The Ewha Medical Journal
Ewha Womans University College of Medicine and Ewha Medical Research Institute
Case Report

Aggressive Clinical Deterioration of Recurrent Extramammary Paget’s Disease: A Case Report

Sewon Lee1,*, Sang Yoon Kim2,*, Heejin Bang3, Kyoung Eun Lee1
1Division of Hematology-Oncology, Department of Internal Medicine, School of Medicine, Ewha Womans University, Seoul, Korea
2Department of Internal Medicine, Myongji Hospital, Hanyang University College of Medicine, Goyang, Korea
3Department of Pathology, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea
Corresponding author: Kyoung Eun Lee, Division of Hematology-Oncology, Department of Internal Medicine, School of Medicine, Ewha Womans University Hospital, 1071, Anyangcheon-ro, Yangcheon-gu, Seoul 07985, Korea, Tel: 82-2-2650-5030, Fax: 82-2-2650-5062, E-mail:

* These authors contributed equally to this work.

© Copyright 2022 Ewha Womans University College of Medicine and Ewha Medical Research Institute. This is an Open-Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Received: Aug 12, 2022Oct 12, 2022; Accepted: Oct 13, 2022

Published Online: Oct 31, 2022


Extramammary Paget’s Disease (EMPD) is a rare intraepithelial malignancy of apocrine bearing glands, which occur usually in the perianal region, vulva, scrotum, penis and ax-illa. Most of the disease are treated by surgical resection and the prognosis is generally good. Even though recurrent disease, it is usually slowly progressed with good prognosis. Here we describe the case of a 70-year-old male who has presented with initially just as an EMPD component of squamous cell carcinoma in inguinal skin, but he showed recur-rence of EMPD. The disease has progressed rapidly, finally he died of that EMPD in 2 months of recurrence. The purpose of this study is to report the rare case of fulminant disease course of EMPD after recurrence.

Keywords: Paget’s disease; extramammary; Aggressive extramammary Paget’s disease


Paget’s disease is a rare intraepithelial neoplasm. It has two sub-types, one is mammary Paget’s disease (MPD) and the other is extramammary Paget’s disease (EMPD) which occurs in other than mammary area. Morphology and histology of these two subtypes are the same. The origin of EMPD is not clear but suggested that they are originated form apocrine bearing glands, such as the perianal region, vulva, scrotum, penis and axilla. The clinical features of EMPD can be non-specific such as chronic eczematous cutaneous disease, therefore misdiagnosis as an inflammatory or infective skin condition is common. Its final diagnosis is often delayed for a long time. The prognosis of this disease entity is variable according to clinical situation and recent analysis of 2,000 EMPD patients showed that EMPD in scrotal lesion, concurrent malignancy, metastatic lesion, old age and male are the risk factors for mortality [14]. Chan et al. reported that 8.3% of EMPD patients showed concurrent malignancy in colon and prostate [5]. Sometimes, there are co-existing squamous cell carcinoma in situ in the skin [6].

Surgical resection with negative margin is the considered to be the standard of care in EMPD, other options include imiquimod 5% topical cream, modified peripheral Mohs surgery and radiation therapy [7,8]. Although recurrence is common, the disease has a slow progression and paucity metastasis, so the prognosis is generally good.

Here, we describe a case of rapid progressed EMPD patient, who showed fulminant disease course in two months.

Case Report

A 70-year-old man presented with discomfort in the right inguinal area. He had a history of skin malignancy in the right inguinal area three years ago and treated with surgical resection (wide excision and split thickness skin graft from thigh). The histopathological study at that time showed mostly squamous cell carcinoma (3×2.5 cm sized with depth of 4 mm invasion) and focal EMPD component (Fig. 1). During the last three years, he did not visit the clinic. This time he visited the hospital due to right inguinal discomfort. In physical examination, he showed palpable right inguinal lumps without obvious skin change. CT scan showed difuse skin thickening and subcutaneous infiltration at right inguinal and pubic area with mild lymph node enlargements. There was no other visceral lesion in the CT scan (Figs. 2A, 2B). Blood test showed no specific finding except for a mild CEA elevation (10.4 ng/mL, reference range 0–5.0 ng/mL). He underwent a punch biopsy in right inguinal lymph nodes area. The pathology showed the consistent findings of EMPD and immunohistochemical stains showed CK7 (+), CEA (+) and HER2 SISH (–). Further groin dissection was planned. However, he wanted to postpone surgery due to private reasons.

Fig. 1. Histopathologic images of skin lesion. (A) Initial skin biopsy of pubic area, the epidermis shows the Paget cells with abundant clear cytoplasm with intracellular and extracellular mucin production (H&E, ×200). (B) Positive staining for CK7 (IHC, ×200). (C) Positive staining for CEA (IHC, ×200). IHC, immunohistochemical.
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Fig. 2. Radiologic findings. (A) Abdomen CT reveals diffuse skin thickening and subcutaneous infiltration at right inguinal and pubic area with lymphadenitis at recurrence (arrows), (B) no other visceral lesion at Abdominal CT of recurrence, (C) FDG-PET CT of after 2 months. (D–F) Abdominal CT after 2 months.
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However, two months later, he visited the clinic again due to severe back pain. Spine MRI showed several metastatic lesions in the lumbar spine, sacrum and pelvic bones. The blood test showed anemia with hemoglobin level of 6.1 g/dL and elevated CEA level (21.2 ng/mL) compared with results obtained two months ago. Endoscopic findings including colonoscopy and duodenofiberscopy showed no bleeding tendency or no specific lesion. Subsequent CT scan showed multiple hepatic metastasis, various lymph nodes enlargements, and bony metastasis in abdomen. However no significant change of inguinal lymphadenopathies was documented as EMPD two months ago. FDG PET scan showed similar findings (Figs. 2C2F). At the time of admission, the level of bilirubin was in normal range, but suddenly he showed jaundice with increasing serum bilirubin level. He underwent liver biopsy and the pathologic results showed mmetastatic carcinoma from the previous EMPD with the same immunohistochemical results of CK7 (+), CEA (+), GCDFP-15(+), HER2 (–) (Fig. 3). We planned chemotherapy for the metastatic EMPD. However just a few days, he showed rapid clinical deterioration with hepatic failure (Fig. 4). Eventually, on the 12nd admission day, he died of the disease.

Fig. 3. Histopathologic images of liver lesion. (A) Liver biopsy, the Paget cells clusters with clear cytoplasm in hepatic sinusoid (H&E, ×100). (B) Positive staining for CK7 (IHC, ×200). (C) Positive staining for CEA (IHC, ×200). IHC, immunohistochemical.
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Fig. 4. The increment of bilirubin within 2 weeks.
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This is the first report about a fulminant disease course of a metastatic, recurrent EMPD to this time in our country.


EMPD is a rare slow-growing cutaneous adenocarcinoma that presents as an erythematous, eczematous plaque outside the mammary gland. This neoplastic lesion is often delayed before diagnosis, but usually resulted good prognosis. The range of EMPD recurrence is very wide, for the example, the recurrence of EMPD in vulva varies from 12% to 61% [5,9]. On multiple variate analysis, dermal invasion, lymph node metastasis and elevated serum CEA associated with poor prognosis have been reported [10]. The analysis from large scale patients showed that surgery is a protective factor and radiation is a risk factor for EMPD survival [4]. Although the invasion of dermis is uncommon, if once the EMPD invades into the dermis, that could get metastatic characteristics [11]. Interestingly, Chanda et al. reported that 46% of patients with EMPD associated with an underlying carcinoma developed metastatic disease, compared to 18% of patients with a non-invasive disease [12]. In a large study of 1,439 patients with invasive EMPD, disease specific five year survival was 94.9% (95% CI 92.7%–96.5%) for localized disease, 84.9% (95% CI 77.4%–90.0%) for regional disease and 52.5% (95% CI 29.3%–71.3%) for distant disease. For patients diagnosed with distant spread the outlook was still favorable since more than half of all patients were alive at 5 years of observation [13].

In the case of our patient, he had the risk factor of concurrent skin squamous cell carcinoma, his EMPD presented just as a minor component of that skin squamous cell carcinoma. However, after relapse, EMPD was the only lesion except squamous cell carcinoma. Meanwhile, the most interesting things in this case is that he rapidly progressed to death within three months after diagnosis of relapse. Actually this patient visited EMPD recurrence after 3 years of primary treatment, and there was an evidence of dermal invasion such as subcutaneous infiltrative lesions in the CT scan without visceral or distant metastasis. However, two month’s break resulted in distant failure and finally death. Thus, the findings of regional node involvement mimicking lymphadenitis would be a grave sign for rapid distant progression. Recently one study has shown that systemic treatment of EMPD in the disease is metastatic, especially some EMPD showed HER2 positivity and anti-HER2 therapy could result in a durable response and durable survival [14].

It is still uncertain whether long standing local recurrent disease will transform to invasive form. Chang et al. reported that chemokine receptors, CXCR4 and CXCR7 are associated with poor outcome and that they can be used as prognostic biomarkers [15]. In the recent basic and translational research, many other disease mechanisms are under elucidation including RAS-RAF-MEK-ERK signaling, PI3K-AKT-mTOR signaling and androgen-AR signaling. In the future, diagnostic and therapeutic application of this research outcome would make the management of EMPD much better.


EMPD is an intraepithelial malignancy, which shows recurrence and occasional metastasis, with usually good prognosis. Although several studies reported this disease entity, the focus was on the initial skin lesions with limited experience of disease locations and surgical outcomes. This study is the first report of a poor clinical outcome in three months of presentation involving aggressive deterioration of metastatic EMPD. The findings aid physicians in selectively managing EMPD patients, especially those diagnosed with the disease concomitant with squamous cell carcinoma of skin, for enhanced clinical out-comes.


We are grateful to Dr. Min Sun Cho in the Pathology department of Ewha Womans University hospital for her contribution to this work.

Conflict of Interest

No potential conflict of interest relevant to this article was reported.

Author Contribution

Conceptualization: Lee KE

Formal Analysis: Kim SY, Bang H, Lee KE

Investigation: Lee S, Bang H, Lee KE

Methodology: Lee S, Bang H, Lee KE

Project Administration: Lee S, Lee KE

Writing – Original Draft: Lee S, Kim SY, Lee KE

Writing – Review & Editing: Lee S, Kim SY, Bang H, Lee KE

Ethics Approval and Consent to Participate

This study was done in Ewha Womans University Mokdong Hospital and the study was approved by our own Institutional Review Board (No. EUMC 2018-08-031, Ewha Womans Medical Center).



Tanaka VDA, Sanches JA, Torezan L, Niwa AB, Festa Neto C. Mammary and extramammary Paget's disease: a study of 14 cases and the associated therapeutic difficulties. Clinics. 2009; 64(6):599-606


Lopes Filho LL, Lopes IMRS, Lopes LRS, Enokihara MMSS, Michalany AO, Matsunaga N. Mammary and extramammary Paget's disease. An Bras Dermatol. 2015; 90(2):225-231


Lloyd J, Flanagan AM. Mammary and extramammary Paget's disease. J Clin Pathol. 2000; 53(10):742-749


Yao H, Xie M, Fu S, Guo J, Peng Y, Cai Z, et al. Survival analysis of patients with invasive extramammary Paget disease: implications of anatomic sites. BMC Cancer. 2018; 18(1):403


Chan JYW, Li GKH, Chung JHP, Chow VLY. Extramammary Paget’s disease: 20 years of experience in Chinese population. Int J Surg Oncol. 2012; 2012:416418


Baldovini C, Betts CM, Reggiani C, Reggiani M, Foschini MP. Ultrastructural examination of a case of pagetoid Bowen disease exhibiting immunohistochemical features in common with extramammary Paget disease. Am J Dermatopathol. 2015; 37(7):e83-e86


Guerra R, Misra S. Management of extramammary Paget's disease: a case report and review of the literature. Case Rep Dermatol Med. 2013; 2013:436390


Mehrtens SH, Tharakaram S. Extramammary Paget’s disease. N Engl J Med. 2017; 376(17):e35-e35


Nitecki R, Davis M, Watkins JC, Wu YE, Vitonis AF, Muto MG, et al. Extramammary Paget disease of the vulva: a case series examining treatment, recurrence, and malignant transformation. Int J Gynecol Cancer. 2018; 28(3):632-638


Zhang N, Gong K, Zhang X, Yang Y, Na Y. Extramammary Paget's disease of scrotum—report of 25 cases and literature review. In: Droller MJ, editor. Urologic oncology: seminars and original investigations. Amsterdam: Elsevier. 2010; p. 28-33


Fukuda K, Funakoshi T. Metastatic extramammary Paget’s disease: pathogenesis and novel therapeutic approach. Front Oncol. 2018; 8:38


Chanda JJ. Extramammary Paget's disease: prognosis and relationship to internal malignancy. J Am Acad Dermatol. 1985; 13(6):1009-1014


Karam A, Dorigo O. Treatment outcomes in a large cohort of patients with invasive extramammary Paget's disease. Gynecol Oncol. 2012; 125(2):346-351


Ichiyama T, Gomi D, Fukushima T, Kobayashi T, Sekiguchi N, Sakamoto A, et al. Successful and long-term response to trastuzumab plus paclitaxel combination therapy in human epidermal growth factor receptor 2-positive extramammary Paget's disease: a case report and review of the literature. Mol Clin Oncol. 2017; 7(5):763-766


Chang K, Li GX, Kong YY, Shen XX, Qu YY, Jia ZW, et al. Chemokine receptors CXCR4 and CXCR7 are associated with tumor aggressiveness and prognosis in extramammary Paget disease. J Cancer. 2017; 8(13):2471-2477