Value of biomarkers in distinguishing indeterminate core needle biopsy samples of thyroid nodules

Abstract

Background: Core needle biopsy (CNB) is now more frequently used for the preoperative diagnosis of thyroid nodules. Based on morphology alone, 5%-20% of CNB samples cannot be determined as malignant or benign. Compared to fine-needle biopsy (FNB), samples collected by CNB are more accessible for various tests. Therefore, studying the application of biomarkers in distinguishing indeterminate CNB samples of thyroid nodules is a practical need. Methods: Patients with thyroid nodules with both CNB and matched resected specimens were reviewed. Cases classified as indeterminate lesions, follicular neoplasms and suspicious for malignancy were retrieved. All CNB samples were stained by immunohistochemistry (IHC) using antibodies against CK19, Galectin-3, HBME-1, and CD56 and detected by next-generation sequencing (NGS) using a target panel. With the help of these biomarkers, all CNB samples were reclassified. Taking the classification of resected specimens as the gold standard, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of each biomarker for discriminating malignancy from benignity were calculated. Results: The sensitivity, specificity, PPV, NPV and accuracy were 93.55%, 60.00%, 93.55%, 60.00% and 88.89% for CK19; 93.55%, 40.00%, 90.63%, 50.00% and 86.11% for Galectin-3; 77.42%, 100.00%, 100.00%, 41.67% and 80.56% for HBME-1; 66.13%, 100.00%, 100.00%, 32.26% and 70.83% for CD56; and 91.94%, 100.00%, 100.00%, 66.67% and 93.06% for pathogenic mutation. Conclusions: The application of biomarkers is very effective in distinguishing indeterminate CNB samples of thyroid nodules. Gene testing by NGS using a target panel has very high accuracy. The limitation of tumor quantity is the main reason for the weakened power of NGS. IHC plays an important role in cases with negative NGS results. The combination of NGS and IHC is a reliable “rule in” test for malignancy.