Subcategorization of Bethesda System Category III by Ultrasonography

Bethesda System category III (atypia of undetermined significance/follicular lesion of undetermined significance [AUS/FLUS]) creates a dilemma because of heterogeneity. The aim of this study was to assess whether ultrasonography (US) contributes to differentiating AUS from FLUS and may suggest characteristics of malignancy within category III.

From April 2011 to April 2012, 433 thyroid nodules that had been interpreted as nuclear atypia (AUS group; n = 322) or microfollicular architecture (FLUS group; n = 111) were included in the retrospective study. Final diagnoses were acquired in 327 nodules after surgery and clinico-radiological follow-up. The AUS group and FLUS group were compared in terms of US features (composition, echogenicity, margin, shape, and calcifications), US diagnosis (probably benign, malignant), malignancy rate, and final malignant histology.

In univariate and multivariate analysis, the AUS group more frequently had non-circumscribed margins, taller-than-wide shape, and an US diagnosis suggestive for malignancy than the FLUS group did. The risk of malignancy was significantly higher in the AUS group than it was in the FLUS group (51.0% vs.8.1%; p < 0.001). There was a significant difference in the presence of a BRAF mutation between the AUS group and the FLUS group (47.6% vs. 4.2%; p < 0.001). Of the patients with malignancy, papillary thyroid carcinoma was found more frequently in the AUS group than in the FLUS group (97.7% vs. 66.7%; p = 0.004). The incidence of follicular thyroid carcinoma was significantly higher in the FLUS group than it was in the AUS group (33.3% vs.1.6%; p = 0.004).

Bethesda System category III subcategorization into AUS and FLUS can be supported by US features. In Bethesda III nodules, US features may further help in predicting a malignant histology.