Primary extramammary Paget’s disease with colon cancer
Year: 2025
Type: article
Abstract: Dear Editor, Extramammary Paget’s disease (EMPD) is a rare skin cancer with a predilection for the genitalia and axillae. The tumor presents as erythematous or leukoplakia-like plaques, which slowly enlarge to form erosions and occasionally nodules or masses.[1,2] Primary EMPD is distinguished from secondary EMPD. Secondary EMPD is defined as an infiltration of underlying cancer of the rectum, anus, urethra, bladder, vagina, or uterus, leading to the formation of a rash on adjacent skin.[3,4] Herein, we report a case of primary EMPD with colorectal cancer. A 75-year-old male was referred to our hospital for the evaluation of a nodule on the root of his penis. His past medical history was unremarkable. Physical examination revealed that a reddish dome-shaped nodule, 10 mm in diameter, on the root of the penis [Figure 1a] and enlarged lymph nodes in the left inguinal region. We performed a biopsy on the nodule to make a diagnosis. Histopathological examination showed proliferation of atypical cells with abundant pale cytoplasm in the epidermis and dermis, showing an infiltrative pattern with numerous lymphovascular invasions [Figure 1b and c]. In immunohistochemical examination, the cells were diffusely positive for cytokeratin 7 (CK7) [Figure 1d], cytokeratin 20 (CK20) [Figure 1e], gross cystic disease fluid protein-15 (GCDFP-15) [Figure 1f], GATA-binding protein 3 (GATA3) [Figure 1g], and human epidermal growth factor type 2 (HER2), whereas caudal-type homeobox protein 2 (CDX-2) and Uroplakin-r were negative. It has been shown that the expression of GATA3 is associated with secondary EMPD with bladder urothelial carcinoma.[5] However, computed tomography imaging did not show any evidence of tumors in the urinary tract system, and no tumor cells were detected by urine cytology. Therefore, the patient was diagnosed as having primary EMPD with lymph node metastasis and he underwent radiotherapy. Both the nodule and enlarged lymph nodes tended to shrink with radiotherapy (intensity-modulated radiation therapy). One month after the start of radiotherapy, anemia progressed rapidly. The patient was referred to the department of gastroenterology for examination of anemia, and upper and lower gastrointestinal endoscopy was performed. The lower endoscopy revealed a mass in the transverse colon, and a biopsy was performed. Histopathological examination showed that proliferation of atypical tall columnar cells with chromatin-rich round or irregularly shaped nuclei with adherent glandular ducts [Figure 1h]. Immunohistochemical examination revealed that the cells were negative for CK7 [Figure 1i] and GATA3. The cells were positive for CK20 [Figure 1j] and CDX-2 [Figure 1k]. Therefore, a diagnosis of primary EMPD with transverse colon cancer was made.Figure 1: (a) A nodule on the left root of the penis and the white dotted line indicates depigmentation. (b) Tumor cells proliferated in the epidermis and dermis (H and E, ×40). (c) High magnification view of showed Paget’s cells in the epidermis (H and E, ×200). (d) Immunohistochemical staining: The tumor cells were positive for CK7 (H and E, ×200) (e) and positive for CK20 (H and E, ×200) (f) and positive for gross cystic disease fluid protein-15 (H and E, ×200) (g) and positive for GATA-binding protein 3 (H and E, ×200). (h) Atypical cells proliferated with glandular formation in the colon (H and E, ×40). (i) The tumor cells of the colon were negative for CK7 (H and E, ×200) (j) and positive for CK20 (H and E, ×200) (k) and positive for caudal-type homeobox protein 2 (H and E, ×200).EMPD was first identified in 1889 and it is characterized by proliferation of Paget’s cells within the epidermis.[1,2] In immunohistochemical examination, the cells are usually positive for CK7 and GCDFP-15. Secondary EMPD is associated with an underlying malignancy such as carcinoma of the colon, anus, bladder, urethra, uterus, or vagina. It typically presents with contiguous skin lesions from adjacent organs such as the anus, glans penis, and perineum. Results of immunohistochemical examination such as CK20, GCDFP-15, and GATA3 are also useful for differential diagnosis.[3-5] Our patient had a nodule on the root of his penis. However, there was no evidence of a lesion in the urethra, glans penis, or anus. Initially, we started radiation therapy for the tumor as primary EMPD. The colon tumor was found 1 month later. Although it was necessary to differentiate skin metastasis of colon cancer because primary skin tumor was positive for CK20, the histopathological features of the colon tumor were different from those of the skin nodule. There were a few reports of EMPD with other malignancies.[6-8] About 25% of EMPD are thought to be associated with other malignancies, with the frequency depending on the site of tumor origin.[3,6] Approximately 11%–20% of vulvar EMPD have been reported to be associated with visceral malignancies[6]. In addition, it has been reported that the risk of developing colorectal adenocarcinoma in patients with anal Paget’s disease including secondary EMPD was 18.5%.[7] There have been several reports of EMPD of the vulva preceding a urogenital malignancy, but the time between diagnosis of EMPD and discovery of the malignancy was reported to range from 1 to 14 years.[8] In conclusion, clinical physicians have to be careful about the possibility of double cancer in EMPD. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent form. In the form the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that his name and initials will not be published and due efforts will be made to conceal the identity, but anonymity cannot be guaranteed. Data availablilty statement Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.
Source: Dermatologica Sinica
Authors: Anna Takeuchi, Hiromi Higaki-Mori, Yuichi Yoshida
Institution: Tottori University
Language: English
Topic: Cancer and Skin Lesions
Subfield: Dermatology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $70
OpenAlex ID: W4407808970