Paget disease of the vulva

Paget disease of the vulva

In this review, we provide an overview of the clinical aspects, histopathology, molecular genetics, and treatment options for Vulvar Paget’s Disease (VPD), a rare skin disease, most commonly found in postmenopausal Caucasian women. The underlying cause of VPD remains not well understood. VPD is rarely associated with an underlying urogenital, gastrointestinal or vulvar carcinoma. In approximately 25% of the cases, VPD is invasive; in these cases, the prognosis is worse than in non-invasive cases. Recurrence rates in invasive VPD are high: 33% in cases with clear margins, and even higher when surgical margins are not clear, regardless of invasion. Historically, surgical excision has been the treatment of choice. Recent studies show that imiquimod cream may be an effective and safe alternative.

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.

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Extramammary Paget's disease in two brothers

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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.

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Psoriasis with extramammary paget disease in a male: a case report

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Psoriasis with extramammary paget disease in a male: a case report

Psoriasis is a chronic inflammatory skin disease that is characterized by erythematous, sharply demarcated papules and plaques covered by scales [1]. Extramammary Paget disease (EMPD) is a rare neoplastic condition of the skin or its underlying appendages commonly found in the vulva, perianal region, scrotum, penis, and axilla [2]. Clinically the condition presents as a well-demarcated, thickened, pruritic, erythematous, or white scaly plaque with irregular borders [3,4]. Microscopically EMPD involves large cells with vacuolated cytoplasm and centrally located nuclei characterized as Paget cells [5]. The disease is categorized into primary or secondary EMPD with primary EMPD originating from intraepidermal cells and secondary EMPD coming from an underlying neoplasm [2,5]. However, there is no report suggesting the association of psoriasis with EMPD, or psoriasis admixed with EMPD. In this paper, we present a case of extensive psoriasis in a male combined with penoscrotal EMPD.

Metastatic extramammary Paget's disease responding to weekly paclitaxel.

Metastatic extramammary Paget's disease responding to weekly paclitaxel.

Metastatic extramammary Paget's disease (EMPD) is a rare cancer with no validated systemic treatment. Regimens including FECOM 5-fluorouracil (5-FU, epirubicin, carboplatin, vincristine and mitomycin C), 5-FU/cisplatin and single agent docetaxel exhibited varying levels of efficacy in case reports. A 58-year-old man with EMPD diffusely metastatic to bone presented with worsening shortness of breath, significant pancytopenia and disseminated intravascular coagulation (DIC). He was started on low-dose heparin for the DIC and weekly paclitaxel. Initially requiring almost daily transfusions, his shortness of breath improved after two doses of paclitaxel, and he became transfusion-independent after only three doses. Correlating with his disease course, the patient's prepaclitaxel carcinoembryonic antigen level of 62.1 ng/mL decreased to 7.4 ng/mL on 3-month follow-up, and he showed no progression of disease on imaging. With no validated chemotherapy regimen currently, this case can help guide consideration of paclitaxel in future treatment of metastatic EMPD.

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The role of sentinel lymph node biopsy in the management of invasive extramammary Paget's disease: Multi-center, retrospective study of 151 patients

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The role of sentinel lymph node biopsy in the management of invasive extramammary Paget's disease: Multi-center, retrospective study of 151 patients

We collected 151 patients with invasive extramammary Paget's disease. The rate of LN metastasis in patients without lymphadenopathy was 15%. On the other hand, patients with lymphadenopathy had LN metastasis in 80%. No difference in survival between patients with or without SLN metastasis. Patients with lymphadenopathy showed worse survival than those with positive SLN.

A Case of Triple Extramammary Paget's Disease

A Case of Triple Extramammary Paget's Disease

We report a 74‐year‐old Japanese man with triple extramammary Paget's disease; the genital and both of the axillar regions were simultaneously involved. Literature review revealed that 27 cases of triple extramammary Paget's disease have been reported in Japan, but there are no reports of triple extramammary Paget's disease from countries other than Japan, although 2 cases of double extramammary Paget's disease are reported. In all 28 cases, including our case, the genital lesion preceded the axillary lesions. All cases except one were male and only the exceptional female case was reported to have an the invasive tumor in the dermis. We speculate that extramammary Paget's disease may appear multi‐centrically.

Combination chemotherapy of low-dose 5-fluorouracil and cisplatin for advanced extramammary Paget’s disease

Combination chemotherapy of low-dose 5-fluorouracil and cisplatin for advanced extramammary Paget’s disease

We retrospectively analyzed the efficacy of combination chemotherapy consisting of infusions of 5-fluorouracil (5-FU, 600 mg/m2/body, 5 days/week) and cisplatin (5–10 mg/body, 5–7 days/week) administered intravenously for 8–24 h (low-dose FP).

The overall survival ranges (medians) were 5–51 months (12) in all 22 patients, 6–51 months (13) in the 13 patients showing complete response or PR, and 5–12 months (11) in the 6 SD patients. The reported palliative effects of low-dose FP include control of pain and improvement of lymphedema.

 

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Metastatic Extramammary Paget’s Disease of Scrotum Responds Completely to Single Agent Trastuzumab in a Hemodialysis Patient: Case Report, Molecular Profiling and Brief Review of the Literature

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Metastatic Extramammary Paget’s Disease of Scrotum Responds Completely to Single Agent Trastuzumab in a Hemodialysis Patient: Case Report, Molecular Profiling and Brief Review of the Literature

Extramammary Paget’s disease (EMPD) is a rare cancer. Although EMPD is usually noninvasive and treated with local therapy, once metastatic the prognosis of EMPD is poor and treatment options are limited. We report a case of a complete response to single agent trastuzumab in a hemodialysis patient with metastatic Her2/neu overexpressed EMPD of the scrotum. Molecular profiling of his case as well as 12 other EMPD and 8 mammary Paget disease (MPD) cases was completed and revealed multiple biomarker aberrations. Overexpression of Her2 was frequently noted (30%–40%) in both EMPD and MPD patients and when present can be effectively treated with Her2 targeted agents. Trastuzumab therapy can be safely utilized in a hemodialysis patient. In addition, multiple protein overexpression and loss were seen in EMPD including PD-1, PD-L1, PTEN, and AR as well as PIK3CA mutation. These findings may lead to possible therapeutic interventions targeting these pathways in a disease with few effective treatment options.

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Metastatic extramammary Paget’s disease with pancytopenia and disseminated intravascular coagulation responding to weekly paclitaxel: a case report

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Metastatic extramammary Paget’s disease with pancytopenia and disseminated intravascular coagulation responding to weekly paclitaxel: a case report

Metastatic Extramammary Paget’s Disease (EMPD) is a rare cancer that currently has no validated treatment. Regimens including FECOM (5-FU, epirubicin, carboplatin, vincristine, and mitomycin C), trastuzumab in HER-2 expressing disease, 5-FU/cisplatin, or single agent docetaxel have been used in different case reports with varying levels of efficacy. A 58 year-old gentleman with EMPD diffusely metastatic to bone with bone marrow invasion presented with worsening shortness of breath and was found to have significant pancytopenia and disseminated intravascular coagulation (DIC). He was started on low-dose heparin for the DIC and weekly paclitaxel. Initially requiring daily transfusions of platelets and packed red blood cells, his shortness of breath improved after two doses of paclitaxel, and he became transfusion-independent after only three doses of paclitaxel. Carcinoembryonic Antigen (CEA) levels have been shown to correlate with tumor progression and parallel disease course. This patient’s pre-paclitaxel CEA of 62.1 ng/mL was also observed to decrease to 20.6 ng/mL after three doses. With no current validated chemotherapy regimen, this case can help guide consideration of paclitaxel in future treatment of metastatic EMPD. 

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The Effectiveness of Mapping Biopsy in Patients with Extramammary Paget's Disease

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The Effectiveness of Mapping Biopsy in Patients with Extramammary Paget's Disease

Extramammary Paget's disease (EMPD) is an intraepithelial carcinoma usually occurring on the skin or mucosa of the perineum. Clinically, it resembles eczema or dermatitis, and misdiagnosis and treatment delays are common. The treatment of choice for EMPD is a wide excision with adequate margins. Wide excision with intraoperative frozen biopsy and Mohs micrographic surgery are common methods; however, these are associated with a high recurrence rate and long operation time, respectively.

Methods

Between January 2010 and June 2013, 21 patients diagnosed with EMPD underwent mapping biopsy. Biopsy specimens were collected from at least 10 areas, 2 cm from the tumor margin. When the specimens were positive for malignancy, additional mapping biopsy was performed around the biopsy site of the positive result, and continued until no cancer cells were found. Based on the results, excision margins and reconstruction plans were established preoperatively.

Results

The patients (18 male, 3 female) had a mean age of 66.5 years (range, 50-82 years). Almost all cases involved in the perineal area, except one case of axillary involvement. Permanent biopsy revealed one case (4.8%) of positive cancer cells on the resection margin, in which additional mapping biopsy and re-operation was performed. At the latest follow-up (mean, 27.4 months; range, 12-53 months), recurrence had not occurred.

Conclusions

Preoperative mapping biopsy enables accurate resection margins and a preoperative reconstructing plan. Additionally, it reduces the operation time and risk of recurrence. Accordingly, it represents an effective alternative to Mohs micrographic surgery and wide excision with intraoperative frozen biopsy.

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Multicentric Primary Extramammary Paget Disease: A Toker Cell Disorder?

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Multicentric Primary Extramammary Paget Disease: A Toker Cell Disorder?

Toker cells are epithelial clear cells found in the areolar and nipple areas of the breast, vulvar region, and other apocrine gland–bearing areas of the skin. Toker cells have been implicated in the pathogenesis of clear cell papulosis, cutaneous hamartoma with pagetoid cells, and rare cases of primary extramammary Paget disease (EMPD) but not in secondary EMPD with underlying adenocarcinoma. The pathogenesis of primary EMPD is not well defined. We report a case of multicentric primary EMPD with evidence of Toker cell proliferation and nonaggressive biologic behavior in a 63-year-old white man. A detailed description of the morphologic and biologic features of Toker cells and their possible carcinogenetic links also are discussed. Based on the observation and follow-up of our patient, we hypothesize that multicentric primary EMPD starts with Toker cell hyperplasia and can potentially evolve to carcinoma in the genital region.

Extramammary Paget disease (EMPD), which was first described by Crocker1 in a patient with erythematous patches on the penis and scrotum, is morphologically identical to mammary Paget disease (MPD) of the nipple. The principal difference between EMPD and MPD is anatomic location.

A multicenter study on extramammary Paget's disease in Korea

A multicenter study on extramammary Paget's disease in Korea

In our study, EMPD was more common in male than in female patients (ratio: 3.9:1), which contrasts with findings from studies performed in Western populations. As a result of this pattern of male predominance, the most common sites of disease were the scrotum, penile shaft, and pubic area. A total of 27 associated malignancies were identified in 26 (14.4%) of 181 patients, which included stomach cancer (n = 6), rectal cancer (n = 3), colon cancer (n = 3), anal cancer (n = 2), pancreatic can- cer (n = 2), liver cancer (n = 2), and other cancers (n = 9). Of the eight patients who tested positive for CK20, five (62.5%) had an accompanying internal malig- nancy. Of the 11 patients who tested negative for CK20, two (18.2%) had a true associated malignancy. Of the 193 patients diagnosed with EMPD, 58% underwent conventional wide excisions and 11.2% had MMS. Nine- teen (33.3%) of the 57 patients in the conventional exci- sion group showed recurrence, but only two (12.5%) of the 16 patients in the MMS group experienced recur- rence. Of the 181 patients for whom follow-up data were available, 88 (48.6%) belonged to the ANED group, 41 (22.6%) to the AWD group, nine (5.0%) to the DOD group, two (1.1%) to the DOAC group, 12 (6.6%) to the DOUD group, and 29 (16%) to the FUL group. These findings have important implications for the management and treatment of Korean EMPD patients.

Interventions for the treatment of Paget’s disease of the vulva

Interventions for the treatment of Paget’s disease of the vulva

We found no reliable evidence to inform decisions about different interventions for women with Paget’s disease of the vulva. Ideally, a multicentre RCT of reasonable size is needed. In particular, evidence regarding the increasing use of imiquimod would be helpful to women and clinicians alike. Well-designed non-randomised studies, that use multivariate analysis to adjust for baseline imbalances, as well as other key methodological strengths, are also lacking.

Dermo beta brachytherapy with 188Re in extramammary Paget’s disease

Dermo beta brachytherapy with 188Re in extramammary Paget’s disease

Extramammary Paget’s disease (EMPD) is a rare neo-plastic pathology involving the vulva, scrotum, and peri-anal areas, and it is characterized by a slow and insidious course. EMPD may also be associated with internal malignancy, and its clinical presentation features long-standing pruritic lesions, eczema-like, refractory to any therapy. The therapeutic approach depends on the extent of involvement; wide surgical excision is the first choice among treatments, but other forms of therapy, alone or in combination, include imiquimod 5%, photodynamic therapy, Mohs surgery as well as external beam radiotherapy and Brachytherapy. In the present paper a new therapeutic alternative is proposed: Dermo-Beta-Brachytherapy (DBBT) with 188Re.

Confocal Microscopy To Noninvasively Detect Skin Cancer: An Emerging Technology To Avoid Unnecessary Skin Biopsy

Confocal Microscopy To Noninvasively Detect Skin Cancer: An Emerging Technology To Avoid Unnecessary Skin Biopsy

Skin cancer is the most common type of cancer worldwide. In the United States, the incidence is rising, with over two million people diagnosed each year [1]. More cases of skin cancer are diagnosed each year than breast, prostate, lung, and colon cancer combined. The lifetime risk of developing skin cancer is estimated to be 20%[2]. Although nonmelanoma skin cancer is rarely fatal and associated with a very low mortality rate, melanoma can be highly fatal. Approximately 76,000 individuals will be diagnosed with invasive melanoma in 2012 [3]. Skin cancer can be easily cured with early detection and excision. Early detection is essential, especially for melanoma, which has a grim prognosis once it has metastasized. Today, detection requires a biopsy to definitively determine if a lesion is malignant or benign.

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A review of extramammary paget’s disease: Clinical presentation, diagnosis, management and prognosis

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A review of extramammary paget’s disease: Clinical presentation, diagnosis, management and prognosis

Extramammary Paget’s Disease (EMPD) is a rare neoplastic lesion, which represents less than 1% of vulvar neoplasms. The lesion generally appears as eczema and the most frequently reported symptom is the itch. Also because of these poor clinical features, there is usually a delay in its diagnosis, based on the typical biopsy histological pattern. It has a good prognosis in absence of malignancy, but can result in a heavy quality of life impairment because of frequent recurrence with necessity of ablative therapies and anxiety for possible cancerization. Rarely EMPD can be invasive or associated to adenocarcinoma or other kinds of cancer. The first choice therapy is the surgical excision, with inguinal lymphadenectomy in case of infiltrative disease. However, many other conservative therapies, including the topical use of antiblastic, immuno-modulating, and hormone-modulating drugs, are used against EMPD even if still off label. After completion of this article, the reader should be able to recall the clinical manifestations of the EMPD, the histological pattern which allows its diagnosis, and to state the options for a treatment, which should be conservative and at the same time as radical as possible. 

Potential Use of Bisphosphonates in Invasive Extramammary Paget’s Disease: An Immunohistochemical Investigation

Potential Use of Bisphosphonates in Invasive Extramammary Paget’s Disease: An Immunohistochemical Investigation

Invasive extramammary Paget’s disease (EMPD) is relatively rare and is reported to be highly metastatic to lymph nodes or even other organs, including bone. Histologically, EMPD shows significant numbers of lymphocytes around the tumor mass, suggesting the possible development of novel immunomodulatory therapy for EMPD by targeting these infiltrating lymphocytes. Previously, bisphosphonates (BPs) were administered for the treatment of malignancy, especially osteolytic bone disease. Recent reports also suggested that BPs might have a direct antitumor effect through several pathways beyond their beneficial effect on bone metastasis. Among them, the abrogation of immunosuppressive cells, myeloid derived suppressor cells (MDSC), by BPs might be one of the optimal methods to induce an antitumor immune response both locally and at sites remote from the tumor. In this study, we employed immunohistochemical staining for immunosuppressive macrophages and cytotoxic T cells in the lesional skin of patients with noninvasive EMPD and those with invasive EMPD.

Comparison of Foxp3(+) Regulatory T cells and CD163(+) Macrophages in Invasive and Non-invasive Extramammary Paget's Disease

Comparison of Foxp3(+) Regulatory T cells and CD163(+) Macrophages in Invasive and Non-invasive Extramammary Paget's Disease

Regulatory T cells (Tregs), identified by the expression of CD4, CD25 and Foxp3, together with immunosuppressive macrophages, such as CD163+ M2 macrophages, are involved in maintaining peripheral tolerance. The aim of this study was to elucidate the involvement of Tregs and CD163+ macrophages in invasive and non-invasive extramammary Paget's disease. The presence of CD4+CD25+Foxp3+ Tregs, CD163+ M2 macrophages and matrix metalloproteinase-9+ cells was examined immunohistologically in fixed sections of lesional skin from 10 patients with non-invasive extramammary Paget's disease and 7 patients with invasive extramammary Paget's disease. Fewer CD4+CD25+Foxp3+ Tregs were observed in non-invasive extramammary Paget's disease than in invasive extramammary Paget's disease. In contrast, higher numbers of CD163+ macrophages and metalloproteinase-9+ cells were detected only in invasive extramammary Paget's disease. These findings suggest that the induction of immunosuppressive cells in extramammary Paget's disease differs according to the tumour stage.

Appropriate use criteria for Mohs micrographic surgery

Appropriate use criteria for Mohs micrographic surgery

This report addresses the appropriate use of Mohs micrographic surgery (MMS) in the treatment of cutaneous neoplasms. In the United States in 2006, there were an estimated 3.5 million nonmelanoma skin cancers diagnosed, and it is projected that there will be nearly 4 million new cases of nonmelanoma skin cancer diagnosed in the United States each year.1 Similarly, the incidence of melanoma in situ continues to increase with an estimated 55,560 to be newly diagnosed in 2012,2 with many of these likely to be of the lentigo maligna (LM) subtype.3

Because of this epidemic of skin cancer and an increase in the number of dermatologists trained in MMS, the use of this treatment modality has expanded significantly in recent years. In fact, the use of MMS increased by 400% from 1995 to 2009, and currently 1 in 4 skin cancers is being treated with MMS.4 As the incidence of skin cancer continues to climb and the field of MMS continues to advance, dermatologists, primary care providers, Mohs surgeons, and the health care community in general will need to understand how to best use MMS in the treatment of skin cancer.

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