histopathology results. Similarly, 21.9% of the patients were diagnosed asbenign, 58.8% as suspicious, and 19.4% as malignant in FNAC and all of these cases were diagnosed as malignant in final histopathology results. A correlation was determined between the two measurements (Cohen's kappa(κ)=0.557; p<0.001). The test's sensitivity was 47%, and the specificity was 99.1%. According to the FNAC results, the rate of being diagnosed with malignancy (positive predictive value (PPV)) was 93.9%, and the rate of being diagnosed as benign (negative predictive value (NPV)) was 85.8% for the individuals initially diagnosed as benign. Although FNAB remains the most important diagnostic tool to identify benigncases with a high accuracy rate, the operation decision is not clear in suspicious atypia of undetermined significance/follicular lesions of undetermined significance (AUS/FLUS) cytology findings. In conclusion, this study highlights the importance of FNA results andhelps in surgical decision-making by emphasizing that the possibility of malignancy in the post-operative final histopathology report is higher, especially in the presence of suspicious FNAC results.

Clinico-cytopathological subcategorization in thyroid nodules of atypia of undetermined significance/follicular lesion of undetermined significance using the TIRADS and Bethesda classifications.

Bethesda category III - atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) is a heterogeneous class of the Bethesda system for thyroid nodules. In order to clarify the therapeutic road for clinicians, this category was subclassified based on the cytopathological features. In this study, we evaluated the risk of malignancy, surgical outcome, demographic characteristics, and correlation of ultrasound features with the final outcome in patients with thyroid nodules based on AUS/FLUS subclassification. After evaluating 867 thyroid nodules from three different centers, 70 (8.07%) were initially diagnosed as AUS/FLUS. The cytopathologists re-interpreted the FNA samples and subclassified them into five subcategories: architectural atypia, cytologic atypia, cytologic and architectural atypia, and Hürthle cell AUS/FLUS, and atypia, which was not specified. Based on the suspicious ultrasound features, an appropriate ACR TI-RADS score was allocated to each nodule. Finally, the malignancy rate, surgical outcomes, and ACR TI-RADS scores were evaluated among Bethesda category III nodules. Among the 70 evaluated nodules, 28 (40%) were subclassified as Hürthle cell AUS/FLUS, 22 (31.42%) as cytologic and architectural atypia, 8 (11.42%) as architectural atypia, 7 (10%) as cytologic atypia, and 5 (7.14%) as atypia which was not specified. The overall malignancy rate was 34.28%, and the architectural atypia and Hürthle cell nodules displayed lower malignancy compared to other groups (P-Value<0.05). Utilizing ACR TI-RADS scores showed no statistical significance between Bethesda III subcategorization and ACR TI-RADS scores. However, ACR TI-RADS can be a reliable predictor for Hürthle cell AUS/FLU nodules. ACR TI-RADS helps evaluate malignancy only in the Hürthle cell AUS/FLUS subcategory of AUS/FLUS. Besides, cytopathological reporting based on the suggested AUS/FLUS subclassification could help clinicians take appropriate measures to manage thyroid nodules.

Chronic Lymphocytic Thyroiditis May Limit the Utility of Molecular Testing in AUS/FLUS Thyroid Nodules

IntroductionChronic lymphocytic thyroiditis (CLT) may increase the likelihood of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) results in thyroid nodules by fine needle aspiration (FNA). Gene expression classifier (GEC) and Thyroid Sequencing (ThyroSeq) may better stratify rate of malignancy (ROM) of AUS/FLUS thyroid nodules. This study compares the utility of molecular tests in determining malignancy in surgical patients with concomitant AUS/FLUS thyroid nodules and CLT. MethodsA retrospective review of 1648 patients with index thyroid nodules who underwent FNA and thyroidectomy at a single institution was performed. Patients with concomitant AUS/FLUS thyroid nodules and CLT were subdivided into three diagnostic groups: FNA only, FNA with GEC, and FNA with ThyroSeq. Patients with AUS/FLUS thyroid nodules without CLT were subdivided into similar groups. Final histopathology of the cohorts was further stratified into benignity and malignancy and analyzed using Chi-squared statistics. ResultsOf 463 study patients, 86 had concomitant AUS/FLUS thyroid nodules and CLT with a 52% ROM, and the difference of ROM among FNA only (48%), suspicious GEC (50%), or positive ThyroSeq (69%) was not significant. In 377 patients with AUS/FLUS thyroid nodules without CL, ROM was 59%. ROM among these patients was significantly higher when molecular testing was used (FNA only 51%, suspicious GEC 65%, and positive ThyroSeq 68%; P < 0.05). ConclusionsMolecular tests may have limited value in predicting malignancy in surgical patients with concomitant AUS/FLUS thyroid nodules and CLT.

A Comprehensive Study on the Diagnosis and Management of Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features.

Background: Since the noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTPs) was introduced in 2016, most retrospective studies have included cases diagnosed as encapsulated follicular variant of papillary thyroid carcinoma. We investigate a cohort diagnosed with NIFTP at resection. Methods: Retrospective institutional cohort of NIFTP from 2016 to 2022, including clinical, cytological, and molecular data for 319 cases (6.6% of thyroid surgeries, 183 cases as NIFTP-only). Results: The patient cohort had unifocal or multifocal thyroid nodules. Female:male ratio was 2.7:1, mean age was 52 years and median NIFTP size was 2.1 cm. NIFTP was associated with multiple nodules in 23% patients (n = 73) and 12% of NIFTP were multifocal (n = 39). Fine needle aspiration (FNA) of NIFTP (n = 255) were designated as nondiagnostic = 5%, benign = 13%, atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) = 49%, follicular neoplasm/suspicious for follicular neoplasm (FN/SFN) = 17%, suspicious for malignancy = 12%, or malignant = 4%. Molecular alterations were identified in 93% (n = 114), RAS or RAS-like. Thyroid Imaging Reporting and Data System (TI-RADS) score 4 was recorded in 50% of NIFTP, followed by scores 3 and 5 (26% and 20%, respectively). We also investigated the factors associated with extent of surgery. In our NIFTP-only group (n = 183), 66% were identified after hemithyroidectomy (HT) and 34% after total thyroidectomy (TT). On univariate analysis, TT patients demonstrated higher Bethesda category by FNA, more often had aberrant preoperative thyroid function, and/or underwent an FNA of additional nodule(s). With multivariable regression, Bethesda V NIFTP, in the presence of other nodules being evaluated by FNA and aberrant preoperative thyroid function, independently predicts TT. Bethesda II NIFTP correlated significantly with HT. Fifty-two patients (28%) with NIFTP-only had at least one postoperative surveillance ultrasound. In the NIFTP-only cohort, no HT patients had completion thyroidectomy or received postoperative radioactive iodine. No recurrence or metastases were recorded with median follow-up of 35 months (6-76 months; n = 120). Conclusions: Given this large cohort of NIFTP, including a large subset of isolated NIFTP-only, some with >6 years of follow-up and no tumor recurrences, consensus practical guidelines are needed for adequate postoperative management. Given the American Thyroid Association (ATA) provides guidelines for management of low-risk malignancies, guidance regarding that for borderline/biologically uncertain tumors, including NIFTP, is a reasonable next step.

Atypia of undetermined significance/follicular lesion of undetermined significance (Bethesda Category - III) in thyroid cytology: Experience from a tertiary health care center from Eastern India

Introduction: Fine-needle aspiration (FNA) cytology is a reliable method to diagnose thyroid lesions. The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) is universally followed for thyroid cytology reporting. Out of the six categories described, Category III, atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) is the most heterogeneous one. Materials and Methods: In this study conducted in a tertiary health care center in Eastern India over 2 ½-year period, 868 thyroid FNAs were performed and the cytology smears were interpreted using the TBSRTC. There were 32 FNAs in Category III. Histopathology report was available in nine cases. Results: The risk of malignancy (ROM) considering noninvasive follicular thyroid carcinoma with papillary nuclear features (NIFTP) as benign was 9.3% and by considering NIFTP as malignant was 21.8%. Conclusion: The ROM for AUS/FLUS in our study was within the revised ROM criteria. In Category III, surgery is preferable in nodules which harbor suspicious features either clinically or according to ultrasound findings.

Association of ultrasonographically determined anatomical location of Bethesda 3 thyroid nodules with differentiated thyroid cancer.

The size of a thyroid nodule and certain sonographic features, such as marked hypoechogenicity, microcalcifications, taller-than-wide shape, microlobulated, or irregular margins, indicate the greater malignancy risk. The frequency of the atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) category among cytology reports from thyroid fine-needle aspirations ranges from 0.8% to 28%, whereas the risk of malignancy of these nodules varies from 6% to 97%. This retrospective analysis investigated whether the preoperative ultrasonographic location of Bethesda 3 thyroid nodules is a predictive risk factor for differentiated thyroid cancer (DTC). A total of 387 patients who underwent total thyroidectomy for a nodule with AUS/FLUS cytology and diagnosed with a DTC at five tertiary referral centers between 2010 and 2020 were retrospectively analyzed. The location of the thyroid nodule with AUS/FLUS cytology was categorized into two groups: one group was composed of the isthmus, upper lobe, middle lobe, and lower lobe, whereas the latter consisted of right lobe, left lobe, and isthmus. DTC was diagnosed in 40.6% (n=157) of the operated nodules. Multiple logistic regression analysis has revealed that hypoechogenicity of the nodule (odds ratio [OR]=2.929, p<0.001) was the only independent predictive factor for the malignancy of the nodules with AUS/FLUS, whereas the location of the nodule, age, and sex were not significantly independent risk factors. Multifocality and contralateral benign nodules were independent predictive factors for multicentricity (OR=3.5, p=0.002; OR=5.5, p=0.001, respectively). As the first study investigating the association between a Bethesda 3 nodule location and the risk of malignancy by evaluating postoperative cytology reports, the results showed that nodule location with AUS/FLUS on fine-needle aspiration biopsy was not a predictive risk factor for the diagnosis of DTC.

The Risk of Malignancy in the Atypia of Undetermined Significance/Follicular Lesion of Undetermined Significance (AUS/FLUS) Category Subgroups: A Thai Institute Experience

The Risk of Malignancy in the Atypia of Undetermined Significance/Follicular Lesion of Undetermined Significance (AUS/FLUS) Category Subgroups: A Thai Institute Experience

An artificial neural network for the prediction of the risk of malignancy in category III Bethesda thyroid lesions.

The diagnosis of cases of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) by fine needle aspiration cytology (FNAC) is challenging for both cytopathologists and clinicians. It is extremely difficult to predict the risk of malignancy based on cytological features alone. In this study, we attempted to construct an artificial neural network (ANN) model to predict the risk of malignancy in FNAC cases of AUS/FLUS in thyroid lesions based on cytological features. We included two groups of AUS/FLUS cases: (1) 29 cases of histopathologically proven malignancy, and (2) 32 cases that had either been histopathologically proven to be benign, or for which no progress of malignancy on follow-up had been observed in the last 2 years. Cytological characteristics were analysed semi-quantitatively by two independent observers (TS and PD). Based on these data, we tried to generate an artificial neural network (ANN) model to differentiate between malignant and benign cases. The performance of the ANN was assessed using the confusion matrix and receiving operator curve. There were 29 malignant cases of AUS/FLUS (histopathologically proven) and 32 benign/follow-up cases in this study. There were 41 cases in the training set, 9 cases in the validation set and 11 cases in the test set. In the test group, the ANN model successfully distinguished between all benign (5/5) and malignant cases (6/6). The area under the receiver operating curve was 1. The present ANN model is well structured and coherent to distinguish malignant from benign outcomes in AUS/FLUS cases on cytology smears with no error. This is an open-ended ANN model, and additional parameters and more cases could be included to make the model more robust.

EVALUATION AND MANAGEMENT OF THYROID NODULES AT A TERTIARY CARE PEDIATRIC CANCER CENTER IN TURKEY

The object of this study is to search the characteristics of children and adolescents with thyroid nodules and analyze our institutional experience in the management of thyroid nodules.The complaints of these patients, physical examination findings, diagnostic features, results of radiologic researches, choise of the most appropriate modality to these patients' thyroid nodule assessment, and the management of the pathology results were revealed. Patients who applied to the pediatric endocrinology or oncology outpatient clinic of Ankara City Hospital with the diagnosis of thyroid nodule were examined. All patients who has pathology result as benign, atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS), follicular neoplasm/ suspicious for a follicular neoplasm (FN/SFN), suspicious for malignancy (SM), and malignant were searched. A total of 130 patients presented with thyroid nodules. Female male ratio was 1,95:1. The youngest patient was 68 months old. At admission there was no goiter in 71.5% of the patients on physical examination. Of all patients 36% of them underwent fine needle aspiration biopsy and 8 of the 76 patients who underwent biopsy were diagnosed with papillary thyroid cancer. One patient diagnosed with follicular thyroid cancer Patients that diagnosed cancer, 4.6% of them treated with radioactive iodine. Although most pediatric thyroid nodules are benign, distinguishing benign from malignant lesions is crucial. Interdepartmental communication and competence are very important in the follow-up of patients with thyroid nodules. Because of an increased risk of cancer in the pediatric population, diagnostic and therapeutic procedures for pediatrics need further research including multicenter studies to attain universal consensus regarding the diagnosis and management.

The combination of BRAFV600E mutation and Chinese Thyroid Imaging Reporting and Data System is helpful in the management of AUS/FLUS thyroid nodules.

To explore the utility of the BRAFV600E mutation in combination with the Chinese Thyroid Imaging Reporting and Data System (C-TIRADS) in the management of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) thyroid nodule (TN). 138 AUS/FLUS TNs in 129 patients were included. Each TN underwent preoperative BRAFV600E mutation analysis and was classified using the C-TIRADS. Histopathologic diagnosis served as reference standard. 46 benign TNs and 92 malignant TNs were identified. The C-TIRADS 4C and 5 (OR = 10.409, P = 0.000), BRAFV600E mutation (OR = 36.493, P = 0.000) were independent predictors of malignant nodules. There were significant differences in malignancy rate among the different C-TIRADS TNs (P = 0.000), and these TNs with higher C-TIRADS were associated with increased malignancy rate (P for trend = 0.000). The rate of the nodule with BRAFV600E mutation increased with the increase of C-TIRADS (P for trend = 0.001). For AUS/FLUS TNs without BRAFV600E mutation, the malignancy rates of the C-TIRADS 3, 4A, 4B, 4C, and 5 were 0%, 21.4%, 20.8%, 70.8%, and 100%, respectively (P = 0.000), and the malignancy rate increased from C-TIRADS 3 to C-TIRADS 5 (P for trend = 0.000). C-TIRADS and BRAFV600E mutation had similar diagnostic efficacy (P > 0.05), and the sensitivity, negative predictive value, and accuracy of the combination were significantly higher than BRAFV600E gene or C-TIRADS alone (P < 0.05). C-TIRADS can effectively provide risk stratification for AUS/FLUS nodules. The combination is helpful in selecting appropriate management for AUS/FLUS patients.