Extramammary Paget's disease: a review of the literature

Extramammary Paget's disease (EMPD) is a rare cutaneous malignancy. The disease typically affects older individuals aged 60–80 years and is seen most frequently in postmenopausal Caucasian women and Asian men. EMPD exhibits a predilection for the genital and perianal regions and may be associated with an underlying carcinoma in adjacent organs. EMPD presents a challenge in both diagnosis and management. Often treated empirically as various dermatitides, the correct diagnosis is frequently delayed by many years. Following diagnosis, an extensive search for an associated malignancy should be initiated. If invasive disease is present on biopsy, a sentinel lymph node biopsy may guide further treatment. Mohs micrographic surgery appears to be superior to wide local excision when considering tissue sparing ability and disease recurrence. Nonsurgical interventions have also been investigated with varied results. Regardless of treatment method, long-term follow-up is recommended to monitor for local disease recurrence, development of internal malignancy, regional lymphadenopathy, or distant metastasis.     

EXTRAMAMMARY PAGET''S DISEASE AND PROSTATIC CARCINOMA

A patient with perianal extramammary Paget's disease (EMPD) occurring simultaneously with prostatic adenocarcinoma is presented. Four previously reported cases of genital EMPD associated with prostatic carcinoma are reviewed. The use of immunohistologic techniques to help establish the diagnosis in some cases, and the relationship of EMPD to underlying adenocarcinoma of sweat glands and of the lower urinary and gastrointestinal tracts is discussed. The importance of a directed search for internal malignancy in the individual patient with EMPD is emphasised.     

Apocrine Carcinoma of the Groin Possibly Associated with Extramammary Paget's Disease

Apocrine carcinoma is a rare malignancy with invasive potential. It presents as painless, slow-growing, firm or cystic, red nodules with focal ulcerations. The tumor is capable of hematogenous dissemination to the liver, lungs, and bone as well as lymphatic spread. In addition, apocrine carcinomas cause intra-epidemial pagetoid spread. We report a case of an apocrine carcinoma related with extensive extramammary Paget''s disease (EMPD). The relationship between apocrine carcinoma and EMPD remains to be understood. Co-existing cases with apocrine carcinoma and EMPD are discussed to better understand the relationship between these two malignant apocrine tumors.     

Extramammary Paget's Disease of External Genitalia with Bowenoid Features

Extramammary Paget''s disease (EMPD) is an uncommon intraepithelial adenocarcinoma, primarily affecting the apocrine-bearing skin. Bowen disease is an intraepithelial squamous cell carcinoma having the potential to become invasive carcinoma. The histopathological concomitant features between EMPD and Bowen disease have been described. One theory is that primary EMPD arises multicentrically, within the epidermis from the pluripotent stem cells. Herein, we describe a case of EMPD that had bowenoid features, and review the previous cases associated with the origin of EMPD.     

Axillary involvements in genital Paget's disease.

Simultaneous occurrence of bilateral axillary Paget's disease in a 61-year-old male with genital Paget's disease of 2 years' duration was presented. Invasive adenocarcimoma was found in the genital lesion. No regional lymph node metastases ware apparent. The lesions were excised in toto. There has been no recurrence 14 months later. Four previously reported cases of double or triple extramammary Paget's disease, together with two more cases were summarized. Generally, the axillary lesions were clinically insignificant, faintly erythematous patches and could hardly be identified without histological examination.     

Ectopic extramammary Paget's disease affecting the upper abdomen

Summary We present 57-year-old man in whom ectopic extramammary Paget's disease (EMPD) affected the upper abdomen. Although the clinical appearance was suggestive of Bowen's disease or superficial basal cell epithelioma (BCE), the biopsy specimen showed EMPD histologically. Only 12 cases of ectopic EMPD have been reported (including this case). In our 20 year experience of 129 EMPD, this is the first ectopic case. Thus, the frequency of ectopic EMPD is 0–78% (one of 129) in our study. The male/female ratio in the reported 12 cases is 2 : 1. nearly the same as EMPD in general (2:1:1, in our 129 cases). The mean age of the 12 patients is 65.8 years, which is not significantly different from ordinary EMPD (66–;4 years, in our 129 cases). Comparing ectopic EMPD to ordinary EMPD, clinically and histologically. we could find no difference. As they appear to be the same disease, ectopic and ordinary EMPD may share similar origins and mechanisms of occurrence. We support the hypothesis that Paget's cells originate from the remaining pluripotential germinative cells which are able to differentiate into many kinds of secreting glands.     

Treatment of extramammary Paget's disease by radiotherapy

Summary Extramammary Paget's disease (EMPD) is a rare cutaneous malignancy, which usually occurs in the elderly. Wide local excision is the recommended treatment, although this may not always be feasible. We report our experience of EMPD treated by radiotherapy In five patients. The radiotherapy was well tolerated in each case, and there were no signs of recurrence during follow-up (6 months-8 years). This study shows that radiotherapy is a useful alternative therapy for EMPD. and should be considered particularly in elderly patients who may not tolerate surgery.     

Extramammary Paget's disease mimicking acantholytic squamous cell carcinoma in situ: a case report

Background: Extramammary Paget's disease (EMPD) is an uncommon skin neoplasm characterized by Paget's cells with pale‐staining cytoplasm in the epidermis, and cases with distinguished acantholysis but lacking characteristic Paget's cells were rarely reported in the literature. Methods: An 80‐year‐old male with lesion on scrotum was screened histologically and immunohistologically for the diagnosis of his tumor. Results: Histological examination showed acanthosis with cellular atypia and focal acantholysis, consistent with acantholytic squamous cell carcinoma in situ (SCCIS). No characteristic Paget's cells were observed in low magnification. Immunohistochemical staining showed carcinoembryonic antigen (CEA), cytokeratin 7 (CK7) and cytokeratin 8 (CK8) to be strongly expressed in the nests and singly arranged large tumor cells, and the surrounding epidermis was positive for CK5/6 and negative for CEA. Sporadic periodic acid‐schiff (PAS)‐positive cells could be seen in some areas. Conclusions: These findings strongly indicated the diagnosis of EMPD mimicking acantholytic SCCIS. Du X, Yin X, Zhou N, Zhang G, Shi H, Cao S. Extramammary Paget's disease mimicking acantholytic squamous cell carcinoma in situ: a case report.     

Penoscrotal Paget's disease

Paget's disease (PD) denotes an initially intra-epidermal adenocarcinoma that can later invade the dermis and metastasise. Among the extramammary forms of PD (EMPD), penoscrotal presentations are rarer than the vulvar and perianal forms. Once diagnosis has been confirmed by histopathological examination, a search for associated neoplasia must be conducted, although penoscrotal EMPD is less frequently associated with underlying neoplasia than mammary PD (MPD). The associated cancer most often involves a neighbouring organ, with prostate cancer being the most common, or in some cases consists of underlying cutaneous adnexal tumours. First-line therapy consists of surgical excision. Alternatives to surgery (imiquimod, CO₂ laser vaporisation, dynamic phototherapy) may be considered in certain cases.     

Extramammary Paget's disease of the groin with underlying carcinoma and fatal outcome

Extramammary Paget's disease (EMPD) is considered to be an intraepithelial adenocarcinoma. Typically involved anatomical sites are the vulvar, perianal, perineal, scrotal and penile regions. Clinically, the lesions present as well-defined, moist, erythematous plaques usually accompanied by pruritus. An unusual feature of EMPD is its association with cutaneous, adnexal-structure adenocarcinomas and its association with internal malignancies. Histopathological examination shows epidermal acanthosis and elongated rete ridges. Paget's cells are large intraepidermal cells with a large nucleous and abundant pale cytoplasm. Recent studies of perianal and vulvar EMPD have described distinct immunohistochemical subtypes termed cutaneous and endodermal. Cutaneous EMPD is characteristically positive for cytokeratin (CK)7, negative for CK20, and positive for gross cystic disease fluid protein (GCDFP)15+, whereas endodermal EMPD shows a CK7+ CK20+ GCDFP15− phenotype. Surgery remains the treatment of choice, with either wide surgical excision or Mohs' micrographic surgery. We present a case of EMPD with an underlying carcinoma, which combined immunohistochemical findings suggestive of the cutaneous subtype (positive for CK7, GCDFP15, mucin (MUC)1, human epidermal growth factor receptor (HER)2/neu positive) and the endodermal subtype, frequently associated with internal malignancy (CK20, MUC2, CDX-2 positve); however, our patient had no associated internal malignancy.     

A Case of Triple Extramammary Paget's Disease

We report a 74-year-old Japanese man with triple extramammary Paget's disease; the genital and both of the axillar regions were simultaneously involved. Literature review revealed that 27 cases of triple extramammary Paget's disease have been reported in Japan, but there are no reports of triple extramammary Paget's disease from countries other than Japan, although 2 cases of double extramammary Paget's disease are reported. In all 28 cases, including our case, the genital lesion preceded the axillary lesions. All cases except one were male and only the exceptional female case was reported to have an the invasive tumor in the dermis. We speculate that extramammary Paget's disease may appear multi-centrically.     

Mammary Paget's disease and extra‐mammary Paget's disease: two morphologically similar but biologically different diseases

Background: The cells of origin of mammary Paget's disease (MPD) and extra‐mammary Paget's disease (EMPD) have been a controversial subject. The purpose of this study is to examine the expression of the human epidermal growth factor receptor 2 (HER2) pathway members in these two diseases. Design: HER2, AKT, pAKT, PTEN, epidermal growth factor receptor (EGFR) and pEGFR were examined in 16 MPD and 14 EMPD cases. HER2 was graded on a scale from 0 to 3. A score of 3 was considered positive. For AKT, pAKT, PTEN, EGFR and pEGFR, a semi‐quantitative scoring system was used. A score >100 was considered positive. Fisher's exact test was used to analyze the data. Results: HER2 was overexpressed in 87.5% MPD and 35.7% EMPD. While AKT was expressed in all cases, pAKT was expressed in 87.5% MPD and 92.9% EMPD. Both EGFR and pEGFR were negative in all cases. PTEN was positive in 62.5% MPD and 71.4% EMPD. For pAKT+ group, HER2–/PTEN+ was recorded in 0% MPD and 38.5% EMPD (P = .01). Conclusions: In a subset of EMPD, AKT is not activated by HER2 overexpression or by loss of PTEN, which is not the case in MPD. These data suggest that these two diseases are biologically different. Liu W, Iqbal J, Khoury T. Mammary Paget's disease and extramammary Paget's disease: two morphologically similar but biologically different diseases.     

A study of clinical and aetiological factors and possible associations of lichen sclerosus in males

Lichen sclerosus is a chronic skin condition with a predilection for the genital area. In the present study, 35 male patients with lichen sclerosus were interviewed and examined. Blood screens were performed and histology was requested if not already performed. The findings indicate that lichen sclerosus in males exists as a spectrum of disease, ranging from a mild form with white plaques and few symptoms to a severe form with inflammation, atrophy and scarring with possible urological consequences. In many areas it differs from the condition in females; the association with autoimmune disease is weaker and there is less perianal and extragenital involvement The association with malignancy in males is of lesser significance than initially believed.     

Mapping biopsy with punch biopsies to determine surgical margin in extramammary Paget's disease

It is difficult to determine the appropriate resection margin of extramammary Paget's disease (EMPD). A high recurrence rate is reported in spite of using Mohs micrographic surgery (MMS), which is performed commonly. Preoperative mapping biopsy is easier to perform than MMS. In Japan, the following method is recommended instead of MMS: well‐defined border and margins histologically confirmed by mapping biopsy should be resected with 1‐cm margin and ill‐defined border with 3‐cm margin. This study aimed to evaluate the accuracy of the Japanese guideline and to assess our mapping biopsy method compared with MMS. Preoperative mapping biopsy specimens were obtained beyond the clinical border for at least four directions in each patient. To confirm the presence of residual Paget's cells postoperatively, narrow specimens were obtained along the surgical margin. Retrospective evaluation of 17 EMPD patients was conducted concerning histological spread of Paget's cells and recurrence ratio. There were 86 directions showing a well‐defined border, and in 9.3% (8/86), Paget's cells were still observed at 1‐cm resection line. On the other hand, there were 21 directions showing an ill‐defined border, and unnecessary radical resection was performed in 90% (19/21) of directions with 3‐cm resection line. Although postoperative histological examination showed residual Paget's cells in 47% (8/17) of patients and additional resections were not performed, recurrence rate was only 5.9% (1/17). The resection line of EMPD should be based not on clinical features, but on mapping biopsy. Mapping biopsy is equivalent to MMS concerning recurrence rate and, though conventional, is useful method to treat EMPD.     

Evaluation of positron emission tomography imaging to detect lymph node metastases in patients with extramammary Paget's disease

Patients with extramammary Paget's disease (EMPD) have a relatively good prognosis, when spread of the tumor cells is limited to the epidermis. However, invasive EMPD has a poor prognosis, when the patients have regional lymph node metastasis. Detection of nodal metastasis is thus mandatory to manage EMPD. To evaluate the ¹⁸F‐fluorodeoxyglucose positron emission tomography (FDG‐PET) imaging to assess lymph node metastasis, 15 patients with histologically proven primary EMPD were enrolled in this study. All patients underwent whole‐body PET prior to sentinel lymph node biopsy (SLNB). The maximum standardized uptake value (SUVmax) of more than 2.5 was evaluated as positive PET indicative of malignancy. Among 14 cases with the primary genital lesions, 11 cases underwent bilateral SLNB of the inguinal nodal basin and the remaining three cases unilateral SLNB. One case with a primary axillary lesion underwent unilateral SLNB of the axillary nodal basin. Therefore, a total of 26 regional basins were investigated. In general, nodal basins can be categorized into four groups: (i) histologically negative and PET negative (true negative); (ii) histologically positive and PET negative (false negative); (iii) histologically positive and PET positive (true positive); and (iv) histologically negative and PET positive (false positive) groups. In the 26 nodal basins, there were 19 true negative and seven true positive cases, and neither false negative nor false positive cases were observed. The mean SUVmax was significantly higher in the true positive basins (8.03 ± 3.34) than in the true negative basins (0.26 ± 0.56). The SUVmax value may be useful for detection of nodal metastasis.     

乳房外Paget病32例临床与组织病理分析

目的:探讨乳房外Paget病的临床、组织病理学特征、恶性程度与预后.方法:收集32例乳房外Paget病患者资料,观察和分析其临床和组织病理学特征,并用免疫组化检测其的表达.结果:发病率男高于女,临床误诊率高,术后易复发,免疫组化CK7、EMA、CEA表达阳性,32例乳房外Paget病中P53、bcl-2有不同程度的阳性表达,且显著高于对照组(P＜0.05).结论:乳房外Paget病为低度恶性的皮肤肿瘤,有特殊的临床及组织病理特点,免疫组化提示有腺体分化能力,可判断恶性程度及预后.首选手术治疗,需长期随访.     

Axillary Paget's disease

A case of axillary Paget's disease in a female was presented. Histopathological study revealed various types of apocrine poral duct tumors showing benignancy, premalignancy or malignancy, and Paget's cells in the epidermis as well as in the latter lesions. Relationship between Paget's cell and the malignant cell was discussed.     

HER-2/neu expression in extramammary Paget disease: a clinicopathologic and immunohistochemistry study of 47 cases with and without underlying malignancy

Extramammary Paget disease (EMPD) is an infrequent skin cancer sometimes representing a secondary event caused by extension of an underlying carcinoma. Her-2/neu overexpression in breast cancer is correlated with a more aggressive behavior, but anti-Her-2/neu therapy improves survival in these patients. We investigated Her-2/neu expression by immunohistochemistry in cases of EMPD with and without underlying malignancy to try to correlate with tumor recurrence, progression and possible targeted therapy. Forty-seven cases were analyzed (6 from the scrotum, 7 perianal region, 1 axilla and 33 vulva). Two cases had invasive EMPD (one from vulva and one from scrotum). The overall Her-2/neu expression was 31.9%. Of the noninvasive EMPD of the vulva (32 cases), Her-2/neu was shown in 38%. The case of invasive vulvar EMPD was negative. All six scrotal EMPD lacked Her2/neu expression. Her-2/neu was expressed in two of seven perianal cases (33.3%). The EMPD on the axilla (one case) was negative. Eighteen cases had recurrence, and of these, 44.4% expressed Her-2/neu in the initial lesion. A high proportion of EMPD showed Her-2/neu expression (31.9%), indicating that these patients may benefit from targeted therapy. The proportion of positive cases was higher in lesions that had recurred at last follow up (44.4%), suggesting a more aggressive behavior.     

Topical imiquimod in the treatment of extramammary Paget's disease: A 10 year retrospective analysis in an Asian tertiary centre

Extramammary Paget's disease (EMPD) is a rare intraepithelial adenocarcinoma usually found in apocrine‐rich areas. Although surgery remains standard treatment, topical imiquimod has emerged as a promising drug for the treatment of EMPD in recent years. We present our experience in treating EMPD in Asian skin successfully with topical imiquimod 5% cream, over the past 10 years in our tertiary institution.