What is the next step in management for a 2 cm solid thyroid nodule classified as TR4 (Thyroid Imaging, Reporting and Data System) according to the ACR (American College of Radiology) TI-RADS (Thyroid Imaging, Reporting and Data System) system in an adult patient?

Management of a 2 cm TR4 Thyroid Nodule

Proceed immediately with ultrasound-guided fine-needle aspiration (FNA) biopsy of this nodule, as ACR TI-RADS explicitly recommends FNA for all TR4 nodules ≥1.5 cm, and this 2 cm solid hypoechoic nodule meets both the size and risk category criteria. 1, 2

Rationale for FNA in This Case

The combination of features in this nodule substantially elevates malignancy risk and mandates tissue diagnosis:

• Size threshold exceeded: At 2.0 cm, this nodule is well above the 1.5 cm threshold that triggers FNA recommendation for TR4 lesions per ACR TI-RADS guidelines 1, 2
• Solid composition: Solid nodules carry significantly higher malignancy risk compared to cystic nodules, with solid composition being one of the most statistically significant predictors of malignancy 1, 3
• Hypoechoic appearance: Marked hypoechogenicity is a well-established suspicious sonographic feature strongly associated with increased malignancy risk, particularly for papillary thyroid carcinoma 1, 3
• TR4 classification: This represents moderately suspicious features with 4-6 TI-RADS points, placing it in a category where the risk-benefit ratio strongly favors tissue diagnosis 1, 2

Technical Approach to FNA

Use ultrasound guidance for the procedure, as this approach is superior to palpation-guided biopsy:

• Real-time needle visualization ensures accurate sampling of the target lesion 1
• Allows confirmation that tissue is obtained from the solid component rather than any cystic areas 1
• Enables marker clip placement for future reference if needed 1
• Superior accuracy, patient comfort, and cost-effectiveness compared to palpation-guided technique 1

Pre-FNA Workup

Before performing FNA, obtain the following:

• Measure serum TSH: This determines whether the nodule is autonomously functioning, which would alter management 1, 4, 5
• Complete neck ultrasound: Evaluate cervical lymph nodes for suspicious features such as loss of fatty hilum, microcalcifications, cystic change, or hypervascularity 1
• Consider serum calcitonin: This screens for medullary thyroid carcinoma, which has higher sensitivity than FNA alone and detects 5-7% of thyroid cancers that FNA may miss 1

Management Based on FNA Results

The Bethesda System will classify the cytology into one of six categories, each with specific management implications:

Bethesda II (Benign, 1-3% malignancy risk)

• Surveillance with repeat ultrasound at 12-24 months is appropriate 1
• Surgery only indicated if compressive symptoms develop or cosmetic concerns are significant 1
• For nodules >4 cm, consider surgery due to increased false-negative rate 1

Bethesda III/IV (Indeterminate, 12-34% malignancy risk)

• Molecular testing for BRAF, RAS, RET/PTC, and PAX8/PPARγ mutations to refine malignancy risk 1, 5
• Presence of any mutation indicates 97% probability of malignancy 1
• For Bethesda IV (follicular neoplasm) with normal TSH and "cold" scan, surgery is required for definitive diagnosis as FNA cannot distinguish follicular adenoma from carcinoma 1

Bethesda V/VI (Suspicious or Malignant)

• Immediate referral to endocrine surgeon for total or near-total thyroidectomy 1
• Pre-operative neck ultrasound to assess lymph node compartments 1
• Compartment-oriented lymph node dissection if metastases suspected or proven 1

Bethesda I (Nondiagnostic/Inadequate)

• Repeat FNA under ultrasound guidance is mandatory, as inadequate samples occur in 5-20% of cases 1
• If repeat FNA remains nondiagnostic, consider core needle biopsy (CNB) which has superior diagnostic accuracy 1

Critical Pitfalls to Avoid

• Do not delay FNA based on nodule homogeneity: The report describes "homogeneous echogenicity" of the thyroid gland, but the nodule itself is hypoechoic and solid—these suspicious features override any perceived homogeneity 1
• Do not skip FNA for "functioning" nodules without confirmation: Only hyperfunctioning nodules (low TSH with hot scan) can safely avoid FNA, as they are rarely malignant 4
• Do not override reassuring FNA if clinical concerns persist: False-negative results occur in up to 11-33% of cases, so maintain clinical vigilance 1
• Do not perform radionuclide scanning in euthyroid patients: Thyroid scintigraphy is not helpful for determining malignancy risk when TSH is normal—ultrasound features are far more predictive 1

Expected Outcomes and Prognosis

If malignancy is confirmed, prognosis is generally excellent:

• Differentiated thyroid carcinomas (papillary and follicular) have 10-year survival rates of 99% and 95% respectively 6
• Most thyroid cancers are indolent, and the majority of small thyroid cancers would never cause clinical problems 6
• However, tissue diagnosis is essential before considering any treatment approach, including active surveillance 1

The ACR TI-RADS system was specifically designed to balance the need to identify clinically significant cancers while minimizing unnecessary biopsies—this 2 cm TR4 nodule clearly falls on the side requiring tissue diagnosis. 6, 2