EMPD Report

Doença de Paget vulvar: uma série de casos no sul do Brasil

Doença de Paget vulvar: uma série de casos no sul do Brasil

A doença de Paget vulvar é rara e manifesta-se clinicamente como lesão cutânea eritematosa pruriginosa com áreas de hiperqueratose. O presente relatório descreve os dados de diagnóstico, manejo e resultados de uma série de casos de mulheres diagnosticadas com doença de Paget vulvar em um hospital terciário no sul do Brasil. A doença de Paget vulvar tem uma morbidade significativa e os dados disponíveis são limitados, especialmente no Brasil. Devido à raridade da doença, não há ensaios clínicos randomizados disponíveis na literatura e, portanto, é difícil comparar os resultados do tratamento cirúrgico com outras modalidades terapêuticas.

Extramammary Paget’s Disease Manifested by Intraepithelial Adenocarcinoma of the Vulva and Anus Combined with Invasive Adenocarcinoma of the Ampullary Part of the Rectum

Extramammary Paget’s Disease Manifested by Intraepithelial Adenocarcinoma of the Vulva and Anus Combined with Invasive Adenocarcinoma of the Ampullary Part of the Rectum

The author of the given paper describes an unusual combination of two diseases: extramammary Paget’s disease manifested by intraepithelial adenocarcinoma of the vulva and anus combined with invasive adenocarcinoma of the ampullary part of the rectum and describes the atypical manifestations of these diseases.

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Five- and 10-year survival in extramammary Paget's disease: A focus on wide local excision

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Five- and 10-year survival in extramammary Paget's disease: A focus on wide local excision

This study aimed to analyze extramammary Paget's disease (EMPD)-specific survival, overall survival, and recurrence rate (RR) in patients with EMPD in South Korea, with a focus on wide local excision. Based on the survival and RRs obtained, surgical treatment of EMPD with wide local excision provides fair curative resection.

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Efficacy of Abemaciclib in the Management of Refractory Metastatic Extramammary Paget’s Disease

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Efficacy of Abemaciclib in the Management of Refractory Metastatic Extramammary Paget’s Disease

Published systemic therapy options for metastatic extramammary Paget's disease have largely been anecdotal due to the rarity of this disease, which has precluded the ability to conduct clinical trials. We describe the favorable response of a 72-year-old man with extramammary Paget's disease, whose disease has been controlled with the CDK4/6 inhibitor, abemaciclib. The rationale behind the selection of this therapy is discussed.

Evidence-Based Clinical Practice Guidelines for Extramammary Paget Disease

Evidence-Based Clinical Practice Guidelines for Extramammary Paget Disease

Extramammary Paget disease (EMPD) is a frequently recurring malignant neoplasm with metastatic potential that presents in older adults on the genital, perianal, and axillary skin. Extramammary Paget disease can precede or occur along with internal malignant neoplasms. The key findings were as follows: (1) Multiple skin biopsies, including those of any nodular areas, are critical for diagnosis. (2) Malignant neoplasm screening appropriate for age and anatomical site should be performed at baseline to distinguish between primary and secondary EMPD. (3) Routine use of sentinel lymph node biopsy or lymph node dissection is not recommended. (4) For intraepidermal EMPD, surgical and nonsurgical treatments may be used depending on patient and tumor characteristics, although cure rates may be superior with surgical approaches. For invasive EMPD, surgical resection with curative intent is preferred. (5) Patients with unresectable intraepidermal EMPD or patients who are medically unable to undergo surgery may receive nonsurgical treatments, including radiotherapy, imiquimod, photodynamic therapy, carbon dioxide laser therapy, or other modalities. (6) Distant metastatic disease may be treated with chemotherapy or individualized targeted approaches. (7) Close follow-up to monitor for recurrence is recommended for at least the first 5 years.

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Prognostic value of treatment options for extramammary Paget’s disease: a SEER database analysi

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Prognostic value of treatment options for extramammary Paget’s disease: a SEER database analysi

Extramammary Paget’s disease (EMPD) is a common subtype of Paget’s disease. Still, there are lacking reports concerning its clinical features, treatment options, and prognosis. EMPD had distinct clinical features from MPD. Age, gender, chemotherapy, tumor grade and stage are independent prognostic factors for EMPD. While surgery’s protective role was supported, radiotherapy and chemotherapy could be unfavorable treatments concerning EMPD prognosis.

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Prevalence of extramammary Paget’s disease in urban China: a population-based study

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Prevalence of extramammary Paget’s disease in urban China: a population-based study

Extramammary Paget’s disease (EMPD) is a rare intraepithelial adenocarcinoma that significantly impacts quality of life due to its chronic and symptomatic nature. A population-based study using data from China’s Urban Employee and Resident Basic Medical Insurance in 2016 aimed to assess EMPD prevalence and its demographic patterns in China, where no national data previously existed. The study identified 84 cases, revealing a crude prevalence of 0.04 per 100,000 population, with regional variations ranging from 0.01 in North/Northeast China to 0.08 in Southwest China. The condition was more common in males (0.05) than females (0.03) and most prevalent among individuals aged 70–79 (0.28). This prevalence is notably lower compared to Western countries, and the Chinese patients were generally younger with a significant male predominance. Further research is needed to explore the underlying mechanisms of EMPD.

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Ectopic extramammary Paget disease in thoracic location

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Ectopic extramammary Paget disease in thoracic location

Extramammary Paget disease (EMPD) is a rare skin cancer that affects areas with a high concentration of apocrine glands including genital, axillary, and anal skin. When it affects other locations it is called ectopic extramammary Paget disease (E-EMPD) and is uncommon. To date, there are only 45 case reports to the best of our knowledge. The clinical manifestation is typically a soft, red or bright pink patch or plaque with scattered white islands of hyperkeratosis and erosion. Diagnostic confirmation requires conventional histology with immunohistochemistry. The importance of immunohistochemical staining for the diagnosis of primary neoplasia, without underlying malignancy, is highlighted. We report the first Latin American confirmed case, to our knowledge, of primary E-EMPD in a 55-year-old man with a 1-year history of asymptomatic thoracic plaque.

Genitourinary extramammary Paget’s disease: review and outcome in a multidisciplinary setting

Genitourinary extramammary Paget’s disease: review and outcome in a multidisciplinary setting

Extramammary Paget’s disease (EMPD) is a rare malignant disease originating from the apocrine glands involving the perineum, vulva, axilla, scrotum, and penis. To study the clinical presentation, extent of disease, efficacy of treatment, and survival outcomes of the cases in a single institution. Retrospective observation data analysis of 19 EMPD cases was performed. Demographic information, clinical management records, and histopathologic data of individual cases were obtained from the inpatient hospital data registry.

Genomic Alterations as Potential Therapeutic Targets in Extramammary Paget’s Disease of the Vulva

We identified all patients with primary vulvar EMPD who were treated at our institution and underwent paired tumor-normal massively parallel sequencing of 410-468 cancer-related genes (MSK-IMPACT assay). EMPD of the vulva samples sequenced from 2014 to 2019 were reviewed and somatic mutations identified, with specific focus on mutations of potential therapeutic targets. Clinical data were abstracted from electronic medical records. Microsatellite instability (MSI) was assessed by MSIscore.

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.

Extramammary Paget’s Disease and Melanoma: 2 Cases of Double Cancers

Extramammary Paget’s Disease and Melanoma: 2 Cases of Double Cancers

Extramammary Paget’s disease (EMPD) is a rare intraepidermal neoplastic disease. There is a well-known relationship between EMPD and underlying malignancy. However, only a few cases of EMPD and cutaneous melanoma have been reported previously. In this case report we present 2 cases of such double cancers: one as a collision tumor, the other at separate sites. We discuss the pathogenesis, treatment, and importance of a thorough clinical and radiological examination and review the literature.

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Comparison of the biomarkers for targeted therapies in primary extra‐mammary and mammary Paget's disease

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Comparison of the biomarkers for targeted therapies in primary extra‐mammary and mammary Paget's disease

Primary Extra‐mammary Paget's disease (EMPD) is a very rare cutaneous adenocarcinoma affecting anogenital or axillary regions. It is characterized by a prolonged course with recurrences and eventually distant metastatic spread for which no specific therapy is known.

Eighteen EMPD (13 vulvar and five scrotal) and ten mammary Paget's disease (MPD) cases were comprehensively profiled for gene mutations, fusions and copy number alterations, and for therapy‐relevant protein biomarkers).

Mutations in TP53 and PIK3CA were the most frequent in both cohorts: 7/15 and 5/15 in EMPD; 1/6 and 4/7 in MPD HER2 gene amplification was detected in 4/18 EMPD (3 vulvar and 1 scrotal case) in contrast to MPD where it was detected in the majority (7/8) of cases. TOP2A gene amplification was seen in 2/12 EMPD and 1/6 MPD, respectively. Similarly, no difference in estrogen receptor expression was seen between the EMPD (4/15) and MPD (3/10). Androgen receptor was also expressed in the majority of both cohorts (12/16 EMPD) and (7/8 MPD).Here ARv7 splice variant was detected in 1/7 EMPD and 1/4 MPD cases, respectively. PD‐L1 expression on immune cells was exclusively observed in three vulvar EMPD. In contrast to MPD, six EMPDs harbored a “high” tumor mutation burden (≥10 mutations/Mb). All tested cases from both cohorts were MSI stable.

Extramammary Paget’s disease: what do we know and how do we treat?

Extramammary Paget’s disease: what do we know and how do we treat?

The complexity of Extramammary Paget’s Disease (EMPD) has been apparent for decades with minimal improvements in diagnostic and therapeutic options. This rare carcinoma generally afflicts individuals greater than 60 years old and more often Caucasians than any other ethnicity.1 There are a multitude of case series, case reports, and retrospective studies, offering various treatment protocols; however, there is insufficient evidence for clear management guidelines. The heterogeneity of this disease in its presentation, location, depth of invasion and its typical multidisciplinary approach to management make it difficult to treat. The association with other malignancies is a well-described phenomenon and should inform treatment and long term management.2 Use of biomarkers shows promise in diagnosis and treatment monitoring. As immunotherapy (IO) is becoming a mainstay for many cancers, there is growing support for the use of these agents in advanced EMPD patients.

A Case of Chronic and Relapsing Paget Disease of the Vulva

A Case of Chronic and Relapsing Paget Disease of the Vulva

Extramammary Paget disease is a rare neoplastic condition that more commonly affects postmenopausal Caucasian women. Although the vulvar area is the most frequently affected location, it corresponds solely to 1 to 2% of all vulvar malignancies. A 72-year-old female patient was observed in our outpatient clinic with a 2-year history of an erythematous and pruritic plaque on the vulva. Histopathology and immunohistochemistry studies were compatible with extramammary Paget disease of the vulva. Associated neoplastic conditions were excluded. Due to multiple relapses, the patient was submitted to three surgical interventions, including a total vulvectomy, and to external radiotherapy. The present case illustrates the chronic and recurrent nature of extramammary Paget disease despite aggressive procedures as well as the challenge in obtaining tumor-free resection margins.

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Expression of PD-1 and PD-L1 in Extramammary Paget Disease: Implications for Immune-Targeted Therapy

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Expression of PD-1 and PD-L1 in Extramammary Paget Disease: Implications for Immune-Targeted Therapy

Extramammary Paget disease (EMPD) is a locally aggressive cutaneous malignancy that usually arises in anogenital or axillary skin. Immune checkpoint inhibitors targeting programmed cell death receptor (PD-1) and/or its ligand (PD-L1) are approved for the treatment of several types of cancer, and response to these generally correlates with increased PD-L1 expression by tumor cells. The expression of PD-L1 and composition and density of the tumor-associated immune infiltrate in EMPD have been little studied. To determine whether EMPD might be amenable to immune checkpoint blockade, we analyzed the expression of PD-1 and PD-L1 and the composition and density of the tumor-associated immune infiltrate in EMPD and evaluated associations between biomarker expression and clinicopathologic parameters. Twenty-one EMPD tumors were evaluated for tumor cell PD-L1 expression and for relative expression and distribution of CD3, CD8, PD-1, and PD-L1 in the tumor-associated immune infiltrate by using a combination of visual and image analysis (Aperio ImageScope). In addition, PD-L1 expression was assessed in 10 cases of mammary Paget disease (MPD). In EMPD cases, PD-L1 was expressed by tumor cells (3/21; 14%) and the tumor-associated immune infiltrate (15/21; 71%), and PD-1 was expressed by the tumor-associated immune infiltrate in all cases analyzed (18/18). However, PD-L1 expression by EMPD tumor cells did not correlate with the density of CD3-, CD8-, or PD-1-positive cells in the tumor-associated immune infiltrate or other clinicopathologic parameters. Furthermore, the density of CD3, CD8, PD-1, and PD-L1 in the tumor-associated immune infiltrate did not correlate with any clinicopathologic parameters evaluated with the exception that CD3 positive values were significantly higher in patients who were still alive (median, 1310 cells/mm2; range, 543–2115;) than in those who died (median, 611 cells/mm2; range, 481–908; p = 0.049). In all MPD cases, PD-L1 was absent in tumor cells but present in the tumor-associated immune infiltrate, and PD-L1 expression in lymphocytes was lower in patients with HER2/neu-positive than in those with HER2/neu-negative disease (p = 0.07). Our findings raise the possibility of therapeutic targeting of the PD-1/PD-L1 axis in EMPD.

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Topical Combination of Fluorouracil and Calcipotriene as a Palliative Therapy for Refractory Extramammary Paget Disease.

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Topical Combination of Fluorouracil and Calcipotriene as a Palliative Therapy for Refractory Extramammary Paget Disease.

Extramammary Paget disease (EMPD), a rare intraepithelial adenocarcinoma, poses a therapeutic challenge with high postoperative recurrence rates and a limited number of effective local treatment options. This retrospective case series of 3 women with recurrent, refractory EMPD was conducted at Beth Israel Deaconess Medical Center, Boston, Massachusetts and Washington University School of Medicine, St Louis, Missouri. All patients were treated with a 1:1 mixture of fluorouracil, 5%, cream and calcipotriene, 0.005%, cream or ointment.

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Extramammary Paget disease

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Extramammary Paget disease

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.

【少見癌症】Extramammary Paget's Disease（EMPD)

【少見癌症】Extramammary Paget's Disease（EMPD)

顧名思義，既然叫做「Extramammary」，表示這個診斷原本最常發生在乳房。乳腺是全身上下最大的 apocrine gland ，如果 Paget's disease 發生在乳房，通常在乳房內都能找到 infiltrating ductal carcinoma 或者 DCIS。

但是，發生 EMPD 時，並不一定能找到相對應的侵襲性癌症或原位癌。若 EMPD 位於生殖器官，能找到其他癌症的機率為 4-7%；若 EMPD 位於肛門周邊，能找到其他癌症的機率則是 25-35%。

EMPD 在組織學上的特徵就是 adenocarcinoma 的癌細胞（在此又特稱 Paget's Cell）侵犯到表皮（epidermis）。可以分為：

  • Primary EMPD ：沒有合併其他癌症存在，單獨出現。

  • Secondary EMPD ：合併有其他 adenocarinoma 存在。

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Accumulation of exhausted CD8+ T cells in extramammary Paget’s disease

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Accumulation of exhausted CD8+ T cells in extramammary Paget’s disease

Cancer immunotherapy has highlighted the clinical relevance of enhancing anti-tumor response of CD8+ T cells in several cancer types. Little is known, however, about the involvement of the immune system in extramammary Paget’s disease (EMPD). We exam- ined the cytotoxicity and the effector functions of CD8+ T cells using paired samples of peripheral blood and tumors by flow cytometry. Expression levels of perforin, granzyme B, IFN-g, TNF-a, and IL-2 in CD8+ tumor-infiltrating lymphocytes (TILs) were significantly lower than those in CD8+ T cells of peripheral blood. Significantly higher expression of PD- 1 was found in CD8+TILs than in CD8+ T cells of peripheral blood. A high number of CD8+ cells was significantly associated with poor overall survival (OS) adjusted with age, sex, and clinical stage (hazard ratio [HR] = 5.03, P = 0.045, 95% confidence interval [CI] 1.03– 24.4). On the other hand, the number of PD-1+ cells was not associated with OS or dis- ease-free survival (DFS). Moreover, we found that tumor cells produced immunosuppres- sive molecule indoleamine 2,3-dyoxygenae (IDO). In conclusion, CD8+ TILs displayed an exhausted phenotype in EMPD. IDO expression seemed more relevant in inducing CD8 exhaustion than PD-1 upregulation or PD-L1 expression by immune cells. Restoring the effector functions of CD8+ TILs could be an effective treatment strategy for advanced EMPD.

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