What is the purpose and application of the Bethesda scoring system in evaluating thyroid nodule fine-needle aspiration results?

Bethesda Scoring System for Thyroid Nodule Fine-Needle Aspiration

Purpose and Classification

The Bethesda System for Reporting Thyroid Cytopathology (BSRTC) is a standardized six-category classification system that stratifies thyroid nodules by malignancy risk to guide clinical management decisions, with each category carrying a specific risk of malignancy that directly determines whether observation, repeat biopsy, molecular testing, or surgery is indicated. 1

The system categorizes FNA results into six diagnostic groups 1:

Category I: Nondiagnostic/Unsatisfactory

• Malignancy risk: 6.3-20% 2, 3
• Requires repeat FNA under ultrasound guidance 4
• If repeat FNA remains nondiagnostic, assess the number of suspicious ultrasound features to determine next steps 4

Category II: Benign

• Malignancy risk: 1-3% 4, 2
• Highly reliable for ruling out malignancy 4
• Observation is appropriate for asymptomatic nodules <2 cm with close clinical follow-up 5
• Repeat FNA in 6-12 months if the nodule persists or grows 5

Category III: Atypia of Undetermined Significance (AUS)/Follicular Lesion of Undetermined Significance (FLUS)

• Malignancy risk: 11-23% 3, 6
• Represents indeterminate cytology requiring additional evaluation 1
• Molecular diagnostic testing (BRAF V600E, RET/PTC, RAS, PAX8/PPARγ) or gene expression classifiers may assist in management decisions 1
• Hypocellularity is a common factor causing diagnostic difficulty in this category 7
• Consider repeat FNA or molecular testing before proceeding to surgery 4, 5

Category IV: Follicular Neoplasm (FN)/Suspicious for Follicular Neoplasm (SFN)

• Malignancy risk: 20-40% 3, 6
• Follicular neoplasms are difficult to definitively diagnose by FNA alone and may require histological examination 4
• When TSH is normal and thyroid scan shows "cold" appearance, surgery should be considered for definitive diagnosis 4, 5
• Molecular testing can significantly improve diagnostic accuracy, with 97% of mutation-positive nodules being malignant 4
• Core needle biopsy may be necessary if repeat FNA remains indeterminate 4

Category V: Suspicious for Malignancy

• Malignancy risk: 74.2% 2
• Immediate referral for surgical consultation for total or near-total thyroidectomy 4, 5
• Proceed directly to surgery without frozen section examination 5

Category VI: Malignant

• Malignancy risk: 95.6-98% 5, 2
• Positive predictive value of 96-98% 5
• Immediate surgical intervention with total or near-total thyroidectomy 4, 5
• The Bethesda system is highly effective in predicting aggressive variants of papillary thyroid carcinoma, with 92% of aggressive variants (tall cell, diffuse sclerosing, columnar) correctly identified as malignant or suspicious on pre-operative cytology 2

Clinical Application and Key Considerations

Standardization Benefits

• The BSRTC provides uniform diagnostic terminology that allows comparison of management strategies across different institutions 8
• Achieves approximately 95% diagnostic accuracy and has fundamentally transformed thyroid nodule management by more than doubling the surgical yield of malignancy 5
• Use of the Bethesda system results in a lower rate of surgery for nonmalignant nodules (9% vs 20% with older classification systems) 7

Critical Pitfalls to Avoid

• Categories III (AUS/FLUS) and IV (FN/SFN) show overlapping 95% confidence intervals for malignancy risk (11-23% vs 20-29%), suggesting similar risks that require careful clinical judgment 3
• The distinction between categories III and IV has some degree of subjectivity, and use of BSRTC is heterogeneous across institutions 6
• Each institution should establish its own malignancy rates for indeterminate categories to guide local management protocols 6
• Do not rely on thyroid function tests (TSH, T3, T4) for malignancy assessment, as most thyroid cancers present with normal thyroid function 4

Adjunctive Testing for Indeterminate Results

• Molecular testing for BRAF, RAS, RET/PTC, and PAX8/PPARγ mutations is increasingly used for categories III and IV 1, 4
• Gene expression classifiers may demonstrate high predictive value for cytologically indeterminate nodules 6
• Serum calcitonin measurement should be part of the diagnostic workup to screen for medullary thyroid cancer, which has higher sensitivity than FNA alone 4, 5
• Complete cervical lymph node ultrasound evaluation is mandatory when thyroid nodules are discovered, as lymph node metastases alter surgical planning 5