Retrospective Analysis of Cancer-Specific Gene Expression Panel for Thyroid Fine Needle Aspiration Specimens.

Abstract Background: While molecular testing is a promising strategy for preoperative assessment of cytologically indeterminate thyroid nodules, thyroid fine needle aspiration biopsy (FNA) presents unique challenges for molecular assays, including contaminating peripheral blood mononuclear cells (PBMC) and variable numbers of evaluable epithelial thyroid cells. Moreover, the newly recognized entity, noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), has added an additional challenge to the currently available molecular diagnostic platforms. New diagnostic tools are still needed to correctly distinguish benign and malignant thyroid nodules preoperatively.Methods: Twenty-two transcript splice variants from 12 genes we previously identified as discriminating benign from malignant thyroid nodules were characterized in 80 frozen thyroid tumors from 8 histological subtypes. Isoforms detectable in PBMC were excluded, and the 5 most discriminating isoforms were further validated by real-time quantitative PCR (qPCR) on intraoperative FNA samples from 59 malignant tumors, 55 benign nodules, and 23 NIFTP samples. The qPCR threshold cycle values for each transcript were normalized to the thyrocyte-specific thyroid peroxidase isoform 1 (TPO1) and z-transformed. Receiver operating characteristic (ROC) analyses of the composite transcript scores were used to evaluate classification of thyroid FNAs by the 5-gene isoform expression panel.Results: A molecular signature was developed by combining expression levels of specific isoforms of CDH3, FNDC4, HMGA2, KLK7, and PLAG1. FNAs containing at least 12-36 thyrocytes were sufficient for this assay. The 5-gene composite score achieved an area under the ROC curve (AUC) of 0.86 for distinguishing malignant from benign nodules, with a specificity of 91%, sensitivity of 75%, negative predictive value of 91% and positive predictive value of 74%.Conclusion: Our newly developed 5-gene isoform expression panel distinguishes benign from malignant thyroid tumors and, may help distinguish benign from malignant thyroid nodules in the context of the new NIFTP subtype.

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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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Managing Thyroid Nodules in Qatar During the COVID19 Pandemic

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.1717 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A841-A842

Author(s):

Zaina Alamer ◽

Gowri Karuppasamy ◽

Arwa Alsaud ◽

Tania Jaber ◽

Hanan Farghaly ◽

...

Keyword(s):

High Risk ◽

Early Detection ◽

Fine Needle Aspiration ◽

Medical Staff ◽

Thyroid Nodules ◽

Needle Aspiration ◽

Morbidity And Mortality ◽

American Thyroid Association ◽

Fine Needle ◽

Thyroid Fine Needle Aspiration

Abstract Background: The Coronavirus disease 2019 (COVID-19) pandemic impacted health care systems in all countries, including Qatar. Hamad Medical Corporation (HMC); In compliance with recommendations, suspended all non-urgent procedures, including thyroid fine needle aspiration biopsies (FNAB). Thyroid nodules are second most common cause of referral to HMC endocrine clinic. FNABs are gold standard to differentiate benign from malignant nodules.1- 2 Methods: Our approach includes a teleconsultation to obtain patient’s history and risk factors. Reviewing neck ultrasound (US), obtaining a calcitonin level if indicated, considering comorbidities associated with a high risk of COVID-19 morbidity and mortality.3 Results: We developed a pathway triaging thyroid (FNAB) to:1-Urgent: patients at higher risk of aggressive thyroid malignancy. Benefits of early detection and treatment outweigh the risk of COVID-19 exposure.4 FNAB should not be delayed.2-Semi-urgent: patients at low risk for COVID-19 and high suspicion thyroid nodules, but no evidence that early detection improves survival2, FNAB may be delayed up to 12 months.3-Non-urgent: patients with asymptomatic nodules that have low or intermediate suspicion US pattern.2 Also, includes nodules with ATA high suspicion US pattern in pregnant women and patients at high risk for COVID-19. The risks outweigh the benefits. FNAB should be delayed until outbreak is controlled.4 When urgent FNAB is indicated, safety of patients and medical staff needs to be addressed.5 We recommend testing patient for COVID-19 before FNAB, utilizing US guidance with rapid on-site adequacy evaluation in all cases. Cervical lymph node FNAB with TG washout should be done if indicated. The patient should wear a mask. All medical staff involved should wear personal protective equipment (PPE). The operator should wear N95 mask and face shield. The patient should be informed about cytopathology results via telemedicine. Conclusion: Triaging thyroid (FNAB) during the COVID-19 pandemic should be based on nodule characteristics and risk of COVID-19 morbidity and mortality. Our group recommends deferring FNAB for asymptomatic patients.4FNAB should not be delayed in selected patients who benefit from early detection and intervention. Table1: Triage of Thyroid fine needle aspiration biopsies (FNAB). ATA: American thyroid association. US: ultrasound.

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Combined quantitation of HMGA2 mRNA, microRNAs, and mitochondrial-DNA content enables the identification and typing of thyroid tumors in fine-needle aspiration smears

BMC Cancer ◽

10.1186/s12885-019-6154-7 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 3

Author(s):

Sergei E. Titov ◽

Mikhail K. Ivanov ◽

Pavel S. Demenkov ◽

Gevork A. Katanyan ◽

Eugenia S. Kozorezova ◽

...

Keyword(s):

Differential Diagnosis ◽

Molecular Markers ◽

Fine Needle Aspiration ◽

Real Time Pcr ◽

Thyroid Nodules ◽

Nuclear Dna ◽

Malignant Tumors ◽

Needle Aspiration ◽

Thyroid Tumors ◽

Fine Needle

Abstract Background Analysis 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. Nonetheless, in clinical practice, applications of existing diagnostic solutions based on the detection of somatic mutations or analysis of gene expression are limited by their high cost and difficulties with clinical interpretation. The aim of our work was to develop an algorithm for the differential diagnosis of thyroid nodules on the basis of a small set of molecular markers analyzed by real-time PCR. Methods A total of 494 preoperative FNA samples of thyroid goiters and tumors from 232 patients with known histological reports were analyzed: goiter, 105 samples (50 patients); follicular adenoma, 101 (48); follicular carcinoma, 43 (28); Hürthle cell carcinoma, 25 (11); papillary carcinoma, 121 (56); follicular variant of papillary carcinoma, 80 (32); and medullary carcinoma, 19 (12). Total nucleic acids extracted from dried FNA smears were analyzed for five somatic point mutations and two translocations typical of thyroid tumors as well as for relative concentrations of HMGA2 mRNA and 13 microRNAs and the ratio of mitochondrial to nuclear DNA by real-time PCR. A decision tree–based algorithm was built to discriminate benign and malignant tumors and to type the thyroid cancer. Leave-p-out cross-validation with five partitions was performed to estimate prediction quality. A comparison of two independent samples by quantitative traits was carried out via the Mann–Whitney U test. Results A minimum set of markers was selected (levels of HMGA2 mRNA and miR-375, − 221, and -146b in combination with the mitochondrial-to-nuclear DNA ratio) and yielded highly accurate discrimination (sensitivity = 0.97; positive predictive value = 0.98) between goiters with benign tumors and malignant tumors and accurate typing of papillary, medullary, and Hürthle cell carcinomas. The results support an alternative classification of follicular tumors, which differs from the histological one. Conclusions The study shows the feasibility of the preoperative differential diagnosis of thyroid nodules using a panel of several molecular markers by a simple PCR-based method. Combining markers of different types increases the accuracy of classification.

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Preoperative evaluation and predictive value of fine-needle aspiration and frozen section of thyroid nodules

Journal of the American College of Surgeons ◽

10.1016/s1072-7515(98)00221-x ◽

1998 ◽

Vol 187 (5) ◽

pp. 494-502 ◽

Cited By ~ 69

Author(s):

Loretta A Boyd ◽

Richard C Earnhardt ◽

John T Dunn ◽

Henry F Frierson ◽

John B Hanks

Keyword(s):

Fine Needle Aspiration ◽

Predictive Value ◽

Thyroid Nodules ◽

Frozen Section ◽

Preoperative Evaluation ◽

Needle Aspiration ◽

Fine Needle

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THE RISK OF THYROID CANCER IN PATIENTS WITH THYROID NODULE 3 CM OR LARGER

Endocrine Practice ◽

10.4158/ep-2020-0136 ◽

2020 ◽

Vol 26 (11) ◽

pp. 1286-1290

Author(s):

Edy Kornelius ◽

Shih-Chang Lo ◽

Chien-Ning Huang ◽

Yi-Sun Yang

Keyword(s):

Thyroid Cancer ◽

Positive Predictive Value ◽

Thyroid Carcinoma ◽

Thyroid Nodule ◽

Fine Needle Aspiration ◽

Predictive Value ◽

Thyroid Nodules ◽

Fine Needle Aspiration Biopsy ◽

Needle Aspiration ◽

Fine Needle

Objective: There are conflicting data on the risk of thyroid cancer in thyroid nodules 3 cm or larger, and few such studies on this issue have been conducted in Asia. This study aimed to examine the risk of thyroid cancer in patients with thyroid nodules 3 cm or larger. Methods: This was a 7-year retrospective study conducted in a tertiary referral hospital in Taiwan. All patients with a thyroid nodule measuring ≥3 cm who underwent thyroid operation with or without fine-needle aspiration biopsy (FNAB) were included. The prevalence rate of thyroid cancer, as well as the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and false-negative rate of FNAB for thyroid nodule ≥3 cm were also examined. Results: A total of 132 patients were included in this study. Thyroid cancer was detected in 19 of 132 (14.4%) thyroid nodules measuring ≥3 cm. The performance of FNAB for detecting cancer in nodules 3 cm or larger without considering other ultrasonography parameters was relatively poor with a sensitivity of 50%, but the specificity (100%), PPV (100 %), and NPV (93.4 %) were excellent. Conclusion: The risk of thyroid cancer for thyroid nodules ≥3 cm in this study was low. The PPV and NPV of FNAB were high for the detection of cancer in large nodules. The decision to perform thyroidectomy should not be solely based on nodule size and should include other factors, such as ultrasound characteristics and surgical risk. Abbreviations: ATA = American Thyroid Association; FNAB = fine-needle aspiration biopsy; mPTC = micropapillary thyroid carcinoma; NPV = negative predictive value; PPV = positive predictive value; PTC = papillary thyroid carcinoma

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Comparison of Elastographic Strain Index and Thyroid Fine-Needle Aspiration Cytology in 631 Thyroid Nodules

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2013-2672 ◽

2013 ◽

Vol 98 (12) ◽

pp. 4790-4797 ◽

Cited By ~ 24

Author(s):

Flavia Magri ◽

Spyridon Chytiris ◽

Valentina Capelli ◽

Margherita Gaiti ◽

Francesca Zerbini ◽

...

Keyword(s):

Negative Predictive Value ◽

Fine Needle Aspiration ◽

Predictive Value ◽

Fine Needle Aspiration Cytology ◽

Thyroid Nodules ◽

Needle Aspiration ◽

Aspiration Cytology ◽

Strain Index ◽

Fine Needle ◽

Needle Aspiration Cytology

Context: Ultrasound (US) elastography (USE) was recently been reported as a sensitive, noninvasive tool for identifying thyroid cancer. However, the accuracy of this technique is hampered by the intra- and interoperator variability, some US features of the nodule, and the coexistence of autoimmune thyroid disease (ATD). Objectives: The purpose of this article was to assess the accuracy of USE findings in the differential diagnosis of thyroid nodules compared with other US features to evaluate its feasibility in the presence of ATDs and identify the strain index (SI) cutoff with the highest diagnostic performance. Design: We evaluated 528 consecutive patients for a total of 661 thyroid nodules. All nodules underwent fine-needle aspiration cytology (FNAC) and USE evaluation. The SI was calculated as a ratio of the nodule strain divided by the strain of the softest part of the surrounding normal tissue. Results: The median SI value was significantly higher in THY4 and THY5 than in THY2 nodules in ATD-positive, ATD-negative, and ATD-unknown patients. The cutoff of SI for malignancy was estimated to be 2.905 by receiver operating characteristic curve analysis in a screening set (379 FNAC results), and then tested in a replication set (252 FNAC results). In all cases, a SI value of ≥2.905 conferred to the nodule a significantly greater probability of being malignant. This SI cutoff had the greatest area under the curve, sensitivity, and negative predictive value, compared with the conventional US features of malignancy. Conclusion: The elastographic SI has a high sensitivity, specificity, and negative predictive value for the diagnosis of thyroid malignancy both in the presence and in the absence of ATD. If our data on USE are also confirmed in THY3 nodules, FNAC could be avoided in a number of thyroid nodules with certain features.

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Impact of Molecular Testing in the Diagnosis of Thyroid Fine Needle Aspiration Cytology: Data from Mainland China

Disease Markers ◽

10.1155/2014/912182 ◽

2014 ◽

Vol 2014 ◽

pp. 1-6 ◽

Cited By ~ 4

Author(s):

Hui-qin Guo ◽

Huan Zhao ◽

Zhi-hui Zhang ◽

Yan-li Zhu ◽

Ting Xiao ◽

...

Keyword(s):

Fine Needle Aspiration ◽

Fine Needle Aspiration Cytology ◽

Thyroid Nodules ◽

Needle Aspiration ◽

Molecular Testing ◽

Benign Lesions ◽

Aspiration Cytology ◽

Fine Needle ◽

Thyroid Fine Needle Aspiration ◽

Needle Aspiration Cytology

Background. The molecular work-up of thyroid nodules from fine needle aspiration samples has given clinicians a new level of diagnostic information. The aim of the present study was to evaluate the utility of molecular analysis in thyroid fine needle aspiration samples from a Chinese population.Methods. Specimens were collected from thyroid nodules by fine needle aspiration. Cytology diagnosis and genes analysis were performed and correlated with histology outcome.Results. A total of 83 patients with thyroid nodules were enrolled, including 20 benign lesions and 63 papillary carcinomas. BRAF and RAS mutations and RET/PTC gene rearrangements were found in 65.1%, 0%, and 1.6% of papillary carcinomas, respectively. No gene alterations were found in benign lesions. The combination of BRAF testing and cytology improved the accuracy of cytology from 69.9% to 89.2%(P<0.05). Moreover, BRAF testing confirmed 82.4% of papillary carcinomas with suspicious cytology and identified 33.3% of papillary carcinomas with atypia cytology.Conclusions. Of the three candidate markers, BRAF testing showed diagnostic utility in fine needle aspiration. Combining BRAF testing with cytology improves the accuracy of fine needle biopsy. Those who have positive BRAF and malignant or suspicious malignant cytology can undergo thyroidectomy without a frozen section.

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