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?

Abstract

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.

A Comprehensive Approach to the Thyroid Bethesda Category III (AUS) in the Transition Zone Between 2nd Edition and 3rd Edition of The Bethesda System for Reporting Thyroid Cytopathology: Subcategorization, Nuclear Scoring, and More

“…AUS-A subcategory and AUS-A2 subgroup significantly indicated BNs on histological examination. Considering the relationship of three-dimensional groups with high ROM, which is emphasized in some previous studies [ 31 , 32 ] and in the current study, perhaps architectural atypia, as well as nuclear atypia, may be nature-defining. So, detailed definition of architectural features as well as nuclear scoring and raising awareness in terms of three-dimensional groups may be useful in the correct evaluation of thyroid cytology.…”

“…The NS2 was significantly more common in FNAs of BNs. Guleria et al [ 31 ] and Kaymaz et al [ 32 ] used similar nuclear scoring models as in the current study and showed that the NS2-3 group was more frequently associated with malignancy. However, in these studies, ROM of NSs were not presented separately, and their focal/diffuse status was not evaluated.…”

“…And also, three-dimensional groups show the highest ROM value with close to significance. Gularia et al [ 31 ] and Kaymaz et al [ 32 ] showed that cases containing a three-dimensional group had higher ROM values. So, a more skeptical investigation of FNAs with three-dimensional groups for an additional evidence of malignancy may be argued.…”

“…Additionally, the authors stated that the presence of four or more atypical nuclear features or coexistence of nuclear grooves and inclusions may be associated with malignancy. Kaymaz et al stated that membrane irregularities such as pseudoinclusion, nuclear contour irregularity, and nuclear grooves were associated with malignancy, and also, nuclear elongation and overlapping were predictive for malignancy [ 32 ]. FNAs with nuclear grooves revealed the highest risk of malignancy, and in multivariate analysis, the presence of nuclear grooves resulted as an independent significant predictor for malignancy with the highest value of odds ratio as the authors have reported.…”

Predictors of Malignancy in Thyroid Nodules Classified as Bethesda Category III

“…Kaymaz et al. ( 24 ) reviewed the pathologic results of 209 AUS/FLUS nodules and found that the overall rate of malignancy was 27.8%, which decreased to 26.4% if only the nodules with nuclear atypia were assessed. This suggests that all nuclear properties are not equally effective in predicting the malignancy risk.…”