“Atypia of Undetermined Significance/Follicular Lesion of Undetermined Significance” in Bethesda System for Reporting Thyroid Cytopathology: Prediction of Malignant Risk in Subcategories with BRAF Mutation Results
Jiyeon Hyeon, Soomin Ahn, Young Lyun Oh. Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
Background: The “Atypia of Undetermined Significance/Follicular Lesion of Undetermined Significance (AUS/FLUS)” category in the Bethesda System for Reporting Thyroid Cytopathology is a heterogeneous category of cases that are not clearly benign or malignant.
Design: We conducted a retrospective analyses correlating cytologic and histologic evaluation of thyroid nodules which were interpreted as 'AUS/FLUS' category on initial fine needle aspiration (FNA) in our institution for 13 months. The cases in AUS/FLUS category were classified into two subgroups according to the predominance of nuclear atypia (AUS) or microfollicular architecture (FLUS). Additionally, in a proportion of those cases, analyses for BRAF gene mutations were performed.
Results: Of 6402 thyroid FNAs, 551 (8.6%) were diagnosed as AUS/FLUS. Of the 551 cases, 431 (6.7% of 6402) were AUS and 120 (1.9% of 6402) were FLUS. Follow up cytologic or histologic outcome data were available for 388 cases which consisted of 315 AUS and 73 FLUS. Of 388 cases, repeated FNA without histologic evaluation were performed in 157 cases and they were diagnosed as follows: unsatisfactory, 1.9%; benign, 59.9%; AUS/FLUS, 21.6%; suspicious for a follicular neoplasm, 2.5%; suspicious for malignancy, 5.1% and malignancy, 8.9%. Histologic confirmation with or without repeated FNA data were obtained in 231 cases, of which 74 (32%) were benign and 157 (68%) were malignant. In the AUS, 21.2% (41/193) were benign and 78.8% (152/193) were malignant on histologic outcome. In contrast, in the FLUS, 86.8% (33/38) were benign and 13.2% (5/38) were malignant on histologic outcome (P<.001). Meanwhile, in the AUS/FLUS, 135 cases had adequate BRAF mutation analysis results and were accompanied with histologic diagnosis. BRAF mutations were found in 87 AUS cases, 86 of which were papillary carcinoma. In contrast, there was no BRAF mutation in FLUS. In correlating the molecular results with histologic outcome, we found that the cancer probability for AUS cases with BRAF mutation was 98.9%, while the cancer probability for those cases without BRAF mutation was 68.8% (P<.001).
Conclusions: The subcategory 'AUS' indicates a higher risk of malignancy than subcategory 'FLUS'. Therefore, it is important to report the subcategorized group of AUS/FLUS with potential clinical implication. In addition, BRAF molecular test is helpful in predicting malignant risk of AUS cases.
Tuesday, March 5, 2013 1:00 PM
Poster Session IV # 89, Tuesday Afternoon