Atypical aspirates of the breast: a dilemma in current cytology practice.

Aims: The probabilistic approach is widely adopted for breast fine needle aspiration cytology. However, a definite cytological diagnosis is not always possible for C3 (atypia) cases, which poses a management dilemma as this represents a mixed category of benign and malignant cases. It would be beneficial to be able to predict malignancy based on specific cytological features in C3 aspirates.

Methods: A comprehensive panel of cytological features (including quantitative, cytomorphological and background features) in a large cohort of C3 breast aspirates with subsequent histological excisions was evaluated to identify relevant morphological criteria predicting the risk of subsequent malignancy.

Results: A total of 229 C3 specimens with histological follow-up were included. Malignant outcome was found in 30.1% of specimens and the majority were invasive cancers. Features that showed a significant association with malignant outcome included older age (p=0.001), lower percentage of epithelial cell clusters and high percentage of single cells (p=0.002), cribriform architecture in cell clusters (p=0.034), presence of intracellular mucin (p=0.027), increased cell clusters without myoepithelial cells (p=0.048), diminished fibromyxoid stromal fragments (p=0.001), reduced bipolar nuclei (p=0.021) and the presence of necrosis (p=0.023). Except for the percentages of single cells and cell clusters without myoepithelial cells, all other features were shown to be independent risk predictors in multivariate analysis.

Conclusions: C3 aspirates were associated with a significant probability of histological malignancy. Certain quantitative, cytomorphological and background features were potentially helpful in predicting the risk of a malignant outcome. The prediction could be clinically useful in the management of C3 cases.