RESULTS
A total of 451 patients with a thyroid nodule undergoing USFNA, molecular profile testing and surgery were included in the study. Baseline patient characteristics are shown in Table 1. Most patients were female and had a mean dominant thyroid nodule size of 2.1cm (standard deviation of 1.1cm). 325 patients (72.1%) underwent thyroid lobectomy. The overall prevalence of malignancy, excluding cases of NIFTP, was 78.5% of the cohort. The prevalence of postoperative malignancy by USFNA Bethesda category was 56.7% (55/97) for Bethesda III, 75.7% (109/144) for Bethesda IV, 80.1% (86/104) for Bethesda V and 100% for Bethesda VI lesions. 138 patients showed evidence of aggressive thyroid cancer of which 79 had central neck lymph node metastasis.
Select mutations of dominant thyroid nodules were strongly associated with specific Bethesda categories (Table 2). Almost all BRAF V600E mutations were associated with Bethesda V and VI (P<0.0001). Only 4 of 97 (4.1%) nodules with BRAF V600E mutations had a Bethesda category III or IV, all of which were malignant on postoperative pathology. RAS and EIF1AX mutations, copy number alterations and GEP were strongly associated with Bethesda categories III and IV (P≤0.01). Figure 1 illustrates the above findings by displaying the frequency of Bethesda categories among different molecular mutations. Thyroid nodules with an identified molecular mutation were more likely to harbour thyroid cancer. Specifically, nodules with a BRAF V600E, TERT or RET mutation were most likely to harbour an aggressive thyroid cancer (Table 3).
Other identified molecular mutations were less associated with aggressive disease. NIFTP was mostly associated with RAS-type mutations. No molecular mutations were identified in 43.9% of patients; of those patients, 128 had a thyroid cancer. Overall, those with no identified molecular mutation had a lower incidence of aggressive thyroid cancer compared to those with an identified mutation (12.6% vs 44.3%, P<0.01). When classified according to malignancy on postoperative pathology, statistically significant associations to Bethesda category by molecular mutation were identified in patients with BRAF V600E, RAS, PTEN and EIF1AX mutations, copy number alterations and GEP (Supplemental Table 1). The presence of an identified molecular mutation on USFNA predicted postoperative malignancy.