In 1874, Sir James Paget first described Paget disease of the nipple, also known as mammary Paget disease. In 1889, extramammary Paget disease (EMPD) of the scrotum and penis was identified. Although mammary and extramammary Paget disease are both characterized by epidermal Paget cells and share a similar clinical presentation, their uniqueness lies in anatomical location and histogenesis. EMPD presents as an erythematous plaque on apocrine gland bearing areas (i.e. vulva, perineum, perianal region, scrotum, and penis) in older men and women. It can be a focal, multifocal, or an ectopic process. Immunohistochemical staining allows for differentiation between primary and secondary EMPD in addition to the many other disease entities that clinically resemble this malignancy. When diagnosing a patient with EMPD, a full history and physical should be performed given the possibility of an underlying malignancy. Surgical excision currently is first line therapy and the prognosis is often favorable. Recent advances within the field have examined the expression of chemokine receptors within tumors, which may be applicable in determining prognosis. This review addresses the history, epidemiology, pathogenesis, clinical presentation, histopathology, differential diagnosis, diagnosis, management, and new observations with respect to extramammary Paget disease.
Extramammary Paget disease (EMPD) is a rare dermatologic condition that frequently presents in areas where apocrine sweat glands are abundant, most commonly the vulva, although perineal, scrotal, perianal, and penile skin may also be affected. Lesions clinically present as erythematous, well-demarcated plaques that may become erosive, ulcerated, scaly, or eczematous. Extramammary Paget disease has a female predominance and usually occurs in the sixth to eighth decades of life. Professionals disagree about many aspects of EMPD, for example, the prevalence of concurrent vulvar adenocarcinoma or invasive EMPD, association with regional and distant cancers, and recurrence rates following surgical excision. Early recognition is imperative because the diagnosis is frequently delayed and there is a high incidence of associated invasive disease.
Background: Perianal Paget’s disease (PPD) is a rare intraepithelial adenocarcinoma of the anal margin. Primary PPD likely represents intra-epithelial neoplasm from an apocrine source, whereas secondary disease may represent“pagetoid” spread from an anorectal malignancy.
Case presentation: Histologic CDX-2 and CK20 are hallmark markers for colorectal-derived Paget’s cells. Interestingly, our primary PPD patient presented both positive and no internal malignancy was identified. In addition, a negative CK7 marker was observed in our case in contrast with previously reported. Surgical excision is the standard treatment; however, previous studies have demonstrated good response with Imiquimod 5% cream in patients with vulval extramammary Paget disease (EMPD). The efficiency of Imiquimod treatment for PPD has not been well described. Our PPD patient was successfully treated using Imiquimod 5% cream.
Conclusions: This study describes a primary cutaneous PPD patient CDX-2+/CK20+/CK7- without invasion of the dermis and no associated colorectal carcinoma effectively treated using topical Imiquimod therapy, suggesting that Imiquimod might potentially be considered as a first-line treatment for PPD.
Advanced extramammary Paget's disease does not have a standardized treatment guideline as its incidence is low and has been rarely reported in literature. Here we describe a case of metastatic extramammary Paget's disease successfully treated with topical 5-fluorouracil (5-FU) and systemic pemetrexed. The therapy was safe without any appreciable adverse effects like diarrhea, rash, neutropenia or fatigue; maintaining remission for more than 6 months. Thus, we propose 5-FU and pemetrexed as the first-line therapy for advanced extramammary Paget's disease, especially for aged patients with unresectable skin lesions.
Extramammary Paget’s Disease (EMPD) is a rare intraepithelial adenocarcinoma. It mostly affects women in their seventies. EMPD develops principally in the apocrine genital, anal, and axillary zones . We conducted a retrospective study at the University Hospital of Reims over a period of 20 years (1994- 2014). 9 patients were included of which 7 were female. The median age of onset was 78 years (60-91). The diagnosis time ranged from a few months to 5 years prior to diagnosis. Vulvar localization remains by far the most common localization. 6 patients, all females, had pruritus (vulvar); 2 (22%) felt pain from the lesions.
RATIONALE: Biological therapies, such as imiquimod, may stimulate the immune system in different ways and stop tumor cells from growing. Applying topical imiquimod to the vulva may be an effective treatment for recurrent Paget's disease.
PURPOSE: This clinical trial is studying how well topical imiquimod works in treating patients with recurrent Paget's disease of the vulva.
OBJECTIVES: To assess the clinical and histologic effects of topical imiquimod therapy on recurrent extramammary Paget's disease.
Eight patients from two institutions were enrolled. Complete clinical and histologic response was achieved in 6 (75%) patients by the 12-week follow-up appointment. Of the two remaining patients, one had a complete clinical response but no significant histologic response; the other patient was removed from the study protocol secondary to intolerable local irritation. Two patients continue to have no evidence of disease after a median follow-up of 35 months. Five are alive with disease. No patients progressed to invasive cancer while receiving therapy.
Authors’ conclusions: We found no reliable evidence to inform decisions about different interventions for women with Paget’s disease of the vulva. Ideally, a multicentre RCT of reasonable size is needed. In particular, evidence regarding the increasing use of imiquimod would be helpful to women and clinicians alike. Well-designed non-randomised studies, that use multivariate analysis to adjust for baseline imbalances, as well as other key methodological strengths, are also lacking.
Extramammary Paget’s Disease (EMPD) is a rare neoplastic lesion, which represents less than 1% of vulvar neoplasms. The lesion generally appears as eczema and the most frequently reported symptom is the itch. Also because of these poor clinical features, there is usually a delay in its diagnosis, based on the typical biopsy histological pattern. It has a good prognosis in absence of malignancy, but can result in a heavy quality of life impairment because of frequent recurrence with necessity of ablative therapies and anxiety for possible cancerization. Rarely EMPD can be invasive or associated to adenocarcinoma or other kinds of cancer. The first choice therapy is the surgical excision, with inguinal lymphadenectomy in case of infiltrative disease. However, many other conservative therapies, including the topical use of antiblastic, immuno-modulating, and hormone-modulating drugs, are used against EMPD even if still off label. After completion of this article, the reader should be able to recall the clinical manifestations of the EMPD, the histological pattern which allows its diagnosis, and to state the options for a treatment, which should be conservative and at the same time as radical as possible.
Of the 27 published cases that describe imiquimod treatment of EMPD, 6 report treatment failure (22%), but factors that may contribute to treatment failure are not well understood. In the present patient, treatment with imiquimod may have been complicated by variable lesion thickness, which inhibited uniform penetration of imiquimod, or the presence of invasive disease not detected on initial biopsy. The efficacy of imiquimod to treat extensive invasive EMPD has not been demonstrated, and surgical approaches remain the most appropriate treatment for invasive disease. Variable responses to topical imiquimod use among patients suggest that other factors may be important in determining response to therapy.
Surgical management of extramammary Paget disease (EMPD) remains a therapeutic mainstay, but alternative treatments for primary limited cutaneous EMPD in the anogenital area that avoid cosmetic and functional defects after extensive tissue removal are under investigation. Local recurrence of EMPD can be significant,1 highlighting the insidious nature of EMPD and the need to identify more effective treatments. The topical immunomodulator imiquimod, 5%, has been reported to induce clinical and histologic resolution of superficial EMPD,2-12 but several cases of imiquimod failure have also been described.13-17 Herein, we present a case of genital EMPD considered to be limited to in situ disease at the beginning of treatment with topical imiquimod that proved refractory, with demonstration of invasive disease during treatment. We also review the current literature (articles published in English and obtained through PubMed, Ovid, and GoogleScholar searches conducted between July 1, 2009, and August 31, 2010) regarding successes (n = 21) and failures (n = 6) of imiquimod therapy for EMPD and present characteristics that could portend treatment failure.
This cancer shares many histologic similarity with Paget's disease of the breast. Clinically, patients present with itchy pink to red scaly areas, resembling a chronic eczema. There may be scattered islands of white hyperkeratosis. These areas may be scattered and multicentric, involving the vulva and perineum. It is a slow growing and progressive cancer which requries a wide local excision. In addition, there are occasional cases which are really underlying invasive adenocarcinomas which have secondarily spread to the overlying skin in 10-20% of cases. Underlying adenocarcinoma in 10-20% of cases represent secondary metastasis to the skin, not true extramammary Paget's disease. In these cases, the pathologist must perform a diligent search to identify a primary adenocarcinoma.
This successful treatment of a perianal-located EMPD by topical imiquimod warrants further investigations.
Conclusion: Although there is not extensive experience with the use of topical imiquimod 5 percent in the treatment of EMPD, the reported cases of successful use of this agent in limited extent EMPD are promising. Larger scope, randomized controlled trials are needed to determine the true safety and efficacy of imiquimod in comparison to the other therapy modalities currently used to manage EMPD. To the best of our knowledge, the treatment of EMPD of the thigh with imiquimod is not reported elsewhere in the literature, and we report our case as further evidence of the potential role imiquimod may play in this disorder.