Testing for BRAF (V600E) Mutation in Thyroid Nodules with Fine-Needle Aspiration (FNA) Read as Suspicious for Malignancy (Bethesda V, Thy4, TIR4): a Systematic Review and Meta-analysis

In patients with thyroid fine-needle aspiration (FNA) report of suspicious for malignancy (SFM), both lobectomy and thyroidectomy might be considered. BRAF mutation analysis could guide towards accurate surgical therapy. The primary outcome was the reliability of BRAF (V600E) in detecting malignancy in nodules with FNA reading of SFM. The secondary outcome was to analyze its positive predictive value (PPV) and negative predictive value (NPV) considering the surgical histology as gold standard. A literature search of online databases was performed in June 2019. BRAF prevalence among thyroid nodules with FNA read as SFM according to the most popular classification systems (i.e., Bethesda V, Thy4, TIR4 category) was searched. The random-effects model was used. Three hundred sixty original articles were identified and 34 were finally included in the study. There were 1428 thyroid nodules with FNA read as SFM and 1287 (90.1%) lesions underwent surgery with a cancer rate 89.6%. The pooled prevalence of BRAF (V600E) mutation among all nodules with SFM cytology was 47% (95% CI = 40 to 54, I2 = 85.5%). Pooled PPV and NPV of BRAF testing were 99% (95% CI, 97-99) and 24% (95% CI, 16-32), respectively. BRAF (V600E) mutation was found in about one in two nodules with thyroid FNA read as SFM, its PPV to detect cancers was excellent, and its NPV was very poor. The routine BRAF testing in FNA read as SFM cannot be recommended. BRAF (V600E) test may be useful to extend surgical approach in selected cases with further suspicious clinical/ultrasound features.