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Peer-reviewedCC BY-NCAnnals of surgical treatment and research

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

4 affiliations
  1. 1Division of Endocrine Surgery, Department of Surgery, Chung-Ang University Gwangmyeong Hospital, Chung-Ang University College of Medicine, Gwangmyeong, Korea.
  2. 2Division of Endocrine Surgery, Department of Surgery, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Korea.
  3. 3Department of Pathology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Korea.
  4. 4Division of Endocrinology, Department of Internal Medicine, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Korea.

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.

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BibTeX
@article{back2026enhancing,
  title = {{Enhancing diagnostic accuracy with core needle biopsy and immunohistochemistry in indeterminate thyroid nodules: a retrospective diagnostic accuracy study.}},
  author = {Kyorim Back and Ra-Yeong Song and Hee Sung Kim and Yun Jae Chung},
  journal = {Annals of surgical treatment and research},
  year = {2026},
  month = oct,
  doi = {10.4174/astr.2026.111.4.220},
  url = {https://europepmc.org/article/MED/42909164},
  note = {CC BY-NC},
}
RIS
TY  - JOUR
TI  - Enhancing diagnostic accuracy with core needle biopsy and immunohistochemistry in indeterminate thyroid nodules: a retrospective diagnostic accuracy study.
AU  - Kyorim Back
AU  - Ra-Yeong Song
AU  - Hee Sung Kim
AU  - Yun Jae Chung
PY  - 2026
DA  - 2026/10/08
JO  - Annals of surgical treatment and research
DO  - 10.4174/astr.2026.111.4.220
UR  - https://europepmc.org/article/MED/42909164
AB  - 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.
SN  - 2288-6575
SN  - 2288-6796
ER  -