What is the recommended treatment approach for a Thyroid Imaging Reporting and Data System (TI-RADS) category 3 thyroid nodule?

Management of TI-RADS Category 3 Thyroid Nodules

TI-RADS 3 thyroid nodules should be managed with ultrasound surveillance rather than immediate fine-needle aspiration (FNA), with biopsy reserved only for nodules ≥1.5 cm or those with high-risk clinical features. 1

Risk Stratification and Malignancy Rate

TI-RADS 3 nodules carry a very low malignancy risk:

• Overall malignancy rate is only 2.0% in TI-RADS 3 nodules, with 75% being cytologically benign when biopsied 2
• Among TI-RADS 3 nodules that underwent surgical resection, only 17% (8 of 48) were confirmed as carcinoma 2
• No TI-RADS 3 nodules were associated with Bethesda category V or VI (suspicious or malignant) diagnoses in a large series of 2,306 cases 3
• TI-RADS 3 nodules have a negative predictive value of 94.6% compared with Bethesda scoring and 100% compared with histopathology 4

Recommended Management Algorithm

For TI-RADS 3 Nodules ≥1.5 cm:

• Perform ultrasound-guided FNA to exclude malignancy 1
• This size threshold balances the risk of missing clinically significant cancers against unnecessary biopsies 1

For TI-RADS 3 Nodules <1.5 cm:

• Ultrasound surveillance at 12-24 month intervals is appropriate 1
• No immediate FNA is required unless high-risk clinical features are present 5

High-Risk Clinical Features That Lower the FNA Threshold:

Even for nodules <1.5 cm, consider FNA if any of the following are present:

• History of head and neck irradiation (increases malignancy risk 7-fold) 5
• Family history of thyroid cancer, particularly medullary carcinoma or familial syndromes 5
• Age <15 years or male gender 5
• Suspicious cervical lymphadenopathy 5
• Rapidly growing nodule 5
• Firm, fixed nodule on palpation 5
• Vocal cord paralysis or compressive symptoms 5

Alternative Size Threshold Consideration

Some evidence suggests considering FNA for TI-RADS 3 nodules ≥2.5 cm rather than 1.5 cm to further reduce unnecessary biopsies while maintaining safety 4. Lowering the current 1.5 cm threshold to 1.0 cm would identify 7 additional malignant nodules but would also result in 118 additional benign nodules undergoing follow-up 6.

Initial Workup Before Surveillance

Prior to initiating surveillance, complete the following:

• Measure TSH levels to assess thyroid function 1
• High-resolution ultrasound to document baseline nodule characteristics 5
• Assess for suspicious ultrasound features that might warrant reclassification (microcalcifications, marked hypoechogenicity, irregular margins, absence of peripheral halo, central hypervascularity) 5

Surveillance Protocol

For TI-RADS 3 nodules not meeting FNA criteria:

• Repeat ultrasound at 12-24 month intervals to assess for interval growth or development of suspicious features 1
• Monitor for compressive symptoms including dysphagia, dyspnea, or voice changes 5
• If nodule grows to ≥1.5 cm or develops suspicious features, proceed to FNA 1

When to Consider Surgery Without FNA

Surgery may be appropriate for TI-RADS 3 nodules only when:

• Compressive symptoms are present and clearly attributable to the nodule 5
• Cosmetic concerns are significant and patient-driven 5
• Large nodules (>4 cm) due to increased false-negative rate of FNA 5

Critical Pitfalls to Avoid

• Do not perform FNA on TI-RADS 3 nodules <1.5 cm without high-risk features, as this leads to overdiagnosis and overtreatment of clinically insignificant cancers 5
• Do not rely on thyroid function tests (TSH, T3, T4) for malignancy assessment, as most thyroid cancers present with normal thyroid function 5
• Do not override surveillance recommendations based solely on patient anxiety—the evidence strongly supports the safety of observation for appropriately selected TI-RADS 3 nodules 2, 4

Role of Molecular Testing

Molecular testing is generally not indicated for TI-RADS 3 nodules, as the pretest probability of malignancy is so low (2%) that molecular markers add minimal clinical value 5. Molecular testing should be reserved for Bethesda III (AUS/FLUS) or IV (follicular neoplasm) categories if FNA is performed 5.

Thermal Ablation Considerations

Thermal ablation is not indicated for TI-RADS 3 nodules unless they cause clinical symptoms such as compression or cosmetic concerns and are ≥2 cm in maximal diameter 7. Thermal ablation requires either confirmed benign pathology with symptomatic nodules or confirmed malignancy in highly selected cases 7.