Cancer prevalence in the subcategories of the indeterminate class III (AUS/FLUS) of the Bethesda system for thyroid cytology: a meta-analysis

Purpose The indeterminate cytologic report represents a major challenge in the field of thyroid nodule. The indeterminate class III of the Bethesda classification system (i.e., AUS/FLUS) includes a heterogeneous group of subcategories characterized by doubtful nuclear and/or architectural atypia. The study aim was to conduct a systematic review and meta-analysis to evaluate the rate of malignancy in each subcategory of Bethesda III. Methods PubMed, CENTRAL, and Scopus databases were searched until April 2020. Original articles reporting data on the subcategories of Bethesda III were included. The histological diagnosis was the reference standard to classify true/false negative and true/false positive cases. Results The pooled cancer prevalence in each subcategory of Bethesda III was estimated using a random-effects model. Twenty-three papers with 4241 nodules were included. Overall, 1163 (27.4%) were malignant. The cancer rate observed in the subcategories ranged from 15%, in “Hürthle cell aspirates with low risk pattern”, to 44%, in “Focal cytologic atypia”. Conclusions The overall cancer rate found in the Bethesda III ranged more largely than that originally estimated (10–30%) and varied among any scenarios. These evidence-based data represent a reference for the clinical management of these patients.