Toker cells revisited

Toker cells are inconspicuous cytokeratin 7 positive cells that should be distinguished from intraepidermal involvement by malignant cells seen in Paget's disease (PD) of the nipple. The aim of our study was to quantitatively assess the number and pattern of distribution of Toker cells in nipples without PD in mastectomy specimens. Sequential sections from the nipple of 173 mastectomies were evaluated using HE and immunohistochemistry. Two breast pathologists reviewed the stains and recorded the number and pattern of distribution of CK7 positive cells (CK7+) and their HER2/neu, ER and PR status. There were 152/173 (88.4%) cases with CK7+ cells. The mean number of CK7+ cells per section was 22 (range 0-200) and the mean number of CK7+ cells per field at 10x was 10 (range 0-106). 10/37 (27%) of nipples from prophylactic mastectomies and 15/136 (11.1%) of mastectomies for cancer displayed over 10 CK7+ cells in an area of 10x. In 32/173 (18.5%) CK7+ cells formed small groups or clusters. Notably these cells were not restricted to the basal part of the epidermis. None of the groups/clusters of Toker cells were appreciated on HE stain and all were HER2/neu, ER and PR negative. The absence of any CK7+ cells in 20 cases occurred in hyperpigmented epidermis, possibly obscuring rare positive cells. Toker cells are frequently present in the epidermis of the nipple and are more prevalent than appreciated on routine HE stain. These cells can be present in clusters and can have pagetoid pattern of distribution. They occur in nipples of cancer patients with or without PD and in prophylactic mastectomies performed for high risk patients. The substantial number and the clustering of Toker cells should not be mistaken for PD of the nipple. Unlike PD, Toker cells have small bland nuclei and are characterized by CK7+ and HER2/neu ER and PR negative immunoprofile.