What is the recommended management for a thyroid nodule classified as Bethesda 2 (Bethesda System for Reporting Thyroid Cytopathology) that is larger than 4 centimeters (cm) in size?

Management of Bethesda 2 Thyroid Nodules >4 cm

For a Bethesda 2 (benign) thyroid nodule larger than 4 cm, observation with ultrasound surveillance is the appropriate management unless the patient has compressive symptoms, cosmetic concerns, or documented growth, in which case surgical excision or thermal ablation should be considered. 1

Primary Management Strategy: Active Surveillance

• Bethesda 2 nodules are cytologically benign and do not require routine surgical excision based on size alone, even when exceeding 4 cm 2, 3, 4
• The false-negative rate for benign cytology in nodules ≥4 cm is only 5.2%, which is comparable to smaller nodules (5.9%), contradicting older concerns about unreliable cytology in large nodules 2
• Recent evidence demonstrates that nodules ≥4 cm actually have a lower malignancy rate (23%) compared to smaller nodules (53%), making size alone an insufficient indication for surgery 2
• The sensitivity of fine-needle aspiration in nodules ≥4 cm is 93.8% with acceptable specificity of 62.2% 3

Indications for Intervention

Surgical excision or thermal ablation becomes appropriate when:

• Compressive symptoms are present (dysphagia, dyspnea, voice changes) 1, 3
• Cosmetic concerns significantly affect quality of life 1
• Documented nodule growth on serial ultrasound surveillance 1
• Patient anxiety that cannot be managed conservatively 1

Intervention Options

Surgical Approach

• Thyroid lobectomy is the standard surgical option for unilateral benign nodules, preserving contralateral thyroid function 5
• Total thyroidectomy should be reserved for bilateral nodularity or if intraoperative findings reveal unexpected malignancy with high-risk features 5

Thermal Ablation (Alternative to Surgery)

• Radiofrequency or microwave ablation is an acceptable alternative for benign nodules ≥2 cm causing symptoms or cosmetic issues (strong recommendation, moderate-quality evidence) 1
• Thermal ablation requires confirmation of benign pathology via biopsy and is contraindicated in patients with severe bleeding tendency, contralateral vocal cord paralysis, or severe cardiopulmonary disease 1
• Local anesthesia with 1-2% lidocaine is used, with needle insertion via isthmus or lateral neck approach 1

Critical Surveillance Protocol

For nodules managed conservatively:

• Repeat ultrasound at 6-12 month intervals initially to monitor for growth 5
• Repeat fine-needle aspiration if ultrasound characteristics change or significant growth occurs (>20% increase in two dimensions with minimum 2mm increase) 1
• Thyroid function testing should be performed to exclude autonomously functioning adenomas 1

Common Pitfalls to Avoid

• Do not perform routine diagnostic lobectomy based solely on size ≥4 cm in the setting of benign cytology without other clinical indications 2, 3, 4
• Do not assume higher malignancy risk in large nodules—contemporary data refutes this outdated concern 2, 4
• Do not ignore patient symptoms—many patients with large nodules undergo thyroidectomy appropriately for symptom relief regardless of benign cytology 3
• Ensure adequate sampling during initial fine-needle aspiration—if the specimen is inadequate (Bethesda 1), repeat the biopsy rather than proceeding directly to surgery 1

Special Considerations

• The overall malignancy rate in surgically excised nodules ≥4 cm ranges from only 7.2% to 23%, substantially lower than historical estimates 2, 3
• Smaller nodules (<2 cm) paradoxically carry higher malignancy risk than larger nodules when controlled for Bethesda class 4
• For Bethesda 2 specifically, the risk of malignancy on final histopathology is approximately 6-11%, which is acceptably low for conservative management 4, 6