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New Molecular Testing for Cytologically Indeterminate Thyroid Nodules
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New Molecular Testing for Cytologically Indeterminate Thyroid Nodules

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Endocrinology and Metabolism".

Deadline for manuscript submissions: closed (30 November 2022) | Viewed by 5906

Special Issue Editor

Dr. Claudio Casella

E-Mail Website
Guest Editor
Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy
Interests: endocrine surgery; thyroid surgery; parathyroid surgery: thyroid cancer; hyperthyroidism; hyperparathyroidism

Special Issue Information

Dear Colleagues, 

The malignancy of thyroid nodules with indeterminate cytology may be determined by molecular testing instead by surgery?

Thyroid nodules are highly prevalent in the general population and fine-needle aspiration (FNA) is commonly used as the standard preoperative tool for their diagnosis. With a percentage over 20%, FNA of thyroid nodules has an indeterminate cytology (Bethesda class III or IV). Since the clinical management of the thyroid rests on the risk of malignancy (ROM) in a given nodule, this distinction between “benign” and “possibly malignant” is of paramount clinical importance. Surgery can be avoided if the nodules are diagnosed as benign pre-operatively. More than 60% of surgeries for thyroid nodule with indeterminate cytology could be avoided if their nature could be determined by a molecular test, without surgery. The 2015 guidelines of the American Thyroid Association (ATA) for thyroid lesions in adults also recommended that molecular testing be employed for the assessment of the risk of malignancy.

Recently, remarkable progress has been made towards understanding the molecular genetics of thyroid cancer. Consequently, several molecular tests that improve the accuracy of pre-operative diagnosis of cytologically indeterminate thyroid nodules have been developed. In the recent literature several scientific reports have appeared that report on the use of molecular tests for diagnosis in thyroid nodules.

This Special Issue aims to collect papers on molecular studies in Cytologically Indeterminate Thyroid Nodules, to increase the knowledge of this disease to prompt further research for those with a special interest in the field. This Special Issue is dedicated to all original research articles and reviews, exploring Cytologically Indeterminate Thyroid Nodules, focus on diagnostic approach, therapeutic targets, pathological effects and signaling pathways. Purely clinical investigations are not suitable but clinical submissions with some component of deep molecular studies are quite welcome.

Dr. Claudio Casella
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • thyroid nodules
  • FNA indeterminate cytology
  • thyroid cancer
  • molecular tests

Published Papers (3 papers)

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9 pages, 711 KiB  
Article
Radiofrequency Ablation of Indeterminate Thyroid Nodules: The First North American Comparative Analysis
by Peter P. Issa, Mahmoud Omar, Chad P. Issa, Yusef Buti, Mohammad Hussein, Mohamed Aboueisha, Ali Abdelhady, Mohamed Shama, Grace S. Lee, Eman Toraih and Emad Kandil
Int. J. Mol. Sci. 2022, 23(19), 11493; https://doi.org/10.3390/ijms231911493 - 29 Sep 2022
Cited by 11 | Viewed by 1926
Abstract
Thyroid nodules can be classified as benign, malignant, or indeterminate, the latter of which make up 10–30% of nodules. Radiofrequency ablation (RFA) has become an attractive and promising therapy for the treatment of benign thyroid nodules. However, few studies have investigated the safety [...] Read more.
Thyroid nodules can be classified as benign, malignant, or indeterminate, the latter of which make up 10–30% of nodules. Radiofrequency ablation (RFA) has become an attractive and promising therapy for the treatment of benign thyroid nodules. However, few studies have investigated the safety and efficacy of RFA for the management of indeterminate thyroid nodules. In this study, 178 patients with thyroid nodules diagnosed as benign (Bethesda II) or indeterminate (Bethesda III/IV) by preoperative cytopathological analysis were included. Patients in the benign and indeterminate cohorts had similar thyroid nodule volume reduction rates at 65.60% and 64.20%, respectively (p = 0.68). The two groups had similar nodular regrowth rates, at 11.2% for benign nodules and 9.40% for indeterminate nodules (p = 0.72). A total of three cases of transient dysphonia were reported. RFA of indeterminate thyroid nodules was comparable to that of benign thyroid nodules in all parameters of interest, including volume reduction rate. To our best knowledge, our work is the first North American analysis comparing benign and indeterminate thyroid nodules and suggests RFA to be a promising modality for the management of indeterminate thyroid nodules. Full article
(This article belongs to the Special Issue New Molecular Testing for Cytologically Indeterminate Thyroid Nodules)
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11 pages, 1428 KiB  
Article
Cytomolecular Classification of Thyroid Nodules Using Fine-Needle Washes Aspiration Biopsies
by Giulia Capitoli, Isabella Piga, Vincenzo L’Imperio, Francesca Clerici, Davide Leni, Mattia Garancini, Gabriele Casati, Stefania Galimberti, Fulvio Magni and Fabio Pagni
Int. J. Mol. Sci. 2022, 23(8), 4156; https://doi.org/10.3390/ijms23084156 - 09 Apr 2022
Cited by 8 | Viewed by 2087
Abstract
Fine-needle aspiration biopsies (FNA) represent the gold standard to exclude the malignant nature of thyroid nodules. After cytomorphology, 20–30% of cases are deemed “indeterminate for malignancy” and undergo surgery. However, after thyroidectomy, 70–80% of these nodules are benign. The identification of tools for [...] Read more.
Fine-needle aspiration biopsies (FNA) represent the gold standard to exclude the malignant nature of thyroid nodules. After cytomorphology, 20–30% of cases are deemed “indeterminate for malignancy” and undergo surgery. However, after thyroidectomy, 70–80% of these nodules are benign. The identification of tools for improving FNA’s diagnostic performances is explored by matrix-assisted laser-desorption ionization mass spectrometry imaging (MALDI-MSI). A clinical study was conducted in order to build a classification model for the characterization of thyroid nodules on a large cohort of 240 samples, showing that MALDI-MSI can be effective in separating areas with benign/malignant cells. The model had optimal performances in the internal validation set (n = 70), with 100.0% (95% CI = 83.2–100.0%) sensitivity and 96.0% (95% CI = 86.3–99.5%) specificity. The external validation (n = 170) showed a specificity of 82.9% (95% CI = 74.3–89.5%) and a sensitivity of 43.1% (95% CI = 30.9–56.0%). The performance of the model was hampered in the presence of poor and/or noisy spectra. Consequently, restricting the evaluation to the subset of FNAs with adequate cellularity, sensitivity improved up to 76.5% (95% CI = 58.8–89.3). Results also suggest the putative role of MALDI-MSI in routine clinical triage, with a three levels diagnostic classification that accounts for an indeterminate gray zone of nodules requiring a strict follow-up. Full article
(This article belongs to the Special Issue New Molecular Testing for Cytologically Indeterminate Thyroid Nodules)
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13 pages, 468 KiB  
Perspective
Prospects of Testing Diurnal Profiles of Expressions of TSH-R and Circadian Clock Genes in Thyrocytes for Identification of Preoperative Biomarkers for Thyroid Carcinoma
by Arcady Putilov
Int. J. Mol. Sci. 2022, 23(20), 12208; https://doi.org/10.3390/ijms232012208 - 13 Oct 2022
Cited by 1 | Viewed by 1232
Abstract
Thyroid Nodules (TN) are frequent but mostly benign, and postoperative rate of benign TN attains the values from 70% to 90%. Therefore, there is an urgent need for identification of reliable preoperative diagnosis markers for patients with indeterminate thyroid cytology. In this study, [...] Read more.
Thyroid Nodules (TN) are frequent but mostly benign, and postoperative rate of benign TN attains the values from 70% to 90%. Therefore, there is an urgent need for identification of reliable preoperative diagnosis markers for patients with indeterminate thyroid cytology. In this study, an earlier unexplored design of research on preoperative biomarkers for thyroid malignancies was proposed. Evaluation of reported results of studies addressing the links of thyroid cancer to the circadian clockwork dysfunctions and abnormal activities of Thyroid-Stimulating Hormone (TSH) and its receptor (TSH-R) suggested diagnostic significance of such links. However, there is still a gap in studies of interrelationships between diurnal profiles of expression of circadian clock genes and TSH-R in indeterminate thyroid tissue exposed to different concentrations of TSH. These interrelationships might be investigated in future in vitro experiments on benign and malignant thyrocytes cultivated under normal and challenged TSH levels. Their design requires simultaneous measurement of diurnal profiles of expression of both circadian clock genes and TSH-R. Experimental results might help to bridge previous studies of preoperative biomarkers for thyroid carcinoma exploring diagnostic value of diurnal profiles of serum TSH levels, expression of TSH-R, and expression of circadian clock genes. Full article
(This article belongs to the Special Issue New Molecular Testing for Cytologically Indeterminate Thyroid Nodules)
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