title: Evaluation of ThyroSeq v2 performance in thyroid nodules with indeterminate cytology.
abstract: ThyroSeq v2 claims high positive (PPV) and negative (NPV) predictive values in a wide range of pretest risks of malignancy in indeterminate thyroid nodules (ITNs) (categories B-III and B-IV of the Bethesda system). We evaluated ThyroSeq v2 performance in a cohort of patients with ITNs seen at our Academic Cancer Center from September 2014 to April 2016, in light of the new diagnostic criteria for non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). Our study included 182 patients (76% female) with 190 ITNs consecutively tested with ThyroSeq v2. Patient treatment followed our institutional thyroid nodule clinical pathway. Histologies of nodules with follicular variant papillary thyroid carcinoma or NIFTP diagnoses were reviewed, with reviewers blinded to molecular results. ThyroSeq v2 performance was calculated in nodules with histological confirmation. We identified a mutation in 24% (n =45) of the nodules. Mutations inRASwere the most prevalent (n =21), but the positive predictive value of this mutation was much lower (31%) than that in prior reports. In 102 resected ITNs, ThyroSeq v2 performance was as follows: sensitivity 70% (46-88), specificity 77% (66-85), PPV 42% (25-61) and NPV 91% (82-97). The performance in B-IV nodules was significantly better than that in B-III nodules (area under the curve 0.84 vs 0.57, respectively;P= 0.03), where it was uninformative. Further studies evaluating ThyroSeq v2 performance are needed, particularly in B-III.
authors.affiliation: Department of Head and Neck-Endocrine OncologyH. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA pablo.valderrabano@moffitt.org.
authors.forename: Pablo
authors.initials: P
authors.lastname: Valderrabano
authors.affiliation: Department of Anatomic PathologyH. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
authors.forename: Laila
authors.initials: L
authors.lastname: Khazai
authors.affiliation: Department of Anatomic PathologyH. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
authors.forename: Marino E
authors.initials: ME
authors.lastname: Leon
authors.affiliation: Department of Biostatistics and BioinformaticsH. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
authors.forename: Zachary J
authors.initials: ZJ
authors.lastname: Thompson
authors.affiliation: Department of Biostatistics and BioinformaticsH. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
authors.forename: Zhenjun
authors.initials: Z
authors.lastname: Ma
authors.affiliation: Department of Head and Neck-Endocrine OncologyH. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
authors.forename: Christine H
authors.initials: CH
authors.lastname: Chung
authors.affiliation: Department of Head and Neck-Endocrine OncologyH. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
authors.forename: Julie E
authors.initials: JE
authors.lastname: Hallanger-Johnson
authors.affiliation: Department of Head and Neck-Endocrine OncologyH. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
authors.forename: Kristen J
authors.initials: KJ
authors.lastname: Otto
authors.affiliation: Department of Head and Neck-Endocrine OncologyH. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
authors.forename: Kara D
authors.initials: KD
authors.lastname: Rogers
authors.affiliation: Department of Anatomic PathologyH. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Centeno
authors.affiliation: Department of Head and Neck-Endocrine OncologyH. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
authors.forename: Bryan
authors.initials: B
authors.lastname: McIver
mesh_terms: D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques; D011237:Predictive Value of Tests; D013964:Thyroid Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D016606:Thyroid Nodule / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology
keywords: molecular diagnosis; non-invasive follicular thyroid neoplasms with papillary-like nuclear features; thyroid cancer; thyroid cytology; thyroid genetics; thyroid nodules