Assessment of inflammatory parameters as predictive markers for malignancy in thyroid nodules: a study on the correlation with Bethesda classification.

OBJECTIVE: The study aimed to assess the predictive significance of inflammatory parameters as potential markers for malignancy in individuals with thyroid nodules. METHOD: Nine hundred and ninety-one patients with thyroid nodules who had undergone thyroid fine-needle aspiration biopsy were included and classified according to the Bethesda system. Neutrophil lymphocyte ratio (NLR) and systemic immune-inflammation index (SII) values obtained from hemogram parameters were determined for each patient. The study examined the correlation between the Bethesda classification and NLR/SII levels. In addition, a comparison was made between the inflammatory parameters of the benign and malignant Bethesda groups. RESULTS: Five hundred and seventy-three patients were classified as Bethesda 2 (benign), 34 as Bethesda 6 (malignant). A correlation was observed between the Bethesda classification and NLR and SII levels (r: 0.230, p < 0.001; r: 0.207 p < 0.001, respectively). NLR and SII values were significantly higher in the malignant group (p < 0.001). The cutoff value for SII in predicting benign and malignant thyroid nodules was 489.86 × 103/mm3 with a sensitivity of 88.2% and a specificity of 63.7%. The cutoff value for NLR for the same prediction was 2.06 with a sensitivity of 82.4% and a specificity of 83.4%. CONCLUSIONS: The findings of this study indicate that SII and NLR may be valuable prognostic markers for predicting the malignancy of thyroid nodules.

OBJETIVO: Evaluar parámetros inflamatorios como posibles marcadores de malignidad en individuos con nódulos tiroideos. MÉTODO: Se incluyeron 991 pacientes con nódulos tiroideos que se sometieron a biopsia por aspiración con aguja fina y se clasificaron según el sistema de Bethesda. Se determinaron los valores de la relación neutrófilo-linfocito (NLR) y el índice de inflamación inmunitaria sistémica (SII). El estudio exploró la correlación entre la clasificación de Bethesda y los valores de NLR/SII, y comparó los parámetros inflamatorios de los grupos benignos y malignos de Bethesda. RESULTADOS: Se clasificaron 573 pacientes como Bethesda 2 (benigno) y 34 como Bethesda 6 (maligno). Se observó una correlación entre la clasificación de Bethesda y los valores de NLR y SII (r: 0.230; r: 0.207). Los valores de NLR y SII fueron mayores en el grupo maligno (p < 0.001). El valor de corte para SII en la predicción de nódulos tiroideos benignos y malignos fue de 489.86 × 103/mm3, con una sensibilidad del 88.2% y una especificidad del 63.7%; para NLR fue de 2.06, con una sensibilidad del 82.4% y una especificidad del 83.4%. CONCLUSIONES: El SII y el NLR pueden ser valiosos marcadores pronósticos para predecir la malignidad de los nódulos tiroideos.

Classification of Benign-Malignant Thyroid Nodules Based on Hyperspectral Technology.

In recent years, the incidence of thyroid cancer has rapidly increased. To address the issue of the inefficient diagnosis of thyroid cancer during surgery, we propose a rapid method for the diagnosis of benign and malignant thyroid nodules based on hyperspectral technology. Firstly, using our self-developed thyroid nodule hyperspectral acquisition system, data for a large number of diverse thyroid nodule samples were obtained, providing a foundation for subsequent diagnosis. Secondly, to better meet clinical practical needs, we address the current situation of medical hyperspectral image classification research being mainly focused on pixel-based region segmentation, by proposing a method for nodule classification as benign or malignant based on thyroid nodule hyperspectral data blocks. Using 3D CNN and VGG16 networks as a basis, we designed a neural network algorithm (V3Dnet) for classification based on three-dimensional hyperspectral data blocks. In the case of a dataset with a block size of 50 × 50 × 196, the classification accuracy for benign and malignant samples reaches 84.63%. We also investigated the impact of data block size on the classification performance and constructed a classification model that includes thyroid nodule sample acquisition, hyperspectral data preprocessing, and an algorithm for thyroid nodule classification as benign and malignant based on hyperspectral data blocks. The proposed model for thyroid nodule classification is expected to be applied in thyroid surgery, thereby improving surgical accuracy and providing strong support for scientific research in related fields.

Changes in thyroid cytology reporting in the 3rd edition of the Bethesda system.

Reporting fine-needle aspiration of thyroid nodules in the Bethesda classification is a practice widely used internationally and by us. The revised third edition of the Bethesda System of Reporting Thyroid Cytopathology brings changes in terminology, content, and new chapters. In terms of terminology, an obvious change is the removal of the two-word names of three categories while maintaining the six diagnostic categories of the previous versions - new: BI - non-diag- nostic, BIII - atypia of undetermined significance, BIV - follicular neoplasia. In the detailed description of the findings within the individual categories, the ter- minological changes adopted by the fifth edition of the WHO classification of thyroid neoplasia are respected - in particular, the recommended name follicular thyroid nodular disease for the most frequently represented category BII - benign. In the evaluation itself, the diagnostic specifications accepted by the current WHO classification of histopathological findings are reflected in the individual categories - if they are applicable at the cytological level. Targeted attention will need to be paid to high grade features. The revised version brings new chapters dedicated to molecular testing and evaluation of the paediatric population.

Accuracy and diagnostic performance of the Bethesda system for reporting thyroid cytopathology in a tertiary endocrine surgical referral center in Belgium.

BACKGROUND: The Bethesda System for Reporting Thyroid Cytopathology is a commonly used classification for fine needle aspiration (FNA) cytology of suspicious thyroid nodules. The risk of malignancy (ROM) for each category has recently been analyzed in three international databases. This paper compares the diagnostic performance of the Bethesda classification in a high-volume referral center in Belgium. METHODS: All consecutive thyroid procedures were registered in a prospective database from January 2010 till August 2022. Patient and surgical characteristics, preoperative Bethesda categories, and postoperative pathology results were analyzed. RESULTS: Out of 2219 consecutive thyroid procedures, 1226 patients underwent preoperative FNA. Papillary thyroid cancer was the most prevalent malignancy (N = 119, 70.4%), followed by follicular (N = 17, 10.1%) and medullary thyroid cancer (N = 15, 8.9%). Micropapillary thyroid cancer was incidentally found in 46 (3.8%) patients. Bethesda categories I, II, III, IV, V, and VI, respectively, represented 250 (20.4%; ROM 4.4%), 546 (44.5%; ROM 3.8%), 96 (7.8%; ROM 20.8%), 231 (18.8%; ROM 15.2%), 62 (5.1%; ROM 72.6%), and 41 (3.3%; ROM 90.2%) patients. Overall ROM was 13.8%. An negative predictive value (NPV) of 96.2% was found. Overall specificity was 64.2% with a positive predictive value (PPV) of 31.9%. Diagnostic accuracy was 67.8%. Compared to international databases (CESQIP, EUROCRINE, and UKRETS), ROM in this study appeared lower for Bethesda category IV (15.2 vs. 26.7% and p = 0.612). CONCLUSION: Despite being validated in numerous studies, ROM based on preoperative FNA cytology classified according to the Bethesda classification may vary among surgical centers and countries as this study reveals a higher NPV and lower PPV.

An Improved k-Nearest Neighbor Algorithm for Recognition and Classification of Thyroid Nodules.

OBJECTIVES: To complete the task of automatic recognition and classification of thyroid nodules and solve the problem of high classification error rates when the samples are imbalanced. METHODS: An improved k-nearest neighbor (KNN) algorithm is proposed and a method for automatic thyroid nodule classification based on the improved KNN algorithm is established. In the improved KNN algorithm, we consider not only the number of class labels for various classes of data in KNNs, but also the corresponding weights. And we use the Minkowski distance measure instead of the Euclidean distance measure. RESULTS: A total of 508 ultrasound images of thyroid nodules, including 415 benign nodules and 93 malignant nodules, were used in the paper. Experimental results show the improved KNN has 0.872549 accuracy, 0.867347 precision, 1 recall, and 0.928962 F1-score. At the same time, we also considered the influence of different distance weights, the value of k, different distance measures on the classification results. CONCLUSIONS: A comparison result shows that our method has a better performance than the traditional KNN and other classical machine learning methods.

Evaluating Postoperative Outcomes and Investigating the Usefulness of EU-TIRADS Scoring in Managing Pediatric Thyroid Nodules Bethesda 3 and 4

Objective: The aim was to assess postoperative outcomes in pediatric thyroid nodules with atypia of undetermined significance (AUS/FLUS) or suspicious for a follicular neoplasm (SFN) and their respective the European-Thyroid Imaging Reporting and Data System (EU-TIRADS) scores. Methods: Forty-four pediatric patients at a single center with thyroid nodules classified as AUS/FLUS or SFN from August 2019 to December 2022 were retrospectively reviewed. Data on demographics, thyroid function, nodule size, and ultrasonographic features were collected. Postoperative pathologies were categorized into benign, low-risk, and malignant neoplasms according to the World Health Organization 2022 criteria, and EU-TIRADS was used for retrospective radiological scoring. Results: Among 21 (47.7%) of patients who had surgical intervention, 72% had Bethesda 3 and 28% had Bethesda 4 thyroid nodules. Post-surgical histopathological classifications were 43% benign, 19% low-risk, and 38% malignant. Of note, EU-TIRADS 3 and 5 scores were present in 44% and 56% of the benign cases, respectively. Malignant cases tended to produce higher EU-TIRADS scores, with 64% rated as EU-TIRADS 5. Bethesda category 4 nodules had a 66% malignancy rate, significantly higher than the 27% in category 3. Conclusion: A substantial proportion of histologically benign cases were classified as EU-TIRADS 5, suggesting that EU-TIRADS may lead to unnecessary biopsies in benign cases. Malignant cases were more likely to have a higher EU-TIRADS score, indicating a positive correlation with malignancy risk, particularly in Bethesda 4 cases. However, the EU-TIRADS system's predictive value for malignancy in Bethesda 3 cases was poorer.

Rendimiento del sistema Bethesda en el diagnóstico citopatológico del nódulo tiroideo en un centro universitario (Hospital de Clínicas) de Uruguay, diez años de experiencia / Performance of the Bethesda SYSTEM in the cytopathological diagnosis of the thyroid nodule in a university center (Hospital de Clínicas) in Uruguay, ten years of experience / Desempenho do sistema Bethesda no diagnóstico citopatológico de nódulos tireoidianos em um centro universitário (Hospital de Clínicas) no Uruguai, dez anos de experiencia

Resumen: Introducción: el estudio citológico por punción ecoguiada se caracteriza por ser rápido, confiable, mínimamente invasivo y rentable. Permite reducir procedimientos quirúrgicos innecesarios y clasifica apropiadamente a los pacientes con nódulos sospechosos o malignos para una intervención quirúrgica oportuna. Objetivo: el objetivo del presente estudio es evaluar la correlación citológica-anatomopatológica del sistema Bethesda en un centro universitario (Hospital de Clínicas) de Uruguay. Metodología: se realizó un estudio de tipo observacional, retrospectivo, descriptivo, basado el análisis de historias clínicas de pacientes sometidos a cirugía tiroidea en el Hospital de Clínicas, en el período comprendido entre enero de 2008 y diciembre de 2018. Resultados: del total inicial de 119 pacientes, 93 cumplieron los criterios de inclusión. El rango de edad de la muestra fue entre 15 y 79 años. Del total de puncionados 49,5% (46) fueron informados como benignos y 50,5% (47) como malignos. Se calculó en forma global una sensibilidad de 96% (0,96) con IC 1,0-0,90, especificidad de 98% (0,97) con IC 1,0-0,93, un VPP de 98% y VPN de 96%. La sensibilidad diagnóstica para la categoría IV, V y VI fue de 96%, con una especificidad de 100, 94 y 100% respectivamente. Conclusiones: el sistema Bethesda aplicado a las PAAF de nódulos tiroideos potencia la certeza diagnóstica y asiste en la decisión terapéutica. En nuestra institución contamos con una buena correlación citopatológica, similar a otros trabajos reportados en la literatura, lo que permite predecir adecuadamente el riesgo de malignidad y facilitar la toma de decisiones.

Summary: Introduction: the ultrasound-guided fine needle aspiration biopsy (FNAB) study is characterized by being fast, reliable, minimally invasive, and cost-effective. It reduces unnecessary surgical procedures and appropriately classifies patients with suspicious or malignant nodules for timely surgical intervention. Objective: the objective of this study is to evaluate the cytological-pathological correlation of the Bethesda System in a university center (Hospital de Clínicas) in Uruguay. Methodology: an observational, retrospective, descriptive study was carried out, based on the analysis of medical records of patients undergoing thyroid surgery at the Hospital de Clínicas, in the period between January 2008 and December 2018. Results: of the initial total of 119 patients, 93 met the inclusion criteria. The age range of the sample was between 15 and 79 years. Of the total of punctured, 49.5% (46) were reported as benign and 50.5% (47) as malignant. A sensitivity of 96% (0.96) with CI 1.0-0.90, specificity of 98% (0.97) with CI 1.0-0.93, a PPV of 98% and NPV of 96%. The diagnostic sensitivity for categories IV, V and VI was 96% with a specificity of 100, 94 and 100% respectively. Conclusions: the Bethesda system applied to FNA of thyroid nodules enhances diagnostic certainty and assists in the therapeutic decision. In our institution we have a good cytopathological correlation, similar to other works reported in the literature. This makes it possible to adequately predict the risk of malignancy and facilitate decision-making.

Resumo: Introdução: o estudo citológico por punção guiada por ultrassom caracteriza-se por ser rápido, confiável, minimamente invasivo e de baixo custo. Permite reduzir procedimentos cirúrgicos desnecessários e classificar adequadamente pacientes com nódulos suspeitos ou malignos para intervenção cirúrgica oportuna. Objetivo: avaliar a correlação citológico-patológica do Sistema Bethesda em um centro universitário (Hospital de Clínicas) no Uruguai. Metodologia: foi realizado um estudo observacional, retrospectivo, descritivo, baseado na análise de prontuários de pacientes submetidos à cirurgia de tireoide no Hospital de Clínicas, no período janeiro de 2008-dezembro de 2018. Resultados: do total inicial de 119 pacientes, 93 preencheram os critérios de inclusão. A faixa etária da amostra foi entre 15 e 79 anos. Do total de punções, 49,5% (46) foram relatadas como benignas e 50,5% (47) como malignas. No geral, uma sensibilidade de 96% (0,96) com IC 1,0-0,90, uma especificidade de 98% (0,97) com IC 1,0-0,93, um VPP de 98% e VPN de 96%. A sensibilidade diagnóstica para as categorias IV, V e VI foi de 96% com especificidade de 100, 94 e 100%, respectivamente. Conclusões: o sistema Bethesda aplicado à PAAF de nódulos tireoidianos aumenta a certeza diagnóstica e auxilia na decisão terapêutica. Em nossa instituição temos uma boa correlação citopatológica, semelhante a outros trabalhos relatados na literatura. Isso permite prever adequadamente o risco de malignidade e facilitar a tomada de decisão.

The Diagnostic Efficacy of the American College of Radiology (ACR) Thyroid Imaging Report and Data System (TI-RADS) and the American Thyroid Association (ATA) Risk Stratification Systems for Thyroid Nodules.

BACKGROUND: This study is aimed at evaluating the diagnostic efficacy of ultrasound-based risk stratification for thyroid nodules in the American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS) and the American Thyroid Association (ATA) risk stratification systems. METHODS: 286 patients with thyroid cancer were included in the tumor group, with 259 nontumor cases included in the nontumor group. The ACR TI-RADS and ATA risk stratification systems assessed all thyroid nodules for malignant risks. The diagnostic effect of ACR and ATA risk stratification system for thyroid nodules was evaluated by receiver operating characteristic (ROC) analysis using postoperative pathological diagnosis as the gold standard. RESULTS: The distributions and mean scores of ACR and ATA rating risk stratification were significantly different between the tumor and nontumor groups. The lesion diameter > 1 cm subgroup had higher malignant ultrasound feature rates detected and ACR and ATA scores. A significant difference was not found in the ACR and ATA scores between patients with or without Hashimoto's disease. The area under the receiver operating curve (AUC) for the ACR TI-RADS and the ATA systems was 0.891 and 0.896, respectively. The ACR had better specificity (0.90) while the ATA system had higher sensitivity (0.92), with both scenarios having almost the same overall diagnostic accuracy (0.84). CONCLUSION: Both the ACR TI-RADS and the ATA risk stratification systems provide a clinically feasible thyroid malignant risk classification, with high thyroid nodule malignant risk diagnostic efficacy.

Malignancy Rate of Bethesda Class III Thyroid Nodules Based on the Presence of Chronic Lymphocytic Thyroiditis in Surgical Patients.

Background: Hashimoto's thyroiditis (HT), also known as chronic lymphocytic thyroiditis (CLT), may interfere with the accurate cytological diagnosis of thyroid nodules. Recently, HT has been considered a premalignant condition for thyroid cancer development. The diagnosis of atypia of undetermined significance/follicular lesions of undetermined significance (AUS/FLUS) thyroid nodules is challenging and evidence for the malignancy risk of AUS/FLUS thyroid nodules coexisting with CLT is scarce. Therefore, we assessed the malignancy risk of AUS/FLUS thyroid nodules according to the presence of background CLT. Methods: This study included 357 surgically resected thyroid nodules with AUS/FLUS cytology. Cases with concomitant malignant nodules were excluded. CLT was defined based on the pathologic report after thyroid surgery. Results: Among 357 tumors, 130 tumors (36%) were confirmed to have coexisting CLT, and 170 tumors (48%) were determined to be malignant after thyroidectomy. Malignancy rates were similar in both groups (48% in each) regardless of background CLT (62/130 with CLT vs. 108/227 without CLT). In the group with CLT, thyroiditis was more frequent in the final pathology (12% with CLT vs. 1% without CLT, P = 0.003). In multivariate analysis, positive BRAFV600E mutation, highly suspicious sonographic features (K-TIRADS 5), and smaller thyroid nodules were significant factors for thyroid malignancies. Conclusion: The malignancy rate of thyroid nodules with AUS/FLUS cytology was comparable irrespective of the presence of underlying CLT.

Evaluation of thyroid nodules by shear wave elastography: a review of current knowledge.

PURPOSE: Shear wave elastography (SWE), as a tool for diagnosing thyroid malignancy, has gathered considerable attention during the past decade. Diverging results exist regarding the diagnostic performance of thyroid SWE. METHODS: A comprehensive literature review of thyroid SWE was conducted using the terms "Thyroid" and "shear wave elastography" in PubMed. RESULTS: The majority of studies found SWE promising for differentiating malignant and benign thyroid nodules on a group level, whereas results are less convincing on the individual level due to huge overlap in elasticity indices. Further, there is lack of consensus on the optimum outcome reflecting nodule elasticity and the cut-off point predicting thyroid malignancy. While heterogeneity between studies hinders a clinically meaningful meta-analysis, the results are discussed in a clinical perspective with regard to applicability in clinical practice as well as methodological advantages and pitfalls of this technology. CONCLUSION: Technological as well as biological hindrances seem to exist for SWE to be clinically reliable in assessing benign and malignant thyroid nodules. Structural heterogeneity of thyroid nodules in combination with operator-dependent factors such as pre-compression and selection of scanning plane are likely explanations for these findings. Standardization and consensus on the SWE acquisition process applied in future studies are needed for SWE to be considered a clinically reliable diagnostic tool for detection of thyroid cancer.

Analysis of intra-observer and inter-observer variability of pathologists for non-benign thyroid fine needle aspiration cytology according to Bethesda system categories.

AIM: To examine the intra- and inter-observer variability for non-benign thyroid cytological subcategories according to the Bethesda classification system after the second review. METHODS: Between November 2018 and May 2019, thyroid fine needle aspiration biopsies of 381 nodules were retrospectively evaluated. Among them, 74 non-benign (category III-VI) thyroid biopsies, analyzed according to the Bethesda system (pathologist 1:40 vs pathologist 2:34) by two independent pathologists, were reassessed by the same pathologists and by a cytopathologist. In this observer-blinded study, weighted Cohen's kappa was used to assess the intra-observer agreement, and Krippendorff's alpha was used to assess the inter-observer agreement. RESULTS: At the first and second evaluations of pathologists 1 and 2, the percentage agreement was 62.5% for pathologist 1 and 58.8% for pathologist 2. The intra-observer agreement was substantial (κ = 0.705) for pathologist 1, and moderate (κ = 0.447) for pathologist 2. In the second evaluation of pathologist 1 and 2, which was compared with the cytopathologist, the agreement percentage of pathologist 1 with the cytopathologist was 50.0%, and that of pathologist 2 was 56.8%. The inter-observer agreement was below the lowest acceptable limit for an overall agreement (α = 0.634) among the three raters. The inter-observer agreement was only acceptable between the cytopathologist and the second pathologist, while it was low between the other raters. In the evaluation of the non-benign nodules, the mean category score of the cytopathologist was 3.22 and lower than both pathologists (3.73 and 3.58, respectively). CONCLUSIONS: The intra-observer agreement of pathologists was moderate-to-substantial in the evaluation of non-benign thyroid biopsies according to the Bethesda reporting system. However, the inter-observer agreement was below the lowest acceptable limit when the cytopathologist was taken as a reference.

Cancer prevalence in the subcategories of the indeterminate class III (AUS/FLUS) of the Bethesda system for thyroid cytology: a meta-analysis.

PURPOSE: The indeterminate cytologic report represents a major challenge in the field of thyroid nodule. The indeterminate class III of the Bethesda classification system (i.e., AUS/FLUS) includes a heterogeneous group of subcategories characterized by doubtful nuclear and/or architectural atypia. The study aim was to  conduct a systematic review and meta-analysis to evaluate the rate of malignancy in each subcategory of Bethesda III. METHODS: PubMed, CENTRAL, and Scopus databases were searched until April 2020. Original articles reporting data on the subcategories of Bethesda III were included. The histological diagnosis was the reference standard to classify true/false negative and true/false positive cases. RESULTS: The pooled cancer prevalence in each subcategory of Bethesda III was estimated using a random-effects model. Twenty-three papers with 4241 nodules were included. Overall, 1163 (27.4%) were malignant. The cancer rate observed in the subcategories ranged from 15%, in "Hürthle cell aspirates with low risk pattern", to 44%, in "Focal cytologic atypia". CONCLUSIONS: The overall cancer rate found in the Bethesda III ranged more largely than that originally estimated (10-30%) and varied among any scenarios. These evidence-based data represent a reference for the clinical management of these patients.

Presurgical Stratification of Thyroid Nodules - Is it really Needed? Current Guidelines versus Real Life.

Background: Thyroid surgery has various benign and malignant indications. A complete pre-surgical evaluation guides the selection of cases and determines the appropriate extent of the intervention. Minimizing the number of unneeded thyroidectomies could reduce hospitalization costs, as well as post-surgery complications and iatrogenic hypothyroidism. The aim of this study was to retrospectively evaluate the presenting reasons of patients admitted to the hospital for thyroid surgeries and to estimate the need of total thyroidectomies. Methodology: The study included patients admitted in all three Surgical Departments in Timisoara Emergency County Hospital, between January 1st 2018 and December 31st 2019 (2 years). Results: A number of 1036 thyroid surgeries had been performed in 1027 patients and were retrospectively analyzed, comparing the pre-surgical diagnosis with the pathology report. Suspicion of malignancy, compression or functional autonomy was described in 326 /824 total thyroidectomy cases. Cancer was detected in 338 out of the 1027 patients (32.92%), including 39 borderline lesions. A proportion of 80.7% were papillary thyroid cancers. The current presurgical evaluation generated a number of 475 cases displaying differences between the presurgical and postsurgical diagnostic. The phenomenon was observed both in total thyroidectomy and in lobectomy interventions: 22.8% of the lobectomies were diagnosed with thyroid cancer. Conclusion: Our findings confirm that a reliable multidisciplinary approach with standardized presurgical clinical, biochemical and ultrasound evaluation is crucial in patients with indication for thyroid surgery, in order to avoid unnecessary surgeries.

Diagnostic utility of fine needle aspiration cytology in pediatric thyroid nodules based on Bethesda Classification.

OBJECTIVES: The Bethesda system for reporting cytopathology (TBSRTC) has been widely adopted in the management of thyroid nodules. Based on the limited pediatric data available, the implied malignancy risk for each of the categories may be significantly different in pediatrics vs. adults, especially in the indeterminate categories (Bethesda Class III or IV). We report the diagnostic utility of fine needle aspiration (FNA) biopsy at our institution based on the Bethesda system and the risk of malignancy in each category. METHODS: We retrospectively reviewed all patients who underwent a thyroid FNA at our tertiary pediatric hospital from 12/1/2002 to 11/30/2018. FNA results were classified according to TBSRTC. Patient demographics, cytology, histopathology, radiological and clinical follow-ups were examined. RESULTS: A total of 171 patients were included with 203 cytological samples. Average age at initial FNA was 14.7 years (range 6.9-18.6 years). The numbers of nodules reported for Bethesda categories I-VI were 29, 106, 22, 14, 6 and 26, respectively, and the rate of malignancy was: 13.8, 4.7, 22.7, 35.7, 83.3 and 100%, respectively. Use of ultrasound guidance reduced the non-diagnostic rate from 38.1 to 11.5%. Introduction of on-site adequacy testing further reduced the non-diagnostic rate to 6.5% since 2014. CONCLUSIONS: The risk of malignancy for thyroid nodules in this pediatric cohort is higher than reported in adults. However, rates described here are much closer to adult ranges than previously published pediatric cohorts. The addition of adequacy testing improved the non-diagnostic rate of FNA procedures performed with ultrasound guidance.

Improving Diagnostic Performance for Thyroid Nodules Classified as Bethesda Category III or IV: How and by Whom Ultrasonography Should be Performed.

BACKGROUND: The purpose of this prospective study is to evaluate if the association of Bethesda system and a 3-categories Ultrasonography (US) risk stratification system proposed by the American Association of Clinical Endocrinologists/American College of Endocrinology/Associazione Medici Endocrinologi improves the performance of cytology alone in III or IV categories and if further variables such as US provider (radiologist; endocrinologist, or endocrine surgeon both coming from a dedicated team) influence the accuracy of the diagnostic. METHODS: 570 consecutive patients with complete clinical records, affected by Bethesda III or IV nodules, have been addressed to two public referral surgical centers of Western Sicily. Age, sex, autoimmunity, nodule size, and US provider were recorded. Fisher's exact test was used for the univariate analysis; Odd's ratios were calculated for the multivariate analysis. RESULTS: 248 patients had malignancy at histology, 322 were benign. The mean age was 52 years for the malignancy group and 58 y for the benign group (P < 0.001). At univariate analysis, autoimmunity was correlated with benign group (P < 0.001), and US risk 2 and 3 were correlated with malignancy (nearly 10-folds, P < 0.001); In addition, no difference was found concerning nodule size. At multivariate analysis, US risk 2 and 3 were strong predictors of malignancy (P < 0.0001) especially if cytology was Bethesda IV; endocrinologist and surgeon were more accurate in predicting malignancy compared with the radiologist (P < 0.01). CONCLUSIONS: In the context of indeterminate nodules, the American College of Endocrinology/American Association of Clinical Endocrinologists/Associazione Medici Endocrinologi US risk stratification system strongly improves the results of Bethesda system especially when performed from dedicated endocrinologist or endocrine surgeon.

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

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

Comparison of ACR TI-RADS, Kwak TI-RADS, ATA guidelines and KTA/KSThR guidelines in combination with SWE in the diagnosis of thyroid nodules.

OBJECTIVE: To compare the diagnostic efficacy of ACR TI-RADS, Kwak TI-RADS, ATA guidelines and KTA/KSThR guidelines in combination with shear wave elastography (SWE) for thyroid nodules. METHODS: The retrospective study included 566 thyroid nodules with maximum diameter≥5 mm which confirmed by FNA cytology or/and surgical pathology. The sensitivity, specificity, accuracy, Youden index of diagnosis of thyroid nodules by ACR TI-RADS, Kwak TI-RADS, ATA guidelines, KTA/KSThR guidelines and SWE were calculated. The ROC curve was drawn to determine the cut-off values of the four ultrasound classification systems and SWE Emax. The diagnostic efficacy of the four ultrasound classification systems in combination with SWE were calculated and compared with those of pre-combination. RESULTS: The ROC curves indicated that the cut-off value of ACR TI-RADS, Kwak TI-RADS, ATA guidelines, KTA/KSThR guidelines and Emax of SWE was TR5, 4c, high-suspicion, high-suspicion, and 41.7 kPa, respectively, and the area under the ROC curve (AUC) was 0.907(0.879-0.934), 0904(0.876-0.932), 0.894(0.863-0.924), 0.888(0.856-0.919), 0.886(0.859-0.913), respectively. After combination with SWE, the the sensitivities of the four ultrasound classification systems for the diagnosis of nodules were improved, and the differences were statistically significant (all P≤0.001); the specificities were decreased, but the differences were not statistically significant (all P > 0.05); the accuracies were improved, but only the difference of ACR TI-RADS was statistically significant (x2 = 4.45, P = 0.035); the differences in the AUCs were not significant (all P > 0.05). CONCLUSIONS: The four ultrasound classification systems and SWE all had high performance in the diagnosis of thyroid nodules. The four classification systems in combination with SWE were all beneficial to the differential diagnosis of nodules, and ACR TI-RADS in combination with SWE was more effective, especially for TR3 and TR4 nodules.

Clinicopathologic Characteristics of Thyroid Nodules Positive for the THADA-IGF2BP3 Fusion on Preoperative Molecular Analysis.

Background: Thyroid adenoma-associated (THADA)-IGF2BP3 fusions have been identified as an oncogenic event in thyroid neoplasms. However, the prevalence of this gene fusion and associated phenotypical and clinical features are not well defined. The aim of this study was to characterize thyroid nodules positive for THADA-IGF2BP3 fusions on preoperative molecular analysis, review surgical outcomes, and explore potential impact of the fusion detection on patient management. Methods: Thyroid nodules positive for THADA-IGF2BP3 fusion on ThyroSeq v3 genomic classifier (GC) testing of fine needle aspiration (FNA) (n = 30) samples from November 2017 to August 2019 were identified. Demographic and clinical data were obtained by retrospective chart review; pathology slides were re-examined. Results: Thirty nodules positive for THADA-IGF2BP3 fusion on FNA were identified, representing ∼2% of 1280 nodules that underwent molecular analysis. Of the 27 nodules with available cytology diagnosis data, 22 (81%) were diagnosed as atypia of undetermined significance, 3 (11%) as follicular neoplasm, and 1 (4%) each were benign, and suspicious for malignancy. No additional mutations or gene fusions were identified in any of the nodules. Of the 24 cases with available clinical data, 22 (92%) THADA-IGF2BP3-positive nodules were managed surgically, 14 (64%) by thyroid lobectomy, and 8 (36%) by total thyroidectomy. Of the patients who had initial lobectomy, 3 (21%) had completion surgery. On surgical pathology, 7 (32%) THADA-IGF2BP3-positive nodules were malignant (six encapsulated follicular variant papillary thyroid carcinomas (EFVPTC), one minimally infiltrative FVPTC), 10 (45%) noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP), and 5 (23%) follicular adenomas (FA). THADA-IGF2BP3-positive malignancies were intrathyroidal, without aggressive histology. Nodule size was similar between malignant nodules, NIFTP, and FA (2.6, 2.7, and 2.3 cm, respectively; p = 0.77). On limited follow-up (mean, 18 months) available for six patients with malignant fusion-positive nodule and 4 patients with NIFTP, no tumor recurrences were found. Conclusions: In this series of patients, 77% of THADA-IGF2BP3 fusion-positive thyroid nodules were thyroid tumors requiring surgery, either papillary carcinoma or NIFTP. However, all cancers were low risk, predominantly encapsulated FVPTCs and thus can likely be adequately treated with lobectomy.

Combining the American Thyroid Association's Ultrasound Classification with Cytological Subcategorization Improves the Assessment of Malignancy Risk in Indeterminate Thyroid Nodules.

Background: The risk of malignancy (RoM) of indeterminate thyroid nodules (ITNs) shows a high variability in interinstitutional cohorts. The RoM is partially associated with the cytological degree of atypia and the ultrasound (US) pattern. This study evaluated the cancer risk of ITNs by jointly considering the cytological subcategory and the American Thyroid Association (ATA)-based US risk classification. Methods: This study features a retrospective cohort from two Brazilian centers comprising 238 ITNs with confirmed outcomes. US classification, according to ATA-based guidelines, and cytological subcategorization were determined. The cytological subgroups were as follows: (1) nuclear atypia (NA) related to papillary thyroid carcinoma (PTC) but insufficient to categorize the cytology as suspicious for malignancy; (2) architectural atypia without NA (AA); (3) both architectural and nuclear atypia (ANA); (4) oncocytic pattern (OP) without NA; and (5) NA not related to PTC (NANP). NA was divided into three subgroups: nuclear size and shape, nuclear membrane appearance, and/or chromatin aspects. Results: The overall frequency of malignancy was 39.5%. Among the cytological subcategories, the highest RoM was related to the NA (43.9%) and to the ANA (43.5%), followed by AA (29.4%), and OP (9.4%). NA was positively and independently associated with cancer (odds ratio [OR]: 4.5; confidence interval [CI: 1.2-16.6]) as was the occurrence of ANA (OR 6.6 [CI 1.5-29.5]). AA and OP were not independently associated with cancer. Both ATA-based high- and intermediate-risk categories showed an independent association with cancer (OR 6.8 [CI 2.9-15.5] and OR: 2.6 [CI 1.1-5.8], respectively). ITNs with cytological findings of NA or ANA when combined with intermediate US patterns had RoM values of 47.5% and 56.7%, respectively. Both cytological subcategories, when combined with the ATA high-suspicion class reached an RoM >70%. The type of NA with the highest odds for cancer was related to the nuclear membrane (OR 11.5). Conclusions: The RoM of ITNs can reach almost 80% when both NA and ATA-based high-risk US features are present. The presence of such cytological features also increased the RoM in the ATA-based intermediate-risk US category. In addition, AA and OP were not independently related to higher cancer risk. These results strengthen the recommendations for combing cytological subcategorization and US risk classification in the workup for ITNs before the decision of a molecular testing, clinical observation, or diagnostic surgery.

Impact of a genomic classifier on indeterminate thyroid nodules: an institutional experience.

INTRODUCTION: Indeterminate thyroid cytology (ITC) occurs in 20% to 25% of cases, and the associated risk of malignancy ranges from 5% to 30%. The genomic classifier ThyroSeq (CBLPath/UPMC, Rye Brook, NY), a targeted next-generation sequencing technology, could classify ITC nodules as malignant and nonmalignant. We sought to characterize our institutional experience with ThyroSeq testing. MATERIALS AND METHODS: We retrospectively identified all patients seen from January 2015 through November 2019 who had ITC nodules analyzed with ThyroSeq. Relevant clinical, pathologic, and resection data were reviewed. RESULTS: Of the 133 cases identified, diagnostic categories included atypia (or follicular lesion) of undetermined significance) (n = 65 [48.9%]), suspicious for follicular neoplasm (SFN) (n = 48 [36.1%]), and suspicious for Hürthle cell neoplasm (n = 20 [15.0%]). About half of the papillary thyroid carcinoma (PTC) cases (n = 9 [56.3%]) and more than one-third of the noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) cases (n = 3/8 [37.5%]) were classified as SFN. Most patients (n = 87 [65.4%]) did not undergo resection; of these, 73 (83.9%) were negative for all molecular alterations. Of the 54 cases with molecular alterations, isolated RAS or RAS-like variants were most common (n = 35 [64.8%]); 9 (25.7%) were identified in PTC and 8 (22.9%) in NIFTP. NRAS was the most common alteration (n = 20 [37.0%]), followed by HRAS (n = 6 [11.1%]), which was mostly detected in NIFTP cases (n = 4 of 6 [66.7%]). CONCLUSION: Resection was avoided in 73 patients (54.9%) because of negative ThyroSeq results. ThyroSeq v2 and v3 offered a more accurate categorization of ITC nodules, improved patient management, and reduced unnecessary surgical procedures.