The thyroid risk score (TRS) for nodules with indeterminate cytology

Cytology is the gold standard method for the differential diagnosis of thyroid nodules, though 25–30% of them are classified as indeterminate. We aimed to set up a ‘thyroid risk score’ (TRS) to increase the diagnostic accuracy in these cases. We prospectively tested 135 indeterminate thyroid nodules. The pre-surgical TRS derived from the sum of the scores assigned at cytology, EU-TIRADS classification, nodule measurement, and molecular characterization, which was done by our PTC-MA assay, a customized array able to cost-effectively evaluate 24 different genetic alterations including point mutations and gene fusions. The risk of malignancy (ROM) increased paralleling the score: in the category >4 and ≤ 6 (low suspicion), >6 ≤ 8 (intermediate suspicion), and >8 (high suspicion); ROM was 10, 47 and 100%, respectively. ROC curves selected the score >6.5 as the best threshold to differentiate between malignant and benign nodules (P < 0.001). The TRS > 6.5 had a better performance than the single parameters evaluated separately, with an accuracy of 77 and 82% upon inclusion of noninvasive follicular thyroid neoplasm with papillary-like nuclear features among malignant or benign cases, respectively. In conclusion, for the first time, we generated a score combining a cost-effective molecular assay with already validated tools, harboring different specificities and sensitivities, for the differential diagnosis of indeterminate nodules. The combination of different parameters reduced the number of false negatives inherent to each classification system. The TRS > 6.5 was highly suggestive for malignancy and retained a high accuracy in the identification of patients to be submitted to surgery.

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Punção Aspirativa de Nódulos da Tiroide: Vale a Pena Repetir?

Acta Médica Portuguesa ◽

10.20344/amp.8215 ◽

2017 ◽

Vol 30 (6) ◽

pp. 472

Author(s):

Vera Fernandes ◽

Tânia Pereira ◽

Catarina Eloy

Keyword(s):

Fine Needle Aspiration ◽

Thyroid Nodules ◽

Significant Proportion ◽

Cost Effective ◽

Needle Aspiration ◽

Fine Needle ◽

High Concordance ◽

Benign Nodules ◽

Cytology Result ◽

Undetermined Significance

Introduction: The fine-needle aspiration has a significant role in assessing the malignancy risk of thyroid nodules. There is uncertainty regarding the value of repeat fine-needle aspiration in benign nodules. This study aims to evaluate the concordance of results in consecutive fine-needle aspiration and to study the relevance of repetition in benign results.Material and Methods: Retrospective study of the 4800 thyroid nodules fine-needle aspiration held in Instituto de Patologia e Imunologia Molecular da Universidade do Porto between January 1, 2014 and May 2, 2016. Of the initial sample, we selected the repeated fine-needle aspiration on the same nodule.Results: The first fine-needle aspiration result of the 309 nodules underwent revaluation was non-diagnostic in 103 (33.3%), benign in 120 (38.8%) and atypia/follicular lesion of undetermined significance in 86 (27.8%). The agreement between the first and second fine-needle aspiration was significantly higher in cases with an initial benign result (benign: 85.8%, non-diagnostic: 27.2% and atypia/ follicular lesion of undetermined significance: 17.4%, p < 0.005). The fine-needle aspiration repeating motifs in initially benign nodules (n = 78) were repetition suggestion in 58, nodule growth in 17 and suspicious ultrasonographic features in 3.Discussion: The fine-needle aspiration repetition in nodules with initial non-diagnostic and atypia/follicular lesion of undetermined significance result changed the initial diagnosis in a significant proportion of patients, modifying their therapeutic approach. The high concordance of results in initially benign nodules makes fine-needle aspiration repetition not cost-effective in most cases.Conclusion: The fine-needle aspiration should be repeated when the initial cytology result is non-diagnostic or atypia/follicular lesion of undetermined significance.

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Somatic genetic alterations in a large cohort of pediatric thyroid nodules

Endocrine Connections ◽

10.1530/ec-19-0069 ◽

2019 ◽

Vol 8 (6) ◽

pp. 796-805 ◽

Cited By ~ 9

Author(s):

Barbora Pekova ◽

Sarka Dvorakova ◽

Vlasta Sykorova ◽

Gabriela Vacinova ◽

Eliska Vaclavikova ◽

...

Keyword(s):

High Frequency ◽

Detection Rate ◽

Thyroid Nodules ◽

Pediatric Patients ◽

Distant Metastases ◽

Genetic Alterations ◽

Papillary Thyroid ◽

Benign Lesions ◽

Benign Nodules ◽

Generation Sequencing

There is a rise in the incidence of thyroid nodules in pediatric patients. Most of them are benign tissues, but part of them can cause papillary thyroid cancer (PTC). The aim of this study was to detect the mutations in commonly investigated genes as well as in novel PTC-causing genes in thyroid nodules and to correlate the found mutations with clinical and pathological data. The cohort of 113 pediatric samples consisted of 30 benign lesions and 83 PTCs. DNA from samples was used for next-generation sequencing to identify mutations in the following genes: HRAS, KRAS, NRAS, BRAF, IDH1, CHEK2, PPM1D, EIF1AX, EZH1 and for capillary sequencing in case of the TERT promoter. RNA was used for real-time PCR to detect RET/PTC1 and RET/PTC3 rearrangements. Total detection rate of mutations was 5/30 in benign tissues and 35/83 in PTCs. Mutations in RAS genes (HRAS G13R, KRAS G12D, KRAS Q61R, NRAS Q61R) were detected in benign lesions and HRAS Q61R and NRAS Q61K mutations in PTCs. The RET/PTC rearrangement was identified in 18/83 of PTCs and was significantly associated with higher frequency of local and distant metastases. The BRAF V600E mutation was identified in 15/83 of PTCs and significantly correlated with higher age of patients and classical variant of PTC. Germline variants in the genes IDH1, CHEK2 and PPM1D were found. In conclusion, RET/PTC rearrangements and BRAF mutations were associated with different clinical and histopathological features of pediatric PTC. RAS mutations were detected with high frequency in patients with benign nodules; thus, our results suggest that these patients should be followed up intensively.

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Comparative Analysis of Diagnostic Value for Shear Wave Elastography and Real-Time Elastographic Imaging for Thyroid Nodules

Journal of Medical Imaging and Health Informatics ◽

10.1166/jmihi.2019.2594 ◽

2019 ◽

Vol 9 (2) ◽

pp. 334-338

Author(s):

Qing Yang ◽

Wenhong Zhou ◽

Jiyu Li ◽

Guojun Wu ◽

Feng Ding ◽

...

Keyword(s):

Differential Diagnosis ◽

Positive Predictive Value ◽

Negative Predictive Value ◽

Shear Wave ◽

Predictive Value ◽

Thyroid Nodules ◽

Shear Wave Elastography ◽

Roc Curves ◽

Diagnostic Value ◽

Sensitivity Specificity

Objective: To compare the diagnostic value of shear wave elastography (SWE) and real-time elastography (RTE) in the diagnosis of benign and malignant thyroid nodules. Methods: A total of 34 patients who ever received thyroidectomy in our hospital from January 2016 to January 2018 were identified. Meanwhile, all the patients received SWE and RTE before surgery, and all the diagnoses were confirmed by pathological examinations. With respect to SWE technique, the Subject Operating Characteristics (ROC) curves were drawn, in order to obtain the optimal threshold and then make differential diagnoses of benign and malignant thyroid nodules. In terms of RTE, the Rago 5 scoring method was utilized to make differential diagnoses of benign and malignant thyroid nodules. Besides, the pathological examinations after surgery could be considered as the golden standard. At last, the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of SWE and RTE were calculated, respectively. Results: A total of 51 thyroid nodules were identified, and 41 nodules were benign, 10 nodules were malignant. On the basis of ROC curves, with respect to SWE, the best threshold for differential diagnosis of benign and malignant thyroid nodules is 38.3 kPa. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of SWE were 72.7% (8/11), 85% (34/40), 82.4% (42/51), 68.4% (13/19), and 87.5% (35/40), respectively. And the diagnostic indicators of RTE were 81.8% (9/11), 87.5% (35/40), 84.3% (43/51), 73.7% (14/19), and 90.0% (36/40). The sensitivity of quasi-static elastography in differential diagnosis of benign and malignant thyroid nodules with diameter ≤1 cm was 87.5% (7/8), and the sensitivity of SWE was 50.0% (5/10). In addition, the accuracy of SWE in differential diagnosis of benign and malignant thyroid nodules with diameter ≥3 cm was 100% (6/6), and the accuracy of RTE for this kind of thyroid nodules was 66.7% (4/6). Conclusion: Both SWE and RTE technology have good application value in differential diagnosis of benign and malignant thyroid nodules. But, SWE is preferable when making diagnosis of benign and malignant thyroid nodules with diameter ≥3 cm, and RTE was superior in detecting benign and malignant thyroid nodules with diameter ≤1 cm.

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Benign Aspirates on Follow-Up FNA May Be Enough in Patients with Initial Atypia of Undetermined Significance/Follicular Lesion of Undetermined Significance

International Journal of Endocrinology ◽

10.1155/2014/354612 ◽

2014 ◽

Vol 2014 ◽

pp. 1-8 ◽

Cited By ~ 4

Author(s):

Ga Ram Kim ◽

Jung Hyun Yoon ◽

Eun-Kyung Kim ◽

Hee Jung Moon ◽

Jin Young Kwak

Keyword(s):

Thyroid Nodules ◽

Surgical Excision ◽

Needle Aspiration ◽

Risk Of Malignancy ◽

Benign Nodules ◽

Benign Thyroid Nodules ◽

Benign Thyroid ◽

Undetermined Significance

Background.Management of thyroid nodules with benign aspirates following atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) is not well established. We reviewed the risk of malignancy and the role of ultrasound (US) features among thyroid nodules with benign results following initial AUS/FLUS diagnoses.Methods.From December 2009 to February 2011, a total of 114 nodules in 114 patients diagnosed as benign on follow-up fine-needle aspiration (FNA) after AUS/FLUS results were included in our study. Eight among 114 nodules were confirmed pathologically and 106 were clinically observed by a follow-up FNA or US. Suspicious US features were defined as markedly hypoechogenicity, irregular or microlobulated margin, presence of microcalcifications, and taller than wide shape.Results.There were 110 (96.5%) benign nodules and 4 (3.5%) malignant nodules. Two (4.8%) among 42 nodules without suspicious US features and 2 (2.8%) out of 72 nodules with suspicious US features were confirmed as malignancy, but there were no significant associations between the malignancy rate and US features (P=0.625).Conclusion.Clinical follow-up instead of surgical excision or continuous repeat FNA may be enough for benign thyroid nodules after AUS/FLUS. The role of US features might be insignificant in the management of these nodules.

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Molecular markers in the diagnosis of thyroid nodules

Arquivos Brasileiros de Endocrinologia & Metabologia ◽

10.1590/s0004-27302013000200001 ◽

2013 ◽

Vol 57 (2) ◽

pp. 89-97 ◽

Cited By ~ 19

Author(s):

Laura S. Ward ◽

Richard T. Kloos

Keyword(s):

Predictive Value ◽

High Sensitivity ◽

High Specificity ◽

Cost Effective ◽

Needle Aspiration ◽

Molecular Diagnostic ◽

Risk Of Malignancy ◽

Benign Nodules ◽

Low Sensitivity ◽

Rule Out

An indeterminate thyroid nodule cytology result occurs about every sixth fine-needle aspiration. These indeterminate nodules harbor a 24% risk of malignancy (ROM); too high to ignore, but driving surgery where most nodules are benign. Molecular diagnostics have emerged to ideally avoid surgery when appropriate, and to trigger the correct therapeutic surgery when indicated, as opposed to an incomplete diagnostic surgery. No current molecular test offers both high sensitivity and high specificity. A molecular diagnostic test with high sensitivity (e.g. Afirma Gene Expression Classifier sensitivity 90%) offers a high Negative Predictive Value when the ROM is relatively low, such as < 30%. Only such tests can "rule-out" cancer. In this setting, a molecularly benign result suggests the same ROM as that of operated cytologically benign nodules (~6%). Thus, clinical observation can replace diagnostic surgery; increasing quality of life and decreasing medical costs. However, its low specificity cannot "rule-in" cancer as a suspicious result has a Positive Predictive Value (PPV) of ~40%, perhaps too low to routinely reflex to definitive cancer surgery. Conversely, high specificity tests (BRAF, RAS, PPAR/PAX-8, RET/PTC, PTEN) offer high PPV results, and only these tests can "rule-in" cancer. Here a positive molecular result warrants definitive therapeutic surgery. However, their low sensitivity cannot "rule-out" cancer and a negative molecular result cannot dissuade diagnostic surgery; limiting their cost-effectiveness. Whether or not there is a useful and cost-effective role to sequentially combine these approaches, or to modify existing approaches, is under investigation.

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Comprehensive Analysis of the Prognostic Values of the TRIM Family in Hepatocellular Carcinoma

Frontiers in Oncology ◽

10.3389/fonc.2021.767644 ◽

2021 ◽

Vol 11 ◽

Author(s):

Weiyu Dai ◽

Jing Wang ◽

Zhi Wang ◽

Yizhi Xiao ◽

Jiaying Li ◽

...

Keyword(s):

Gene Expression ◽

Hepatocellular Carcinoma ◽

Survival Analysis ◽

Risk Score ◽

Roc Curves ◽

Genetic Alterations ◽

Pathway Enrichment Analysis ◽

Family Risk ◽

Cox Regression Analysis ◽

Family Gene

BackgroundAccumulating studies have demonstrated the abnormal expressions and prognostic values of certain members of the tripartite motif (TRIM) family in diverse cancers. However, comprehensive prognostic values of the TRIM family in hepatocellular carcinoma (HCC) are yet to be clearly defined.MethodsThe prognostic values of the TRIM family were evaluated by survival analysis and univariate Cox regression analysis based on gene expression data and clinical data of HCC from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The expression profiles, protein–protein interaction among the TRIM family, prediction of transcription factors (TFs) or miRNAs, genetic alterations, correlations with the hallmarks of cancer and immune infiltrates, and pathway enrichment analysis were explored by multiple public databases. Further, a TRIM family gene-based signature for predicting overall survival (OS) in HCC was built by using the least absolute shrinkage and selection operator (LASSO) regression. TCGA–Liver Hepatocellular Carcinoma (LIHC) cohort was used as the training set, and GSE76427 was used for external validation. Time-dependent receiver operating characteristic (ROC) and survival analysis were used to estimate the signature. Finally, a nomogram combining the TRIM family risk score and clinical parameters was established.ResultsHigh expressions of TRIM family members including TRIM3, TRIM5, MID1, TRIM21, TRIM27, TRIM32, TRIM44, TRIM47, and TRIM72 were significantly associated with HCC patients’ poor OS. A novel TRIM family gene-based signature (including TRIM5, MID1, TRIM21, TRIM32, TRIM44, and TRIM47) was built for OS prediction in HCC. ROC curves suggested the signature’s good performance in OS prediction. HCC patients in the high-risk group had poorer OS than the low-risk patients based on the signature. A nomogram integrating the TRIM family risk score, age, and TNM stage was established. The ROC curves suggested that the signature presented better discrimination than the similar model without the TRIM family risk score.ConclusionOur study identified the potential application values of the TRIM family for outcome prediction in HCC.

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FNAC IN THE MANAGEMENT OF SOLITARY THYROID NODULE

The Professional Medical Journal ◽

10.29309/tpmj/2006.13.04.4934 ◽

2006 ◽

Vol 13 (04) ◽

pp. 596-603

Author(s):

SOHAIL RAZA ◽

HAMAD RAZA ◽

ZAHID SAEED ◽

Mubasher Ahmed

Keyword(s):

Thyroid Nodule ◽

Thyroid Nodules ◽

Fine Needle Aspiration Biopsy ◽

Cost Effective ◽

Needle Aspiration ◽

Military Hospital ◽

Solitary Thyroid Nodule ◽

Benign Nodules ◽

Histopathological Results

Objective: To determine the significant role of FNAC upon other diagnosticmodalities in pre-operative investigations of patients presenting with solitary thyroid nodules and to compare the postoperative histopathological results with the results of FNAC. Design: A Comparative study. Place and Duration ofStudy: Department of Surgery Combined Military Hospital Quetta and Combined Military Hospital Rawalpindi fromDecember 1999 to December 2001. Patients and Methods: In this study 46 patients with solitary thyroid nodule werestudied. Only 2 patients were toxic while remaining 44 were with euthyroid. In this study only one case was suspectedto be malignant clinically out of 5 malignant cases. All 46 patients under went thyroid scanning, ultrasound examinationand fine needle aspiration biopsy and the diagnostic accuracy was assessed. Results: 36 patients (78.26%) wereoperated while 10(21.73%) were managed conservatively. There were 5(10.86%) malignant nodules while 41(89.13%)were benign. All the 5 cases with malignancy were with ‘cold’ nodules on scan as most of others, while ‘solid’ onultrasound examination and so were most of other benign nodules. All cases diagnosed malignant pre-operatively onFNAC, proved to be malignant on histopathology after surgery and the others diagnosed as benign on FNAC provedto be benign. Conclusion: This study shows that conventional investigations for evaluation of solitary thyroid nodulesare inaccurate in identifying the malignant from the benign nodules and their routine use in such patients should beabandoned, while the use of FNAC should be encouraged more in our hospitals as this technique is with high degreeof sensitivity and specificity, cost effective and safe.

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Preoperative detection of malignancy in fine-needle aspiration cytology (FNAC) smears with indeterminate cytology (Bethesda III, IV) by a combined molecular classifier

Journal of Clinical Pathology ◽

10.1136/jclinpath-2020-206445 ◽

2020 ◽

Vol 73 (11) ◽

pp. 722-727 ◽

Cited By ~ 1

Author(s):

Sergei Titov ◽

Pavel S Demenkov ◽

Sergei A Lukyanov ◽

Sergei V Sergiyko ◽

Gevork A Katanyan ◽

...

Keyword(s):

Differential Diagnosis ◽

Molecular Markers ◽

Fine Needle Aspiration ◽

Predictive Value ◽

Thyroid Nodules ◽

Needle Aspiration ◽

Cytological Analysis ◽

Fine Needle ◽

Risk Of Malignancy ◽

Indeterminate Cytology

AimsAnalysis of molecular markers in addition to cytological analysis of fine-needle aspiration (FNA) samples is a promising way to improve the preoperative diagnosis of thyroid nodules. Previously, we have developed an algorithm for the differential diagnosis of thyroid nodules by means of a small set of molecular markers. Here, we aimed to validate this approach using FNA cytology samples of Bethesda categories III and IV, in which preoperative detection of malignancy by cytological analysis is impossible.MethodsA total of 122 FNA smears from patients with indeterminate cytology (Bethesda III: 13 patients, Bethesda IV: 109 patients) were analysed by real-time PCR regarding the preselected set of molecular markers (the BRAF V600E mutation, normalised concentrations of HMGA2 mRNA, 3 microRNAs, and the mitochondrial/nuclear DNA ratio). The decision tree–based classifier was used to discriminate between benign and malignant tumours.ResultsThe molecular testing detected malignancy in FNA smears of indeterminate cytology with 89.2% sensitivity, 84.6% positive predictive value, 92.9% specificity and 95.2% negative predictive value; these characteristics are comparable with those of more complicated commercial tests. Residual risk of malignancy for the thyroid nodules that were shown to be benign by this molecular method did not exceed the reported risk of malignancy for Bethesda II histological diagnosis. Analytical-accuracy assessment revealed required nucleic-acid input of ≥5 ng.ConclusionsThe study shows feasibility of preoperative differential diagnosis of thyroid nodules of indeterminate cytology using a small panel of molecular markers of different types by a simple PCR-based method using stained FNA smears.

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Contrast-Enhanced Ultrasound in the Differential Diagnosis and Risk Stratification of ACR TI-RADS Category 4 and 5 Thyroid Nodules With Non-Hypovascular

Frontiers in Oncology ◽

10.3389/fonc.2021.662273 ◽

2021 ◽

Vol 11 ◽

Author(s):

Yanfang Wang ◽

Tiantian Dong ◽

Fang Nie ◽

Guojuan Wang ◽

Ting Liu ◽

...

Keyword(s):

Risk Factors ◽

Differential Diagnosis ◽

Risk Stratification ◽

Risk Score ◽

Thyroid Nodules ◽

Validation Cohort ◽

Contrast Enhanced Ultrasound ◽

Derivation Cohort ◽

Contrast Enhanced ◽

Independent Risk Factors

ObjectiveThis study aims to investigate the value of contrast-enhanced ultrasound (CEUS) in the differential diagnosis and risk stratification of ACR TI-RADS category 4 and 5 thyroid nodules with non-hypovascular.MethodsFrom January 2016 to December 2019 in our hospital, 217 ACR TI-RADS category 4 and 5 nodules with non-hypovascular in 210 consecutive patients were included for a derivation cohort. With surgery and/or fine-needle aspiration (FNA) as a reference, conventional ultrasound (US) features and CEUS features were analyzed. Multivariate logistic regression analysis was used to screen the independent risk factors and establish a risk predictive model. Between January 2020 and March 2021, a second cohort of 100 consecutive patients with 101 nodules were included for an external validation cohort. The model was converted into a simplified risk score and was validated in the validation cohort. The area under the receiver operating characteristic curves (AUC) were used to assess the models’ diagnostic performance.ResultsMicro-calcification, irregular margin, earlier wash-out, centripetal enhancement, and absence of ring enhancement were independent risk factors and strongly discriminated malignancy in the derivation cohort (AUC = 0.921, 95% CI 0.876–0.953) and the validation cohort (0.900, 0.824–0.951). There was no significant difference (P = 0.3282) between the conventional US and CEUS in differentiating malignant non-hypovascular thyroid nodules, but a combination of them (the predictive model) had better performance than the single method (all P <0.05), with a sensitivity of 87.0%, specificity of 86.2%, and accuracy of 86.6% in the derivation cohort. The risk score based on the independent risk factors divided non-hypovascular thyroid nodules into low-suspicious (0–3 points; malignancy risk <50%) and high-suspicious (4–7 points; malignancy risk ≥ 50%), the latter with nodule ≥10mm was recommended for FNA. The risk score showed a good ability of risk stratification in the validation cohort. Comparing ACR TI-RADS in screening suitable non-hypovascular nodules for FNA, the risk score could avoid 30.8% benign nodules for FNA.ConclusionsCEUS is helpful in combination with conventional US in differentiating ACR TI-RADS category 4 and 5 nodules with non-hypovascular. The risk score in this study has the potential to improve the diagnosis and risk stratification of non-hypovascular thyroid nodules.

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Value of Thyroid Imaging Reporting and Data System in Initial Bethesda Category III Thyroid Nodules

Scientific Programming ◽

10.1155/2021/3482111 ◽

2021 ◽

Vol 2021 ◽

pp. 1-7

Author(s):

Caoxin Yan ◽

Zhiyan Luo ◽

Zimei Lin ◽

Shouxing Xu ◽

Yunkai Luo ◽

...

Keyword(s):

Thyroid Nodules ◽

Univariate Analysis ◽

Data System ◽

Thyroid Imaging ◽

Increased Risk ◽

Risk Of Malignancy ◽

Clinicopathologic Parameters ◽

Bethesda System ◽

Benign Nodules

Background. To evaluate the role of Thyroid Imaging Reporting and Data System (TI-RADS) in predicting malignancy for cytological Bethesda system III nodules. Method. The study included 188 thyroid nodules with first Bethesda system III cytology on surgery or repeat FNA. Patients' clinicopathologic parameters and ultrasonographic (US) nodule characteristics were evaluated according to benignity and malignancy. Using the TI-RADS classification system, thyroid nodules were categorized. Results. The size of malignant nodules was significantly lower than that of benign nodules ( P < 0.001). Thyroid nodules associated with concomitant thyroid carcinoma had a significantly increased risk of malignancy ( P < 0.001). Univariate analysis indicated that there were significant differences in the images of benign and malignant nodules in terms of solid composition, hypoechogenicity or marked hypoechogenicity, a taller-than-wide or irregular shape, ill-defined margins, and microcalcifications presence ( P < 0.05). TI-RADS categories 4c (OR = 8.3, 95% CI 3.8–18.1; P = 0.043) and 5 (OR = 9.4; 95% CI 1.2–74.2; P = 0.026) were predictive for malignancy. Conclusions. The TI-RADS US evaluation may assist the physician in deciding whether to proceed with follow-up, repeating FNA, or surgical intervention.

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