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.