Monica M DiLorenzo1, Jeffrey L Miller2, Madalina Tuluc3, Zi-Xuan Wang3, Vincent W Savarese2, Edmund A Pribitkin1. 1. Department of Otolaryngology, Head, and Neck Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania. 2. Department of Endocrinology, Thomas Jefferson University, Philadelphia, Pennsylvania. 3. Department of Pathology, Thomas Jefferson University, Philadelphia, Pennsylvania.
Abstract
OBJECTIVE: False-positive BRAF analysis on fine-needle aspiration (FNA) has rarely been reported in the literature but may become more common with the advent of assays that can detect the BRAF V600E mutation in only 2% of otherwise wild-type thyroid cells. We present the case of an indeterminate BRAF-positive FNA that showed no evidence of cancer on final surgical pathology. METHODS: Case report and literature review. RESULTS: An 87-year-old female with an indeterminate 1.7-cm nodule but BRAF-positive cytology underwent thyroid lobectomy. Final pathology revealed a benign adenomatoid nodule. An area rich in tumor cells from the nodule was identified, labeled, and microdissected for molecular testing, which demonstrated only wild-type BRAF, at the analytical limit of the assay. CONCLUSION: Increasingly sensitive BRAF assays using dual-priming oligonucleotide-based multiplex polymerase chain reaction analysis can detect the BRAF V600E mutation when present in only 2% of a population of wild-type cells. This increases the risk of false-positive results, particularly in cases of indeterminate FNA. Clinicians must caution patients in these circumstances that BRAF molecular testing may not have a 100% positive predictive value.
OBJECTIVE: False-positive BRAF analysis on fine-needle aspiration (FNA) has rarely been reported in the literature but may become more common with the advent of assays that can detect the BRAFV600E mutation in only 2% of otherwise wild-type thyroid cells. We present the case of an indeterminate BRAF-positive FNA that showed no evidence of cancer on final surgical pathology. METHODS: Case report and literature review. RESULTS: An 87-year-old female with an indeterminate 1.7-cm nodule but BRAF-positive cytology underwent thyroid lobectomy. Final pathology revealed a benign adenomatoid nodule. An area rich in tumor cells from the nodule was identified, labeled, and microdissected for molecular testing, which demonstrated only wild-type BRAF, at the analytical limit of the assay. CONCLUSION: Increasingly sensitive BRAF assays using dual-priming oligonucleotide-based multiplex polymerase chain reaction analysis can detect the BRAFV600E mutation when present in only 2% of a population of wild-type cells. This increases the risk of false-positive results, particularly in cases of indeterminate FNA. Clinicians must caution patients in these circumstances that BRAF molecular testing may not have a 100% positive predictive value.