Diagnostic accuracy of Afirma gene expression classifier, Afirma gene sequencing classifier, ThyroSeq v2 and ThyroSeq v3 for indeterminate (Bethesda III and IV) thyroid nodules: a meta-analysis.

Objective: The management of thyroid nodules with indeterminate cytology (ITN) is still a challenge. To evaluate the performance of commercial molecular tests for ITN, we performed this comprehensive meta-analysis. Methods: We performed an electronic search using PubMed/Medline, Embase, and the Cochrane Library. Studies assessing the diagnostic accuracy of Afirma gene expression classifier (GEC), Afirma gene sequencing classifier (GSC), ThyroSeq v2 (TSv2), or ThyroSeq v3 (TSv3) in patients with ITN (only Bethesda category III or IV) were selected; Statistical analyses were performed by using Stata. Results: Seventy-one samples (GEC, n = 38; GSC, n = 16; TSv2, n = 9; TSv3, n = 8) in 53 studies, involving 6490 fine needle aspirations (FNAs) with ITN cytology with molecular diagnostics (GEC, GSC, TSv2, or TSv3), were included in the study. The meta-analysis showed the following pooled estimates: sensitivity 0.95 (95% CI: 0.94-0.97), specificity 0.35 (0.28-0.43), positive likelihood ratio (LR+) 1.5 (1.3-1.6), and negative likelihood ratio (LR-) 0.13 (0.09-0.19), with the best performance for TSv3 (area under the ROC curve 0.95 (0.93-0.96), followed by TSv2 (0.90 (0.87-0.92)), GSC (0.86 (0.82-0.88)), and GEC (0.82 (0.78-0.85)); the best rule-out property was observed for GSC (LR-, 0.07 (0.02-0.19)), followed by TSv3 (0.11 (0.05-0.24)) and GEC (0.16 (0.10-0.28), and the best rule-in was observed for TSv2 (LR+, 2,9 (1.4-4.6)), followed by GSC (1.9 (1.6-2.4)). A meta-regression analysis revealed that study design, Bethesda category, and type of molecular test were independent factors. Conclusion: We showed that in patients with ITN, TSv3 has the best molecular diagnostic performance, followed by TSv2, GSC, and GEC. As regards rule-out malignancy, GSC, and rule-in, TSV2 is superior to other tests.

The Incidence of Thyroid Cancer in Bethesda III Thyroid Nodules: A Retrospective Analysis at a Single Endocrine Surgery Center.

BACKGROUND: Fine-needle aspiration cytology (FNAC) is widely used to diagnose and monitor thyroid nodules. The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) is the standard for interpreting FNAC specimens. The risk of malignancy in Bethesda III nodules, also known as Atypia of Undetermined Significance (AUS), varies significantly throughout several studies published worldwide. This retrospective study examines the risk of cancer in thyroid FNAC categorized as Bethesda III as identified in the final histopathology of thyroidectomy specimens at a single endocrine surgery center. METHODS: This retrospective cohort analysis included 1038 consecutive patients who underwent elective thyroid surgery with complete follow-up data between January 2020 and March 2024. Preoperative data on clinical and pathological characteristics have been collected. The final histopathology report from the thyroidectomy specimen was compared to the results of the preoperative FNAC on nodules that were judged to be Bethesda category III. Statistical methods were performed using SPSS version 29. RESULTS: A total of 670 ultrasound-guided FNACs (64.5%) performed during the study period were included in the final analysis. The study population was predominantly female, represented by 79.6% of patients with a mean age of 42.5 (SD 12.1), while 20.4% were male and significantly older with mean age of 45.13 years (p = 0.02). The FNAC inadequacy rate was 5.1%, which was associated with a high risk of malignancy (6 out of 34; 17.6%). Out of the total sample size of 170 patients classified as group III, 57 were found to have malignancies in final surgical histopathology, representing 33.5% of the cases within this category. The secondary gender-related outcome analysis showed that female patients classified under the Bethesda II category had a significantly higher risk of malignancy, with a rate of 21.2%, compared to males who had a malignancy rate of 3.4% in the same Bethesda category (p = 0.001, chi-square test). However, the female patients exhibited prognostically superior non-invasive tumors compared to male individuals (p = 0.02, chi-square test). CONCLUSION: This study's results indicate that Bethesda categories II and III are associated with a higher risk of malignancy in comparison to the reports of the first and third editions of the TBSRTC, particularly for female patients classified under category II.

Comparison of Fine-Needle Aspiration Cytopathology with Histopathological Examination of the Thyroid Gland in Patients Undergoing Elective Thyroid Surgery: Do We Still Need Fine-Needle Aspiration Cytopathology?

BACKGROUND: The thyroid gland is responsible for various functions, but it is susceptible to pathologies. The gold standard for preliminarily diagnosing thyroid abnormalities is fine-needle aspiration cytology (FNAC), although it has some limitations; thus, postoperative histopathological examination confirms the diagnosis. The aim of the present study was to compare preoperative FNAC results with postoperative histopathological examination. METHODS: This study is a retrospective study based on FNAC and postoperative histopathology examination, which were compared and analyzed. RESULTS: This study included 344 patients between 18 and 86 years old (mean age: 53.06 ± 13.89), comprising 274 females and 70 males (mean ages 52.72 ± 13.86 and 54.39 ± 14.05, respectively) with a 3.9:1 female-to-male ratio. Statistical significance between the FNAC and histopathology results was observed (p = 0.0000), and 86 (25.00%) patients were found to have been diagnosed incorrectly based on FNAC. The sensitivity of FNAC was 92.31%, and its specificity was 82.08%, with positive and negative predictive values of 68.57% and 96.08%, respectively. CONCLUSIONS: Due to many factors, FNAC may lead to over- or under-diagnosis, increasing the chances of complications associated with the selected treatment. However, we do not have any other more accurate tools; therefore, FNAC should still remain as the gold standard of preliminary examination.

Molecular Genetics Augment Cytopathologic Evaluation and Surgical Planning of Pediatric Thyroid Nodules.

PURPOSE: Molecular genetic testing in conjunction with cytopathology may improve prediction of malignancy in thyroid nodules, particularly those with indeterminate cytology (Bethesda III/IV). Though now commonplace in adults, pediatric data are limited. This study examines molecular genetics of pediatric nodules with correlation to cytologic and histologic classification at time of surgery and the distribution of mutations. METHODS: Retrospective chart review of 164 patients <22 years who underwent surgical resection of a thyroid nodule between 2002 and 2020 with molecular testing on fine-needle aspiration biopsy (FNA) or final histopathology. RESULTS: 85 (52 %) of 164 patients undergoing thyroid resection had available molecular genetic testing. BRAF V600E testing was performed on the FNA samples of 73 (86 %) patients and on 15 (18 %) surgical specimens; 31 (37 %) were positive. Of the remaining 54 patients, 21 had additional mutation/fusion testing. In 17 (81 %) cases, an alternate mutation/fusion was identified including 8 gene fusions, 3 DICER1 mutations, 4 NRAS mutations, one BRAF variant, and one unknown variant. BRAF, DICER1 mutations, and gene fusions predicted malignancy. Greater than 95 % of BRAF mutations were in Bethesda V/VI lesions and associated with classic variant PTC whereas fusions and DICER1 mutations clustered in Bethesda IV nodules. Bethesda III nodules harbored BRAF and NRAS mutations. In Bethesda IV nodules, a gene fusion or DICER mutation altered the surgical decision-making (upfront thyroidectomy rather than lobectomy) in 70 % of nodules submitted for genetic testing. CONCLUSION: Expanded molecular genetic testing on FNA of pediatric thyroid nodules, particularly Bethesda III/IV, may improve prediction of malignancy and augment surgical decision-making. LEVEL OF EVIDENCE: III.

Thyroid FNA cytology: Impact of the COVID-19 pandemic and vaccination in a Brazilian series.

BACKGROUND: The coronavirus disease 2019 pandemic prompted changes in medical practice, with a reduction in cytopathology volumes and a relative increase in the malignancy rate during lockdown and the initial postlockdown period. To date, no study has evaluated the impact of these changes on the volume of rapid on-site evaluation (ROSE) or on the frequency of cases according to The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) categories after vaccination. METHODS: Ultrasound-guided thyroid fine-needle aspiration (FNA) and ROSE assessments performed from January 2019 to May 2022 were evaluated retrospectively according to TBSRTC categories for three periods: prepandemic (period 1), from transmission to expansion (period 2), and after vaccination (period 3). RESULTS: There were 7531 nodules from 5815 patients. FNA cases increased throughout the pandemic despite a drop during lockdown. The frequency of TBSRTC categories changed. Nondiagnostic cases had an increase of 18.1% in period 2 and 76.2% after vaccination compared with prepandemic levels. Malignant cases increased from 2.3% to 4.2% in period 2 and to 5.1% in period 3, representing increases of 83.1% and 121.2%, respectively, compared with period 1. Data corrected by time showed increases in categories IV, V, and VI and a decrease in benign nodules during the two pandemic periods. ROSE was performed in 787 cases during the prepandemic period, and there were decreases of 29.4% and 22.8% in periods 2 and 3, respectively. The ROSE-to-category I ratio was reduced significantly after vaccination. CONCLUSIONS: Increased volume with sustained lower benign rates and higher malignant rates before and after vaccination indicate better selection of patients for FNA. A worse adequacy rate was correlated with a decrease in the number of ROSE assessments.

TSH level as a risk factor of thyroid malignancy for nodules in euthyroid patients.

Objective: With the increased prevalence of incidental thyroid cancer, determining the predictors of thyroid malignancy has become a source of debate. This study aimed to determine the impact of thyroid stimulating hormone (TSH) levels on rates of thyroid cancer in euthyroid patients. Methods: A retrospective study included 421 patients who underwent thyroidectomy at a tertiary hospital between 2016 and 2020. Patients' demographics, history of cancer, pre-operative workup and final histology reports were obtained. The study sample was divided into two groups based on the final histopathology (benign vs malignant). The two groups were compared using the appropriate statistical tests to determine the predictors of thyroid cancer in euthyroid patients. Results: TSH levels were significantly higher in patients with malignant nodules compared to those with benign nodules (1.94 vs 1.62, p = 0.002). It was 1.54 times more likely for thyroid nodules to be malignant when TSH levels were higher (p = 0.038). Meanwhile, larger nodules (> 4 cm) were significantly more prevalent in benign nodules (43.1%) than in malignant nodules (21.1%). Larger nodules decreased the possibility of thyroid cancer by 24% (OR = 0.760, p-value = 0.004). Conclusions: High TSH levels in euthyroid patients were significantly correlated with the risk of thyroid malignancy. In addition, as Bethesda category proceeded toward malignancy, TSH levels increased. High TSH levels and small nodule diameters can be used as additional parameters in predicting thyroid cancer in euthyroid patients.

Stratifying indeterminate cytology thyroid nodules by combining Thyroid Imaging Reporting and Data Systems (TI-RADS) and The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC)

Objective@#To determine the risk of malignancy of Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) indeterminate Thyroid Nodules (Bethesda III, IV and V) by combining cytologic (TSBRTC) and Thyroid Imaging Reporting and Data Systems (TI-RADS) ultrasonographic features based on final histopathology.@*Methods@#Design: Retrospective review of records. Setting: Tertiary Private Training Hospital. Participants: 551 records. @*Results@#Among 81 eligible participants, 59 out of 84 nodules (70.24%) wer malignant on histopathology. The malignancy risk of Bethesda classification was 60.87% (28 out of 46) for Bethesda III, 57.14% (8 out of 14) for Bethesda IV and 95.83% for Bethesda V. The malignancy risk for TI-RADS categories was 0 % (0/1) for TI-RADS 2, 50% (10 out of 20) for TI-RADS 3, 71.05 % for TI-RADS 4 and 91.67 % for TI-RADS 5. The highest risk of malignancy (100%) was associated with [Bethesda IV/TI-RADS 1, 2, and 3], [Bethesda V/TI-RADS 1, 2 and 3 [Bethesda IV and V/TI-RADS 1, 2 and 3] and [Bethesda IV/TI-RADS 5]. The lowest risk of malignancy (33.33%) was associated with [Bethesda III/TI-RADS1, 2 and 3]. A high Bethesda classification (Bethesda V) was almost 5x more likely to have a malignant anatomorphology compared with Bethesda III (p = .05) while a TI-RADS 4 or 5 category was almost 5x more likely to have a malignant anatomorphology compared to TI-RADS 1, 2 or 3 (p = .026).@*Conclusion@#This study showed that TI-RADS scoring is a sensitive diagnostic classification in recognizing patients with thyroid cancer and combining Bethesda classification and TI-RADS scoring increases the sensitivity in the diagnosis of malignant thyroid nodules. A higher likelihood of malignancy is associated with higher Bethesda classification and TI-RADS scoring.

The Role of Frozen Section Examination in Thyroid Surgery.

In endocrine pathology, frozen section (FS) examination is most commonly used for the intraoperative evaluation of thyroid and parathyroid tumors, as well as cervical lymph nodes. In the past, frozen section was considered a fundamental tool in thyroid surgery. However, with advancements in preoperative ultrasound and fine-needle aspiration biopsy (FNAB), there have been increasing queries about its routine use due to the improved preoperative diagnosis. Nowadays, while the use of FS during thyroidectomy has decreased, it is still used as an additional method for different purposes intraoperatively. FS may not always provide definitive results. If FS will alter the surgical plan or extent, it should be applied. Routine FS is not recommended for evaluating thyroid nodules. But in addition to FNAB, if FS results may change the operation plan or extent, they can be utilized. FS should not be applied for thyroid lesions smaller than 1 cm, and the entire lesion should not be frozen for FS. For the assessment of thyroid nodules, the use of FS is recommended based on the Bethesda categories of FNAB. In Bethesda I category nodules, FS may contribute to distinguishing between malignant and benign lesions and guide surgical treatment. In Bethesda II nodules, where the malignancy rate is low, the performance of FNAB and FS can be compared, but it's not recommended due to the lack of a significant contribution to the surgical strategy. The sensitivity of FS in Bethesda III and IV nodules is low; its contribution to the diagnosis is limited, and it does not provide an apparent benefit to treatment; therefore, it is not recommended. In Bethesda V nodules, FS can effectively confirm the malignancy diagnosis, contribute to the surgical strategy, and reduce the possibility of completion thyroidectomy, and accordingly, it is recommended for use. Nonetheless, in Bethesda V nodules with a benign FS report, the malignancy rate remains high, so it should not be used to rule out malignancy. In Bethesda VI nodules, the performance of FS is lower or comparable to FNAB and does not significantly contribute to the treatment strategy; hence, it is not recommended. Particularly in patients with papillary thyroid cancer, intraoperative FS can be effective in detecting extrathyroidal extension and can assist the surgeon in determining the extent of thyroid surgery and central neck dissection. FS has high sensitivity and specificity in evaluating the lymphatic status of the central region intraoperatively and can be used to determine the extent of central compartment node dissection. During thyroidectomy, FS examination can be used in recognizing parathyroid tissue and distinguishing it from fatty tissue, thymus, thyroid, lymph nodes, especially in differentiating metastatic lymph nodes.

Thyroid incidentalomas.

Thyroid nodules are very common. Most of them are benign non-secerning incidentally found nodules - thyroid incidentalomas. Ultrasound (US) is an essential initial diagnostic tool in thyroid nodules management. Based on the US character, thyroid nodules should be classified to one of the US risk categories (TIRADS - Thyroid Imaging Reporting and Data System). Based on the US risk category and size, some nodules should be referred to fine needle aspiration with cytological evaluation of the sample (FNAC), some should be followed just by US, and some require no follow-up. Further management depends on the FNAC (Bethesda category) and US risk category. In most nodules (Bethesda category II, repeatedly Bethesda category I, some of the nodules of Bethesda category III), just defensive management is recommended (US and/or clinical follow-up, or no follow-up). Usually, only few cases require diagnostic (Bethesda categories III, IV and V) or therapeutic (Bethesda V and VI) surgery. In decision-making of management of nodules Bethesda category III and V, molecular testing for mutations associated with thyroid cancer and serum calcitonin could be useful.

Comparison of Conventional Smear and Liquid-Based Cytology in Adequacy of Thyroid Fine-Needle Aspiration Biopsies without an Accompanying Cytopathologist.

Objectives: In this study, we aimed to compare the adequacy of conventional smear (CS) and liquid-based cytology (LBC) methods in thyroid fine-needle aspiration biopsy (FNAB) samples obtained without an accompanying cytopathologist during the procedure. Furthermore, we aimed to investigate the presence of a significant difference between the rates of nodules classified as Bethesda Category III and malignancy in both techniques and the features of the nodules affecting malignancy. Methods: A total of 625 nodules from 572 patients who were found suitable for biopsy were included in this retrospective study. FNABs were performed by interventional radiologists without an accompanying cytopathologist during the procedures. The specimens were either prepared using CS or LBC preparation methods. Cytopathological diagnostic adequacy and cytopathological results of the specimens were evaluated according to Bethesda category, and the relationship between the morphological findings was evaluated retrospectively. Results: Of all the biopsy preparations, 338 (54.1%) of them were transferred to pathology in liquid-based solution and 287 (45.9%) were transferred as CS. Malignancy rates of the biopsy samples were found similar in both LBC and CS methods. Considering the nodules classified as Bethesda Category II, III, IV, V, and VI, there was no statistical difference between the results of both methods. Non-diagnostic biopsy rate was higher in the specimens prepared by CS method (p<0.001). Conclusion: In this study, the adequacy rate of FNAB was found significantly higher in LBC method compared to the CS method. LBC was more practical and faster than the CS method. We think that LBC method may be preferred in FNAB of thyroid nodules.

Diagnostic accuracy of fine needle aspiration biopsy versus postoperative histopathology for diagnosing thyroid malignancy.

INTRODUCTION: Ultrasound-guided fine needle aspiration biopsy (FNAB) is currently widely used for the initial screening of patients with thyroid nodules enabling prevention of unnecessary surgery. The purpose of this study was to retrospectively analyse the diagnostic accuracy of thyroid FNAB compared with postoperative histopathology of a large cohort from Azerbaijan. METHODS: We evaluated the FNAB results of 738 patients who underwent thyroid surgery at the National Centre of Oncology in Azerbaijan. The measures of diagnostic accuracy were calculated for the ultrasound-guided preoperative FNAB results (based on the six diagnostic categories of the Bethesda classification) compared with postoperative histopathologic results (benign or malignant) for correspondent areas. RESULTS: Considering both DC V and DC VI categories (387 cases) as 'cytologic-positive' and DC II category (72 cases) as 'cytologic-negative', we found 14 false-positive and 10 false-negative results. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy were 97.4%, 86.1%, 96.4%, 81.6% and 94.8%, respectively. Conversely, when considering only the DC VI category as 'cytologic-positive', the sensitivity, specificity, PPV, NPV and diagnostic accuracy of FNA were 93.2%, 100%, 100%, 81.6% and 97.1%, respectively. CONCLUSIONS: The results of our cohort demonstrated high levels of diagnostic accuracy, supporting FNAB's role as a reliable diagnostic tool in the preoperative evaluation of thyroid nodules. The sensitivity, specificity, NPV, PPV and accuracy of thyroid FNAB in our institution were comparable with those of other institutions.

Caracterización de enfermos con cáncer de tiroides operados en el Hospital Clínico Quirúrgico General "Freyre de Andrade" / Characterization of Patients with Thyroid Cancer Operated on in "Freyre de Andrade" General Clinical Surgical Hospital

Introducción: El cáncer de tiroides es el tumor más común de los malignos originados en órganos endocrinos (más del 92 por ciento) y comprende un grupo de tumores que son diferentes clínicamente, epidemiológicamente y en cuanto a pronóstico. Objetivo: Caracterizar a los enfermos con cáncer de tiroides operados en el Hospital Clínico Quirúrgico General "Freyre de Andrade". Métodos: Se realizó un estudio descriptivo, retrospectivo de corte longitudinal en el Hospital Clínico Quirúrgico General "Freyre de Andrade" en el período 2014-2019. El universo estuvo constituido por 32 enfermos operados de cáncer de tiroides. Fueron analizadas variables sociodemográficas, clasificación de Bethesda, diagnóstico histológico, técnica quirúrgica empleada y complicaciones. Resultados: El cáncer de tiroides predominó en mujeres (87,5 por ciento) entre 51 - 60 años (25,0 por ciento). Según la clasificación de Bethesda prevaleció la categoría VI (15,62 por ciento). Predominó el carcinoma papilar (65,62 por ciento). A todos los enfermos se le realizó una tiroidectomía total y las complicaciones fueron el hematoma posoperatorio (6,25 por ciento) y el granuloma (6,25 por ciento). Conclusiones: El cáncer tiroideo predomina en mujeres entre la quinta y sexta década de la vida. La técnica quirúrgica que se utiliza es la tiroidectomía total con baja morbilidad. Predomina la variante histológica del carcinoma papilar(AU)

Introduction: Thyroid cancer is the most common malignant tumor originating in endocrine organs (more than 92 percent) and comprises a group of clinically, epidemiologically and prognostically different tumors. Objective: To characterize patients with thyroid cancer operated on at Freyre de Andrade General Clinical Surgical Hospital. Methods: A descriptive, retrospective and longitudinal study was carried out at Freyre de Andrade General Clinical Surgical Hospital in the period 2014-2019. The universe consisted of 32 patients operated on for thyroid cancer. Sociodemographic variables, Bethesda classification, histological diagnosis, used surgical technique and complications were analyzed. Results: Thyroid cancer predominated in women (87.5 percent) between 51 and 60 years of age (25.0 percent). According to the Bethesda classification, category VI prevailed (15.62 percent). Papillary carcinoma predominated (65.62 percent). All patients underwent total thyroidectomy, while the complications were postoperative hematoma (6.25 percent) and granuloma (6.25 percent. Conclusions: Thyroid cancer predominates in women between the fifth and sixth decades of life. The used surgical technique is total thyroidectomy, reporting low morbidity. The histological variant of papillary carcinoma predominates(AU)

Intraoperative frozen section performance for thyroid cancer diagnosis.

Objective: A primary medical relevance of thyroid nodules consists of excluding thyroid cancer, present in approximately 5% of all thyroid nodules. Fine-needle aspiration biopsy (FNAB) has a paramount role in distinguishing benign from malignant thyroid nodules due to its availability and diagnostic performance. Nevertheless, intraoperative frozen section (iFS) is still advocated as a valuable tool for surgery planning, especially for indeterminate nodules. Methods: To compare the FNAB and iFS performances in thyroid cancer diagnosis among nodules in Bethesda Categories (BC) I to VI. The performance of FNAB and iFS tests were calculated using final histopathology results as the gold standard. Results: In total, 316 patients were included in the analysis. Both FNAB and iFS data were available for 272 patients (86.1%). The overall malignancy rate was 30.4%% (n = 96). The FNAB sensitivity, specificity, and accuracy for benign (BC II) and malignant (BC V and VI) were 89.5%, 97.1%, and 94.1%, respectively. For all nodules evaluated, the iFS sensitivity, specificity, and accuracy were 80.9%, 100%, and 94.9%, respectively. For indeterminate nodules and follicular lesions (BC III and IV), the iFS sensitivity, specificity, and accuracy were 25%, 100%, and 88.7%, respectively. For BC I nodules, iFS had 95.2% of accuracy. Conclusion: Our results do not support routine iFS for indeterminate nodules or follicular neoplasms (BC III and IV) due to its low sensitivity. In these categories, iFS is not sufficiently accurate to guide the intraoperative management of thyroidectomies. iFS for BC I nodules could be an option and should be specifically investigated.

Intraoperative frozen section performance for thyroid cancer diagnosis

ABSTRACT Objective: A primary medical relevance of thyroid nodules consists of excluding thyroid cancer, present in approximately 5% of all thyroid nodules. Fine-needle aspiration biopsy (FNAB) has a paramount role in distinguishing benign from malignant thyroid nodules due to its availability and diagnostic performance. Nevertheless, intraoperative frozen section (iFS) is still advocated as a valuable tool for surgery planning, especially for indeterminate nodules. Subjects and methods: To compare the FNAB and iFS performances in thyroid cancer diagnosis among nodules in Bethesda Categories (BC) I to VI. The performance of FNAB and iFS tests were calculated using final histopathology results as the gold standard. Results: In total, 316 patients were included in the analysis. Both FNAB and iFS data were available for 272 patients (86.1%). The overall malignancy rate was 30.4%% (n = 96). The FNAB sensitivity, specificity, and accuracy for benign (BC II) and malignant (BC V and VI) were 89.5%, 97.1%, and 94.1%, respectively. For all nodules evaluated, the iFS sensitivity, specificity, and accuracy were 80.9%, 100%, and 94.9%, respectively. For indeterminate nodules and follicular lesions (BC III and IV), the iFS sensitivity, specificity, and accuracy were 25%, 100%, and 88.7%, respectively. For BC I nodules, iFS had 95.2% of accuracy. Conclusion: Our results do not support routine iFS for indeterminate nodules or follicular neoplasms (BC III and IV) due to its low sensitivity. In these categories, iFS is not sufficiently accurate to guide the intraoperative management of thyroidectomies. iFS for BC I nodules could be an option and should be specifically investigated

Cancer rate of Bethesda category II thyroid nodules.

Aim Thyroid nodules are very common and may be found in more than 50% of the population. Fine-needle aspiration cytology (FNAC) of thyroid nodules is a very useful diagnostic tool with high sensitivity and predictive value for diagnosis. The Bethesda System for Reporting Thyroid Cytopathology (BSRTC) uses six categories for thyroid cytology reporting (I-nondiagnostic, IIbenign, III-atypia of undetermined significance (AUS)/ follicular lesion of undetermined significance (FLUS), IV-follicular neoplasm/suspicious for follicular neoplasm (SFN), V-suspicious for malignancy, and VI-malignant. Our objective was to determine the malignancy rate in Bethesda II nodules. Methods From June 2010 to May 2020 a retrospective analysis was performed among 1166 patients who underwent thyroid surgery for benign thyroid diseases in our institution. Thyroid cytopathological slides and Ultrasound (US) reports were reviewed and classified according to the BSRTC. Data collected included age, gender, cytological features, and histological type of thyroid cancer. Results During the study period, 44.77% (522/1166) of patients with an FNA categorized as Bethesda II underwent thyroid surgery. Incidental malignancy was found in 1.53% (8/522) cases of Bethesda II. The most common malignant tumour type was papillary thyroid carcinoma. Conclusion The current study demonstrates that incidental thyroid carcinoma can be diagnosed after thyroidectomy even in patients with an FNA categorized as Bethesda II.

Ultrasound criteria (EU-TIRADS) to identify thyroid nodule malignancy risk in adolescents. Correlation with cyto-histological findings.

INTRODUCTION: Thyroid nodule (TN) harbouring a thyroid carcinoma are more common in paediatric than adult patients. In paediatric population, the evaluation of a TN should require specific paediatric tools for its diagnostic and therapeutic management. High-resolution ultrasonography and cytological evaluation after fine-needle aspiration biopsy (FNAB) remain the cornerstones of evaluation of TN. OBJECTIVES: To evaluate in paediatric TN for the first time the usefulness and precision of the ultrasound criteria defined by the "Thyroid Imaging Reporting and Data System (EU-TIRADS) 2017 in adults" to establish the ultrasound indication for the practice of FNAB and stratify the risk of malignancy. PATIENTS AND METHODS: 24 paediatric patients under age 18 years with thyroid nodules were attended in the last 15 years, 24 of them (31 nodules; age: 15.2 ±â€¯2.2 years; 18 women) met the inclusion criteria: FNAB with Bethesda classification and ultrasound with EU-TIRADS score. EU-TIRADS score were evaluated retrospectively. Fourteen patients underwent surgery and the definitive histological diagnosis was obtained, this allowed the calculations of sensitivity, specificity and positive and negative predictive values of the EU-TIRADS and Bethesda classification. Data on the largest diameters of the nodules were collected. RESULTS: Of the overall 31 nodules, the distribution by EU-TIRADS (T) category was: T1 (3.2%), T2: 2 (6.4%), T3: 7 (22.6%), T4: 16 (51.6%) and T5: 5 (16.1%). All malignant nodules were included in EU-TIRADS category 4 or 5. By the other hand, 13 of the 25 benign nodules were also included in the EU-TIRADS 4 category, and one in the 5. The distribution by categories of Bethesda's classification (B): BI: 6 (19.4%), BII: 14 (45.2%), BIII: 5 (16.1%), BIV: 2 (6.5%), BV: 0 and BVI: 4 (12.9%). The pathological diagnosis of the 14 patients who underwent surgery was: 6 papillary carcinomas and 8 with benign lesions: 6 nodular hyperplasia and 2 follicular adenoma. The percentage of malignancy was 42%. The sensitivity of the EU-TIRADS classification to detect malignant nodules was 100%, the specificity was 25%, PPV 44% and NPV 100%. The sensitivity of the Bethesda classification to detect malignant nodules was 86%, the specificity was 75%, PPV 67% and NPV 90%. The analysis of the largest diameter of the nodules did not show statistically significant differences between benign and malignant lesions. CONCLUSIONS: EU-TIRADS for ultrasonographic criteria classification in combination with the clinical history is an adequate and reproducible method to estimate suspicion of malignancy of paediatric TN. It is also a reliable diagnostic tool to decide which nodules will be candidates for FNAB.

Ultrasound criteria (EU-TIRADS) to identify thyroid nodule malignancy risk in adolescents. Correlation with cyto-histological findings. / Criterios ecográficos (EU-TIRADS) para identificar el riesgo de malignidad de los nódulos tiroideos en adolescentes. Correlación con los hallazgos cito-histológicos.

INTRODUCTION: Thyroid nodule (TN) harboring a thyroid carcinoma are more common in pediatric than adult patients. In pediatric population, the evaluation of a TN should require specific pediatric tools for its diagnostic and therapeutic management. High-resolution ultrasonography and cytological evaluation after fine-needle aspiration biopsy (FNAB) remain the cornerstones of evaluation of TN. OBJECTIVES: To evaluate in pediatric TN for the first time the usefulness and precision of the ultrasound criteria defined by the"Thyroid Imaging Reporting and Data System (EU-TIRADS) 2017 in adults" to establish the ultrasound indication for the practice of FNAB and stratify the risk of malignancy. PATIENTS AND METHODS: 24 pediatric patients under age 18 years with thyroid nodules were attended in the last 15 years, 24 of them (31 nodules; age: 15.2 ± 2.2 years; 18 women) met the inclusion criteria: FNAB with Bethesda classification and ultrasound with EU-TIRADS score. EU-TIRADS score were evaluated retrospectively. Fourteen patients underwent surgery and the definitive histological diagnosis was obtained, this allowed the calculations of sensitivity, specificity and positive and negative predictive values of the EU-TIRADS and Bethesda classification. Data on the largest diameters of the nodules were collected. RESULTS: Of the overall 31 nodules, the distribution by EU-TIRADS (T) category was: T1 (3.2%), T2: 2 (6.4%), T3: 7 (22.6%), T4: 16 (51.6%) and T5: 5 (16.1%). All malignant nodules were included in EU-TIRADS category 4 or 5. By the other hand, 13 of the 25 benign nodules were also included in the EU-TIRADS 4 category, and one in the 5. The distribution by categories of Bethesda's classification (B): BI: 6 (19.4%), BII: 14 (45.2%), BIII: 5 (16.1%), BIV: 2 (6.5%), BV: 0 and BVI: 4 (12.9%). The pathological diagnosis of the 14 patients who underwent surgery was: 6 papillary carcinomas and 8 with benign lesions: 6 nodular hyperplasia and 2 follicular adenoma. The percentage of malignancy was 42%. The sensitivity of the EU-TIRADS classification to detect malignant nodules was 100%, the specificity was 25%, PPV 44% and NPV 100%. The sensitivity of the Bethesda classification to detect malignant nodules was 86%, the specificity was 75%, PPV 67% and NPV 90%. The analysis of the largest diameter of the nodules did not show statistically significant differences between benign and malignant lesions. CONCLUSIONS: EU-TIRADS for ultrasonographic criteria classification in combination with the clinical history is an adequate and reproducible method to estimate suspicion of malignancy of pediatric TN. It is also a reliable diagnostic tool to decide which nodules will be candidates for FNAB.

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 and 40%. The aim of this study was to determine the malignancy rate in Bethesda III nodules. MATERIAL AND METHODS: 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. 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. CONCLUSIONS: 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.

The comparison of the histopathological results of the thyroid fine-needle aspiration biopsies in the 795 patients with thyroidectomy.

BACKGROUND: We aimed to evaluate the effectiveness of preoperative fine-needle aspiration biopsies (FNAB) by the postthyroidectomy pathology results. METHOD: Seven hundred and ninety-five patients with FNAB and following thyroid operations which have been performed between April 2008 and December 2019 were included in this study. By comparing the results of the FNAB and final pathologies, the specificity, sensitivity, FNR, false positivity ratio (FPR), accuracy and also the effect of nodule diameter on these have been evaluated. In Bethesda III subgroup according to FNAB, we investigated the malignancy rates and in whom this risk has been increased more. RESULTS: In our study, the sensitivity of FNAB is 73.40%, the specificity is 95.33%, the accuracy is 91.81%, FNR is 26.60% and FPR is 4.67%. In the patients with nodules ≥4 cm and < 4 cm respectively, we calculated the sensitivity 20.0% vs 79.76%, specificity 95.73% vs 95.19%, accuracy 89.82% vs 92.78%, FNR 80.0% vs 20.24%, FPR 4.27% vs 4.8%. CONCLUSION: Thyroid FNAB is an easy procedure with a high specificity and sensitivity. Nevertheless, when the nodule diameter was ≥4 cm, increased FNR and decreased sensitivity should be kept in mind while evaluating the patients.

Atypia of undetermined significance/follicular lesion of undetermined significance: Asian vs. non-Asian practice, and the Singapore experience.

The Bethesda System for Reporting Thyroid Cytopathology has paved the way for comparisons of the practice of thyroid cytology in many different regions. However, there have been comparatively few studies documenting differences between Asian and non-Asian practice. Here, we aim to compare a few key parameters between the two regions, focusing on the indeterminate category of atypia of undetermined significance (AUS)/follicular lesion of undetermined significance (FLUS). We compared its incidence, resection rates (RRs), risk of malignancy (ROM), rate of repeat fine needle aspiration (rFNA), ROMs of cytomorphologic subcategories of nuclear atypia (AUS-N) vs. architectural atypia (AUS-A), and, finally, the incidence of papillary thyroid carcinoma (PTC) vs. follicular neoplasms (FNs) in resected AUS/FLUS cases in Asian and non-Asian regions. Where possible, these metrics were compared with the Singapore experience from a tertiary referral institution. While the incidence of AUS/FLUS was similar in both regions, we found geographical differences in the RRs and ROMs, which may reflect a higher collective threshold for surgery in Asian countries. However, both cohorts showed higher ROMs in the AUS-N subcategory as compared to the AUS-A subcategory, supporting the subclassification of the AUS/FLUS based on the presence of nuclear atypia. We also observed a higher incidence of AUS-N coupled with a higher incidence of PTC in resected AUS/FLUS nodules in Asian cohorts, while AUS-A and follicular-patterned neoplasms featured more prominently in the non-Asian cohorts. These incidences may account for the starkly different molecular approaches that we noted-in Asian (chiefly Korean and Chinese) centers, BRAF mutational analysis was favored, while gene panels and gene expression classifiers were more frequently applied in non-Asian centers (chiefly in the United States of America). Overall, the data from Singapore appears more closely aligned to non-Asian trends, despite its geographical location in Southeast Asia and its predominantly Asian population. We conclude that there is significant heterogeneity in the outcomes of the AUS/FLUS categories between and within regions, which is only partially explained by regional variations, and may also reflect different regional diagnostic and management practices. This highlights the importance of understanding the local context in the interpretation of indeterminate Bethesda categories, rather than adopting a "one-size fits all" approach.