Lundquist K, Kohler S, Rouse R V
Department of Pathology, Stanford University Medical Center, California 94305, USA.
Am J Surg Pathol. 1999 Feb;23(2):212-9. doi: 10.1097/00000478-199902000-00011.
Histologically, extramammary Paget's disease and mammary Paget's disease (MPD) are characterized by large atypical cells distributed throughout the epidermis. Although classic examples of these disorders are easily diagnosed on morphologic grounds, some cases may cause differential diagnostic problems. Immunohistology with a wide variety of antibodies has been used as an aid for the identification of Paget cells, for their distinction from other entities, and for investigation of the origin or nature of the disorder. Recently, cytokeratin 7 has been proposed as a specific and 100% sensitive marker for Paget's disease. We studied 22 cases of mammary Paget's disease and 22 cases of extramammary Paget's disease with and without an underlying malignancy for their reactivity with monoclonal antibodies to cytokeratin 7 (CK7) and cytokeratin 20 (CK20). Our studies show that anti-CK7 is an effective but not 100% sensitive marker for Paget cells, staining 21 of 22 cases of mammary Paget's disease and 19 of 22 cases of extramammary Paget's disease, whereas CK20 stained 0 of 17 cases of mammary Paget's disease and 6 of 19 cases of extramammary Paget's disease. We also demonstrate that CK7, but not CK20, highlights intraepidermal clear cells with bland nuclear features (Toker cells) that have been reported in 11% of normal nipples. By using CK7 as a marker, however, we were able to identify Toker cells in most of the nipples we studied: 8 of 15 nipples from mastectomy patients without Paget's disease, and 15 of 18 autopsy cases (both male and female) with normal breasts and nipples. It also permitted us to perform more extensive phenotyping on them, showing that Toker cells share similar antigens with Paget cells and with cells lining the underlying normal lactiferous ducts. In 7 of 15 cases containing CK20-positive Merkel cells, CK7 was also seen to stain Merkel cells. In infrequent cases, Toker cells or Merkel cells may be so numerous focally that a CK7 stain may raise the possibility of involvement of the nipple by Paget's disease. An awareness of the CK7 reactivity of Toker cells and Merkel cells as well as attention to the cytologic features of the case should avoid this problem.
组织学上，乳腺外佩吉特病和乳腺佩吉特病（MPD）的特征是大的非典型细胞分布于整个表皮。尽管这些疾病的典型病例基于形态学很容易诊断，但有些病例可能会引起鉴别诊断问题。使用多种抗体进行免疫组织化学已被用于辅助识别佩吉特细胞，将其与其他实体区分开来，并研究该疾病的起源或性质。最近，细胞角蛋白7被提议作为佩吉特病的一种特异性且100%敏感的标志物。我们研究了22例乳腺佩吉特病和22例乳腺外佩吉特病，包括有无潜在恶性肿瘤的病例，观察它们与抗细胞角蛋白7（CK7）和细胞角蛋白20（CK20）单克隆抗体的反应性。我们的研究表明，抗CK7是一种有效的但并非100%敏感的佩吉特细胞标志物，22例乳腺佩吉特病中有21例、22例乳腺外佩吉特病中有19例呈阳性染色，而CK20在17例乳腺佩吉特病中均为阴性，在19例乳腺外佩吉特病中有6例呈阳性染色。我们还证明，CK7而非CK20能突出显示表皮内具有温和核特征的透明细胞（托克尔细胞），在11%的正常乳头中曾有报道。然而，通过使用CK7作为标志物，我们能够在我们研究的大多数乳头中识别出托克尔细胞：15例无佩吉特病的乳房切除患者的乳头中有8例，18例乳房和乳头正常的尸检病例（包括男性和女性）中有15例。这也使我们能够对它们进行更广泛的表型分析，表明托克尔细胞与佩吉特细胞以及下方正常输乳管内衬细胞具有相似的抗原。在15例含有CK20阳性默克尔细胞的病例中有7例，CK7也可见于默克尔细胞染色。在少数情况下，托克尔细胞或默克尔细胞可能在局部数量众多，以至于CK7染色可能会增加乳头受佩吉特病累及的可能性。了解托克尔细胞和默克尔细胞的CK7反应性以及关注病例的细胞学特征应可避免这一问题。
