The Bethesda System Revisited: Malignancy Risk Estimation and NIFTP Impact in a Large Cohort From Northern India

Thyroid nodules are common in clinical practice, and fine-needle aspiration cytology (FNAC) remains the primary test for malignancy risk assessment. The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) standardizes interpretation and guides management. This study evaluated the distribution of Bethesda categories, risk of neoplasia (RON) and malignancy (ROM), and the impact of non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) on risk stratification.

A retrospective review of 2578 thyroid FNACs (2016-2024) was conducted at King George's Medical University, Lucknow. Cytological diagnoses were classified using TBSRTC (2017 and 2023). Histopathological correlation was available in 1043 cases (40.5%). RON and ROM were calculated for each category, with ROM assessed before and after excluding NIFTP. Smears were independently reviewed by two cytopathologists, and diagnostic metrics (sensitivity, specificity, accuracy) were derived using histopathology as reference; 95% confidence intervals were estimated by exact binomial methods.

Most cases were Benign (73.2%), followed by Malignant (7.2%) and Follicular Neoplasm (6.1%). Malignancy was confirmed in 245 cases. ROM ranged from 3.7%-9.9% (Benign) to 58.6%-100% (Malignant), showing a progressive rise across categories. Reclassification of NIFTP notably reduced ROM for indeterminate categories (AUS: 43.2% → 31.8%; FN: 40.2% → 28.4%; SM: 52.4% → 42.9%).

TBSRTC reliably stratifies malignancy risk in thyroid nodules. Reclassification of NIFTP has a substantial impact on ROM in indeterminate categories, underscoring the need for precise cytologic-histologic correlation and regional validation to optimize patient management.