Current Evidence, Selective Indications, and the Role of Lymph-Node Assessment in Intraoperative Frozen Section in Thyroid Cancer Surgery: A Literature Review

TL;DR

This review examines when intraoperative frozen section is still useful in thyroid cancer surgery, finding it most valuable for central lymph-node assessment in papillary thyroid carcinoma.

Contribution

The paper provides a comprehensive synthesis of over two decades of evidence to clarify the current role of intraoperative frozen section in thyroid cancer surgery.

Findings

Frozen section has high specificity but limited sensitivity in Bethesda III–IV and V cytology, offering minimal help in cases with high preoperative uncertainty.

Frozen section reliably detects macrometastases in central compartment lymph nodes of papillary thyroid carcinoma, enabling real-time surgical adjustments.

Intraoperative assessment of desmoplastic stromal reaction in medullary thyroid carcinoma shows promise as a prognostic marker but remains investigational.

Abstract

Background/Objective: Intraoperative frozen section (FS) has long been used in thyroid surgery; however, its routine usefulness has shrunk with high-resolution ultrasound, standardized cytology, and molecular diagnostics. This narrative review synthesizes >20 years of evidence to clarify where FS still adds clinically meaningful value and where it does not. Methods: This study constitutes a narrative review of the contemporary literature spanning more than two decades, integrating prospective and retrospective evidence on FS performance in indeterminate/suspicious cytology (Bethesda III–V), NIFTP recognition, central compartment lymph nodes in papillary thyroid carcinoma (PTC), and prognostic intraoperative markers in medullary thyroid carcinoma (MTC). It also examines how guidelines and emerging technologies influence intraoperative decision-making. Results: FS shows high specificity but limited sensitivity in Bethesda III–IV and Bethesda V cytology, offering minimal incremental diagnostic help in the settings with greatest preoperative uncertainty. FS cannot diagnose NIFTP because definitive classification requires complete capsular examination, incompatible with intraoperative pathology workflows. The most consistent value is FS of central compartment lymph nodes in PTC: it reliably detects macrometastases, enables real-time tailoring of surgical extent, and may reduce staged completion operations. In MTC, intraoperative assessment of desmoplastic stromal reaction appears promising as a prognostic marker; however, it remains investigational and not yet embedded in standard surgical algorithms. Guidelines internationally therefore de-emphasize routine FS. Meanwhile, evolving tools (quantitative imaging, molecular profiling, AI) are reshaping intraoperative decision-support, increasingly positioning FS as one component of a multimodal framework rather than a standalone arbiter. Conclusions: Routine FS is largely unsupported in modern risk-stratified thyroid practice due to the low sensitivity in key cytologic gray zones and inability to diagnose NIFTP. Its selective strength persists most clearly in central neck lymph-node assessment in PTC, where it can directly change intraoperative management. Future operative strategies will likely treat FS as an adjunct—contextualized and amplified by imaging, molecular data, and AI—rather than as a default diagnostic step.