Genito-Urinary Extramammary Pagets disease: Recognition and outcomes of distinct histological subtypes

Introduction & Objectives: Genito-Urinary Extramammary Pagets Disease (EMPD) is a rare neoplasm that occurs in regions abundant in apocrine glands, or as a secondary intraepithelial spread of EMPD associated with another underlying carcinoma. The former occurs on peno-scrotal skin and can be in-situ or invasive. The latter occurs primarily on the inner precpuce or glans. Management and prognosis differ between these subtypes.

Materials & Methods: All patients treated for Genito-Urinary EMPD between January 2003 and July 2017 at our specialist unit were identified through histology samples coded as "Pagets". Surgical management, positive margin rate, nodal involvement and survival (Kaplan Meier analysis) were assessed.

Results: 30 cases were identified, with a median age at diagnosis of 73 years (IQR 70.3 to 79.8). There were 7 cases of primary in-situ apocrine EMPD and 14 of invasive apocrine tumours. There were 8 cases of secondary urothelial-related disease, of which 2 cases showed invasion. There was 1 case of urethral squamous cell carcinoma related disease.

All 30 patients underwent surgical management with wide local excision (n=24), glansectomy (n=4), circumcision (n=1) or distal urethrectomy (n=1). 50% of those who had a wide local excision had microscopic positive margins despite a 2cm macroscopic surgical margin beyond the visible disease. However, this did not affect overall survival.

2/7 patients with in-situ apocrine EMPD recurred with further in-situ disease. None of the patients with in-situ EMPD died of their disease.

10/14 invasive apocrine tumours had pathological nodal staging with either inguinal dynamic sentinel lymph node biopsies (DSNB) and/or groin dissection +/- pelvic lymph node dissection. 5 patients had inguinal and/or pelvic node involvement with extracapsular spread (ECS) and 1 had one inguinal node involved without ECS. 1,3 and 5-year overall survival for all the invasive apocrine EMPD was 83%, 55% and 37% respectively.

7/9 secondary EMPD had a previous history of urothelial bladder cancer (6 had cystectomy). Survival data was available for 4 of these patients with 3 dying within 9, 11 and 16 months of EMPD diagnosis.

Conclusions: Genito-Urinary EMPD is a rare malignancy that can be categorised into three different entities. It is important to recognise these subtypes as they have different pathobiology and outcomes. In-situ apocrine disease has an excellent prognosis. Node positive invasive apocrine disease carries a poor prognosis despite adjuvant / palliative chemotherapy. Secondary Urothelial EMPD occurs on the glans / inner prepuce, has a poor prognosis and is often diagnosed several years after the initial cancer diagnosis.