Enhancing diagnostic accuracy with core needle biopsy and immunohistochemistry in indeterminate thyroid nodules: a retrospective diagnostic accuracy study

Abstract

Purpose Accurate preoperative cancer diagnosis is important for establishing treatment strategies. Core needle biopsy (CNBx) has become the second diagnostic tool for previously indeterminate cytology by fine-needle aspiration (FNA), such as Bethesda III or IV, but uncertainty remains. Immunohistochemistry (IHC) can offer improved diagnostic accuracy by staining patterns of specific markers. This study aimed to evaluate the usefulness of CNBx combined with various IHC methods for indeterminate nodules. Methods We retrospectively reviewed 233 patients who underwent CNBx + IHC and were previously classified as Bethesda III/IV at FNA. The sensitivity, specificity, and accuracy of CNBx + 4 IHC markers were analyzed to assess the prediction of malignancy risk. Additionally, we performed IHC staining on both preoperative and postoperative specimens and compared their concordance. Results CNBx with galectin-3 (GAL-3), Hector Battifora mesothelial-1 (HBME-1), cytokeratin 19 (CK-19), and cluster of differentiation 56 (CD56) increased the diagnostic accuracy up to 65.5%, 76.4%, 51.3%, and 67.7%, respectively. Among the individual markers, HBME-1 showed the highest sensitivity (75.0%), whereas CD56 showed the highest specificity (91.7%). The combination of GAL-3, HBME-1, and CK-19 yielded the highest overall diagnostic accuracy (86.7%). A 2-marker combination, GAL-3 + HBME-1, presented fair accuracy of 80.6%. The concordance rates of the IHC staining results before and after surgery were moderate (κ = 0.448, P = 0.001) for HBME-1, slight (κ = 0.168, P = 0.227) for GAL-3, fair (κ = 0.263, P = 0.109) for CK-19, and fair (κ = 0.222, P = 0.180) for CD56. Only HBME-1 showed agreement significantly greater than chance. Conclusion IHC staining is cost-effective and simpler than commercially available molecular testing and may help reduce diagnostic uncertainty.