Which Thyroid Imaging Reporting and Data System (TIRADS) categories require biopsy?

TIRADS Biopsy Indications

TIRADS systems use nodule size combined with risk category to determine biopsy thresholds, with higher-risk categories requiring biopsy at smaller sizes: generally, TIRADS 3 nodules ≥1.5 cm, TIRADS 4 nodules ≥1.0 cm, and TIRADS 5 nodules ≥1.0 cm warrant fine needle aspiration, though nodules <1 cm are typically observed regardless of TIRADS category unless high-risk features are present. 1, 2, 3

Size-Based Biopsy Thresholds by TIRADS Category

TIRADS 3 (Mildly Suspicious)

• Observation without FNA is recommended for nodules <1.5 cm 2
• Follow-up ultrasound surveillance is the appropriate management strategy for these smaller nodules 2
• The malignancy risk for TIRADS 3 is approximately 0.7-0.8% 4, 5

TIRADS 4 (Moderately Suspicious)

• FNA is recommended for nodules ≥1.0 cm 3
• TIRADS 4 is subdivided into 4A (one suspicious feature), 4B (two suspicious features), and 4C (three or four suspicious features) 4, 5
• Malignancy risks increase progressively: 4A (1.2-1.8%), 4B (6.1%), 4C (9.8-14.4%) 4, 5
• For nodules with ≥3 suspicious features (TIRADS 4C), repeat FNA should be considered even if initial cytology is benign, regardless of size 4

TIRADS 5 (Highly Suspicious)

• FNA is recommended for nodules ≥1.0 cm 3
• Malignancy risk ranges from 22-31% 4, 5
• These nodules have five suspicious ultrasound features 5

Critical Exception: The <1 cm Rule

A fundamental principle across TIRADS systems is that nodules <1 cm generally should NOT undergo FNA, even if classified as high-risk, unless specific high-risk clinical features are present. 1

Exceptions warranting biopsy in nodules <1 cm:

• Subcapsular location 1
• Suspicious metastatic cervical lymphadenopathy 1, 2
• History of head and neck irradiation 2
• Family history of thyroid cancer 2
• Suspicious physical exam findings (firm, fixed nodule, rapid growth) 2

Rationale for Conservative Approach to Small Nodules

The conservative management of nodules <1 cm is based on several key principles:

• Smaller papillary thyroid cancers have lower potential for relapse after treatment 1, 2
• The clinical significance of detecting small papillary thyroid cancers is generally low 1, 2
• Overall thyroid cancer rate in nodules is only 3-5%, with generally favorable prognosis 1, 2
• The primary goal of TIRADS is to minimize unnecessary FNA procedures 1, 2

Important Pitfalls and Caveats

Functional Status Consideration

• Hyperfunctioning thyroid nodules (HTNs) have very high negative predictive value for malignancy 6
• Over 80% of autonomous nodules may be classified as TIRADS 4A or higher based on ultrasound features alone, but thyroid scintigraphy can prevent unnecessary biopsies by identifying these benign hyperfunctioning nodules 6
• Integration of thyroid scintigraphy should be considered, particularly in iodine-deficient regions 6

Benign Cytology with High TIRADS Score

• Nodules with benign cytology but TIRADS 4C or 5 classification warrant repeat FNA 4
• The malignancy risk remains elevated (9.8-22.2%) even after initial benign cytology in these high-risk categories 4
• Odds ratios for malignancy in TIRADS 4C and 5 with benign cytology are 19.4 and 50.6, respectively 4

Nondiagnostic Cytology Management

• Nondiagnostic nodules with ≥2 suspicious features should undergo repeat FNA 5
• Malignancy risks for nondiagnostic nodules: TIRADS 4B (6.1%), 4C (14.4%), 5 (31%) 5
• Nondiagnostic nodules with 0-1 suspicious features can be followed with ultrasound surveillance 5

Size-Malignancy Relationship

• An inverse relationship exists between nodule size and malignancy risk 7
• Nodules <12 mm with TIRADS 4-5 are highly suspicious and should be prioritized for FNA 7
• Sensitivity for detecting malignancy with TIRADS ≥4 is 91.67% 7