Bethesda Thyroid System: Categories, Role in Clinical Domain, Future, and More

Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) is a widely used procedure for thyroid nodule biopsies. It allows cytological diagnoses to be grouped into definitive categories with accuracy. Thus, it promotes communication among clinicians and pathologists and helps determine clinical management strategies.

The Bethesda System categorises thyroid fine needle aspiration (FNA) biopsy results, which help identify the risk of cancer, guide treatment plans, and improve patients’ condition. This article looks at the categories of the Bethesda System, its role in medical management, updates in this system, risks, future, and more. 

Understanding the Bethesda System Categories

Bethesda's system is grouped into six different categories, each of which has a different degree of suspicion for malignancy. With these categories varying from the sample being benign to the possibilities of cancer, it ensures a seamless detection and management of diseases. The six categories are discussed below: 

• Category I: Non-diagnostic or Unsatisfactory

This category is assigned when there is a lack of proper representation of the material collected by the FNA. It may be due to a poor sample, low cellularity, or a wrong technical step during the approach. 

Under such circumstances, the patient will require undergoing another biopsy. The chances of having cancer in Category I are minimally significant since the specimen provided is very cellular for use in any diagnosis.

• Category II: Benign Lesion

If the cytological biopsy does not report malignancy, it becomes benign. This category includes benign colloid nodules, hyperplastic nodules, and cystic lesions. The potential risk of malignancy in this category is minimal, usually not more than 3% of Category II cancers. 

• Category III: Atypia of Undetermined Significance

Category III is rendered for atypia or cellular change that does not clearly establish a diagnosis of benignancy or malignancy. The criteria are usually architectural or cytological changes, including minor nuclear atypia, that cannot ensure the presence of malignancy. 

The risk of malignancy in Category III is considered intermediate, at 5% to 15%. This category demands close clinical follow-up and repeat biopsies or molecular testing in order to assess the possibility of malignancy.

• Category IV: Follicular Neoplasm or Suspicion for a Follicular Neoplasm

Category IV refers to those nodules characterised by cytology suspicious of follicular neoplasm, namely follicular adenoma and follicular carcinoma. Such lesions are marked by cellular atypia or have a concerning follicular architecture consistent with some neoplastic process.

The malignancy risk in Category IV is high, ranging usually from 15% to 30%. This requires proper diagnosis through surgical resection, usually accompanied by histopathological evaluation.

• Category V: Suspicious for Malignancy (SM)

This category covers the FNA demonstrating significant cytologically suspicious features of malignancy, such as papillary thyroid carcinoma (PTC) or medullary thyroid carcinoma (MTC). The malignancy risk of Category V is relatively high, usually between 60% and 75%. 

Other immediate surgical interventions are often indicated in this case in terms of diagnosis confirmation and deciding on the ideal treatment.

• Category VI: Malignant

Category VI is assigned when the cytological findings demonstrate malignancy, such as papillary thyroid carcinoma, anaplastic thyroid carcinoma, or other thyroid neoplasms. The malignancy risk is 98% to 100% in this category and deserves immediate treatment, usually through surgery for patient management.

Diagnostic Reliability and Limitations of the Bethesda System  

The Bethesda System offers a clear way to classify thyroid FNA results, improving consistency in diagnoses across different medical facilities. Its effectiveness is well-supported by research, showing that pathologists generally agree on results and that there is little variation in their findings. This helps to lower the chances of false-positive and false-negative results, boosting confidence in diagnoses.

However, the Bethesda System does have some drawbacks. The subjective nature of cytopathology, especially in categories like atypia of undetermined significance (Category III) and follicular neoplasm (Category IV), can lead to different interpretations. 

Additionally, the system does not cover all thyroid lesions, particularly those that are atypical or indeterminate and do not fit into the defined categories. This can create issues with overdiagnosis or underdiagnoses, thus causing misinterpretation or incomplete classification.

Role of Bethesda System in Clinical Management

Here is the role of the Bethesda System in clinical management, ensuring patient care and treatment decisions: 

• Impact on Patient Care and Decision-Making

The Bethesda System directly influences clinical decision-making by providing a clear matrix for managing thyroid nodules. The classification directs the subsequent step in the patient's care in terms of whether to pursue additional diagnostic tests, follow-up, or immediately undergo surgery. 

• Integration with Molecular Testing

Molecular testing may further augment the Bethesda system for risk stratification. Such situations are in the form of auguring between Category III and IV paired for the purposes of determining further molecular testing for genetic events, such as BRAF (B-Raf Proto-Oncogene, Serine/Threonine Kinase), RAS (Rat Sarcoma Virus), or RET/PTC (Rearranged in Transfection / Papillary Thyroid Carcinoma).

Risk of Malignancy Associated with Each Category of Bethesda System

The Bethesda System for Reporting Thyroid Cytopathology categorises the risk of cancer in thyroid nodules into six groups with risks 0–3% to 98%:

• Category I: Non-diagnostic or unsatisfactory; cancer risk 1–4%
• Category II: Benign; cancer risk 0–3%
• Category III: Atypia or follicular lesion of undetermined significance; cancer risk 5% to 15%
• Category IV: Follicular neoplasm; cancer risk 15% to 30%
• Category V: Suspect malignancy, with cancer risk of 60% to 75%
• Category VI: Malignant, with a cancer risk of 98% to 100%.

Updates and Revisions in the Bethesda System

Since its inception, the Bethesda System has been modified several times to enhance more precise diagnosis. Initially, upgrades were directed towards bettering risk stratifications and ensuring more consistent classification.

Meanwhile, more recent modifications widened clarifications for indeterminate categories, fixed interpretation challenges, and delivered predictive value for malignancies. These amendments, thus, enhanced clinical decisions and the management of patients.

Future Perspectives of Bethesda Thyroid System

The Bethesda Thyroid System is moving towards an excellent future as constant innovations improve diagnosis accuracy. The TBSRTC third edition, released in 2023, includes the newest updates regarding thyroid cytology, as well as the 2022 World Health Organisation (WHO) classification of thyroid tumours. The new updates involve:

• Report Simplification: The TBSRTC has a name for each of its six diagnostic categories.
• Updated Malignancy Risk: The cancer risk of each group has now been updated.
• Unified Nomenclature: The TBSRTC complies with the 2022 WHO classification of thyroid tumors.
• Subgrouping of Atypia of Undetermined Significance (AUS): The AUS category has been split into two subgroups for optimal risk assessment.
• Extension of Ancillary Tests: Two novel chapters on molecular and ancillary testing have now joined TBSRTC.
• Application Referred to Paediatric Thyroid Nodules: People can use TBSRTC to report thyroid cytology in children.
• Eliminating Other Names: To reduce confusion, several alternate names for diagnostic groups have been eliminated.

Conclusion

The Bethesda Thyroid System has greatly transformed the diagnosis and management of thyroid cancer by offering clinicians a structured, evidence-based framework for guiding patient care. 

Although it has limitations, its integration with molecular testing and emerging technologies is likely to improve diagnostic accuracy and patient outcomes further. The evolving field of cytopathology continues to use the Bethesda System as an essential tool in the ongoing efforts towards greater understanding and treatment of thyroid diseases.