INTRODUCTION
The widespread use of medical imaging has contributed to the increased
incidence of thyroid nodules detected and incidental thyroid cancer
diagnosed. [1] Studies suggest that the number of ultrasound guided
fine needles aspirations (USFNAs) performed has doubled and the number
of thyroid surgeries performed has increased by nearly 30% over the
last decade. [1] Currently, USFNA is the standard diagnostic method
for thyroid nodules. Although USFNA specimens are categorized according
to the Bethesda classification, 24%-57% of thyroid USFNAs have an
indeterminate result. [2-4] As a consequence, thyroid lobectomy is
often performed for diagnostic and potentially therapeutic purposes. In
roughly 60% of patients with indeterminate cytology, the thyroid nodule
is benign. [4] In these patients, molecular testing of thyroid
nodules has become an adjunct to USFNA biopsy to reduce the likelihood
of unnecessary diagnostic surgery. [5]
Mutations that are uncovered with molecular testing of thyroid nodules,
namely BRAF V600E or RAS-type mutations, can assist with uncovering the
phenotype of the nodule (benign versus malignant) as well as whether the
tumor may be an aggressive variant. Mutations of the BRAF V600E gene,
found in 35-70% of papillary thyroid carcinomas (PTC), lead to the
activation of BRAF kinase and chronically stimulate the MAPK signaling
pathway. [7,8] The BRAF V600E mutation has been strongly associated
with classic and tall cell variant of PTC. [8] This mutation has
also been shown to correlate with aggressive tumor characteristics
including multifocality, extrathyroidal extension, regional or distant
metastases and an advanced tumor stage at presentation. [8-15]
Moreover, studies have shown that BRAF V600E mutations are associated
with tumor recurrence and poor prognosis. [14,15] Mutation in the
three RAS genes (HRAS, KRAS, and NRAS) are found in follicular adenomas
and follicular carcinomas, as well as in the follicular variant of PTC
and more recently for non-invasive follicular neoplasm with
papillary-like nuclear features (NIFTP). [7] RAS mutations result in
permanent RAS activation which chronically stimulate the MAPK and
PI3K/AKT signaling pathways. [7] They are associated
follicular-patterned neoplasms, with less prominent nuclear features of
PTC, more frequent encapsulation and a lower rate of lymph node
metastases than those with BRAF V600E mutations. [16-18] According
to a recent study, RAS mutations in malignant thyroid nodules, when
isolated, are associated with low-risk features and a favorable
prognosis. [16-18]
In this study, the association between Bethesda category and molecular
mutation assessed with ThyroSeq V3 or ThyGeNEXT in patients with thyroid
nodules undergoing thyroidectomy is explored to better tailor patient
diagnosis and treatment.