Deep learning-based computer-aided diagnosis system for the automatic detection and classification of lateral cervical lymph nodes on original ultrasound images of papillary thyroid carcinoma: a prospective diagnostic study.

PURPOSE: This study aims to develop a deep learning-based computer-aided diagnosis (CAD) system for the automatic detection and classification of lateral cervical lymph nodes (LNs) on original ultrasound images of papillary thyroid carcinoma (PTC) patients. METHODS: A retrospective data set of 1801 cervical LN ultrasound images from 1675 patients with PTC and a prospective test set including 185 images from 160 patients were collected. Four different deep leaning models were trained and validated in the retrospective data set. The best model was selected for CAD system development and compared with three sonographers in the retrospective and prospective test sets. RESULTS: The Deformable Detection Transformer (DETR) model showed the highest diagnostic efficacy, with a mean average precision score of 86.3% in the retrospective test set, and was therefore used in constructing the CAD system. The detection performance of the CAD system was superior to the junior sonographer and intermediate sonographer with accuracies of 86.3% and 92.4% in the retrospective and prospective test sets, respectively. The classification performance of the CAD system was better than all sonographers with the areas under the curve (AUCs) of 94.4% and 95.2% in the retrospective and prospective test sets, respectively. CONCLUSIONS: This study developed a Deformable DETR model-based CAD system for automatically detecting and classifying lateral cervical LNs on original ultrasound images, which showed excellent diagnostic efficacy and clinical utility. It can be an important tool for assisting sonographers in the diagnosis process.

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.

Prognostic implications of extranodal extension in papillary thyroid carcinomas: A propensity score matching analysis and proposal for incorporation into current tumor, lymph node, metastasis staging.

BACKGROUND: The current American Joint Committee on Cancer tumor, lymph node, metastasis cancer staging system for papillary thyroid carcinoma places low weight on extranodal extension. This study examined the prognostic implications of extranodal extension in papillary thyroid carcinoma patients and attempted to design a new staging system incorporating extranodal extension. METHODS: We reviewed data from 6,165 consecutive papillary thyroid carcinoma patients from 2012 to 2018. Patients with extrathyroidal extension or extranodal extension were included and then divided into 3 groups: extrathyroidal extension (papillary thyroid carcinoma with extrathyroidal extension but without extranodal extension, N = 457); extranodal extension (papillary thyroid carcinoma with extranodal extension but without extrathyroidal extension, N = 116); and extrathyroidal extension and extranodal extension (papillary thyroid carcinoma with both extrathyroidal extension and extranodal extension, N = 116). Recurrence-free survival and cancer-specific survival were compared before and after adjusting for differences using propensity score matching owing to observed heterogeneity in baseline characteristics in the original cohort. Recurrence-free survival and cancer-specific survival were also compared between patients with and without extranodal extension after matching at a 1:1 ratio. Cox proportional hazards regression analyses were used to identify the relationships of factors associated with structural recurrent disease in the node-positive subset. Then a new staging system incorporating extranodal extension was established, and the discrimination of the new staging system for recurrence-free survival and cancer-specific survival was investigated. RESULTS: Of the 6,165 patients with papillary thyroid carcinoma, extrathyroidal extension was found in 573 (9.3%) patients, and extranodal extension was observed in 232 (3.8%) patients. The recurrence-free survival and cancer-specific survival rates of patients with extranodal extension were similar to those of patients with extrathyroidal extension (all P > .05). Patients with extrathyroidal extension and extranodal extension experienced worse recurrence-free survival than patients with extrathyroidal extension or extranodal extension and even worse cancer-specific survival than patients with extrathyroidal extension (all P < .05). The recurrence-free survival and cancer-specific survival rates of patients with extranodal extension were worse than those of patients without extranodal extension (P = .003; P = .048). Cox proportional hazards regression analysis demonstrated that after propensity score matching, extranodal extension (hazard ratio 1.911; 95% confidence interval 1.568-3.609; P < .001) remained an independent predictor of structural recurrent disease in patients with node-positive papillary thyroid carcinoma. After incorporating extranodal extension into the current tumor, lymph node, metastasis classification, the new staging system presented a better discrimination for recurrence-free survival and cancer-specific survival for those with lymph node metastasis. CONCLUSION: Papillary thyroid carcinoma patients with extranodal extension present worse prognosis, and incorporating extranodal extension in tumor, lymph node, metastasis classification identifies poor-risk patients more accurately.

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.

An 8 miRNA-Based Risk Score System for Predicting the Prognosis of Patients With Papillary Thyroid Cancer.

BACKGROUND: Dysregulation of microRNAs (miRNAs) in papillary thyroid cancer (PTC) might influence prognosis of PTC. This study is aimed to develop a risk score system for predicting prognosis of PTC. METHODS: The miRNA and gene expression profiles of PTC were obtained from The Cancer Genome Atlas database. PTC samples were randomly separated into training set (n = 248) and validation set (n = 248). The differentially expressed miRNAs (DE-miRNAs) in the training set were screened using limma package. The independent prognosis-associated DE-miRNAs were identified for building a risk score system. Risk score of PTC samples in the training set was calculated and samples were divided into high risk group and low risk group. Kaplan-Meier curves and receiver operating characteristic (ROC) curve were used to assess the accuracy of the risk score system in the training set, validation set and entire set. Finally, a miRNA-gene regulatory network was visualized by Cytoscape software, followed by enrichment analysis. RESULTS: Totally, 162 DE-miRNAs between tumor and control groups in the training set were identified. An 8 independent prognosis-associated DE-miRNAs, (including miR-1179, miR-133b, miR-3194, miR-3912, miR-548j, miR-6720, miR-6734, and miR-6843) based risk score system was developed. The area under ROC curve in the training set, validation set and entire set was all above 0.93. A miRNA-gene regulatory network involving the 8 DE-miRNAs were built and functional enrichment analysis suggested the genes in the network were significantly enriched into 13 pathways, including calcium signaling pathway and hedgehog signaling pathway. CONCLUSION: The risk score system developed this study might be used for predicting the prognosis of PTC. Besides, the 8 miRNAs might affect the prognosis of PTC via hedgehog signaling pathway and calcium signaling pathway.

Influence of Nomenclature Changes on Trends in Papillary Thyroid Cancer Incidence in the United States, 2000 to 2017.

CONTEXT: US papillary thyroid carcinoma (PTC) incidence recently declined for the first time in decades, for reasons that remain unclear. OBJECTIVE: This work aims to evaluate PTC incidence trends, including by histologic subtype and size, and noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). DESIGN: This descriptive study uses US Surveillance, Epidemiology, and End Results-18 cancer registry data (2000-2017). PATIENTS: Participants included individuals diagnosed with PTC (2000-2017) or NIFTP (2016-2017). RESULTS: During 2000 to 2015, PTC incidence increased an average 7.3% per year, (95% CI, 6.9% to 7.8%) during 2000 to 2009, and 3.7% per year (95% CI, 0.2% to 7.3%) during 2009 to 2012, before stabilizing in 2012 to 2015 (annual percentage change [APC] = 1.4% per year, 95% CI, -1.8% to 4.7%) and declining in 2015 to 2017 (APC = -4.6% per year, 95% CI, -7.6% to -1.4%). The recent declines were observed for all sizes of PTC at diagnosis. Incidence of follicular variant of PTC (FVPTC) sharply declined in 2015 to 2017, overall (APC = -21.1% per year; 95% CI, -26.5% to -15.2%) and for all tumor sizes. Observed increases in encapsulated papillary carcinoma (classical PTC subtype) and NIFTP each accounted for 10% of the decline in FVPTC. Classical PTC incidence continuously increased (2000-2009, APC = 8.7% per year, 95% CI, 8.1% to 9.4%; 2009-2017, APC = 1.0% per year, 95% CI, 0.4% to 1.5%), overall and for all sizes except smaller than 1 cm, as did incidence of other PTC variants combined (2000-2017, APC = 5.9% per year, 95% CI, 4.0% to 7.9%). CONCLUSION: The reasons underlying PTC incidence trends were multifactorial. Sharp declines in FVPTC incidence during 2015 to 2017 coincided with clinical practice and diagnostic coding changes, including reclassification of noninvasive encapsulated FVPTC from a malignant to in situ neoplasm (NIFTP). Observed increases in NIFTP accounted for 10% of the decline in FVPTC.

Ultrasound findings of noninvasive follicular thyroid neoplasm with papillary-like nuclear features compared with those of follicular variant of papillary carcinoma and encapsulated papillary carcinoma: a single-institution study in Japan.

Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is a new entity adopted by the newest World Health Organization classification. It is differentiated from follicular variant papillary thyroid carcinoma (FVPTC) and regarded as non-malignant disease. Here, we compared the ultrasound findings of NIFTP (n = 40) with those of FVPTC (n = 94) and encapsulated PTC (encap-PTC) (n = 157). The NIFTP group showed benign findings on ultrasound significantly more frequently than the FVPTC group based on the Japan Society of Ultrasonics in Medicine criteria: a regular shape (p < 0.001), well edge definition (p = 0.007), smooth character (p < 0.001), isoechoic and homogeneous internal echoes (p < 0.001), lack of punctate microcalcification (p = 0.027), and a regular marginal hypoechoic zone (p < 0.001). Compared to encap-PTC, NIFTP has a significantly higher incidence of benign findings: isoechoic and homogeneous internal echoes (p < 0.001), lack of punctate microcalcification (p < 0.001), and a regular marginal hypoechoic zone (p = 0.004). Based on the ultrasound classification (USC) system at Kuma Hospital, no cases were classified as malignant (USC ≥3.5), but 55.4% of the FVPTCs and 53.5% of the encap-PTCs were diagnosed as malignancy. However, on cytology, the incidence of NIFTP classified as Bethesda-V or -VI (PTC) was very high at 86.9%. All patients underwent surgical treatment, but none of the NIFTP patients showed postoperative recurrence. Although avoiding surgery might be difficult because of the high incidence of malignant cytology, overtreatment (including extensive surgery) for NIFTP can be avoided by paying close attention to the lack of malignant findings on ultrasound.

Ensemble Deep Learning Model for Multicenter Classification of Thyroid Nodules on Ultrasound Images.

BACKGROUND Thyroid nodules are extremely common and typically diagnosed with ultrasound whether benign or malignant. Imaging diagnosis assisted by Artificial Intelligence has attracted much attention in recent years. The aim of our study was to build an ensemble deep learning classification model to accurately differentiate benign and malignant thyroid nodules. MATERIAL AND METHODS Based on current advanced methods of image segmentation and classification algorithms, we proposed an ensemble deep learning classification model for thyroid nodules (EDLC-TN) after precise localization. We compared diagnostic performance with four other state-of-the-art deep learning algorithms and three ultrasound radiologists according to ACR TI-RADS criteria. Finally, we demonstrated the general applicability of EDLC-TN for diagnosing thyroid cancer using ultrasound images from multi medical centers. RESULTS The method proposed in this paper has been trained and tested on a thyroid ultrasound image dataset containing 26 541 images and the accuracy of this method could reach 98.51%. EDLC-TN demonstrated the highest value for area under the curve, sensitivity, specificity, and accuracy among five state-of-the-art algorithms. Combining EDLC-TN with models and radiologists could improve diagnostic accuracy. EDLC-TN achieved excellent diagnostic performance when applied to ultrasound images from another independent hospital. CONCLUSIONS Based on ensemble deep learning, the proposed approach in this paper is superior to other similar existing methods of thyroid classification, as well as ultrasound radiologists. Moreover, our network represents a generalized platform that potentially can be applied to medical images from multiple medical centers.

A closer look at NIFTP.

Despite the rise in the incidence of papillary thyroid carcinoma (PTC) during the last 30 years, the mortality rate due to PTC has remained static. One reason for this phenomenon is the indolent nature of some of the tumors that are diagnosed as PTC. A subgroup of tumors, which often exhibited such indolent behavior, was encapsulated/well-circumscribed follicular lesions that showed PTC nuclear features. Despite their indolent behavior, these tumors were managed as was any other PTC, often with total thyroidectomy and radioactive iodine (RAI) treatment. In order to prevent overtreatment of these tumors, they were recently reclassified as "non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP)." Since it is proposed that NIFTP be managed in a more conservative manner, its diagnosis is now based on strict histological criteria. The genetic basis of these diagnostic criteria and the utility of molecular markers in the diagnosis of NIFTP are currently being scrutinized. The aim of this review is to discuss the events that led to the emergence of the term NIFTP, as well as its histological and molecular background.

Did Introducing a New Category of Thyroid Tumors (Non-invasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features) Decrease the Risk of Malignancy for the Diagnostic Categories in the Bethesda System for Reporting Thyroid Cytopathology?

In 2016, Nikiforov et al. (JAMA Oncol 2:1023-1029, 2016) proposed replacing the term "non-invasive encapsulated follicular variant of papillary thyroid carcinoma" (FVPTC) with the term "non-invasive follicular thyroid neoplasm with papillary-like nuclear features" (NIFTP). In 2018, to avoid the misdiagnosis of papillary thyroid cancer as NIFTP, the authors proposed changes to the criteria for NIFTP classification. Some previous studies evaluated the impact of NIFTP on the risk of malignancy (ROM) in the fine-needle aspiration cytology (FNAC) diagnostic categories according to the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). However, little is known about the influence of an NIFTP diagnosis on ROM on the basis of the revised criteria. The aim of this study was to assess the influence of NIFTP on ROM using the revised diagnostic criteria. The present study included 998 thyroid nodules that were diagnosed and resected at the same medical center. All specimens with a diagnosis of cancer were reviewed to identify NIFTP according to the revised 2018 criteria. Additionally, molecular diagnostics were performed to detect the BRAF p.V600E mutation and TERT promoter mutations in all the NIFTP cases. The number of cases that met the revised criteria was determined, and the ROM was calculated in each of the FNAC diagnostic categories. Only five cases (2.3% of all papillary thyroid carcinoma diagnoses) were considered NIFTP, according to the 2018 criteria. With respect to the FNAC category, one case was a follicular neoplasm or suspicious for a follicular neoplasm (FN/SFN), three cases were suspicious for malignancy (SM), and one case was malignant (M). The ROM decreased in each of the Bethesda categories (0.7% in FN/SFN, 4.3% in SM, and 0.5% in M) when a diagnosis of NIFTP was taken into account. These reductions were not statistically significant. These data indicate that the NIFTP entity has very little impact on ROM for the diagnostic categories of the Bethesda system.

Practice Paradigms Before and After Introduction of the Diagnosis-Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features (NIFTP): an Institutional Experience.

The recently adopted terminology of "Noninvasive follicular thyroid neoplasm with papillary-like nuclear features" (NIFTP) reflects the indolent behavior of these tumors. In contrast to conventional papillary thyroid carcinomas, NIFTP can be managed conservatively. The purpose of this study was to investigate changes in surgical and pathologic practice patterns at our institution since the introduction of the NIFTP diagnosis in 2016. A retrospective analysis of all thyroid specimens received in our laboratory between January 2015 and April 2017 was performed. The final cohort consisted of 1508 thyroidectomy specimens from 1508 patients (1153 (76.5%) women and 355 (23.5%) men), of which 1011 (67%) were total thyroidectomies and 497 (33%) were partial thyroidectomies. There were 558 (69.2%) total thyroidectomies and 248 (30.8%) partial thyroidectomies performed prior to introduction of the NIFTP diagnosis and 453 (64.5%) and 249 (35.5%) total and partial thyroidectomies, respectively, after the change in nomenclature. Within a year following the initial use of this diagnosis, 67 NIFTP cases were identified (9.5% of all thyroidectomies), whereas compared with the year preceding it, malignant diagnoses decreased from 54.5 (439) to 44.6% (313), and the benign category remained unchanged from 44.5 (367) to 45.9% (322). For the entirely submitted 67 NIFTP cases, the mean number of blocks submitted was 14.7 (0.98 blocks/g); for malignant lesions 17.7 (0.92 blocks/g); and for benign lesions 16.6 (0.75 blocks/g). The results of our study suggest that NIFTP are encountered in almost 10% of thyroidectomies at our institution with expected shifts in cytology and surgical pathology diagnoses as a result of the change in nomenclature. During this time period, significant shifts towards less aggressive surgical management were not observed. All 67 NIFTP nodules were submitted entirely with no significant difference in the number of cassettes submitted for NIFTP nodules as compared with follicular variant papillary thyroid carcinoma (PTC), classic variant PTC, or follicular adenoma.

Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features (NIFTP): An Update.

Based on evidence accumulated over the past three decades showing that noninvasive encapsulated follicular variant of papillary thyroid carcinoma has an indolent clinical behavior and a RAS-like molecular profile similar to follicular adenoma, the Endocrine Pathology Society working group in 2016 proposed to rename this entity as "noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP)" in order to eliminate the term "carcinoma" from the diagnosis. It is a major evidence-based attempt initiated by an international group of endocrine pathologists to tackle the epidemic of thyroid cancer overdiagnosis and overtreatment. However, its creation and continuous existence are not without controversies. NIFTP has sparked a wave of follow up studies aiming to decipher the exact nature of this new entity. In this review, we summarize the rationale, diagnostic criteria, controversies and subsequent changes to the NIFTP concept, and their impact on patient care and pathology practice.

Noninvasive follicular thyroid neoplasm with papillary-like nuclear features and the risk of malignancy in The Bethesda System for the Reporting of Thyroid Cytopathology.

INTRODUCTION: The Bethesda System for the Reporting of Thyroid Cytopathology (TBSRTC) is used to categorize and diagnose thyroid nodules by fine needle aspiration biopsy (FNAB). Each category in TBSRTC is associated with an estimated risk of malignancy (ROM). A subset of noninvasive encapsulated follicular variant of papillary thyroid carcinoma (niEFVPTC) was reclassified as a nonmalignant tumor: noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). We studied the impact of this reclassification on the reported ROM in TBSRTC. MATERIAL AND METHODS: We searched our institutional files for thyroid FNAB with surgical follow-up. ROM for each TBSRTC category was calculated. Subsequently, cases of niEFVPTC were reviewed and reclassified as NIFTP, if appropriate. ROM for each category was then recalculated after the reclassification. RESULTS: Twenty-six NIFTP were identified; the corresponding FNABs were distributed among all six TBSRTC categories. The majority of NIFTP FNAB were in the AUS/FLUS and suspicious for malignancy (SUSP) categories, 12 (46.2%) and 8 (30.8%), respectively. While the ROM changed for all diagnostic categories, the greatest change in ROM after reclassification was seen in these two categories. Absolute ROM for AUS/FLUS decreased from 25.0% to 21.0% and SUSP, from 71.7% to 58.3%, changes that were statistically significant. CONCLUSIONS: The reclassification of niEFVPTC to NIFTP has significantly impacted the ROM in the TBSRTC at our institution. While there was a decrease in ROM for all categories, the greatest reduction to ROM was in the categories of AUS/FLUS and FN. These changes to the ROM should help guide surgical approach moving forward.

The clinicopathologic characteristics of familial and sporadic papillary thyroid carcinoma in Turkish patients

Background/aim: The aim of this study is to investigate clinicopathologic features of familial papillary thyroid carcinoma (fPTC) and compare them with sporadic papillary thyroid carcinoma (sPTC) in Turkish patients. A retrospective analysis of the papillary thyroid carcinoma (PTC) cases, with or without family history with a follow-up around 10 years was performed. Materials and methods: A series of patients with fPTC (82 fPTC families with 146 affected individuals) were compared with patients with sPTC (n = 112). The clinicopathologic features [(age, gender, histologic subtype, tumour size, bilaterality, multifocality, extrathyroidal extension (ETE), lymph node metastasis (LNM)] and treatment procedures (lymph node dissection, radioactive iodine ablation), and the outcomes like recurrences in the neck region, distant metastasis, and the need for reoperation were compared between the groups. Results: When the groups were compared, there was no significant difference in age (P = 0.449), and tumour size (P = 0.898) between familial and sporadic PTC patients. fPTC group had a significantly higher risk of male gender (P=0.001), bilaterality (P = 0.004), multifocality (P = 0.011), LNM (P = 0.013), ETE (P = 0.040), and distant metastasis (P ≤ 0.0001) than the sPTC group. However, recurrence rate was similar between the 2 groups (P = 0.436). Conclusion: The results of this study confirms a more aggressive nature in fPTC patients, in terms of bilaterality, multifocality, ETE, LNM, and distant metastasis, compared to sPTC patients in Turkish population.

Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is rare, benign lesion using modified stringent diagnostic criteria: Reclassification and outcome study.

BACKGROUND: Rigid diagnostic criteria for NIFTP have been recently proposed. The frequency of NIFTP using the new criteria is unknown, and whether abortive papillae are associated with BRAFV600E mutation has not been studied. The aim of this study is to identify NIFTP by a retrospective review of Follicular Variant of Papillary Thyroid Carcinoma (FVPTC), and to study its incidence as well as the association between immunohistochemical BRAFV600E expression and abortive papillae in NIFTP. DESIGN: Thyroid tumors diagnosed as FVPTC or NIFTP over a period of 18 years (2000-2017) were identified using the laboratory information system. The final pathology reports were reviewed and potential NIFTP were retrieved. The archived slides for these cases were independently reviewed by 2 pathologists. BRAFV600E (clone: VE1) immunostain was performed on representative tumor blocks. Clinical information including follow-up data was obtained from the electronic medical records. RESULTS: Among the 1918 cases with the diagnosis of papillary thyroid carcinoma (PTC), 589 (30.7%) of FVPTC and 136 cases of potential NIFTP were identified. After the review of the archived pathology slides, 29 lesions were morphologically reclassified as NIFTP. Four (13.7%) of these were positive for BRAFV600E; no association was found between the presence of abortive papillae and BRAFV600Eexpression (p=0.3). Exclusion of the 4 cases with BRAFV600Eexpression resulted in 25 lesions of final NIFTP, representing 4.2% of the FVPTC and 1.3% of the PTC. The mean age of the NIFTP patients was 50 years, 87.5% were females. The mean size of the lesions was 1.4 cm (0.1-4.0 cm). Intranuclear pseudoinclusions were not identified, and abortive papillae were identified in 60% of NIFTP. The average follow-up was 70 (28-166) months. There were no adverse events (recurrence or metastasis) in the NIFTP group. CONCLUSION: When strictly defined, NIFTP comprises 1.3% of cases perviously classified as PTC. In morphological NIFTP, no correlation is found between the presence of abortive papillae and the BRAFV600E expression. Intranuclear pseudo-inclusions are not observed in NIFTP. Modification of current morphological criteria to include BRAFV600E immunohistochemistry test may stratify NIFTP with benign outcome.

Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features is Rare: A Population Based Study of Incidence.

The renaming of encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC) to noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) was proposed by a group of experts in 2016 to prevent overtreatment of indolent, low-risk thyroid cancers. The aim of this study was to estimate the incidence and outcome for patients meeting the NIFTP criteria in a well-defined geographic region. Our cohort consisted of 134 patients with papillary thyroid carcinoma from the Region of Southern Denmark (RSD), 2007 to 2011. Patients were retrieved from the Danish Thyroid Cancer (DATHYRCA) Database. All potential NIFTP cases were reviewed by a thyroid pathologist. We identified no cases meeting all diagnostic criteria, but one probable NIFTP case from 2007 to 2011. The patient was treated according to the national guidelines and is alive and recurrence-free after 106 months of follow-up. Molecular testing showed KRAS mutation. In a population based set up the incidence rate of NIFTP is very low.

Noninvasive Follicular Thyroid Neoplasm With Papillary-Like Nuclear Features in Children: An Institutional Experience and Literature Review.

BACKGROUND: Papillary thyroid carcinoma (PTC) in children has a distinctive set of clinicopathologic features and molecular signature compared to their adult counterparts. The recent recommendation to reclassify encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC) without invasion as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is based on evidence derived almost exclusively from studies in adults. Clinicopathologic studies restricted to pediatric NIFTP are limited. METHODS: We retrospectively analyzed all pediatric PTC and NIFTP diagnosed and treated in our institution from 1999 to 2016 (n = 31). RESULTS: Using recently published consensus diagnostic criteria, we identified 3 NIFTP and 2 infiltrative follicular variants of papillary thyroid carcinoma (FVPTC) among 31 cases. Two of the NIFTP cases were initially diagnosed as EFVPTC. All 3 patients with NIFTP had unifocal tumors of lower American Joint Committee on Cancer (AJCC) classification (T2 or lower) and were free of lymph node or distant metastasis. Total (n = 1) or completion (n = 2) thyroidectomy was performed in all cases, and only 1 NIFTP patient received subsequent radioablative therapy. No residual or recurrent disease has been observed during follow-up (15-138 months) in patients with NIFTP. CONCLUSIONS: Our experience with NIFTP in children is similar to outcomes reported in adult studies, suggesting that pediatric NIFTP behave indolently as evidenced by the absence of local recurrence in our cohort.

Correlation between TERT C228T and clinic-pathological features in pediatric papillary thyroid carcinoma.

The aims of the present study were to reveal the prevalence of the TERT C228T mutation in pediatric papillary thyroid carcinoma (PPTC) and to further investigate the role of the TERT C228T mutation in PPTC. We also tested another TERT mutation, TERT C250T, although this was not detected in PPTC patients. In this study, 48 patients with PPTC (41 with classic PPTC) were enrolled. DNA was extracted from PPTC tissues and TERT C228T mutation analysis was performed. Chi-squared analysis, Fisher's exact test, and a t-test were applied to test the significance of differences. The TERT C228T mutation presented in 13 (27.1%) of the 48 PPTC patients and 10 (24.4%) of the 41 classical PPTC patients. There were significant differences between PPTC patients with the TERT C228T mutation and those without in terms of modified radical neck dissection, multifocality, capsular invasion, extrathyroidal invasion, and American Joint Committee on Cancer (AJCC) tumor stage (P<0.05). In classical PPTC, there were additional significant differences in other clinic-pathological features, such as AJCC nodal stage (P=0.009) and American Thyroid Association (ATA) PPTC stage (P=0.021) between patients with and without the TERT C228T mutation. These findings indicate that the TERT C228T mutation is significantly correlated with certain aggressive clinic-pathological features of PPTC.

miR-222 expression is correlated with the ATA risk stratifications in papillary thyroid carcinomas.

BACKGROUND: miR-222 is one of the most consistently overexpressed miRNAs in papillary thyroid carcinoma (PTC). Previous studies demonstrated that miR-222 overexpression conferred high-risk features in PTC patients, suggesting its value in risk-stratification. However, studies in term of miR-222's utility on stratifying PTCs are lacking. METHODS: One hundred patients including 10 with multinodular goiter and 90 with PTC were enrolled. Formalin-fixed paraffin-embedded samples were exploited for miR-222 quantitative reverse transcriptase- polymerase chain reaction (RT-PCR) analysis. Correlations between miR-222 expression and different clinicopathological features, Tumor-node-metastasis (TNM) staging and ATA risk level were analyzed. RESULTS: miR-222 expression of the PTC group was significantly higher than that of the goiter group (P < .001). Furthermore, miR-222 expression was significantly higher in PTCs with advanced features like larger tumor, capsular invasion, vascular invasion and lymph nodes metastasis. The majority of patients (61%) were in stage I group (similar to ATA low-risk) by TNM staging system. As to the ATA system, the majority (73%) were in intermediate-risk group (similar to TNM stage II and III roughly). Contrary to previous report, here we found that miR-222 expression was correlated with the ATA risk level (P < .001), but not with the TNM staging (P = .122). CONCLUSION: In the present study, we demonstrated that miR-222 overexpression was correlated with advanced features like capsular invasion, vascular invasion, larger tumor size and lymph node metastasis in PTCs. Most importantly, miR-222 expression was correlated with ATA risk levels, suggesting its potential value in PTC risk-stratification.