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Extramammary Paget disease (EMPD) represents a rare cutaneous adenocarcinoma that most often affects older adults and poses significant diagnostic and management challenges due to its capacity to mimic benign dermatoses, its potential association with internal malignancies, and its variable clinical course. Because delayed diagnosis and high recurrence rates remain common, this course reviews EMPD, which typically presents as red, well-defined plaques that may become erosive, ulcerated, scaly, or eczematous, arising in apocrine-rich areas, and its multimodal management strategies, including surgery, radiation, topical agents, or systemic treatments, depending on disease extent. This activity outlines recognition, diagnostic accuracy, epidemiology, pathology, staging, and risk-stratified management of EMPD across intraepidermal, invasive, and metastatic presentations. Participants will also gain an in-depth understanding of the disease’s clinical heterogeneity, current recommendations for surgical and nonsurgical interventions, the role of lymph node assessment, and the importance of long-term surveillance. This activity for healthcare professionals is designed to enhance the learner's competence in identifying EMPD, performing the recommended evaluation, selecting evidence-based therapeutic strategies, and implementing an appropriate interprofessional approach to manage this condition, thereby optimizing outcomes for patients with this uncommon yet complex malignancy. Objectives: Identify the clinical features that distinguish extramammary Paget disease from benign inflammatory dermatoses. Apply evidence-based diagnostic studies to detect associated internal malignancies. Select appropriate management strategies for extramammary Paget disease by disease stage. Collaborate with the interprofessional team members to optimize care coordination and outcomes for patients with extramammary Paget disease. Access free multiple choice questions on this topic.

Extramammary Paget disease (EMPD) is a rare cutaneous adenocarcinoma that primarily affects older adults, typically those between 50 and 80 years of age. Data from the Surveillance, Epidemiology, and End Results (SEER) program indicate that the incidence of EMPD is highest among Asian men, followed by Caucasians and African Americans. Approximately 10% to 30% of patients have an associated internal malignancy, most commonly involving the colon, breast, or genitourinary tract.[1][2] Several aspects of EMPD remain controversial, including the true prevalence of concurrent vulvar adenocarcinoma or invasive EMPD, its association with regional or distant malignancies, and recurrence rates following surgical excision.[3] The disease usually arises in areas with a high density of apocrine glands, most frequently the vulva, but also the perineal, scrotal, perianal, and penile regions.[1][2] Treatment typically involves surgical excision, but may also include radiotherapy, photodynamic therapy, systemic or topical chemotherapy, and, in some cases, targeted therapy for metastatic disease.[3] Because EMPD often mimics benign infectious or inflammatory dermatoses, diagnosis is frequently delayed, leading to increased morbidity.[4]

The etiology of primary EMPD has been the subject of extensive debate, yet current evidence supports an apocrine origin. Secondary extramammary Paget disease reflects direct extension from an underlying adnexal adenocarcinoma or a visceral malignancy, most frequently urothelial or anorectal, with occasional cervical, prostatic, ovarian, or endometrial involvement. Immune-mediated mechanisms also contribute to both the development and progression of EMPD.[1][3][1][2][4] Studies of vulvar EMPD reveal an immune environment with reduced populations of CD41 and CD81 cells and a lower CD81/FOXP31 ratio. FOXP31 T-regulatory cells appear more abundant along the dermal-epidermal junction in vulvar disease, potentially supporting the survival of Paget cells within the epidermis.[5]

EMPD represents a rare cutaneous adenocarcinoma with reported incidence rates ranging from 0.1 to 2.4 cases per 1,000,000 person-years. The disorder predominantly affects older adults between 50 and 80 years of age, with peak incidence in the seventh decade. Epidemiologic patterns vary by region and sex. Western populations demonstrate a higher prevalence among women because vulvar disease predominates, reflected in male-to-female ratios ranging from 1:2 to 1:7. Asian studies report a near 1:1 distribution, suggesting potential genetic or environmental influences. SEER database analysis identified 1,439 EMPD cases from 1973 to 2007, with 67% occurring in women, and demonstrated the highest incidence among Asian men, followed by Caucasians and African Americans. The incidence among men has risen by approximately 3% annually since the 1970s, likely due to improved recognition. Prevalence in mainland China reached 0.4 per 1,000,000 individuals in 2016, while European estimates range from 0.6 to 0.7 per 1,000,000 person-years.[1][2][3] Although EMPD primarily manifests as a cutaneous neoplasm, associations with underlying visceral malignancies frequently emerge, most often involving the colon, breast, or genitourinary tract. Secondary EMPD accounts for approximately 18% of cases, with site-specific risks of about 25% for perianal involvement and 6% each for penoscrotal and vulvar disease. Subsequent malignancies most commonly arise within the first 5 years after diagnosis, reaching an excess absolute risk of nearly 97.4 cancers per 10,000 patient-years. A European registry similarly documented second primary tumors in 8.6% of EMPD patients, most often within the first year of follow-up. Comprehensive evaluation and long-term surveillance remain essential, particularly for patients with extensive or invasive disease.[4][5][6]

The pathophysiology of EMPD remains incompletely understood and appears to be multifactorial. EMPD is broadly classified as either a primary or a secondary disease. Primary EMPD is believed to arise from pluripotent keratinocyte stem cells or apocrine gland duct cells within the epidermis and adnexal structures. A prevailing theory suggests that it originates from Toker cells, benign intraepithelial glandular cells normally found in the genital and nipple epithelium. These cells share morphologic and immunophenotypic similarities with malignant Paget cells, implying malignant transformation early in disease development. Secondary EMPD, by contrast, occurs through epidermotropic spread or direct extension from an underlying visceral adenocarcinoma, most commonly involving colorectal, bladder, or cervical epithelium. Immunohistochemical studies support this mechanism, as secondary lesions often share identical staining profiles with their associated internal carcinomas.[1][2][3] Recent molecular investigations have revealed multiple genomic alterations implicated in EMPD tumorigenesis. Somatic mutations in TP53, ERBB2, ERBB3, NRAS, BRAF, PIK3CA, AKT1, and KMT2C have been identified, with recurrent ERBB2 (HER2) amplification and CDKN2A deletion associated with tumor progression and recurrence. These findings suggest a crucial role for HER2-mediated signaling pathways, including RAS/RAF–MEK–ERK and PI3K–AKT–mTOR, in promoting cellular proliferation and survival. Studies have also identified FOXA1 mutations, GAS6–FOXA1 fusion events, and overexpression of the FOXA1–estrogen receptor axis, implicating hormonal signaling in the pathogenesis of some cases, particularly vulvar EMPD.

Recent molecular investigations have revealed multiple genomic alterations implicated in EMPD tumorigenesis. Somatic mutations in TP53, ERBB2, ERBB3, NRAS, BRAF, PIK3CA, AKT1, and KMT2C have been identified, with recurrent ERBB2 (HER2) amplification and CDKN2A deletion associated with tumor progression and recurrence. These findings suggest a crucial role for HER2-mediated signaling pathways, including RAS/RAF–MEK–ERK and PI3K–AKT–mTOR, in promoting cellular proliferation and survival. Studies have also identified FOXA1 mutations, GAS6–FOXA1 fusion events, and overexpression of the FOXA1–estrogen receptor axis, implicating hormonal signaling in the pathogenesis of some cases, particularly vulvar EMPD. The tumor immune microenvironment also appears to play an important role in EMPD pathobiology. Histologic analyses of vulvar EMPD have demonstrated reduced CD4 and CD8 lymphocyte infiltration and increased FOXP3 regulatory T cells, contributing to an immunosuppressive milieu favorable for tumor persistence and subclinical extension. Variable expression of immune checkpoint molecules, eg, PD-L1 and PD-L2, has been reported, with some studies noting their presence in tumor cells and infiltrating lymphocytes, while others find minimal expression. Cases exhibiting higher PD-L1/PD-L2 expression and lower CD8 T-cell density have been correlated with poorer recurrence-free survival, suggesting that immune evasion mechanisms may influence disease progression and prognosis. Collectively, EMPD likely represents a heterogeneous disease process arising from distinct cellular origins with complex molecular and immune interactions. Understanding these mechanisms not only clarifies their diverse clinical presentations but also provides a rationale for emerging targeted and immunomodulatory therapies.[4][7]

In EMPD, the proliferative neoplastic cell is the Paget cell. These cells have ample pale cytoplasm and large pleomorphic nuclei, sometimes with a prominent nucleolus. Mitoses are commonly present. Occasional cells have an eccentric nucleus and the appearance of a signet ring (see Image. Extramammary Paget Disease). In early lesions, the cells are arranged singly or in small groups, sometimes with the glandular formation in the basal layer of the epidermis. The entire thickness of the epidermis can be involved, although the greatest concentration of tumor cells is in the lower part of the epidermis. The pagetoid cells usually spread into the contiguous epithelium of eccrine ducts and hair follicles. Uncommonly, Paget cells may invade the dermis.[1][2][3] Unlike the majority of cases of mammary Paget's disease, the Paget cells in EMPD contain ample mucin, which may be confirmed by staining with Alcian blue, mucicarmine, Periodic acid–Schiff (PAS), and colloidal iron. Immunohistochemistry is often used to diagnose Paget disease and to identify the likely cell of origin. Paget cells usually stain for markers of eccrine and apocrine derivation, including low-molecular-weight cytokeratins, PAS, gross cystic disease fluid protein (GCDFP-15), and carcinoembryonic antigen (CEA). However, S100 staining is negative.[4][7] Furthermore, EMPD and mammary Paget's disease show characteristic, although slightly different, immunophenotypes. Primary intra-epidermal Paget disease is positive for GCDFP-15, positive for CK7, and negative for CK20 markers. Conversely, Paget disease that has spread from an underlying internal carcinoma (EMPD) stains negative for GCDFP-15, negative for CK7, and positive for CK20 markers. The main histological differential diagnoses to exclude in the vulva are superficial spreading malignant melanoma (PAS-negative, S100-positive, cytokeratin-negative, CEA-negative) and anogenital intraepithelial neoplasia (S100-negative, PAS-negative).[4][7]

The primary lesions of EMPD present as erythematous, scaly plaques that remain well delineated and typically measure several centimeters (see Image. Extramammary Paget Lesion). Later stages may show crusting, weepy erosions, or ulcerations. Scattered erosions and white scale can produce a classic “strawberries and cream” appearance. Involved areas expand slowly with a sharply defined transition between affected and unaffected skin. Lesions frequently appear nonspecific and often mimic eczema, psoriasis, or candidiasis, leading to repeated trials of topical treatments before proper diagnosis. A median diagnostic delay of 2 years has been documented. Pruritus represents the most common presenting symptom, although burning, tenderness, and edema may also occur. Hypopigmentation or hyperpigmentation may occasionally develop, and long-standing lesions may become altered by trauma, excoriation, or superimposed infection.[1][2] Hard nodules and regional lymph node enlargement may form in association with an underlying carcinoma. "Underpants-pattern erythema" represents a distinctive manifestation of genital EMPD that begins in the groin and spreads peripherally to areas covered by underwear. Tumor invasion of the lymphatic system drives this pattern and confers an ominous prognosis because of its link to rapidly fatal distant metastases.[3][4][7]

Diagnostic Evaluation The diagnosis of EMPD must prompt a comprehensive laboratory evaluation to identify any underlying malignancy. Required examinations depend on lesion location and may include a cervicovaginal smear, rectocoloscopy, cystoscopy, abdominal ultrasound or computed tomography scanning, gastroduodenal fibroscopy, mammography, intravenous urography, and measurement of serum tumor markers, eg, CEA, CA 19–9, and CA 15–3 (see Images. Paget Disease of the Long Bone and Paget Disease Pelvis). Long-Term Surveillance Long-term clinical follow-up remains essential, as some patients develop recurrences more than 15 years after initial treatment. Noninvasive EMPD typically warrants biannual follow-up for 3 years, followed by annual visits for 10 years. Invasive disease or EMPD associated with a distant tumor requires more frequent surveillance, ranging from 3 to 4 visits per year, with biopsy of any suspicious lesion. Perianal EMPD follow-up involves an annual complete examination, punch biopsy of new lesions, and proctosigmoidoscopy, with colonoscopy every 2 to 3 years. Vulvar EMPD follow-up incorporates regular vulvar inspection, punch biopsies of recurrent lesions to exclude invasive disease, and hysteroscopy or periodic pelvic ultrasound assessments. Lymph Node Evaluation Hatta and colleagues proposed a lymph node staging system in which N0 denotes absence of lymph node involvement, N1 indicates unilateral involvement, and N2 reflects bilateral or distant-site disease. The Kaplan-Meier survival curve from this study demonstrates progressively reduced survival with advancing nodal status. This staging framework creates a management dilemma when treating a patient with histologically confirmed EMPD but no clinically detectable lymphadenopathy. Recent literature has addressed this challenge by examining the roles of sentinel lymph node biopsy with or without complete lymph node dissection and the appropriateness of elective lymph node dissection in invasive EMPD. These surgical strategies derive from the concept that metastases first travel through the lymphatic system before systemic dissemination and that interrupting this pathway may limit progression to widespread disease.

Surgery remains the gold standard for the management of EMPD. The primary goal of treatment is complete resection of the tumor with histologically negative margins while preserving function and cosmesis. Due to the multifocal and sometimes ill-defined nature of EMPD, local recurrence remains frequent, and adjunctive therapies, including radiation, topical therapy, or systemic treatment, may be indicated depending on disease stage, patient comorbidity, and margin status. Management strategies can be divided into intraepidermal (noninvasive), invasive, and metastatic disease, in accordance with the Evidence-Based Clinical Practice Guidelines for Extramammary Paget Disease published by Kibbi et al in 2022. Surgical Management Approaches Surgical management remains the cornerstone of treatment for EMPD, aiming to achieve complete tumor removal while preserving function and cosmesis. Traditional wide local excision WLE has evolved with emerging evidence supporting narrower margins and advanced techniques. Margin-controlled approaches, eg, Mohs micrographic surgery and complete circumferential peripheral and deep margin assessment (CCPDMA), now offer improved margin assessment and lower recurrence rates. Wide local excision Wide local excision (WLE) historically served as the standard surgical approach for EMPD. The discontinuous and multifocal spread of Paget cells beyond visible margins prompted earlier recommendations for peripheral margins ranging from 2 to 5 cm. More recent evidence supports the adequacy of 1 to 2 cm margins for well-defined lesions without increasing the risk of recurrence. Murata et al. demonstrated reliable histopathologic clearance with a 1 cm margin, noting an average microscopic extension of only 0.33 mm beyond the clinically visible border. Additional studies have reported no meaningful difference in recurrence rates between margins of 2 cm or less and those greater than 2 cm, indicating minimal benefit from extensive resections. Preoperative mapping biopsies may help delineate subclinical disease, particularly for ill-defined lesions. In such cases, positive biopsies are more common within 2 cm of the clinical border, whereas sites 2 cm or more away are typically negative. Therefore, mapping biopsies may be unnecessary for well-defined lesions when standard margins of 1 to 2 cm can be achieved.

Preoperative mapping biopsies may help delineate subclinical disease, particularly for ill-defined lesions. In such cases, positive biopsies are more common within 2 cm of the clinical border, whereas sites 2 cm or more away are typically negative. Therefore, mapping biopsies may be unnecessary for well-defined lesions when standard margins of 1 to 2 cm can be achieved. While negative margins are desired, multiple studies have shown that positive margins do not necessarily predict recurrence or affect survival, suggesting multicentric disease biology. Functional and cosmetic preservation is critical in perineal and perianal EMPD, and therefore, the extent of resection should be individualized. Margin-controlled surgery Given the high recurrence rates after conventional excision, margin-controlled surgery, eg, Mohs micrographic surgery (MMS) or CCPDMA, is increasingly recommended. These techniques employ en face ("front on") sectioning to evaluate 100% of peripheral and deep margins, unlike traditional “bread-loaf” techniques that sample only portions of the specimen. MMS provides real-time intraoperative margin assessment under frozen section and may be enhanced with immunohistochemical stains, eg, cytokeratin 7 (CK7) or carcinoembryonic antigen (CEA), to improve detection of Paget cells. Retrospective analyses report recurrence rates of 11% to 22% with MMS compared to 26.5% to 37% with conventional WLE. A staged excision technique using rush permanent sections can also be employed, allowing confirmation of negative margins on permanent histology before definitive reconstruction. This approach maximizes oncologic control while conserving tissue and optimizing functional and aesthetic results. According to the Evidence-Based Clinical Practice Guidelines for Extramammary Paget Disease, margin-controlled surgery (MMS or CCPDMA) with en face sectioning is preferred when negative margins are sought for both intraepidermal and invasive EMPD. Radiation Therapy

A staged excision technique using rush permanent sections can also be employed, allowing confirmation of negative margins on permanent histology before definitive reconstruction. This approach maximizes oncologic control while conserving tissue and optimizing functional and aesthetic results. According to the Evidence-Based Clinical Practice Guidelines for Extramammary Paget Disease, margin-controlled surgery (MMS or CCPDMA) with en face sectioning is preferred when negative margins are sought for both intraepidermal and invasive EMPD. Radiation Therapy Radiotherapy serves as an effective alternative or adjunct to surgery. This modality may be used with curative intent in patients who are not surgical candidates or as an adjuvant treatment following surgery for persistent, recurrent, or incompletely resected disease. Several retrospective studies, including that by Hata et al, have demonstrated favorable outcomes with radiation doses around 60 Gy, achieving 5-year local progression-free rates exceeding 80%, with minimal grade 3 or higher toxicity.[1][2] Postoperative adjuvant radiation has also demonstrated excellent local control, with no recurrences observed during a median follow-up of 38 months. Guidelines recommend radiotherapy for patients in whom surgery is contraindicated or when residual disease remains, and further resection would cause excessive morbidity. Nonsurgical and Topical Therapies For patients unsuitable for surgical intervention due to comorbidity, advanced age, or refusal, several nonsurgical options can be considered. Topical 5% imiquimod cream, an immune response modifier that activates toll-like receptor 7, has demonstrated meaningful antitumor activity in EMPD, including complete response rates up to 70% after several months of therapy.[3][5]However, recurrences are frequent, and long-term follow-up is required. Treatment duration should generally be extended for at least 6 months to optimize efficacy. Imiquimod cream may be considered for recurrent, superficial, or multifocal lesions or as neoadjuvant therapy to reduce tumor size before surgery. However, caution is advised, as data suggest a higher recurrence rate following initial imiquimod cream use before subsequent surgery.

For patients unsuitable for surgical intervention due to comorbidity, advanced age, or refusal, several nonsurgical options can be considered. Topical 5% imiquimod cream, an immune response modifier that activates toll-like receptor 7, has demonstrated meaningful antitumor activity in EMPD, including complete response rates up to 70% after several months of therapy.[3][5]However, recurrences are frequent, and long-term follow-up is required. Treatment duration should generally be extended for at least 6 months to optimize efficacy. Imiquimod cream may be considered for recurrent, superficial, or multifocal lesions or as neoadjuvant therapy to reduce tumor size before surgery. However, caution is advised, as data suggest a higher recurrence rate following initial imiquimod cream use before subsequent surgery. Photodynamic therapy (PDT) and carbon dioxide laser ablation are additional options for carefully selected cases of intraepidermal disease, though recurrence rates remain significant. Close surveillance following treatment is mandatory. Systemic and Targeted Therapies For metastatic EMPD, systemic therapy may involve chemotherapy, targeted therapy, or immune checkpoint inhibitors. Reported regimens include vincristine, docetaxel, carboplatin, 5-fluorouracil, etoposide, and mitomycin C.[3][5] Targeted and immunotherapeutic approaches have been explored in small series with encouraging results. An interprofessional approach involving dermatology, surgical oncology, medical oncology, and radiation oncology is recommended. Whenever possible, clinical trial participation should be encouraged.[7][8][9]

Benign Inflammatory and Infectious Dermatoses EMPD frequently mimics chronic inflammatory skin conditions, especially when limited to the epidermis, including: Eczema (contact or seborrheic dermatitis): EMPD can appear as an erythematous or scaly lesion resembling chronic eczema; however, EMPD typically persists despite topical corticosteroid therapy. Psoriasis: Sharply demarcated erythematous plaques may mimic well-localized psoriatic lesions, though the absence of typical silvery scaling and refractoriness to standard psoriatic treatments should raise suspicion. Lichen simplex chronicus: Chronic pruritic plaques due to repeated scratching may clinically resemble EMPD but differ histologically. Candidiasis or intertrigo: Commonly occurs in intertriginous zones; candidiasis may show satellite pustules, whereas EMPD lesions are persistent and fail antifungal treatment. Tinea cruris (“jock itch”): Ringed or scaly lesions with central clearing may mimic EMPD; direct microscopic examination and fungal culture help exclude dermatophyte infection. Chronic balanitis or vulvitis: Particularly relevant for genital presentations; chronic irritation or infection can closely mimic early EMPD. Malignant and Premalignant Lesions EMPD must be distinguished from other cutaneous malignancies and intraepithelial neoplasms, as the treatment and prognosis differ significantly, including: Melanoma (especially amelanotic melanoma): May resemble erythematous or depigmented plaques.[1][2] Immunohistochemistry distinguishes melanoma (S-100, HMB-45, Melan-A positive) from EMPD (CK7, CEA positive). Bowen disease (squamous cell carcinoma in situ): Presents as a scaly, erythematous patch; histopathology reveals atypical keratinocytes in the epidermis, whereas Paget cells have large, pale cytoplasm and express mucin. Basal cell carcinoma (superficial type): Can mimic EMPD in the genital or perianal area but lacks the Pagetoid spread pattern histologically.

Bowen disease (squamous cell carcinoma in situ): Presents as a scaly, erythematous patch; histopathology reveals atypical keratinocytes in the epidermis, whereas Paget cells have large, pale cytoplasm and express mucin. Basal cell carcinoma (superficial type): Can mimic EMPD in the genital or perianal area but lacks the Pagetoid spread pattern histologically. Pagetoid variant of urothelial carcinoma or adenocarcinoma of anorectal or vulvar origin: Secondary EMPD represents epidermotropic spread from an underlying malignancy (eg, colorectal, urothelial, prostatic, or mammary carcinoma). Thus, identification of a potential primary source is crucial.[7][8][9] These lesions share histologic features but differ immunohistochemically. Markers CK20 and GCDFP-15 can help differentiate primary EMPD (typically positive CK7, positive GCDFP-15, negative CK20) from secondary involvement (often positive CK20, positive uroplakin III, or positive MUC2 depending on origin).[3][4] Other Cutaneous Neoplastic Conditions Other cutaneous neoplastic conditions that are included in the differential diagnosis of EMPD include: Pagetoid spread of cutaneous adnexal carcinoma: Can clinically and histologically resemble EMPD; diagnosis requires full histologic and immunohistochemical evaluation. Langerhans cell histiocytosis: Pagetoid pattern with epidermal involvement may lead to confusion; Langerhans cells show CD1a and langerin positivity, unlike Paget cells. Secondary EMPD Associated With Underlying Malignancy Because EMPD can represent epidermotropic spread from visceral adenocarcinoma, particularly of the colorectal, urinary tract, prostate, or cervix, the differential diagnosis must include evaluation for underlying internal malignancy. Appropriate workup may include colonoscopy, cystoscopy, prostate evaluation, and radiologic imaging (CT or MRI), depending on the lesion site and immunohistochemical profile.[5][6]

A standardized and universally accepted staging system for EMPD has not yet been established. Because EMPD represents a rare and heterogeneous malignancy with variable degrees of epidermal and dermal invasion, developing a consistent staging framework remains a challenge. Nevertheless, staging plays a critical role in guiding management, estimating prognosis, identifying high-risk populations, and facilitating the development of evidence-based treatment strategies. Traditionally, EMPD has been described according to the following extents of disease involvement: Intraepidermal (noninvasive) disease confined to the epidermis Invasive disease with dermal invasion and potential for lymphatic or hematogenous spread Metastatic disease with regional lymph node or distant metastases (see Image. Paget Disease Skull) Because deeper invasion correlates with worse prognosis, assessment of tumor thickness and lymphovascular invasion is key in clinical evaluation and treatment planning. Proposed TNM-Based Classification While no validated tumor–node–metastasis (TNM) system exists specifically for EMPD, Ohara and colleagues proposed a provisional TNM staging framework following a retrospective study of 301 Japanese patients with invasive EMPD.[9][10] The proposed classification integrates several prognostic factors, including tumor thickness, lymphovascular invasion, regional lymph node metastases, and distant metastases. Site-Specific Staging Considerations Because EMPD most often affects areas with apocrine glands, staging approaches may vary slightly based on anatomical site. In cases of vulvar EMPD, staging can be performed according to the American Joint Committee on Cancer (AJCC) system for vulvar carcinoma, particularly when there is dermal invasion or regional lymph node involvement. This approach facilitates uniform prognostic assessment and allows comparison with other vulvar malignancies that share similar biological behavior.[7][8]

The prognosis of EMPD depends primarily on the presence or absence of dermal invasion, nodal metastasis, and associated internal malignancy. A SEER analysis of cases from 1973 to 2013 reported a 5-year disease-specific survival (DSS) of 87% overall, with survival of 92% for localized, 77% for regional, and 16% for distant disease. Depth of invasion is the strongest pathologic prognostic factor. Noninvasive or superficially invasive lesions (<1 mm) have excellent outcomes, while invasion >1 mm significantly increases the risk of lymph node metastasis and decreased survival.[9][10] The number of metastatic lymph nodes correlates with prognosis better than the site of involvement. Patients older than 65 years, perianal or vaginal location, and the presence of associated internal malignancy are predictors of worse outcome. Registry data show internal cancers occur in approximately one-third of patients and are associated with reduced overall survival. Therefore, localized in situ EMPD carries an excellent prognosis after complete excision, whereas invasive, nodal, or metastatic disease portends poorer outcomes and warrants interprofessional management and long-term surveillance.[11]

Complications of EMPD include: Local recurrence: Common due to multifocal or ill-defined margins, even after complete excision. Invasion and metastasis: Dermal invasion may lead to nodal or distant spread, worsening prognosis. Associated internal malignancy: Occurs in up to one-third of cases and significantly reduces survival. Treatment-related morbidity: Wide excision or radiation can cause functional, cosmetic, and wound-healing complications. Psychological impact: Chronic symptoms, sexual dysfunction, and body-image changes can affect quality of life.

Early recognition and biopsy of suspicious, persistent eczematous or erythematous lesions in the genital, perianal, or axillary regions are essential to prevent delayed diagnosis of EMPD. Clinicians should maintain a high index of suspicion in postmenopausal women and older men with chronic lesions unresponsive to topical therapy. Patient education should emphasize the importance of long-term follow-up given the high risk of local recurrence and the possible association with underlying or synchronous malignancies. Patients should be counseled to promptly report new or recurrent symptoms such as pruritus, pain, or erythema. Clear communication about surgical options, the potential need for interprofessional evaluation, and realistic outcomes improves engagement, adherence, and overall quality of care.

EMPD is a rare cutaneous adenocarcinoma that primarily affects apocrine-rich areas, most commonly the vulva, perianal, scrotal, and axillary regions. Lesions often present as erythematous, scaly plaques with slow expansion and may mimic benign dermatoses, leading to delayed diagnosis. EMPD can occur as a primary cutaneous malignancy or secondary to underlying visceral or adnexal tumors, emphasizing the need for thorough evaluation and long-term surveillance. Surgical excision, particularly margin-controlled techniques such as Mohs micrographic surgery or CCPDMA, remains the cornerstone of treatment, while radiation, topical, and systemic therapies play roles in selected patients. Early recognition, precise staging, and multidisciplinary management are essential to reduce recurrence and optimize outcomes. Effective management relies on coordinated skills and responsibilities across the healthcare team. Physicians and advanced practitioners must maintain vigilance for persistent or atypical lesions, promptly coordinate biopsies, and interpret pathology results. Surgeons and oncologists collaborate to define resection margins, evaluate nodal involvement, and plan adjuvant therapy when needed. Pathologists confirm diagnosis and assess margins, while nurses provide perioperative care, patient education, and recurrence surveillance. Pharmacists support systemic therapy management, including dosing, monitoring for toxicity, and addressing drug interactions. Robust interprofessional communication through case conferences, shared documentation, and coordinated follow-up enhances patient safety, streamlines care, and ensures patient-centered decision-making, ultimately improving oncologic outcomes and quality of life.