Endocrine Abstracts

Objectives: Despite the increasing role of molecular profiling, the association between mutation expression and pre-operative cytology for thyroid nodules has not been established.

Methods: We collected data on patients who underwent molecular profiling of thyroid nodules in Bethesda categories III to VI from two tertiary academic hospitals and via systematic literature review. We tested the associations between Bethesda categories and molecular mutation stratified by risk levels, according to the 2015 ATA guidelines. When thyroidectomy was preformed, we also evaluated association with postoperative diagnosis and aggressivity of disease based on histopathological variants, nodal metastasis or extra-thyroidal extension.

Results: We analyzed data from 452 nodules in our institutional cohort and 3912 nodules from the systematic literature review. A significant positive correlation was found between Bethesda categories and mutations, demonstrated by an increase in the intermediate to high-risk mutation rate in the higher BSRTC categories (Rs = 0.660, P≤ 0.001). In the institutional cohort malignancy rate for BSRTC III and IV was 56.7% and 75.7%, respectively. The most common mutation was BRAFV600E, with 95.9% (93/97) of those patients in Bethesda category V or VI (P<.001). All had confirmed thyroid cancer on pathology, with aggressive tumor behavior in most (60%). Patients with low-risk mutation, as H, K or N RAS alterations showed an association with Bethesda categories III and IV ( P≤.01). In mutation-negative nodules of BSATC III to VI who underwent surgery, we found a lower incidence of aggressive thyroid cancer compared to those with an identified mutation (12.6% vs 44.3%, P<.01).

Conclusion: We found positive correlation between cytology results and molecular testing. These findings may provide clinicians with better interpretation for BSRTC results and may contribute to the identification of aggressive thyroid nodules associated with indeterminate Bethesda categories.