Mayo Clinic Cancer Center Experience of Metastatic Extramammary Paget Disease 1998-2012

Mayo Clinic Cancer Center Experience of Metastatic Extramammary Paget Disease 1998-2012

Extramammary Paget disease (EMPD) is a rare cutaneous malignancy. The most common presentation of EMPD is the vulva followed by perianal involvement. Most cases are localized to the dermis with treatment focused on surgery, topical treatment or radiotherapy. Recurrence is frequent despite therapies utilized. Metastatic extramammary Paget disease is uncommon and, as such, standard treatment guidelines do not exist. This study sought to evaluate the treatment regimens and outcomes of patients treated at a Mayo Clinic Center from 1998-2012. Cancer registry inquiry revealed 261 patients with report advanced Paget disease during these years. Ten cases of metastatic EPMD were identified with sufficient documentation for review. This review reveals support for utilizing localized radiation therapy for bulky disease sequentially with systemic chemotherapy consisting of carboplatin and paclitaxel or irinotecan. Further studies are necessary to define the optimal treatment regimen.

,

A matter of margins: Surgical and pathologic risk factors for recurrence in extramammary Paget's disease

,
A matter of margins: Surgical and pathologic risk factors for recurrence in extramammary Paget's disease

Medical records of patients seeking care for EMPD from 1/1992–9/2015 were reviewed. Follow-up was restricted to 5 years following primary surgery. Recurrence-free survival (RFS) was estimated using the Kaplan-Meier method. Risk factors were evaluated for an association with recurrence and positive margins, respectively, using Cox proportional hazards regression and logistic regression.

Inclusion of males allowed us to examine the influence of a different surgical approach (MMS) on margin status and recurrence rates in EMPD. In contrast to prior studies including solely vulvar EMPD, we observed strong association between margin status and recurrence risk. Risk of positive margins was significantly higher after WLE compared to MMS. MMS should be explored to improve outcomes in gynecologic patients with EMPD.

,

Wide local excision of perianal Paget’s disease with gluteal flap reconstruction: an interdisciplinary approach

,
Wide local excision of perianal Paget’s disease with gluteal flap reconstruction: an interdisciplinary approach

Perianal Paget’s disease (PPD) is an extremely rare condition characterized as intraepithelial adenocarcinoma of unclear etiology. It can be either primary or secondary. The disease typically presents as an eczema-like, erythematous, and painful skin lesion that is associated with pruritus. It is usually misdiagnosed as a common anorectal problem. Surgical excision is the preferred treatment of PPD, with the specific technique being dependent upon disease invasiveness. 

Primary invasive triple extramammary Paget's disease with regional lymph node metastasis

Primary invasive triple extramammary Paget's disease with regional lymph node metastasis

Extramammary Paget's disease (EMPD) is a rare intraepidermal carcinoma and predominantly involves apocrine gland-bearing areas, such as anogenital regions and axillae. EMPD usually involves a solitary area and, less often, two areas in the same patient (double EMPD). The simultaneous involvement of bilateral axillae and anogenital region, called triple extramammary Paget's disease (TEPD), is an extremely rare subgroup of diseases that has been reported mostly from studies conducted in Japan. Because of its rarity, the clinical course, pathology/immunohistochemical staining features, and prognosis of TEPD are still unclear. Herein, to our knowledge, we present the first case of primary invasive TEPD with regional lymph node metastasis in Taiwan, and review the literature.

, , ,

Mohs with CK-7 staining: 98% 5-year cure rate for extramammary Paget disease

, , ,
Mohs with CK-7 staining: 98% 5-year cure rate for extramammary Paget disease

Mohs surgery with cytokeratin-7 immunohistochemistry staining effected complete removal of extramammary Paget disease and resulted in a 5-year, 95% recurrence-free cure rate. The results are significantly better than the often-cited 77% cure rate seen with Mohs surgery alone, Dr. Ali Alexander Damavandy said at the annual meeting of the American College of Mohs Surgery.

“These are statistically significant and clinically substantial results,” said Dr. Damavandy, a procedural dermatology fellow at the University of Pennsylvania, Philadelphia. “With this method you can tell a patient that in 5 years, he has a 95% chance of still not having the tumor. The high recurrence-free rate we have seen supports the view that Mohs surgery with cytokeratin-7 [CK-7] immunohistochemistry should be considered the curative treatment of choice for both primary and recurrent extramammary Paget disease of the skin.”

,

Primary extramammary invasive Paget’s vulvar disease: what is the standard, what are the challenges and what is the future for radiotherapy?

,
Primary extramammary invasive Paget’s vulvar disease: what is the standard, what are the challenges and what is the future for radiotherapy?

Primary invasive Extramammary Paget’s vulvar disease is a rare tumor that is challenging to control. Wide surgical excision represents the standard treatment approach for Primary invasive Extramammary Paget’s vulvar disease. The goal of the current study was to analyze the appropriate indications of radiotherapy in Primary invasive Extramammary Paget's vulvar disease because they are still controversial.

Discussion:

We searched the Cochrane Gynecological Cancer Group Trials Register, Cochrane Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE database up to September 2015. Radiotherapy was delivered as a treatment in various settings: i) Radical in 28 cases (range: 60–63 Gy), ii) Adjuvant in 25 cases (range: 39–60 Gy), iii) Salvage in recurrence of 3 patients (63 Gy) and iv) Neoadjuvant in one patient (43.3 Gy). A radiotherapy field that covered the gross tumor site with a 2–5 cm margin for the microscopic disease has been used. Radiotherapy of the inguinal, pelvic or para-aortic lymph node should be considered only for the cases with lymph node metastases within these areas.

Summary:

Radiotherapy alone is an alternative therapeutic approach for patients with extensive inoperable disease or medical contraindications. Definitive radiotherapy can be used in elderly patients and/or with medical contraindications. Adjuvant radiotherapy may be considered in presence of risk factors associated with local recurrence as dermal invasion, lymph node metastasis, close or positive surgical margins, perineal, large tumor diameter, multifocal lesions, extensive disease, coexisting histology of adenocarcinoma or vulvar carcinoma, high Ki-67 expression, adnexal involvement and probably in overexpression of HER-2/neu. Salvage radiotherapy can be given in inoperable loco-regional recurrence and to those who refused additional surgery.

,

A pilot study of topical imiquimod therapy for the treatment of recurrent extramammary Paget's disease

,
A pilot study of topical imiquimod therapy for the treatment of recurrent extramammary Paget's disease

Eight patients from two institutions were enrolled. Complete clinical and histologic response was achieved in 6 (75%) patients by the 12-week follow-up appointment. Of the two remaining patients, one had a complete clinical response but no significant histologic response; the other patient was removed from the study protocol secondary to intolerable local irritation. Two patients continue to have no evidence of disease after a median follow-up of 35 months. Five are alive with disease. No patients progressed to invasive cancer while receiving therapy.

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.

,

Extramammary Paget's disease in two brothers

,
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.

, ,

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

, ,
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.

,

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

,
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.

 

, ,

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

, ,
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.

,

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

,
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. 

, , ,

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

, , ,
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.

, , ,

Multicentric Primary Extramammary Paget Disease: A Toker Cell Disorder?

, , ,
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.

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