False-negative BRAF V600E mutation results on fine-needle aspiration cytology of papillary thyroid carcinoma

Abstract

BackgroundThe BRAF V600E mutation is highly specific for papillary thyroid carcinoma (PTC). A test for this mutation can increase the diagnostic accuracy of fine-needle aspiration cytology (FNAC), but a considerably high false-negative rate for the BRAF V600E mutation on FNAC has been reported. In this study, we investigated the risk factors associated with false-negative BRAF V600E mutation results on FNAC.MethodsBRAF V600E mutation results of 221 PTC nodules between December 2011 and June 2013 were retrospectively reviewed. BRAF V600E mutation results on both preoperative FNAC and postoperative formalin-fixed, paraffin-embedded (FFPE) samples were compared. We investigated the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of BRAF V600E mutation results on FNAC. And, we identified the risk factors associated with false-negative results.ResultsOf 221 PTC nodules, 150 (67.9%) on FNAC and 185 (83.7%) on FFPE samples were BRAF V600E mutation positive. The sensitivity, specificity, PPV, and NPV for BRAF V600E mutation testing with FNAC were 80.5, 97.2, 99.3, and 49.3%, respectively. Thirty-six (16.3%) BRAF V600E mutation-negative nodules on FNAC were mutation positive on FFPE sample analysis. Risk factors for these false-negative results were age, indeterminate FNAC results (nondiagnostic, atypia of undetermined significance (AUS), and findings suspicious for PTC), and PTC subtype.ConclusionFalse-negative rate of BRAF mutation testing with FNAC for thyroid nodules is increased in cases of old age, indeterminate FNAC pathology results, and certain PTC subtypes. Therapeutic surgery can be considered for these cases. A well-designed prospective study with informed consent of patients will be essential for more informative results.

Nomograms for the prediction of lateral lymph node metastasis in papillary thyroid carcinoma: Stratification by size

“…LND is only recommended for PTC patients with positive FNAC-proven LLNM according to the ATA guidelines ( 1 ). Notably, ultrasound-guided FNAC is not available in some institutions, and the false-negative rate of FNAC can be as high as 16.7% ( 15 ). Accurate evaluation factor for LLNM is necessary for distinguishing high-risk PTC patients.…”

<p>MFAP2 is a Potential Diagnostic and Prognostic Biomarker That Correlates with the Progression of Papillary Thyroid Cancer</p>

“…Thanks to the discovery of the role BRAF played in PTC, the accuracy of FNAC (Fine Needle Aspiration cytology) to diagnose PTC increased rapidly when detection of BRAF mutation was included as an index. 19,20 However, several studies have demonstrated that it is not enough to diagnose PTC only with BRAF V600E alone. 21,22 So, there has been increasing effort to search for other gene mutations that are highly correlated with PTC and we have made great achievements.…”

A comparative analysis of eight machine learning models for the prediction of lateral lymph node metastasis in patients with papillary thyroid carcinoma

“…Consecutive patients who underwent initial thyroid resection at our institution between January 2019 and March 2022 were reviewed. The exclusion criteria were as follows: (1) non-PTCs or other subtypes than classic PTC; (2) history of prior treatment for head and neck cancer; (3) history of cervical radiation exposure in childhood; (4) family history of thyroid cancer; (5) history with other malignancy; (6) incomplete clinical data; (7) loss to follow-up; (8) patients who underwent non-curative surgery (residual tumor or lymph node detected within 6 months of initial surgery). A total of 1236 patients were enrolled in this study.…”

“…However, the diagnostic sensitivity of ultrasound to cervical LNM is only about 20% to 40% ( 5 , 6 ). And the false negative rate of FNAC can be as high as 16.7% ( 7 ). Hence, occult LLNM has been reported to occur in up to 55% of PTC patients with clinically negative (cN0) lateral neck ( 8 ).…”