What is the next step in management for a patient with a thyroid biopsy showing intermediate cellularity, follicular cells, and predominantly microfollicular groups with mild nuclear atypia, consistent with atypia of undetermined significance (AUS)?

Management of Thyroid Nodule with Atypia of Undetermined Significance (AUS)

For a thyroid biopsy showing atypia of undetermined significance with microfollicular groups and mild nuclear atypia, await the molecular testing results to guide management—if molecular testing shows malignant mutations (particularly BRAF V600E), proceed directly to surgical resection; if molecular testing is benign or negative, active surveillance with repeat ultrasound is appropriate. 1

Understanding Your AUS Diagnosis and Risk Stratification

Your biopsy falls into Bethesda Category III (AUS/FLUS), which carries a baseline malignancy risk of 5-15%, though this can vary significantly based on specific cytologic features and molecular results. 1, 2

Critical point about nuclear atypia: The presence of "mild nuclear atypia" in your report is significant—studies show that nuclear atypia specifically (as opposed to architectural atypia alone) carries a substantially higher malignancy risk of 42-79%, with one study showing 65.8% malignancy rate when nuclear features predominate. 3, 4 Your "predominantly microfollicular groups" suggests architectural atypia as well, which may lower the overall risk compared to pure nuclear atypia. 5, 6

Molecular Testing: The Critical Next Step

The molecular analysis already submitted is the appropriate next step and will fundamentally determine your management path. 1

If Molecular Testing Shows Mutations:

• BRAF V600E mutation: This is 100% specific for papillary thyroid carcinoma—proceed directly to surgery (total thyroidectomy preferred). 1, 3
• RAS, RET/PTC, or PAX8/PPARγ mutations: Approximately 97% of mutation-positive nodules are malignant—surgical resection is warranted. 2, 7
• Molecular testing positive cases: 75% of patients with identified genetic alterations undergo surgical treatment. 7

If Molecular Testing is Negative or Benign:

• Active surveillance is appropriate when molecular testing predicts malignancy risk ≤5% (comparable to cytologically benign nodules). 1
• Only 18% of patients with no genetic alterations identified undergo surgery, emphasizing the value of molecular testing in avoiding unnecessary intervention. 7
• Surveillance protocol: Repeat ultrasound at 12-24 months to assess for interval growth or development of suspicious features. 2, 8

Ultrasound Features That Modify Risk

While awaiting molecular results, review your ultrasound characteristics—these independently affect malignancy probability: 2, 9

High-risk ultrasound features that increase concern:

• Spiculated or irregular margins 9
• Marked hypoechogenicity (darker than surrounding thyroid tissue) 9
• Microcalcifications 9
• Absence of peripheral halo 2
• Central hypervascularity (chaotic internal blood flow) 2

If your nodule has ≥2 of these suspicious features combined with nuclear atypia on cytology, this substantially increases malignancy risk and may warrant proceeding to surgery even with negative molecular testing. 3, 9

Clinical Risk Factors That Lower Threshold for Surgery

Certain clinical factors independently increase your malignancy risk and should prompt more aggressive management: 3

• History of head and neck irradiation (increases risk 7-fold) 3
• Family history of thyroid cancer (particularly medullary carcinoma or familial syndromes) 3
• Age <15 years or male gender 3
• Rapidly growing nodule 3
• Suspicious cervical lymphadenopathy on ultrasound 3

Specific Cytologic Features in Your Report

Your report mentions "predominantly microfollicular groups"—this architectural pattern has specific implications: 5, 6

Research shows that AUS cases with more than rare nuclear inclusions or grooves carry a 75% malignancy rate versus 9% without these features. 5 Conversely, specimens with moderate or large amounts of thin colloid and absent or few nuclear inclusions have an 88% rate of benign disease. 5

Ask your pathologist: Does your specimen show nuclear inclusions, nuclear grooves, or abundant thin colloid? This information can further refine your risk even before molecular results return. 5

Surgical Decision-Making (If Indicated)

If molecular testing or clinical context indicates surgery: 3

• Lobectomy is acceptable for: Unifocal disease <4 cm without suspicious lymphadenopathy 3
• Total thyroidectomy is recommended for: BRAF mutation confirmed, bilateral nodules present, or suspicious cervical lymph nodes identified 3
• Pre-operative neck ultrasound should assess lymph node compartments 3
• Consider measuring serum calcitonin to screen for medullary thyroid carcinoma (higher sensitivity than FNA alone) 3

Common Pitfalls to Avoid

Do not proceed to surgery before molecular results return unless you have multiple high-risk clinical factors or highly suspicious ultrasound features—molecular testing prevents unnecessary surgery in more than half of AUS cases. 7

Do not rely on repeat FNA as the next step—molecular testing is more definitive for risk stratification in AUS cases. 1

Do not assume all AUS cases require surgery—the NCCN explicitly restructured their algorithm to deemphasize mandatory intervention and allow active surveillance when molecular diagnostics predict low risk. 1

What Happens Next: Practical Timeline

1. Await molecular testing results (typically 1-2 weeks) 2
2. Review results with your endocrinologist, integrating ultrasound features and clinical risk factors 2
3. If positive molecular testing: Referral to endocrine surgeon for surgical planning 3
4. If negative molecular testing and low-risk ultrasound: Active surveillance with repeat ultrasound at 12-24 months 2, 8
5. If negative molecular testing but high-risk ultrasound or clinical features: Consider surgical consultation despite negative molecular results 3