title: Intraepidermal cytokeratin 7 immunoreactive cells in the non-neoplastic nipple may represent interepithelial extension of lactiferous duct cells.
abstract: OBJECTIVE
  The interpretation of cytokeratin 7 (CK7)-positive cells in the epidermis of the nipple has been controversial. These cells have been described in Paget's disease of the nipple, and they have also been cited as benign 'Toker' cells or as Merkel cells. Having observed CK7+ cells in histologically unremarkable nipple biopsies, we sought to assess the distribution of CK7+ cells in Paget's disease of the nipple and in histologically unremarkable nipple.
  
  
  RESULTS
  Representative sections from 37 cases of Paget's disease of the nipple and 32 cases of histologically unremarkable nipple were obtained. The histologically unremarkable nipple sections were taken from prophylactic mastectomies (n=17) and from autopsies of patients who did not have breast cancer (n=15). CK7 immunostaining was performed on sections from formalin-fixed paraffin blocks. Sequential sections were immunostained with antibodies to low-molecular weight cytokeratin-CAM 5.2 and HER-2/neu. CK7+ cells were present in the epidermis around the opening of the lactiferous ducts in Paget's disease (95%) and in histologically unremarkable nipple (45%) cases. CK7+ cells diminished in number with increasing distance from the orifice of the lactiferous ducts. The lactiferous duct epithelium in Paget's disease and in histologically unremarkable nipple was CK7+ in all specimens when this element was present. CAM5.2 immunostaining had a similar but weaker pattern of reactivity. HER-2/neu reactivity was seen in 68% cases of Paget's disease and was negative in all cases of histologically unremarkable nipple. Tumour cells in two cases of Paget's disease were CK7-. In one of these, the underlying breast carcinoma was also CK7-, the only CK7- tumour in this series. In the other case, the normal lactiferous duct was CK7+ and no underlying carcinomatous tissue was available to study.
  
  
  CONCLUSIONS
  The presence of CK7+ cells does not equate to Paget's disease of the nipple. Intraepidermal CK7+ cells in the non-neoplastic nipple can be a manifestation of interepithelial extension of benign lactiferous duct cells. The increased presence of CK7+ cells in Paget's disease probably results either from neoplastic transformation of native intraepithelial lactiferous duct cells or form direct extension/migration of neoplastic cells into the nipple. The distribution of CK7 immunoreactive cells in the nipple epidermis can be helpful in the diagnosis of Paget's disease of the nipple.
authors.affiliation: Department of Pathology, New York Presbyterian Hospital, Weill Cornell Center, New York, NY 10021, USA.
authors.forename: D X
authors.initials: DX
authors.lastname: Yao
authors.forename: S A
authors.initials: SA
authors.lastname: Hoda
authors.forename: A
authors.initials: A
authors.lastname: Chiu
authors.forename: L
authors.initials: L
authors.lastname: Ying
authors.forename: P P
authors.initials: PP
authors.lastname: Rosen
mesh_terms: D015415:Biomarkers; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism / Q000473:pathology*; D003937:Diagnosis, Differential; D004817:Epidermis / Q000737:chemistry / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D053552:Keratin-7; D007633:Keratins / Q000032:analysis*; D009558:Nipples / Q000737:chemistry / Q000473:pathology*; D010144:Paget's Disease, Mammary / Q000378:metabolism / Q000473:pathology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis
chemical_list: D015415:Biomarkers; D053552:Keratin-7; D007633:Keratins; D018719:Erb-b2 Receptor Tyrosine Kinases; C400901:CAM 5.2 antigen; C507497:KRT7 protein, human