When is a fine-needle aspiration (FNA) biopsy of the thyroid recommended for a patient with a thyroid nodule?

When to Perform Fine-Needle Aspiration (FNA) of Thyroid Nodules

FNA should be performed for any thyroid nodule >1 cm with suspicious ultrasound features (hypoechogenicity, microcalcifications, irregular margins, solid composition, or absence of peripheral halo), and for nodules <1 cm if microcalcifications are present or if high-risk clinical factors exist. 1

Size-Based Thresholds for FNA

Nodules ≥1 cm:

• Perform FNA for any nodule >1 cm with suspicious ultrasonographic features including hypoechogenicity, microcalcifications, irregular borders, solid composition, or absence of peripheral halo 1
• Perform FNA for any nodule >4 cm regardless of ultrasound appearance due to increased false-negative rate and higher risk of compressive symptoms 1
• Nodules >2 cm should undergo evaluation even without suspicious features due to increased malignancy risk 1

Nodules <1 cm:

• FNA is indicated for subcentimeter nodules only if microcalcifications are present (highly specific for papillary thyroid carcinoma) 2
• FNA should be performed if suspicious features exist PLUS high-risk clinical factors (history of head/neck irradiation, family history of thyroid cancer, suspicious cervical lymphadenopathy, age <15 years) 1
• Research demonstrates that malignancy rates in nodules <1 cm may actually be higher than in larger nodules (4.9% vs 1.5%), particularly when hypoechoic with microcalcifications and round shape 3

High-Risk Ultrasound Features Requiring FNA

The following features warrant FNA in nodules ≥1 cm:

• Microcalcifications (hyperechoic spots ≤1 mm representing psammoma bodies, highly specific for papillary thyroid carcinoma) 1, 2
• Marked hypoechogenicity (darker than surrounding thyroid parenchyma) 1
• Irregular or microlobulated margins (infiltrative borders rather than smooth contours) 1
• Solid composition (higher malignancy risk than cystic nodules) 1
• Absence of peripheral halo (loss of thin hypoechoic rim normally surrounding benign nodules) 1
• Central hypervascularity (chaotic internal vascular pattern) 1

Perform FNA if ≥2 suspicious ultrasound features are present in nodules >1 cm 1

High-Risk Clinical Factors That Lower FNA Threshold

These factors warrant FNA even for smaller nodules (<1 cm) when combined with suspicious ultrasound features:

• History of head and neck irradiation (increases malignancy risk approximately 7-fold) 1
• Family history of thyroid cancer, particularly medullary carcinoma or familial syndromes 1
• Age <15 years or male gender (higher baseline malignancy probability) 1
• Rapidly growing nodule (suggests aggressive biology) 1
• Firm, fixed nodule on palpation (indicates extrathyroidal extension) 1
• Vocal cord paralysis or compressive symptoms (suggest invasive disease) 1
• Suspicious cervical lymphadenopathy 1
• Focal FDG uptake on PET scan 1

When FNA is NOT Indicated

Pure cystic nodules without solid components or suspicious features can be safely observed 1

For nodules <1 cm classified as high-risk by ultrasound but lacking microcalcifications or high-risk clinical factors, FNA may not be routinely recommended to avoid overdiagnosis of clinically insignificant papillary microcarcinomas 1

Technical Approach

Ultrasound guidance is mandatory for FNA rather than palpation-guided biopsy, as it allows real-time needle visualization, confirms accurate sampling, and is superior in terms of accuracy, patient comfort, and cost-effectiveness 1, 4

For mixed solid-cystic nodules, FNA should target the solid portion, as this carries the highest malignancy risk 1

Management Based on FNA Results

Bethesda II (Benign):

• Surveillance with repeat ultrasound at 12-24 months is appropriate, as malignancy risk is only 1-3% 1
• However, if microcalcifications are present, consider repeat FNA in 6 months given discordance between cytology and high-risk imaging 2

Bethesda III/IV (Indeterminate):

• Consider molecular testing for BRAF, RAS, RET/PTC, and PAX8/PPARγ mutations (97% of mutation-positive nodules are malignant) 1
• Repeat FNA under ultrasound guidance for inadequate samples 1

Bethesda V/VI (Suspicious/Malignant):

• Immediate referral for total or near-total thyroidectomy 1

Critical Pitfalls to Avoid

Do not override a reassuring FNA when worrisome clinical findings persist, as false-negative results occur in up to 11-33% of cases 1

Measure serum calcitonin as part of the diagnostic workup to screen for medullary thyroid cancer, which has higher sensitivity than FNA alone (detects 5-7% of thyroid cancers that FNA may miss) 1

For follicular neoplasms (Bethesda IV), recognize that FNA cannot distinguish follicular adenoma from carcinoma—surgery is required for definitive diagnosis 1, 5

Perform complete neck ultrasound to evaluate cervical lymph nodes when thyroid nodules with suspicious features are identified 2