Management of 2×2 cm Thyroid Nodule with Solid and Cystic Components
For a patient with a 2×2 cm thyroid nodule containing both solid and cystic components, perform ultrasound-guided fine-needle aspiration (FNA) of the solid portion of the nodule. 1, 2
Rationale for FNA of the Solid Component
The solid component carries the highest malignancy risk and should be the primary target for biopsy. The 2025 Chinese guidelines for thyroid nodules explicitly state that FNAB is the preferred diagnostic method and should be performed to confirm pathological diagnosis before any treatment decisions 1. Current evidence demonstrates that:
- Mixed cystic-solid nodules have a malignancy rate of approximately 5-14%, with the risk increasing when the solid portion comprises ≥50% of the nodule 3, 4
- Large cystic/solid nodules (≥2 cm) have a false-negative FNA rate of 30% when sampling is inadequate, making proper technique critical 5
- Eccentric solid components and microcalcifications significantly increase malignancy risk in partially cystic nodules 4
Why Not Biopsy the Cystic Component
The cystic portion should generally not be the primary biopsy target because:
- Cystic fluid aspiration has limited diagnostic value - bloody fluid is present in 81% of both benign and malignant cystic lesions, making fluid characteristics unreliable for diagnosis 3
- Pure cystic nodules have only a 4% malignancy rate, while the solid component drives the cancer risk 3
- FNA of cystic areas yields insufficient material for diagnosis in 20% of cystic papillary cancers, compared to 0% in solid papillary carcinomas 3
Why Core Needle Biopsy is Not First-Line
While core needle biopsy (CNB) provides histological architecture, FNA remains the preferred initial diagnostic method 1, 6:
- FNA achieves approximately 95% diagnostic accuracy for thyroid nodules 6
- CNB is reserved for cases where FNA is nondiagnostic or indeterminate after repeat attempts 1
- The 2025 guidelines specify that "cystic and cavernous nodules in US can undergo FNAB once, and other nodules need to undergo FNAB twice or in combination with CNB" 1
Proper Technique for Mixed Nodules
Ultrasound guidance is mandatory to ensure accurate sampling of the solid component 2, 6:
- Target the solid portion specifically, particularly if it is eccentric in location 4
- Avoid aspirating only cystic fluid, as this leads to false-negative results 3, 5
- If initial FNA is inadequate, repeat under ultrasound guidance before considering CNB 1, 2
Additional Diagnostic Considerations
Beyond the FNA procedure itself:
- Measure TSH levels to determine if the nodule is autonomously functioning 1, 2
- Perform complete neck ultrasound to evaluate cervical lymph nodes for suspicious features 1
- Consider serum calcitonin measurement to screen for medullary thyroid cancer, which has higher sensitivity than FNA alone 2, 6
Management Based on FNA Results
The cytology results will determine next steps 1, 2, 6:
- Malignant (Bethesda VI) or Suspicious (Bethesda V): Immediate referral for total or near-total thyroidectomy 2, 6
- Follicular neoplasm (Bethesda IV): Consider surgery for definitive diagnosis, as FNA cannot distinguish follicular adenoma from carcinoma 1, 2
- Atypia/Follicular lesion of undetermined significance (Bethesda III): Consider molecular testing (BRAF, RAS, RET/PTC, PAX8/PPARγ) or repeat FNA 2
- Benign (Bethesda II): Surveillance with repeat ultrasound at 12-24 months 2
- Nondiagnostic/Inadequate (Bethesda I): Repeat FNA under ultrasound guidance 2, 6
Critical Pitfall to Avoid
Do not rely on aspiration of cystic fluid alone or assume a mixed nodule is benign without cytological confirmation of the solid component. Large cystic/solid nodules have the highest false-negative rate (30%) when improperly sampled, and malignancy cannot be excluded based on clinical characteristics or fluid appearance 3, 5. The 2025 guidelines emphasize that thermal ablation or any definitive treatment requires pathological confirmation via biopsy first 1.