Morphological Features Predictive of Malignancy in Cytology Smears of Atypical Proliferative Breast Diseases: A Cross-sectional Study

Introduction: Breast lesions comprise about 34-40% of lesions evaluated by fine-needle aspiration in surgical practice. FineNeedle Aspiration Cytology (FNAC) is increasingly used as a simple and cost-effective method to assess the nature of breast lesions, with high sensitivity and reasonable specificity, which helps in planning further treatment. However, a small percentage of breast lesions cannot be confidently diagnosed as benign or malignant and are termed grey-zone lesions. These include reactive atypia seen in some benign conditions and atypia of malignancy. Aim: To analyse the cytological features of atypical proliferative breast diseases associated with a malignant diagnosis on histopathologic examination. Materials and Methods: This was a cross-sectional study involving FNAC smears of all patients diagnosed as proliferative breast disease with atypia in the Department of Pathology, Government Medical College, Kozhikode, Kerala, India, from January 2018 to June 2021. Clinical and cytological features were studied, and patients were followed-up until June 2022. The lesions were classified histologically into benign and malignant lesions. The cytological features in the FNAC smears were studied. The data were entered into spreadsheets in Microsoft Excel, and the variables were analysed using Statistical Package for the Social Sciences (SPSS) version 16.0 for Windows. The Chi-square test was used to evaluate features significantly associated with a histological diagnosis of malignancy. Results: The study included a total of 162 cases diagnosed as proliferative breast disease with atypia on FNAC. Histopathological follow-up was available for these cases, with 73 benign and 89 malignant. Clinical features that were statistically significant in subjects with malignant histopathological diagnoses included age over 40 years, presence of a hard and fixed breast lump, and nipple changes. Cytological features predictive of a malignant histological diagnosis included clusters with ill-defined borders, loosely cohesive or cribriform clusters, clusters with markedly reduced or absent myoepithelial cells, reduced stromal fragments, numerous singly scattered atypical cells, markedly reduced or absent bipolar bare nuclei in the background, high mitotic rate, and necrosis. The nuclear features that were statistically significant included marked nuclear enlargement, nuclear pleomorphism, irregular nuclear contour, nuclear overlapping, and coarse nuclear chromatin. Conclusion: The diagnosis of malignancy requires a multifaceted approach, including correlation with clinical, radiological, and pathological features. For an unequivocal cytological diagnosis of malignancy, a constellation of cytomorphological features is needed; a single morphological feature cannot reliably distinguish between benign and malignant lesions. Proper knowledge of the various cytomorphological features of malignancy can help predict malignancy even if all classical cytological features are not present. Cytological study can be a useful adjunct in triaging cases where prompt histopathological assessment is mandatory.