Diagnostic Accuracy of Fine Needle Aspiration Cytology in Thyroid Nodules in Thammasat University Hospital

Background: Fine needle aspiration (FNA) cytology is a key investigation of thyroid nodules. There are several reports of FNA accuracy, which ranges from 75.0% to 94.8%, while false negative rates are 5.8% to 21.5%. In Thailand, there is no available data of FNA accuracy according to the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). The present study reported single-institute data of FNA accuracy, that could be used in thyroid nodule management. Objective: To determine the diagnostic accuracy of FNA cytology results of thyroid nodules collected in Thammasat University (TU) Hospital. Materials and Methods: The present study was a retrospective study collected cytologic results of all thyroid nodules that subsequently had definitive histopathologic diagnoses. The data were gathered from clinics at TU Hospital that performed thyroid nodule FNA between May 2011 and November 2014. The FNA cytology results were classified according to TBSRTC. Each cytopathologic result was compared with its postoperative tissue histopathology. The malignancy rate, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were calculated. Results: The present study included 197 thyroid nodule FNA cytology results. The sensitivity and specificity were 77.8% and 65.4%, respectively. The calculated PPV was found to be 47.7%, and the NPV was 87.9%. The accuracy of these results was 69.0%. The malignancy rate of the unsatisfactory group was 6.25%, benign group 8.05%, atypia of undetermined significance or follicular lesion of unknown significance 22.22%, follicular neoplasm/suspicious for follicular neoplasm 14.20%, suspicious for malignancy 73.68%, and malignant 100%. Conclusion: The FNA cytology in TU Hospital has comparable sensitivity to the other studies. Interestingly, the malignancy rate in the follicular neoplasm category is lower than that of the other institutes because of a high false positive rate in this category. This causes lower specificity and accuracy, which may cause a higher rate of unnecessary operations. Keywords: FNA; Thyroid nodule; Diagnostic accuracy

Rate of malignancy for thyroid nodules with AUS/FLUS cytopathology in a tertiary care center – a retrospective cohort study

Background Thyroid nodules are stratified through fine-needle aspiration (FNA) and are often categorized using The Bethesda System for Reporting Thyroid Cytopathology, which estimates the risk of malignancy for six cytopathological categories. The atypia of undetermined significance (AUS) and follicular lesion of undetermined significance (FLUS) categories have varying malignancy rates reported in the literature which can range from 6 to 72.9%. Due to this heterogeneity, we assessed the malignancy rate and effectiveness of repeat FNA (rFNA) for AUS/FLUS thyroid cytopathology at our institution. Methods Electronic health records of patients with AUS/FLUS thyroid cytopathology on FNA at our center since the implementation of the Bethesda System on May 1, 2014–December 31, 2019 were retrospectively reviewed. Patient demographics, treatment pathway, and pathology results were collected. The treatment pathway of the nodules, the rFNA results, and the malignant histopathology results were reported. Malignancy rates were calculated as an upper and lower limit estimate. Results This study described 182 AUS/FLUS thyroid nodules from 177 patients. In total, 24 thyroid nodules were deemed malignant upon histopathology, yielding a final malignancy rate of 13.2–25.3%. All of the malignancies were variants of papillary thyroid carcinoma. The malignancy rate of the nodules which underwent resection without rFNA (21.5%) was lower than the malignancy rate of the nodules which underwent resection after rFNA (43.8%). 45.5% of the rFNA results were re-classified into more definitive categories. Conclusion The malignancy rate of AUS/FLUS thyroid cytopathology at our center is in line with the risk of malignancy stated by the 2017 Bethesda System. However, our malignancy rate is lower than some other Canadian centers and approximately half of our rFNAs were re-classified, highlighting the importance of establishing center-specific malignancy and rFNA re-classification rates to guide treatment decisions.

Comparison of Afirma GEC and GSC to Nodules Without Molecular Testing in Cytologically Indeterminate Thyroid Nodules

Background Analysis of cytologically indeterminate thyroid nodules with Afirma Gene Expression Classifier (GEC) and Genomic Sequencing Classifier (GSC) can reduce surgical rate and increase malignancy rate of surgically resected indeterminate nodules. Methods Retrospective cohort analysis of all adults with cytologically indeterminate thyroid nodules from January 2013 through December 2019. We compared surgical and malignancy rates of those without molecular testing to those with GEC or GSC, analyzed test performance between GEC and GSC, and identified variables associated with molecular testing. Results 468 indeterminate thyroid nodules were included. No molecular testing was performed in 273, 71 had GEC, and 124 had GSC testing. Surgical rate was 68% in the group without molecular testing, 59% in GEC, and 40% in GSC. Malignancy rate was 20% with no molecular testing, 22% in GEC, and 39% in GSC (p = 0.022). GEC benign call rate (BCR) was 46%, sensitivity 100%, specificity 61% and PPV 28%. GSC BCR was 60%, sensitivity 94%, specificity 76%, and PPV 41%. Those with no molecular testing had larger nodule size, pre-operative growth of nodules, and constrictive symptoms, and those who underwent surgery in the no molecular testing group had higher BMI, constrictive symptoms, higher TIRADS and Bethesda classification. Type of provider was also associated with the decision to undergo surgery. Conclusion Implementation of GEC showed no effect on surgical or malignancy rate, but GSC resulted in significantly lower surgical and higher malignancy rates. This study provides insight into the factors that affect the real- world use of these molecular markers preoperatively in indeterminate thyroid nodules.

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

BackgroundHashimoto’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.MethodsThis 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.ResultsAmong 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.ConclusionThe malignancy rate of thyroid nodules with AUS/FLUS cytology was comparable irrespective of the presence of underlying CLT.

Malignancy Rate and Malignancy Risk Assessment in Different Lesions of Uncertain Malignant Potential in the Breast (B3 Lesions): An Analysis of 192 Cases from a Single Institution

<b><i>Background:</i></b> The question of how to deal with B3 lesions is of emerging interest. <b><i>Methods:</i></b> In the breast diagnostics of 192 patients between 2009 and 2016, a minimally invasive biopsy revealed a B3 lesion with subsequent resection. This study investigates the malignancy rate of different B3 subgroups and the risk factors that play a role in obtaining a malignant finding. <b><i>Results:</i></b> The distribution of B3 lesions after minimally invasive biopsy was as follows: atypical ductal hyperplasia (ADH), 7.3%; flat epithelial atypia (FEA), 7.8%; lobular neoplasia (LN), 7.8%; papilloma (Pa), 49.5%; phylloidal tumour (PT), 8.9%; radial sclerosing scar (RS), 3.1%; mixed findings, 10.4%; and other B3 lesions, 5.2%. Most B3 lesions were detected by stereotactic vacuum-assisted biopsy (44.3%), 36.5% by ultrasound-assisted biopsy, and 19.3% by magnetic resonance imaging-assisted biopsy. Most B3 lesions (55.2%) were verified by surgical resection, whereas 30.7% were downgraded to a benign lesion. About 14.1% of the cases were upgraded to malignant lesions, 9.4% to ductal carcinoma in situ and 4.7% to invasive carcinoma. In relation to individual B3 lesions, the following malignancy rates were found: 28.6% (ADH), 13.3% (FEA), 33.3% (LN), 12.6% (Pa), 5.9% (PT), and 0% (RS). The most important risk factor was increasing age. Postmenopausal status was considered an increased risk for an upgrade (<i>p =</i> 0.015). A known malignancy in the ipsilateral breast was a significant risk factor for a malignant upgrade (<i>p =</i> 0.003). <b><i>Conclusion:</i></b> Increasing knowledge about B3 lesions allows us to develop a “lesion-specific” therapy approach in the heterogeneous group of B3 lesions, with follow-up imaging for some lesions with less malignant potential and concordance with imaging or further surgical resection in cases of disconcordance with imaging or higher malignant potential.

Malignancy Rate of Indeterminate Findings on FDG-PET/CT in Cutaneous Melanoma Patients

Background: The use of 18F-2-Fluor-2-desoxy-D-glucose Positron Emission Tomography/Computed Tomography FDG-PET/CT in clinical routine for staging, treatment response monitoring and post treatment surveillance in metastatic melanoma patients has noticeably increased due to significant improvement of the overall survival rate in melanoma patients. However, determining the dignity of the findings with increased metabolic activity on FDG-PET/CT can be sometimes challenging and may need further investigation. Purpose: We aimed to investigate the malignancy rate of indeterminate findings on FDG-PET/CT in metastatic cutaneous melanoma patients. Methods: This single-center retrospective study included cutaneous melanoma patients who underwent FDG-PET/CT in clinical routine between 2015 and 2017 with findings reported as indeterminate and therefore requiring further evaluation. The dignity of the included findings was determined by subsequent imaging and, if required, additional histopathology. The impact of the outcome on the clinical management was also reported. Results: A total of 842 FDG-PET/CT reports of 244 metastatic cutaneous melanoma patients were reviewed. Sixty indeterminate findings were included. Almost half of all indeterminate findings were lymph nodes, lung nodules and cerebral lesions. In total, 43.3% of all included findings proved to be malignant. 81% of all malignant lesions were metastases of cutaneous melanoma, while 19% of all malignant lesions could be attributed to other primary malignancies, such as lung, breast, thyroid and colorectal cancers. Malignant findings influenced clinical management in 60% of the cases. Conclusion: Indeterminate findings on FDG-PET/CT in metastatic cutaneous melanoma patients should be further investigated. Almost one out of every two indeterminate findings on FDG-PET/CT is malignant. The majority of the findings are melanoma manifestations, however, in a significant percentage, other primary tumors are found. Upon verification, patient management is changed in most cases.

Malignancy Risk in 18F-FDG-Avid Thyroid Incidentalomas: Controversies and Limitations

Introduction: The prevalence of malignancy in thyroid incidentalomas (TI) discovered on 18F-FDG-PET or PET/CT varies between 0% and 63.6%. The pooled malignancy rate according to three systematic reviews is 33-35%. The 2015 American Thyroid Association (ATA) guidelines recommend that such nodules, when one centimeter or larger in size, should undergo further investigation with thyroid ultrasound (US) and fine-needle aspiration (FNA) cytology. Objectives: The objective of our study was to determine the rate of malignancy amongst TI discovered incidentally on 18F-FDG-PET or PET/CT, examine their clinicopathologic characteristics, and assess the usefulness of maximum standardized uptake values (SUVmax) in differentiating benign and malignant lesions. Methods: We performed an electronic medical record search looking at all 18F-FDG-PET or PET/CT reports during the study period of 12/01/2015 to 05/31/2019 that included the keyword ‘thyroid’ in the impression. Exclusion criteria included a history of thyroid disease or malignancy, known lesion(s) detected on previous clinical or radiological examinations and diffuse radiotracer uptake. Of the 476 reports reviewed, 136 cases were included in the study. Results: Common indications included initial staging or restaging of lymphoma (diffuse large B-cell, mantle-cell, T-cell types) (27.9%), lung adenocarcinoma (18.4%), head and neck cancer (16.9%) and breast cancer (11%). Fifty-eight (42.6%) patients had metabolically inactive lesions; five (8.6%) underwent further investigation with thyroid US and 3 subsequently with FNA (5%). All 3 had benign cytology. Seventy-seven (56.6%) patients had metabolically active lesions and 25 (32.5%) underwent imaging with thyroid US. Twelve (15.6%) had FNA; eight (66.7%) had benign cytology, two (16.7%) revealed atypia of undetermined significance and two (16.7%) were malignant. Biopsy for the two patients with malignant cytology showed follicular cell neoplasm of oncocytic hurtle cell type, and invasive follicular carcinoma with focal insular and papillary features and extensive capsular and vascular invasion. The mean SUVmax in malignant vs benign lesions was 9.05 and 6.41 respectively. Conclusion: The malignancy rate was 2.6% amongst all patients with 18F-FDG-avid TI and 8% amongst patients with metabolically active lesions who were investigated with thyroid US+/- FNA. This is significantly lower than malignancy rates previously reported in the literature. The evident inhomogeneity in the literature is likely multifactorial and may be explained in part by a dissimilarity among studies, and an informed decision by some to avoid invasive testing in the context of poor prognosis from underlying non-thyroidal cancer. Research is needed to determine the cohort of patients who could potentially benefit from further evaluation and treatment.

Comparison of Four Ultrasonography-Based Risk Stratification Systems in Thyroid Nodules with Nondiagnostic/Unsatisfactory Cytology: A Real-World Study

We compared American Thyroid Association (ATA) guidelines, Korean (K)-Thyroid Imaging, Reporting and Data Systems (TIRADS), EU-TIRADS, and American College of Radiology (ACR) TIRADS in diagnosing malignancy for thyroid nodules with nondiagnostic/unsatisfactory cytology. Among 1143 nondiagnostic/unsatisfactory aspirations from April 2011 to March 2016, malignancy was detected in 39 of 89 excised nodules. The minimum malignancy rate was 7.82% in EU-TIRADS 5 and 1.87–3.00% in EU-TIRADS 3–4. In the other systems, the minimum malignancy rate was 14.29–16.19% in category 5 and ≤3% in the remaining categories. Although the EU-TIRADS category ≥ 5 exhibited the highest positive likelihood ratio (LR) of only 2.214, category ≥ 5 in the other systems yielded the highest positive LR of >5. Receiver operating characteristic (ROC) curves of all systems to predict malignancy were located statistically above the diagonal nondiscrimination line (P for ROC curve: EU-TIRADS, 0.0022; all others, 0.0001). The areas under the ROC curve (AUCs) were not significantly different among the four systems. The ATA guidelines, K-TIRADS, and ACR TIRADS may be useful to guide management for nondiagnostic/unsatisfactory nodules. The EU-TIRADS, although also useful, exhibited inferior performance in predicting malignancy for nondiagnostic/unsatisfactory nodules in Korea, an iodine-sufficient area.

Diagnostic Algorithm for Metastatic Lymph Nodes of Differentiated Thyroid Carcinoma

We aimed to evaluate appropriate strategies for interpreting fine-needle aspiration cytology (FNAC) and thyroglobulin concentrations obtained through aspiration (FNA-Tg) results based on the sonographic features of lymph nodes (LNs). Consecutive patients who underwent ultrasound-guided FNAC and FNA-Tg for metastatic LNs from differentiated thyroid carcinomas (DTCs) from January 2014 to December 2018 were reviewed retrospectively. LNs were categorized sonographically as suspicious, indeterminate, or benign. The optimal FNA-Tg cutoff for metastatic LNs was evaluated preoperatively, after lobectomy, and after total thyroidectomy. The diagnostic performances of FNA-Tg, FNAC, and their combination were analyzed based on the sonographic features of LNs. The malignancy rates of LNs were analyzed based on the sonographic features, FNAC, and FNA-Tg results. Of the 1543 LNs analyzed, 528 were benign, whereas 1015 were malignant. FNA-Tg increased the sensitivity and accuracy of FNAC for LNs. The malignancy rate of LNs found to be malignant by FNAC or elevated FNA-Tg ranged from 82% to 100%, regardless of the sonographic features. The malignancy rate of LNs with indeterminate or benign FNAC findings and low FNA-Tg were stratified according to their sonographic features. We propose a diagnostic algorithm, based on combined FNAC, FNA-Tg, and ultrasound features of LNs, for diagnosing metastatic LNs of DTCs.

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

<b><i>Background:</i></b> 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. <b><i>Methods:</i></b> 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. <b><i>Results:</i></b> 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. <b><i>Conclusion:</i></b> 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.