Thyroid Molecular Testing: Sensitivity Versus Specificity and the Distinction Between Neoplastic Entities

Summary: Introduction: Molecular testing of indeterminate thyroid nodules serves as a tool towards enhanced patient care through adding data points towards an even more accurate pre-operative risk of malignancy (ROM). Our institution recently adopted ThyroSeq-v3 as our thyroid molecular platform and chose to retrospectively examine ThyroSeq data in our cohort. Materials and Methods: Cases with ThyroSeq-v3 testing and follow-up surgical pathology results were included (11/23-03/24). Data on demographics, Bethesda diagnosis, and molecular alteration categories was tabulated (Table1, Figure1). Sensitivity (SN), specificity (SP), positive and negative predictive value (PPV, NPV) were calculated (Table2). Results: Sixty-one fine needle aspiration (FNA) cytology cases were submitted for ThyroSeq testing during the study timeframe. Of which, 18 had histopathology. Majority of cases that underwent surgery displayed positive ThyroSeq results (16/18, 88.9%). Eight cases displayed low-risk (RAS-like) ROM; the remaining 8 cases displayed copy-number-alteration (CNA) (indeterminate ROM) (Fig1). All ""low-risk/RAS-like"" cases displayed neoplastic histology: 3 benign- 2 follicular adenomas (FA), 1 oncocytic adenoma (OA), and 5 Malignant or non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP)- 2 follicular variant (FV) of papillary thyroid carcinoma (PTC), 1 encapsulated-FVPTC, 1 NIFTP, 1 PTC. All CNA cases showed benign histopathology (4/8 FA, 2/8 OA, 2/8 non-neoplastic). ThyroSeq showed 100% SN and NPV, however, SP and PPV were low (15.3% and 31.2% respectively) (table 1). Conclusions: In our cohort we found ThyroSeq to be a sensitive test with a high NPV, and therefore could be used reliably as a rule-out test for malignancy to avoid unnecessary surgery in cases displaying negative molecular results. However, due to the non-discrimination between benign and malignant neoplastic entities, molecular findings could not be further utilized to predict tumor type or other prognostic information. Our study will be followed up on a larger sample to explore the possibility of additional SP/PPV once the data becomes available.