Follow-up of atypia and follicular lesions of undetermined significance in thyroid fine needle aspiration cytology.

To report our experience of atypia of undetermined significance (AUS)/follicular lesion of undetermined significance (FLUS) rate and outcome. Among 7658 patients with 19 569 nodules, 524 (2.7%) nodules were diagnosed as AUS/FLUS on fine needle aspiration (FNA). After exclusion of patients with simultaneous nodules that were suspicious for follicular neoplasm or malignancy or that were malignant, 368 (4.8%) patients were diagnosed as AUS/FLUS. The outcome of 146 patients who had undergone surgery or repeated fine needle aspirate at the time of preparation of this study was evaluated. The original FNAs were matched to repeated FNAs and thyroidectomy or diagnostic lobectomy specimens. Seventy-two (19.6%) of the 368 patients had directly undergone surgery, either a lobectomy or a thyroidectomy: of these, 27 (37.5%) had neoplastic nodules (21 were malignant). Seventy-four (20.1%) of the 368 patients had repeat FNA. On second FNA, 47 of 74 (63.5%) were benign, three were suspicious for follicular neoplasm, one was malignant and 23 (31.1%) were non-diagnostic. Four patients had a third FNA: two were AUS/FLUS, one was malignant and one non-diagnostic. One patient had a fourth FNA, which was diagnosed as AUS/FLUS. Sixteen (21.6%) of 74 patients with repeat FNA had surgery: three of these had neoplastic nodules (two were malignant). Overall, 88 of the 368 (23.9%) patients had a thyroidectomy of which 30 (34.1%) were neoplastic and 23 (26.1%) malignant. The neoplastic rate for patients who were once diagnosed with AUS/FLUS was 8.2% and the malignancy rate 6.3%. The malignancy rate for patients on follow-up at the time we prepared the study was 15.7% (23/146); 222 remained on follow-up without surgery or repeat FNA or were managed elsewhere. Although in this category repeat FNA is expected rather than excision, we suggest evaluation of all AUS/FLUS patients in multidisciplinary meetings to decide management and recommend follow-up of all patients with this diagnosis.

Dincer N ，Balci S ，Yazgan A ，Guney G ，Ersoy R ，Cakir B ，Guler G ... -  《-》

Malignancy rate in thyroid nodules classified as Bethesda category III (AUS/FLUS).

Ho AS ，Sarti EE ，Jain KS ，Wang H ，Nixon IJ ，Shaha AR ，Shah JP ，Kraus DH ，Ghossein R ，Fish SA ，Wong RJ ，Lin O ，Morris LG ... -  《-》

The impact of atypia/follicular lesion of undetermined significance and repeat fine-needle aspiration: 5 years before and after implementation of the Bethesda System.

Limited studies have examined the impact of the Bethesda System for Reporting Thyroid Cytopathology (BSRTC) and specifically the category of atypia or follicular lesion of undetermined significance (AUS/FLUS). We studied their effects on reporting rates, subsequent management, and surgical outcome over a 10-year period, 5 years before and after implementation of the BSRTC. A retrospective review of thyroid fine-needle aspiration (FNA) reports from 2003 to 2012 was performed. Diagnoses made before BSRTC were reclassified into the most appropriate category. Repeat FNA results for all AUS/FLUS cases were recorded. Surgical follow-up results were matched by side and size of the targeted nodule. Incidental microcarcinomas were not considered "malignant" on excision. Malignancy rates were calculated based on excision and by all aspirated specimens. Initial AUS/FLUS cases increased from 3% to 7% (P = .001) with implementation of the BSRTC. The nondiagnostic rate decreased from 19% to 10% (P = .026). Differences in malignancy rates before and after implementation of the BSRTC were not significant for all diagnostic categories. More repeat FNAs and fewer surgical excisions were performed after an initial AUS/FLUS diagnosis. Repeat FNA reclassified 56% of AUS/FLUS cases into a definitive category. The malignancy risks for AUS/FLUS plus benign and AUS/FLUS plus AUS/FLUS repeat FNAs were elevated compared with single benign and AUS/FLUS diagnoses. AUS/FLUS cases are increasing with the implementation of the BSRTC. Given the potential increase in repeat FNAs as a result, it may be important to alert the clinician regarding the elevated malignancy risk of a benign or AUS/FLUS diagnosis associated with a prior AUS/FLUS finding.

Sullivan PS ，Hirschowitz SL ，Fung PC ，Apple SK ... -  《-》

Thyroid nodules classified as atypia or follicular lesions of undetermined significance deserve further research: Analysis of 305 surgically confirmed nodules.

The objective of the present study was to determine the malignancy risk for nodules categorised as atypia or follicular lesions of undetermined significance atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) and to investigate the predictors of malignancy. All nodules diagnosed as AUS/FLUS on fine needle aspiration (FNAs) performed between January 2011 and December 2015 were retrospectively reviewed. Clinical data, ultrasonographic features, follow-up data and the final pathological results were recorded. After further exclusion, only nodules that underwent surgical excision were included in the final analysis. The malignancy rate and the range of malignancy rates were calculated. Clinical and ultrasound features were examined to determine the predictors of malignancy. During the study period, FNA was performed on 9938 nodules, and 1019 (10.2%) nodules were diagnosed as AUS/FLUS. After further exclusion, 976 nodules were evaluated. After the initial diagnosis of AUS/FLUS, 139 (14.2%) patients underwent surgery, 518 (53.1%) had repeated FNAs. A total of 305 (31%) had undergone surgical excision at different time points. For surgically confirmed nodules, the malignancy rate after the initial FNA was 34.5% (the lower and upper thresholds for the malignancy rate were 19.3% and 66.3%, respectively), and 37.9% after the repeated FNA. No ultrasound feature was determined as a predictor, whereas age (>55 years) was a predictor for malignancy. The overall malignancy rate for nodules diagnosed as AUS/FLUS and the malignancy rate for nodules that underwent repeated FNA after AUS/FLUS were higher than the expected malignancy rates of the National Cancer Institute. It is, therefore, suggested that the current recommendations should be reconsidered.

Turkyilmaz S ，Ulusahin M ，Celebi B ，Cekic AB ，Mungan S ，Kucuktulu U ，Tasdelen A ，Guner A ，Cinel A ... -  《-》

The prediction of malignant risk in the category "atypia of undetermined significance/follicular lesion of undetermined significance" of the Bethesda System for Reporting Thyroid Cytopathology using subcategorization and BRAF mutation results.

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. We conducted an analysis of cytologic and histologic evaluations of thyroid nodules that had been interpreted as AUS/FLUS on fine-needle aspiration (FNA) at a single institution from April 2011 to April 2012. Those cases were classified into 2 subgroups according to the predominance of nuclear atypia (AUS) or microfollicular architecture (FLUS). In addition, for a number of these cases, BRAF gene mutation analyses were performed. Of 6402 thyroid FNAs performed, 431 cases were diagnosed as AUS and 120 as FLUS. Follow-up cytologic or histologic outcome data were available for 315 AUS cases and 73 FLUS cases. Among AUS cases, 52.7% were malignant on repeat FNA or histologic diagnosis. In contrast, for FLUS, 6.8% were malignant on repeat FNA or histologic diagnosis. Among AUS/FLUS cases, 147 had adequate BRAF mutation analysis, which accompanied the histologic diagnosis. BRAF mutations were found in 87 AUS cases, 86 of which were papillary carcinoma. In contrast, there was only 1 case of BRAF mutation in FLUS. Correlating molecular results with histologic outcome revealed a 98.9% cancer probability for AUS cases with BRAF mutation. The AUS subcategory indicates a higher risk of malignancy than the FLUS subcategory. Furthermore, BRAF molecular testing is helpful in stratifying the malignant risk of AUS cases into high-risk and low-risk groups.

Hyeon J ，Ahn S ，Shin JH ，Oh YL ... -  《-》