Toker cells are probably precursors of Paget cell carcinoma: a morphological and ultrastructural description

Abstract

The present paper documents an investigation of the morphology, immunohistochemistry, and ultrastructure of Toker cells (TC), aiming for a better definition of these elements and better understanding of their histogenesis. We studied 12 nipples removed for nipple adenoma from twelve patients and a case of supernumerary nipple. In addition four cases of Paget's carcinoma (PC) restricted to the nipple without underlying tumor were studied for comparison. All cases were stained with hematoxylin and eosin (H&E), Alcian blue pH 2.5 and periodic acid-Schiff (PAS) preceded by diastase digestion and with immunohistochemistry using antisera anti cytokeratin 7, cytokeratin 20, protein S100, GCDFP-15, c-Erb-B2, CAM 5.2, and epithelial membrane antigen (EMA). Two cases from the nipple adenoma series were studied by electron microscopy. In seven cases within the series of 12 nipple adenomas as well as in the case of supernumerary nipple, keratin 7 antibody highlighted numerous cells located within the nipple epidermis which in three cases showed dendritic processes. These same elements were also positive with CAM 5.2. All these same elements were negative with Alcian Blue (AB), PAS and the other antisera employed. Ultrastructural examination demonstrated that these cells differed from keratinocytes while they presented the same features as the glandular cells seen in the related nipple adenoma. The cells constituting Paget's carcinoma showed more irregular nuclei and were more easily seen in the context of the epidermis. The immunocytochemical profile of the cancer cells was similar to that of TC, but in addition the neoplastic cells were c-Erb-B2 and EMA positive in all cases, and one case also displayed numerous cells immunoreactive with anti GCDFP-15 antibody. Keratin 7 highlighted dendritic cells in two cases and AB, PAS was negative in all patients. The immunocytochemical profile and the ultrastructural features of TC are similar to those of the glandular cells constituting the ducts and the adenoma. These findings together with the localization of TC near or around the openings of the lactiferous sinuses indicate that TC might be ductal cells with a dendritic aspect and migrate through the galactophorous ostia. PC cells not related to ductal carcinomas have a similar but not superimposable immunohistochemical profile to TC, and in two cases the neoplastic elements were also dendritic which suggests that these same cells are likely to be the neoplastic counterpart of TC.