Multidisciplinary Approach for the Management of Penoscrotal Extramammary Paget's disease –An eUROGEN study

Highlights

• Penoscrotal extramammary Paget's disease is a rare condition and the management should involve a multidisciplinary approach.

• Surgical excision of the lesion with a 5 mm macroscopic margin and additional mapping biopsies in our cohort produces results that are comparable to those of other published case series.

• Following histological confirmation of the disease, we propose an algorithm for the stratification of these patients to aid management.

Abstract

Introduction

We reviewed the medical and surgical management and long-term outcomes for patients diagnosed with penoscrotal extramammary Pagets disease (EMPD) within an eUROGEN centre.

Patients and Methods

Retrospective review of cases from an institutional database with biopsy proven penoscrotal EMPD.

Results

A total of 10 patients were identified with penoscrotal EMPD over a 10-year period. Two patients had a previous history of gastrointestinal and urogenital cancers (20%) and no synchronous or metachronous cancers were identified. Eight patients with non-invasive EMPD (80%) underwent wide local excision of the affected skin, with at least a 5mm macroscopic resection margin and in selected cases simultaneous multiple mapping biopsies around the lesion were performed. Residual disease was present at the margins in seven patients (87.5%), of which three required further surgical excision or adjuvant topical immunotherapy (42.8%). Recurrence after complete excision was 12.5% and was successfully treated with topical imiquimod immunotherapy and CO₂ laser therapy. Two patients (20%) had invasive carcinoma and metastatic disease at diagnosis.

Conclusion

Reported recurrence rates of non-invasive penoscrotal EMPD are high and residual disease is present in most cases requiring either close clinical surveillance or adjuvant treatment. We propose an algorithm in the management of this rare disease.

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.