Background: The Bethesda System for Reporting Thyroid Cytopathology is the standard for interpreting fine needle aspiration (FNA) specimens. The “atypia of undetermined significance/follicular lesion of undetermined significance” (AUS/FLUS) category, known as Bethesda Category III, has been ascribed a malignancy risk of 5–15%, but the probability of malignancy in AUS/FLUS specimens remains unclear. Our objective was to determine the risk of malignancy in thyroid FNAs categorized as AUS/FLUS at a comprehensive cancer center. Methods: The management of 541 AUS/FLUS thyroid nodule patients treated at Memorial Sloan–Kettering Cancer Center between 2008 and 2011 was analyzed. Clinical and radiologic features were examined as predictors for surgery. Target AUS/FLUS nodules were correlated with surgical pathology. Results: Of patients with an FNA initially categorized as AUS/FLUS, 64.7% (350/541) underwent immediate surgery, 17.7% (96/541) had repeat FNA, and 17.6% (95/541) were observed. Repeat FNA cytology was...

/pdf/malignancy-rate-in-thyroid-nodules-classified-as-bethesda-2qhugue62n.pdf

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

Thyroid nodules are common. The clinical importance of thyroid nodules is related to excluding malignancy (4.0 to 6.5% of all thyroid nodules), evaluate their functional status and assess for the presence of pressure symptoms. Incidental thyroid nodules are being diagnosed with increasing frequency in the recent years with the use of newer and highly sensitive imaging techniques. The high prevalence of thyroid nodules necessitates that the clinicians use evidence-based approaches for their assessment and management. New molecular tests have been developed to help with evaluation of malignancy in thyroid nodules. This review addresses advances in thyroid nodule evaluation, and their management considering the current guidelines and supporting evidence.

/pdf/thyroid-nodule-update-on-diagnosis-and-management-1j8yixouf2.pdf

Thyroid nodule update on diagnosis and management.

Thyroid fine-needle aspiration has developed into a key test in the evaluation of thyroid nodules. Although the interpretation of thyroid aspirates containing mild abnormalities is problematic, the introduction of the atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) category in The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) has helped to delineate such cases in a systematic and clinically meaningful manner. Herein the authors review the cytomorphologic features associated with the AUS/FLUS interpretation and summarize the results of studies conducted since the implementation of TBSRTC.

https://acsjournals.onlinelibrary.wiley.com/doi/pdf/10.1002/cncy.20178

The atypical thyroid fine‐needle aspiration: Past, present, and future

BACKGROUND:

At present, thyroid fine-needle aspiration (FNA) specimens are diagnosed using a tiered classification scheme, with the most popular of these being the 5-tiered and 6-tiered systems. In this study, the authors present their institutional experiences using these 2 different systems and evaluate their efficacy based on the surgical follow-up.



METHODS:

Thyroid FNA specimens and their corresponding surgical resection specimens were collected between 2007 and 2009. The following diagnostic categories are used in both systems: unsatisfactory/nondiagnostic, benign, follicular neoplasm/suspicious for follicular neoplasm, suspicious for malignancy, and malignant. An additional category termed atypia of undetermined significance/follicular lesion of undetermined significance was used for atypical cases in the 6-tiered system. Statistical analysis was performed by comparing the different diagnostic categories.



RESULTS:

The case cohort included a total of 7686 thyroid FNA specimens representing 3962 nodules and 3724 nodules, respectively, in the 5-tiered and 6-tiered systems. Negative predictive values for the benign categories (96.9% vs 97.5%; P = 1) and positive predictive values for both the follicular neoplasm categories (26.5% vs 32.1%; P = .2531) and the malignant categories (99.1% vs 99.4%; P = 1) were similar. The most significant differences between the 5-tiered and 6-tiered systems were the percentage of cases classified as benign (83.9% vs 55.4%; P < .0001) and as follicular neoplasms (4.6% vs 23.8%; P < .0001). It is interesting to note that fewer patients were referred for surgery in the 5-tiered system compared with the 6-tiered one (9.1% vs 36.5%; P < .0001).



CONCLUSIONS:

Use of either the 5-tiered or 6-tiered reporting systems for thyroid FNA specimens can potentially affect the clinical management of patients with thyroid nodules. Cancer (Cancer Cytopathol) 2012. © 2011 American Cancer Society.

Comparison of 5-tiered and 6-tiered diagnostic systems for the reporting of thyroid cytopathology: a multi-institutional study.

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.



METHODS

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.



RESULTS

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.



CONCLUSIONS

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. Cancer (Cancer Cytopathol) 2014;122:368–376. © 2014 American Cancer Society.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/cncy.21396

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.

BACKGROUND:
Atypia of undetermined significance is a controversial category in thyroid fine-needle aspiration (FNA), not only for its questioned clinical utility, but also for its very existence as an expression of uncertainty. The current study was performed to investigate the potential impact of eliminating this category on the sensitivity and specificity for detecting thyroid neoplasms by FNA.

METHODS:
Forty cases originally diagnosed as atypia of undetermined significance with histologic follow-up were selected for the present study. These cases were reinterpreted blindly by 2 experienced reviewers, who eliminated atypia of undetermined significance as a diagnostic possibility and reclassified these cases as either benign, follicular neoplasm, suspicious for malignancy, or malignant. Twenty-six cases of atypia of undetermined significance were randomly selected and reevaluated 6 months later to study intraobserver variation.

RESULTS:
After eliminating the atypia of undetermined significance category, the sensitivity for detecting papillary thyroid carcinoma (PTC) was reduced from 100% to 27% (P = .04). In those atypia of undetermined significance cases that were reclassified as benign, 37% had PTC. In those reclassified as follicular neoplasm or suspicious for malignancy, 38% were histologically proven to be benign lesions. Unanimous interobserver and intraobserver agreement was observed in only 60% of cases.

CONCLUSIONS:
Eliminating the diagnosis of atypia of undetermined significance substantially decreases the sensitivity of thyroid FNAs and increases both false-positive and false-negative rates. In addition, it increases interobserver and intraobserver variability. Therefore, the atypia of undetermined significance category should not be eliminated; but we advocate minimizing its use. Cancer (Cancer Cytopathol) 2009. © 2009 American Cancer Society.

Thyroid fine‐needle aspiration with atypia of undetermined significance

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Thyroid fine‐needle aspiration with atypia of undetermined significance