The thyroid risk score (TRS) for nodules with indeterminate cytology

Abstract

Cytology is the gold standard method for the differential diagnosis of thyroid nodules, though 25-30% of them are classified as indeterminate. We aimed to set up a 'thyroid risk score' (TRS) to increase the diagnostic accuracy in these cases. We prospectively tested 135 indeterminate thyroid nodules. The pre-surgical TRS derived from the sum of the scores assigned at cytology, EU-TIRADS classification, nodule measurement, and molecular characterization, which was done by our PTC-MA assay, a customized array able to cost-effectively evaluate 24 different genetic alterations including point mutations and gene fusions. We found that the risk of malignancy (ROM) increased paralleling the score: in the category >4 and ≤ 6 (low suspicion), >6 ≤ 8 (intermediate suspicion), and >8 (high suspicion), ROM was 10%, 47% and 100%, respectively. ROC curves selected the score >6.5 as the best threshold to differentiate between malignant and benign nodules (P<0.001). The TRS>6.5 had a better performance than the single parameters evaluated separately, with an accuracy of 77% and 82% upon inclusion of noninvasive follicular thyroid neoplasm with papillary-like nuclear features among malignant or benign cases, respectively. We generated for the first time a score combining a cost-effective molecular assay with already validated tools, harboring different specificities and sensitivities, for the differential diagnosis of indeterminate nodules. The combination of different parameters reduced the number of false negatives inherent to each classification system. The TRS >6.5 was highly suggestive for malignancy and retained a high accuracy in the identification of patients to be submitted to surgery.

Oxidative Stress Correlates with More Aggressive Features in Thyroid Cancer

“…The molecular profile of tumor samples was characterized by a custom mass spectrometry PTC-MA panel (Sequenom, Agena, San Diego, CA, USA), as we previously reported [ 26 , 27 ]. In particular DNA and RNA were extracted from the nuclear fractions using an All Prep DNA/RNA kit (Qiagen, Hilden, Germany).…”

Current Status and Challenges of US-Guided Radiofrequency Ablation of Thyroid Nodules in the Long Term: A Systematic Review

“…In these cases, contrast-enhanced rather than non-enhanced ultrasound might provide useful information on the treatment outcome [ 51 , 52 ]. Additional classifiers based not only on clinical and US features, but also on molecular markers [ 53 ] and artificial intelligence might help predict treatment response as well as nodule behaviour over time [ 54 ].…”

DIAGNOSIS OF ENDOCRINE DISEASE: Usefulness of genetic testing of fine-needle aspirations for diagnosis of thyroid cancer

“…In this singlecenter study, a locally validated, limited but low-cost mutation panel was applied in the context of a larger scope evaluation of the ultrasound, cytology, and other clinical data for each thyroid nodule (50). These additional diagnostic data were combined with genetic results to create a thyroid risk score, which showed promising accuracy despite the limited sensitivity of the genetic test on its own (61). The success of this approach, although producing accuracy below the initial validation studies of molecular diagnostic tests used in the United States, opens the possibility of a standardized, integrated score combining genomic classifiers with ultrasound and cytology data such as nodule size and TI-RADS category compared to the standard of care which assesses nodule features with separate scoring systems.…”

“…Consistent data across cohorts have elucidated the malignancy risk at the level of individual mutations and gene fusions for certain high-risk genetic alterations. For example, the >98% ROM for a nodule with a BRAFV600E mutation as well as for essentially all coexisting mutations (excluding TSHR or other mutations associated with benign disease) has been well established (61,78,90,91). Moreover, data show worse disease-free survival in BRAFV600E mutant carcinomas than in carcinomas with RAS-like driver mutations such as BRAFK601E, RAS, or PAX8-PPARG (84).…”