Young Investigator Challenge: Molecular testing in noninvasive follicular thyroid neoplasm with papillary-like nuclear features.

Background: Molecular testing provides an important ancillary study for thyroid nodules with indeterminate cytology. The nomenclature shift to "noninvasive follicular thyroid neoplasm with papillary-like nuclear features" (NIFTP) will impact the performance of molecular tests. For the current study, the authors reviewed the performance of the Afirma gene-expression classifier (GEC) and the University of Pittsburgh Medical Center (UPMC) targeted mutation panel tests in thyroid nodules that were subsequently diagnosed as NIFTP on surgical resection.

Methods: In total, 302 nodules were sent for molecular testing between June 2012 and June 2016. These cases were retrospectively reviewed to identify patients who underwent subsequent surgical resection and were diagnosed with follicular variant of papillary thyroid carcinoma (FVPTC). Twenty-five nodules that were diagnosed as FVPTC met the initial inclusion criteria. These cases were reviewed using strict criteria to identify NIFTP.

Results: Eight cases met criteria for NIFTP, and 4 NIFTPs underwent Afirma testing. Cytology diagnoses were all Bethesda category III, with 3 diagnosed as atypia of undetermined significance (AUS) and 1 diagnosed as follicular lesion of undetermined significance (FLUS). All of these nodules were identified as "suspicious" using GEC. Four NIFTPs underwent testing at UPMC, all using ThyroSeq V2. The cytology diagnoses for these nodules also were category III, with the exception of 1 nodule that was category IV, suspicious for follicular neoplasm. All NIFTPs were positive for mutations, all of which were RAS mutations (NRAS, KRAS). One patient who had a nodule classified as NIFTP had metastatic carcinoma identified in a lymph node. Another who had a 6-cm tumor had coexisting NRAS and TERT mutations.

Conclusions: The current results indicate that NIFTP is a rare tumor if defined by strict criteria, that both the GEC and UPMC methods indicate abnormalities in NIFTP, and further independent study will be needed to better characterize the molecular and clinical characteristics of NIFTP. Cancer Cytopathol 2016;124:893-900. © 2016 American Cancer Society.