A Positive Dermcidin Expression Is an Unfavorable Prognostic Marker for Extramammary Paget’s Disease

Extramammary Paget’s disease is recognized as an apocrine-origin cutaneous tumor and is localized in the intraepithelial skin lesion. However, its advanced form is intractable, and there is currently no therapeutic option with a satisfactory level of clinical outcome. Therefore, it is of great importance to identify a potential biomarker to estimate tumor advancement in extramammary Paget’s disease. Dermcidin is an antimicrobial peptide derived from the eccrine gland and is identified as a biomarker in various malignancies. To investigate the potential of dermcidin in extramammary Paget’s disease, we investigated dermcidin expression in tumors using the immunostaining technique. Although previous studies have reported that extramammary Paget’s disease has no positive staining against dermcidin, 14 out of 60 patients showed positive staining of dermcidin in our study. To clarify the characteristics of positive dermcidin in extramammary Paget’s disease, we investigated the clinical characteristics of positive dermcidin extramammary Paget’s disease patients. Positive dermcidin patients showed a significantly high frequency of lymph node metastasis. We next investigated the impact of positive dermcidin on overall survival. Univariate analysis identified that positive dermcidin showed a significantly increased hazard ratio in overall survival, suggesting that dermcidin might be a prognostic factor for extramammary Paget’s disease.

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Imiquimod 5% cream as a therapeutic option for extramammary Paget's disease

The Journal of Dermatology ◽

10.1111/1346-8138.14117 ◽

2017 ◽

Vol 45 (2) ◽

pp. 216-219 ◽

Cited By ~ 12

Author(s):

Masahide Sawada ◽

Junji Kato ◽

Toshiharu Yamashita ◽

Akihiro Yoneta ◽

Tokimasa Hida ◽

...

Keyword(s):

Therapeutic Option ◽

Paget’S Disease ◽

Paget's Disease ◽

Extramammary Paget’S Disease ◽

Extramammary Paget's Disease

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Mucosal Invasion, but Not Incomplete Excision, Has Negative Impact on Long-Term Survival in Patients With Extramammary Paget’s Disease

Frontiers in Oncology ◽

10.3389/fonc.2021.642919 ◽

2021 ◽

Vol 11 ◽

Author(s):

Hiroki Hashimoto ◽

Yumiko Kaku-Ito ◽

Masutaka Furue ◽

Takamichi Ito

Keyword(s):

Paget’S Disease ◽

Paget's Disease ◽

Extramammary Paget’S Disease ◽

Disease Specific Survival ◽

Boundary Area ◽

Incomplete Excision ◽

Tumor Involvement ◽

The Impact ◽

Disease Specific ◽

Extramammary Paget's Disease

BackgroundExtramammary Paget’s disease (EMPD) sometimes spreads from the skin to mucosal areas, and curative surgical excision of these areas is challenging. The aim of this study is to analyze the impact of mucosal involvement and surgical treatment on the survival of patients with EMPD.MethodsWe conducted a retrospective review of 217 patients with EMPD. We also assessed the associations between tumor involvement in boundary areas (anal canal, external urethral meatus, vaginal introitus), prognostic factors, and survival in 198 patients treated with curative surgery.ResultsOf 217 patients, 75 (34.6%) had mucosal boundary area involvement. Lesions in these areas were associated with frequent lymphovascular invasion (p = 0.042), lymph node metastasis (p = 0.0002), incomplete excision (p < 0.0001), and locoregional recurrence (p < 0.0001). Boundary area involvement was an independent prognostic factor associated with disease-specific survival, per multivariate analysis (HR: 11.87, p = 0.027). Incomplete excision was not significantly correlated with disease-specific survival (HR: 1.05, p = 0.96).ConclusionBoundary area tumor involvement was a major risk factor for incomplete excision, local recurrence, and poor survival outcomes. However, incomplete removal of primary tumors was not significantly associated with poor prognosis. A less invasive surgical approach for preserving anogenital and urinary functions may be acceptable as the first-line treatment for resectable EMPD.

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Nomograms for predicting cancer-specific and overall survival in patients with invasive extramammary Paget’s disease

Future Oncology ◽

10.2217/fon-2021-0372 ◽

2021 ◽

Author(s):

Xiang Gao ◽

Xi Zhong ◽

Hai-Ning Chen ◽

Dujanand Singh ◽

Lie Yang ◽

...

Keyword(s):

Overall Survival ◽

Cox Regression ◽

Paget’S Disease ◽

Tumor Location ◽

Paget's Disease ◽

Extramammary Paget’S Disease ◽

Cancer Specific Survival ◽

Treatment Design ◽

Extramammary Paget's Disease ◽

Good Calibration

Aim: To develop nomograms for predicting cancer-specific survival (CSS) and overall survival (OS) in patients with invasive extramammary Paget’s disease (iEMPD). Patients & methods: Retrospective data of 1955 patients with iEMPD were collected from the Surveillance, Epidemiology, and End Results database. Nomograms for predicting CSS and OS were established using competing risk regression and Cox regression, respectively, and were internally validated. Results: Five (age, surgery, tumor location, stage and concurrent malignancy) and eight (gender, age, race, marital status, surgery, tumor location, stage and lymph node metastasis) clinicopathological factors were utilized to construct nomograms for predicting CSS and OS, respectively. The concordance indices of the nomograms for predicting CSS and OS were 0.78 and 0.73, respectively. The validation of the nomograms showed good calibration and discrimination. The decision curve analyses confirmed the clinical utility of these nomograms. Conclusion: The nomograms can be a reliable tool for treatment design and prognostic evaluation of iEMPD.

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CDK4: A Novel Therapeutic Target for Extramammary Paget’s Disease

Frontiers in Oncology ◽

10.3389/fonc.2021.710378 ◽

2021 ◽

Vol 11 ◽

Author(s):

Hiroki Hashimoto ◽

Yumiko Kaku-Ito ◽

Yoshinao Oda ◽

Takamichi Ito

Keyword(s):

Targeted Therapy ◽

Cyclin D1 ◽

Therapeutic Target ◽

Regional Lymph Node ◽

Paget’S Disease ◽

Paget's Disease ◽

Extramammary Paget’S Disease ◽

The Impact ◽

Cdk4 Expression ◽

Extramammary Paget's Disease

BackgroundThe outcome of extramammary Paget’s disease (EMPD) is poor when it progresses to metastasis because of the lack of effective systemic therapies. Recently, CDK4-targeted therapy has attracted attention as a potential therapeutic target for some cancers. The aim of this study was to analyze the impact of CDK4 expression on the survival of patients with EMPD.MethodsWe retrospectively reviewed 110 patients with EMPD. We conducted immunohistochemical analysis of CDK4 and cyclin D1 expression, and assessed the association between their expression and survival.ResultsMost EMPD lesions (108/110, 98.2%) were positive for CDK4 staining and there was a positive correlation between CDK4 expression and cyclin D1 expression (r = 0.54, p < 0.001). Tumor thickness (p = 0.0003) and the presence of regional lymph node metastasis (p = 0.015) were significantly associated with high CDK4 expression. Regarding invasive EMPD, the multivariate analysis did not show the correlation between the expression of CDK4/cyclin D1 and survival outcomes (HR: 3.14, p = 0.14).ConclusionThe overexpression of CDK4 was identified as a major risk factor for disease progression. CDK4-targeted therapy could thus be a novel treatment option for unresectable EMPD.

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Definitive Radiotherapy for Penoscrotal Extramammary Paget’s Disease: A Case Report with Long-Term Follow-Up

Clinical Medicine Insights Case Reports ◽

10.1177/11795476211009251 ◽

2021 ◽

Vol 14 ◽

pp. 117954762110092

Author(s):

Gen Suzuki ◽

Kazutaka Machida ◽

Akito Asato ◽

Sho Seri ◽

Chika Ikemoto ◽

...

Keyword(s):

Therapeutic Option ◽

Multidisciplinary Treatment ◽

Paget’S Disease ◽

Treatment Strategies ◽

Paget's Disease ◽

Severe Toxicity ◽

Extramammary Paget’S Disease ◽

Treatment Team ◽

Extramammary Paget's Disease

Penoscrotal extramammary Paget’s disease (EMPD) is a rare intraepithelial adenocarcinoma in older male patients, and no effective nonsurgical treatment strategies are currently available. The aim of this study was to report the usefulness of external radiotherapy (RT) for penoscrotal EMPD in an inoperable elderly patient. This report presents the treatment of an 89-year-old man with widespread penoscrotal EMPD. A multidisciplinary treatment team decided on radical RT. The patient received a radiation dose of 61.8 Gy in 30 fractions through electron and photon beams. His treatment tolerance was good, and no severe toxicity had been observed up the last follow-up. At 6.5 years after the RT, the patient showed no evidence of recurrence. Definitive RT resulted in excellent disease control and minimal toxicity; thus, it could be a promising nonsurgical therapeutic option for penoscrotal EMPD, even in extremely elderly individuals.

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