Histopathological findings of 687 thyroid nodules, suspicious for malignancy on ultrasound, with an indeterminate cytopathological diagnosis after the combination of the Bethesda System and BRAF mutation status.

Objective: The conflicting results of the Bethesda system for reporting thyroid cytopathology (BSRTC) and B-Raf proto-oncogene (BRAF) mutation status during pre-operative fine-needle aspiration cytology (FNAC) of thyroid nodules create a dilemma for clinicians in devising appropriate treatment strategies for patients. This study provides a report on the histopathological findings of 687 thyroid nodules with an indeterminate cytological diagnosis after the combination of the BSRTC and BRAF mutation status.

Material and methods: The clinical data of patients with thyroid nodules, suspicious of malignancy at ultrasound (US), who underwent US-guided FNAC between December 2020 and March 2023 at our cancer center were reviewed. Patients with an indeterminate diagnosis, that is, conflicting results of the BSRTC and BRAF mutation status after FNAC, were enrolled. The following four combinations of BSRTC and BRAF mutation status were considered indeterminate: (1) Group 1, BSRTC I and positive for a BRAF mutation; (2) Group 2, BSRTC II and positive for a BRAF mutation; (3) Group 3, BSRTC III and positive for a BRAF mutation; and (4) Group 4, BSRTC V and negative for a BRAF mutation. Finally, only patients who underwent surgical treatment at our center were included in the data analysis.

Results: Among the 1,044 eligible patients, 687 underwent surgical treatment. Of the 687 patients, 117 were in Group 1, 14 in Group 2, 394 in Group 3, and 162 in Group 4. Histopathological examination showed that 677 (98.5%) patients had papillary thyroid cancer, including 585 with papillary thyroid microcarcinoma, whereas only 10 (1.5%) had benign nodules. The malignancy rates were 98.3%, 100%, 98.7%, and 98.1% for Groups 1 to 4, respectively. Among the 387 patients in category 4A by the thyroid imaging reporting and data system (TI-RADS 4A) through the US, the malignancy rate was 98.4%, and for the 116 nodules <5 mm in diameter in the US, the malignancy rate was 99.1%. When combining TI-RADS 4A and a nodule diameter <5 mm, the malignancy rate was 98.9% (88/89). A total of 179 patients (26.1%) had histopathologically confirmed central cervical lymph node metastasis, and 46 (6.8%) had lateral cervical lymph node metastasis. Two nodules in Group 1, five nodules in Group 3, and three nodules in Group 4 were determined to be benign post-surgery. The benign thyroid nodules included seven dysplastic, one adenomatous, one fibrotic, and one hyperplastic.

Conclusion: Thyroid nodules, suspicious of malignancy on US, after the combined interpretation of BSRTC and BRAF mutation status following pre-operative FNAC had a high risk of malignancy. Repeat US-guided FNAC for indeterminate thyroid nodules is highly recommended in clinical practice.