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
667 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:
667 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:
2026-08-11 | Treatment Strategies for Extramammary Paget Disease: A Narrative Review of Current Status and Future Directions
Background: Extramammary Paget disease (EMPD) is a rare epithelial malignancy that arises in the apocrine gland-bearing skin. Although localized intraepidermal EMPD generally follows an indolent clinical course, invasive EMPD is associated with lymph node metastasis, distant dissemination, and poor survival. Owing to its rarity, high-level evidence is limited and treatment strategies remain incompletely standardized, particularly for advanced disease. Recent advances in molecular profiling have revealed actionable therapeutic targets and created new opportunities for precision medicine. Methods: A narrative review was conducted using the PubMed database through May 2026. Relevant literature regarding the epidemiology, prognostic factors, surgical and non-surgical management, lymph node management, radiotherapy, systemic therapies, molecularly targeted therapies, and future therapeutic directions for EMPD is reviewed and summarized. Results: Surgical excision remains the standard treatment for resectable localized EMPD. Margin-controlled approaches, including Mohs micrographic surgery, complete circumferential peripheral and deep margin assessments, and mapping biopsy-guided excision, have contributed to improved local disease control. Radiotherapy, topical imiquimod, and photodynamic therapy provide alternative treatment options for patients who are unsuitable candidates for surgery; however, recurrence remains a major challenge. The management of regional lymph node metastases includes sentinel lymph node biopsy, lymph node dissection, and adjuvant radiotherapy in selected patients. For metastatic disease, conventional chemotherapy based on taxanes and fluoropyrimidine/platinum combinations has demonstrated moderate antitumor activity but limited durability. Molecular characterization of EMPD has identified several promising therapeutic targets. HER2 overexpression or amplification, observed in approximately 30–40% of cases, has emerged as the most clinically validated biomarker, with trastuzumab-based therapies demonstrating substantial efficacy. Immune checkpoint inhibitors have shown activity in selected patients, particularly those with a high tumor mutational burden, although predictive biomarkers remain inadequately defined. Additional emerging targets include androgen receptor signaling, TROP2, NECTIN4, FOXM1, and PIK3CA-associated pathways. Conclusions: In addition to conventional surgery- and chemotherapy-based approaches, biomarker-driven precision oncology is gaining attention as a treatment strategy for EMPD. HER2-targeted therapies, antibody–drug conjugates, and rationally selected immunotherapeutic strategies are expected to play increasingly important roles in the treatment of advanced disease. Continued translational research, international collaboration, and prospective clinical trials are essential to establish evidence-based treatment algorithms and improve outcomes in patients with this rare but potentially aggressive malignancy.
2026-08-09 | Aminolevulinic acid photodynamic therapy for extensive genital extramammary Paget disease in older patients: A retrospective clinical case series.
Extramammary Paget disease (EMPD) involving the genital and anogenital region is difficult to manage when lesions are extensive, chronic, or located across functionally sensitive sites. In older patients with diabetes, cardiovascular disease, or advanced local involvement, wide excision may lead to considerable perioperative burden, delayed healing, and anatomical impairment. To describe the short-term clinical outcomes and symptom relief associated with aminolevulinic acid photodynamic therapy (ALA-PDT) in older patients with extensive EMPD who were unsuitable for disfiguring surgery or declined surgical treatment. We retrospectively reviewed three histologically confirmed EMPD cases affecting the mons pubis, penile root or foreskin, scrotum, inguinal region, and adjacent proximal thigh. All patients received lesion preparation by debridement followed by topical 10% ALA-PDT using a standardized illumination regimen. At the 3-month evaluation, erosive and exudative areas had re-epithelialized, and nodular lesions showed marked reduction or flattening. Pruritus and local pain improved rapidly and had resolved within 2 weeks after treatment initiation. Mild transient erythema was the only treatment-related reaction. No clinically apparent regrowth or progression was observed during the 12-month clinical and dermoscopic follow-up. In this small retrospective series, ALA-PDT was associated with short-term clinical control and palliative benefit in older patients with extensive genital EMPD, while preserving genital anatomy without creating large surgical defects. These preliminary findings support further evaluation of optimized PDT-based conservative strategies for difficult-to-treat EMPD.
2026-08-03 | Treatment outcomes and influencing factors of photodynamic therapy in extramammary Paget's disease: a retrospective analysis of 31 cases.
Extramammary Paget's disease (EMPD) is a rare intraepithelial adenocarcinoma for which surgical excision often causes functional/cosmetic impairment. Photodynamic therapy (PDT) offers a noninvasive alternative, but data on its efficacy and influencing factors remain limited. To evaluate efficacy of 5‑aminolevulinic acid (ALA)‑PDT monotherapy for localized EMPD over one year, and identify baseline predictors of response. This retrospective study included 31 patients with histologically confirmed localized EMPD treated with ALA‑PDT alone. Responses were assessed at 3, 6, and 12 months. Objective response rate (ORR), disease control rate (DCR), and associated response factors were analyzed by Fisher's exact test. At 3 months, ORR was 90.3% (28/31) and DCR 100% (31/31), with no complete responses (CR). At 6 months, CR was 19.4% (6/31), ORR 67.7% (21/31), DCR 83.9% (26/31). At 12 months (n = 30), CR remained 19.4% (6/30), ORR declined to 36.7% (11/30), and DCR to 56.7% (17/30). Lesion diameter ≤5 cm and absence of exudation predicted better 6‑month response (p = 0.020 and p = 0.006); diameter ≤5 cm remained significant at 12 months (p = 0.002). ALA-PDT monotherapy achieves high short‑term responses in localized EMPD, but efficacy declines substantially by 12 months. Lesion diameter ≤5 cm and non-exudative morphology predict better responses.
2026-08-01 | Proteomic and metabolomic profiling reveals dysregulation of immune states, mucin-type glycosylation and steroid metabolism in extramammary Paget's disease.
Extramammary Paget's disease is a rare cutaneous adenocarcinoma characterized by mucin-rich Paget cells and chronic inflammation, yet its molecular basis remains unclear. To systematically characterize the proteomic and metabolomic landscape of EMPD, uncover immune heterogeneity, and identify molecular pathways underlying tumor progression and microenvironment remodeling. We performed integrated proteomic and metabolomic analyses on 92 male tumor patients and 30 healthy controls, identifying 10,217 proteins and 1466 metabolites. Extramammary Paget's disease lesions exhibited broad activation of inflammatory pathways. Immune profiling further uncovered substantial inflammatory heterogeneity, delineating immune-cold and immune-hot subtypes, with the latter associated with stronger invasive potential. Aberrant mucin-type glycosylation was also prominent, featuring Tn-modified MUC1 and MUC5AC accompanied by elevated GALNT7, GALNT6, GALNT4, and ST6GAL1, which correlated with inflammatory intensity. Metabolomic data demonstrated elevated levels of testosterone, dehydroepiandrosterone, and related intermediates in tumor tissues, indicating an androgen-enriched metabolic profile in extramammary Paget's disease. These findings reveal immune, glycoproteomic, and metabolomic pathways in extramammary Paget's disease pathogenesis and provide novel insights for molecular classification and therapeutic targeting.
2026-07-28 | Wide Excision and Flap Reconstruction in Perineal Extramammary Paget's Disease Patients.
Background and Objectives: Extramammary Paget's Disease (EMPD) of the perineal region is a rare intraepidermal adenocarcinoma requiring wide excision, resulting in extensive defects that are challenging to reconstruct while preserving contour and function. This descriptive case series evaluated a reconstructive selection strategy using pedicled superficial circumflex iliac artery perforator (SCIP) flaps and pedicled anterolateral thigh (ALT) flaps for perineal defects following wide excision of EMPD. Materials and Methods: This retrospective case series reviewed patients with perineal EMPD who underwent wide excision followed by reconstruction using pedicled SCIP flaps or pedicled ALT flaps. Patient demographic and lesion characteristics, operative and flap characteristics, post-reconstruction complications, oncologic outcomes, and satisfaction were analyzed. Results: 15 patients (mean age 63 years, SD 7.3) were included in this case series. Ten patients underwent reconstruction using pedicled SCIP flaps (mean 106 cm2, SD 23.3), and five patients with pedicled ALT flaps (mean 245.2 cm2, SD 41.2). All flaps survived, but one patient developed limited partial necrosis managed with secondary healing. During a mean follow-up of 17.7 months (SD 1.3), one patient (6.7%) developed recurrence and eventually distant metastasis resulting in death. Among the 14 surviving patients, 13 (92.9%) reported overall satisfaction with cosmetic and functional outcomes assessed using a non-validated ordinal scale. Conclusions: Pedicled SCIP and ALT flap reconstruction provides reliable, well-vascularized tissue coverage for perineal EMPD defects and achieves generally favorable short-term outcomes. The choice between flap types should be tailored to the defect size, location, and patient characteristics.
2026-08-11 | Treatment Strategies for Extramammary Paget Disease: A Narrative Review of Current Status and Future Directions
Background: Extramammary Paget disease (EMPD) is a rare epithelial malignancy that arises in the apocrine gland-bearing skin. Although localized intraepidermal EMPD generally follows an indolent clinical course, invasive EMPD is associated with lymph node metastasis, distant dissemination, and poor survival. Owing to its rarity, high-level evidence is limited and treatment strategies remain incompletely standardized, particularly for advanced disease. Recent advances in molecular profiling have revealed actionable therapeutic targets and created new opportunities for precision medicine. Methods: A narrative review was conducted using the PubMed database through May 2026. Relevant literature regarding the epidemiology, prognostic factors, surgical and non-surgical management, lymph node management, radiotherapy, systemic therapies, molecularly targeted therapies, and future therapeutic directions for EMPD is reviewed and summarized. Results: Surgical excision remains the standard treatment for resectable localized EMPD. Margin-controlled approaches, including Mohs micrographic surgery, complete circumferential peripheral and deep margin assessments, and mapping biopsy-guided excision, have contributed to improved local disease control. Radiotherapy, topical imiquimod, and photodynamic therapy provide alternative treatment options for patients who are unsuitable candidates for surgery; however, recurrence remains a major challenge. The management of regional lymph node metastases includes sentinel lymph node biopsy, lymph node dissection, and adjuvant radiotherapy in selected patients. For metastatic disease, conventional chemotherapy based on taxanes and fluoropyrimidine/platinum combinations has demonstrated moderate antitumor activity but limited durability. Molecular characterization of EMPD has identified several promising therapeutic targets. HER2 overexpression or amplification, observed in approximately 30–40% of cases, has emerged as the most clinically validated biomarker, with trastuzumab-based therapies demonstrating substantial efficacy. Immune checkpoint inhibitors have shown activity in selected patients, particularly those with a high tumor mutational burden, although predictive biomarkers remain inadequately defined. Additional emerging targets include androgen receptor signaling, TROP2, NECTIN4, FOXM1, and PIK3CA-associated pathways. Conclusions: In addition to conventional surgery- and chemotherapy-based approaches, biomarker-driven precision oncology is gaining attention as a treatment strategy for EMPD. HER2-targeted therapies, antibody–drug conjugates, and rationally selected immunotherapeutic strategies are expected to play increasingly important roles in the treatment of advanced disease. Continued translational research, international collaboration, and prospective clinical trials are essential to establish evidence-based treatment algorithms and improve outcomes in patients with this rare but potentially aggressive malignancy.
2026-08-09 | Aminolevulinic acid photodynamic therapy for extensive genital extramammary Paget disease in older patients: A retrospective clinical case series.
Extramammary Paget disease (EMPD) involving the genital and anogenital region is difficult to manage when lesions are extensive, chronic, or located across functionally sensitive sites. In older patients with diabetes, cardiovascular disease, or advanced local involvement, wide excision may lead to considerable perioperative burden, delayed healing, and anatomical impairment. To describe the short-term clinical outcomes and symptom relief associated with aminolevulinic acid photodynamic therapy (ALA-PDT) in older patients with extensive EMPD who were unsuitable for disfiguring surgery or declined surgical treatment. We retrospectively reviewed three histologically confirmed EMPD cases affecting the mons pubis, penile root or foreskin, scrotum, inguinal region, and adjacent proximal thigh. All patients received lesion preparation by debridement followed by topical 10% ALA-PDT using a standardized illumination regimen. At the 3-month evaluation, erosive and exudative areas had re-epithelialized, and nodular lesions showed marked reduction or flattening. Pruritus and local pain improved rapidly and had resolved within 2 weeks after treatment initiation. Mild transient erythema was the only treatment-related reaction. No clinically apparent regrowth or progression was observed during the 12-month clinical and dermoscopic follow-up. In this small retrospective series, ALA-PDT was associated with short-term clinical control and palliative benefit in older patients with extensive genital EMPD, while preserving genital anatomy without creating large surgical defects. These preliminary findings support further evaluation of optimized PDT-based conservative strategies for difficult-to-treat EMPD.
2026-08-03 | Treatment outcomes and influencing factors of photodynamic therapy in extramammary Paget's disease: a retrospective analysis of 31 cases.
Extramammary Paget's disease (EMPD) is a rare intraepithelial adenocarcinoma for which surgical excision often causes functional/cosmetic impairment. Photodynamic therapy (PDT) offers a noninvasive alternative, but data on its efficacy and influencing factors remain limited. To evaluate efficacy of 5‑aminolevulinic acid (ALA)‑PDT monotherapy for localized EMPD over one year, and identify baseline predictors of response. This retrospective study included 31 patients with histologically confirmed localized EMPD treated with ALA‑PDT alone. Responses were assessed at 3, 6, and 12 months. Objective response rate (ORR), disease control rate (DCR), and associated response factors were analyzed by Fisher's exact test. At 3 months, ORR was 90.3% (28/31) and DCR 100% (31/31), with no complete responses (CR). At 6 months, CR was 19.4% (6/31), ORR 67.7% (21/31), DCR 83.9% (26/31). At 12 months (n = 30), CR remained 19.4% (6/30), ORR declined to 36.7% (11/30), and DCR to 56.7% (17/30). Lesion diameter ≤5 cm and absence of exudation predicted better 6‑month response (p = 0.020 and p = 0.006); diameter ≤5 cm remained significant at 12 months (p = 0.002). ALA-PDT monotherapy achieves high short‑term responses in localized EMPD, but efficacy declines substantially by 12 months. Lesion diameter ≤5 cm and non-exudative morphology predict better responses.
2026-08-01 | Proteomic and metabolomic profiling reveals dysregulation of immune states, mucin-type glycosylation and steroid metabolism in extramammary Paget's disease.
Extramammary Paget's disease is a rare cutaneous adenocarcinoma characterized by mucin-rich Paget cells and chronic inflammation, yet its molecular basis remains unclear. To systematically characterize the proteomic and metabolomic landscape of EMPD, uncover immune heterogeneity, and identify molecular pathways underlying tumor progression and microenvironment remodeling. We performed integrated proteomic and metabolomic analyses on 92 male tumor patients and 30 healthy controls, identifying 10,217 proteins and 1466 metabolites. Extramammary Paget's disease lesions exhibited broad activation of inflammatory pathways. Immune profiling further uncovered substantial inflammatory heterogeneity, delineating immune-cold and immune-hot subtypes, with the latter associated with stronger invasive potential. Aberrant mucin-type glycosylation was also prominent, featuring Tn-modified MUC1 and MUC5AC accompanied by elevated GALNT7, GALNT6, GALNT4, and ST6GAL1, which correlated with inflammatory intensity. Metabolomic data demonstrated elevated levels of testosterone, dehydroepiandrosterone, and related intermediates in tumor tissues, indicating an androgen-enriched metabolic profile in extramammary Paget's disease. These findings reveal immune, glycoproteomic, and metabolomic pathways in extramammary Paget's disease pathogenesis and provide novel insights for molecular classification and therapeutic targeting.
2026-07-28 | Wide Excision and Flap Reconstruction in Perineal Extramammary Paget's Disease Patients.
Background and Objectives: Extramammary Paget's Disease (EMPD) of the perineal region is a rare intraepidermal adenocarcinoma requiring wide excision, resulting in extensive defects that are challenging to reconstruct while preserving contour and function. This descriptive case series evaluated a reconstructive selection strategy using pedicled superficial circumflex iliac artery perforator (SCIP) flaps and pedicled anterolateral thigh (ALT) flaps for perineal defects following wide excision of EMPD. Materials and Methods: This retrospective case series reviewed patients with perineal EMPD who underwent wide excision followed by reconstruction using pedicled SCIP flaps or pedicled ALT flaps. Patient demographic and lesion characteristics, operative and flap characteristics, post-reconstruction complications, oncologic outcomes, and satisfaction were analyzed. Results: 15 patients (mean age 63 years, SD 7.3) were included in this case series. Ten patients underwent reconstruction using pedicled SCIP flaps (mean 106 cm2, SD 23.3), and five patients with pedicled ALT flaps (mean 245.2 cm2, SD 41.2). All flaps survived, but one patient developed limited partial necrosis managed with secondary healing. During a mean follow-up of 17.7 months (SD 1.3), one patient (6.7%) developed recurrence and eventually distant metastasis resulting in death. Among the 14 surviving patients, 13 (92.9%) reported overall satisfaction with cosmetic and functional outcomes assessed using a non-validated ordinal scale. Conclusions: Pedicled SCIP and ALT flap reconstruction provides reliable, well-vascularized tissue coverage for perineal EMPD defects and achieves generally favorable short-term outcomes. The choice between flap types should be tailored to the defect size, location, and patient characteristics.
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