MON-LB097 The Genomic Landscape of Preoperative FNAs Positive for the Afirma GSC Medullary Thyroid Cancer Classifier

Background The Afirma Genomic Sequencing Classifier (GSC) uses RNA sequencing to assess FNA specimens from cytologically indeterminate thyroid nodules, which are also tested for specific molecular aberrations associated with thyroid cancer via a suite of highly accurate malignancy classifiers. This suite can also be applied independently to Bethesda V/VI nodules. The Afirma Xpression Atlas (XA) is an optional add-on test to GSC and the malignancy classifiers that reports nucleotide variants and fusions across 511 cancer-associated genes. Medullary thyroid cancer (MTC) is a rare subtype of thyroid cancer that can appear in every Bethesda category. Herein, we report the prevalence and genomic landscape of MTC classifier positive (MTC+) FNA samples in a CLIA certified clinical laboratory. Methods All Afirma GSC and malignancy classifier tests run between July 2017 and November 2018 were deidentified and examined for MTC+ cases. Afirma XA was run on all MTC cases and all variants and fusions were tabulated. Results Examination of 22,130 FNAs revealed 77 MTC cases. Among consecutive GSC tests, 28 were Bethesda III (0.16% out of 17,245) and 27 were Bethesda IV (0.65% out of 4,182). Provider-ordered testing was done on an additional 14 and 8 MTC cases from Bethesda V and VI nodules, respectively. Examining all MTC+ samples revealed that 55.8% harbored a RET variant (+/- others), 9.1% contained a KRAS variant (+/- others), 6.5% had an HRAS variant, 2.6% possessed fusions, and 26.0% included no variant/fusion. Conclusions In indeterminate FNA samples, the Afirma GSC can help to clarify the risk of MTC. In our cohort, the Afirma XA identified a variant or fusion in 74.0% of MTC+ FNAs. Limitations of this study include the lack of knowledge regarding germline RET status (which should be checked in all patients with an identified RET variant or confirmed MTC) and final pathology on MTC+ samples. Future studies may investigate how the preoperative identification of a known MTC driver mutation in a biopsy sample can inform the pre-operative evaluation, the surgical plan, and the potential role of targeted therapy. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. Abstracts presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.