Mammary foam cells. Characterization by immunohistochemistry and in situ hybridization

Cells showing abundant, finely vacuolized cytoplasm (foam cells) are found frequently in most benign lesions of the breast and in certain malignant breast tumours. The origin of mammary foam cells (FCs) has not been clarified, and we therefore studied the morphological features of mammary FCs in a series of 50 benign lesions. The FCs were subdivided, on the basis of their distribution into FCs lining the glandular lumina, intraluminal FCs, intraepithelial-pagetoid FCs, and stromal FCs. The lesions were tested with a panel of antibodies against macrophage (MAC 387, CD68) and epithelial (epithelial membrane antigen [EMA], gross cystic disease fluid protein 15 [GCDFP15] and cytokeratin) markers. The lesions were examined for the presence of PIP/GCDFP15-specific mRNA by an in situ hybridization technique. Three different types of FCs were identified. Type A FCs are epithelial cells (positivity with EMA and cytokeratin) and show apocrine differentiation (positivity with GCDFP15 antiserum and expression of PIP/GCDFP15 mRNA). Type B FCs are of macrophage origin, as they are positive with the macrophage markers and lack cytokeratin and PIP/GCDFP15 mRNA. Finally, type C FCs show an intermediate profile between an epithelial cell and a macrophage: they are both CD68 and GCDFP15 positive and show a thin peripheral rim of positivity with anti-cytokeratin antibody. They lack PIP/GCDFP15 mRNA. Our results indicate the possibility of a spectrum of phenotypes in mammary FCs, from epithelial-apocrine cells to macrophage-derived phagocytic cells.