Non‐invasive (intracapsular) carcinoma ex pleomorphic adenoma: recognition of focal carcinoma by HER‐2/neu and MIB1 immunohistochemistry

Abstract

Non-invasive carcinoma ex pleomorphic adenoma is defined as a carcinoma arising within the boundaries of a pleomorphic adenoma (PA), but which fails to display invasion beyond the capsule of host PA. Alternative names are intracapsular, in situ, or focal carcinoma. The true nature of non-invasive carcinoma ex-PA is still controversial; for example, it is not clear whether it represents early but genuine carcinomatous changes with the genetic make-up of malignant cells, or simply cytological, possibly metaplastic or 'bizarre' changes in PA. Strong overexpression and amplification of HER-2/neu protein has recently been demonstrated in invasive carcinoma ex-PA. In addition, data from breast cancer studies suggest that amplification of HER-2/neu and overexpression of its gene product is mainly involved in the initiation of breast oncogenesis. We sought to establish whether this method could help to demonstrate that what is described as non-invasive carcinoma ex-PA is really a genuine malignancy, albeit in an early phase. Eleven cases of non-invasive carcinoma (in situ) ex-PA were studied for HER-2/neu status using immunohistochemistry and fluorescent in-situ hybridization (FISH). Cells of focal non-invasive carcinoma ex-PA were strongly positive for HER-2/neu protein, while the cells of the maternal PA were always negative. Two cases of low-grade non-invasive myoepithelial carcinoma ex-PA were negative. In four cases out of a total of six tumours studied by FISH, we detected amplification of HER-2/neu gene signals in tumour cells of focal, non-invasive, carcinoma. The current data suggest that non-invasive carcinoma ex PA is a genuine carcinoma within a PA. However, the presence of cyto-nuclear atypia is not sufficient to make a definite diagnosis of malignant change, which requires a combination of morphology and immunohistochemistry.