Is subdivision of Atypia of Undetermined Significance AUS/Follicular lesion of undetermined significance cases according to detailed nuclear features vital for assessing the risk of malignancy?

Background: It has been known that the "atypia of undetermined significance (AUS)/follicular lesion of undetermined significance (FLUS)" category is the most problematic category in Bethesda system due to its highly heterogeneous morphological features. Recently, it has been reported that aspirates including nuclear atypia in the AUS/FLUS category have a higher risk of malignancy. Aims: This study aimed to assess each nuclear property in aspirates with cytological atypia and also to determine the relationship with the risk of malignancy. Material and Methods: We reviewed 980 AUS/FLUS fine-needle aspirations (FNAs) performed between '2012 and 2019' at a single institution. We classified these aspirates into four groups: AUS-N (nuclear atypia), AUS-A (architectural atypia), AUS-H (Hurthle cell change), and AUS-O (other). Nuclear features were detailed sub-classified; size and shape (enlargement, elongation, and overlapping), membrane irregularities (irregular contours, grooves, pseudoinclusion), and chromatin characteristics (pale chromatin). The estimated risk of malignancy (ROM) was calculated for each subgroup. Results: Of 980 AUS/FLUS cases, follow-up histological outcome data were available for 209 cases. Among these cases, the estimated ROM was 27.8%. The ROM were 26.4%, 15.4%, and 22.5% for AUS-N, A, and H, respectively. The most common nuclear findings associated with ROM were nuclear groove (67.9%); irregular contours (76.9%) suspected pseudoinclusion (100%) and overlapping (56%) (P < 0,001). But nuclear findings such as nuclear enlargement, mild pleomorphism, or pale chromatin have a similar ROM as architectural atypia. Conclusion: Although it is known that the presence of cytological atypia in an AUS/FLUS nodule increases the estimated risk of malignancy, all nuclear properties are not equally effective in predicting malignancy risk. Emphasizing nuclear atypia details in reports of AUS case may be a more sensitive way to identify nodules with a high risk of malignancy.