What are the Bethesda criteria for thyroid cytopathology?

The Bethesda System for Reporting Thyroid Cytopathology

The Bethesda System for Reporting Thyroid Cytopathology classifies thyroid fine-needle aspiration (FNA) results into six standardized diagnostic categories that guide clinical management based on malignancy risk.

The Six Bethesda Categories

1. Category I: Nondiagnostic or Unsatisfactory

   • Specimens with insufficient follicular cells for diagnosis
   • Risk of malignancy: 5-10%
   • Management: Repeat FNA with ultrasound guidance

2. Category II: Benign

   • Includes nodular goiter, colloid goiter, hyperplastic/adenomatoid nodules, Hashimoto's thyroiditis
   • Risk of malignancy: ≤5%
   • Management: Clinical follow-up with ultrasound surveillance at 12-18 months initially, then 3-5 year intervals if stable 1

3. Category III: Atypia of Undetermined Significance (AUS) or Follicular Lesion of Undetermined Significance (FLUS)

   • Specimens with architectural and/or nuclear atypia more pronounced than benign changes but insufficient for categories IV-VI
   • Risk of malignancy: 15-30% (higher than originally estimated) 2
   • Management: Repeat FNA, molecular testing, or lobectomy depending on clinical risk factors and ultrasound features

4. Category IV: Follicular Neoplasm or Suspicious for Follicular Neoplasm

   • Includes Hürthle cell neoplasms
   • Risk of malignancy: 15-40%
   • Management: Surgical lobectomy for definitive diagnosis 3

5. Category V: Suspicious for Malignancy

   • High suspicion but not conclusive for malignancy
   • Risk of malignancy: 60-75%
   • Management: Surgical intervention (lobectomy or total thyroidectomy)

6. Category VI: Malignant

   • Includes papillary thyroid carcinoma, medullary thyroid carcinoma, anaplastic carcinoma, lymphoma
   • Risk of malignancy: 97-99%
   • Management: Total thyroidectomy or lobectomy based on tumor size and other risk factors

Clinical Application and Management

Molecular Testing Considerations

• Molecular diagnostic testing may be useful for evaluating indeterminate FNA samples (Categories III and IV) 3
• Tests may detect individual mutations (BRAF V600E, RET/PTC, RAS, PAX8/PPARγ) or use pattern recognition approaches with molecular classifiers
• If molecular testing suggests benign lesion (risk ≤5%), active surveillance may be appropriate 3
• If molecular testing suggests malignancy, surgical intervention is recommended

Special Considerations

• Hürthle cell neoplasms: Molecular diagnostics may not perform well; clinical risk factors and sonographic patterns should guide management 3
• NIFTP: Non-invasive follicular thyroid neoplasm with papillary-like nuclear features is a reclassification of certain encapsulated non-invasive follicular PTC variants with excellent prognosis 3
• Pediatric thyroid disease: The 2023 update includes specific risk of malignancy and management algorithms for pediatric patients 4

Pitfalls to Avoid

• Do not rely solely on nodule size for management decisions; consider ultrasound features and clinical context
• False-negative results can occur; a reassuring FNA should not override worrisome clinical findings 3
• Avoid overdiagnosis and overtreatment of small, subclinical papillary thyroid carcinomas 3
• Remember that certain entities (follicular carcinomas, NIFTP) cannot be definitively diagnosed by FNA alone 3

Evolution of the Bethesda System

• Originally established in 2007 at the NCI State of the Science Conference
• Updated in 2017 with revised malignancy risk estimates and consideration of NIFTP 5
• Further refined in 2023 with single names for each category, updated risk of malignancy ranges, and simplified subcategorization of AUS 4

The Bethesda System has proven to be an excellent standardized reporting framework for thyroid FNA with high sensitivity, specificity, and accuracy when correlated with histopathological diagnoses 6. It provides clear management guidelines for clinicians and helps identify patients who require surgical intervention versus those who can be managed with observation.