Salivary duct carcinoma in situ of the parotid gland.

AIMS: To describe three cases of purely in situ salivary duct carcinoma, so as better to define the entity. METHODS AND RESULTS: Three primary tumours of the parotid gland are presented, in each case composed of cysts and ducts and lined by high nuclear grade epithelial cells. All parts of each tumour were surrounded by a myoepithelial cell rim and there was no evidence of invasion. The tumour cells expressed immunohistochemical markers seen in invasive salivary duct carcinoma of usual (high-grade) type. In two cases the androgen receptor (AR) reaction was strong, but there was no immunohistochemical expression of HER2 protein or gene amplification by in situ hybridization. In the remaining case, fewer nuclei stained for AR, but both HER2 protein and gene amplification were demonstrated. CONCLUSIONS: Salivary duct carcinoma in situ is morphologically similar to breast ductal carcinoma in situ and, although our cases are few, salivary duct carcinoma in situ can possibly be subdivided into luminal and non-luminal cell types, as can analogous mammary neoplasms. The present study cannot determine whether low-grade cribriform cystadenocarcinoma, architecturally similar but immunohistochemically different, is part of the spectrum of salivary duct carcinoma in situ, or whether it represents a separate entity.

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

AIMS: 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. METHODS AND RESULTS: 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. CONCLUSIONS: 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.

Polymorphous low-grade adenocarcinoma of the salivary glands with transformation to high-grade carcinoma.

AIMS: Polymorphous low-grade adenocarcinoma of the minor salivary glands is an infiltrative neoplasm characterized by bland-looking tumour cells arranged in diverse architectural patterns. It is considered to be of low-grade malignant potential in that nodal metastases are seen in only a minority, and distant spread is rare. Even more unusual is the transformation of polymorphous low-grade adenocarcinoma to a histologically high-grade carcinoma, i.e. dedifferentiation. In this paper, we describe the clinicopathological and immunohistochemical findings in two further examples. METHODS AND RESULTS: Two patients presented each with a tumour of the palate. Histopathological examination showed the typical morphological, cytological and immunohistochemical features of a polymorphous low-grade adenocarcinoma. In one case there was a second component of high-grade carcinoma showing nuclear atypia, markedly increased mitotic activity and MIB1 index, as well as prominent zones of necrosis. It expressed epithelial markers and androgen receptors, and thus resembled salivary duct carcinoma. Similar tumour tissue was observed in one of the cervical nodal metastases, which was biopsied at the same time as the palate. In the second patient, a high-grade component was discovered when the tumour recurred in the palate 13 years after the initial biopsy. Whilst morphologically similar to that in first case, there were significant immunohistochemical differences such as retention of some of the polymorphous low-grade adenocarcinoma profile and absence of androgen receptor expression. CONCLUSIONS: Polymorphous low-grade adenocarcinoma was first described relatively recently, and as experience with it continues to accumulate, it is becoming clear that late recurrences and metastases, whilst still infrequent, may not be quite as rare as previously thought. Reports of histological transformation are even scarcer, and most occurred at least 13 years after the polymorphous low-grade adenocarcinoma was initially recognized. It is a real possibility that this phenomenon, like clinical progression, may also be encountered more often as time passes. Therefore, we believe that, whilst polymorphous low-grade adenocarcinoma is certainly far less aggressive than, for example, adenoid cystic carcinoma, it nevertheless remains a true malignancy with a potential to prove fatal in a minority of patients.

Sclerosing polycystic adenosis of parotid gland with dysplasia and ductal carcinoma in situ. Report of three cases with immunohistochemical and ultrastructural examination.

We describe three cases of sclerosing polycystic adenosis (SPA) of the parotid gland, a salivary condition analogous to fibrocystic disease of the breast. For the first time, immunoreactivity for oestrogen and progesterone receptors was demonstrated, suggesting a possible participation of hormone stimulation in its pathogenesis. In addition, all our cases showed foci of dysplasia of the ductal epithelium, which in one case was severe enough to amount to carcinoma in situ. This feature that has not previously been reported in SPA.