What is the significance of a thyroid nodule with Fine Needle Aspiration (FNA) showing follicular cells with atypia of undetermined significance (Bethesda Category 3) and significant cyst fluid noted during the procedure?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: May 9, 2025View editorial policy

Personalize

Help us tailor your experience

Which best describes you? Your choice helps us use language that's most understandable for you.

From the Guidelines

I strongly recommend proceeding with the ENT evaluation for this thyroid nodule, ensuring that both the FNA pathology report and thyroid ultrasound images are forwarded to the ENT specialist prior to the appointment. The finding of follicular cells with atypia of undetermined significance (Bethesda Category 3) represents an indeterminate cytology result with a malignancy risk of approximately 10-30% 1. The presence of significant cyst fluid noted during the procedure is relevant information that may influence management decisions.

Key considerations for the ENT specialist include:

  • Review of the FNA pathology report to confirm the Bethesda Category 3 diagnosis
  • Evaluation of the thyroid ultrasound images to assess nodule characteristics, such as size, composition, and suspicious features
  • Discussion of the patient's medical history, symptoms, and family history of thyroid disease or cancer
  • Consideration of molecular testing of the FNA sample to detect individual mutations or pattern recognition approaches using molecular classifiers 1

The ENT specialist will need to determine appropriate next steps, which may include:

  • Repeat FNA in 3-6 months to monitor for changes in nodule characteristics or cytology results
  • Molecular testing of the sample to help inform management decisions
  • Consideration of surgical management depending on clinical risk factors, nodule characteristics, and patient preference
  • Development of an appropriate surveillance or treatment plan to minimize the risk of malignancy and optimize patient outcomes 1.

From the Research

Thyroid Nodule Evaluation

  • The patient has been referred to ENT for evaluation of a thyroid nodule with FNA showing follicular cells with atypia of undetermined significance (Bethesda Category 3) 2, 3, 4, 5, 6.
  • The interventional radiologist noted significant cyst fluid during the procedure, and the FNA path report and thyroid ultrasound are required for further evaluation.

Atypia of Undetermined Significance (AUS)

  • AUS is a diagnostic category in the Bethesda System for Reporting Thyroid Cytopathology, with a reported frequency of 2.7% to 5.5% in various studies 2, 3, 6.
  • The malignancy rate for AUS ranges from 5-15% to 29.8% in different studies, highlighting the need for careful follow-up and management 2, 3, 4, 5, 6.

Management and Follow-up

  • Repeat FNA is a common follow-up approach for AUS, with 20.1% to 44% of patients undergoing repeat FNA in various studies 2, 3, 6.
  • Surgery is also a management option, with 23.9% to 46.4% of patients undergoing surgical intervention after an AUS diagnosis 2, 3, 6.
  • Ultrasonography is useful in predicting malignancy, with sensitivity, specificity, and positive and negative predictive values of 79.4%, 90.5%, 71%, and 93.75%, respectively 4.

Predictors of Malignancy

  • Cytological subcategory (FLUS or AUS) and ultrasonography can provide different risks of malignancy for nodules initially classified as Bethesda category III 4.
  • Nuclear atypia is significantly more predictive of malignancy than architectural atypia, with a malignancy rate of 36.8% versus 14.7% 5.
  • Irregular margins on ultrasonography are also predictive of malignancy 5.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.