RARE DISEASE
Extramammary Paget disease
Extramammary Paget disease
Extramammary Paget disease
Drug discovery
0
drugs
With orphan designations
Overview
Extramammary Paget Disease (EMPD) is a rare intraepithelial adenocarcinoma primarily affecting apocrine gland-rich areas (genital, perianal, axillary). It presents as erythematous, pruritic plaques mimicking eczema, often with delayed diagnosis due to nonspecific appearance. Primary EMPD originates in the epidermis, while secondary forms link to underlying malignancies (e.g., colorectal, urothelial). Surgical excision (Mohs or wide local) is first-line, but recurrence rates reach 30–60%. Prognosis is favorable for localized disease but declines with dermal invasion or metastases [1][2][5][8][12].
Therapies
Surgical: Mohs micrographic surgery (lower recurrence) or wide local excision [1][4][11].
Nonsurgical: Topical imiquimod, radiotherapy, photodynamic therapy, and CO2 laser for non-resectable cases [3][14][15].
Systemic: Chemotherapy, anti-HER2 agents (e.g., trastuzumab), or immune checkpoint inhibitors for metastatic disease [7][15][19].
Categories: rare gynecological and obstetric diseases, rare neoplastic diseases, rare skin diseases
Research Papers
657 drug discovery papers about Extramammary Paget disease, with 2 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
657 drug discovery papers about Extramammary Paget disease, with 2 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-07-10 | Etoposide as Late-Line Therapy for Metastatic Extramammary Paget's Disease: A Case Series.
Extramammary Paget's disease (EMPD) is a rare cutaneous carcinoma that typically arises in apocrine gland-rich areas. Advanced or metastatic disease is associated with poor prognosis and limited therapeutic options. Due to its rarity, no standard chemotherapy regimen has been established. Agents such as docetaxel, cisplatin, and 5-fluorouracil have been used, but evidence supporting their efficacy remains limited. Etoposide has occasionally been reported to provide temporary benefit in advanced EMPD, although its effectiveness remains poorly characterized. We report a case series of three patients with metastatic EMPD treated with oral etoposide as third- or fourth-line therapy. They had experienced disease progression despite prior therapies, including docetaxel, S-1, and low-dose FP (5-fluorouracil and cisplatin) therapy. Oral etoposide was administered at 50 mg/day for 3-4 weeks followed by a 1-2 week rest period. Additional radiation therapy was provided for metastatic lesions in two patients. Two patients achieved a partial response on imaging, while one showed stable disease. Serum carcinoembryonic antigen levels decreased markedly in two evaluable patients, indicating a biological response. The average progression-free survival was 7.7 months. Adverse events included alopecia and neutropenia in one patient, both manageable. Although all patients eventually died from disease progression, etoposide provided disease control and symptomatic relief. These findings suggest that oral etoposide may represent a feasible and relatively well-tolerated late-line treatment option for metastatic EMPD.
2026-07-09 | Metastatic extramammary Paget's disease successfully treated by trastuzumab deruxtecan: a rare case report.
Metastatic extramammary Paget's disease (mEMPD) is a rare cancer with a poor prognosis. Approximately 40% of cases overexpress the Her2/neu protein, making it a critical therapeutic target for precision-based systemic treatment. A 73-year-old man presented with a chronic erythematous patch on the left supra-pubic and scrotal area that had been slowly enlarging over months. A tender right groin mass developed recently. Imaging revealed right inguinal lymphadenopathy with necrosis, para-aortic lymph node involvement, bladder wall lesions, and right hydronephrosis. A skin biopsy confirmed the diagnosis of extramammary Paget's disease (EMPD), and invasive EMPD was subsequently confirmed through the excision of metastatic lymph nodes in the right groin. The immunochemical stains of the carcinoma reveal low Her2/neu expression (++/+++). Next-generation sequencing (NGS) demonstrated a high tumor mutation burden (30Muts/Mb), along with ERBBR2, PIK3CA, and PTEN mutations. Initially, he received trastuzumab and pembrolizumab. However, there was no clinical response. Then, he was treated with trastuzumab deruxtecan (anti-Her2/neu antibody-drug conjugates, ADC). A partial response was noted clinically and radiologically, including the regression of lymphadenopathy and bladder lesion. EMPD with low Her2/neu expression and high TMB may benefit more from anti-Her2/neu ADC rather than from immune checkpoint inhibitors combined with anti-Her2/neu antibodies. HER2-targeted strategies, including trastuzumab-docetaxel and T-DM1, show high efficacy in mEMPD. This paradigm shift toward molecularly driven, customized treatments optimizes clinical outcomes while maintaining patient performance status in this rare malignancy.
2026-07-07 | 5-Aminolevulinic Acid-Induced Fluorescence-Guided Margin Mapping and Slow Mohs Surgery for Localized Extramammary Paget Disease: A Retrospective Exploratory Comparative Study.
Extramammary Paget disease (EMPD) often extends beyond its clinically visible borders, making surgical margin control difficult, particularly in anatomically sensitive regions. This retrospective exploratory study compared 5-aminolevulinic acid (5-ALA)-induced fluorescence-guided margin mapping with slow Mohs surgery for localized EMPD, with emphasis on final margin clearance, treatment-process efficiency, tissue preservation, reconstruction requirement, patient-reported satisfaction, and crude recurrence proportion. We retrospectively reviewed 60 patients with biopsy-confirmed localized EMPD treated between January 2021 and June 2025. Patients underwent either ALA fluorescence-guided surgery (n = 32) or slow Mohs surgery (n = 28). In the ALA fluorescence-guided group, 20% 5-ALA cream was applied topically for 3 hours before surgery, and fluorescence-positive borders were visualized using 405-nm excitation light. The planned surgical margin was placed 1 cm beyond the outer fluorescence-positive border into fluorescence-negative skin. Slow Mohs surgery was performed using staged paraffin-section histopathological assessment until negative margins were achieved. The primary endpoint was feasibility of final histopathological margin clearance. Secondary endpoints included first-pass positive margin rate, treatment-process duration, hospital stay, defect-to-visible-lesion area ratio, flap/graft repair rate, wound complication rate, patient-reported satisfaction, and crude recurrence proportion. Final negative margins were achieved in all patients. In the ALA fluorescence-guided group, 3 patients had first-pass positive margins, yielding a first-pass positive margin rate of 9.3% (3/32); all three achieved negative margins after additional excision. Compared with the slow Mohs group, the ALA fluorescence-guided group had a shorter treatment-process duration indicator (112.25 ± 9.34 min vs 2.42 ± 0.22 days, P < 0.001), a lower defect-to-visible-lesion area ratio (1.42 ± 0.10 vs 1.90 ± 0.07, P < 0.001), a lower flap/graft repair rate (28.1% vs 75.0%, P = 0.0008), and higher exploratory patient-reported satisfaction scores (8.24 ± 0.68 vs 7.26 ± 0.39, P < 0.001). Crude recurrence proportions were 12.5% in the ALA fluorescence-guided group and 10.7% in the slow Mohs group (P = 1.000). ALA-induced fluorescence-guided margin mapping may serve as a tissue-sparing adjunct within a pathology-driven surgical strategy for selected patients with localized EMPD. In this exploratory cohort, it was associated with shorter treatment-process duration, smaller relative defects, lower reconstruction requirement, and higher exploratory patient-reported satisfaction. These findings should not be interpreted as evidence of oncologic equivalence to slow Mohs surgery. Prospective studies with standardized recurrence-time assessment are needed to determine long-term oncologic durability.
2026-07-10 | Etoposide as Late-Line Therapy for Metastatic Extramammary Paget's Disease: A Case Series.
Extramammary Paget's disease (EMPD) is a rare cutaneous carcinoma that typically arises in apocrine gland-rich areas. Advanced or metastatic disease is associated with poor prognosis and limited therapeutic options. Due to its rarity, no standard chemotherapy regimen has been established. Agents such as docetaxel, cisplatin, and 5-fluorouracil have been used, but evidence supporting their efficacy remains limited. Etoposide has occasionally been reported to provide temporary benefit in advanced EMPD, although its effectiveness remains poorly characterized. We report a case series of three patients with metastatic EMPD treated with oral etoposide as third- or fourth-line therapy. They had experienced disease progression despite prior therapies, including docetaxel, S-1, and low-dose FP (5-fluorouracil and cisplatin) therapy. Oral etoposide was administered at 50 mg/day for 3-4 weeks followed by a 1-2 week rest period. Additional radiation therapy was provided for metastatic lesions in two patients. Two patients achieved a partial response on imaging, while one showed stable disease. Serum carcinoembryonic antigen levels decreased markedly in two evaluable patients, indicating a biological response. The average progression-free survival was 7.7 months. Adverse events included alopecia and neutropenia in one patient, both manageable. Although all patients eventually died from disease progression, etoposide provided disease control and symptomatic relief. These findings suggest that oral etoposide may represent a feasible and relatively well-tolerated late-line treatment option for metastatic EMPD.
2026-07-09 | Metastatic extramammary Paget's disease successfully treated by trastuzumab deruxtecan: a rare case report.
Metastatic extramammary Paget's disease (mEMPD) is a rare cancer with a poor prognosis. Approximately 40% of cases overexpress the Her2/neu protein, making it a critical therapeutic target for precision-based systemic treatment. A 73-year-old man presented with a chronic erythematous patch on the left supra-pubic and scrotal area that had been slowly enlarging over months. A tender right groin mass developed recently. Imaging revealed right inguinal lymphadenopathy with necrosis, para-aortic lymph node involvement, bladder wall lesions, and right hydronephrosis. A skin biopsy confirmed the diagnosis of extramammary Paget's disease (EMPD), and invasive EMPD was subsequently confirmed through the excision of metastatic lymph nodes in the right groin. The immunochemical stains of the carcinoma reveal low Her2/neu expression (++/+++). Next-generation sequencing (NGS) demonstrated a high tumor mutation burden (30Muts/Mb), along with ERBBR2, PIK3CA, and PTEN mutations. Initially, he received trastuzumab and pembrolizumab. However, there was no clinical response. Then, he was treated with trastuzumab deruxtecan (anti-Her2/neu antibody-drug conjugates, ADC). A partial response was noted clinically and radiologically, including the regression of lymphadenopathy and bladder lesion. EMPD with low Her2/neu expression and high TMB may benefit more from anti-Her2/neu ADC rather than from immune checkpoint inhibitors combined with anti-Her2/neu antibodies. HER2-targeted strategies, including trastuzumab-docetaxel and T-DM1, show high efficacy in mEMPD. This paradigm shift toward molecularly driven, customized treatments optimizes clinical outcomes while maintaining patient performance status in this rare malignancy.
2026-07-07 | 5-Aminolevulinic Acid-Induced Fluorescence-Guided Margin Mapping and Slow Mohs Surgery for Localized Extramammary Paget Disease: A Retrospective Exploratory Comparative Study.
Extramammary Paget disease (EMPD) often extends beyond its clinically visible borders, making surgical margin control difficult, particularly in anatomically sensitive regions. This retrospective exploratory study compared 5-aminolevulinic acid (5-ALA)-induced fluorescence-guided margin mapping with slow Mohs surgery for localized EMPD, with emphasis on final margin clearance, treatment-process efficiency, tissue preservation, reconstruction requirement, patient-reported satisfaction, and crude recurrence proportion. We retrospectively reviewed 60 patients with biopsy-confirmed localized EMPD treated between January 2021 and June 2025. Patients underwent either ALA fluorescence-guided surgery (n = 32) or slow Mohs surgery (n = 28). In the ALA fluorescence-guided group, 20% 5-ALA cream was applied topically for 3 hours before surgery, and fluorescence-positive borders were visualized using 405-nm excitation light. The planned surgical margin was placed 1 cm beyond the outer fluorescence-positive border into fluorescence-negative skin. Slow Mohs surgery was performed using staged paraffin-section histopathological assessment until negative margins were achieved. The primary endpoint was feasibility of final histopathological margin clearance. Secondary endpoints included first-pass positive margin rate, treatment-process duration, hospital stay, defect-to-visible-lesion area ratio, flap/graft repair rate, wound complication rate, patient-reported satisfaction, and crude recurrence proportion. Final negative margins were achieved in all patients. In the ALA fluorescence-guided group, 3 patients had first-pass positive margins, yielding a first-pass positive margin rate of 9.3% (3/32); all three achieved negative margins after additional excision. Compared with the slow Mohs group, the ALA fluorescence-guided group had a shorter treatment-process duration indicator (112.25 ± 9.34 min vs 2.42 ± 0.22 days, P < 0.001), a lower defect-to-visible-lesion area ratio (1.42 ± 0.10 vs 1.90 ± 0.07, P < 0.001), a lower flap/graft repair rate (28.1% vs 75.0%, P = 0.0008), and higher exploratory patient-reported satisfaction scores (8.24 ± 0.68 vs 7.26 ± 0.39, P < 0.001). Crude recurrence proportions were 12.5% in the ALA fluorescence-guided group and 10.7% in the slow Mohs group (P = 1.000). ALA-induced fluorescence-guided margin mapping may serve as a tissue-sparing adjunct within a pathology-driven surgical strategy for selected patients with localized EMPD. In this exploratory cohort, it was associated with shorter treatment-process duration, smaller relative defects, lower reconstruction requirement, and higher exploratory patient-reported satisfaction. These findings should not be interpreted as evidence of oncologic equivalence to slow Mohs surgery. Prospective studies with standardized recurrence-time assessment are needed to determine long-term oncologic durability.
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