What is the next step in management for a patient with thyroid biopsy results showing macrophages only?

Management of Thyroid Biopsy Showing Only Macrophages

Repeat the fine-needle aspiration biopsy (FNAB) immediately, as a specimen containing only macrophages is nondiagnostic and inadequate for clinical decision-making. 1

Understanding the Result

A thyroid biopsy showing only macrophages represents an inadequate/nondiagnostic specimen that cannot exclude malignancy or provide meaningful diagnostic information. 2, 3

• Macrophages are commonly seen in thyroid nodules with cystic degeneration or hemorrhagic change, but their presence alone does not constitute an adequate sample for diagnosis. 2
• Histiocytic aggregates can occasionally mimic features of papillary thyroid carcinoma with nuclear grooves and chromatin clearing, but without follicular cells present, no definitive diagnosis can be made. 2
• The presence of only macrophages after two biopsies suggests either technical sampling issues or a predominantly cystic lesion. 3

Immediate Next Steps

Repeat FNAB with Optimized Technique

Perform a third FNAB using improved sampling technique to obtain diagnostic follicular cells. 1, 3

• Target solid components of the nodule under ultrasound guidance, avoiding cystic or hemorrhagic areas where macrophages predominate. 3
• Consider using a whirling technique rather than to-and-fro motion if the nodule contains calcifications or fibrotic areas, as this may improve specimen adequacy. 4
• Ensure on-site cytology evaluation if available to confirm specimen adequacy before completing the procedure. 3

Consider Core Needle Biopsy (CNB)

If a third FNAB remains nondiagnostic, proceed to core needle biopsy, which has superior diagnostic performance in challenging nodules. 3, 4

• CNB demonstrates significantly lower unsatisfactory rates compared to FNAB (3.7% vs. 33.3%) in difficult-to-sample nodules. 4
• This approach is particularly valuable for nodules with extensive calcification, fibrosis, or predominantly cystic architecture. 3, 4

Risk Stratification During Workup

Ultrasound Re-evaluation

Perform dedicated thyroid ultrasound to assess features that determine urgency and guide sampling strategy. 5

• High-risk features requiring aggressive pursuit of diagnosis include: microcalcifications, solid hypoechoic composition, taller-than-wide shape, irregular margins, and central vascularity. 5, 3
• Evaluate for suspicious cervical lymph nodes, which would mandate definitive tissue diagnosis regardless of nodule size. 5
• Nodules ≥1-1.5 cm with suspicious features warrant persistent attempts at diagnosis. 5

TSH Measurement

Obtain TSH level if not already done to identify hyperfunctioning nodules that require different management. 5

• Hyperfunctioning ("hot") nodules on thyroid scintigraphy have extremely low malignancy risk and may not require further biopsy attempts. 5

Common Pitfalls to Avoid

• Do not accept a nondiagnostic result as reassuring. Two inadequate biopsies do not exclude malignancy and should not delay further diagnostic efforts. 1
• Do not assume cystic nodules are benign. Papillary thyroid carcinoma frequently undergoes cystic degeneration, and macrophage-rich aspirates may represent sampling of the cystic component rather than the solid tumor. 2
• Do not perform molecular testing on macrophage-only specimens. Molecular markers require follicular epithelial cells and cannot be interpreted from histiocytes alone. 1
• Avoid sampling only the cystic portion. Direct the needle specifically toward any solid components visible on ultrasound. 3

If Diagnosis Remains Elusive

For nodules with persistently nondiagnostic cytology despite optimized technique and CNB, management depends on ultrasound risk stratification. 5

• High-suspicion nodules: Consider diagnostic surgical excision (lobectomy) given the significant malignancy risk despite nondiagnostic biopsies. 1
• Low-suspicion nodules <1 cm: May be followed with serial ultrasound at 6-12 month intervals if clinical risk factors are absent. 1, 5
• Intermediate-suspicion nodules: Repeat ultrasound in 3-6 months; if growth or development of high-risk features occurs, proceed to surgical excision. 5