What does a Thyroid Imaging Reporting and Data System (TIRADS) category 4 thyroid nodule indicate?

TIRADS 4 Classification

TIRADS 4 indicates a thyroid nodule with intermediate-to-high suspicion for malignancy based on ultrasound features, and fine-needle aspiration biopsy is recommended for nodules ≥1.0 cm in this category. 1

Understanding the TIRADS 4 Category

TIRADS 4 nodules demonstrate a combination of moderately suspicious ultrasound characteristics that elevate malignancy risk above benign-appearing nodules but fall short of the highly suspicious features seen in TIRADS 5. 1 The classification is based on specific sonographic features:

• Solid composition carries higher malignancy risk compared to cystic nodules 2, 1
• Hypoechoic appearance (darker than surrounding thyroid tissue) is a well-established suspicious feature 2, 1
• Irregular or microlobulated margins suggest infiltrative growth patterns 2
• Absence of peripheral halo (loss of the thin hypoechoic rim around benign nodules) 2
• Central hypervascularity with chaotic internal blood flow patterns 2

Malignancy Risk

The actual malignancy risk for TIRADS 4 nodules varies by study but generally ranges from 13-58% depending on the specific constellation of features present. 3, 4 Research demonstrates:

• TIRADS 4 nodules have a 57.9% risk of malignancy in surgical series 4
• TIRADS ≥4 can detect malignant nodules with 91.67% sensitivity and 52.8% specificity 3
• Nodules with TIRADS 4 classification and diameter <12 mm are particularly high-risk and warrant immediate evaluation 3

Clinical Management Algorithm

For TIRADS 4 Nodules ≥1.0 cm:

Proceed directly to ultrasound-guided fine-needle aspiration (FNA) because the intermediate-to-high suspicion pattern warrants tissue diagnosis. 2, 1 The algorithmic approach includes:

• Perform ultrasound-guided FNA targeting the solid component if the nodule is mixed solid-cystic 2
• 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 cancers FNA may miss) 2
• Assess cervical lymph nodes on complete neck ultrasound for suspicious features 2
• Check TSH levels to determine if the nodule is autonomously functioning 2

For TIRADS 4 Nodules <1.0 cm:

Surveillance is generally recommended rather than immediate FNA, unless additional high-risk clinical features are present. 2, 1 Consider FNA even for sub-centimeter nodules when:

• History of head and neck irradiation (increases malignancy risk approximately 7-fold) 2
• Family history of thyroid cancer, particularly medullary carcinoma or familial syndromes 2
• Suspicious cervical lymphadenopathy on ultrasound 2
• Subcapsular location of the nodule 2
• Age <15 years or male gender 2

Management Based on FNA Results

Bethesda II (Benign):

• Continue surveillance with repeat ultrasound at 12-24 months 2
• Malignancy risk drops to only 1-3% with benign cytology 2
• Do not override benign FNA unless highly suspicious clinical features persist, as false-negative rates are 5-10% 1

Bethesda III (AUS/FLUS) or IV (Follicular Neoplasm):

• Perform molecular testing for BRAF, RAS, RET/PTC, and PAX8/PPARγ mutations 2, 5
• Mutation-positive nodules have ~97% probability of malignancy 2
• Repeat FNA under ultrasound guidance if initial sample was inadequate 2, 5
• Consider core needle biopsy if repeat FNA remains nondiagnostic 2

Bethesda V (Suspicious) or VI (Malignant):

• Refer immediately for total or near-total thyroidectomy with pre-operative assessment of cervical lymph node compartments 2, 5

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 2
• Avoid radionuclide scanning in euthyroid patients for malignancy determination—ultrasound features are far more predictive 2, 1
• Do not perform FNA on TIRADS 4 nodules <1 cm without high-risk features, as this leads to overdiagnosis of clinically insignificant papillary microcarcinomas 2, 1
• Recognize that hyperfunctioning nodules (hot on scintigraphy) have very high negative predictive value for malignancy; if TSH is suppressed, obtain thyroid scan before FNA to avoid unnecessary biopsies 6
• Be aware that follicular neoplasms may yield indeterminate FNA results requiring surgical excision for definitive diagnosis, as cytology cannot distinguish follicular adenoma from carcinoma 2, 1

Diagnostic Performance

The TIRADS system demonstrates strong clinical utility:

• Sensitivity: 70.6-100% for detecting malignancy 7, 8
• Specificity: 51.4-90.4% 7, 8
• Negative predictive value: 93.8-100% 7, 8, 4
• Overall accuracy: 60-77.8% 8, 4

All patients with malignant nodules are classified in categories 4 or 5 of TIRADS, confirming the system's reliability for excluding malignancy in lower-risk categories. 8