Utility of BRAF Gene Testing on Thyroid Nodules Diagnosed as Follicular Lesion of Undetermined Significance (FLUS)
Sue Chang, Ryan T Phan, Neda A Moatamed, Sophia K Apple. David Geffen School of Medicine at UCLA, Los Angeles, CA; VA Greater Los Angeles Health System, Los Angeles, CA
Background: The evaluation of thyroid nodules routinely begins with fine needle aspiration (FNA) to triage patient management based on the risk of malignancy. The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) has a category for borderline cases of follicular lesions that do not satisfy all criteria for malignancy. At our institution, we have a 3% rate of diagnosing a lesion as FLUS, based on a computerized search of 2972 cases from 2003-2007. Previous studies have shown that BRAF mutations variably occur in 46-69% of papillary thyroid carcinoma (PTC). Within certain histological subtypes of follicular variant PTC, 26% of cases have also been shown to contain the BRAF mutation. This study assess the value of BRAF mutation analysis by PCR in FNA specimens previously labeled as FLUS.
Design: From March 2007 to March 2011, 36 cases at our institution were diagnosed as FLUS and later had a surgical pathology tissue diagnosis. We used 8 benign and 11 malignant cases of FLUS that appeared to have adequate cells. Genomic DNA was extracted from cells on the previously stained cytology slides, and BRAF V600E mutation analysis was performed by a real-time PCR approach utilizing BRAF wild-type and V600E Taqman probes.
Results: Of the 19 cases selected based on cytology slides, 15 had sufficient DNA for mutation analysis. BRAF V600E mutation was detected in one case (6.7%), which was confirmed as PTC on surgical excision. None of the follicular variant PTC cases tested positive for BRAF mutation. When considering cases with sufficient DNA, the sensitivity of BRAF mutation to detect PTC is 11% and the negative predictive value is 43%. The positive predictive value and specificity are 100%.
|BRAF Mutation||PTC, any variant||Benign||TOTAL|