Objective: We developed a novel dual-component molecular assay as an ancillary method to improve clinical decision-making in patients with cytologically indeterminate thyroid nodules. The assay includes next-generation sequencing (NGS) based detection of mutations in 23 thyroid cancer related genes and digital polymerase chain reaction (dPCR) evaluation of the expression levels of a microRNA strongly associated with thyroid cancer. The method was designed as a rule-out test and preliminary results in a surgical cohort showed a negative predictive value comparable to a negative diagnostic cytology (100%). The aim of this study was to describe the performance of this approach in a real-world cohort of patients undergoing thyroid nodule fine-needle aspiration cytology, whose treatment is defined by the current clinical practice and based on clinical and ultrasonographic data.
Methods: Patients with a cytologically indeterminate nodule (TIR3A and TIR3B according to of the Italian Consensus for Thyroid Cytology) were prospectively enrolled from January 2017 to January 2022 in the thyroid cancer unit at Policlinico Umberto I of Rome. For each consenting patient, residual cytological material from thyroid nodule aspirates was collected washing the needle with a nucleic acid preservative solution, after the preparation of standard cytology smears, with no dedicated passes. The samples were stored at -20°C until molecular testing. Patients underwent either surgery or clinical monitoring based on cytology diagnosis, molecular test results, clinical features, and patients preference. Patients who did not proceed to surgery were monitored clinically for sonographic evidence of growth, development of suspicious US characteristics, or suspicious lymph node appearance. Median follow-up of these patients was 34 months.
Results: In total, 326 cytologically indeterminate thyroid nodules were consecutively collected since January 2017. Molecular analysis was performed on 218 thyroid aspirates from 211 consenting patients (TIR3A, n=163; TIR3B, n=55), displaying a 58% of positive call rate. The benign call rate of the assay was significantly higher in TIR3A (60%) than in TIR3B (44%) nodules (P=0.0411). Among the 63 patients undergoing surgery (cancer prevalence 36%), the molecular assay showed high sensitivity (96%) and negative predictive value (96%). There was only 1 false-negative test result, representing a low-risk neoplasia.
Conclusion: These data confirm that the used dual-component molecular test can increase the diagnostic accuracy of thyroid cytology alone by reducing the number of nodules that will be classified as indeterminate and increasing those that can be reliably classified as benign, thus avoiding a substantial number of diagnostic surgeries.
10 Sep 2022 - 13 Sep 2022