Yao D X, Hoda S A, Chiu A, Ying L, Rosen P P
Department of Pathology, New York Presbyterian Hospital, Weill Cornell Center, New York, NY 10021, USA.
Histopathology. 2002 Mar;40(3):230-6. doi: 10.1046/j.1365-2559.2002.01362.x.
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.
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.
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.
乳头表皮中细胞角蛋白7（CK7）阳性细胞的解读一直存在争议。这些细胞在乳头佩吉特病中已有描述，也被认为是良性的“托克尔”细胞或默克尔细胞。在组织学上无异常的乳头活检中观察到CK7+细胞后，我们试图评估CK7+细胞在乳头佩吉特病和组织学上无异常的乳头中的分布情况。
获取了37例乳头佩吉特病和32例组织学上无异常乳头的代表性切片。组织学上无异常的乳头切片取自预防性乳房切除术（n = 17）和非乳腺癌患者的尸检（n = 15）。对福尔马林固定石蜡包埋块的切片进行CK7免疫染色。连续切片用抗低分子量细胞角蛋白-CAM 5.2和HER-2/neu抗体进行免疫染色。CK7+细胞存在于乳头佩吉特病（95%）和组织学上无异常乳头（45%）病例的输乳管开口周围的表皮中。CK7+细胞数量随着与输乳管开口距离的增加而减少。当存在该成分时，乳头佩吉特病和组织学上无异常乳头中的输乳管上皮在所有标本中均为CK7+。CAM5.2免疫染色具有相似但较弱的反应模式。HER-2/neu反应性在68%的乳头佩吉特病病例中可见，在所有组织学上无异常乳头病例中均为阴性。两例乳头佩吉特病的肿瘤细胞为CK7阴性。其中一例，其下方的乳腺癌也为CK7阴性，是本系列中唯一的CK7阴性肿瘤。另一例中，正常输乳管为CK7+，且没有下方癌组织可供研究。
CK7+细胞的存在并不等同于乳头佩吉特病。非肿瘤性乳头中的表皮内CK7+细胞可能是良性输乳管细胞上皮间延伸的一种表现。乳头佩吉特病中CK7+细胞数量增加可能是由于天然表皮内输乳管细胞的肿瘤转化或肿瘤细胞直接延伸/迁移至乳头所致。乳头表皮中CK7免疫反应性细胞的分布有助于乳头佩吉特病的诊断。
