title: Noninvasive Follicular Variant of Papillary Thyroid Carcinoma and the Afirma Gene-Expression Classifier.
abstract: It is now recognized that noninvasive follicular variant of papillary thyroid carcinoma (NFVPTC) is a distinct subset of FVPTC with an exceedingly indolent clinical course. The Afirma gene-expression classifier (GEC) helps guide clinicians in the management of thyroid nodules with indeterminate fine-needle aspiration (FNA) results. Thyroid surgery is recommended for nodules with a suspicious Afirma result, whereas observation is deemed reasonable for most nodules with a benign result. The aim of this study was to confirm that the Afirma test detects NFVPTCs and to determine how many carcinomas detected by the Afirma GEC represent NFVPTCs.
  
  
  
  From a database of 249 FNAs sent for Afirma testing between January 2012 and October 2014, a search was conducted for cases with a preceding FNA diagnosis of atypia/follicular lesion of undetermined significance (AUS/FLUS) or suspicious for a follicular neoplasm (SFN), a suspicious Afirma result, and a corresponding resection specimen reviewed at Brigham and Women's Hospital. The diagnoses of the prior FNAs and subsequent resection specimens were recorded. Slides for all resection specimens with a diagnosis of FVPTC were reviewed to identify NFVPTCs.
  
  
  
  Sixty-three cases met the inclusion criteria. The preceding FNA diagnosis was AUS/FLUS in 34 (54%) cases and SFN in 29 (46%) cases. The surgical resection specimen demonstrated 16 (25%) FVPTCs, five (8%) follicular thyroid carcinomas, one (2%) classical type PTC, and 41 (65%) benign tumors/nodules. Of the 16 FVPTCs, 14 (88%) were NFVPTCs. Thus, NFVPTCs accounted for 64% of the carcinomas in the cohort.
  
  
  
  These results indicate that the Afirma GEC detects NFVPTCs and that many of the carcinomas detected by Afirma are NFVPTCs. While all care should be individualized and include clinical and sonographic assessment, these results suggest lobectomy as opposed to total thyroidectomy should be considered for nodules with a preceding AUS/FLUS or SFN on cytology and a suspicious Afirma result.
authors.affiliation: 1 Department of Pathology, Brigham and Women's Hospital , Harvard Medical School, Boston, Massachusetts.
authors.forename: Kristine S
authors.initials: KS
authors.lastname: Wong
authors.affiliation: 2 Division of Endocrinology, Brigham and Women's Hospital , Harvard Medical School, Boston, Massachusetts.
authors.forename: Trevor E
authors.initials: TE
authors.lastname: Angell
authors.affiliation: 1 Department of Pathology, Brigham and Women's Hospital , Harvard Medical School, Boston, Massachusetts.
authors.forename: Kyle C
authors.initials: KC
authors.lastname: Strickland
authors.affiliation: 2 Division of Endocrinology, Brigham and Women's Hospital , Harvard Medical School, Boston, Massachusetts.
authors.forename: Erik K
authors.initials: EK
authors.lastname: Alexander
authors.affiliation: 1 Department of Pathology, Brigham and Women's Hospital , Harvard Medical School, Boston, Massachusetts.
authors.forename: Edmund S
authors.initials: ES
authors.lastname: Cibas
authors.affiliation: 1 Department of Pathology, Brigham and Women's Hospital , Harvard Medical School, Boston, Massachusetts.
authors.forename: Jeffrey F
authors.initials: JF
authors.lastname: Krane
authors.affiliation: 1 Department of Pathology, Brigham and Women's Hospital , Harvard Medical School, Boston, Massachusetts.
authors.forename: Justine A
authors.initials: JA
authors.lastname: Barletta
mesh_terms: D018263:Adenocarcinoma, Follicular / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D000328:Adult; D000368:Aged; D044963:Biopsy, Fine-Needle; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D015331:Cohort Studies; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011379:Prognosis; D012189:Retrospective Studies; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D016606:Thyroid Nodule / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D013965:Thyroidectomy / Q000379:methods; D055815:Young Adult