Cytological Sub-Classification of Atypia of Undetermined Significance May Predict Malignancy Risk in Thyroid Nodules

Abstract

<b><i>Background:</i></b> Atypia/follicular lesion of undetermined significance (AUS/FLUS) carries a malignancy risk reaching up to 50%. Based on the reported malignancy rate in a given population, the clinical practice towards such a category varies. We hereby identify clinical parameters for risk stratification to aid in decision-making for either surgical referral or a clinical follow-up. Our aim is to identify clinical parameters that guided both clinicians and patients at our institutions to reach a clinical decision including atypia types. <b><i>Methods:</i></b> A retrospective review of patients with Bethesda III category thyroid nodules from tertiary centres in the Emirate of Abu Dhabi during January 2011 through December 2015 was carried out. Malignancy risk in Bethesda category III nodules and repeat FNA utility were calculated. Parameters that guided both clinicians and patients for appropriate referral to surgery were studied. <b><i>Results:</i></b> Two hundred and two cases were included in the study. Of these, 101 cases underwent surgery initially following the first FNA and 10 cases following FNA repeat. Histology confirmed malignancy in (41%) of cases that went initially to surgery and in (40%) of cases that underwent a repeat FNA. Repeat FNA resulted in 17 (44.74%) cases being re-classified into benign category, 10 (26.3%) being AUS/FLUS category, 6 (15.7%) being both suspicious and malignant, and 5 (13.16%) being unsatisfactory. Repeating FNA resulted in a definitive diagnostic utility in 50% of the cases. Eighty percent of malignant cases demonstrated nuclear atypia. <b><i>Conclusion:</i></b> The relatively high malignancy rate in our institutions, the suspicious radiographic features, the atypia groups, and the repeat FNA predictive value stratified Bethesda III category nodules for proper malignancy prediction and appropriate management.

Performance of Afirma genomic sequencing classifier and histopathological outcome in Bethesda category III thyroid nodules: Initial versus repeat fine‐needle aspiration

“…Several studies have demonstrated the importance of repeat FNA in thyroid nodules with an initial AUS diagnosis. Repeat FNA establishes a definitive diagnosis (TBSRTC category II or VI) in up to 50% of nodules with an initial diagnosis of AUS, reducing unnecessary surgical intervention in benign nodules and providing useful pre‐operative information for malignant nodules 10,11,15,16 . However, a notable portion of nodules remained as AUS after repeat aspiration.…”

“…2 In more recent years, molecular testing incorporated with FNA evaluation has played an important role in further stratification and management of indeterminate thyroid nodules. 6,7 Among several commercially available tests, the Afirma Genomic Sequencing Classifier (GSC) was introduced in 2017, and uses next-generation sequencing, incorporating an ensemble model composed of 12 independent classifiers (10,196 genes with 1115 core genes) and 7 other components (parathyroid, medullary thyroid carcinoma, BRAFV600E, RET/PTC1 and RET/PTC3 detection modules, oncocytic cell index and oncocytic neoplasm index). Compared with its predecessor, the Gene Expression Classifier (GEC), the newer GSC has demonstrated improved specificity and positive predictive value (PPV) while maintaining a high sensitivity and negative predictive value (NPV).…”

“…Studies of TBSRTC category III thyroid nodules reported that repeating FNA resulted in a definitive diagnostic entity in 45%-50% of the cases, in which nearly 45% were recategorized into benign category. 10,11 A case series from one institution suggested repeat FNA cytology can help optimize molecular testing for a subset of cytologically indeterminate thyroid nodules. 12 Accordingly, performing Afirma GEC only on nodules with repeat Bethesda III/IV cytology would reduce the rate of surgery for benign nodules.…”

“…These findings indicate that the pretest probability of malignancy (thus the performance characteristics of Afirma GSC) is similar whether (1) an endocrinologist/surgeon's assessment of concerning clinical/sonographic features is used to refine the selection of a nodule for potential molecular testing based on the initial AUS diagnosis or (2) repeat diagnosis of AUS is used to refine the selection of a nodule for potential molecular testing.Several studies have demonstrated the importance of repeat FNA in thyroid nodules with an initial AUS diagnosis. Repeat FNA establishes a definitive diagnosis (TBSRTC category II or VI) in up to 50% of nodules with an initial diagnosis of AUS, reducing unnecessary surgical intervention in benign nodules and providing useful pre-operative information for malignant nodules 10,11,15,16. However, a notable portion of nodules remained as AUS after repeat aspiration.…”

Atypia and Follicular Lesions of Undetermined Significance in Subsequent Biopsy Result: What Clinicians Need to Know

“…ROM of AUS/FLUS diagnosis according to TBSRTC (2017) is estimated to be 10–30% if noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is considered malignant, and 6–18% if excluding NIFTP from the malignant group [ 3 , 4 ]. However, some authors suggest higher malignancy risk, reaching up to 50% [ 10 ], and even after excluding NIFTP [ 11 ]. Based on the various ROM rates, the clinical practice towards AUS/FLUS category varies.…”