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

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.

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

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.

, ,

Well-demarcated erythematous plaque on the arm

, ,
Well-demarcated erythematous plaque on the arm

A 67-year-old Caucasian man presented with an asymptomatic, well-defined, irregular shaped, erythematous scaly plaque on the left upper arm for five years. There was no cervical or axillary lymphadenopathy. A skin punch biopsy was performed from the plaque. Histopathological examination showed hyperkeratosis, acanthosis and atypical large pale cells with abundant vacuolated cytoplasm in the epidermis. There was no dermal invasion. Tumor cells were positive for cytokeratin 7, but negative for cytokeratin 20, P63 and Melan A by immunohistochemistry.

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

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

Invasive extramammary Paget’s disease (iEMPD) is a rare type of cutaneous malignancy with a heterogeneous prognosis. The purpose of this study is to identify the prognostic factors associated with cancer-specific and overall survival rates in iEMPD and to develop accurate risk stratification models to guide the design of individualized treatment regimens. The nomograms can be a reliable tool for treatment design and prognostic evaluation of iEMPD.

, ,

Overexpression of Janus kinase 2 protein in extramammary Paget’s disease

, ,
Overexpression of Janus kinase 2 protein in extramammary Paget’s disease

Extramammary Paget’s disease is a rare malignant tumor of the skin that occurs primarily in the genitocrural region. Although the prognosis of extramammary Paget’s disease with distant metastasis is poor, an effective therapy has not been established. Because Janus kinase 2 has attracted attention as a therapeutic target in several cancers, we investigated the expression of the Janus kinase 2 protein and the relationship between its level of expression and clinical significance in 53 patients with extramammary Paget’s disease in our hospital. Immunohistochemistry showed that most extramammary Paget’s disease tissues were positive for Janus kinase 2 (50/53, 94.3%), and the immunostaining intensity of Janus kinase 2 was correlated with the degree of invasiveness, lymph node metastasis and distant metastasis. Based on these findings, Janus kinase 2 may be a promising therapeutic target in extramammary Paget’s disease.

, ,

Expression of programmed death-ligand 1 and programmed death-1 in patients with extramammary paget's disease

, ,
Expression of programmed death-ligand 1 and programmed death-1 in patients with extramammary paget's disease

Extramammary Paget's disease (EMPD) is a rare skin cancer and sometimes has fatal prognosis. For progressive cases, therapeutic options are limited. In recent years, treatment with an anti-programmed death-1 (PD-1) antibody has improved the prognosis of various malignancies. In addition, correlations between PD-ligand 1 (PD-L1) expression in tumor cells and favorable responses to anti-PD-1 therapy have been reported for several cancers. There have been a few case series of analysis of PD-L1 expression in patients with EMPD. The purpose of this study was to investigate the relationship between the EMPD and PD-L1/PD-1 expression in Japanese EMPD patients. We investigated 39 patients with EMPD by immunohistochemical staining of PD-L1 and PD-1. We counted the number of tumor cells that were positive for PD-L1 and the number of tumor-infiltrating mononuclear cells (TIMCs) that were positive for PD-L1 and PD-1. We also analyzed correlations between the expression of PD-L1 and PD-1 in EMPD and patients' characteristics. We found that none of the Paget's cells expressed PD-L1. All of the specimens contained TIMCs, and some of the TIMCs expressed PD-L1 and PD-1. However, there was no correlation between the expression of PD-L1/PD-1 in TIMCs and patients' characteristics. Although tumor cells did not express PD-L1 and the expression of PD-L1/PD-1 in TIMCs did not correlate with patients' characteristics, future clinical studies should be carried out to explore another immune escape pathway in EMPD.

,

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

,
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.

Definitive Radiotherapy for Penoscrotal Extramammary Paget’s Disease: A Case Report

Definitive Radiotherapy for Penoscrotal Extramammary Paget’s Disease: A Case Report

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.

, ,

Absence of microsatellite instability in extramammary Paget's disease

, ,
Absence of microsatellite instability in extramammary Paget's disease

Deficiency of DNA mismatch repair (MMR) induces micro-satellite instability (MSI). Pembrolizumab, an antibody targeting PD‐1 (an immune checkpoint inhibitor), is more effective against MMR‐deficient tumours than against MMR‐proficient tumours. The status of MMR is a useful biomarker for predicting the effectiveness of pembrolizumab administration. Although the status of MMR has attracted attention in skin tumours, there are few reports on MSI in extramammary Paget's disease (EMPD). MSI testing showed the occurrence rates of MSI‐high (more than two markers are unstable), MSI‐low (one marker is unstable) and MSS (all markers are stable) tumour tissues were 0% (0/101), 1.0% (1/101) and 99.0% (100/101), respectively. The status of MMR may not be useful for the potential therapeutic application of pembrolizumab.

,

A Case Report of Familial Extramammary Paget's Disease in Female Siblings

,
A Case Report of Familial Extramammary Paget's Disease in Female Siblings

Extramammary Paget’s disease (EMPD) is a rare intraepithelial neoplasm that occurs in apocrine-bearing areas of skin. Most EMPD patients initially present with chronic pruritic eczematous lesions involving genitalia, perineum and perianal area. Familial form of EMPD is extremely rare. Several genetic mutations have been proposed but specific modes of inheritance are still unknown. This article reports two cases of familial extramammary Paget’s disease in female siblings.

,

Margin Assessment of Extramammary Paget's Disease Based on Harmonic Generation Microscopy with Deep Neural Networks

,
Margin Assessment of Extramammary Paget's Disease Based on Harmonic Generation Microscopy with Deep Neural Networks

Surgical borders of extramammary Paget's disease (EMPD) are difficult to be identified via its clinical appearance. In this study, we propose a new diagnostic technique which combines nonlinear harmonic generation microscopy (HGM) with the deep learning method to instantaneously determine whether the imaged 3D stack is malignant EMPD or surrounding normal skin digitally. To demonstrate our proposal, in this study different locations of fresh EMPD surgical samples were 3D imaged starting from the surface up to a depth of 180 m using stain-free HGM. With the followed histopathological examination of the same sample, we mapped the gold-standard results to 3D HGM image stacks with labels for the training of the deep learning model. With only 2095 3D image stacks as training and validation data, the results of EMPD and normal skin tissue classification achieve 98.06% sensitivity, 93.18% specificity and 95.81% accuracy. This study supports our proposed 3D convolutional-neural-network-based technique with a high potential to assist physicians to quickly map the EMPD margins by providing noninvasive instant information regarding the imaged sub-millimeter site as malignant or surrounding normal with a high accuracy.

,

Ectopic extramammary Paget disease in thoracic location

,
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.

Treatment of Metastatic Extramammary Paget Disease with Combination Ipilimumab and Nivolumab: A Case Report

Treatment of Metastatic Extramammary Paget Disease with Combination Ipilimumab and Nivolumab: A Case Report

Metastatic primary cutaneous extramammary Paget disease (EMPD) is a rare clinical entity with a 5-year survival <10% and no standard therapy. We report the first case to our knowl- edge of metastatic EMPD with treatment response to checkpoint inhibitor immunotherapy. The patient had diffusely metastatic disease and previously progressed on cytotoxic chemotherapy and a molecularly targeted agent. Treatment with four cycles of ipilimumab 1 mg/kg plus nivolumab 3 mg/kg resulted in a durable partial response lasting 7 months. Analysis of metastatic tumor tissue failed to identify known predictors of treatment response to immune checkpoint inhibitors, such as high PD-L1 expression, high tumor mutation burden, or micro- satellite instability. These findings support further investigation of immune checkpoint inhibi- tion for the management of metastatic EMPD, which currently has an abysmal prognosis and no standard therapies.

, ,

The Outcome of Chemotherapy for Metastatic Extramammary Paget’s Disease

, ,
The Outcome of Chemotherapy for Metastatic Extramammary Paget’s Disease

The efficacy and survival impact of conventional chemotherapies for metastatic extra- mammary Paget’s disease (EMPD) have not been fully elucidated. This study examined the long- term outcome of chemotherapy for this indication. We conducted a retrospective review of 21 pa- tients with distant metastatic EMPD (14 patients treated with chemotherapy and 7 patients treated without chemotherapy). The response rate of chemotherapy and patient survival were statistically analyzed.

,

Toluidine blue for extramammary Paget’s disease in Mohs micrographic surgery

,
Toluidine blue for extramammary Paget’s disease in Mohs micrographic surgery

We report an elderly gentleman with Extramammary Paget’s disease (EMPD) treated with Mohs micrographic surgery (MMS) using Toluidine blue staining intraoperatively as to detect the Paget’s cells. An elderly man presented with an erythematous plaque on the left inguinal fold which showed in-situ EMPD on histopathological examination. Investigations for secondary EMPD were negative and the patient was treated with MMS. During MMS, the specimens from the patient were stained using Toluidine blue in order to detect the Paget cells and to determine the appropriate negative margin. At 4 years follow up the patient is free of recurrence. Toluidine blue is a fast, user-friendly dye that can be used intraoperatively during MMS as to detect Paget cells and thus to determine the appropriate negative margin.

Hormonal Environment and HER2 Status in Extra-Mammary Paget’s Disease (EMPD)

Hormonal Environment and HER2 Status in Extra-Mammary Paget’s Disease (EMPD)

Extra-mammary Paget’s disease (EMPD) is a rare neoplasm of epithelial origin, whose precise incidence is not clear. Starting from what is already known, we performed a systematic review and meta-analysis to investigate in male and female patients the immunohistochemical expression of biological markers that could serve as potential prognostic/therapeutic factors, including only human epidermal growth factor receptor 2 (HER2/neu), Estrogen Receptor (ER), Progesterone Receptor (PR), and Androgen Receptor (AR). Methods. A literature search was performed of the PubMed, Scopus, and Web of Science databases for English-language studies published from January 2000 to June 2020. Results. A total of 27 studies with 713 patients assessed the role of HER2/neu, AR, ER, and PR expression in male and female with EMPD. The overall rate of HER2/neu expression was 30%, the expression’s rate for ER and AR was 13% and 40%, respectively, and the overall rate for PR was 8%. The subgroup analysis revealed that there is a different expression of molecular markers between male and female patients. Conclusions. This study revealed that AR status and HER2/neu overexpression/amplification have been shown as two fundamental pathogenetic pathways in both female and male patients affected by EMPD.

Well-demarcated erythematous plaque on the arm

A 67-year-old Caucasian man presented with an asymptomatic, well-defined, irregular shaped, erythematous scaly plaque on the left upper arm for five years [Figure 1]. There was no cervical or axillary lymphadenopathy. A skin punch biopsy was performed from the plaque.

DISCUSSION

Extramammary Paget disease is a rare intraepidermal adenocarcinoma that primarily affects apocrine gland-bearing skin most commonly over the anogenital area. When the disease affects nonapocrine bearing skin, it is called ectopic extramammary Paget disease.1 The pathophysiology of ectopic extramammary Paget disease is unknown. Sawada et al. reported the possibility that ectopic extramammary Paget disease originates potentially not only from the apocrine gland but also from the eccrine gland.2 Clinically and histologically, there is no difference between ectopic extramammary Paget disease and conventional one.2 Extramammary Paget disease is well known for its association with malignancy. Chanda reported the incidence of underlying adnexal carcinoma and concurrent internal malignancy associated with extramammary Paget disease as 24% and 12%, respectively.3 The location of the underlying internal malignancy appears to correlate with the site of extramammary Paget disease. For example, the perianal and perineal location is associated with adenocarcinoma of the digestive system and genitourinary malignancy, respectively.4

Till now, there have been 46 cases of ectopic extramammary Paget disease in literature, of which only two cases have been reported in association with internal malignancy. The first case is ectopic extramammary Paget disease of the lateral thigh arising in association with sweat gland carcinoma of the same area,5 the second being ectopic extramammary Paget disease in the midline of the abdomen with underlying colon adenocarcinoma.6

Whole-body evaluation for malignancy should be performed. For evaluation of internal neoplasm, positron emission tomography-computed tomography, upper and lower endoscopy and laboratory tests were recommended. However, the patient refused further testing.7

Extramammary Paget disease is clinically similar to Bowen disease and superficial basal cell carcinoma.8 Thus, clinicians should keep in mind the possibility of ectopic extramammary Paget disease when there is treatment resistance skin lesion with eczematous morphology on the apocrine gland poor regions.

The diagnosis of extramammary Paget disease, in this case, was supported by immunohistochemical findings. Pagetoid cells in pagetoid Bowen disease usually demonstrate immunohistochemical features of squamous cells, which are negative for CK7 and positive for P63.9 In this case, positivity for CK7 but negativity for p63 and Melan A supported the diagnosis of extramammary Paget disease, ruling out Bowen disease and melanoma in situ. A negative result of CK20 immunohistochemical stain supported the diagnosis of primary extramammary Paget disease rather than secondary extramammary Paget disease from an internal malignancy.9 This case has been reported as a rare case of ectopic extramammary Paget disease appearing on an unusual site.

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.

,

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

,
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.

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

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.

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