Thyroid atypia of undetermined significance or follicular lesion of undetermined significance: an indispensable Bethesda 2010 diagnostic category or waste garbage?

Objective: The Bethesda System for Reporting Thyroid Cytopathology (BSRTC) was introduced in thyroid cytology in 2007 and is now generally accepted. BSRTC categories include a morphologic description and risk of malignancy as well as follow-up suggestions in each group. However, the category entitled 'atypia of undetermined significance or follicular lesion of undetermined significance' (AUS/FLUS) is problematic. This category is heterogeneous and has been overused so far.

Study design: Twenty-six studies were included in a meta-analysis. In addition to AUS/FLUS percentage, we analysed repeated AUS/FLUS percentage, cytological and histological correlations, and risk of malignancy and neoplasm for AUS/FLUS. Furthermore, stratification, inter- and intra-observer variability, and the possibility of a switch to another category and its clinical consequences were reviewed.

Results: Out of a total of 81,833 cases, AUS/FLUS accounted for 10.9%, with a 34% risk of malignancy. Persistent AUS/FLUS was found in 21.6% in repeated cytology. Cytohistological correlation was analysed from 16 studies (4,964 cases), revealing 10.4% as AUS/FLUS and a 21.5% risk of malignancy.

Conclusions: An AUS/FLUS category seems to be currently reasonable with clearly defined cytomorphological criteria which do not correspond unequivocally with those of the other categories. An AUS/FLUS category is justified and possible means of its improvement with immunohistochemistry, molecular analysis and imaging are discussed.