We reviewed 59 archival thyroid FNAC specimens of surgically confirmed FVPTC according to histologic subtype: encapsulated FVPTC (
n = 30) and infiltrative FVPTC (n = 29).
Galectin-3 immunostaining and molecular analyses for BRAF and three RAS genes (NRAS, HRAS, and KRAS) were performed.
RESULTS: FNAC diagnoses of FVPTC included benign (5%), atypia of undetermined significance (19%), follicular
neoplasm/suspicious for follicular
neoplasm (14%), suspicious for PTC (29%), and PTC (34%).
Galectin-3 immunostaining was positive in 50% of FNAC specimens. A BRAF mutation was found only in 14 (24%)
tumors with the FNAC diagnosis of PTC or suspicious for PTC: 13 cases with the usual c.1799T>A (p.V600E) mutation and 1 case with a 3 base-pair deletion (c.1799_1801delTGA), resulting in a deletion of
lysine at
codon 601 and a deletion c.1799_1801delTGA that results in a
valine-to-
glutamate substitution at
codon 600 (p.V600_K601>E) while preserving the reading frame. A BRAF K601E mutation was not found. RAS mutations were observed in 18 (33%)
tumors (NRAS, 22%; HRAS, 6%; KRAS, 6%). Mutations of the three RAS genes were detected in
codon 61 but not in
codons 12 and 13. There was a decreasing trend of RAS mutation rates associated with an increasing risk of
malignancy in the FNAC diagnostic categories. The triage efficacy of FNAC to make a recommendation for surgery was 73% for encapsulated
tumors and 79% for infiltrative
tumors. Addition of
galectin-3 or the BRAF test to FNAC showed no significant improvement in the triage efficacy. However, RAS mutations significantly improved the triage efficacy of FNAC. There was no significant difference in the triage efficacy of FNAC,
galectin-3 expression, and the prevalence of somatic mutations between encapsulated and infiltrative
tumors.
CONCLUSION: Thyroid FNAC has a low sensitivity for the detection of FVPTC regardless of histologic subtype. Encapsulated FVPTC and infiltrative FVPTC have similar molecular profiles and rates of
galectin-3 expression. RAS mutational analysis is more useful than BRAF testing to improve the triage efficacy of FNAC for FVPTC.