Clinical and Sonographic Features of Noninvasive Follicular Thyroid Neoplasm With Papillary-Like Nuclear Features: A Retrospective Study.

ABSTRACT: This study was designed to investigate the clinical and sonographic features of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTPs) as compared with classical papillary thyroid carcinoma (cPTC), follicular adenoma (FA), and follicular thyroid carcinoma (FTC). A total of 178 patients were enrolled in this study. The clinical characteristics and sonographic features of thyroid nodules were compared between NIFTP and cPTC or FA/FTC. All nodules were reclassified according to the Thyroid Ultrasound Imaging Reporting and Data System and American Thyroid Association guidelines classification. The mean size of NIFTP was 29.91 ± 14.71 mm, which was larger than that of cPTC ( P = 0.000). Significant difference was found in lymph node metastases between NIFTP and cPTC ( P = 0.000). Most NIFTPs showed solid composition, hypoechoic echogenicity, smooth margin, wider than tall shape, none echogenic foci, absence of halo, and perinodular vascularity, which were similar with FA and FTC. Compared with NIFTP, hypoechoic and very hypoechoic, taller than wide, irregular margin, punctate echogenic foci, absence of halo, and low vascularity were more commonly observed in cPTC. There were statistical differences both in American College of Radiology Thyroid Ultrasound Imaging Reporting and Data System and in American Thyroid Association classification between NIFTP and cPTC ( P < 0.05), but there were no significant differences between NIFTP and FTC/FA ( P > 0.05). The ultrasonographic characteristics of NIFTP were obviously different from cPTC but overlapped with FTC and FA. Ultrasound could help increase preoperative attention of NIFTP in an appropriate clinical setting, which may lead to a more conservative treatment approach.

Analysis of a pre-2017 follicular variant papillary thyroid carcinoma cohort reclassified as noninvasive follicular thyroid neoplasm with papillary-like features (NIFTP): an 11-year retrospective single institution experience.

INTRODUCTION: Noninvasive follicular thyroid neoplasm with papillary-like features (NIFTP), represents a distinct class of thyroid neoplasms with very low risk of adverse outcome and a set of strict histologic criteria. Introduction of NIFTP as a non-cancer has had an appreciable decrease in risk of malignancy and body of literature on this entity continues to grow. In this study, we reviewed clinical, fine-needle aspiration cytology (FNAC), imaging, and molecular findings of histologically proven NIFTPs at our institution. MATERIALS AND METHODS: Thyroid resections during an 11-year period, with histologic diagnosis of follicular variant of papillary thyroid carcinoma (FVPTC), were retrospectively reviewed to identify NIFTP. Ultrasonographic appearance, FNA findings, and molecular findings were also reviewed. RESULTS: Of 244 cases of FVPTC identified, 74 (30%) cases were reclassified as NIFTP. Mean tumor size was 2.5 cm. Of 33 patients with lymph node dissection, none had lymph node metastases. On imaging, 36 NIFTP (49%) showed vascularity, 25 (33%) were isoechoic to hypoechoic, there were calcifications in 14 cases (19%), and 7 cases (9%) showed a hypoechoic rim. Bethesda III/IV was the most common interpretation rendered on FNAC (31%). Seven cases had NRAS mutations and 1 case had BRAF V600E mutation. The remaining cases were either negative for BRAF V600E or had no identifiable molecular alterations. CONCLUSIONS: A significant percentage of tumors previously diagnosed as FVPTC were reclassified as NIFTP. This tumor cannot be reliably diagnosed preoperatively on FNAC, shows no characteristic features on ultrasound and has low suspicion of malignancy. BRAF V600E mutations are infrequent in NIFTP.

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

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

Surgical Management of Low-/Intermediate-Risk Node Negative Thyroid Cancer: A Single-Institution Study Using Propensity Matching Analysis to Compare Thyroid Lobectomy and Total Thyroidectomy.

Background: The approach for surgical treatment of patients with low-/intermediate-risk T1T2N0/Nx well-differentiated thyroid cancer (WDTC)-total thyroidectomy (TT) versus thyroid lobectomy (TL)-remains a controversial topic. Conducting a randomized controlled trial (RCT) would be the gold standard to address this issue. However, this is challenging due to excellent survival outcomes, and therefore, high number of patients and long-term follow-up would be required. As an alternative to RCT, we have used propensity score (PS) matching to determine if T1T2N0/Nx patients selected to have TL had equivalent outcomes to a similar group treated with TT. Methods: After institutional review board approval, a database of 6259 patients with WDTC treated with primary surgery at our institution between 1985 and 2016 was analyzed to identify patients with T1T2N0/Nx cancers. Of 3756 patients identified, 943 were managed by TL and 2813 by TT. To control for possible confounders and reduce potential bias, we selected age, sex, histology, 131I therapy, American Thyroid Association risk, and American Joint Committee Cancer stage as our PS matching criteria. Subsequently, 918 TL patients were successfully matched with 918 TT patients. The Pearson χ2 test or Fisher's exact test was used to compare categorical covariates, and Student's t-test was used for comparison of continuous variables between the two groups. Disease-specific survival (DSS), overall survival (OS), and recurrence-free survival (RFS) were calculated using the Kaplan-Meier method and compared using the log-rank test. Results: After PS matching, there were no significant differences between TL and TT patients for OS (10-year OS: 92.2% vs. 91.3%, p = 0.9668), DSS (10-year DSS: 100% vs. 99.1%, p = 0.1967), or RFS (10-year RFS: 99.5% vs. 98.3%, p = 0.079). Conclusions: For low-/intermediate-risk patients with intrathyroidal thyroid cancer <4 cm, patients selected for TL have similar survival outcomes to a comparable group treated by TT.

Pregnancy-associated plasma protein A mRNA expression as a marker for differentiated thyroid cancer: results from a "surgical" and a "cytological" series.

PURPOSE: Pregnancy-associated plasma protein A (PAPPA) is a metalloproteinase initially described for its role during pregnancy. PAPPA regulates IGF ligands 1 (IGF1) bioavailability through the degradation of IGF-binding protein 4 (IGFBP4). After the cleavage of IGFBP4, free IGF1 is able to bind IGF1 receptors (IGF1R) triggering the downstream signaling. Recently, PAPPA expression has been linked with development of several cancers. No data have been published on thyroid cancer, yet. METHODS: We evaluated PAPPA, insulin-like growth factor (IGF1), IGF1 receptors (IGF1R) and IGF-binding protein 4 (IGFBP4) mRNA expression levels in a "Surgical series" of 94 thyroid nodules (64 cancers, 16 follicular adenomas and 14 hyperplastic nodules) and in a "Cytological series" of 80 nodules from 74 patients underwent to fine-needle aspiration cytology (FNAC). In tissues, PAPPA was also evaluated by western blot. RESULTS: We found that PAPPA expression was increased in thyroid cancer specimen at mRNA and protein levels and that, adenomas and hyperplastic nodules had an expression similar to normal tissues. When applied on thyroid cytologies, PAPPA expression was able to discriminate benign from malignant nodules contributing to pre-surgical classification of the nodules. We calculated a cut-off with a good specificity (91%) which reached 100% when combined with molecular biology. CONCLUSION: These results show that PAPPA could represent a promising diagnostic marker for differentiated thyroid cancer.

Lymph node metastases >5 and metastatic lymph node ratio >0.30 of differentiated thyroid cancer predict response to radioactive iodine.

PURPOSE: The study was designed to elucidate the predictive value of the number of lymph node metastases (LNMs) and lymph node ratio (LNR) for response to therapy restratification system (RTRS). METHODS: From December 2015 to December 2019, 1228 patients who accepted radioactive iodine (RAI) were collected in the study. After 6-8 months, response to RAI was evaluated as complete response (excellent response) and incomplete response (indeterminate, biochemical, and structural incomplete response). The study developed classification tree to determine the optimum LNMs and LNR that predicted response to RAI. Multivariate logistic regression analyses were further analyzed to find independent factors of response to RAI. RESULT: The mean age of patients was 44 ± 12 and 71.09% (873/1228) were females. The best cutoff value of LNMs to affect RAI treatment response determined by classification tree was 5. Further in 388 patients with LNMs >5, the best cutoff value of LNR to affect RAI treatment response determined by classification tree was 0.30. With multivariate analysis, the study found that LNMs (>5), gender, lymph node dissection, and American Thyroid Association (ATA) risk classification were independent predictors of response to RAI for all 1228 patients; and LNR (>0.30), gender, and ATA risk classification for 388 patients with LNMs >5. The sensitivity analysis indicated that whether patients with LNM or not were included, the multivariate logistic regression model was kept stable. On subgroup analysis, no significant interactions were observed between the effect of LNMs/LNR and gender, N stage, ATA risk classification, lymph node dissection, or T stage. CONCLUSIONS: With classification tree, the study found that LNMs and LNR could predict initial response to RAI, and their optimal cutoff values were 5 and 0.30, separately.

Machine learning methods for automated classification of tumors with papillary thyroid carcinoma-like nuclei: A quantitative analysis.

When approaching thyroid gland tumor classification, the differentiation between samples with and without "papillary thyroid carcinoma-like" nuclei is a daunting task with high inter-observer variability among pathologists. Thus, there is increasing interest in the use of machine learning approaches to provide pathologists real-time decision support. In this paper, we optimize and quantitatively compare two automated machine learning methods for thyroid gland tumor classification on two datasets to assist pathologists in decision-making regarding these methods and their parameters. The first method is a feature-based classification originating from common image processing and consists of cell nucleus segmentation, feature extraction, and subsequent thyroid gland tumor classification utilizing different classifiers. The second method is a deep learning-based classification which directly classifies the input images with a convolutional neural network without the need for cell nucleus segmentation. On the Tharun and Thompson dataset, the feature-based classification achieves an accuracy of 89.7% (Cohen's Kappa 0.79), compared to the deep learning-based classification of 89.1% (Cohen's Kappa 0.78). On the Nikiforov dataset, the feature-based classification achieves an accuracy of 83.5% (Cohen's Kappa 0.46) compared to the deep learning-based classification 77.4% (Cohen's Kappa 0.35). Thus, both automated thyroid tumor classification methods can reach the classification level of an expert pathologist. To our knowledge, this is the first study comparing feature-based and deep learning-based classification regarding their ability to classify samples with and without papillary thyroid carcinoma-like nuclei on two large-scale datasets.

The Incidence of Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features: A Meta-Analysis Assessing Worldwide Impact of the Reclassification.

Background: Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) reclassification has significantly influenced the field of thyroidology. However, the extent of this impact depends upon the incidence of NIFTP in a given population. In this meta-analysis, we aimed to obtain robust information about the actual incidence of NIFTP worldwide by reviewing the published data. Methods: Comprehensive literature search was performed using electronic databases of PubMed and Web of Science over a five-year period (January 1, 2016, to January 30, 2021). The incidence of NIFTP was calculated by dividing the number of NIFTPs by the number of papillary thyroid carcinomas (PTCs). Meta-analysis of proportion and their 95% confidence interval [CI] were pooled using the random-effect model. Heterogeneity across the included studies was assessed using I2 statistics. Egger's regression test and funnel plot of estimates were used to evaluate the publication bias. p-Value <0.05 was considered significant. Results: From 505 publications, we included 50 studies, all retrospective, with 100,780 PTCs and 3990 NIFTP from 92 institutions worldwide. The overall incidence of NIFTP was 6.0% [CI 4.4-8.2] among PTCs or thyroid malignancies with a high level of heterogeneity among the included studies (I2 = 98.6%). NIFTP incidence was largely similar in North America and Europe (9.3% vs. 9.6%), with a significantly lower overall rate in Asia (2.1%). There was a significant decline in the reported incidence of NIFTP in non-Asian studies published after 2017 (p = 0.002). On applying our data on global thyroid cancer statistics, this reclassification would affect ∼30,881 patients annually, with a lower impact in Asia compared with North America and Europe. Conclusions: This comprehensive meta-analysis confirms that the worldwide NIFTP incidence is much lower than estimated initially. The NIFTP rates are significantly lower in Asian compared with North American and European countries. Apart from geography, NIFTP rates are significantly influenced by the nature of study, type of database used for sample collection, and the diagnostic criteria used. Introduction of NIFTP may potentially spare over 30,000 patients worldwide annually from clinical and psychological consequences of a thyroid cancer diagnosis.

Decreasing trends in thyroid cancer incidence in South Korea: What happened in South Korea?

BACKGROUND: South Korea has the highest incidence of thyroid cancer in the world. Our study examined the trends in thyroid cancer incidence by the histologic type, cancer stage, and age group and explored possible factors that affected thyroid cancer trends. METHODS: We conducted a descriptive epidemiological study using the national cancer registry data and cause of death data from 1999 to 2016 in South Korea. Age-standardized rates were calculated using Segi's world standard population. Joinpoint regression analysis was applied to determine the changing point of thyroid cancer trends according to histologic type; Surveillance, Epidemiology, and End Results (SEER) summary stage; and age groups by sex. RESULTS: The age-standardized incidence of thyroid cancer in both men and women increased from 6.3 per 100,000 people in 1999 to 63.4 per 100,000 in 2012 but declined from 2012 to 2016, before the debates for over diagnosis of thyroid cancer began in 2014. The age-standardized mortality rate of thyroid cancer, incidence of distant thyroid cancer, and incidence of regional and localized thyroid cancer started to decline since early 2000, 2010, and 2012, respectively. In addition, thyroid cancer prevalence in thyroid nodules showed decreasing trends from 1999-2000 to 2013-2014. CONCLUSIONS: The incidence of thyroid cancer began declining from 2012, before the debates for over diagnosis of thyroid cancer began in 2014. Changes in guidelines for thyroid nodule examinations may have affected this inflection point. Moreover, the debates for over diagnosis of thyroid cancer may have accelerated the decline in thyroid cancer.

Papillary thyroid microcarcinomas: does subtyping predict aggressive clinical behavior?

The most common malignant neoplasm affecting the thyroid gland is papillary thyroid carcinoma (PTC). PTC can demonstrate a number of morphologic variants including, but not limited to, classic, follicular, and tall cell. Each of these morphologic subtypes carry distinct clinical characteristics such that certain variants, like tall cell, behave more aggressively than others. PTCs measuring less than or equal to 1.0 cm are classified as microcarcinomas. Although these lesions are thought to be clinically indolent, we hypothesized that, like their larger counterparts, certain histologic variants may lead to worse patient outcomes. To test our hypothesis, we analyzed our pathology archives between the years 2009 and 2020 for papillary thyroid microcarcinomas and assessed whether different morphologic features correlated with more aggressive clinical behavior. Our findings suggest that certain variants exhibit features that portend a more worrisome clinical course and thus papillary thyroid microcarcinomas should be subtyped to help predict patient outcome.

Thyroid FNA terminology: The case for a single unified international system for thyroid FNA reporting.

The use of reporting terminologies for thyroid FNA cytology enables standardisation and international alignment of the reporting of thyroid cytology results, which is essential. There are currently three major internationally recognised systems: Bethesda (TBS), UK RCPath (Thy), and Italian (TIR). A fourth terminology system used in Japan has identical categories to TBS but with different nomenclature. The aim of this review is to discuss the strengths and weaknesses of the TBS, UK RCPath, and TIR systems, and to make the case for international terminology harmonisation and standardisation.

Outcome of atypia of undetermined significance/follicular lesion of undetermined significance in thyroid fine-needle aspirations: A six-year institutional experience.

BACKGROUND: Atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) is one of six diagnostic categories of The Bethesda System for Reporting Thyroid Cytopathology (BSRTC). The goal of our study is to assess the outcome of cases classified as AUS/FLUS at our institution. METHODS: AUS/FLUS cases were identified by computer searching of the thyroid fine-needle aspiration (FNA) cases performed between 2010 and 2016. Outcomes were categorized as: follow-up surgery, repeat FNA or no follow-up available. Demographics, ultrasound findings and FNA diagnostic criteria were reviewed for AUS/FLUS cases with follow-up surgical pathology diagnosis. RESULTS: Our AUS/FLUS thyroid FNA rate was 6% (117 out of 1984 FNAs). Only 15% of the AUS/FLUS cases had repeat FNA, while 41% underwent surgery. The risk of malignancy (ROM) for cases with follow-up surgery was 17%. When considering all AUS/FLUS cases, the ROM was 7%. Statistically, benign neoplasms were more likely to be single lesions on ultrasound comparing to malignant neoplasms, and to exhibit architectural atypia as opposed to non-neoplastic lesions on FNA. The malignancy rates among patients that directly went to surgical resection (17%) and patients having repeat FNA after the first AUS/FLUS diagnosis followed by surgery (29%) was not significantly different. However, repeat FNA was able to reclassify the majority of cases into more definitive categories. CONCLUSION: The outcome of the thyroid FNAs diagnosed as AUS/FLUS in our institution meets the benchmark statistics for AUS/FLUS rate and ROM. This study constitutes a valuable quality assurance measure and serves as a baseline for subsequent quality improvement.

The role of the size in thyroid cancer risk stratification.

Only a minority of cases of differentiated thyroid carcinoma (DTC) have a poor clinical outcome. Clinical outcomes and molecular aspects were assessed in: 144 DTC ≤ 40 mm without distant metastases (group 1); 50 DTC > 40 mm without distant metastases (group 2); and 46 DTC with distant metastases (group 3). Group 3 had a worse outcome than the other two groups: during the follow-up, patients more frequently had persistent disease, died, or underwent further treatment. The outcomes did not differ between groups 1 and 2. Group 3 had a higher prevalence of TERT promoter mutations than group 2 (32.6% vs 14%). Group 1 had a higher frequency of BRAF mutations than groups 2 or 3 (61.1% vs 16.0% and 26.1%, respectively), while RAS mutations were more common in group 2 than in groups 1 and 3 (16.0% vs 2.1% and 6.5%, respectively). Groups 1 and 2 shared the same outcome, but were genetically distinct. Only lymph node involvement, distant metastases, older age and (among the molecular markers) TERT promoter mutations were independent predictors of a worse outcome. Metastatic DTC had the worst outcome, while the outcome was identical for large and small non-metastatic DTC, although they showed different molecular patterns. TERT promoter mutations emerged as an independent factor pointing to a poor prognosis.

Thyroid malignancy rates according to the Bethesda reporting system in Israel - A multicenter study.

INTRODUCTION: The Bethesda System for Reporting Thyroid Cytopathology was developed in 2007 to facilitate an accurate, reproducible communication of thyroid fine-needle aspiration (FNA) interpretations between clinicians and cytopathologists and to serve as a guide for treatment. Based on large patient series, the system details the risk of malignancy for each category as well as a suggested management for each FNA result. Though this system has been widely adopted, there are only few studies to determine whether results are applicable for Israel. METHODS: A multicenter, retrospective analysis of medical charts of all patients who underwent thyroid surgery between January 1st, 2012 and December 31st, 2016 in four medical centers in Israel was performed. Data was analyzed for the overall risk of malignancy for the Bethesda system groups as well as comparison between the different laboratories performing the test. RESULTS: Records of 810 thyroidectomies in which preoperative cytological reports and final pathology were available and reviewed. The malignancy rates according to the Bethesda groups' I-VI for our cohort were: 27.8%, 17.6%, 41.4%, 41.4%, 86.9%, and 98.1% respectively. Similar results were seen when results were analyzed according to the different laboratories performing the tests. CONCLUSIONS: Post-surgical review of all Bethesda groups had higher malignancy rates than those reported in the original report. These results indicate a difference in the malignancy rates for the different Bethesda system groups in Israel compared to those reported. Physicians are encouraged to use data validated for their own country or patients' community in addition to published values.

Thyroid Carcinoma: Phenotypic Features, Underlying Biology and Potential Relevance for Targeting Therapy.

Thyroid carcinoma consists a group of phenotypically heterogeneous cancers. Recent advances in biological technologies have been advancing the delineation of genetic, epigenetic, and non-genetic factors that contribute to the heterogeneities of these cancers. In this review article, we discuss new findings that are greatly improving the understanding of thyroid cancer biology and facilitating the identification of novel targets for therapeutic intervention. We review the phenotypic features of different subtypes of thyroid cancers and their underlying biology. We discuss recent discoveries in thyroid cancer heterogeneities and the critical mechanisms contributing to the heterogeneity with emphases on genetic and epigenetic factors, cancer stemness traits, and tumor microenvironments. We also discuss the potential relevance of the intratumor heterogeneity in understanding therapeutic resistance and how new findings in tumor biology can facilitate designing novel targeting therapies for thyroid cancer.

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

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

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

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

Effect of the Noninvasive Follicular Thyroid Neoplasm With Papillary-Like Nuclear Features (NIFTP) Nomenclature Revision on Indian Thyroid Fine-Needle Aspiration Practice.

OBJECTIVES: To analyze risk of malignancy (ROM) in Bethesda categories (BCs) and the impact of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) reclassification on malignancy risk and surgical outcome. METHODS: In this retrospective study based on fine-needle aspiration samples with histologic follow-up, ROM was analyzed in BCs. Possible cases of NIFTP were reviewed, followed by the analysis of impact of this reclassification on ROM in BCs. RESULTS: The incidence of NIFTP was 6.9% among excised thyroid nodules and 16.8% among all resected neoplastic lesions. ROM for BCs I to VI was 37.5%, 9.6%, 40.0%, 46.5%, 88.8%, and 96.8%, respectively. Risk of neoplasia was 50.0%, 13.8%, 55.0%, 71.2%, 88.8%, and 96.8% respectively. When NIFTPs were considered nonmalignant lesions, ROM decreased by 6.3%, 4.3%, 20%, 19.1%, 22.5%, and 1.5% in each Bethesda category (I-VI), respectively. Inability to diagnose NIFTP preoperatively led to overtreatment in 16.2%. CONCLUSIONS: Prevalence of NIFTP in Asian countries may be higher than expected. Substantial cases of NIFTP have a benign preoperative cytology; hence, cases of follicular adenoma and adenomatous colloid nodule should be included in the review. NIFTP reclassification has significantly reduced the ROM in indeterminate BCs, suggesting diagnostic lobectomy rather than total thyroidectomy. Countries should establish their own malignancy risk range and parameters.

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

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