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.     

外阴鳞状细胞癌中人乳头瘤病毒感染与端粒酶和生存素的关系

目的:探讨人乳头瘤病毒(HPV)6/11、16/18在外阴鳞状细胞癌(vulvarsquamouscellcarcinoma,VSCC)组织中的感染情况及其与人端粒酶逆转录酶(hTERT)和凋亡抑制基因生存素(survivin)表达的关系。方法:采用PCR检测HPV6/11、16/18在31例VSCC及13名正常人皮肤组织中的感染情况,同时用原位杂交法检测hTERTmRNA的表达,免疫组化法检测生存素蛋白的表达。结果:①HPV6/11、16/18在VSCC患者的阳性率分别为25.81%和38.17%,正常对照者为阴性。VSCC患者与正常对照者HPV16/18阳性率的差异有统计学意义(P<0.05)。②VSCC患者hTERTmRNA、生存素蛋白表达的阳性率与正常对照者比较,差异均有统计学意义(P<0.05),且VSCC患者hTERTmRNA表达与生存素蛋白表达的阳性率呈明显的正相关(P<0.05)。③hTERTmRNA在HPV16/18阳性组中的表达明显强于HPV16/18阴性组,生存素蛋白在HPV16/18阳性组中的表达低于其在HPV16/18阴性组中的表达。结论:HPV感染及hTERT、生存素表达在VSCC发生发展中起一定作用;VSCC中hTERT与生存素的表达具有一定的相关性。     

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.     

乳房外佩吉特病中囊泡病液体蛋白15的表达及其意义

目的：分析乳房外佩吉特（Paget）病中囊泡病液体蛋白（GCDFP）-15的表达及其意义。方法：应用免疫组化方法对20例乳房外Paget病患者的GCDFP-15和细胞角蛋白20（CK20）进行检测。结果：20例患者CK20均为阴性,8例呈侵袭性生长的患者GCDFP-15表达为强阳性或阳性,12例呈原位生长的患者GCDFP-15表达为弱阳性或阴性。结论：GCDFP-15的表达对于判断乳房外Paget病是否呈侵袭性生长有一定意义。     

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.     

Expression of prostate-specific antigen and androgen receptor in extramammary Paget's disease and carcinoma

Prostate-specific antigen (PSA) is a kallikrein-like serine proteinase (human kallikrein 3) produced by epithelial cells of both benign and malignant prostate tissue. In this study, PSA expression was histologically examined in tissue specimens from 34 patients with extramammary Paget's disease (EPD; 31 cases) and extramammary Paget's carcinoma (EPC; three cases), but no associated prostate carcinoma. Tumour cells positive for PSA were found in 17 of the 34 cases. Based on this finding, we examined serum PSA level in the three EPC cases. A high level of serum PSA was observed in one case of EPC, which was correlated with disease progression. Because some reports suggest that 50-80% cases of EPD/EPC express androgen receptor (AR), we also examined expression of AR. Immunohistological staining showed correlation of PSA and AR in expression. These results suggest that PSA and the androgen signalling pathway may be involved in the pathogenesis of EPD.     

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.

     

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.     

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.     

Expression and prognostic significance of Stat5a and E-cadherin in extramammary Paget's disease

BACKGROUND: Stat5 has been shown to regulate the proliferation and inhibition of apoptosis in cancer cells. E-cadherin plays an important role in maintaining epithelial stability and is widely regarded as a prognostic marker in many types of human cancers. The expression of Stat5 has not been investigated in extramammary Paget's disease (EMPD). OBJECTIVES: To study the expression of Stat5a and E-cadherin protein in EMPD and to evaluate the relationships between them. METHODS: Thirty-six tissue samples from 34 cases with primary EMPD were subjected to immunohistochemical staining for Stat5a and E-cadherin. RESULTS: Twenty-nine of 30 in situ EMPD specimens were positive for Stat5a expression, and the staining pattern for Stat5a was mainly nuclear in the majority of Paget's cells. All four invasive specimens and two metastatic lymph node specimens were negative for Stat5a. Twenty-six of 30 in situ EMPD specimens expressed E-cadherin in more than 50% of tumor cells, and three of 30 in situ EMPD specimens expressed E-cadherin in less than 50% of tumor cells. One in situ EMPD specimen and one invasive specimen expressed E-cadherin in less than 25% of tumor cells. Three invasive specimens and two metastatic lymph node specimens were negative, with occasional membranous staining for E-cadherin. There is a significant correlation between the expression of Stat5a and E-cadherin. CONCLUSIONS: Our results showed that these proteins were found in in situ lesions, and it is speculated that these proteins may play some role in the prognosis/invasion of EMPD.     

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.