Core Needle Biopsy (CNB) and Immunohistochemical Markers in Indeterminate Thyroid Nodules: Evidence and Perspectives

Thyroid nodules are a prevalent endocrine condition that requires accurate diagnostic tools to guide appropriate clinical management. Despite advances in imaging and cytology, evaluating thyroid nodules remains challenging, particularly in cases with indeterminate cytology. This narrative review examines the effectiveness of core needle biopsy (CNB) as a diagnostic approach, with a specific focus on its integration with immunohistochemical markers. CNB offers high diagnostic accuracy that improves with operator experience. The inclusion of immunohistochemical markers (CK19, CD56, Galectin-3, and HBME1) further enhances diagnostic precision, particularly in stratifying indeterminate nodules. However, CNB cannot reliably distinguish follicular adenoma from follicular carcinoma preoperatively because diagnosis requires evaluation of complete capsular and/or vascular invasion on the surgical specimen, which remains a fundamental limitation for follicular-patterned nodules. Despite its accuracy, broader adoption remains limited by non-standardized CNB protocols, inter-observer variability for IHC interpretation, and heterogeneous reimbursement policies across health systems, especially outside Western contexts. Comparative data on patient-reported outcomes and local cost-effectiveness in Asian and Indian settings are still variable and require multicenter validation before routine implementation can be generalized. The findings of this review reinforce the growing evidence that supports CNB as an effective diagnostic tool for thyroid nodules, especially when combined with immunohistochemical markers. This approach has the potential to improve diagnostic accuracy, reduce unnecessary surgical interventions, and enhance patient outcomes. Future research should focus on standardizing procedures and conducting large-scale validation studies.