Molecular testing in diagnosis of indeterminate thyroid cytology: Trends and drivers

Abstract

Fine needle aspiration (FNA), the cornerstone of diagnosis in thyroid swellings, fails to render a definitive diagnosis in about 20% to 30% of cases that are reported as indeterminate on cytology. Since the clinical management in thyroid rests on the risk of malignancy (ROM) in a given nodule, this distinction between "benign" and "possibly malignant" assumes paramount clinical importance. Over the last two decades, tremendous progress has been achieved in our understanding of the molecular basis of thyroid pathologies leading to identification of several genetic alterations that could potentially be exploited for diagnostic, prognostic and therapeutic purposes. An array of molecular tests has hit the markets aiming to predict the ROM in thyroid nodules. A deeper understanding of the strengths and limitations of these tests is imperative to be able to judiciously choose the right molecular test in a given case for maximum clinical benefit. This narrative review provides an overview of current status of molecular testing in the evaluation of thyroid nodules encompassing the current status and applications of these tests in diagnostic, prognostic and therapeutic areas along with a brief insight into the future developments in this field.

Utility of a multigene testing for preoperative evaluation of indeterminate thyroid nodules: A prospective blinded single center study in China

“…Samples from other countries need to be transported across large distances entailing high costs. 18 Only a handful of studies describing these methods were published outside USA. The current study aimed to use high throughput sequencing to evaluate the indeterminate FNA samples, owing to the paucity of information in China and East Asia, where overtreatment of thyroid nodules has become a social problem.…”

“…Unfortunately, these clinically validated commercial ancillary molecular tests can only be available in a few developed nations. Samples from other countries need to be transported across large distances entailing high costs 18 . Only a handful of studies describing these methods were published outside USA.…”

Do ACR TI-RADS scores demonstrate unique thyroid molecular profiles?

“…Moreover, there is no consensus on standardof-care and management for cytologically indeterminate thyroid nodules. Of note, genetic alterations are detected in approximately 90% of papillary thyroid carcinomas (PTCs), and more than 60% of thyroid malignancy [13][14][15][16][17][18][19][20][21][22]. Therefore, in order to further risk stratify patients with indeterminate thyroid cytology diagnoses, molecular studies have been utilized to detect genetic alterations and play an important role in the therapeutic triage of thyroid lesions [13,14].…”

Molecular Tests for Risk-Stratifying Cytologically Indeterminate Thyroid Nodules: An Overview of Commercially Available Testing Platforms in the United States

“…Additionally, progress in understanding the molecular pathogenesis of thyroid neoplasms has fueled the development of molecular diagnostic tests for improving the preoperative risk-stratification of cytologically indeterminate thyroid nodules [24]. The primary goal of these molecular tests is to correctly identify benign nodules among those with indeterminate cytology, thereby decreasing the number of unnecessary diagnostic surgeries [25][26][27][28]. The updated versions of thyroid FNA classification schemes are now aligned with the aforementioned changes in histopathologic classification of thyroid neoplasms, applicability of molecular testing, and current recommendations for management.…”