The value of ACR, European, Korean, and ATA ultrasound risk stratification systems combined with RAS mutations for detecting thyroid carcinoma in cytologically indeterminate and suspicious for malignancy thyroid nodules

Abstract

Purpose: The aim of this study was to evaluate the diagnostic value of four commonly utilized ultrasound (US) RSSs, namely, the American College of Radiology [ACR], European [EU], Korean [K] TI-RADSs and American Thyroid Association [ATA] US-based RSS criteria, in combination with activating point mutations of the RAS genes (NRAS, HRAS, and KRAS) for detection of thyroid carcinoma in cytologically indeterminate and suspicious for malignancy thyroid nodules.

Methods: We retrospectively analyzed cytologically indeterminate and suspicious for malignancy thyroid nodules which underwent US, molecular testing and surgery between September 1, 2018, and December 31, 2023. Receiver operating characteristic (ROC) curves were generated, and the area under the curve (AUC, 95% confidence interval [CI]) was calculated.

Results: A total of 100 cytologically indeterminate and 24 suspicious for malignancy thyroid nodules were analyzed. Compared to the four US-based RSSs alone, the diagnostic value of the four US-based RSSs combined with RAS mutations did not significantly improved (cytologically indeterminate, AUC [95% CI] 0.6 [0.5-0.7] and 0.6 [0.5-0.7], respectively, p = 0.70; cytologically suspicious for malignancy, AUC [95% CI] 0.7 [0.5-0.9] and 0.8 [0.6-0.9], respectively, p = 0.23).

Conclusions: The diagnostic value of the four main US-based RSSs (ACR, EU, K, and ATA) was not improved in conjunction with the evaluation of RAS mutations for preoperative risk stratification of cytologically indeterminate thyroid nodules.

Clinical relevance statement: In cytologically indeterminate nodules categorized according to US-based RSSs, isolated RAS positivity does not reliably distinguish between benignity and malignancy.

Keywords: Indeterminate thyroid cytology; RAS; TIRADS.

Fig. 1

Flowchart of patients’ selection. US, ultrasound; TIRADSs, Thyroid Imaging Reporting and Data Systems; ACR, American College of Radiology; EU, European; K, Korean; ATA, American Thyroid Association; MTC, medullary thyroid carcinoma; PDTC/ATC, poorly differentiated and anaplastic thyroid carcinoma; TL, thyroid lymphoma

Fig. 2

Receiver operating characteristic (ROC) curves for ACR, European, Korean and ATA ultrasound risk stratification systems combined with RAS testing in cytologically suspicious for malignancy (TIR4) (A) and indeterminate (TIR3) (B) thyroid nodules

Fig. 3

Malignancy rates stratified by sonographic risk categorizations according to ACR, European, Korean and ATA ultrasound risk stratification systems alone and by sonographic risk categorizations in conjunction with RAS test results (A for TIR4 nodules and B for TIR3 nodules). In the first branch, malignancy rates were reported for sonographic risk categories alone (sonographically very low/low/intermediate suspicion nodules and sonographically high suspicion nodules) before RAS test results (pretest malignancy rates). Nodules from each sonographic category were then assigned a RAS marker test outcome (BCRs and SCRs). New malignancy rates were reported for each sonographic risk category after receiving RAS test results (post-test malignancy rates). BCR, Benign call rates; SCR, suspicious call rates