Nodule size is an independent predictor of malignancy in mutation-negative nodules with follicular lesion of undetermined significance cytology.
BACKGROUND
In thyroid nodule fine-needle aspiration (FNA) cytology, the atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS) category has a 5-15% malignancy risk that increases to 85-99% when mutation testing for BRAF, RAS, RET/PTC, or PAX8/PPARγ is positive. However, negative testing does not exclude malignancy. The study objective was to identify clinical and imaging features that predict cancer in mutation-negative AUS/FLUS thyroid nodules.


METHODS
All patients were reviewed (April 2007 to April 2009) who had AUS/FLUS cytology, negative prospective molecular testing of FNA, and histopathology.


RESULTS
Of the 230 nodules, 12 (5.2%) were malignant in 11 of 190 patients, and known clinical risk factors for thyroid cancer did not predict malignancy. On preoperative imaging, ≥1 suspicious ultrasound feature was identified in 33% of nodules and occurred regardless of histology (P = .23). Malignant mutation-negative AUS/FLUS nodules were larger than benign nodules (mean maximum diameter, 33.6 vs 24.0 mm; P = .007). On multivariate analysis, nodule size remained an independent predictor of malignancy (odds ratio, 1.043; P = .018). We observed no malignancies in 88 mutation-negative AUS/FLUS nodules <18.5 mm.


CONCLUSIONS
Size is an independent predictor of malignancy in mutation-negative AUS/FLUS nodules and the risk increased 4.3% with every millimeter increase in nodule size. Selected patients with small, mutation-negative AUS/FLUS thyroid nodules may be managed with ultrasound surveillance in lieu of thyroidectomy.
Department of Surgery, University of Pittsburgh, Pittsburgh, PA.
Rohtesh S
RS
Mehta
Sally E
SE
Carty
N Paul
NP
Ohori
Steven P
SP
Hodak
Christopher
C
Coyne
Shane O
SO
LeBeau
Mitchell E
ME
Tublin
Michael T
MT
Stang
Jonas T
JT
Johnson
Kelly L
KL
McCoy
Marina N
MN
Nikiforova
Yuri E
YE
Nikiforov
Linwah
L
Yip
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044963:Biopsy, Fine-Needle; D002648:Child; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D013964:Thyroid Neoplasms / Q000473:pathology*; D016606:Thyroid Nodule / Q000235:genetics / Q000473:pathology*