{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T05:14:33Z","timestamp":1785820473697,"version":"3.56.0"},"reference-count":57,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T00:00:00Z","timestamp":1770595200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010609","name":"Gdansk Medical University","doi-asserted-by":"publisher","award":["ST 01-100024"],"award-info":[{"award-number":["ST 01-100024"]}],"id":[{"id":"10.13039\/501100010609","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objectives: Extramammary Paget disease (EMPD) is a rare, slow-growing intraepithelial malignancy arising in apocrine gland-bearing skin, most commonly in the anogenital region. Although often confined to the epidermis, EMPD may be associated with synchronous or underlying malignancies and can progress to invasive disease, making early recognition and compre- hensive staging crucial. Methods: We review current knowledge on the epidemiology, molecular pathogenesis, diagnostic work-up and treatment of EMPD with a particular focus on male genital involvement, and illustrate key clinical issues with two cases of penoscrotal EMPD treated in our center. Clinically, EMPD typically presents as chronic erythematous, pruritic plaques that are frequently misdiagnosed as benign dermatoses, leading to diagnostic delays. Results: Histopathology with immunohistochemistry remains the diagnostic gold standard and guides the search for associated internal malignancies. Wide local excision and Mohs micrographic surgery are the mainstays of treatment, but recurrence is common owing to subclinical extension. Non-surgical modalities\u2014including photodynamic therapy, topical imiquimod, radiotherapy and, in advanced disease, systemic chemotherapy, HER2 targeted agents and immune checkpoint inhibitors\u2014provide additional options in selected patients. Conclusions: A multidisciplinary, biomarker driven approach is essential to individualize management and improve long-term outcomes in this challenging disease.<\/jats:p>","DOI":"10.3390\/jcm15041355","type":"journal-article","created":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T09:41:02Z","timestamp":1770630062000},"page":"1355","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Management of Extramammary Paget Disease of the Male Genital Region: A Narrative Review and Two Case Reports"],"prefix":"10.3390","volume":"15","author":[{"given":"Marta","family":"Labon","sequence":"first","affiliation":[{"name":"Student Research Group, Department of Urology, Medical University of Gda\u0144sk, 80-210 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3296-3453","authenticated-orcid":false,"given":"Katarzyna","family":"Czajkowska","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Medical University of Gda\u0144sk, 80-210 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcin","family":"Matuszewski","sequence":"additional","affiliation":[{"name":"Department of Urology, Medical University of Gda\u0144sk, 80-210 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2017-5417","authenticated-orcid":false,"given":"Mateusz","family":"Czajkowski","sequence":"additional","affiliation":[{"name":"Department of Urology, Medical University of Gda\u0144sk, 80-210 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1159\/000536654","article-title":"Extramammary Paget\u2019s disease of the scrotal and penile: A case report and review of the literature","volume":"108","author":"Yang","year":"2024","journal-title":"Urol. Int."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e311","DOI":"10.3747\/co.20.1353","article-title":"Management of Penoscrotal Extramammary Paget Disease: Case Series and Review of the Literature","volume":"20","author":"Moretto","year":"2013","journal-title":"Curr. Oncol."},{"key":"ref_3","first-page":"93","article-title":"A primer on extramammary Paget\u2019s disease for the urologist","volume":"9","author":"Leong","year":"2020","journal-title":"Int. J. Surg. Oncol."},{"key":"ref_4","first-page":"524","article-title":"Extramammary Paget Disease of the Scrotum: A Contemporary Clinicopathologic Analysis of 20 Cases in the United States","volume":"28","author":"Shabihkhani","year":"2020","journal-title":"Case Rep. Dermatol. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2969","DOI":"10.3390\/curroncol28040260","article-title":"Extramammary Paget\u2019s Disease: Diagnosis, Pathogenesis, and Treatment with Focus on Recent Developments","volume":"28","author":"Ishizuki","year":"2021","journal-title":"Curr. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1111\/ans.12814","article-title":"Extramammary Paget\u2019s disease of the perianal region: A 20-year experience","volume":"87","author":"Rajendran","year":"2017","journal-title":"ANZ J. Surg."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Zhao, D., He, Y., and Wu, J. (2021). Extramammary Paget\u2019s Disease in the Genital Area of a Male: A Case Report and Review of the Literature. Oncol. Lett., 22.","DOI":"10.3389\/fonc.2021.713786"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1001\/jamadermatol.2023.2679","article-title":"Elevated Risk of Visceral Malignant Neoplasms in Extramammary Paget Disease","volume":"159","author":"Maloney","year":"2023","journal-title":"JAMA Dermatol."},{"key":"ref_9","first-page":"10012","article-title":"Extramammary Paget\u2019s disease: What do we know and how do we treat?","volume":"26","author":"Adashek","year":"2019","journal-title":"Can. J. Urol."},{"key":"ref_10","first-page":"197","article-title":"Increased risk and pattern of secondary malignancies in patients with invasive extramammary Paget disease","volume":"21","author":"Karam","year":"2014","journal-title":"Ann. Surg. Oncol."},{"key":"ref_11","first-page":"2275","article-title":"Extramammary Paget\u2019s disease: Updates in the workup and management","volume":"12","author":"Nabavizadeh","year":"2022","journal-title":"Dermatol. Ther."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1159\/000363177","article-title":"Perianal Paget\u2019s Disease Co-Associated with Anorectal Adenocarcinoma: Primary or Secondary Disease","volume":"8","author":"Liao","year":"2014","journal-title":"Case Rep. Gastroenterol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1111\/cup.14223","article-title":"Penile extramammary Paget disease associated with urothelial carcinoma in situ: Case report and literature review","volume":"49","author":"Tiwari","year":"2022","journal-title":"J. Cutan. Pathol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1186\/s13000-017-0638-z","article-title":"GATA3 is a sensitive marker for primary genital extramammary paget disease: An immunohistochemical study of 72 cases with comparison to gross cystic disease fluid protein 15","volume":"12","author":"Zhao","year":"2017","journal-title":"Diagn. Pathol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.ejso.2011.12.008","article-title":"Invasive extramammary Paget\u2019s disease and the risk for secondary tumours in Europe","volume":"38","author":"Siesling","year":"2012","journal-title":"Eur. J. Surg. Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e133","DOI":"10.1111\/jdv.16868","article-title":"Demographic and clinical characteristics of extramammary Paget\u2019s disease patients in Japan from 2000 to 2019","volume":"35","author":"Ghazawi","year":"2021","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1186\/s13023-021-01715-6","article-title":"Prevalence of extramammary Paget\u2019s disease in urban China: A population-based study","volume":"16","author":"Yin","year":"2021","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1016\/j.jaad.2024.05.025","article-title":"Epidemiology of extramammary Paget\u2019s disease among Asian-American subgroups: A surveillance, epidemiology, and end results (SEER) program-based analysis","volume":"91","author":"Joshi","year":"2024","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1308\/rcsann.2023.0006","article-title":"Recurrent primary scrotal extramammary Paget disease: A case report and literature review","volume":"106","author":"Pappas","year":"2024","journal-title":"Ann. R. Coll. Surg. Engl."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1097\/01.dad.0000158291.20440.13","article-title":"Vulvar Clear Cells of Toker Precursors of Extramammary Paget\u2019s Disease","volume":"27","author":"Willman","year":"2005","journal-title":"Am. J. Dermatopathol."},{"key":"ref_21","first-page":"35","article-title":"Multicentric primary extramammary Paget disease: A Toker cell disorder?","volume":"94","author":"Hashemi","year":"2014","journal-title":"Cutis"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1097\/00000478-198401000-00004","article-title":"Extramammary Paget\u2019s disease\u2013evidence for an apocrine origin. An immunoperoxidase study of gross cystic disease fluid protein-15, carcinoembryonic antigen, and keratin proteins","volume":"8","author":"Mazoujian","year":"1984","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"151","DOI":"10.5582\/bst.2011.v5.4.151","article-title":"The expression of HER-2 in extramammary Paget\u2019s disease","volume":"5","author":"Masuguchi","year":"2011","journal-title":"Biosci. Trends"},{"key":"ref_24","first-page":"PO.20.00073","article-title":"Genomic Alterations as Potential Therapeutic Targets in Extramammary Paget\u2019s Disease of the Vulva","volume":"4","author":"Stasenko","year":"2020","journal-title":"JCO Precis. Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1111\/j.1600-0560.2008.01148.x","article-title":"HER-2\/neu expression in extramammary Paget disease: A clinicopathologic and immunohistochemistry study of 47 cases with and without underlying malignancy","volume":"36","author":"Plaza","year":"2009","journal-title":"J. Cutan. Pathol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"oyaf063","DOI":"10.1093\/oncolo\/oyaf063","article-title":"Antibody-drug conjugate (disitamab vedotin) therapy targeting HER2-low or higher advanced extramammary Paget\u2019s disease","volume":"30","author":"Zhang","year":"2025","journal-title":"Oncologist"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1002\/cam4.2820","article-title":"Comparison of the biomarkers for targeted therapies in primary extra-mammary and mammary Paget\u2019s disease","volume":"9","author":"Gatalica","year":"2020","journal-title":"Cancer Med."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Mauzo, S.H., Tetzlaff, M.T., Milton, D.R., Siroy, A.E., Nagarajan, P., Torres-Cabala, C.A., Ivan, D., Curry, J.L., Hudgens, C.W., and Wargo, J.A. (2019). Expression of PD-1 and PD-L1 in Extramammary Paget Disease: Implications for Immune-Targeted Therapy. Cancers, 11.","DOI":"10.3390\/cancers11060754"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3768247","DOI":"10.1155\/2017\/3768247","article-title":"Mammary and Extramammary Paget\u2019s Disease Presented Different Expression Pattern of Steroid Hormone Receptors","volume":"2017","author":"Zhou","year":"2017","journal-title":"BioMed Res. Int."},{"key":"ref_30","first-page":"401","article-title":"Phase II clinical trial of docetaxel and trastuzumab for HER2-positive advanced extramammary Paget\u2019s disease (EMPD-HER2DOC)","volume":"181","author":"Hirai","year":"2019","journal-title":"Br. J. Dermatol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1046\/j.1365-2133.2000.03291.x","article-title":"The use of cytokeratins 7 and 20 in the diagnosis of primary and secondary extramammary Paget\u2019s disease","volume":"142","author":"Ohnishi","year":"2000","journal-title":"Br. J. Dermatol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1097\/00000372-199604000-00003","article-title":"Gross Cystic Disease Fluid Protein-15 Reactivity in Extramammary Paget\u2019s Disease with and without Associated Internal Malignancy","volume":"18","author":"Kohler","year":"1996","journal-title":"Am. J. Dermatopathol."},{"key":"ref_33","first-page":"3426","article-title":"Primary extramammary Paget\u2019s disease: A clinicopathological study of 28 cases","volume":"12","author":"Zhao","year":"2019","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1111\/bjd.14300","article-title":"Clinical and dermoscopic characteristics of extramammary Paget disease: A study of 35 cases","volume":"174","author":"Mun","year":"2016","journal-title":"Br. J. Dermatol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"103105","DOI":"10.1016\/j.pdpdt.2022.103105","article-title":"Clinical and dermoscopic features of extramammary Paget\u2019s disease: A retrospective analysis of 49 cases","volume":"40","author":"Chen","year":"2022","journal-title":"Photodiagn. Photodyn. Ther."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e47","DOI":"10.1016\/j.jaad.2010.09.722","article-title":"In vivo reflectance confocal microscopy of extramammary Paget disease: Diagnostic evaluation and surgical management","volume":"66","author":"Pan","year":"2012","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_37","first-page":"e24","article-title":"Reflectance confocal microscopy for diagnosis of mammary and extramammary Paget\u2019s disease","volume":"27","author":"Guitera","year":"2012","journal-title":"Br. J. Dermatol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1111\/his.13086","article-title":"GATA3 expression in primary vulvar Paget disease: A potential pitfall leading to misdiagnosis of pagetoid urothelial intraepithelial neoplasia","volume":"70","author":"Morbeck","year":"2017","journal-title":"Histopathology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1097\/MNM.0000000000000340","article-title":"Utility of 18F-FDG PET-CT in the diagnosis and staging of extramammary Paget\u2019s disease","volume":"36","author":"Tian","year":"2015","journal-title":"Nucl. Med. Commun."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1111\/1346-8138.13833","article-title":"Evaluation of positron emission tomography imaging to detect lymph node metastases in patients with extramammary Paget\u2019s disease","volume":"44","author":"Fujiwara","year":"2017","journal-title":"J. Dermatol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1684\/ejd.2015.2534","article-title":"Usefulness of sentinel lymph node biopsy for the detection of metastasis in the early stage of extramammary Paget\u2019s disease","volume":"25","author":"Kusatake","year":"2015","journal-title":"Eur. J. Dermatol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1007\/s00256-012-1540-0","article-title":"Magnetic resonance imaging for extramammary Paget\u2019s disease: Radiological and pathological correlations","volume":"42","author":"Akaike","year":"2013","journal-title":"Skelet. Radiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1097\/DSS.0000000000003601","article-title":"Local Recurrence Rates of Extramammary Paget Disease Are Lower After Mohs Micrographic Surgery Compared with Wide Local Excision: A Systematic Review and Meta-Analysis","volume":"49","author":"Kim","year":"2023","journal-title":"Dermatol. Surg."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1016\/j.jaad.2012.12.960","article-title":"Mohs micrographic surgery for extramammary Paget disease: A pooled analysis of individual patient data","volume":"68","author":"Bae","year":"2013","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1097\/DSS.0000000000003736","article-title":"Treatment Outcomes of Adjunct and Stand-alone Photodynamic Therapy in Patients with Extramammary Paget Disease: A Literature Review","volume":"49","author":"Sachdeva","year":"2023","journal-title":"Dermatol. Surg."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"479","DOI":"10.3109\/01443615.2013.790348","article-title":"Imiquimod therapy for extramammary Paget\u2019s disease of the vulva: A viable non-surgical alternative","volume":"33","author":"Sanderson","year":"2013","journal-title":"J. Obstet. Gynaecol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1111\/1346-8138.14247","article-title":"Efficacy of low-dose 5-fluorouracil\/cisplatin therapy for invasive extramammary Paget\u2019s disease","volume":"45","author":"Kato","year":"2018","journal-title":"J. Dermatol."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Hashimoto, H., Kaku-Ito, Y., Furue, M., and Ito, T. (2021). The Outcome of Chemotherapy for Metastatic Extramammary Paget\u2019s Disease. J. Clin. Med., 10.","DOI":"10.3390\/jcm10040739"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1111\/1346-8138.15515","article-title":"Experiences of trastuzumab plus paclitaxel combination therapy in metastatic human epidermal growth factor receptor 2-positive extramammary Paget\u2019s disease: Four cases and a review","volume":"47","author":"Sekiguchi","year":"2020","journal-title":"J. Dermatol."},{"key":"ref_50","first-page":"e72592","article-title":"A Case of Advanced Extramammary Paget\u2019s Disease with a High Tumor Mutation Burden That Showed Partial Lymph Node Regression with Pembrolizumab","volume":"16","author":"Horisaki","year":"2024","journal-title":"Cureus"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1111\/j.1365-2230.2007.02425.x","article-title":"Radiotherapy for extramammary Paget\u2019s disease: Histopathological findings after radiotherapy","volume":"32","author":"Yanagi","year":"2007","journal-title":"Clin. Exp. Dermatol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1097\/DAD.0b013e3181b71481","article-title":"The Role of Immunohistochemistry in Discriminating Primary from Secondary Extramammary Paget Disease","volume":"32","author":"Perrotto","year":"2010","journal-title":"Am. J. Dermatopathol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"154775","DOI":"10.1016\/j.prp.2023.154775","article-title":"Clinicopathological significance of androgen receptor expression in extramammary Paget disease: An analysis of 92 patients","volume":"249","author":"Kuramoto","year":"2023","journal-title":"Pathol. Res. Pract."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1662","DOI":"10.1016\/j.humpath.2015.07.007","article-title":"Androgen receptor, androgen-producing enzymes and their transcription factors in extramammary Paget disease","volume":"46","author":"Azmahani","year":"2015","journal-title":"Hum. Pathol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1038\/modpathol.3800437","article-title":"Androgen receptors are frequently expressed in mammary and extramammary Paget\u2019s disease","volume":"18","author":"Liegl","year":"2005","journal-title":"Mod. Pathol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1309\/P756-XXCB-TV71-U4XV","article-title":"Extramammary Paget disease is characterized by the consistent lack of estrogen and progesterone receptors but frequently expresses androgen receptor","volume":"113","author":"Carcangiu","year":"2000","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Hashimoto, H., Kaku-Ito, Y., Oda, Y., and Ito, T. (2021). CDK4: A Novel Therapeutic Target for Extramammary Paget\u2019s Disease. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.710378"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/4\/1355\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T10:11:27Z","timestamp":1770631887000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/4\/1355"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,9]]},"references-count":57,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["jcm15041355"],"URL":"https:\/\/doi.org\/10.3390\/jcm15041355","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,9]]}}}