乳房外Paget病相关基因的研究进展

乳房外Paget病是一种少见的皮肤恶性肿瘤,常发生于肛门、会阴生殖器部位,皮损特征为红斑、浸润或溃疡等湿疹样表现.很多学者应用免疫组化的方法对乳房外Paget病相关蛋白的表达,进而对有关基因进行研究,从而探讨该病的病因及发病机制.原癌基因Her-2的扩增、黏蛋白基因MUC1、MUC2、MUC5AC的表达模式、角蛋白基因CK7、CK20的表达模式以及GCDFP-15基因的阳性表达等在研究乳房外Paget病的组织发生中均有一定意义.     

Immunohistochemical analysis of human milk fat globulin expression in extramammary Paget's disease

Primary extramammary Paget's disease is thought to be an intraepidermal carcinoma indicating apocrine secretory differentiation. In addition to expression in breast tissue, human milk fat globulin (HMFG) is expressed in the normal apocrine glands and tumours with apocrine differentiation. In this study HMFG expression in extramammary Paget's disease was analysed immunohistochemically in 18 cases of primary extramammary Paget's disease and two cases of secondary extramammary Paget's disease. The proportion and staining pattern of positive tumour cells with the anti-HMFG antibody was variable in each case. Cytoplasmic staining was observed frequently in dermal invasion and metastasis of Paget cells. The variabilities were thought to be due to modulation of the cellular localization of the cell surface component, HMFG, according to changes in cellular differentiation or malignant potency.     

Depigmented extramammary Paget's disease

BACKGROUND: Depigmented extramammary Paget's disease (EMPD) has been reported in a few cases. Depigmented macules or patches may be the only presenting sign or may coexist with the classical erythematous lesions. OBJECTIVES: To investigate the occurrence rate and clinical presentation of depigmentation in EMPD. METHODS: All pathology-proven cases of EMPD diagnosed in our department during 1990-2003 were retrieved. The clinical photographs were reviewed for evidence of local depigmentation. The pathological diagnosis of EMPD in the whitish lesions was confirmed by positive expression of cytokeratin 7 or carcinoembryonic antigen, and/or the presence of intracytoplasmic mucin. RESULTS: Of 19 cases of EMPD, six (30%) manifested depigmented lesions which were confirmed to be EMPD pathologically. In two patients, the hypopigmentation was associated with erythematous lesions at the initial presentation. In four others, the depigmentation developed later as local recurrence after excision, cryotherapy, photodynamic therapy or radiotherapy. The progressive enlargement of the depigmentation and the appearance of separate new white lesions in these four cases suggested that the localized depigmentation was unlikely to be simple postinflammatory hypopigmentation. CONCLUSIONS: Our study suggests that depigmented EMPD may not be rare. Localized depigmentation in the genital area can be an early sign of EMPD and its local recurrence. In patients with an established diagnosis of EMPD, appearance of new white lesions and continuous enlargement of depigmented patches should not be dismissed as simple treatment-induced postinflammatory hypopigmentation or another type of hypopigmented lesion without biopsy confirmation.     

Mammary and extramammary Paget's disease

Ten cases of mammary Paget's disease and 10 cases of extramammary Paget's disease were studied for differences of histologic features in them. Based on the epidermal changes alone, Paget cells in 90% of specimens from lesions of extramammary Paget's disease had abundant mucin that stained well, whereas Paget cells in only 40% of specimens from mammary Paget's disease stained for mucin and faintly at that. In 60% they did not stain at all. The conclusion derived from these observations is that the mucin in Paget cells of extramammary Paget's disease is different from that found in cells of mammary Paget's disease. The Paget cells in these two conditions seem to have different origins, i.e., those of mammary Paget's disease ascend to the epidermis from lactiferous ducts, whereas those of extramammary Paget's disease originate in the epidermis itself.     

Mammary and extramammary Paget's disease

Paget''s disease, described by Sir James Paget in 1874, is classified as mammary and extramammary. The mammary type is rare and often associated with intraductal cancer (93-100% of cases). It is more prevalent in postmenopausal women and it appears as an eczematoid, erythematous, moist or crusted lesion, with or without fine scaling, infiltration and inversion of the nipple. It must be distinguished from erosive adenomatosis of the nipple, cutaneous extension of breast carcinoma, psoriasis, atopic dermatitis, contact dermatitis, chronic eczema, lactiferous ducts ectasia, Bowen''s disease, basal cell carcinoma, melanoma and intraductal papilloma. Diagnosis is histological and prognosis and treatment depend on the type of underlying breast cancer. Extramammary Paget''s disease is considered an adenocarcinoma originating from the skin or skin appendages in areas with apocrine glands. The primary location is the vulvar area, followed by the perianal region, scrotum, penis and axillae. It starts as an erythematous plaque of indolent growth, with well-defined edges, fine scaling, excoriations, exulcerations and lichenification. In most cases it is not associated with cancer, although there are publications linking it to tumors of the vulva, vagina, cervix and corpus uteri, bladder, ovary, gallbladder, liver, breast, colon and rectum. Differential diagnoses are candidiasis, psoriasis and chronic lichen simplex. Histopathology confirms the diagnosis. Before treatment begins, associated malignancies should be investigated. Surgical excision and micrographic surgery are the best treatment options, although recurrences are frequent.     

Multilocular extramammary Paget's disease]

Paget cells were found histologically in a patient with erythemato-erosive lesions on the genitoperineale areas. These cells were also observed in the right axillary skin within a tiny depigmented spot and even in the left axillary skin which was macroscopically almost intact. There were no signs of metastatic or deep-seated adnexal adenocarcinoma. Treatment consisted of radical operation of the pathological lesions with skin grafting and removal of one testicle. After the operation the x-ray irradiation was performed.     

Ultrastructural features of extramammary Paget's disease

Summary In the epidermis of a case of Paget's disease of the vulva two atypical cell variants (type I cells or clear cells and type II cells or dark cells) have been shown, which have the characteristic fine structure of glandular cells. The same finding has been noticed in Paget's disease of the nipple.The authors favor the hypothesis that these cells migrate from the deepseated glandular tissue into the vulvar epithelium.

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Zusammenfassung Die ultrastrukturelle Untersuchung eines Falles von Morbus Paget der Vulva ergab, wie beim Morbus Paget der Mamma, in der Epidermis das Vorhandensein von 2 abnormen Zellstämmen (Zellen vom Typ I, d. h. helle Zellen, und Zellen vom Typ II, d. h. dunkle Zellen), die die ultrastrukturellen Charakteristiken der Zellen vom Typ der Drüsenzellen aufweisen.Die Verff. halten daher die Hypothese einer migratorischen Histogenese der Paget-Zellen vom tiefer gelegenen Drüsengewebe für wahrscheinlicher.

     

Comparative genomic hybridization in extramammary Paget's disease

BACKGROUND: Extramammary Paget's disease (EMPD) is a distinct skin cancer of unknown histogenesis. Data from genome-wide surveys for chromosomal aberrations in EMPD are limited. OBJECTIVES: To identify chromosomal aberrations that are present in EMPD. METHODS: Fifteen cases of EMPD were analysed by comparative genomic hybridization (CGH). We used pooled DNA CGH, instead of studying a single sample. In addition, immunohistochemistry was performed for detection of androgen receptor (AR). RESULTS: The most recurrent change was amplification at chromosomes Xcent-q21 and 19, and loss at 10q24-qter. In addition, expression of AR, located in chromosome X, was found in six cases. CONCLUSIONS: Results suggest that AR may play a role in EMPD tumorigenesis.     

Immunohistochemical stains in extramammary Paget's disease.

The histologic and immunohistochemical characteristics of 49 skin biopsy specimens from 49 patients with extramammary Paget's disease were studied. Patients with extramammary Paget's disease with and without underlying malignant disease were identified. Associated malignant lesions, present in 16 patients (33%), were transitional cell carcinoma of the bladder (n = 8), adenocarcinoma underlying the skin (n = 3), adenocarcinoma of the anus (n = 1), adenocarcinoma of the vulva (n = 1), apocrine carcinoma (n = 1), prostate carcinoma (n = 1), and carcinoma metastatic to the lung (n = 1). The main histologic feature was the presence of Paget's cells, predominantly at the base of the epidermis. In 6% of the cases, well-defined nests of large Paget's cells mimicked melanocytic nests. Carcinoembryonic antigen and Cam 5.2 (a monoclonal antibody that stains 40-kDa, 45-kDa, and 52.5-kDa low molecular weight keratins) were localized to the Paget's cells in 42 of 45 (93%) and 29 of 41 cases (71%), respectively. Forty-four of 46 lesions (96%) were mucin positive, as determined by Hale's colloidal iron stain. Absence of staining for colloidal iron and carcinoembryonic antigen occurred somewhat more frequently in patients with underlying malignant disease than in patients without tumors (13% vs. 0% mucin negative and 13% vs. 3% carcinoembryonic antigen negative, respectively). Although immunohistochemical staining for low molecular weight keratin may be used to confirm the diagnosis of extramammary Paget's disease, Cam 5.2 is not as sensitive as the colloidal iron or carcinoembryonic antigen stain.     

乳房外Paget病治疗进展

乳房外Paget病的治疗主要包括广泛局部切除、Mohs显微手术、放射疗法、光动力疗法、激光治疗、化学疗法、咪喹莫特和5-氟尿嘧啶等方法.对于保留局部组织和降低疾病复发率,Mohs显微手术更有优势,对于其他治疗的研究,结果各不相同.本文就乳房外Paget病的治疗进展进行综述.