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.

Risk of malignancy and neoplasia predicted by three molecular testing platforms in indeterminate thyroid nodules on fine-needle aspiration

2019 ◽  
Vol 47 (9) ◽  
pp. 853-862 ◽  
Author(s):  
Kristen L. Partyka ◽  
Karen Trevino ◽  
Melissa L. Randolph ◽  
Harvey Cramer ◽  
Howard H. Wu
Keyword(s):  
Fine Needle Aspiration ◽  
Thyroid Nodules ◽  
Needle Aspiration ◽  
Molecular Testing ◽  
Fine Needle ◽  
Risk Of Malignancy

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.

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.

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

2020 ◽  
Vol 73 (11) ◽  
pp. 722-727 ◽  
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.

scholarly journals Usefulness of accessible imaging methods in thyroid nodules with indeterminate cytology

2021 ◽  
Vol 28 (1) ◽  
pp. R1-R9
Author(s):  
Pedro Weslley Rosario ◽  
Tiara Grossi Rocha ◽  
Gabriela Franco Mourão
Keyword(s):  
Fdg Pet ◽  
Thyroid Nodules ◽  
Needle Aspiration ◽  
Diagnostic Methods ◽  
Imaging Method ◽  
Fine Needle ◽  
Risk Of Malignancy ◽  
Indeterminate Cytology ◽  
Rule Out

In thyroid nodules (TN) submitted to fine-needle aspiration (FNA), Bethesda categories III and IV are considered ‘indeterminate’ cytology. This result corresponds to 10–25% of all FNAs and the risk of malignancy (RoM) ranges from 10% to 30% for category III and from 15% to 40% for category IV. This review analyzed the practical applicability of accessible imaging method in the management of patients with cytologically indeterminate TN > 1 cm (ITN). When ITN are highly suspicious on ultrasonography (US), the RoM supports surgical indication even in the absence of additional tests. The same can be applied to ITN of intermediate suspicion but with elevated stiffness on elastography. Follow-up without additional tests is acceptable in the case of ITN with low-risk cytology and low-suspicion appearance on US and elastography (if obtained). In the case of ITN without highly suspicious US appearance, 123I scintigraphy may be obtained in patients with TSH < 1–1.5 mIU/L to rule out hyperfunctioning nodules before requesting diagnostic methods that are more expensive and less accessible. In addition, in ITN with not very suspicious US appearance, 18FDG-PET may be obtained. If this method does not reveal nodular uptake, the risk of the nodule corresponding to a macrocarcinoma is sufficiently low in order to allow follow-up. The positive predictive value of focal nodular uptake on 18FDG-PET depends on the pre-test RoM, cytological findings, and maximum SUV. There is currently no evidence for the use of CT, MRI or imaging using 99mTc-MIBI to define the nature of ITN.

scholarly journals Thyroid and Molecular Testing. Advances in Thyroid Molecular Cytopathology

2021 ◽  
Vol 2 (2) ◽  
pp. 77-92
Author(s):  
Esther Diana Rossi ◽  
Philippe Vielh
Keyword(s):  
Thyroid Nodules ◽  
Adult Population ◽  
Needle Aspiration ◽  
Common Finding ◽  
Molecular Testing ◽  
Additional Tool ◽  
Thyroid Cytology ◽  
Hürthle Cell ◽  
Cell Neoplasm ◽  
Undetermined Significance

Thyroid nodules are a common finding in the adult population including the fact that more than 50% of individuals, over the age of 60, have thyroid nodules. The majority have been mostly detected with ultrasonography and 10% by palpation. The majority of these nodules are benign, whereas 5–15% of them are malignant. The pre-operative diagnosis of cancer is a critical challenge in order to ensure that each patient can be treated with the best tailored management with a reduction of unnecessary surgery for benign lesions. Fine needle aspiration cytology (FNAC) represents the first and most important diagnostic tool for the evaluation of thyroid lesions. According to the literature, FNAC is able to render a conclusive diagnosis in up to 70–80% of all cases. For the remaining 20–30% of nodules, cytological diagnoses fall into the category of indeterminate lesions mostly due to the lack of specific morphological features. According to the Bethesda system for reporting thyroid cytopathology (TBSRTC), indeterminate lesions can be sub-stratified into three different subcategories including “atypia of undetermined significance/follicular lesion of undetermined significance-AUS/FLUS”; “follicular or Hürthle cell neoplasm/suspicious for follicular or Hürthle cell neoplasm-FN/SFN”; and “suspicious for malignancy-SFM”. Many of these indeterminate lesions undergo repetition or diagnostic lobectomy. Nonetheless, the majority of these cases will have a benign diagnosis due to the fact that the rate of cancer ranges between 6 and 30%. It stands to reason that the application of ancillary technique, mostly molecular testing, emerged as a critical additional tool for those thyroid indeterminate lesions. Since the early 1990s, material collected from cytological samples yields sufficient and adequate cells for the detection of point mutation or gene fusions. Nonetheless, the further availability of new sequencing technologies such as next-generation sequencing (NGS) has led to more comprehensive molecular applications adopted now in clinical use. The current review investigates the multiple advances in the field of molecular testing applied in thyroid cytology.

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