Cancer Risk Associated with Nuclear Atypia in Cytologically Indeterminate Thyroid Nodules: A Systematic Review and Meta-Analysis

Valderrábano, Pablo; Khazai, Laila; Thompson, Zachary; Sharpe, Susan C.; Tarasova, Valentina; Otto, Kristen J.; Hallanger‐Johnson, Julie; Wadsworth, J. Trad; Wenig, Bruce M.; Chung, Christine H.; Centeno, Barbara A.; McIver, Bryan

doi:10.1089/thy.2017.0419

Cited by 50 publications

(37 citation statements)

References 43 publications

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“…A retrospective analysis by Lee et al, involving 4,933 aspirates was consistent with our malignancy rate (41.2%) in their Bethesda category III cases [25]. The malignancy rate in our institutions is a fact clinicians can base their decisions on along with the following parameters: the clinical presentation, ultrasonographic characteristics and nuclear features [26].…”

Section: Discussionsupporting

confidence: 88%

Risk Stratification of Bethesda III Category Thyroid Nodules

et al. 2019

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Background: Atypia of undetermined significance/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 calculate the malignancy risk in Bethesda category III and to identify clinical parameters that guided both clinicians and patients at our institutions to reach a clinical decision. Methods:A retrospective review of patients with Bethesda category III thyroid nodules from the tertiary centers in the Emirate of Abu Dhabi during January 2011 through December 2015 was carried out. Malignancy risk in Bethesda category III nodules and repeat fineneedle aspiration (FNA) utility were calculated. Parameters guided referral to surgery were studied. Results:A total of 202 cases were included in the study. Of these, 101 cases underwent surgery initially following the first FNA, and 10 cases following repeat FNA. 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, six (15.7%) being both suspicious and malignant, and five (13.16%) being unsatisfactory. Repeating FNA resulted in a definitive diagnostic utility in 50% of the cases. Conclusions:The relatively high malignancy rate in our institutions, the suspicious radiographic features and the repeat FNA predictive value stratified Bethesda category III nodules for appropriate referrals to surgery.

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Section: Discussionsupporting

confidence: 88%

Risk Stratification of Bethesda III Category Thyroid Nodules

et al. 2019

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“…In a meta-analysis including 15 articles, the risk of malignancy varied between these subcategories, with the highest value found for the cytological atypia category (44%, 37% to 52%) 139. Another systematic review that evaluated 20 studies and specifically compared indeterminate thyroid nodules with and without nuclear atypia confirmed increased odds of malignancy in those with nuclear atypia (3.63, 3.06 to 4.35) 140…”

Section: Estimating the Risk Of Thyroid Cancer And Management After Tmentioning

confidence: 98%

Thyroid nodules: diagnostic evaluation based on thyroid cancer risk assessment

Ospina

Iñiguez-Ariza

Castro

2020

BMJ

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Thyroid nodules are extremely common and can be detected by sensitive imaging in more than 60% of the general population. They are often identified in patients without symptoms who are undergoing evaluation for other medical complaints. Indiscriminate evaluation of thyroid nodules with thyroid biopsy could cause a harmful epidemic of diagnoses of thyroid cancer, but inadequate selection of thyroid nodules for biopsy can lead to missed diagnoses of clinically relevant thyroid cancer. Recent clinical guidelines advocate a more conservative approach in the evaluation of thyroid nodules based on risk assessment for thyroid cancer, as determined by clinical and ultrasound features to guide the need for biopsy. Moreover, newer evidence suggests that for patients with indeterminate thyroid biopsy results, a combined assessment including the initial ultrasound risk stratification or other ancillary testing (molecular markers, second opinion on thyroid cytology) can further clarify the risk of thyroid cancer and the management strategies. This review summarizes the clinical importance of adequate evaluation of thyroid nodules, focuses on the clinical evidence for diagnostic tests that can clarify the risk of thyroid cancer, and highlights the importance of considering the patient’s values and preferences when deciding on management strategies in the setting of uncertainty about the risk of thyroid cancer.

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“…With hindsight, some of TIR3A cases, which later proved to be malignant on histology, may have been underestimated due to blood obscuring very focal nuclear atypia. Indeed, aspirates exhibiting nuclear atypia have a higher risk of malignancy, and thus this feature should be mentioned even in TIR3A reports of suboptimal specimens. We are confident that straightforward non‐neoplastic morphology was not seen in our TIR3A specimens.…”

Section: Discussionmentioning

confidence: 99%

“…This is not surprising since conventional PTC represented a frequent outcome of our TIR3B cases (27%). In agreement with a recent meta‐analysis, our results support the importance of mentioning nuclear atypia in cytological reporting of indeterminate nodules as a major indicator of malignancy. Only a few cytological features were associated with benign histology, namely the well‐known characteristics of Hürthle‐cell lesions …”

Section: Discussionmentioning

confidence: 99%

“…Mentioning the presence of many Hürthle cells in follicular‐patterned lesions in the report is important since it can imply a lower cancer risk. By contrast, mentioning the presence of nuclear atypia could help planning closer follow‐up because this feature is linked to a higher cancer risk . Our numbers are too small and may limit the generalisability of our findings.…”

Section: Discussionmentioning

confidence: 99%

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Indeterminate thyroid nodules (TIR3A/TIR3B) according to the new Italian reporting system for thyroid cytology: A cytomorphological study

et al. 2019

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Objective: The Italian reporting system for thyroid cytology classifies indeterminate lesions as TIR3A (low risk) or TIR3B (high risk) and is meant to provide practical guidance rather than a detailed consideration of morphological features. We aimed to assess which cytological features have the most diagnostic value and whether they are effective in classifying nodules as either TIR3A or TIR3B and in predicting histological outcomes.Methods: Thyroid fine-needle aspirates from 111 indeterminate nodules were reviewed blinded to clinical information, TIR3A/TIR3B classification, and histology in order to assess which cytological features (pooled into artefacts, smear background, architectural and nuclear atypia, and oncocytes) differentiate TIR3A from TIR3B, and benign from malignant histological outcomes. Results:Of the cytological features examined, those specific for TIR3B included high cellularity, nuclear atypia, oncocyte predominance and transgressing vessels.Features specific for TIR3A included artefacts, low cellularity and oncocyte sparseness. Other features, such as microfollicules/trabeculae, were non-specific. Due to the different distributions of these features, three TIR3B subgroups were identifiable: follicular lesions with oncocytic changes, pure follicular lesions, and follicular lesions with nuclear atypia, whereas no subgroups were identifiable in TIR3A. Nuclear atypia was a significant indicator of malignancy, whereas oncocyte predominance was not a reliable predictor of malignancy. High cellularity and microfollicules/trabeculae were not indicative of any histological outcome. Conclusions:The majority of the assessed features were good predictors of histological outcomes. The TIR3A category included undefined nodules due to the absence of characterising features, whereas the TIR3B category included nodules with a greater number of distinguishing features. K E Y W O R D Sclassification, cytopathology, Italy, thyroid cancer, thyroid nodule

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Cancer Risk Associated with Nuclear Atypia in Cytologically Indeterminate Thyroid Nodules: A Systematic Review and Meta-Analysis

Abstract: Nuclear atypia is a significant indicator of malignancy in cytologically indeterminate thyroid nodules and needs to be standardized and implemented into clinical practice.

Cited by 50 publications

References 43 publications

Risk Stratification of Bethesda III Category Thyroid Nodules

Risk Stratification of Bethesda III Category Thyroid Nodules

Thyroid nodules: diagnostic evaluation based on thyroid cancer risk assessment

Indeterminate thyroid nodules (TIR3A/TIR3B) according to the new Italian reporting system for thyroid cytology: A cytomorphological study

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