Thyroid nodules are a prevalent clinical finding, particularly in tertiary care hospitals, where advanced imaging often increases detection rates. Fine-needle aspiration cytology (FNAC) is established as the primary cost-effective triage tool for differentiating between benign and malignant lesions.^1,2 To provide a standardised framework for this differentiation, the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) was developed.

In late 2023, the Third Edition of TBSRTC was released, introducing significant changes to harmonise with the 2022 WHO Classification of Thyroid Neoplasms.^3,4 One of the most critical updates is the requirement for a single, standardised name for each of the six diagnostic categories to minimise clinical ambiguity.⁵ The updated categories are: Category I: Nondiagnostic (previously included 'Unsatisfactory'), category II: Benign, category III: Atypia of Undetermined Significance (AUS) (the term 'Follicular Lesion of Undetermined Significance' is now discouraged), category IV: Follicular Neoplasm ( the term ‘Suspicious for Follicular Neoplasm’ is discontinued), category V: Suspicious for Malignancy and category VI: Malignant. The term ‘follicular nodular disease’ replaces previously used terminologies, including ‘hyperplastic nodule’, ‘colloid nodule’, ‘adenomatous nodule’, or ‘benign follicular nodule’.^2,6

Beyond nomenclature, the 2023 update refined the Risk of Malignancy (ROM) for each tier, specifically accounting for the impact of Non-invasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features (NIFTP).^7,8 In Category III, the system now emphasizes subcategorization based on the presence of nuclear atypia, which carries a higher ROM and often necessitates molecular testing or surgical evaluation.^9,10

Despite these global revisions, the diagnostic performance of TBSRTC is subject to institutional variations in cytotechnique and pathologist expertise.¹¹ This cross-sectional study aims to evaluate the spectrum of thyroid lesions and the diagnostic utility—specifically the sensitivity and specificity—of the 2023 Bethesda framework within a tertiary care environment, utilising cytohistological correlation as the definitive benchmark for accuracy.¹².

Objectives

1. To categorise the spectrum of thyroid lesions using the 2023 Third Edition of the Bethesda System.
2. To analyse the frequency and distribution of cases across the six Bethesda diagnostic categories.
3. To calculate the Sensitivity, Specificity, Positive Predictive Value (PPV), and Negative Predictive Value (NPV) of the updated system, considering histopathology as the gold standard

MATERIALS AND METHODS

Study Type- Observational study

Study Design- Cross-sectional study

Study Setting- The study was conducted in the Department of Pathology at Agartala Government Medical College (AGMC & GBPH), Agartala, Tripura.

Study Period- December 2022 to November 2025.

Study Population- Patients who visited the cytology section of the Department of Pathology for FNA of thyroid lesions during the aforementioned period.

Exclusion Criteria-

Cases with damaged or lost cytological materials were excluded from our study.

Sample Size- 281 (determined on the basis of records, Department of Pathology, AGMC and GBPH).

Sampling Technique- Census sampling.

Study Procedure- All cytology smears of thyroid lesions were re-evaluated by two pathologists, and, after review, each case was assigned to one of the categories using the strict criteria of the Third Edition of TBSRTC (2023). The review was done blindly, independent of the previous cytological or histopathological diagnosis. All cases were evaluated in reference to the patient's age, sex, and lesion type. The cytological diagnoses were then compared with corresponding histopathological findings, wherever available.

RESULTS

1. Demographic and Clinical Profile

This cross-sectional study analysed 281 thyroid FNAC cases over a three-year period at our hospital. The patient population ranged from 13 to 81 years, with a mean age of 42.6 years. The study cohort showed a predominant female distribution (n=233; 82.9%) compared to males (n=48; 17.1%), yielding a male-to-female ratio of 1:4.8.

Pie chart 1: Sex distribution of cases

2. Age and Bethesda Category Distribution (2023 Update)

The distribution of the 281 cases across age groups and the Third Edition Bethesda System nomenclature is detailed below. The majority of cases were clustered in the 21–30 and 31–40 year age intervals.

Table 1: Distribution of Bethesda Categories by Age Group (n=281)

3. Spectrum of Cytological Lesions

The cytological spectrum was categorised according to the 2023 Bethesda criteria, with emphasis on the most prevalent benign and malignant manifestations.

1. Benign Lesions (Category II: n=210)

The benign spectrum was dominated by inflammatory and nodular diseases.

Lymphocytic Thyroiditis: 112 cases (53.3%)

Follicular Nodular Disease: 87 cases (41.4%)

Granulomatous Thyroiditis: 11 cases (5.3%)

Bar diagram 1: Spectrum of benign (category II) lesions

1. Malignant Lesions (Category VI: n=20)

Papillary carcinoma remains the most frequent malignancy detected in our tertiary care setting.

Papillary Carcinoma Thyroid: 16 cases (80%)

Medullary Carcinoma Thyroid: 3 cases (15%)

Anaplastic Carcinoma Thyroid: 1 case (5%)

Bar diagram 2: Spectrum of malignant lesions (category VI) lesions

4. Cytohistological Correlation and Diagnostic Performance

Of the 281 cases, 183 underwent surgical resection and histopathological examination (HPE). For statistical analysis, Categories V and VI were grouped as "Positive", while Category II was grouped as "Negative."

Table 2: 2x2 Contingency Table (n=183)

Statistical Parameter Value (%)

Sensitivity 90%

Specificity 98.7%

Positive Predictive Value (PPV) 93.1%

Negative Predictive Value (NPV) 98.1%

Overall Diagnostic Accuracy 97.3%

5. Summary of Histopathological Spectrum

Of the 183 correlated cases, 27 (14.8%) were confirmed as malignant on HPE. The high Negative Predictive Value (98.1%) reinforces the utility of the 2023 Bethesda Category II designation in safely excluding malignancy in a tertiary care setting. The detection of rarer malignancies, such as Medullary and Anaplastic carcinoma, highlights the critical role of FNAC in high-risk patient triaging.

Figure 1. 400x view of Giemsa-stained FNAC smear of Follicular Neoplasm

Figure 2. 400x view of Giemsa-stained FNAC smear of Anaplastic carcinoma, Thyroid

Figure 3. 100x view of H&E stained Histopathology slide of Medullary Carcinoma, Thyroid

Figure 4. 100x view of H&E stained Histopathology slide of Papillary Carcinoma, Thyroid

DISCUSSION

The implementation of the 2023 Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) has revolutionised the diagnostic approach to thyroid nodules by providing a unified nomenclature and refined Risk of Malignancy (ROM) estimates.¹³ Our cross-sectional study in a tertiary care setting confirms that this updated framework maintains high diagnostic integrity while offering clearer communication between pathologists and clinicians.¹⁴

Demographic and Clinical Spectrum

The study observed a marked female predominance (82.9%) with a male-to-female ratio of 1:4.8, which is consistent with global epidemiological data showing thyroid pathologies are significantly more common in women.¹⁵ The peak incidence of nodules in our cohort was observed in the 21–40 year age range (47.7%), similar to findings by Singh P et al., who reported that thyroid lesions are most frequently diagnosed during the reproductive and middle-aged years.¹⁶

Performance of the 2023 Bethesda Categories

Our results showed that Category II (Benign) was the most frequent diagnosis (74.7%), which reflects the high volume of non-neoplastic lesions encountered in a tertiary care setting.¹⁷ The high Negative Predictive Value (98.1%) for Category II in our study is a crucial metric; it supports the 2023 Bethesda recommendation for clinical follow-up rather than surgery for these patients, thereby reducing the burden of unnecessary thyroidectomies.^18,19

In the malignant spectrum, Papillary Thyroid Carcinoma (PTC) accounted for 80% of our Category VI cases. This dominance of PTC is a recurring theme in recent literature, partly due to the increased detection of microcarcinomas and the precise nuclear criteria established in the 2023 update.^20,21

Cytohistological Correlation and Accuracy

The core of our statistical validation was the correlation of 183 surgical cases. By classifying Categories V and VI as "Positive" findings, we achieved a Sensitivity of 90% and a Specificity of 98.7%. This high sensitivity is vital for a screening tool like FNAC, ensuring that fewer malignancies are missed.²²

Our Diagnostic Accuracy of 97.3% is slightly higher than that reported in some previous studies using the 2017 edition, suggesting that the 2023 refinements—such as the subcategorisation of AUS and the stricter definitions for follicular neoplasms—have improved the correlation between cytological suspicion and histopathological reality.^22,23.

Conclusion

This cross-sectional study validates the clinical utility of the 2023 Third Edition of the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) in a tertiary care hospital. By evaluating 281 cases with cytohistological correlation in 183 instances, several key conclusions are drawn:

Exceptional Diagnostic Performance: The updated Bethesda framework yielded a Sensitivity of 90.0% and a remarkably high Specificity of 98.7%. These metrics, combined with a Diagnostic Accuracy of 97.3%, confirm the system's role as a robust preoperative triaging tool.

Safety of Conservative Management: The Negative Predictive Value (NPV) of 98.1% for Category II (Benign) provides strong evidence for the safety of clinical observation, effectively minimising the rate of unnecessary surgical interventions for benign nodules.

Precision in Malignancy Prediction: A Positive Predictive Value (PPV) of 93.1% indicates that the 2023 criteria for Categories V and VI are highly reliable, allowing for confident surgical planning and definitive management.

Impact of 2023 Updates: The revised nomenclature and refined diagnostic criteria successfully harmonise cytological reporting with the latest WHO classification of thyroid neoplasms. This reduces ambiguity in "Indeterminate" cases and facilitates clearer communication within the multidisciplinary team

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