Significance of FNAC, BRAF mutation, and intraoperative frozen section in surgical decision-making of thyroid nodules

Zhaohui Zhu; Chang Su; Guang Chen; Fang Wan; Meishan Jin; Xiumei Duan; Yongxiang Wang; Guimin Wang

doi:10.1002/dc.25135

Significance of FNAC, BRAF mutation, and intraoperative frozen section in surgical decision-making of thyroid nodules

Diagn Cytopathol. 2023 Jul;51(7):441-448. doi: 10.1002/dc.25135. Epub 2023 Apr 12.

Authors

Zhaohui Zhu^{1

2}, Chang Su², Guang Chen², Fang Wan², Meishan Jin³, Xiumei Duan³, Yongxiang Wang⁴, Guimin Wang²

Affiliations

¹ Department of Thyroid and Breast Surgery, The Affiliated Huaian Hospital of Xuzhou Medical University, Huaian, China.
² Department of General Surgery Center, The First Hospital of Jilin University, Changchun, China.
³ Department of Pathology, The First Hospital of Jilin University, Changchun, China.
⁴ Department of Laboratory Medicine, The First Hospital of Jilin University, Changchun, China.

PMID: 37042168
DOI: 10.1002/dc.25135

Abstract

Background: A preoperative method is desired to discriminate benign from malignant thyroid nodules. This retrospective study evaluated the diagnostic performance of BRAF (B-Raf proto-oncogene) mutation (BRAF^V600E ) positivity and fine-needle aspiration cytology (FNAC) relative to intraoperative frozen section pathology.

Methods: Patients underwent preoperative FNAC of thyroid nodules. Cytology specimens were classified according to the Bethesda System for Reporting Thyroid Cytopathology (BSRTC), and analyzed for BRAF^V600E using an amplification-refractory mutation system (ARMS). Thyroid tissue was surgically removed and frozen sections processed for histology. The sensitivities and specificities of each analysis were compared, alone and in combination.

Results: Among 346 patients, 333/358 FNACs (93%) showed malignant nodules; 322 (93%) patients received a pathological diagnosis of papillary thyroid carcinoma (PTC). The sensitivity and specificity of BSRTC VI for malignancy was the highest among the BSRTC categories. Compared with FNAC, the BRAF^V600E analysis had significantly higher sensitivity and specificity. The diagnostic efficacy of frozen section pathology was significantly higher than that of either BSRTC category or BRAF^V600E analysis alone. Combining methods variably improved diagnostic performance. BRAF^V600E was not associated with capsule infiltration, neurovascular infiltration, mono- or multifocal PTC, lymph node metastasis, or clinical stage.

Conclusion: The diagnostic performance of preoperative BRAF^V600E determination was better than that of the BSRTC-FNAC category; combining both improved sensitivity and specificity. Patients with positive malignancy scores from both should be recommended for surgery; those with negative scores require close monitoring. Surgical treatment should include comprehensive intraoperative frozen section assessment. BRAF mutations cannot indicate aggressive treatment.

Keywords: BRAF mutation; Bethesda System for Reporting Thyroid Cytopathology; fine-needle aspiration; frozen section pathology; thyroid nodules.

MeSH terms

Biopsy, Fine-Needle / methods
DNA Mutational Analysis / methods
Frozen Sections
Humans
Mutation
Proto-Oncogene Proteins B-raf / genetics
Retrospective Studies
Thyroid Cancer, Papillary / genetics
Thyroid Neoplasms* / diagnosis
Thyroid Neoplasms* / genetics
Thyroid Neoplasms* / surgery
Thyroid Nodule* / diagnosis
Thyroid Nodule* / genetics
Thyroid Nodule* / surgery

Substances

Proto-Oncogene Proteins B-raf
BRAF protein, human