Brown Heather M, Wilkinson Edward J
Department of Pathology, Immunology and Laboratory Medicine, University of Florida College of Medicine, Gainesville 32610, USA.
Hum Pathol. 2002 May;33(5):545-8. doi: 10.1053/hupa.2002.124787.
Paget disease of the vulva can be mimicked by several disease entities histopathologically, but most of these entities can be clinically distinguished from vulvar Paget disease. However, vulvar Paget disease is in itself a heterogeneous group of epithelial neoplasms that can be similar both clinically and histopathologically. The subtypes of vulvar Paget disease include primary Paget disease arising from a pluripotent stem cell within the epithelium of the vulva, and secondary Paget disease of the vulva. Secondary vulvar Paget disease results from spread of an internal malignancy, most commonly from an anorectal adenocarcinoma or urothelial carcinoma of the bladder or urethra, to the vulvar epithelium. We have recently proposed that these lesions be classified as primary (of cutaneous origin) or secondary (of extracutaneous origin). These subtypes can present similarly as eczematoid skin lesions and may appear similar on routine hematoxylin and eosin-stained slides. Immunohistochemical studies can help differentiate between them. Our current study includes 17 patients with a pathologic diagnosis of vulvar Paget disease. We performed a panel of immunohistochemical stains, including cytokeratin (CK) 7 and 20, carcinoembryonic antigen (CEA), gross cystic disease fluid protein-15 (GCDFP-15), and uroplakin-III (UP-III). Of these 17 patients, 14 (80%) had primary intraepithelial cutaneous Paget disease, 13 without invasion and 1 with associated invasion. Three patients had urothelial carcinoma with spread to the vulva, manifesting as secondary vulvar Paget disease. Immunohistochemically, primary vulvar Paget disease is immunoreactive for CK 7 and GCDFP-15, but uncommonly for CK 20. Vulvar Paget disease secondary to anorectal carcinoma demonstrates CK 20 immunoreactivity but is usually nonreactive for CK 7 and consistently nonimmunoreactive for GCDFP-15. Vulvar Paget disease secondary to urothelial carcinoma is immunoreactive for CK 7 and CK 20 but nonimmunoreactive for GCDFP-15. In addition, we propose the use of a new, commercially available antibody, UP-III, which is specific for urothelium and, in our experience, is immunoreactive in secondary vulvar Paget disease of urothelial origin. The distinction between these 3 types of Paget and Paget-like lesions is essential in that the specific diagnosis has a significant influence on current treatment. The difference in surgical approach to the subtypes of vulvar Paget disease justifies classifying them into distinct lesions, which may be aided by the use of immunohistochemistry, including UP-III.
外阴佩吉特病在组织病理学上可被多种疾病实体所模仿，但其中大多数实体在临床上可与外阴佩吉特病相鉴别。然而，外阴佩吉特病本身是一组异质性上皮性肿瘤，在临床和组织病理学上都可能相似。外阴佩吉特病的亚型包括起源于外阴上皮内多能干细胞的原发性佩吉特病和外阴继发性佩吉特病。外阴继发性佩吉特病是由内部恶性肿瘤扩散所致，最常见的是来自肛管直肠癌或膀胱或尿道的尿路上皮癌扩散至外阴上皮。我们最近提议将这些病变分为原发性（皮肤源性）或继发性（皮肤外源性）。这些亚型可同样表现为湿疹样皮肤病变，在常规苏木精和伊红染色切片上可能看起来相似。免疫组织化学研究有助于区分它们。我们目前的研究纳入了17例经病理诊断为外阴佩吉特病的患者。我们进行了一组免疫组织化学染色，包括细胞角蛋白（CK）7和20、癌胚抗原（CEA）、巨大囊肿病液体蛋白-15（GCDFP-15）和尿路上皮蛋白-III（UP-III）。在这17例患者中，14例（80%）患有原发性上皮内皮肤佩吉特病，13例无浸润，1例伴有浸润。3例患者患有尿路上皮癌并扩散至外阴，表现为继发性外阴佩吉特病。免疫组织化学方面，原发性外阴佩吉特病对CK 7和GCDFP-15呈免疫反应，但对CK 20反应罕见。继发于肛管直肠癌的外阴佩吉特病显示CK 20免疫反应性，但通常对CK 7无反应，对GCDFP-15始终无免疫反应。继发于尿路上皮癌的外阴佩吉特病对CK 7和CK 20呈免疫反应，但对GCDFP-15无免疫反应。此外，我们提议使用一种新的市售抗体UP-III，它对尿路上皮具有特异性，根据我们的经验，在尿路上皮源性继发性外阴佩吉特病中呈免疫反应。区分这三种类型的佩吉特病和佩吉特样病变至关重要，因为具体诊断对当前治疗有重大影响。外阴佩吉特病各亚型手术方式的差异证明将它们分类为不同病变是合理的，免疫组织化学包括UP-III的应用可能有助于此。
