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. 2025 Oct;173(4):848-858.
doi: 10.1002/ohn.1360. Epub 2025 Jul 29.

Refining the Management of Bethesda III Thyroid Nodules by Combining Nuclear Atypia with Sonographic Suspicion

Hao Li  1 , Caroline C Y Lee  1   2 , Hau W Khoo  3 , Manish M Bundele  4 , Jereme Y J Gan  1 , Ernest W Z Fu  1 , Ming Y Lim  1 , Julian P N Goh  3 , Alvin Y Q Soon  3
Affiliations

Refining the Management of Bethesda III Thyroid Nodules by Combining Nuclear Atypia with Sonographic Suspicion

Hao Li et al. Otolaryngol Head Neck Surg. 2025 Oct.

Abstract

Objective: The risk of malignancy (ROM) in thyroid nodules with Bethesda III cytology ranges from 6% to 30%. Further stratification may aide the decision for diagnostic hemithyroidectomy.

Study design: Retrospective chart review.

Setting: Tertiary general hospital.

Methods: Bethesda III thyroid nodules consecutively resected between 2010 and 2016 are reviewed. Sonographic images are matched to the pathologic diagnoses and exported. Blinded to the diagnosis, 2 to 3 radiologists reached a consensus on the ACR-TIRADS, EU-TIRADS, and ATA classification of the nodules. A head and neck pathologist reviewed the cytology for nuclear atypia. Univariate and multivariate analyses are performed.

Results: Out of a total of 243 nodules, 63 (26%) are malignant and 3 (1.2%) are NIFTP. Nuclear atypia, hypoechogenicity, intermediate and high-risk categories in ACR-TIRADS, EU-TIRADS, or ATA are significantly associated with malignancy (including NIFTP) in both univariate and multivariate analysis (P < .001-.028). The area-under-the-receiver-operator-curve of the diagnostic model incorporating sex, nuclear atypia, and sonographic suspicion is 0.714, 0.695, 0.711, and 0.699, respectively, when sonographic suspicion is defined as hypoechogenicity, TR4/5, EU-TIRADS intermediate/high-risk, or ATA moderate/high suspicion. In TR5, EU-TIRADS or ATA high-risk nodules or nodules with marked hypoechogenicity/punctate echogenic foci/irregular margins, nuclear atypia significantly increases the ROM from 6.3%-9.7% to 59.4%-75.0%. Majority of the cancers diagnosed by nuclear atypia and sonographic suspicion are papillary carcinomas.

Conclusion: Diagnostic hemithyroidectomy is recommended in nodules with both AUS-nuclear atypia and high sonographic suspicion. Improved identification of follicular-patterned thyroid carcinomas is required to better manage the other Bethesda III nodules.

Keywords: ATA; Bethesda III; TIRADS; nuclear atypia; risk of malignancy; sonography; thyroid nodule.

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