Factors affecting the risk of malignancy in patients with thyroid fine needle aspiration biopsy results and follicular lesions of undetermined significance

Aim; Thyroid nodules are among the most frequently detected lesions. The importance of their follow-up lies in their malignant potential. The Bethesda classification is commonly used to guide follow-up and treatment strategies. However, Bethesda category III nodules remain the most indeterminate group in terms of clinical management, and the literature demonstrates considerable heterogeneity in this category. Factors contributing to this variability include differences in patient populations, as well as the experience of clinicians, radiologists, and pathologists, and referral patterns across centers. The aim of this thesis is to identify the factors influencing the risk of malignancy in thyroid nodules reported as "atypia of undetermined significance/follicular lesion of undetermined significance" (Bethesda category III) on fine-needle aspiration biopsy. It also seeks to define predictive parameters that may contribute to the management of this group and to evaluate whether the data from our institution are consistent with findings reported in the literature. Methods; In our study, patients who underwent thyroidectomy between December 31, 2013, and December 31, 2023, were retrospectively reviewed. The study included patients aged 18–80 years whose preoperative fine-needle aspiration biopsy results were reported as atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS), who had no chronic renal disease, chronic liver disease, active infectious disease, hematological disorder, or corticosteroid (prednisolone) use, and whose pathological specimens were adequate for evaluation. Demographic characteristics, laboratory results, ultrasonographic findings, pathological data, comorbidities, and thyroid treatment processes were assessed and recorded. Results; A total of 336 nodules with an initial cytological diagnosis of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) and subsequent thyroidectomy were identified within the study cohort. Of the patients, 288 were female and 48 were male. The mean age was 48.6 ± 11.7 years. Younger age and <55 years (p<0.001),euthyroid status (p=0.004), hypoechogenic appearance (p=0.016), solid composition (p=0.004), irregular margins (p=0.001), relatively smaller nodule size (p=0.010), and the presence of an additional malignancy (p=0.008) were found to be significantly associated with malignancy in Bethesda category III nodules. In univariate logistic regression analysis, nodule length (p=0.011) and size (p=0.020), composition (p=0.004), margin regularity (p=0.001), echogenicity (p=0.002), and age grouping (p=0.046) were significantly associated with malignancy; however, significance did not persist in multivariate regression analysis. Conclusion; In our center, the rate of AUS diagnoses was found to be 23%, which is higher than the recommended percentage. The malignancy rate among AUS cases (31.1%) was consistent with the literature. The observation that Bethesda category III nodules were malignant in patients with a primary malignancy represents a novel and valuable contribution to the literature. Although the significance of subpathological categories within AUS has been emphasized in many studies, sufficient differentiation could not be achieved in our study. In conclusion, patients with an additional malignancy, ultrasonographic findings, and age should be carefully evaluated in terms of malignancy risk. Our analyses further demonstrated, through multivariate regression, that multiple parameters should be considered together when assessing the risk of malignancy. Keywords; Bethesda classification, atiypia of undetermined significance (AUS), Follicular lesion of undetermined significance (FLUS), thyroid nodule, fine-needle aspiration biopsy (FNAB)