Highlights
- •AUS/FLUS thyroid nodules were subclassified into major or minor concern of cancer.
- •Risk of malignancy in the major vs. minor concern group was 58.4% vs. 12.6% (P-value <0.001).
- •Inter-pathologist agreement for subclassifying AUS/FLUS nodules was 79%, and the κ value = 0.47.
- •Subclassifying AUS/FLUS cases allows for better preop thyroid nodule cancer risk estimation.
Abstract
Background
The objective of this study was to the assess the risk of malignancy in thyroid lesions
that were diagnosed as AUS/FLUS when using a novel cytology subclassification system
that is based on the presence or absence of papillary features.
Methods
AUS/FLUS case cytology was re-reviewed and subclassified into minor or major concern
groups based upon the absence or presence of papillary features, respectively. The
risk of malignancy (ROM) was calculated and compared between the two groups. Inter-pathologist
agreement in case subclassification was also measured.
Results
The minor concern group had a 12.6% associated ROM, while the major concern group
had a significantly higher ROM (58.4%), (P < 0.001). Based on 108 cases, the inter-pathologist agreement in case subclassification
was 79%, and the κ value was 0.47.
Conclusions
The identification of papillary features significantly increases the ROM in thyroid
lesions with an AUS/FLUS diagnosis.
Graphical abstract

Graphical Abstract
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to The American Journal of SurgeryAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Predictors of malignancy in thyroid nodules classified as Bethesda Category III.Front Endocrinol. 2022; 13 (10.3389/fendo.2022.806028)806028https://doi.org/10.3389/fendo.2022.806028
- Diagnosis of endocrine disease: usefulness of genetic testing of fine-needle aspirations for diagnosis of thyroid cancer.Eur J Endocrinol. 2022; 187 (10.1530/EJE-21-1293): R41-R52https://doi.org/10.1530/EJE-21-1293
- Incidental thyroid nodules on CT: evaluation of 2 risk-categorization methods for work-up of nodules.AJNR Am J Neuroradiol. 2013; 34: 1812-1817https://doi.org/10.3174/ajnr.A3487
- Risk of malignancy according to sub-classification of the atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS) category in the Bethesda system for reporting thyroid cytopathology.Cytopathology. 2017; 28: 65-73https://doi.org/10.1111/cyt.12352
- The impact of implementation of the Bethesda System for Reporting Thyroid Cytopathology on the quality of reporting, "risk" of malignancy, surgical rate, and rate of frozen sections requested for thyroid lesions.Cancer Cytopathol. 2011; 119: 315-321https://doi.org/10.1002/cncy.20174
- Thyroid cytology-nuclear versus architectural atypia within the "Atypia of undetermined significance/follicular lesion of undetermined significance" Bethesda category have significantly different rates of malignancy.Cancer Cytopathol. 2017; 125: 245-256https://doi.org/10.1002/cncy.21823
- Subclassification of the Bethesda category III (AUS/FLUS): a study of thyroid FNA cytology based on ThinPrep slides from the national cancer center in China.Cancer Cytopathol. 2021; 129: 642-648https://doi.org/10.1002/cncy.22417
- 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.Cancer Cytopathol. 2014; 122: 368-376https://doi.org/10.1002/cncy.21396
- Subclassification of Bethesda atypical and follicular neoplasm categories according to nuclear and architectural atypia improves discrimination of thyroid malignancy risk.Thyroid. 2018; 28: 511-521https://doi.org/10.1089/thy.2017.0274
- Risk stratification of thyroid nodules with atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) cytology using ultrasonography patterns defined by the 2015 ATA Guidelines.Ann Otol Rhinol Laryngol. 2017; 126: 625-633https://doi.org/10.1177/0003489417719472
- 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?.J Cytol. 2020; 37: 204-209https://doi.org/10.4103/JOC.JOC_5_20
- The presence of papillary features in thyroid nodules diagnosed as atypia of undetermined significance or follicular lesion of undetermined significance increases cancer risk and should influence treatment.Am J Surg. 2018; 215: 819-823https://doi.org/10.1016/j.amjsurg.2017.12.018
- The 2017 Bethesda system for reporting thyroid cytopathology.Thyroid. 2017; 27: 1341-1346https://doi.org/10.1089/thy.2017.0500
- Clinical impact of second opinion in thyroid fine needle aspiration cytology (FNAC): a study of 922 interinstitutional consultations.Diagn Cytopathol. 2012; 40: 422-429https://doi.org/10.1002/dc.21820
- Subclassification of "atypia of undetermined significance" in thyroid fine-needle aspirates.Diagn Cytopathol. 2014; 42: 23-29https://doi.org/10.1002/dc.23052
- Usefulness of diagnostic qualifiers for thyroid fine-needle aspirations with atypia of undetermined significance.Am J Clin Pathol. 2011; 136: 572-577https://doi.org/10.1309/AJCPO0BQ2YSKPXXP
- Cancer risk associated with nuclear atypia in cytologically indeterminate thyroid nodules: a systematic review and meta-analysis.Thyroid. 2018; 28: 210-219https://doi.org/10.1089/thy.2017.0419
- A simplified Bethesda System for reporting thyroid cytopathology using only four categories improves intra- and inter-observer diagnostic agreement and provides non-overlapping estimates of malignancy risks.Diagn Cytopathol. 2012; 40: E62-E68https://doi.org/10.1002/dc.21697
- Reproducibility of atypia of undetermined significance/follicular lesion of undetermined significance category using the Bethesda System for reporting thyroid cytology when reviewing slides from different institutions: a study of interobserver variability among cytopathologists.Diagn Cytopathol. 2017; 45: 399-405https://doi.org/10.1002/dc.23681
- Inter- and intraobserver reproducibility of thyroid fine needle aspiration cytology: an analysis of discrepant cases.Cytopathology. 2007; 18: 105-111https://doi.org/10.1111/j.1365-2303.2006.00430.x
- A tertiary center's experience with second review of 3885 thyroid cytopathology specimens.J Clin Endocrinol Metab. 2013; 98: 1450-1457https://doi.org/10.1210/jc.2012-3898
- A prospective assessment defining the limitations of thyroid nodule pathologic evaluation.Ann Intern Med. 2013; 159: 325-332https://doi.org/10.7326/0003-4819-159-5-201309030-00006
- Benign call rate and molecular test result distribution of ThyroSeq v3.Cancer Cytopathol. 2019; 127: 161-168https://doi.org/10.1002/cncy.22088
- Cancer risk estimation using American college of radiology thyroid imaging reporting and data system for cytologically indeterminate thyroid nodules.Am J Surg. 2022; 224: 653-656https://doi.org/10.1016/j.amjsurg.2022.02.061
- Preoperative diagnosis of thyroid nodules using the Bethesda System for Reporting Thyroid Cytopathology: a comprehensive review and meta-analysis.Expet Rev Endocrinol Metabol. 2014; 9: 97-110https://doi.org/10.1586/17446651.2014.887435
Article info
Publication history
Published online: February 26, 2023
Accepted:
February 23,
2023
Received in revised form:
December 6,
2022
Received:
November 9,
2022
Publication stage
In Press Journal Pre-ProofIdentification
Copyright
© 2023 Elsevier Inc. All rights reserved.