What are the indications for Fine Needle Aspiration Biopsy (FNAB) of the thyroid?

Indications for Fine Needle Aspiration Biopsy (FNAB) of the Thyroid

Perform ultrasound-guided FNAB for any thyroid nodule >1 cm with suspicious ultrasound features, any nodule >2 cm regardless of appearance, nodules <1 cm with high-risk clinical factors, or when suspicious cervical lymphadenopathy is present. 1

Size-Based Indications

Primary size thresholds:

• Any nodule >1 cm with ≥2 suspicious ultrasound features warrants FNAB 1, 2
• Any nodule >2 cm should undergo evaluation even without suspicious features due to increased malignancy risk 1
• Any nodule >4 cm requires FNAB regardless of ultrasound appearance 1
• Nodules <1 cm require FNAB only when suspicious ultrasound features are combined with high-risk clinical factors 1, 2

Suspicious Ultrasound Features That Trigger FNAB

High-risk sonographic characteristics include:

• Microcalcifications (highly specific for papillary thyroid carcinoma, OR 7.1) 1, 2
• Marked hypoechogenicity (solid nodules darker than surrounding thyroid parenchyma) 1
• Irregular or microlobulated margins (infiltrative borders rather than smooth contours, OR 7.2) 1, 2
• Taller-than-wide shape (strongest predictor with OR 13.7, though sensitivity only 25.9%) 2
• Absence of peripheral halo (loss of thin hypoechoic rim) 1
• Central hypervascularity (chaotic internal vascular pattern) 3, 1
• Solid composition (higher malignancy risk versus cystic nodules) 1

The combination of multiple high-risk features substantially increases overall malignancy risk and strengthens the indication for FNAB 1.

High-Risk Clinical Factors That Lower FNAB Threshold

Patient history and clinical findings that warrant FNAB even for smaller nodules (<1 cm):

• History of head and neck irradiation (increases malignancy risk approximately 7-fold when combined with other features) 3, 1
• Family history of thyroid cancer, particularly medullary thyroid carcinoma or familial syndromes (MEN 2A/2B, familial adenomatous polyposis, Carney complex, Cowden's syndrome) 3, 1
• Age <15 years or male gender (higher baseline malignancy probability) 3, 1
• Rapidly growing nodule (suggests aggressive biology) 3, 1
• Firm, fixed nodule on palpation (indicates extrathyroidal extension) 3, 1
• Vocal cord paralysis or compressive symptoms (suggest invasive disease) 3, 1
• Suspicious cervical lymphadenopathy (enlarged regional lymph nodes) 3, 1
• Subcapsular location of the nodule 1

The presence of 2 or more clinical features virtually assures malignancy, though this is rare 3.

Additional Diagnostic Considerations

Imaging findings that trigger FNAB:

• Focal FDG uptake on PET scan 3
• Incidental thyroid nodules discovered on other imaging studies 4

Laboratory considerations:

• Serum calcitonin measurement may be considered as part of diagnostic evaluation to screen for medullary thyroid cancer, which has higher sensitivity than FNA alone 1
• TSH levels should ideally be known before FNA, as higher TSH levels are associated with increased risk for differentiated thyroid cancer 3

Technical Approach

Ultrasound guidance is mandatory for FNAB as it:

• Allows real-time needle visualization 5
• Achieves 96% diagnostic adequacy rate 4
• Reduces nondiagnostic specimens from 13% in lesions <1.0 cm to 3% in lesions >2.0 cm 4
• Enables evaluation of difficult-to-palpate or nonpalpable lesions 4

When multiple nodules are present, prioritize the largest nodule for initial FNA, as nodule size ≥3 cm carries 3-times greater malignancy risk 1. If FNA yields benign results but clinical suspicion remains high, the second nodule can be evaluated subsequently 1.

Critical Pitfalls to Avoid

Do not rely on thyroid function tests (TSH, T3, T4) for malignancy assessment, as most thyroid cancers present with normal thyroid function 1.

Avoid performing FNA on nodules <1 cm without high-risk features, as this leads to overdiagnosis and overtreatment of clinically insignificant cancers 1.

A reassuring FNA should not override concerns when worrisome clinical findings are present, as false-negative results occur in up to 11-33% of cases 3, 6, 7. Nodules ≥4 cm with negative cytology require close follow-up and repeat FNAB in 6 months 7.

Follicular neoplasms may be difficult to definitively diagnose by FNA alone, potentially requiring histological examination through surgical excision 1. Malignancy rates in follicular lesions range from 12-34% depending on subcategory 1.

For inadequate or nondiagnostic specimens, repeat FNA under ultrasound guidance is recommended 1. If repeat FNA remains nondiagnostic, assess the number of suspicious ultrasound features to guide management 1.