Bethesda Classification System Research Articles

Fate of nondiagnostic thyroid fine needle aspirations.

Thyroid nodules may be detected during the workup of thyroid hormone abnormalities and as incidental findings during unrelated imaging studies. The diagnosis of a thyroid nodule is mainly established by performing fine needle aspiration (FNA) under ultrasound guidance. Thyroid nodules are classified as nondiagnostic, defined in the Bethesda System for Reporting Thyroid Cytopathology as samples with excess blood, cyst fluid only, and lack of thyroid follicular cells. The current study evaluates a series of nondiagnostic FNAs to assess whether repeat sampling improves yield and what patient management, and outcomes are after a nondiagnostic FNA. Thyroid FNAs from 2016 to 2023 were retrieved from our institution archives. All cases were performed under ultrasound guidance and with rapid on-site evaluation. Cases were assigned the Bethesda System Category. Nondiagnostic FNAs were further reviewed for repeat FNA procedures, potential molecular testing, or diagnostic resections. In total 3104 thyroid FNAs were reviewed, with 153 (4.9%) being nondiagnostic. Of the 154 FNAs, there were 129 patients with an average age of 60 and a male-to-female ratio of 1:3.2. Of the 130 patients, there were 50 patients who underwent 55 repeat FNAs. Thirty-seven (67%) of the repeats were benign, 13 (24%) were nondiagnostic again, and 5 (9%) were atypia of undetermined significance (AUS). Molecular testing was performed on repeat FNAs diagnosed AUS. Four cases showed no mutations and had a high likelihood of being benign. One case did have an NRAS Q61R mutation, and resection revealed a noninvasive follicular thyroid neoplasm with papillary-like nuclear features. Seventeen (13% of all cases) with nondiagnostic FNA were resected. Twelve (71%) thyroidectomies showed benign adenomatous nodules. The remainder showed incidental papillary thyroid microcarcinoma (0.1 cm), an infarcted follicular adenoma, a noninvasive follicular thyroid neoplasm with papillary-like nuclear features, and metastatic renal cell carcinoma (2×). Thyroid nodules with nondiagnostic cytology are reassuring of being highly likely a benign nodule. Only 5 of the 55 (9%) repeat FNAs yielded abnormalities, with only one of those being truly a follicular neoplasm (confirmed by molecular testing and resection). No primary thyroid malignancies have been identified in follow-up (repeat FNA or surgery). Clinical and ultrasound follow-up may be more appropriate management for nondiagnostic thyroid FNAs.

The evolving role of interventional cytopathology from thyroid FNA to NGS: Lessons learned at Federico II University of Naples.

Fine-needle aspiration (FNA) guided by ultrasound (US) has emerged as a highly precise diagnostic method for managing thyroid nodules, significantly diminishing unnecessary surgeries. The effectiveness of US-guided FNA is high when a single specialist performs the FNA procedure and the microscopy. This paradigm has paved the way for the evolution of interventional cytopathology, a specialist with a pivotal role in the preoperative diagnostic process, encompassing patient history review, clinical examination, FNA execution under US guidance, preparation, and microscopic interpretation of cytological samples. As the landscape of precision medicine unfolds, molecular testing assumes greater importance in thyroid cytopathology, particularly in refining the risk of malignancy for indeterminate nodules. The updated Bethesda classification system underscores the clinical significance of molecular tests, emphasizing their role in refining diagnostic accuracy. With this evolving landscape, interventional cytopathologists must adapt by acquiring expertise in molecular technologies and addressing ongoing challenges in workflow harmonization and optimization. This paper delves into our decade-long experience as interventional cytopathologists, focusing on recent endeavours to ensure adequate samples not only for microscopic diagnosis but also for molecular testing. Additionally, here we review the challenges of integrating next-generation sequencing (NGS) technology into clinical practice, highlighting the importance of integrating clinically meaningful molecular data into comprehensive molecular cytology reports.

Atypical glandular cells and predictive features of malignancy in Pap smears: A retrospective monocentric study.

The introduction of cytological screening with the Papanicolau smear significantly reduced cervical cancer mortality. However, Pap smear examination can be challenging, being based on the observer ability to decode different cytological and architectural features. This study aims to evaluate the malignancy rate of AGC (atypical glandular cells) category, investigating the relationships between cytological and histological diagnosis. Eighty-nine patients, diagnosed as AGC at cytological evaluation and followed up with biopsy or surgical procedure at Policlinico Gemelli Hospital, Rome, Italy, were included in the study. The cytopathological architectural (feathering, rosette formation, overlapping, loss of polarity, papillary formation, three-dimensional formation) and nuclear (N/C ratio, nuclear enlargement and hyperchromasia, mitoses, nuclei irregularity, evident nucleoli) features of AGC were evaluated. Statistical analyses were performed to assess cyto-histological correlation and determine the relevance of architectural and nuclear features in the diagnosis of malignancy. Of the 89 AGC patients, 48 cases (53.93%) were diagnosed as AGC-NOS and 41 (46.07%) were diagnosed as AGC-FN, according to the Bethesda classification system. The follow-up biopsies or surgical resections revealed malignancy in 46 patients (51.69%). The rates of malignancy for AGC-NOS and AGC-FN were 35.41% and 70.73% respectively. Furthermore, analysing cytopathological features, we found that both architectural and nuclear criteria were statistically significant (p < 0.05). Only overlapping, nuclear irregularity and increased N/C ratio were not found to be statistically significant for detecting malignancy. Cytological diagnosis of glandular lesions remains a valid tool, when appropriate clinical correlation and expert evaluation are available.

Prevalence of non 16/18 high risk human papilloma virus as a quality metric in gynecological cytology.

Human papillomavirus (HPV) is the most common sexually transmitted pathogen that causes anogenital disease. Cervical screening by cytology and HPV testing (co-testing) are important in prevention of cervical cancer. The Bethesda System category of atypical squamous cells (ASC) is used when a neoplastic process cannot be confidently identified. In such cases, the differential diagnosis is broad and includes benign conditions. Monitoring of ASC/SIL ratio is a commonly used laboratory quality assurance measure to prevent over- or under-use of this category. High risk human papillomavirus (hr-HPV) has been used in conjunction with the ASC/SIL ratio in determining whether a particular pathologist is over/under-using the indefinite category. However, the laboratory overall sample population prevalence rate of hr-HPV subtypes has not been previously examined for association with the ASC rate. In this study, the relationships between ASC/SIL ratio and hr-HPV prevalence rate and hr-HPV subtypes (16/18 and non-16/18) to the laboratory ASC prevalence were studied. The results demonstrate that HPV non-16/18 is the main subtype which is associated with ASC-US category. A large proportion of non-16/18 HPV-related cases are seen in young patients, which largely abates by the by fourth decade. In addition, there are differences in the ASC/SIL ratio for HPV 16/18 and non-16/18 types. The overall ASC/SIL ratio is an average of the ASC/SIL rate for the non-16/18 population and the HPV 16/18 population. Instead of basing the laboratory and practitioners' quality indicator solely on ASC/SIL ratio, the overall prevalence of HPV and its subtype ratio should also be reported as they are more reflective of laboratory performance.

Clinicopathologic Features and Cytologic Correlation of ALK-Rearranged Papillary Thyroid Carcinoma: A Series of Eight Cases

Anaplastic lymphoma kinase (ALK) gene fusions are rare in papillary thyroid carcinoma (PTC) but may serve as a therapeutic target. This study aims to evaluate the preoperative cytologic findings and clinicopathologic features of a series of eight ALK-rearranged PTCs from our pathology archives and consultations. All cases were confirmed by ALK D5F3 immunohistochemistry and six with additional targeted RNA-based next-generation sequencing (NGS). The original fine-needle aspiration (FNA) cytology diagnosis included the Bethesda System (TBS) category II in three (37.5%), TBS III in two (25%), TBS V in two (25%), and TBS VI in one (12.5%). Six cases had available FNA cytology and were reviewed. The cytologic features showed microfollicular architecture as well as limited or reduced nuclear elongation and chromatin alterations in all six. Nuclear grooves and pseudoinclusions were absent in two cases, rarely or focally noted in three, and frequently found in one. Two cases initially diagnosed as TBS II, showing microfollicular architecture without well-developed nuclear features, were revised to TBS III (with architectural atypia only). For histologic correlations, four were infiltrative follicular variant PTCs, three as classic subtype PTC with predominant follicular growth, and one as solid/trabecular subtype PTC. All eight cases demonstrated reduced PTC nuclear features with respect to nuclear elongation and chromatin alterations compared to those typically identified in “BRAF-like” PTCs. The NGS testing revealed EML4::ALK fusion in three, STRN::ALK fusion in two, and ITSN2::ALK fusion in one. In conclusion, although ALK-rearranged PTCs have been associated with neutral gene expression profile from a BRAF-RAS scoring perspective, the “RAS-like” nuclear features were more commonly identified in this series, resulting in frequent indeterminate diagnosis of preoperative FNA.

Interpace, Affirma, and Thyroseq Performance Characteristics in 341 Bethesda Category III/IV Thyroid Nodules

Abstract Introduction/Objective Multiple FDA-approved molecular testing platforms are used by our institution for evaluating genomic characteristics of thyroid nodules. We aim to correlate molecular results and final histopathology (HPE) of thyroid nodules with cytologic diagnosis of The Bethesda System (TBS) Category III or IV. Methods/Case Report We included 341 cases of thyroid nodules diagnosed as TBS-III or TBS-IV with subsequent molecular analysis performed on 1 of 5 platforms (Interpace ThyraMIR Thyroid miRNA Classifier, Afirma Genomic Sequencing Classifier, Thyroseq Genomic Classifier, Next-Generation Sequencing (NGS) Fusion Panel, or RosettaGX Reveal Thyroid miRNA Classifier). All findings reported on molecular analysis and all benign or malignant neoplasms diagnosed on final HPE were considered “significant findings.” Performance characteristics of all 5 molecular platforms were analyzed. Results (if a Case Study enter NA) Of 341 cases, 80.1% (n=273) were classified as TBS-III and 19.9% (n=68) were classified as TBS-IV. The overall concordance of molecular and final HPE when available was 60.9% (n=28). Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) are respectively 75.0%, 60.0%, 75.0%, and 60.0% for Interpace; 65.0%, 60.0%, 85.0%, and 33.0% for Afirma; and 75.0%, 50.0%, 75.0%, and 50.0% for Thyroseq platforms. Of TBS-III cases, 66.3% (n=181), 25.6% (n=70), 4.8% (n=13), 1.5% (n=4), and 1.8% (n=5) underwent molecular testing via Interpace, Afirma, Thyroseq, NGS, and Rosetta platforms, respectively. Only 9.2% (n=25) of TBS-III cases had subsequent HPE. Concordance of molecular and final HPE for TBS-III cases was 52.0% (n=13) with a PPV of 75.0% and NPV of 40.0%. Concordances of molecular and final HPE according to molecular platform are: 57.1% (n=4) on Interpace, 53.3% (n=8) on Afirma, and 50.0% (n=1) on Thyroseq. Of TBS-IV cases, 52.9% (n=36), 36.8% (n=25), 5.9% (n=4), 2.9% (n=2), and 1.5% (n=1) underwent molecular testing via Interpace, Afirma, Thyroseq, NGS, and Rosetta platforms, respectively. Only 30.9% (n=21) of TBS-IV cases had subsequent HPE. Concordance of molecular and final HPE for TBS-IV cases was 71.4% (n=15) with a PPV of 86.0% and NPV of 43.0% Concordances of molecular and final HPE according to molecular platform are: 71.4% (n=5), 66.7% (n=6), and 75.0% (n=3) on Interpace, Afirma, and Thyroseq respectively. Conclusion Our study reports similar performance characteristics of 3 commonly used molecular platforms (Interpace, Afirma, and Thyroseq) for genomic evaluation of thyroid nodules.

Prevalence of Human Papilloma virus in potentially malignant oral disorders is a risk factor for development of early dysplasia-A cytological investigation.

The proposed study was planned to screen Human Papilloma Virus (HPV) status in potentially malignant oral disorders (PMOD) and correlated HPV positivity with cytological changes in oral smears. This descriptive cross-sectional study was conducted at University of Health Sciences Lahore, Pakistan from April 2020 to April 2021. Oral smears from N=162 patients with PMODs were taken by the Cytobrush and Manual Liquid Based Cytology was performed followed by p16 antibody detection on immunohistochemistry and HPV-DNA detection by conventional polymerase chain reaction (PCR). The cytological changes were categorized according to the updated Bethesda Classification system 2014. SPSS was used to analyze data and p-Value of <0.05 was considered as statistically significant. Out of total N = 162 patients, the most prevalent lesion [39% (n=63)] was lichen planus. Fifty six percent (n=90) of the patients were habitual chewers and 43% (n=70) were smokers. Pap staining of oral smears revealed atypical squamous cells of undetermined significance (ASCUS) in 45% (n=69) cases and in 2 % (n=4) of the samples diagnosis of atypical squamous cells-cannot exclude high-grade squamous intraepithelial lesion (ASC-H) was made. A total of 37% cases showed HPV positivity by polymerase chain reaction (PCR) while positive p16 expression was observed in 24% of the cases. ASC-H and ASCUS category showed significant association with HPV positivity (p=0.003). Early detection of PMODs by adopting minimally invasive cytological techniques and screening for HPV infection in local population is pivotal to reduce the morbidity and mortality associated with the advanced disease and carcinoma.

A Study to Evaluate Bethesda Grading in Fnac of Thyroid Swellings

Background: FNAC is a commonly used diagnostic test for preoperative evaluation of thyroid swelling. However, FNAC reporting has its own limitations. The Bethesda classification system was created to guide cytopathological diagnoses and to help identify important correlations with malignancy in the final histological study. The present study was undertaken to correlate the FNAC findings in thyroid swellings using Bethesda grading with histopathology. Methodology: This is a prospective study design done in100 patients of thyroid nodules undergoing surgery. The findings of FNAC as per Bethesda grading and histopathology was correlated and the data analyzed statistically. Results: Fine Needle Aspiration Cytology using Bethesda gradinghad a sensitivity of 88.24% and specificity of 96.39%. The accuracy of FNAC was 95% positive predictive value was 83.33%and negative predictive value was 97.56%. Conclusion: FNAC using Bethesda grading in evaluation of thyroid nodule was extremely reliable with a high specificity 96.39% making it a reliable tool in the diagnosis of a thyroid swelling.

High resolution ultrasonography of thyroid nodules: can ultrasonographic assessment obviate the need for invasive aspiration cytology in ultrasonographically benign lesions?

The use of high-resolution ultrasound (HRUS) thyroid imaging has resulted in a significant revolution in the treatment of thyroid nodules. The enigma of thyroid nodules has been a blind spot for radiologists for a long period. Reporting a thyroid nodule as benign or malignant is quite difficult and many times not accurate. The American Collage of Radiology-Thyroid Imaging Reporting and Data System (ACR-TIRADS) 2017 classification has solved this problem to a large extent. However, the classification needed pathological confirmation for it to be highly accurate. We compared our HRUS-based TIRADS labeling of thyroid nodules with thyroid cytopathology using revised Bethesda classification system. Patients detected with thyroid nodules by HRUS were categorized using ACR-TIRADS and further were taken for fine needle aspiration cytology (FNAC) in our department. The pathological results were compared with the initial TIRADS category of the nodule and the effectiveness of the TIRADS classification in categorizing nodules into benign and malignant was assessed using various statistical variables. The initial USG and the FNAC were performed by a single radiologist with over 10 years of experience. A total of 201 patients underwent HRUS followed by FNAC after obtaining written consent in our department. The thyroid nodules labeled as true benign on ACR-TIRADS (TIRADS 2) were all true benign on Bethesda cytopathology (less than Bethesda III), confirming the high accuracy of HRUS. The diagnostic accuracy of HRUS in cases of ACR-TIRADS 3 nodules was approximately 90.6% with an error rate of 9.4%. Nodules labeled as ACR-TIRADS 4 and 5 had error rates of 47% and 10% in labeling nodules as malignant. The ultrasound-based ACR-TIRADS system can accurately predict the likelihood of specific nodules being benign. There is a strong concordance between Bethesda cytology and ACR-TIRADS classification, particularly for benign nodules. In resource-constrained system like ours, patients with TIRADS 2 and 3 nodules can be safely followed obviating the need for an invasive procedure like FNAC.

Human papillomavirus 16/18/45 are not the most frequent genotypes in African American women: analysis in cervical Papanicolaou smears of women in an inner-city hospital.

Cervical cancer is considered the most common human papillomavirus (HPV)-associated disease in women. Primary and secondary prevention methods have been established through Pap tests, HPV molecular testing, and vaccines. Although the most common high-risk HPV (HR-HPV) genotypes in the United States are 16, 18, and 45, there is reported ethnic disparity in the distribution of these genotypes. Data analysis of HPV genotype results on cervical pap tests in our institution between late 2018 and early 2020 was performed. The distribution of HPV genotypes in each Bethesda category was evaluated. A total of 13,160 smears were evaluated; 75.5% were from African American women. Of those tested for HR-HPV (10,060), 1412 (14%) were HR-HPV positive. In all diagnostic categories of the Bethesda classification system, non-16/18/45 HR-HPV genotypes were more prevalent, ranging from 60.8% even in high-grade squamous intraepithelial lesion to 90.4% in negative for intraepithelial lesion or malignancy. In this study with a predominantly African American population, non-16/18/45 HR-HPV genotypes were prevalent in the majority (60.8%) of high-grade squamous intraepithelial lesion cases. Ethnicvariability should be considered when deciding which HPV genotypes to integrate into the HPV vaccine.

Can we rely on the Bethesda classification system in the differentiation of thyroid follicular lesions?

Can we rely on the Bethesda classification system in the differentiation of thyroid follicular lesions?

Comparative study of fine needle aspiration cytology and histopathology in thyroid nodules at a tertiary care hospital: First report from Somalia

BackgroundFNAC is a minimally invasive procedure and cost-effective, especially in developing countries where patients are mostly poor and surgery is not affordable. The present is the first study that examines the correlation between FNAC and histopathology in diagnosing thyroid cancers at a tertiary hospital in Somalia. MethodThis study included 231 patients with thyroid lesions who underwent pre-operative FNACs and histopathologic examination over five years. Investigated clinical parameters include sociodemographic and clinical features and cyto-histopathological findings. ResultsThe mean patient age was 39.3 ± 15.5 years, and there was a significant female predominance (n = 194; 84%), with a female to male ratio of 5.2:1. The overall sensitivity, specificity, and accuracy rate of cyto-histopathology correlation was 91.1%, 96.6%, and 94.9%, respectively. According to the Bethesda classification system of thyroid FNACs, (n = 141, 61%) of cases were Bethesda II (Benign), of which 95.7% of patients had a benign final histological diagnosis, while 4.3% had malignancy (6 false-negative results). Twenty-two patients (9.5%) were Bethesda III, (n = 3,1.3%) were Bethesda IV (suspicious for neoplasm), and all cases had a follicular adenoma on their final histological diagnosis. Forty-four of the patients were Bethesda V, found in 88.6% of its final histological diagnosis, while 11.4% were benign. Bethesda IV accounted for 9.1%, and all patients in this group were papillary thyroid carcinoma on its final histological confirmation. ConclusionOur study findings revealed that FNAC of thyroid lesions has a high accuracy rate, sensitivity, and specificity, allowing appropriate initial diagnostic management. It should be applied as the first investigative tool for thyroid lesions.

Thyroglobulin is a poor predictor of differentiated thyroid cancer in patients who undergo surgery for thyroid nodular diseases.

Thyroglobulin, produced exclusively by thyroid follicular cells, serves as a specific tumor marker for the follow-up of differentiated thyroid cancer (DTC) patients after thyroidectomy. However, its role as a predictor of malignancy in patients with thyroid nodules is controversial. We assessed the potential role of preoperative serum thyroglobulin concentration to predict DTC in patients without a preoperative diagnosis of malignancy who underwent partial or total thyroidectomy. This retrospective study included patients with a preoperative diagnosis of benign multinodular goiter (MNG) or a thyroid nodule with indeterminate cytology (INC) (Bethesda system categories III/IV) who underwent partial or total thyroidectomy between January 2014 and May 2019. We compared the patients' demographic, clinical, imaging, and biochemical data according to their final diagnosis: DTC or benign thyroid nodular disease. Further statistical analysis included odds ratio calculation and receiver operating characteristic (ROC) curve analysis. Of 131 patients who met inclusion and exclusion criteria, the indication for surgery was benign MNG in 69 patients and a thyroid nodule with INC in 62 patients. A final diagnosis of DTC was reported in 18 of the 69 benign MNG patients (26%) and in 30 of the 62 thyroid nodule with INC patients (48%). The preoperative measurements of nodule diameter and serum thyroid-stimulating hormone and thyroglobulin concentrations did not significantly differ between patients with a final diagnosis of DTC and those with benign histology. Preoperative serum thyroglobulin alone is insufficient to differentiate between malignant and benign thyroid nodular disease.

Evaluation of Bethesda IV-V thyroid nodules: clinical experience

Introduction: The malignancy rate in cases operated for thyroid nodule is approximately 5-10%, and although this rate shows significant differences according to Bethesda categories, there is a high risk of malignancy in categories IV and V compared to other categories. In our study, we examined the clinicopathological factors affecting the success of cytological diagnosis in nodules diagnosed with Bethesda IV-V.&#x0D; Material and Method: A total of 780 patients who were diagnosed with thyroid nodules and underwent surgery at our center between 2011 and 2021 were included in the study. The preoperative cytological diagnoses of the patients were categorized using the Bethesda classification system. The demographic data of the patients, Bethesda classification of the nodules, and postoperative histopathological examination results were evaluated in subgroups, and their significance was determined.&#x0D; Results: The age group with the highest number of cases was 45-59 years, and the female/male ratio of the whole cohort was 3:1. The rate of palpable nodules was 41.8% for the malignant diagnosis group and 58.2% for the benign diagnosis group. In both malignant and benign groups,

Non-invasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features (NIFTP) Lowers the Risk of Malignancy in the Bethesda System for Reporting Thyroid Cytopathology Diagnostic Categories.

Background:The introduction of non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) has been shown to decrease the risk of malignancy (ROM) in The Bethesda System for Reporting Thyroid Cytopathology. This knowledge may alter the management of patients with thyroid nodules.Objectives:To correlate cytological diagnosis with histological diagnosis for establishing the ROM of all Bethesda system categories after the introduction of NIFTP.Methods:This was a retrospective cohort study. All consecutive fine-needle aspiration cytology (FNAC) specimens collected from January 1, 2013, to December 31, 2017, at King Abdullah Medical City, Jeddah, Saudi Arabia, were assessed, and patients who underwent surgical excision of thyroid nodules were further analyzed. The ROM and overall ROM for each Bethesda category were calculated with and without considering NIFTP as a malignant tumor.Results:Overall, 1066 FNAC specimens were collected, of which 281 had a surgical correlation. Our cases included 18 (6.4%) non-diagnostic (ND), 109 (38.8%) benign, 28 (9.9%) atypia/follicular lesion of undetermined significance (AUS/FLUS), 39 (13.8%) follicular neoplasm or suspicion for follicular neoplasm (FN/SFN), 20 (7.1%) suspicion for malignancy (SM), and 67 (23.8%) malignant (POM) cases. After considering NIFTP diagnosis on resection specimens, the ROM decreased as follows: ND, 38.8% to 27.7% (P = 0.2388); benign, 21.1% to 11.9% (P = 0.0343); AUS/FLUS, 50% to 39.2% (P = 0.2089); FN/SFN, 53.8% to 33.3% (P = 0.0336); SM, 85% to 75% (P = 0.2147); POM, 95.5% to 88% (P = 0.0582).Conclusion:The introduction of NIFTP would significantly decrease the ROM of thyroid FNAC in both benign and FN/SFN categories of the Bethesda system.

Thyroid FNA performed by cytopathologists accompanied by radiologists guiding the ultrasound provide high-level quality results: A retrospective observational study

BackgroundOn thyroid cytology, false negative and false positive rates are considered parameters for quality control. Nevertheless, there are few studies about medical professional involved in this procedure. We conducted a 4-year cytohistological correlation of thyroid specimens in a single institution. To describe cytological and histological correlation where radiologists guide the ultrasound (US) and cytopathologists perform the thyroid fine needle aspiration (FNA). MethodsRetrospective observational study of thyroid specimens in a Brazilian countryside setting. The ultrasound was performed by radiologists, and the FNA was performed by pathologists. All cases were reviewed by two pathologists following the Bethesda Reporting System for Reporting Thyroid Cytopathology and the World Health Organization's Classification of Tumours of Endocrine Organs. Clinical information, such as sex, age, location, and ultrasound data, was collected from our reports. ResultsFrom a total of 3265 patients, 3703 nodules (391 patients showed more than one nodule) were submitted to FNA. For correlation, there were 168 surgical thyroidectomy specimens. The risk of malignancy for the Bethesda system categories were: nondiagnostic/unsatisfactory = 0/4 (0%); benign = 1/38 (2.6%); atypia of undetermined significance or follicular lesion of undetermined significance = 2/20 (10.0%); follicular neoplasm or suspicious for follicular neoplasm = 3/16 (18.7%); suspicious for malignancy = 63/67 (94.0%); and malignant = 22/23 (95.6%). ConclusionHigh-level quality results can be accomplished with cooperation between cytopathologists performing thyroid FNA accompanied by radiologists guiding the ultrasound.

Testing of mutations on thyroid nodules with indeterminate cytology: A prospective study of 112 patients in Argentina

BackgroundThe study of genetic mutations in thyroid nodules makes it possible to improve the preoperative diagnosis of and reduce unnecessary surgeries on benign nodules. In this study, we analysed the impact of implementing a 7-gene mutation panel that enables mutations to be detected in BRAF and RAS (H/N/K) and the gene fusions PAX8/PPARG, RET/PTC1 and RET/PTC2, in a population in northern Argentina. MethodsWe performed a prospective analysis of 112 fine needle aspirations diagnosed as having indeterminate cytology according to the Bethesda classification system. These include the Bethesda III or atypia of unknown significance/follicular lesion of unknown significance and Bethesda IV or follicular neoplasm/suspicious for follicular neoplasm categories. The mutations of the 7-gene panel were analysed and this information was linked to the available histology and ultrasound monitoring. ResultsThe BRAF V600E and RET/PTC1 mutations were associated with carcinoma in 100% of cases (n = 8), whereas only 37.5% (n = 3) of the nodules with RAS and 17% (n = 1) with PAX8/PPARG mutations were associated with carcinoma. From the histological diagnosis and ultrasound monitoring of patients, we can estimate that this panel has a sensitivity of 86% in detecting malignant carcinoma, a specificity of 77%, a positive predictive value (PPV) of 54% and a negative predictive value (NPV) of 94%. In this study, it was possible to reduce the number of surgeries by 48% in the patients analysed. ConclusionThe implementation of the mutation panel allowed the appropriate surgical strategy to be selected for each patient, the number of two-step surgeries to be reduced, and active follow-up to be established in low-risk patients.

Approach to Bethesda system category III thyroid nodules according to US-risk stratification.

This study evaluated how to manage Bethesda category III (Bethesda III) (atypia of undetermined significance/follicular lesion of undetermined significance [AUS/FLUS]) thyroid nodules according to the Korean Thyroid Imaging Reporting and Data System (K-TIRADS) to reduce unnecessary surgeries. A total of 161 thyroid nodules diagnosed as Bethesda III underwent surgery from 2016 to 2019. Ultrasonography-guided fine-needle aspiration (US-FNA) or core needle biopsy (CNB) was used for repeat examination. K-TIRADS category was assigned to the thyroid nodules. The proportion of malignancy in Bethesda III nodules confirmed by surgery were significantly increased in proportion relative to K-TIRADS with 60.0% low suspicion, 88.2% intermediate suspicion, and 100% high suspicion nodules (p < 0.001). The proportion of malignancy in AUS and FLUS were significantly different (94.2% vs. 40.0% p = 0.003). The proportion of malignancy in AUS increased with K-TIRADS categories, but there was no difference in FLUS. All K-TIRADS high suspicion nodules were AUS as papillary carcinomas (99%), while 80% of FLUS nodules and 50% of follicular carcinomas showed K-TIRADS low suspicion. In 116 nodules with repeat FNA or CNB after initial Bethesda III results, the conclusive result rate was significantly increased in proportion to K-TIRADS with 58.3% low suspicion, 83.3% intermediate suspicion, and 88.8% high suspicion nodules (p = 0.015). K-TIRADS low suspicion nodules of Bethesda III nodules should be managed after risk-benefit consideration rather than immediate surgery or repeat examination. K-TIRADS for Bethesda III nodules can predict papillary carcinoma well, but not follicular carcinoma.

The Prediction of Malignancy Risk in Thyroid Nodules Classified as Bethesda System Category III (AUS/FLUS) and the Role of Ultrasound Finding for Prediction of Malignancy Risk

ObjectiveTo predict the risk of malignancy in category III of the Bethesda System for Reporting Thyroid Cytopathology "Atypia of Undetermined Significance/Follicular Lesion of Undetermined Significance (AUS/FLUS)" at King Abdulaziz Medical City, Riyadh, Saudi Arabia. It also intends to determine other possible contributing predictors of malignancy in thyroid nodules such as age, sex, and ultrasound (US) findings.MethodThis retrospectively designed study included 187 patients (mean age, 43.9 ± 14.1 years) with thyroid nodules, which were diagnosed as AUS/FLUS and all patients included had total thyroidectomy or lobectomy between January 2013 and December 2018 at King Abdulaziz Medical City in Riyadh, Saudi Arabia. The electronic medical records, US images, and final cytopathology and histopathology reports were reviewed and analyzed.ResultThe overall incidence of AUS/FLUS was (46.5%). Multivariate analysis of US features revealed that malignancy was significantly associated with nodules with irregular margins, microcalcification, multiple numbers (P < 0.001), and hypoechogenicity (P 0.04).ConclusionDespite the high rate of malignancy of nodules AUS/FLUS, it is still consistent with previously reported studies. The highly suspicious ultrasound features (irregular margins, microcalcification, multiple nodules, and hypoechogenicity) could be helpful in the diagnosis of thyroid cancer.

Diagnostic Accuracy of Five Different Classification Systems for Thyroid Nodules: A Prospective, Comparative Study.

To compare the diagnostic performance of five different thyroid ultrasound classification systems, and determine which system is optimal for evaluating thyroid nodules and reducing the unnecessary biopsy rate. In this prospective study, 1,010 nodules referred for biopsy during a 2-year period were classified using five classification systems: the Kwak Thyroid Imaging Reporting and Data System (Kwak TI-RADS), the European TI-RADS (EU TI-RADS, the Korean TI-RADS (K TI-RADS), the American College of Radiology TI-RADS (ACR TI-RADS), and the American Thyroid Association (ATA) classification. After fine needle aspiration biopsy, all classifications were compared for all nodules and also particularly for nodules sized 1-3 cm. Sensitivity, specificity, and interobserver agreement were evaluated for each classification system. Of the 939 nodules (after exclusion of Bethesda 3 nodules) finally classified according to the surgical histopathology and cytology results, 73 (7.8%) were malignant and 866 nodules were benign (92.2%). The sensitivity was highest (94.5%) for the ACR TI-RADS and lowest for the Kwak TI-RADS (69%). After exclusion of small (<1 cm) and large nodules (>3 cm); while sensitivity was highest for ATA (97.8%), ACR TI-RADS was the second best classification (91.3%). There was substantial agreement among all classification systems except the Kwak TI-RADS (fair agreement). The ACR TI-RADS was the most sensitive ultrasound risk stratification system for all nodules, while the Kwak TI-RADS was the most specific, ie, the most capable of excluding benign nodules based on the combined cytological and histopathological results. ATA and ACR-TIRADS were the most sensitive classification systems for nodules 1 to 3 cm in size. The ACR TI-RADS had higher sensitivity than the Bethesda classification system when compared according to the histopathological results.