Endocrine Abstracts

Background: Cytology is the gold standard method for the differential diagnosis of thyroid nodules, though 25−30% of them are classified as indeterminate and, in some cases, surgery is required for a definitive diagnosis.

Aim: In order to reduce unnecessary thyroid surgeries, we set up a ‘thyroid risk score’ (TRS) to increase the diagnostic accuracy in a large series of patients with indeterminate cytology and to apply it to a validation series.

Methods: The pre-surgical TRS derived from the sum of the scores assigned at cytology, namely EU-TIRADS classification, nodule measurement, and molecular characterization (24 different genetic alterations, including point mutations and gene fusions, analysed by our customized assay PTC-MA assay until recently and, currently, from a Next-Generation Sequencing-NGS panel). We prospectively tested 136 indeterminate thyroid nodules for the model evaluation, while further 50 patients have been enrolled to date for the model validation.

Results: 66/136 analyzed nodules underwent surgery and 20/66 (30.3%) were malignant. 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. In the new series, 12/50 nodules with TRS > 6 will undergo surgery in order to confirm TRS cut-off.

Conclusions: In conclusion, for the first time, we generated and applied a score combining a cost-effective molecular assay with already validated tools, harboring different specificities and sensitivities. 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. A proper role of the TRS can be also predicted in the evaluation of large nodules routed to surgery in most cases. Indeed, in the era of mini-invasive procedures, a low TRS could favor the possibility to submit older patients and cases with co-morbidities to these techniques. The validation series will give more insights into the accuracy of our present TRS cut-off.