What is the management approach for a patient with a Bethesda 2 (Bethesda System for Reporting Thyroid Cytopathology) thyroid follicular nodule?

Management of Bethesda 2 Thyroid Nodules

Bethesda 2 (benign) thyroid nodules should be managed with clinical and ultrasound surveillance rather than surgery, as the risk of malignancy is extremely low (1-3%) and does not justify surgical intervention in the absence of compressive symptoms or suspicious clinical features. 1

Understanding Bethesda 2 Classification

Bethesda Category II represents cytologically benign nodules, including:

• Nodular goiter
• Colloid goiter
• Hyperplastic/adenomatoid nodules
• Hashimoto's thyroiditis 1

The malignancy risk in this category is approximately 1-3% based on large institutional series 1, 2, 3. Research demonstrates that incidental thyroid carcinoma occurs in only 1.53% of surgically resected Bethesda II nodules 2.

Recommended Management Algorithm

Initial Response to Bethesda 2 Diagnosis

Surveillance is the standard of care for Bethesda 2 nodules without concerning features 1. The following approach should be implemented:

• Measure TSH levels as part of the initial workup to guide subsequent management decisions 4
• Perform high-resolution ultrasound to document baseline nodule characteristics and assess for suspicious features 5
• Avoid immediate surgery unless specific indications are present (see below) 1

Surveillance Protocol

For confirmed Bethesda 2 nodules:

• Repeat ultrasound at 12-24 months to assess for interval growth or development of suspicious features 1
• Monitor for compressive symptoms including dysphagia, dyspnea, or voice changes 1
• Do not rely on repeat TSH or thyroid function tests for malignancy assessment, as most thyroid cancers present with normal thyroid function 5

Indications for Repeat FNA Despite Benign Cytology

Consider repeat FNA if any of the following develop during surveillance:

• Significant nodule growth (>20% increase in two dimensions with minimum 2mm increase in solid component) 1
• Development of new suspicious ultrasound features including:
  • Microcalcifications 5
  • Marked hypoechogenicity 5
  • Irregular or microlobulated margins 5
  • Loss of peripheral halo 5
  • Central hypervascularity 5
• New suspicious cervical lymphadenopathy 5
• Persistent clinical concern despite benign cytology, particularly with high-risk features 5

Absolute Indications for Surgery in Bethesda 2 Nodules

Surgery should be considered for Bethesda 2 nodules only when:

• Compressive symptoms are present and clearly attributable to the nodule 1
• Cosmetic concerns are significant and patient-driven 1
• High-risk clinical features persist including:
  • History of head and neck irradiation 5
  • Family history of thyroid cancer 5
  • Rapidly growing nodule despite benign cytology 5
  • Vocal cord paralysis 5
  • Firm, fixed nodule on palpation 5

Critical Clinical Pitfalls to Avoid

False-Negative Rate Considerations

While Bethesda 2 has excellent negative predictive value, false-negative results occur in up to 11-33% of FNA procedures 5. However, this should not prompt routine surgery but rather:

• Ensure adequate sampling during initial FNA (minimum 6 groups of well-preserved follicular cells, each containing at least 10 cells) 1
• Use ultrasound guidance for all FNA procedures to maximize accuracy 5
• Correlate cytology with ultrasound features - a reassuring FNA should not override worrisome clinical findings 5

Overdiagnosis and Overtreatment

The most common error is unnecessary surgery for benign nodules 5. The rising incidence of thyroid cancer diagnosis is almost entirely due to overdiagnosis of small, clinically insignificant papillary thyroid cancers 1. Conservative management with surveillance is supported by:

• Growing evidence for watchful waiting in low-risk thyroid disease 1
• Recognition that NIFTP (noninvasive follicular thyroid neoplasm with papillary-like nuclear features) accounts for up to 20% of cases previously called cancer and has <1% recurrence risk 1
• Elimination of unnecessary radioactive iodine treatment and completion thyroidectomies 1

When Ultrasound Features Conflict with Benign Cytology

If a nodule has multiple suspicious ultrasound features (≥2 high-risk characteristics) despite Bethesda 2 cytology 6:

• Repeat FNA under ultrasound guidance targeting the most suspicious areas 1
• Consider molecular testing (BRAF V600E, RAS, RET/PTC, PAX8/PPARγ) if repeat FNA remains benign but clinical suspicion persists 1
• Maintain heightened surveillance with ultrasound every 6-12 months 1

Special Populations Requiring Modified Approach

Patients with High-Risk History

For patients with history of head and neck irradiation or family history of thyroid cancer, even Bethesda 2 nodules warrant:

• More frequent surveillance (every 6-12 months rather than annually) 5
• Lower threshold for repeat FNA if any interval changes occur 5
• Consideration of molecular testing as adjunct to cytology 1

Large Nodules (>4 cm)

For Bethesda 2 nodules >4 cm in size:

• Surgery may be considered even without suspicious features due to increased false-negative rate in large nodules 5
• Compressive symptoms are more common and may develop over time 1
• Complete surgical excision allows definitive histologic diagnosis 1

Role of Molecular Testing

Molecular testing is generally not indicated for Bethesda 2 nodules 1. The pretest probability of malignancy is so low (1-3%) that molecular markers add minimal clinical value. Molecular testing should be reserved for:

• Bethesda III (AUS/FLUS) categories 1
• Bethesda IV (follicular neoplasm) categories 1
• Discordance between benign cytology and highly suspicious clinical/ultrasound features 1