A Rare Case of Perianal Extramammary Paget’s Disease Associated with Adenocarcinoma: A Case Report

A Rare Case of Perianal Extramammary Paget’s Disease Associated with Adenocarcinoma: A Case Report | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report A Rare Case of Perianal Extramammary Paget’s Disease Associated with Adenocarcinoma: A Case Report Arda Sakir Yilmaz, Necdet Fqtih Yasar, Orkhan Ulfanov, Aydan Ayse Kose This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7278139/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose Extramammary Paget’s Disease (EMPD) is a rare malignancy commonly affecting anogenital and apocrine gland-rich areas. Perianal EMPD usually presents with skin involvement and, rarely, affects the anal mucosa. Patients typically experience non-specific symptoms such as itching, pain, and erythematous plaques. EMPD has a high recurrence rate and a risk of progression to malignancy. This case report presents a rare perianal EMPD case complicated by adenocarcinoma development. Methods A 58-year-old male patient with chronic perianal lesions was initially misdiagnosed and treated inadequately. Advanced imaging (MRI and PET-CT) confirmed malignancy suspicion, and biopsy revealed invasive adenocarcinoma arising from EMPD. Surgical management included wide local excision, inguinal and iliac lymph node dissection, and perianal reconstruction. Conclusion Early diagnosis and aggressive surgical treatment are crucial in reducing recurrence risk. Lymph node metastases and invasive components significantly impact prognosis. Long-term follow-up and research on molecular markers may contribute to better treatment approaches. Extramammary Paget’s Disease perianal region adenocarcinoma Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction Extramammary Paget’s disease (EMPD) is a rare neoplastic condition that typically arises in areas rich in apocrine glands such as the anogenital region, axilla, and other apocrine-dense zones [ 1 ]. In perianal EMPD, cutaneous involvement is common, while involvement of the anal mucosa is rare [ 2 ]. Only about 70% of EMPD cases present with symptoms [ 3 ], and there are no disease-specific signs or findings. Symptoms are usually localized and may include pruritus, pain, erythematous plaques, and, in advanced stages, ulcerations of the skin [ 4 ]. The most frequent symptom is nonspecific perianal discomfort, observed in approximately 60–70% of cases, while bleeding may occur in 30–40% of patients due to deeper tissue invasion [ 5 ]. Case reports suggest that the risk of malignancy following perianal Paget’s disease is around 70% [ 6 ]. Nevertheless, the absence of specific clinical indicators often delays diagnosis, and patients are frequently treated with simple local interventions [ 7 ]. Once rectal adenocarcinoma develops, the prognosis worsens significantly, highlighting the importance of early diagnosis and effective treatment strategies [ 3 ]. Lymph node metastasis is rare in EMPD but, when present, typically involves the femoral, inguinal, and iliac nodes. Distant metastases most commonly involve the peritoneum, omentum, mesentery, and liver [ 3 ]. Due to its high local recurrence potential, close follow-up is essential to monitor for intraperitoneal and surgical scar metastases [ 8 ]. In this report, we present a rare case of perianal EMPD associated with adenocarcinoma, emphasizing the diagnostic challenges, histopathological findings, and therapeutic approach. Case Report A 58-year-old male with a medical history of diabetes mellitus, hypertension, hyperlipidemia, and hypoplastic right kidney presented with a 1.5-year history of swelling, erythema, and ulceration in the perianal region. He had sought medical attention at multiple institutions, where he received local treatments for non-specific symptoms without significant improvement. Colonoscopy was eventually performed and revealed no pathological findings other than a raised lesion in the perianal skin (Fig. 1 ). Further evaluation with lower abdominal magnetic resonance imaging (MRI) showed multiple round lymphadenopathies (LAPs) in the right inguinal region, the largest measuring 29×19 mm, with no visible fatty hilum and mild heterogeneity—findings interpreted as suggestive of metastasis. Positron Emission Tomography–Computed Tomography (PET-CT) was conducted to identify a primary malignancy, which demonstrated hypermetabolic lesions suspicious for polyps, adenomas, or tumors at the rectosigmoid junction, transverse colon, and ascending colon. Additionally, a 24×18 mm conglomerated lymph node (SUVmax 5.55) and an 11 mm lymph node (SUVmax 3.47) were identified in the right inguinal region. Increased FDG uptake (SUVmax 3.76) was also noted in the perianal area, suggestive of postoperative inflammation or malignancy. A biopsy of the perianal lesion confirmed invasive carcinoma arising in a background of extramammary Paget’s disease, with HER-2 score 3 + positivity in the invasive areas (Figs. 2 & 3 ). Surgical resection was planned based on these findings. After obtaining informed consent, the patient underwent excision of the skin and subcutaneous tissue affected by Paget’s disease with clear margins (Fig. 4 ). Due to suspicion of metastasis, frozen section analysis of excised right inguinal lymph nodes confirmed metastasis, prompting a complete dissection of the inguinal and femoral lymph nodes. Laparotomy was performed to remove pathologic right iliac and obturator lymph nodes. A diverting loop colostomy was created in preparation for flap reconstruction. The patient was repositioned, and bilateral flaps were used to reconstruct the perianal region in cooperation with plastic surgery, with a merocel packed inside a condom placed to prevent postoperative anal stenosis (Fig. 5 ). Postoperatively, the patient was monitored by a multidisciplinary team including plastic surgery. Oral intake was gradually resumed, and the patient was discharged in good condition. Final pathology confirmed adenocarcinoma arising in EMPD, with negative lateral and posterior surgical margins. Metastatic carcinoma was also observed in the iliac, obturator, Cloquet, inguinal, and femoral lymph nodes. Given the metastatic nature of the disease, the patient was referred to medical oncology for adjuvant therapy. Discussion Extramammary Paget’s disease is a rare neoplasm often associated with underlying malignancies such as adenocarcinoma and characterized by indolent clinical progression and a high recurrence rate [ 9 ]. The presence of intraepidermal Paget cells is a significant marker of malignancy risk, with reported associations ranging from 33–86% [ 10 ]. The interval between symptom onset and diagnosis typically ranges from 2 to 4 years [ 11 ]. EMPD is frequently misdiagnosed as dermatitis, eczema, or fungal infection, resulting in delayed diagnosis and inappropriate treatments [ 12 ]. MRI provides detailed anatomical information about the perianal and pelvic regions, while PET-CT is valuable for detecting occult metastases and differentiating between active disease and inflammatory or benign changes [ 13 ]. However, imaging alone is insufficient for diagnosis, which must be confirmed histologically [ 2 ]. Surgical excision remains the gold standard for localized EMPD. Wide local excision is preferred over simple excision due to the high risk of recurrence. Studies have reported recurrence rates approaching 100% with simple excision alone [ 8 , 11 ]. Regardless of the extent of surgery, EMPD requires long-term and comprehensive follow-up due to its recurrence potential [ 14 ]. In our case, a multimodal treatment approach was implemented postoperatively, in line with current oncological recommendations. The patient received systemic chemotherapy with Ploxel-S infusions every 21 days, combined with oral capecitabine taken at home. After two cycles of chemotherapy, four cycles of radiotherapy were administered, followed by continued chemotherapy. At the time of writing, the patient was undergoing the fourth cycle of chemotherapy, with a total of six planned. This approach aims to ensure local control and prevent systemic disease progression, reflecting best practices recommended in the literature. Adjuvant chemotherapy and radiotherapy are generally reserved for advanced or metastatic EMPD. Radiotherapy may be beneficial in cases with positive surgical margins or where re-excision is not feasible, while systemic chemotherapy has shown limited efficacy in localized disease (8). Nevertheless, some studies have reported favorable responses to platinum-based regimens combined with capecitabine. In our case, HER-2 score 3 positivity on immunohistochemical analysis raises the possibility of targeted therapy. Recent studies have shown partial responses in HER-2 positive EMPD cases treated with trastuzumab-based therapies, underlining the prognostic and therapeutic significance of molecular markers such as HER-2 and p53 (12, 15). Additionally, a multidisciplinary treatment strategy was adopted, incorporating oncologic resection and reconstructive surgery. This holistic approach aimed not only to achieve disease control but also to preserve functional and aesthetic outcomes, particularly important in anatomically and socially sensitive regions such as the perianal area. Conclusion This case highlights the diagnostic and therapeutic challenges of adenocarcinoma arising in perianal EMPD. Wide local excision offers improved local control and survival rates compared to simple excision. Nevertheless, further research is needed to evaluate the efficacy of personalized, multimodal treatment strategies in advanced and metastatic disease. For EMPD cases with a risk of progression to invasive cancer, molecular markers such as HER-2 and p53 may guide treatment decisions. Future studies should focus on targeted therapies and individualized treatment strategies based on these biomarkers, aiming to reduce recurrence and improve survival outcomes. Declarations Authors’ contributions: Yilmaz AS: conceptualization (lead), ınvestigation (lead), resources (lead), writing – original draft (lead); Yasar NF: data curation (equal), methodology (lead), project administration (lead), writing – review & editing (lead); Kose AA: resources (supporting), supervision (lead), validation (supporting); Ulfanov O: data curation (lead), resources (supporting); Kose AA: ınvestigation (lead), methodology (supporting), software (equal), writing – original draft (supporting). Sources of funding: There is no funding/sponsorship for this study. Conflict of interests: The authors declare that there is no conflict of interest regarding the publication of this paper. Acknowledgment: Informed consent was obtained from the patients. Declaration: Research data is available and can be shared upon request. Consent to publish: Written informed consent for participation and publication was obtained from all individual participants included in the study. Ethical Approval and accordance: The Eskişehir Osmangazi Non-Interventional Ethics Committee has waived the approval for this case report in accordance with the guidelines of TÜBİTAK – the Scientific and Technological Research Council of Turkey. References Chumbalkara V, Jennings TA, Ainechi S, Lee EC, Lee H. Extramammary Paget’s Disease of Anal Canal Associated With Rectal Adenoma Without Invasive Carcinoma. Gastroenterol Res. 2016;9(6):99–102. doi:10.14740/gr727e. Kusuhara T, Ito T, Matsuoka H, Chohno T, Zozumi M, Ohnishi T. Rare Anal Canal Cancer with Secondary Extramammary Paget’s Disease (Pagetoid Spread) Complicated by Squamous Cell Carcinoma of the Skin. Case Rep Surg. 2021;2021:9944886. doi:10.1155/2021/9944886. Kosano M, Kiniwa Y, Mikoshiba A, Iwaya M, Okuyama R. Clinical Features of Pagetoid Spread: Analysis of Perianal Lesions Associated with Anal Canal Adenocarcinoma and Perianal Primary Extramammary Paget Disease. J Dermatol. 2023;50:546–50. doi:10.1111/1346-8138.16744. Nagai Y, Kazama S, Yamada D, et al. Perianal and Vulvar Extramammary Paget Disease: A Report of Six Cases and Mapping Biopsy of the Anal Canal. Ann Dermatol. 2016;28(5):624–8. doi:10.5021/ad.2016.28.5.624. Li M, Yao X. Goblet Cell Adenocarcinoma of the Anal Canal with Perianal Paget Disease: A Rare Case Report with Literature Review. Medicine (Baltimore). 2023;102(16):e33598. doi:10.1097/MD.0000000000033598. Sarmiento JM, Wolff BG, Burgart LJ, Frizelle FA, Ilstrup DM. Paget's Disease of the Perianal Region--An Aggressive Disease? Dis Colon Rectum. 1997;40(10):1187–94. doi:10.1007/BF02050924. Isik O, Aytac E, Brainard J, et al. Perianal Paget’s Disease: Three Decades Experience of a Single Institution. Int J Colorectal Dis. 2016;31(1):29–34. doi:10.1007/s00384-015-2334-4. Elshikh M, Menias CO, Amer AM, et al. Tumors and Tumorlike Conditions of the Anal Canal and Perianal Region: MR Imaging Findings. RadioGraphics. 2016;36(5):1339–53. doi:10.1148/rg.2016160028. Goldman S, Ihre T, Lagerstedt U, Svensson C. Perianal Paget’s Disease: Report of Five Cases. Int J Colorectal Dis. 1992;7(3):167–9. doi:10.1007/BF00341258. Delaunoit T, Neczyporenko F, Duttmann R, et al. Perianal Paget’s Disease: Case Report and Review of the Literature. Acta Gastroenterol Belg. 2004;67(2):228–31. PMID:15239223. McCarter MD, Quan SH, Busam K, et al. Long-Term Outcome of Perianal Paget’s Disease. Dis Colon Rectum. 2003;46(5):612–6. doi:10.1007/s10350-004-6614-5. Marchesa P, Fazio VW, Oliart S, et al. Long-Term Outcome of Patients With Perianal Paget's Disease. Ann Surg Oncol. 1997;4(6):475–80. doi:10.1007/BF02303765. Ishii K, Takahashi H, Tsuji H, et al. Clinical and Pathological Analysis of Perianal Paget’s Disease: A Case Report and Review of 89 Cases. Cancer Diagn Progn. 2025;5(1):49–55. doi:10.21873/cdp.10152. Kim CW, Kim YH, Cho MS, et al. Perianal Paget’s Disease: Case Report and Literature Review. Ann Coloproctol. 2014;30(5):241–4. doi:10.3393/ac.2014.30.5.241. Guo JJ, Jiao XD, Wu Y, Qin BD, Liu K, Zang YS. Response to Pyrotinib in a Chinese Patient with Bone-Metastatic Scrotal Paget's Disease Harboring Triple Uncommon HER2 Mutation: A Case Report. Onco Targets Ther. 2020;13:6289-6293. Published 2020 Jun 30. doi:10.2147/OTT.S244814 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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2","display":"","copyAsset":false,"role":"figure","size":437639,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003eAxial MRI showing pathological right inguinal lymph nodes with loss of fatty hilum and lobulated contours suggestive of metastasis.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-7278139/v1/df2d2ec8b2bd82023a19d9dd.png"},{"id":91218277,"identity":"0d2177d2-915c-4686-a9ce-b2e8893ab7bb","added_by":"auto","created_at":"2025-09-12 20:27:37","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":284774,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003ePET-CT demonstrating hypermetabolic activity in the right inguinal lymph nodes (SUVmax 5.55) and perianal region (SUVmax 3.76).\u003c/em\u003e\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-7278139/v1/99f0aea01916697f0b4694ac.png"},{"id":91218280,"identity":"32cfca5e-72ef-472e-8a57-921ac2b43fe8","added_by":"auto","created_at":"2025-09-12 20:27:37","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":1342321,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003eIntraoperative view following wide local excision of the Paget-involved skin and subcutaneous tissue.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"Figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-7278139/v1/b30fc137eb2e2912b252c344.png"},{"id":91219875,"identity":"41882327-2ba7-4159-bd9a-eb0414348e54","added_by":"auto","created_at":"2025-09-12 20:59:37","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":1126469,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003ePost-reconstructive image showing bilateral rotational flaps covering the perianal defect and merocel placement to prevent postoperative anal canal stenosis.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"Figure5.png","url":"https://assets-eu.researchsquare.com/files/rs-7278139/v1/dfbc72d95e6c319a6dac6280.png"},{"id":101657317,"identity":"71680379-464a-4213-9247-20e68920de3c","added_by":"auto","created_at":"2026-02-02 10:13:43","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":5950344,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7278139/v1/1a96fe42-6399-4bce-ac4e-e8e2dc635c98.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"A Rare Case of Perianal Extramammary Paget’s Disease Associated with Adenocarcinoma: A Case Report","fulltext":[{"header":"Introduction","content":"\u003cp\u003eExtramammary Paget\u0026rsquo;s disease (EMPD) is a rare neoplastic condition that typically arises in areas rich in apocrine glands such as the anogenital region, axilla, and other apocrine-dense zones [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. In perianal EMPD, cutaneous involvement is common, while involvement of the anal mucosa is rare [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Only about 70% of EMPD cases present with symptoms [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e], and there are no disease-specific signs or findings. Symptoms are usually localized and may include pruritus, pain, erythematous plaques, and, in advanced stages, ulcerations of the skin [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. The most frequent symptom is nonspecific perianal discomfort, observed in approximately 60\u0026ndash;70% of cases, while bleeding may occur in 30\u0026ndash;40% of patients due to deeper tissue invasion [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eCase reports suggest that the risk of malignancy following perianal Paget\u0026rsquo;s disease is around 70% [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Nevertheless, the absence of specific clinical indicators often delays diagnosis, and patients are frequently treated with simple local interventions [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Once rectal adenocarcinoma develops, the prognosis worsens significantly, highlighting the importance of early diagnosis and effective treatment strategies [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Lymph node metastasis is rare in EMPD but, when present, typically involves the femoral, inguinal, and iliac nodes. Distant metastases most commonly involve the peritoneum, omentum, mesentery, and liver [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Due to its high local recurrence potential, close follow-up is essential to monitor for intraperitoneal and surgical scar metastases [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eIn this report, we present a rare case of perianal EMPD associated with adenocarcinoma, emphasizing the diagnostic challenges, histopathological findings, and therapeutic approach.\u003c/p\u003e"},{"header":"Case Report","content":"\u003cp\u003eA 58-year-old male with a medical history of diabetes mellitus, hypertension, hyperlipidemia, and hypoplastic right kidney presented with a 1.5-year history of swelling, erythema, and ulceration in the perianal region. He had sought medical attention at multiple institutions, where he received local treatments for non-specific symptoms without significant improvement. Colonoscopy was eventually performed and revealed no pathological findings other than a raised lesion in the perianal skin (Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003eFurther evaluation with lower abdominal magnetic resonance imaging (MRI) showed multiple round lymphadenopathies (LAPs) in the right inguinal region, the largest measuring 29\u0026times;19 mm, with no visible fatty hilum and mild heterogeneity\u0026mdash;findings interpreted as suggestive of metastasis. Positron Emission Tomography\u0026ndash;Computed Tomography (PET-CT) was conducted to identify a primary malignancy, which demonstrated hypermetabolic lesions suspicious for polyps, adenomas, or tumors at the rectosigmoid junction, transverse colon, and ascending colon. Additionally, a 24\u0026times;18 mm conglomerated lymph node (SUVmax 5.55) and an 11 mm lymph node (SUVmax 3.47) were identified in the right inguinal region. Increased FDG uptake (SUVmax 3.76) was also noted in the perianal area, suggestive of postoperative inflammation or malignancy.\u003c/p\u003e\n\u003cp\u003eA biopsy of the perianal lesion confirmed invasive carcinoma arising in a background of extramammary Paget\u0026rsquo;s disease, with HER-2 score 3\u0026thinsp;+\u0026thinsp;positivity in the invasive areas (Figs. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e \u0026amp; \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e). Surgical resection was planned based on these findings. After obtaining informed consent, the patient underwent excision of the skin and subcutaneous tissue affected by Paget\u0026rsquo;s disease with clear margins (Fig. \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e). Due to suspicion of metastasis, frozen section analysis of excised right inguinal lymph nodes confirmed metastasis, prompting a complete dissection of the inguinal and femoral lymph nodes. Laparotomy was performed to remove pathologic right iliac and obturator lymph nodes. A diverting loop colostomy was created in preparation for flap reconstruction. The patient was repositioned, and bilateral flaps were used to reconstruct the perianal region in cooperation with plastic surgery, with a merocel packed inside a condom placed to prevent postoperative anal stenosis (Fig. \u003cspan class=\"InternalRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003ePostoperatively, the patient was monitored by a multidisciplinary team including plastic surgery. Oral intake was gradually resumed, and the patient was discharged in good condition. Final pathology confirmed adenocarcinoma arising in EMPD, with negative lateral and posterior surgical margins. Metastatic carcinoma was also observed in the iliac, obturator, Cloquet, inguinal, and femoral lymph nodes. Given the metastatic nature of the disease, the patient was referred to medical oncology for adjuvant therapy.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eExtramammary Paget\u0026rsquo;s disease is a rare neoplasm often associated with underlying malignancies such as adenocarcinoma and characterized by indolent clinical progression and a high recurrence rate [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. The presence of intraepidermal Paget cells is a significant marker of malignancy risk, with reported associations ranging from 33\u0026ndash;86% [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. The interval between symptom onset and diagnosis typically ranges from 2 to 4 years [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. EMPD is frequently misdiagnosed as dermatitis, eczema, or fungal infection, resulting in delayed diagnosis and inappropriate treatments [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eMRI provides detailed anatomical information about the perianal and pelvic regions, while PET-CT is valuable for detecting occult metastases and differentiating between active disease and inflammatory or benign changes [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. However, imaging alone is insufficient for diagnosis, which must be confirmed histologically [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eSurgical excision remains the gold standard for localized EMPD. Wide local excision is preferred over simple excision due to the high risk of recurrence. Studies have reported recurrence rates approaching 100% with simple excision alone [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Regardless of the extent of surgery, EMPD requires long-term and comprehensive follow-up due to its recurrence potential [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eIn our case, a multimodal treatment approach was implemented postoperatively, in line with current oncological recommendations. The patient received systemic chemotherapy with Ploxel-S infusions every 21 days, combined with oral capecitabine taken at home. After two cycles of chemotherapy, four cycles of radiotherapy were administered, followed by continued chemotherapy. At the time of writing, the patient was undergoing the fourth cycle of chemotherapy, with a total of six planned. This approach aims to ensure local control and prevent systemic disease progression, reflecting best practices recommended in the literature.\u003c/p\u003e\u003cp\u003eAdjuvant chemotherapy and radiotherapy are generally reserved for advanced or metastatic EMPD. Radiotherapy may be beneficial in cases with positive surgical margins or where re-excision is not feasible, while systemic chemotherapy has shown limited efficacy in localized disease (8). Nevertheless, some studies have reported favorable responses to platinum-based regimens combined with capecitabine.\u003c/p\u003e\u003cp\u003eIn our case, HER-2 score 3 positivity on immunohistochemical analysis raises the possibility of targeted therapy. Recent studies have shown partial responses in HER-2 positive EMPD cases treated with trastuzumab-based therapies, underlining the prognostic and therapeutic significance of molecular markers such as HER-2 and p53 (12, 15).\u003c/p\u003e\u003cp\u003eAdditionally, a multidisciplinary treatment strategy was adopted, incorporating oncologic resection and reconstructive surgery. This holistic approach aimed not only to achieve disease control but also to preserve functional and aesthetic outcomes, particularly important in anatomically and socially sensitive regions such as the perianal area.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis case highlights the diagnostic and therapeutic challenges of adenocarcinoma arising in perianal EMPD. Wide local excision offers improved local control and survival rates compared to simple excision. Nevertheless, further research is needed to evaluate the efficacy of personalized, multimodal treatment strategies in advanced and metastatic disease.\u003c/p\u003e\u003cp\u003eFor EMPD cases with a risk of progression to invasive cancer, molecular markers such as HER-2 and p53 may guide treatment decisions. Future studies should focus on targeted therapies and individualized treatment strategies based on these biomarkers, aiming to reduce recurrence and improve survival outcomes.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions:\u0026nbsp;\u003c/strong\u003eYilmaz AS: conceptualization (lead), ınvestigation (lead), resources (lead), writing \u0026ndash; original draft (lead); Yasar NF: data curation (equal), methodology (lead), project administration (lead), writing \u0026ndash; review \u0026amp; editing (lead); Kose AA: resources (supporting), supervision (lead), validation (supporting); Ulfanov O: data curation (lead), resources (supporting); Kose AA: ınvestigation (lead), methodology (supporting), software (equal), writing \u0026ndash; original draft (supporting).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSources of funding:\u003c/strong\u003e There is no funding/sponsorship for this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interests:\u003c/strong\u003e The authors declare that there is no conflict of interest regarding the publication of this paper.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgment:\u0026nbsp;\u003c/strong\u003eInformed consent was obtained from the patients.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDeclaration:\u003c/strong\u003e Research data is available and can be shared upon request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to publish:\u003c/strong\u003e Written informed consent for participation and publication was obtained from all individual participants included in the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical Approval and accordance:\u003c/strong\u003e The Eskişehir Osmangazi Non-Interventional Ethics Committee has waived the approval for this case report in accordance with the guidelines of T\u0026Uuml;BİTAK \u0026ndash; the Scientific and Technological Research Council of Turkey.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eChumbalkara V, Jennings TA, Ainechi S, Lee EC, Lee H. Extramammary Paget\u0026rsquo;s Disease of Anal Canal Associated With Rectal Adenoma Without Invasive Carcinoma. Gastroenterol Res. 2016;9(6):99\u0026ndash;102. doi:10.14740/gr727e.\u003c/li\u003e\n \u003cli\u003eKusuhara T, Ito T, Matsuoka H, Chohno T, Zozumi M, Ohnishi T. Rare Anal Canal Cancer with Secondary Extramammary Paget\u0026rsquo;s Disease (Pagetoid Spread) Complicated by Squamous Cell Carcinoma of the Skin. Case Rep Surg. 2021;2021:9944886. doi:10.1155/2021/9944886.\u003c/li\u003e\n \u003cli\u003eKosano M, Kiniwa Y, Mikoshiba A, Iwaya M, Okuyama R. Clinical Features of Pagetoid Spread: Analysis of Perianal Lesions Associated with Anal Canal Adenocarcinoma and Perianal Primary Extramammary Paget Disease. J Dermatol. 2023;50:546\u0026ndash;50. doi:10.1111/1346-8138.16744.\u003c/li\u003e\n \u003cli\u003eNagai Y, Kazama S, Yamada D, et al. Perianal and Vulvar Extramammary Paget Disease: A Report of Six Cases and Mapping Biopsy of the Anal Canal. Ann Dermatol. 2016;28(5):624\u0026ndash;8. doi:10.5021/ad.2016.28.5.624.\u003c/li\u003e\n \u003cli\u003eLi M, Yao X. Goblet Cell Adenocarcinoma of the Anal Canal with Perianal Paget Disease: A Rare Case Report with Literature Review. Medicine (Baltimore). 2023;102(16):e33598. doi:10.1097/MD.0000000000033598.\u003c/li\u003e\n \u003cli\u003eSarmiento JM, Wolff BG, Burgart LJ, Frizelle FA, Ilstrup DM. Paget\u0026apos;s Disease of the Perianal Region--An Aggressive Disease? Dis Colon Rectum. 1997;40(10):1187\u0026ndash;94. doi:10.1007/BF02050924.\u003c/li\u003e\n \u003cli\u003eIsik O, Aytac E, Brainard J, et al. Perianal Paget\u0026rsquo;s Disease: Three Decades Experience of a Single Institution. Int J Colorectal Dis. 2016;31(1):29\u0026ndash;34. doi:10.1007/s00384-015-2334-4.\u003c/li\u003e\n \u003cli\u003eElshikh M, Menias CO, Amer AM, et al. Tumors and Tumorlike Conditions of the Anal Canal and Perianal Region: MR Imaging Findings. RadioGraphics. 2016;36(5):1339\u0026ndash;53. doi:10.1148/rg.2016160028.\u003c/li\u003e\n \u003cli\u003eGoldman S, Ihre T, Lagerstedt U, Svensson C. Perianal Paget\u0026rsquo;s Disease: Report of Five Cases. Int J Colorectal Dis. 1992;7(3):167\u0026ndash;9. doi:10.1007/BF00341258.\u003c/li\u003e\n \u003cli\u003eDelaunoit T, Neczyporenko F, Duttmann R, et al. Perianal Paget\u0026rsquo;s Disease: Case Report and Review of the Literature. Acta Gastroenterol Belg. 2004;67(2):228\u0026ndash;31. PMID:15239223.\u003c/li\u003e\n \u003cli\u003eMcCarter MD, Quan SH, Busam K, et al. Long-Term Outcome of Perianal Paget\u0026rsquo;s Disease. Dis Colon Rectum. 2003;46(5):612\u0026ndash;6. doi:10.1007/s10350-004-6614-5.\u003c/li\u003e\n \u003cli\u003eMarchesa P, Fazio VW, Oliart S, et al. Long-Term Outcome of Patients With Perianal Paget\u0026apos;s Disease. Ann Surg Oncol. 1997;4(6):475\u0026ndash;80. doi:10.1007/BF02303765.\u003c/li\u003e\n \u003cli\u003eIshii K, Takahashi H, Tsuji H, et al. Clinical and Pathological Analysis of Perianal Paget\u0026rsquo;s Disease: A Case Report and Review of 89 Cases. Cancer Diagn Progn. 2025;5(1):49\u0026ndash;55. doi:10.21873/cdp.10152.\u003c/li\u003e\n \u003cli\u003eKim CW, Kim YH, Cho MS, et al. Perianal Paget\u0026rsquo;s Disease: Case Report and Literature Review. Ann Coloproctol. 2014;30(5):241\u0026ndash;4. doi:10.3393/ac.2014.30.5.241.\u003c/li\u003e\n \u003cli\u003eGuo JJ, Jiao XD, Wu Y, Qin BD, Liu K, Zang YS. Response to Pyrotinib in a Chinese Patient with Bone-Metastatic Scrotal Paget\u0026apos;s Disease Harboring Triple Uncommon HER2 Mutation: A Case Report. Onco Targets Ther. 2020;13:6289-6293. Published 2020 Jun 30. doi:10.2147/OTT.S244814\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Extramammary Paget’s Disease, perianal region, adenocarcinoma","lastPublishedDoi":"10.21203/rs.3.rs-7278139/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7278139/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e\u003cp\u003eExtramammary Paget\u0026rsquo;s Disease (EMPD) is a rare malignancy commonly affecting anogenital and apocrine gland-rich areas. Perianal EMPD usually presents with skin involvement and, rarely, affects the anal mucosa. Patients typically experience non-specific symptoms such as itching, pain, and erythematous plaques. EMPD has a high recurrence rate and a risk of progression to malignancy. This case report presents a rare perianal EMPD case complicated by adenocarcinoma development.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eA 58-year-old male patient with chronic perianal lesions was initially misdiagnosed and treated inadequately. Advanced imaging (MRI and PET-CT) confirmed malignancy suspicion, and biopsy revealed invasive adenocarcinoma arising from EMPD. Surgical management included wide local excision, inguinal and iliac lymph node dissection, and perianal reconstruction.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eEarly diagnosis and aggressive surgical treatment are crucial in reducing recurrence risk. Lymph node metastases and invasive components significantly impact prognosis. Long-term follow-up and research on molecular markers may contribute to better treatment approaches.\u003c/p\u003e","manuscriptTitle":"A Rare Case of Perianal Extramammary Paget’s Disease Associated with Adenocarcinoma: A Case Report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-12 20:27:32","doi":"10.21203/rs.3.rs-7278139/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"39d67c65-4a08-4801-98f9-593ff1bfee73","owner":[],"postedDate":"September 12th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-02-02T10:12:35+00:00","versionOfRecord":[],"versionCreatedAt":"2025-09-12 20:27:32","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7278139","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7278139","identity":"rs-7278139","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}