Preoperative diagnosis of benign thyroid nodules with indeterminate cytology.
BACKGROUND
Approximately 15 to 30% of thyroid nodules evaluated by means of fine-needle aspiration are not clearly benign or malignant. Patients with cytologically indeterminate nodules are often referred for diagnostic surgery, though most of these nodules prove to be benign. A novel diagnostic test that measures the expression of 167 genes has shown promise in improving preoperative risk assessment.


METHODS
We performed a 19-month, prospective, multicenter validation study involving 49 clinical sites, 3789 patients, and 4812 fine-needle aspirates from thyroid nodules 1 cm or larger that required evaluation. We obtained 577 cytologically indeterminate aspirates, 413 of which had corresponding histopathological specimens from excised lesions. Results of a central, blinded histopathological review served as the reference standard. After inclusion criteria were met, a gene-expression classifier was used to test 265 indeterminate nodules in this analysis, and its performance was assessed.


RESULTS
Of the 265 indeterminate nodules, 85 were malignant. The gene-expression classifier correctly identified 78 of the 85 nodules as suspicious (92% sensitivity; 95% confidence interval [CI], 84 to 97), with a specificity of 52% (95% CI, 44 to 59). The negative predictive values for "atypia (or follicular lesion) of undetermined clinical significance," "follicular neoplasm or lesion suspicious for follicular neoplasm," or "suspicious cytologic findings" were 95%, 94%, and 85%, respectively. Analysis of 7 aspirates with false negative results revealed that 6 had a paucity of thyroid follicular cells, suggesting insufficient sampling of the nodule.


CONCLUSIONS
These data suggest consideration of a more conservative approach for most patients with thyroid nodules that are cytologically indeterminate on fine-needle aspiration and benign according to gene-expression classifier results. (Funded by Veracyte.).
Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. ekalexander@partners.org
Erik K
EK
Alexander
Giulia C
GC
Kennedy
Zubair W
ZW
Baloch
Edmund S
ES
Cibas
Darya
D
Chudova
James
J
Diggans
Lyssa
L
Friedman
Richard T
RT
Kloos
Virginia A
VA
LiVolsi
Susan J
SJ
Mandel
Stephen S
SS
Raab
Juan
J
Rosai
David L
DL
Steward
P Sean
PS
Walsh
Jonathan I
JI
Wilde
Martha A
MA
Zeiger
Richard B
RB
Lanman
Bryan R
BR
Haugen
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D014408:Biomarkers, Tumor / Q000235:genetics; D044963:Biopsy, Fine-Needle; D003937:Diagnosis, Differential; D004311:Double-Blind Method; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011446:Prospective Studies; D012333:RNA, Messenger / Q000032:analysis; D012680:Sensitivity and Specificity; D013961:Thyroid Gland / Q000473:pathology*; D016606:Thyroid Nodule / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D055815:Young Adult
D014408:Biomarkers, Tumor; D012333:RNA, Messenger