Urologic Oncology: Seminars and Original Investigations
Original StudyMultidisciplinary Approach for the Management of Penoscrotal Extramammary Paget's disease –An eUROGEN study
Introduction
Extramammary Pagets disease (EMPD) is a rare intraepithelial neoplasm with an incidence of 6 per million person-years [1]. It usually affects the apocrine gland-bearing areas, such as the vulva, perianal skin and axilla [2]. Penoscrotal EMPD accounts for only 14% of reported cases of EMPD [2].
Macroscopically the lesions appear as well-circumscribed erythematous pruritic plaque which can also ulcerate, bleed and encrustate. [2,[3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14]]. It is frequently misdiagnosed as eczema, seborrhoeic dermatitis, contact dermatitis, lichen sclerosus, psoriasis or fungal infection, leading to a delayed diagnosis and onward specialist referral; failure to respond to topical treatment prescribed erroneously for psoriasis is a common clinical feature [2,5].
Microscopically EMPD is characterized by the presence of Paget cells [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16]. These are atypical glandular-like cells, larger than keratinocytes with a granular amphophilic to basophilic cytoplasm [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16]. They occasionally have a signet-ring appearance due to the presence of intra-cytoplasmic sialomucin making them appear paler than the adjacent keratinocytes and forming nests within the basal and parabasal zones of the skin [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16]. Confirmatory immunohistochemical testing is almost always performed with cytokeratin-7 (CK7) immunostaining [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16].
Previous reports suggest that EMPD is a cutaneous marker for coexisting malignancies and the underlying malignancy is related to the location of EMPD [2,4,[13], [14], [15], [16], [17], [18]]. Vulvar EMPD has been associated with tumours of the female genitourinary system, perianal EMPD with gastrointestinal adenocarcinoma and penoscrotal EMPD with tumours of the urinary or gastrointestinal tract in approximately 11% of patients [[2], [3], [4],16,17]. Anogenital EMPD has also been associated with subjacent adnexal carcinoma [19]. The associated malignancy may be synchronous or metachronous – preceding or succeeding the diagnosis of EMPD.
The European Reference Networks (ERN) are an EU initiative for rare cancers and the eUROGEN workstream oversees rare genital malignancies. This allows centralisation of rare cancers to specialist centres and this study includes patients from one such centre.
Once a diagnosis of EMP is confirmed, treatment is tailored to each individual case followed by close surveillance. The study aims to review the management using a multidisciplinary approach with dermatologists and oncologists in order to limit the extent of surgical resection. We present the outcomes within an eUROGEN centre and propose a multidisciplinary management algorithm.
Section snippets
Patients and Methods
All cases with EMPD located in the penoscrotal area and treated within a single eUROGEN centre were identified via a pathology database and underwent a specialist pathology re-review. A retrospective review of the medical records was conducted following approval from the local governance committee. We performed a literature search using Pubmed/Medline EMBASE and Cochrane Library databases to identify other published case series and existing evidence regarding the management of this disease.
Results
We identified 10 cases of penoscrotal EMPD treated in our institution since 2007 (Table 1).
Discussion
Currently there is no consensus or guidelines available on the staging, prognosis and management for penoscrotal EMPD due to the rarity of the disease. This is the largest published cohort from a single centre in Europe. The majority of clinicians use anecdotal experience and previous published case series to manage these cases and Table 2 provides a summary of the 16 case series published in the literature.
Penoscrotal EMPD is frequently misdiagnosed leading to a delayed specialist referral [[2]
Conclusion
Penoscrotal EMPD is rare and predominantly diagnosed in elderly men. Surgical excision with macroscopically clear margins is the primary treatment in our series and in previous published reports. The recurrence rate in our cohort is high due to most cases being R1 resections as surgery relied on macroscopic clearance. However, the advanced age and comorbidities in this patient cohort often precludes offering further extensive surgery and adjuvant topical or laser treatment was used. The results
Ethical standards
This is a retrospective study with anonymized data collection approved by our local governance committee. All clinical photographs and histological imaging were taken with patient consent.
Conflict of interest
We declare no completing interest.
Acknowledgment
This study was supported by the NIHR Biomedical Research Centre University College London Hospital.
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