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Background: Hürthle cell-rich nodules (HCNs) encompass non-neoplastic to malignant lesions. There is paucity of literature on the frequency distribution of HCNs among Bethesda categories, histologic follow-up, risk of malignancy (ROM), and risk of neoplasia (RON). The objective of this retrospective, multi-institutional study was to determine the prevalence of the cytologic diagnostic category and surgical outcomes of patients with HCN., Methods: Nine tertiary health centers representing 6 Asian countries participated. Cases were retrieved from respective databases. The Bethesda System for Reporting Thyroid Cytopathology was used. Cytology results were correlated with surgical diagnoses., Results: Of 42,190 thyroid aspirates retrieved, 760 (1.8%) had a Hürthle cell predominance. Most (61%) were categorized as atypia of undetermined significance/follicular lesion of undetermined significance, Hürthle cell type" (AUS-H); 35% were categorized as follicular neoplasm, Hürthle cell type (FN-H); and 4% were categorized as suspicious for malignancy (SFM). Histologic follow-up was available for 288 aspirates (38%). Most were benign on resection (66%), and the most common histologic diagnosis was Hürthle cell adenoma (28.5%). The ROM for AUS-H, FN-H, and SFM, as calculated on resected nodules, was 32%, 31%, and 71%, respectively; and the RON was 47%, 81%, and 77%, respectively. The 5 institutions that had an AUS-H:HCN ratio below 0.5 diagnosed HCN less frequently as AUS-H than as FN-H., Conclusions: This is the largest, contemporary, multi-institutional series of HCNs with surgical follow-up. Although there was wide interinstitutional variation in prevalence and surgical outcomes, there was no significant difference in the ROM among institutions. The categories AUS-H and FN-H had a similar ROM for resected nodules., (© 2019 American Cancer Society.)

Objective: To evaluate the clinical significance and compare the imaging features according to the Thyroid Image Reporting and Data System (TIRADS) between atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) subcategories., Design & Patients: A total of 192 thyroid nodules in 188 patients (mean age: 50·2 ± 11·8 years) that had been initially diagnosed as AUS/FLUS on US-guided fine needle aspiration (US-FNA) were included. One cytopathologist retrospectively reviewed the cytology slides, subcategorizing cytology results into AUS and FLUS. A TIRADS category was assigned to each thyroid nodule according to the number of suspicious US features. Clinical, US features and malignancy rates were compared between the two subcategories., Results: Of the 192 AUS/FLUS lesions, 149 (77·6%) were subcategorized as AUS and 43 (22·4%) as FLUS. Of the 192 AUS/FLUS nodules, 82 (42·7%) were malignant. The malignancy rates between AUS and FLUS subcategories were not significantly different, 45·6% to 32·6%, respectively (P = 0·127). When applying TIRADS, significant differences were seen in TIRADS category between benign and malignant nodules in the AUS subcategory (P < 0·001), but not in the FLUS subcategory (P = 0·414). The malignancy rates in TIRADS categories 3, 4a, 4b, 4c and 5 were 15·4%, 22·2%, 33·3%, 57·1% and 80·0% (P < 0·001) in AUS nodules and 40·0%, 50·0%, 23·5%, 22·2% and 0·0% (P = 0·414) in FLUS nodules, respectively., Conclusion: Suspicious US features are useful in predicting malignancy among AUS subcategories but not in FLUS subcategories. Subcategorization into AUS and FLUS cytology may be helpful in deciding upon treatment or management of thyroid nodules., (© 2015 John Wiley & Sons Ltd.)

Purpose: To evaluate the clinical value of additional von Kossa staining on cytology in thyroid nodules with echogenic spots on ultrasound (US)., Materials and Methods: 342 thyroid nodules were analyzed for cytology and von Kossa staining was performed to detect microcalcifications. We compared diagnostic performances and accuracies of FNA and FNA with von Kossa staining to detect malignancy. We evaluated associations of aggressive pathologic features and von Kossa positivity in the surgically confirmed papillary thyroid carcinoma (PTC) group., Results: Two hundred and thirty two (67.8%) nodules were malignant and 110 (32.2%) were benign on cytopathology. Compared to cytology alone, additional von Kossa staining slightly improved sensitivity from 89.7% to 90.9% (P=0.081). In 207 cases of surgically confirmed PTC, von Kossa positivity was an independent predictor of central lymph node metastasis in PTCs by multivariate analysis (odds ratio, 2.218; P=0.021)., Conclusions: Adding von Kossa staining to cytology improved the sensitivity of thyroid nodules with echogenic spots on US. Positive von Kossa stains in PTCs may also be useful in predicting central lymph node metastasis., (Copyright © 2016 Elsevier GmbH. All rights reserved.)

Objectives: The purpose of this study was to investigate the level of conclusive results obtained with ultrasound (US)-guided core needle biopsy (CNB) and how this method should be applied for diagnosis of thyroid nodules., Methods: From January 2013 to November 2014, US-guided CNB was performed in 84 thyroid lesions of 83 patients. Based on CNB pathologic reports, thyroid nodules were divided into 2 categories: conclusive (nodules reaching a definite pathologic diagnosis suggesting benignity or malignancy) and inconclusive (nodules that were not able to reach a definite diagnosis because of ambiguous results). Medical records and US examinations were reviewed and compared., Results: The mean age of the 83 patients ± SD was 49.7 ± 14.1 years. Of the 84 thyroid nodules, 73 (86.9%) were diagnosed as benign or malignant and 11 (13.1%) as inconclusive by CNB pathologic analysis. Among the 11 nodules with inconclusive results, the possibility of a follicular neoplasm was suggested in 8 nodules (72.7%). No significant difference was seen in tumor size and US features when comparing the nodules with conclusive and inconclusive results (all P >.05)., Conclusions: Ultrasound-guided CNB may have supplemental roles in addition to US-guided fine-needle aspiration for diagnosis of selected cases. A considerable proportion of inconclusive results are seen on US-guided CNB, especially for diagnosis of follicular lesions, which must be considered when using this method for diagnosis of thyroid nodules., (© 2015 by the American Institute of Ultrasound in Medicine.)

Some morphologic parameters have been studied to help predict the BRAF(V600E) mutation using cytopathologic specimens, which can indicate which nodules should undergo further testing. The aim of this study was to investigate the value of cytomorphologic parameters to predict the BRAF(V600E) mutation in nodules read as "suspicious for malignancy" on cytology. This study included 142 resected nodules which were diagnosed as "suspicious for malignancy" on cytology in 142 patients. At our institution, BRAF(V600E) mutation analysis was performed at the request of the referring clinicians based on the clinical features of the patients, or the judgment of the radiologists performing US-FNA because suspicious US features were observed on the targeted nodule during this study period. Cytology smears were re-reviewed to assess the presence and amount of polygonal eosinophilic (plump) cells and microfollicles, and the presence of intranuclear pseudoinclusions, irregular nuclear membranes, nuclear grooves, sickles cells, psammoma bodies, and cystic changes. We evaluated the diagnostic performances of the cytomorphologic features to predict the BRAF(V600E) mutation. Polygonal eosinophilic (plump) cells, microfollicles, intranuclear pseudoinclusions, sickle cells, and cystic changes were significantly associated with the BRAF(V600E) mutation. The mutation was not present in all 6 thyroid nodules with microfollicles larger than 20% on cytology. Additionally, polygonal eosinophilic (plump) cells larger than 20%, cystic changes, and sickle cells on cytology had a high specificity of 95%, 96.7%, and 81.7%, respectively. Excluding 6 nodules with microfollicles larger than 20% on cytology, there were 82 (60.3%) nodules with the BRAF(V600E) mutation among the 136 nodules. Among the 136 nodules, there were 95 nodules with polygonal eosinophilic (plump) cells larger than 20%, cystic changes, or sickle cells on cytology. Of the 95 nodules, 69 (72.6%) had the mutation. Cytomorphologic features can help select nodules for the BRAF(V600E) mutation test among nodules read as "suspicious for malignancy" on cytology., (Copyright © 2015 Elsevier GmbH. All rights reserved.)

The object of this study is to evaluate the additional role of RAS mutation in detecting thyroid malignancy among BRAF mutation-negative nodules diagnosed as atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) on cytology.From December 2009 to December 2011, 202 BRAF mutation-negative thyroid nodules diagnosed as AUS/FLUS cytology in 201 patients were included in this study. RAS mutation analysis was performed using residual material from ultrasonography-guided fine needle aspiration (US-FNA) cytology testing for K-RAS, N-RAS, and H-RAS codons 12/13 and 61 point mutations. The authors evaluated the association between RAS mutation status and cytopathologic characteristics.Of the 202 BRAF mutation-negative thyroid nodules with AUS/FLUS cytology, 4 were considered insufficient for mutation analysis. Of the 198 thyroid nodules, 148 (74.7%) were confirmed as benign and 50 (25.3%) as malignant. Thirty-one (15.7%) of the 198 thyroid nodules were positive for any RAS mutation, 4 positive for K-RAS 12/13, 26 for N-RAS 61, and 1 positive for H-RAS 61. Seven (22.6%) of the RAS mutation positive nodules were malignant, 1 with K-RAS 12/13, 6 with N-RAS 61. Twenty-four (77.4%) of the 31 nodules positive for K-RAS 12/13 (N = 3), N-RAS 61 (N = 20), or H-RAS 61 (N = 1) mutations were proven benign. None of the 198 thyroid nodules were positive for K-RAS 61, N-RAS 12/13, or H-RAS 12/13 mutations.N-RAS 61 mutation is the most common mutation detected among BRAF mutation-negative nodules with AUS/FLUS cytology. RAS mutation has limited value in predicting malignancy among BRAF mutation-negative thyroid nodules with AUS/FLUS cytology and further, investigation is anticipated to evaluate the true role of RAS mutation in thyroid malignancy.

A decision to perform fine needle aspiration (FNA) on thyroid nodules mainly depends on sonographic features. We investigated if lymph node metastasis (LNM) risk differed by tumor size of thyroid cancers without suspicious sonographic features. Three hundred sixty patients with thyroid cancers with benign looking sonographic features were grouped by nodule size on ultrasonography (US) (≤ or >1 cm). The clinicopathologic parameters were compared between the groups. A multivariate analysis was performed to discover the independent factors predicting the presence of LNM. The nodules greater than 10 mm on US (n = 157) demonstrated a larger tumor size on histology (17.9 ± 14.5 vs. 5.6 ± 2.4 mm, P < 0.001), a lower frequency of classical papillary thyroid carcinoma (PTC) (58.6 vs. 87.2 %, P < 0.001), and a higher frequency of follicular variant PTC and follicular thyroid carcinoma (19.7 and 17.8 % vs. 9.4 and 1.5 %, respectively, P < 0.01). In subgroup analysis of 269 patients with classical PTC, the larger nodule size on US was associated with a higher prevalence of LNM (28.3 vs. 14.7 %, P = 0.007). A multivariate analysis revealed that classical PTC, extrathyroidal extension, and the US nodule size >10 mm were independent predictive factors of LNM after adjusting for age, sex, TSH level, and multifocality. Thyroid cancers larger than 10 mm with benign US features are more likely to be nonclassical PTC than those with smaller diameters. The larger ones also have an increased risk of LNM in classical PTC. These cases require a more aggressive approach to FNA.