EMPD Report

Paget Disease, Extramammary

Paget Disease, Extramammary

Introduction

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.

Rare perianal extramammary Paget disease successfully treated using topical Imiquimod therapy

Rare perianal extramammary Paget disease successfully treated using topical Imiquimod therapy

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.

Extramammary Paget Disease

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.

Successful treatment of metastatic extramammary Paget's disease with pemetrexed monotherapy systemically and 5-fluorouracil topically

Abstract 
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.

Evidence-Based Screening Recommendations for Occult Cancers in the Setting of Newly Diagnosed Extramammary Paget Disease

Evidence-Based Screening Recommendations for Occult Cancers in the Setting of Newly Diagnosed Extramammary Paget Disease

To identify the rates of associated and occult cancers in patients with extramammary Paget disease (EMPD) discovered using cancer screening methods at a tertiary medical center; to propose evidence-based cancer screening guidelines at the time of diagnosis of EMPD; and to clarify terminology associating EMPD with underlying malignancies.

All patients diagnosed with EMPD should undergo cancer screening. At minimum, evaluation should include age-appropriate screening and the addition of urine cytology, mammography, and prostate-specific antigen blood test—if not already performed—may be of particular use. An algorithm for evaluation of patients with newly diagnosed EMPD is proposed.

Metastatic Extramammary Paget’s Disease: Pathogenesis and Novel Therapeutic Approach

Metastatic Extramammary Paget’s Disease: Pathogenesis and Novel Therapeutic Approach

Metastatic EMPD is an aggressive skin adenocarcinoma with poor prognosis. Since current chemotherapeutic regimens are only moderately effective, improving clinical outcomes is imperative. The basic and translational research to date has provided an insight into the mechanisms promoting metastasis of EMPD that provide potential therapeutic targets for new drug development. Seemingly, Paget cells augment the ability of proliferation and survival by activating the RAS–RAF–MEK–ERK signaling, PI3K–AKT–mTOR signaling, or androgen–AR signaling. In addition, the interaction of Paget cells with other cells, such as LECs and CD163+Arg1+ macrophages in a tumor through the CXCR4–SDF-1 signaling and RANKL–RANK signaling, respectively, could establish a favorable tumor microenvironment to promote metastasis of Paget cells. Furthermore, recent genomic analysis of MMR has revealed that a decent percentage of EMPD comprises MMR-deficient EMPD cases that might achieve durable clinical response by an anti-PD-1 antibody. Hence, we are now beginning to understand multiple aspects involved in the pathogenesis of metastatic EMPD, and these findings will be sure to lead to better treatments for patients with metastatic EMPD in the future.

 

Efficacy of low-dose 5-fluorouracil/cisplatin therapy for invasive extramammary Paget’s disease

Efficacy of low-dose 5-fluorouracil/cisplatin therapy for invasive extramammary Paget’s disease

Extramammary Paget's disease (EMPD) is one of the cutaneous adenocarcinomas. The effective chemotherapy for advanced EMPD has not been established. This study was designed to evaluate the efficacy of combination 5‐fluorouracil (500 mg/body, 7 days/week) and cisplatin (5 mg/body 5 days/week) for invasive EMPD. Seventeen EMPD patients with multiple metastases who visited our dermatology clinic between October 2004 and May 2016 (mean age, 76.9 years; 10 men, seven women) were retrospectively analyzed. Eight EMPD patients underwent low‐dose 5‐fluorouracil/cisplatin therapy and nine patients chose best supportive care. The average number of treatment cycles was 12.3. All patients had a confirmed response, four (50%) showed a partial response, two (25%) stable disease and two progressive disease. The median times to progression‐free and overall survival were 25.0 and 77.4 weeks, respectively. There was no severe (grade 3 and 4) adverse event. Although not significant, the survival of the patients treated with low‐dose 5‐fluorouracil/cisplatin therapy showed a trend toward improved survival as compared with best supportive care (P = 0.08, log–rank test). This regimen had low risk and relatively high disease control rate, suggesting that this regimen be recommended as one of the treatment options for advanced EMPD.

Genito-Urinary Extramammary Pagets disease: Recognition and outcomes of distinct histological subtypes

Genito-Urinary Extramammary Pagets disease: Recognition and outcomes of distinct histological subtypes

ntroduction & Objectives: Genito-Urinary Extramammary Pagets Disease (EMPD) is a rare neoplasm that occurs in regions abundant in apocrine glands, or as a secondary intraepithelial spread of EMPD associated with another underlying carcinoma. The former occurs on peno-scrotal skin and can be in-situ or invasive. The latter occurs primarily on the inner precpuce or glans. Management and prognosis differ between these subtypes.

Extramammary Paget Disease of the Vulva: A Case Series Examining Treatment, Recurrence, and Malignant Transformation.

Extramammary Paget Disease of the Vulva: A Case Series Examining Treatment, Recurrence, and Malignant Transformation.

Patients with EMPD in this series have a high rate of recurrence. Many undergo multi-modal therapy often with multiple providers. However, patients experience relatively long disease-free intervals with a low rate of associated malignancy. We propose an algorithm for management that focuses on symptom control and minimizing morbidity of treatment intervention once invasive disease has been excluded.

Chemokine Receptors CXCR4 and CXCR7 are Associated with Tumor Aggressiveness and Prognosis in Extramammary Paget Disease

Chemokine Receptors CXCR4 and CXCR7 are Associated with Tumor Aggressiveness and Prognosis in Extramammary Paget Disease

Chemokines are involved in many aspects of oncogenesis, including regulation of cancer cell growth, dissemination and host-tumor response. However, the potential of the chemokine receptors, CXCR4 and CXCR7, in serving as biomarkers in extramammary Paget's disease (EMPD) has been rarely examined. Expressions of CXCR4 and CXCR7 were evaluated in 92 EMPD specimens by immunohistochemistry. High expression of CXCR4 and CXCR7 were both correlated with regional lymph node metastasis and presence of lymphovascular invasion. High expression of CXCR7 also correlated with the depth of invasion. The prognostic value of these two chemokines were also investigated in progression-free survival (PFS) and cancer-specific survival (CSS). Both high expression of CXCR4 and CXCR7 were indicative of shorter PFS and CSS. In the combined prognostic model, concomitant high expression of CXCR4 and CXCR7 were suggestive of poor prognosis compared with the other two groups. In the multivariate analysis, depth of invasion, combined prognostic model and regional lymph node metastasis at diagnosis were the independent prognostic factors for EMPD patients for PFS, and the former two factors independently impacted CSS. Our results demonstrated that CXCR4 and CXCR7 can be used as prognostic biomarkers and prediction of aggressiveness of EMPD. Therapy targeting CXCR4 and CXCR7 may helpful to prevent EMPD progression and improve the prognosis of EMPD.

Spectrum of Changes in Anogenital Mammary-like Glands in Primary Extramammary (Anogenital) Paget Disease and Their Possible Role in the Pathogenesis of the Disease

Spectrum of Changes in Anogenital Mammary-like Glands in Primary Extramammary (Anogenital) Paget Disease and Their Possible Role in the Pathogenesis of the Disease

To determine whether a subset of primary extramammary Paget disease (EMPD) may originate in anogenital mammary-like glands (AGMLG), the authors studied 181 specimens of EMPD, detailing alterations in AGMLG. The latter were identified in 33 specimens from 31 patients. All patients were women, ranging in age from 38 to 93 years (median, 65 y). However, by analogy with mammary Paget disease, rare cases of primary EMPD may originate in AGMLG with a subsequent upward migration of the neoplastic cells into the epidermis and possible later breach through the basal membrane. Usual ductal hyperplasia and atypical duct hyperplasia can then be regarded as earlier precursor lesions, linking both ends of the spectrum.

GATA3 is a sensitive marker for primary genital extramammary paget disease: an immunohistochemical study of 72 cases with comparison to gross cystic disease fluid protein 15

GATA3 is a sensitive marker for primary genital extramammary paget disease: an immunohistochemical study of 72 cases with comparison to gross cystic disease fluid protein 15

Background

GATA-binding protein 3 (GATA3) has been identified as a sensitive marker for breast carcinoma but its sensitivity in primary genital extramammary Paget diseases (EMPDs) has not been well studied.

Results

Positive GATA3 staining was seen in all 71 (100%) intraepithelial diseases, 25/26 (96%; female 10/10, male 15/16) invasive adenocarcinomas and 14/15 (93%; female 3/3, male 11/12) metastatic adenocarcinomas, respectively. Positive GCDFP15 staining was seen in 46/71 (65%; female 28/34 or 82%, male 18/37 or 49%) intraepithelial diseases, 20/26 (77%; female 9/10, male 11/16) invasive adenocarcinomas, and 12/15 (80%; female 2/3, male 10/12) metastatic adenocarcinomas, respectively (GATA3 versus GCDFP15: p < 0.01 for both intraepithelial disease and invasive adenocarcinoma, p = 0.28 for metastatic adenocarcinoma). In positive-stained cases, GATA3 stained more tumor cells than GCDFP15 (79% versus 25% for intraepithelial disease, 71% vs 34% for invasive adenocarcinoma, 73% vs 50% for metastatic adenocarcinoma, p < 0.01 for all 3 components).

Conclusions

Our findings indicate that GATA3 is a very sensitive marker for primary genital EMPDs and is more sensitive than GCDFP15.

Extramammary Paget`s Disease: A Real Challenge for Geriatricians

Extramammary Paget`s Disease: A Real Challenge for Geriatricians

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 [1]. 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.

Topical Imiquimod in Treating Patients With Recurrent Paget's Disease of the Vulva

Topical Imiquimod in Treating Patients With Recurrent Paget's Disease of the Vulva

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.

Mechanisms of immune evasion in extramammary Paget disease

Mechanisms of immune evasion in extramammary Paget disease

mmune evasion by cancer is a well-recognized mechanism that promotes tumour growth and metastases which in recent years has been shown to be amenable to therapeutic exploitation. Extramammary Paget disease (EMPD) is a rare form of skin cancer affecting apocrine glands in anogenital regions. The prognosis of the disease is good if treated early by surgical removal of the tissue, with a 5-year survival rate close to 95%.[1] The prognosis is worse for invasive disease, partly due to the lack of definitive treatment options in this setting.[2] Understanding the mechanisms of EMPD evolution has the potential to identify new treatment targets for this entity. In this edition of the BJD, Fujimura et al.[3] have looked into a suspected link between Langerhans cells (LCs) and regulatory T-cell (Treg) activity in EMPD that could contribute to the immunosuppressive environment that supports tumour growth and invasion by immune evasion.

Primary invasive triple extramammary Paget's disease with regional lymph node metastasis

Primary invasive triple extramammary Paget's disease with regional lymph node metastasis

Extramammary Paget's disease (EMPD) is a rare intraepidermal carcinoma and predominantly involves apocrine gland-bearing areas, such as anogenital regions and axillae. EMPD usually involves a solitary area and, less often, two areas in the same patient (double EMPD). The simultaneous involvement of bilateral axillae and anogenital region, called triple extramammary Paget's disease (TEPD), is an extremely rare subgroup of diseases that has been reported mostly from studies conducted in Japan. Because of its rarity, the clinical course, pathology/immunohistochemical staining features, and prognosis of TEPD are still unclear. Herein, to our knowledge, we present the first case of primary invasive TEPD with regional lymph node metastasis in Taiwan, and review the literature.

Mohs with CK-7 staining: 98% 5-year cure rate for extramammary Paget disease

Mohs with CK-7 staining: 98% 5-year cure rate for extramammary Paget disease

Mohs surgery with cytokeratin-7 immunohistochemistry staining effected complete removal of extramammary Paget disease and resulted in a 5-year, 95% recurrence-free cure rate.

The results are significantly better than the often-cited 77% cure rate seen with Mohs surgery alone, Dr. Ali Alexander Damavandy said at the annual meeting of the American College of Mohs Surgery.

“These are statistically significant and clinically substantial results,” said Dr. Damavandy, a procedural dermatology fellow at the University of Pennsylvania, Philadelphia. “With this method you can tell a patient that in 5 years, he has a 95% chance of still not having the tumor. The high recurrence-free rate we have seen supports the view that Mohs surgery with cytokeratin-7 [CK-7] immunohistochemistry should be considered the curative treatment of choice for both primary and recurrent extramammary Paget disease of the skin.”

A pilot study of topical imiquimod therapy for the treatment of recurrent extramammary Paget's disease

A pilot study of topical imiquimod therapy for the treatment of recurrent extramammary Paget's disease

Results

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.

Clinical and pathological characteristics of extramammary Paget’s disease: report of 246 Chinese male patients

Clinical and pathological characteristics of extramammary Paget’s disease: report of 246 Chinese male patients

Extramammary Paget’s disease (EMPD) is a rare cutaneous neoplasm. The aim of this study was to elaborate the clinical and pathological features of Chinese EMPD male patients. The study comprised 246 patients with EMPD at our institute from January 1993 to December 2012. Scrotum was the most common initial site. The average age of onset was 63.9 years but the mean delay in diagnosis was 3.6 years. EPMD spread exclusively to the inguinal lymph nodes and the right inguinal lymph nodes are more likely to suffered Paget cells infiltration. Accompanying malignancies were found in 20 patients. Pathological examination revealed 63 patients defined as invasive EMPD. Immunohistochemical detection showed various expression levels of EMA, CEA, CK7, HER2/neu, Ki67, P53, CK20 and S100 in tumor tissues, but negative expression of VIM, LCA and HMB45. HER2/neu protein exhibited a significant association with invasive EMPD. A novel histological type of EMPD with CK7-/S100+ was identified. Elevated serum PSA level was observed in only 16% patients. Invasive EMPD often had advanced age of onset. Metastatic EMPD showed significantly shorter in the delay in diagnosis and the greater length of skin lesion in contrast to others. This study demonstrates the clinical and pathological features of Chinese male EMPD patients, and may provide implications for the management of Chinese EMPD patients.

Extramammary Paget's disease in two brothers

Extramammary Paget's disease in two brothers

Extramammary Paget's disease (EMPD), which is considered to be an adenocarcinoma of the apocrine glands, is a rare, slow-growing neoplasm. The standard treatment for local EMPD is surgical resection, however, so far, no effective treatment is found for advanced EMPD. Trastuzumab, which is a recombinant monoclonal antibody against the human epidermal growth factor receptor 2 HER2 has been proved to be effective in the treatment of advanced EMPD in some cases where HER2 protein is overexpressed. Herein, we report two cases of EMPD in two brothers. The younger brother who presented as local EMPD on the scrotum received surgical resection and had no recurrence in 15 months following. The older brother suffered from invasive EMPD also on the scrotum with inguinal region multiple metastatic lymph nodes and was treated with combination chemotherapy and Trastuzumab to target HER2 consecutively after a wide surgical excision.