Unusual Presentation of Ectopic Extramammary Paget Disease
Extramammary Paget disease (EMPD) is a malignant tumor typically found in apocrine-rich areas of the skin, particularly in the anogenital region. Some germinative apocrine-differentiating cells might exist on the trunk, preferentially in Asian individuals. Ectopic EMPD arises in nonapocrine-bearing areas, specifically the nongerminative milk line. We present a case of a 67-year-old Thai man with a slowly progressive, pruritic, erythematous to brown plaque on the right lower back of 30 years’ duration. Histopathologic examination of 2 scouting biopsies revealed a proliferation of large cells with pleomorphic nuclei, prominent nucleoli, and abundant pale to clear cytoplasm within the epidermis. In one of the biopsies, tumor cells were found in the dermis with an infiltrative growth pattern. Immunohistochemically, the tumor cells were positive for cytokeratin 7, carcinoembryonic antigen, and gross cystic disease fluid protein 15. Based on these findings, a diagnosis of ectopic EMPD was made.
Practice Points
- Ectopic extramammary Paget disease (EMPD) is a rare presentation of EMPD that is histologically identical to EMPD.
- Ectopic EMPD can be associated with underlying malignancy and therefore warrants a thorough workup.
Comment
Extramammary Paget disease is a malignant tumor typically found in apocrine-rich areas of the skin, particularly the anogenital skin. It is categorized as primary or secondary EMPD. Primary EMPD arises as an intraepithelial adenocarcinoma, with the Toker cell as the cell of origin.3 Secondary EMPD represents a cutaneous extension of an underlying malignancy (eg, colorectal, urothelial, prostatic, gynecologic).4
Ectopic EMPD arises in nonapocrine-bearing areas, specifically the nongerminative milk line. A review of the literature using Google Scholar and the search term ectopic extramammary Paget disease showed that there have been at least 30 cases of ectopic EMPD reported. Older men are more commonly affected, with a mean age at diagnosis of approximately 68 years. Although the tumor is most commonly seen on the trunk, cases on the head, arms, and legs have been reported.5
This tumor is most frequently seen in Asian individuals, as in our patient, with a ratio of approximately 3:1.5 Interestingly, triple or quadruple EMPD was reported in 68 Japanese patients but rarely has been reported outside of Japan.6 It is thought that some germinative apocrine-differentiating cells might preferentially exist on the trunk of Asians, leading to an increased incidence of EMPD in this population5; however, the exact reason for this racial preference is not completely understood, and more studies are needed to investigate this association.
,Diagnosis of ectopic EMPD is made histologically. Tumor cells have abundant pale cytoplasm and large pleomorphic nuclei with prominent nucleoli. The cells are arranged in small groups or singly within the basal regions of the epidermis. In longstanding lesions, the entire thickness of the epidermis may be involved. Uncommonly, the tumor cells may invade the dermis, such as in our patient. On immunohistochemistry, the tumor cells stain positive for carcinoembryonic antigen, epithelial membrane antigen, and low-molecular-weight cytokeratins (eg, cytokeratin 7). Many of the tumor cells also express gross cystic disease fluid protein 15, which helps exclude cutaneous invasion of secondary EMPD.7-9 Cases of primary cutaneous apocrine carcinoma can have similar histologic and immunohistochemical findings to invasive EMPD, which further supports the possible apocrine derivation of Paget disease. In our patient, we considered the diagnosis of primary cutaneous apocrine adenocarcinoma with epidermotropism; however, we favored the diagnosis of ectopic EMPD with dermal invasion given the extensive epidermal-only involvement seen in one of the biopsies, which would be unusual for primary cutaneous apocrine adenocarcinoma.
Our patient had no identified underlying malignancy upon further workup; however, many cases of EMPD have been associated with an underlying malignancy.9-15 Several authors have reported a range of underlying malignancies associated with EMPD, with the incidence ranging from 11% to 45%.9-15 The location of the underlying internal malignancy appears to be closely related to the location of the EMPD.11 It is recommended that a thorough workup for internal malignancies be performed, including a full skin examination, lymph node examination, colonoscopy, cystoscopy, and gynecologic/prostate examination, among others.
No known differences in the prognosis or associated underlying malignancies between ectopic and ordinary EMPD have been reported; however, it has been noted that EMPD with invasion into the dermis does correlate with a more aggressive course and worse prognosis.8 Treatment includes surgical removal by Mohs micrographic surgery or wide local excision. Long-term follow-up is required since recurrences can be frequent.11-15
