scholarly journals Highly Sensitive and Specific Molecular Test for Mutations in the Diagnosis of Thyroid Nodules: A Prospective Study of BRAF-Prevalent Population

2020 ◽  
Vol 21 (16) ◽  
pp. 5629 ◽  
Author(s):  
Yoon Young Cho ◽  
So Young Park ◽  
Jung Hee Shin ◽  
Young Lyun Oh ◽  
Jun-Ho Choe ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Prospective Study ◽  
Thyroid Nodules ◽  
Needle Aspiration ◽  
Genetic Alterations ◽  
Braf V600e ◽  
Molecular Testing ◽  
Molecular Test ◽  
Indeterminate Cytology ◽  
A Prospective Study

Molecular testing offers more objective information in the diagnosis and personalized decision making for thyroid nodules. In Korea, as the BRAF V600E mutation is detected in 70–80% of thyroid cancer specimens, its testing in fine-needle aspiration (FNA) cytology specimens alone has been used for the differential diagnosis of thyroid nodules until now. Thus, we aimed to develop a mutation panel to detect not only BRAF V600E, but also other common genetic alterations in thyroid cancer and to evaluate the diagnostic accuracy of the mutation panel for thyroid nodules in Korea. For this prospective study, FNA specimens of 430 nodules were obtained from patients who underwent thyroid surgery for thyroid nodules. A molecular test was devised using real-time PCR to detect common genetic alterations in thyroid cancer, including BRAF, N-, H-, and K-RAS mutations and rearrangements of RET/PTC and PAX8/PPARr. Positive results for the mutation panel were confirmed by sequencing. Among the 430 FNA specimens, genetic alterations were detected in 293 cases (68%). BRAF V600E (240 of 347 cases, 69%) was the most prevalent mutation in thyroid cancer. The RAS mutation was most prevalently detected for indeterminate cytology. Among the 293 mutation-positive cases, 287 (98%) were diagnosed as cancer. The combination of molecular testing and cytology improved sensitivity from 72% (cytology alone) to 89% (combination), with a specificity of 93%. We verified the excellent diagnostic performance of the mutation panel applicable for clinical practice in Korea. A plan has been devised to validate its performance using independent FNA specimens.

Molecular Diagnostics of Thyroid Tumors

2011 ◽  
Vol 135 (5) ◽  
pp. 569-577 ◽  
Author(s):  
Yuri E. Nikiforov
Keyword(s):  
Thyroid Cancer ◽  
Molecular Markers ◽  
Fine Needle Aspiration ◽  
Thyroid Nodules ◽  
Needle Aspiration ◽  
Genetic Alterations ◽  
Braf V600e ◽  
Fine Needle ◽  
Molecular Alterations ◽  
Diagnostic Use

Abstract Context.—Thyroid cancer is the most common type of endocrine malignancy and its incidence is steadily increasing. Papillary carcinoma and follicular carcinoma are the most common types of thyroid cancer and represent those tumor types for which use of molecular markers for diagnosis and prognostication is of high clinical significance. Objective.—To review the most common molecular alterations in thyroid cancer and their diagnostic and prognostic utility. Data Sources.—PubMed (US National Library of Medicine)–available review articles, peer-reviewed original articles, and experience of the author. Conclusions.—The most common molecular alterations in thyroid cancer include BRAF and RAS point mutations and RET/PTC and PAX8/PPARγ rearrangements. These nonoverlapping genetic alterations are found in more than 70% of papillary and follicular thyroid carcinomas. These molecular alterations can be detected in surgically resected samples and fine-needle aspiration samples from thyroid nodules and can be of significant diagnostic use. The diagnostic role of BRAF mutations has been studied most extensively, and recent studies also demonstrated a significant diagnostic utility of RAS, RET/PTC, and PAX8/PPARγ mutations, particularly in thyroid fine-needle aspiration samples with indeterminate cytology. In addition to the diagnostic use, BRAF V600E mutation can also be used for tumor prognostication, as this mutation is associated with higher rate of tumor recurrence and tumor-related mortality. The use of these and other emerging molecular markers is expected to improve significantly the accuracy of cancer diagnosis in thyroid nodules and allow more individualized surgical and postsurgical management of patients with thyroid cancer.

scholarly journals Ultrasonography Classification of the American Thyroid Association for Predicting Malignancy in Thyroid Nodules >1cm with Indeterminate Cytology: A Prospective Study

2018 ◽  
Vol 50 (08) ◽  
pp. 597-601 ◽  
Author(s):  
Tiara Rocha ◽  
Pedro Rosario ◽  
Alexandre Silva ◽  
Maurício Nunes ◽  
Tulio Silva ◽  
...  
Keyword(s):  
Prospective Study ◽  
Thyroid Nodules ◽  
Thyroid Neoplasms ◽  
Needle Aspiration ◽  
American Thyroid Association ◽  
Molecular Tests ◽  
Indeterminate Cytology ◽  
A Prospective Study ◽  
Doppler Analysis

AbstractThe objective of this prospective study was to evaluate the ultrasonography classification of the American Thyroid Association (ATA) for predicting malignancy in thyroid nodules >1 cm with indication for fine-needle aspiration (FNA) whose cytology was indeterminate. Additionally, the combination of the ATA classification with Doppler analysis was evaluated. All patients with thyroid nodules >1 cm were eligible. Each nodule was assigned to one of the ATA categories. Exclusively or predominantly intranodular vascularity was considered suspicious. One hundred and thirty-seven patients with 143 nodules underwent FNA and those with indeterminate cytology (Bethesda category III or IV) were selected. All patients were referred for surgery. Among the 143 nodules evaluated, 92 were benign, 33 were malignant, 13 were noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP), and 5 were tumors of uncertain malignant potential (TUMP). The rate of malignancy, including NIFTP and TUMP in this definition, was 80%, 42.8%, 13%, 10%, and 23% for nodules with a high suspicion, intermediate suspicion, low suspicion, very low suspicion, and undefined ultrasonographic pattern, respectively. Considering NIFPT and TUMP as benign, these rates were 72%, 22.4%, 4.3%, 0%, and 15.4%, respectively. The addition of Doppler analysis did not significantly improve the prediction of malignancy obtained with the ATA classification alone. The results of this prospective study show the usefulness of the ATA ultrasonographic classification for predicting malignancy specifically in thyroid nodules >1 cm with indeterminate cytology. The ATA category of the nodule should influence the decision for follow-up, molecular tests, or surgery.

scholarly journals Study of BRAF and RAS Mutations in Thyroid Nodules with Indeterminate Cytology and Papillary Thyroid Cancer

2020 ◽  
Vol 1 (2) ◽  
pp. 105-112
Author(s):  
Abd ELmogheth Madani Sahar ◽  
◽  
Gotsiridze Irine ◽  
Keyword(s):  
Decision Making ◽  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Thyroid Nodules ◽  
Genetic Alterations ◽  
Genetic Change ◽  
Braf V600e ◽  
Secondary Outcome ◽  
Papillary Thyroid ◽  
Indeterminate Cytology

OBJECTIVES Thyroid cancer Treatment decision-making is often guided by tumor tissue molecular analysis. The aim of this study was the detection of BRAF, NRAS and HRAS mutations in Georgian patients with thyroid cancer and determination of the frequency of these mutations in the respective populations. SETTING Diagnostic molecular laboratory located in Tbilisi, Georgia. PARTICIPANTS 116 patients with thyroid cancer participated in the study. PRIMARY AND SECONDARY OUTCOME MEASURES Genetic change is the main force of thyroid tumor development, based on new methods of managing thyroid cancer. The latest significant genetic discovery in thyroid cancer is the BRAF-T1799A (V600E) transformation (the gene for B-type RAF kinase, BRAF). Since the initial report of this breakthrough in thyroid cancer years ago, rapid progress has been made. The BRAF mutation is the most common genetic change in thyroid cancer. BRAF and NRAS mutations are frequent genetic alterations found in thyroid nodules. These molecular markers establish a differential diagnosis and facilitate clinical decision-making. Prevalence of thyroid nodule-associated mutations has not been studied in Georgia. We evaluated BRAF, NRAS and HRAS mutations in Georgian patients with indeterminate cytology or diagnosed with papillary thyroid cancer (PTC). RESULTS BRAF (V600E), NRAS (G12C, G12D, Q61R, and Q61K) and HRAS (G12C, G13R, and Q61R) were determined in the DNA extracted from fine needle aspirate specimens. In total, 116 patient samples were analyzed using competitive-specificTaqMan PCR (Cast PCR TM). In these samples, 36 were diagnosed as papillary thyroid carcinoma, and 80 were indeterminate by Bethesda system for reporting thyroid cytopathology (BSRTC III-V). BRAF (V600E) mutation was the most frequent genetic alteration found in 31% of all analyzed samples. Specifically, this mutation was present in 61% of PTC cases and 18% of cases classified as indeterminate (BSRTC III-V). NRAS mutations were present in 16% of PTC and 30% of indeterminate cytology samples. NRAS G12D and Q61R were most prevalent at 36.6% and 40% of all NRAS mutations. BSRTC IV category of indeterminate cytology had the highest frequency of NRAS mutations at 43%. From analyzed samples, HRAS (Q61R) mutation was present in only one PTC case.

Contemporary Management of Thyroid Nodules

2021 ◽  
Vol 73 (1) ◽  
Author(s):  
Kristen Kobaly ◽  
Caroline S. Kim ◽  
Susan J. Mandel
Keyword(s):  
Thyroid Nodules ◽  
Cervical Lymphadenopathy ◽  
Standard Technique ◽  
Clinical History ◽  
Needle Aspiration ◽  
Annual Review ◽  
Publication Date ◽  
Molecular Testing ◽  
Risk Of Malignancy ◽  
Indeterminate Cytology

Thyroid nodules are common in the general population, with higher prevalence in women and with advancing age. Approximately 5% of thyroid nodules are malignant; the majority of this subset represents papillary thyroid cancer. Ultrasonography is the standard technique to assess the underlying thyroid parenchyma, characterize the features of thyroid nodules, and evaluate for abnormal cervical lymphadenopathy. Various risk stratification systems exist to categorize the risk of malignancy based on the ultrasound appearance of a thyroid nodule. Nodules are selected for fine-needle aspiration biopsy on the basis of ultrasound features, size, and high-risk clinical history. Cytology results are classified by the Bethesda system into six categories ranging from benign to malignant. When cytology is indeterminate, molecular testing can further risk-stratify patients for observation or surgery. Surveillance is indicated for nodules with benign cytology, indeterminate cytology with reassuring molecular testing, or non-biopsied nodules without a benign sonographic appearance. Expected final online publication date for the Annual Review of Medicine, Volume 73 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals ACR TI-RADS and ATA US scores are helpful for the management of thyroid nodules with indeterminate cytology

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Thayse Lozovoy Madsen Barbosa ◽  
Cleo Otaviano Mesa Junior ◽  
Hans Graf ◽  
Teresa Cavalvanti ◽  
Marcus Adriano Trippia ◽  
...  
Keyword(s):  
Thyroid Nodules ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Needle Aspiration ◽  
Molecular Testing ◽  
American Thyroid Association ◽  
Institutional Review ◽  
The Us ◽  
Risk Of Malignancy ◽  
Indeterminate Cytology

Abstract Background Cytologically indeterminate thyroid nodules currently present a challenge for clinical decision-making. The main aim of our study was to determine whether the classifications, American College of Radiology (ACR) TI-RADS and 2015 American Thyroid Association (ATA) guidelines, in association with The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC), could be used to stratify the malignancy risk of indeterminate thyroid nodules and guide their clinical management. Methods The institutional review board approved this retrospective study of a cohort of 140 thyroid nodules in 139 patients who were referred to ultrasound-guided fine-needle aspiration cytology (FNAC) from January 2012 to June 2016 with indeterminate cytological results (44 Bethesda III, 52 Bethesda IV and 44 Bethesda V) and in whom pre-FNAC thyroid US images and histological results after surgery were available. Each included nodule was classified by one radiologist blinded to the cytological and histological diagnoses according to the ACR TIRADS scores and the US patterns as recommended in the 2015 ATA guidelines. The risk of malignancy was estimated for Bethesda, TI-RADS scores, ATA US patterns and their combination. Results Of the 140 indeterminate thyroid nodules examined, 74 (52.9%) were histologically benign. A different rate of malignancy (p < 0.001) among Bethesda III, IV and V was observed. The rate of malignancy increased according to the US suspicion categories (p < 0.001) in both US classifications (TI-RADS and ATA). Thyroid nodules classified as Bethesda III and the lowest risk US categories (very low, low and intermediate suspicion by ATA and 2, 3 and 4a by TI-RADS) displayed a sensitivity of 95.3% for both classifications and a negative predictive value of 94.3 and 94.1%, respectively. The highest risk US categories (high suspicion by ATA and 4b,4c and 5 by TI-RADS) were significantly associated with cancer (odds ratios [ORs] 14.7 and 9.8, respectively). Conclusions Ultrasound classifications, ACR TI-RADS and ATA guidelines, may help guide the management of indeterminate thyroid nodules, suggesting a conservative approach to nodules with low-risk US suspicion and Bethesda III, while molecular testing and surgery should be considered for nodules with high-risk US suspicion and Bethesda IV or V.

scholarly journals Hashimoto Thyroiditis and Thyroid Ultrasound: A Prospective Study

2021 ◽  
Author(s):  
Anabela Zunino ◽  
Claudia Vazquez ◽  
Laura Delfino ◽  
Adriana Reyes ◽  
Alicia Lowenstein
Keyword(s):  
Prospective Study ◽  
Thyroid Nodules ◽  
Thyroid Volume ◽  
Hashimoto Thyroiditis ◽  
Needle Aspiration ◽  
Thyroid Peroxidase ◽  
Papillary Thyroid ◽  
Immunological Activity ◽  
Benign Nodules ◽  
A Prospective Study

Abstract Purpose We performed a prospective study in patients with positive thyroid peroxidase antibodies (TPOAb), to describe their ultrasound (US) patterns and the prevalence of thyroid nodules. Methods In 195 consecutive patients, with positive TPOAb, thyroid US was performed by the same physician and equipment and categorized into four echographic patterns (EP). We determined the prevalence of thyroid nodules and their etiology confirmed by cytology or histology. Results The median TPOAb was 526 IUI/ml. EP1 or normal US was present in 9,7%; EP2 or early/indeterminate stage in 29,4%; EP3 or established thyroiditis in 45,4% and EP4 or advanced/late stage in 15,5% of the patients. TPOAb (median = 857 UI / ml) (p = 0.001), TSH and thyroid volume ​​were higher in EP3. A higher degree of fibrosis was associated with TPOAb > 1000 IU/ml(p = 0,003). Thyroid nodules were reported on US at 47,2% of HT. Fine needle aspiration(FNA) was performed in 49/60 nodules. Cytology: BII: 41 patients (83,7%), B V: 1 patient (2%): suspicious for lymphoma; B VI: 3 patients(6,1%) : Papillary thyroid carcinoma. Benign cytology was present in 56% of EP3 (p = 0,048). Conclusions Higher TPOAb, TSH levels, and thyroid volume were associated with EP3. Fibrosis correlated with TPOAb > 1000 IU/ml. In our population, benign nodules were associated with established thyroiditis patterns. The increased inflammation and immunological activity of Hashimoto thyroiditis (HT) could be a favorable environment for growth factors for benign nodular development.

scholarly journals Diagnostic Value of Molecular Testing in Sonographically Suspicious Thyroid Nodules

2020 ◽  
Vol 4 (9) ◽  
Author(s):  
Maxwell M Wang ◽  
Katrina Beckett ◽  
Michael Douek ◽  
Rinat Masamed ◽  
Maitraya Patel ◽  
...  
Keyword(s):  
Thyroid Nodules ◽  
Medical Center ◽  
Diagnostic Value ◽  
Needle Aspiration ◽  
Molecular Testing ◽  
American Thyroid Association ◽  
Indeterminate Nodules ◽  
Thyroid Fine Needle Aspiration ◽  
Indeterminate Cytology ◽  
Risk Categories

Abstract Objective Molecular testing can refine the diagnosis for the 20% of thyroid fine-needle aspiration biopsies that have indeterminate cytology. We assessed the diagnostic accuracy of molecular testing based on ultrasound risk classification. Methods This retrospective cohort study analyzed all thyroid nodules with indeterminate cytology at an academic US medical center (2012-2016). All indeterminate nodules underwent reflexive molecular testing with the Afirma Gene Expression Classifier (GEC). Radiologists performed blinded reviews to categorize each nodule according to the American Thyroid Association (ATA) ultrasound classification and the American College of Radiology Thyroid Imaging, Reporting and Data System. GEC results and diagnostic performance were compared across ultrasound risk categories. Results Of 297 nodules, histopathology confirmed malignancy in 65 (22%). Nodules by ATA classification were 8% high suspicion, 44% intermediate, and 48% low/very low suspicion. A suspicious GEC result was more likely in ATA high-suspicion nodules (81%) than in nodules of all other ATA categories (57%; P = .04). The positive predictive value (PPV) of GEC remained consistent across ultrasound categories (ATA high suspicion, 64% vs all other ATA categories, 48%; P = .39). The ATA high-suspicion category had higher specificity than a suspicious GEC result (93% vs 51%; P &lt; .01). A suspicious GEC result did not increase specificity for the ATA high-suspicion category. Conclusion The PPV of molecular testing remained consistent across ultrasound risk categories. However, a suspicious GEC result was very likely in ATA high-suspicion nodules and did not improve specificity in this sonographic category.

scholarly journals Could Negative Tc-99m-Methoxyisobutylisonitrile (MIBI) Scintigraphy Obviate the Need for Surgery for Bethesda III and IV Thyroid Nodules?

Surgeries ◽  
2021 ◽  
Vol 2 (3) ◽  
pp. 260-267
Author(s):  
Stella Armefti ◽  
Jasmin Mettler ◽  
Matthias Schmidt ◽  
Michael Faust ◽  
Marianne Engels ◽  
...  
Keyword(s):  
Negative Predictive Value ◽  
Predictive Value ◽  
Thyroid Nodules ◽  
Needle Aspiration ◽  
University Hospital ◽  
Molecular Testing ◽  
High Negative Predictive Value ◽  
Indeterminate Cytology ◽  
Sensitivity Specificity ◽  
Mibi Scintigraphy

In about 20% of all cases, the fine needle aspiration cytology (FNAC) results are equivocal, delivering the two common categories of indeterminate cytology, Bethesda III and IV. The observed rates of malignancy vary widely among institutions, with the urgent need for a more precise risk stratification. 99mcTc methoxyisobutylisonitrile scintigraphy (MIBI) is less expensive than molecular testing and has been shown to have a high negative predictive value. For this reason, the results of MIBI scintigraphy in adult patients with indeterminate FNAC were collected, and correlated with the final pathology reports of surgical specimens. Patients receiving FNAC, MIBI scintigraphy and surgery for sonographic suspicious hypofunctional thyroid nodules between 2015 and 2019 at the University Hospital of Cologne, Germany were identified. Sensitivity, specificity, positive predictive and negative predictive value of MIBI scintigraphy were calculated. Seventy-eight patients with sonographic suspicious hypofunctional thyroid nodules underwent surgery after interdisciplinary case discussion of both FNAC and MIBI results. In 49 (62.5%) cases, FNAC consisted of Bethesda III and IV results. In 39 (79.6%) of these cases, MIBI scintigraphy resulted in mismatch and intermediary results, but in only 4 (10.2%) of these cases was a carcinoma diagnosed. The negative predictive value of MIBI scintigraphy was 90–100%, respectively. Relying on the negative predictive value of MIBI match results might have obviated the need for surgery in 20.4% cases; one papillary microcarcinoma, however, would have been missed. MIBI scintigraphy has an underused potential for improving the diagnostic precision of hypofunctional thyroid nodules.

scholarly journals A new molecular-genetic panel in the algorithm of diagnosis and treatment in patients with tiroid nodules

2021 ◽  
Vol 23 (2) ◽  
pp. 75-82
Author(s):  
Pavel N. Romashchenko ◽  
Nicolay A. Maistrenko ◽  
Denis S. Krivolapov ◽  
Maria S. Simonova
Keyword(s):  
Thyroid Cancer ◽  
Thyroid Nodules ◽  
Molecular Genetic ◽  
Threshold Value ◽  
Needle Aspiration ◽  
Braf V600e ◽  
Diagnosis And Treatment ◽  
Sodium Iodide Symporter ◽  
Limit Value ◽  
Number Of Patients

The increase in the number of patients with thyroid nodules requires the development of the most effective methods of preoperative diagnosis, allowing timely detection and differentiation of follicular neoplasia and highly differentiated cancer. A comprehensive study was carried out, which made it possible to optimize the diagnosis and choice of therapeutic tactics in patients of this category through the use of a new molecular genetic panel. Results of examination and surgical treatment of 60 patients suffering from benign and malignant thyroid gland formations are analyzed, pre-operative diagnosis of which was supplemented by immunocytochemical and molecular genetic methods of studying cellular material obtained during fine-needle aspiration biopsy. The threshold value of the Galektin-3 expression level for the differential diagnosis of follicular neoplasia in the direction of adenomas or well-differentiated thyroid cancer was determined. The significance of the BRAF V600E gene mutation in the detection of papillary thyroid cancer, the features of its clinical course and the determination of rational surgical tactics was proved. The limit value of the sodium-iodide symporter for predicting the resistance of thyroid cancer to radioactive iodine therapy, which determines the need to expand the scope of surgical intervention, has been established. The place of these molecular genetic markers in the algorithm of diagnosis and treatment in patients with thyroid nodules was determined.

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