Background: Fine-needle aspiration (FNA) of breast specimens can be difficult and between 10-25% of the lesions ultimately are classified as "atypical," even by the most experienced cytopathologist. The goal of this study was to identify a molecular mechanism that reliably distinguishes benign and malignant (or pre-malignant) lesions and that could be used as an adjunct in these morphologically ambiguous cases.
Methods: Because all malignancies represent clonal proliferations, assessment of clonality represents a potential molecular mechanism for making this distinction. Excess material preserved from breast FNAs was examined using the human androgen receptor locus clonality assay. This assay allows determination of clonality on the basis of X chromosome inactivation as detected by polymerase chain reaction analysis of genomic DNA after methylase-sensitive restriction digestion.
Results: In this pilot study, 25 cases showed reproducible results. All malignant cases (9 of 9) were monoclonal, whereas 10 of 12 benign cases were polyclonal. Of four atypical cases, two were monoclonal and both were found to be malignant after surgical resection. Monoclonality was observed in two benign cases that were hyperplastic lesions.
Conclusions: These preliminary results suggest that this test may provide a non-morphologic molecular mechanism for the objective categorization of breast FNAs.