, ,

Genetic Alterations and Prognosis in Extramammary Paget’s Disease

, ,
Genetic Alterations and Prognosis in Extramammary Paget’s Disease

Extramammary Paget’s Disease (EMPD) is a relatively rare skin cancer that typically appears in genital area. As a result, little is known about the association between genetic changes and prognosis for people diagnosed with this condition. This study was conducted in Japan using a national database. This database included people who had undergone comprehensive genomic profiling tests to examine genetic changes in their cancer. We aimed to explore the relationship between specific genetic changes and the prognosis of EMPD cases. To do this, we analyzed 167 cases from the database, focusing on 127 people for whom survival data was available. Our main goal was to see how genetic alterations might impact patient survival. In our cohort, a gene called ‘CDKN2A’ was most frequently altered (56%), and we found that changes to CDKN2A (such as loss) was linked to poorer prognosis. Similarly, cases with changes to a gene called ‘BRCA2’ were also associated with a poorer prognosis. We further noted that earlier testing for genetic changes could lead to better treatment planning and outcomes. In conclusion, identifying CDKN2A genetic changes in EMPD may be related to poor prognosis. These novel findings may help doctors create more personalized treatment plans for people with EMPD. Understanding these genetic factors also opens new research opportunities in EMPD.

,

Navigating the Maze: Insights from a Case Series of Vulval Extramammary Paget’s Disease

,
Navigating the Maze: Insights from a Case Series of Vulval Extramammary Paget’s Disease

Extramammary Paget’s remains a rare neoplastic condition, which although shares the name with Paget’s disease of the breast, is a distinct entity. The condition predominantly affects the epidermis of the vulval skin of postmenopausal women. In this case series, we present the cases of two geriatric patients who were diagnosed with this rare condition and the different treatment options available in managing the disease. Despite its rarity, understanding of this neoplastic condition is vital due to its potential for misdiagnosis and its impact on patient quality of life.

, ,

Modified Mohs surgery reduces recurrence of extramammary Paget's disease

, ,
Modified Mohs surgery reduces recurrence of extramammary Paget's disease

A Mayo Clinic study found that a multidisciplinary surgical approach guided by modified Mohs surgery achieved better recurrence-free survival for patients with female extramammary Paget's disease (EMPD) when compared with traditional wide local excision (WLE). The findings were recently published in the American Journal of Obstetrics and Gynecology (AJOG).

Margin-controlled surgery, including modified Mohs surgery, has previously been shown to improve outcomes in male genital EMPD. The investigators embarked on this study to see if this finding held true for female anatomy.

The Mayo Clinic investigators had observed frequent EMPD recurrences following the traditional surgical approach; thus, they sought a more effective surgical method, according to Kelly H. Bruce, M.D., M.S.

,

Independent Risk Factors for Postoperative Recurrence of Patients with Primary Extramammary Paget’s Disease: A Retrospective Analysis

,
Independent Risk Factors for Postoperative Recurrence of Patients with Primary Extramammary Paget’s Disease: A Retrospective Analysis

Primary extramammary Paget’s disease (EMPD) is a rare type of intraepithelial adenocarcinoma that shares histological features with Paget's disease but affects areas rich in apocrine glands outside the breast. It predominantly manifests in regions like the vulva, perianal, scrotum, and penile areas, with symptoms such as pruritus, erythema, and occasionally nodules or exudation. Unlike mammary Paget’s disease, primary EMPD affects both sexes, with a higher prevalence in Asian men and white women. The disease is rare, with an incidence of approximately 0.4-0.6 per million person-years in Europe and China. Despite its slow growth and nonspecific symptoms, primary EMPD carries significant morbidity due to high recurrence rates following surgical resection, prompting studies to identify prognostic factors like ill-defined tumor borders, exudation, and nodules.

A recent retrospective study from the First Affiliated Hospital of Chongqing Medical University aimed to analyze factors influencing postoperative recurrence of primary EMPD. The study enrolled 40 Chinese patients diagnosed between 2009 and 2019, predominantly male (77.5%), with a median age of 75.52 years. Clinical characteristics such as ill-defined tumor borders, presence of exudation, and nodules on the lesions were identified as significant risk factors for recurrence in multivariate analysis. Despite advancements in surgical techniques like wide local excision and Mohs micrographic surgery, the study highlighted challenges in early diagnosis due to misdiagnosis and delayed treatment, often mistaken for common dermatological conditions. The findings underscored the importance of vigilant clinical assessment and the need for tailored surgical approaches to improve outcomes in primary EMPD. This study contributes insights into managing primary EMPD by identifying specific clinical features associated with recurrence risk. Further research with larger cohorts and longer follow-up periods is necessary to validate these findings and refine treatment strategies for this challenging disease.

,

National incidence and survival of extramammary Paget disease 2013–2020 in England: reporting a total of 740 cases

,
National incidence and survival of extramammary Paget disease 2013–2020 in England: reporting a total of 740 cases

Extramammary Paget disease (EMPD) is a rare cancer primarily affecting genital and perianal areas, first described in 1889. Diagnosis can be delayed due to its subtle symptoms, but it's crucial as it often signals underlying malignancies, most commonly urothelial or anorectal. Recent epidemiological data from England suggest a fluctuating annual incidence around 0.17 per 100,000 person-years, with a noticeable decrease during the COVID-19 pandemic, highlighting its impact on diagnostic and healthcare services.

Recurrence of Quadruple Extramammary Paget’s Disease after 12 Years: A Case Report and Literature Review

Recurrence of Quadruple Extramammary Paget’s Disease after 12 Years: A Case Report and Literature Review

Extramammary Paget’s disease (EMPD) is a rare skin cancer that tends to be multicentric, with quadruple EMPD cases being scarcely reported. Case Presentation: We report the case of an 81-year-old man with heterochronous quadruple EMPD. Twelve years after total resection of EMPD, the patient developed erythematous lesions on the resection margin in the lower abdomen, umbilical region, and both axillae. Histological examination revealed that all lesions were in situ EMPD. We reviewed six reported cases of quadruple EMPD with respect to race, sex, site, recurrence, time to recurrence, serum carcinoembryonic antigen, and depth. All patients were elderly Japanese males. In all but one case, the lesions were located in the apocrine region, which is a common site in such as the genital and axillary areas. Our case was the only heterochronous quadruple EMPD. The lesions were limited to the epidermis; therefore, they were unlikely to cause metastasis. It has been reported that the therapeutic effects of imiquimod can be expected in in situ EMPD. Therefore, quadruple EMPD may be a good indication of treatment option. EMPD is a disease whose pathogenesis is not yet clear; however, it is hoped that the origin and aetiology of EMPD will be elucidated from the clinical features of multiple EMPD in the future.

Clinicopathological Correlation and Recurrence Outcome of Adnexal Involvement on Primary Extramammary Paget’s Disease (EMPD)

Clinicopathological Correlation and Recurrence Outcome of Adnexal Involvement on Primary Extramammary Paget’s Disease (EMPD)

Primary extramammary Paget's disease (EMPD) is a rare type of cancer that appears as well-defined red plaques, often misdiagnosed due to its similarity to other skin conditions. This study aimed to evaluate the clinicopathological correlation of primary EMPD with adnexal features by analyzing 43 confirmed cases in patients aged 45-95. Expert dermatopathologists, blinded to initial diagnoses, conducted thorough histopathological evaluations. Statistical analyses included Pearson’s Chi-square, Mann-Whitney U, Spearman’s Correlations, Kaplan-Meier, log-rank tests, and Cox regression to assess correlations and recurrence predictions.

The results showed significant associations between adnexal involvement and the site of lesions, as well as between adnexal depth and EMPD subtypes. Smaller, non-invasive EMPD lesions were associated with longer recurrence-free periods, while the primary EMPD subtype was the only independent predictor for recurrence time. The study concludes that adnexal proliferation is crucial for both clinicopathological correlations and recurrence predictions, highlighting its importance in the diagnosis and prognosis of primary EMPD.

, , ,

Whole genome sequencing of HER2-positive metastatic extramammary Paget’s disease

, , ,
Whole genome sequencing of HER2-positive metastatic extramammary Paget’s disease

Extramammary Paget’s disease (EMPD) is a rare cancer that occurs within the epithelium of the skin, arising predominantly in areas with high apocrine gland concentration such as the vulva, scrotum, penis and perianal regions. Here, we aim to integrate clinicopathological data with genomic analysis of aggressive, rapidly-progressing de novometastatic EMPD responding to HER2-directed treatment in combination with other agents, to attain a more comprehensive understanding of the disease landscape

,

Unusual case of extramammary Paget disease of the oral mucosa: A case report and literature review

,
Unusual case of extramammary Paget disease of the oral mucosa: A case report and literature review

Paget disease is an intraepithelial neoplastic proliferation, commonly occurring in the breast and apocrine-rich areas, often associated with an underlying internal malignancy. Extramammary Paget disease (EMPD) of the oral cavity is exceedingly rare, with only eight reported cases, four of which were associated with an underlying internal malignancy. Here, we report a case of oral EMPD involving the buccal mucosa and gingiva of an 81-year-old male with no known underlying internal malignancy. The Paget cells were positive for CK7, CK20, CAM5.2, and androgen receptor, but negative for SOX10 and p63. The immunophenotype, association with internal malignancies, and treatment approaches for oral EMPD are reviewed.

,

Incidence and Survival of Extramammary Paget’s Disease from the Surveillance, Epidemiology, and End Results (SEER) Database

,
Incidence and Survival of Extramammary Paget’s Disease from the Surveillance, Epidemiology, and End Results (SEER) Database

Extramammary Paget’s Disease (EMPD) is a rare intraepithelial neoplasm predominantly affecting the anogenital regions of older, female, and Asian patients. It often progresses insidiously, leading to diagnostic delays spanning years. This study, conducted through a retrospective review of EMPD patients from 22 SEER registries between 2004 and 2020, aimed to analyze contemporary trends in incidence and survival across sexes. The data included various demographics and clinical factors, and age-adjusted incidence rates were calculated over a 20-year period. Survival estimates were assessed using Kaplan-Meier curves, while Cox proportional hazards models were utilized to identify factors associated with all-cause mortality. The study included 3608 patients, with a higher incidence in Asian patients, who had a rate double that of white patients. Notably, the incidence increase was significant only among white patients. Females had a better ten-year survival rate (63.0%) compared to males (53.4%). Multivariable analysis revealed that older age, advanced disease stage, and treatment delays were linked to poorer overall survival, while primary surgical treatment significantly reduced mortality risk compared to no cancer-directed treatment. The study highlights the rising incidence of EMPD and emphasizes the importance of early, complete surgical resection in improving long-term survival outcomes.

,

Preoperative mapping biopsies with local excision in the treatment of Extramammary Paget Disease

,
Preoperative mapping biopsies with local excision in the treatment of Extramammary Paget Disease

Surgical excision of extramammary Paget disease (EMPD) is associated with a high local recurrence rate. This study found that PMB before local excision significantly reduced the risk of recurrence when treating EMPD. Further studies are necessary to compare the recurrence rates of PMB, Mohs micrographic surgery and WLE for EMPD.

,

Extramammary Paget Disease of Oral Mucosa: Case Report with Literature Review

,
Extramammary Paget Disease of Oral Mucosa: Case Report with Literature Review

Extramammary Paget disease (EPMD) of the oral mucosa is an unusual and extremely rare condition, with fewer than ten cases documented. Here, we report a case of EMPD extensively involving oral mucosa and underlying salivary ducts in a 72-year-old male and review published clinical, histologic, immunophenotypic, and prognostic features of this rare entity.

,

Long-Term Complete Response and Survival in Metastatic Extramammary Paget’s Disease Treated With Trastuzumab Plus Paclitaxel: A Case Report

,
Long-Term Complete Response and Survival in Metastatic Extramammary Paget’s Disease Treated With Trastuzumab Plus Paclitaxel: A Case Report

Extramammary Paget’s disease is a rare skin cancer that usually arises from the secretory cells of the apocrine glands. In most cases, an extramammary Paget’s tumor occurs as a single intraepithelial form not associated with another cancer, although rarely, it may be associated with other loco-regional or distant cancer. In this case report, we have observed a long-lasting complete response with anti-HER2 plus paclitaxel.

A familial case of extramammary Paget disease: Analysis of whole-exome sequencing

A familial case of extramammary Paget disease: Analysis of whole-exome sequencing

Extramammary Paget disease (EMPD) is a rare, cutaneous malignancy that is most likely to occur in the genital area of the elderly population. Although there have been several reports on familial EMPD, its pathogenic germline mutations have not been analyzed. We herein report the results of the genetic analysis of an EMPD patient with a family history of the same disease, affecting her mother and sister.

Treatment of extramammary Paget's disease with imiquimod in a real-life setting: a multicenter retrospective analysis in Spain

Treatment of extramammary Paget's disease with imiquimod in a real-life setting: a multicenter retrospective analysis in Spain

Topical imiquimod has shown to be an effective treatment for EMPD, although available evidence supporting its use is based on case reports and small series of patients. To investigate the therapeutic outcomes and analyze potential clinico-pathological factors associated with imiquimod response in a large cohort of EMPD patients.

,

Identification of a rare MET variant in a familial case of extramammary Paget’s disease

,
Identification of a rare MET variant in a familial case of extramammary Paget’s disease

Extramammary Paget’s disease (EMPD) is an intraepithelial adenocarcinoma that primarily affects the genital and axillary areas in elderly individuals. A limited number of paired familial EMPD cases (i.e., parent-offspring, siblings) have been reported, whereas the genetics of these cases have not yet been adequately studied.  We report the first familial case of EMPD involving three affected siblings.  The tumour-only multigene panel testing using surgical specimens revealed a heterozygous c.2997A>C (p.Glu999Asp) nonsynonymous variant in the proto-oncogene MET (NM_000245.4) in the three affected siblings. The germline multi-gene panel testing using peripheral blood lymphocytes revealed the same missense MET variant in all five family members, including the two asymptomatic offspring (51 and 37 years of age). The MET variant we identified could be involved in EMPD carcinogenesis. Further genomic analyses of familial cases of EMPD are warranted to validate the pathogenic relevance of MET variants in EMPD development.

Anatomic Subtype Differences in Extramammary Paget Disease

Anatomic Subtype Differences in Extramammary Paget Disease

How do disease presentation and treatment in extramammary Paget disease (EMPD) differ by anatomic subtype? This meta-analysis of 135 studies found that, despite typically being intraepidermal, vulvar disease was more likely treated with radical surgery. Nearly one-third of vulvar cases recurred, predominantly locally in the skin and mucosa and one-third of perianal EMPD cases recurred; however, one-third of those recurrences presented as regional or distant metastasis and penoscrotal EMPD was least likely to recur.

,

FOXM1: a new therapeutic target of extramammary Paget disease

,
FOXM1: a new therapeutic target of extramammary Paget disease

Extramammary Paget disease (EMPD) is a rare skin cancer that primarily affects older individuals predominantly in areas with apocrine sweat glands. Although most early EMPD lesions are indolent, patients with metastatic EMPD have a poor prognosis due to the lack of effective systemic treatment. In this study, we investigated the role of forkhead box M1 (FOXM1), a potent transcription factor, in EMPD and assessed the potential of FOXM1 as a therapeutic target. Immunohistochemistry of 112 primary and 17 metastatic EMPD samples revealed that FOXM1 expression increased with tumor progression. Patients in whom FOXM1 was expressed in more than 10% of tumor cells had significantly shorter disease-specific survival than the other patients (p = 0.0397). In in vitro studies using our newly established EMPD cell line, KS-EMPD-1, we found high expression of FOXM1. Knockdown of FOXM1 impaired tumor cell viability, migration, and invasion. Inhibition of FOXM1 using thiostrepton also reduced tumor cell viability in a dose-dependent manner. These findings suggest that FOXM1 is a promising therapeutic target for patients with EMPD.

,

Untargeted metabolomics yields insight into Extramammary Paget's disease mechanisms

,
Untargeted metabolomics yields insight into Extramammary Paget's disease mechanisms

Extramammary Paget's disease (EMPD) is a rare cutaneous malignancy, commonly affecting the external genitalia and perianal area of the elderly with unclear pathogenesis. Metabolomics provides a novel perspective for uncovering the metabolic mechanisms of a verity of cancers. Here, we explored the metabolome of EMPD using an untargeted strategy. Results showed that a total of 896 metabolites were identified and 87 metabolites including 37 up-regulated and 50 down-regulated significantly in EMPD were sought out. This study was the first to reveal the metabolome profile of EMPD. Our results demonstrate that IDO1/TDO2-initialized KYN metabolic pathway may play a vital role in the development and progression of EMPD, which may serve as a potential therapeutic target for treating EMPD.

,

How to Surveil Perianal Paget's Disease: A Case Report

,
How to Surveil Perianal Paget's Disease: A Case Report

Perianal Paget’s disease (PPD) is a rare manifestation of extramammary Paget’s disease. It is characterized by the presence of malignant glandular epithelial cells within the squamous epithelium. There is a well-established but poorly understood association between PPD and underlying malignancy. Due to the rarity of the disease, there are no established guidelines for treatment or surveillance of PPD. We present the unusual case of a 73-year-old woman with primary PPD without an underlying malignant lesion. The rarity of the disease renders its management and surveillance an ongoing challenge. Our case of PPD without an underlying malignancy poses the question of the most appropriate surveillance for this rare disease.

© myEMPD.com • Helping those with extramammary Paget’s disease (EMPD).