Triage of patients with AUS/FLUS on thyroid cytopathology: effectiveness of the multimodal diagnostic techniques

The management of patients with thyroid cytopathologic diagnosis of atypia (or follicular lesion) of undetermined significance (AUS/FLUS) is a complex clinical problem. The purpose of this study was to develop a practical triage scheme based on multiple diagnostic tests in general use. We performed a retrospective cohort study involving 15,335 consecutive patients with a referral diagnosis of thyroid nodule between April 2011 and March 2015 using an institutional database. We obtained 904 patients with an initial cytopathologic diagnosis of AUS/FLUS who underwent repeat fine-needle aspiration or core needle biopsy, 388 of whom had a corresponding histopathological diagnosis for excised index lesions. The diagnostic performance of ultrasound (US) findings, repeat biopsy, and BRAF(V) (600E) mutation in cytopathologic specimens were evaluated individually or as a set. Of the 388 resected AUS/FLUS cases, 338 (87.1%) were thyroid cancer. The positive likelihood ratios (LRs) for BRAF(V) (600E) mutation and repeat biopsy result of suspicious for malignant cell (SMC) or worse were 11.6 (95% CI = 1.7-77.8) and 13.7 (95% CI = 4.6-41.0), respectively. The absence of suspicious findings on US combined with cytologic result of less than SMC or negative BRAF(V) (600E) mutation produced negative LRs ranging from 0.06 to 0.15, corresponding to negative predictive values of over 90% in both primary and referral settings. For patients with AUS/FLUS cytopathology, clinical decision making can be guided by a simple triage scheme based on US findings, repeat biopsy, or BRAF(V) (600E) mutation.