Breast Lesions in Women ≤ 40 Years: Diagnostic Accuracy and Risk of Malignancy of Fine Needle Aspiration Cytology Based on the World Health Organization Breast Cytology Reporting System—A Systematic Review and Meta Analysis

INTRODUCTION: Breast cancer is the most common malignancy and the leading cause of cancer deaths among women worldwide. Diagnostic vigilance is vital as malignant cases in young women show higher proliferation and lower hormone-regulated gene expression, indicating more aggressive cases. The proposed IAC-IARC-WHO reporting system will adopt and update the current IAC Yokohama System for reporting breast cytology, which has five categories. This review evaluates the diagnostic accuracy of FNAC in women aged ≤ 40 using the WHO reporting system. MATERIAL AND METHODS: Studies were identified, screened, and assessed; data extracted, quality evaluated, and information synthesized based on predefined criteria. We performed a comprehensive search in PubMed/MEDLINE, Embase, and Scopus using Boolean operators for keywords up to December 2025. Eligible observational and case series studies with at least 20 participants were included. Study quality was assessed with QUADAS-3 to evaluate bias and applicability. Diagnostic categories were assigned to the WHO Reporting System for analysis and ROM calculation by consensus. RESULTS: Five studies with 245 FNAC procedures in women ≤ 40 years, 231 confirmed histopathologically. Pooled sensitivity was 81.33%, specificity 97.53%, and diagnostic accuracy 87.01%. The risk of malignancy (ROM) by WHO reporting system category ranged from 3.3% to 4.0% in the Benign category, reached 93.3% in the Suspicious for Malignancy category, and 100% in the Malignant category. The inadequate/unsatisfactory category showed a high ROM of 66.7%. These estimates are subject to significant spectrum bias because three of the five included studies enrolled only histologically confirmed malignant cases (true negatives = 0). Consequently, pooled specificity and NPV are based on only two studies with mixed benign and malignant cases. CONCLUSION: The present systematic review shows the high specificity and PPV, indicating that malignant or suspicious diagnoses in women aged 40 and under are highly reliable and need urgent management. Slightly lower sensitivity and NPV in this group highlight diagnostic challenges. ROM analysis confirms the WHO Reporting System's prognostic value: benign results have low ROM, while insufficient/inadequate, Atypical, SM, and Malignant categories have high ROM.