Introduction
Extramammary Paget’s disease (EMPD) of the scrotal or penile skin was first described by Crocker1 as a rare cuta- neous neoplasm that was clinically and histopathologi- cally similar to mammary Paget’s disease, which was first reported by James Paget.2 EMPD has diverse clinical manifestations which include exfoliative, exudative, verrucous, or even hypopigmented patches that are accom- panied by pruritus or burning sensations, which ulti- mately mimic treatment-refractory eczema. This disease predominantly affects women and is primarily found in areas rich in apocrine or eccrine glands. Commonly affected areas include the vulva, anus, axilla, penile shaft, and groin, and less common areas include the eyelid and umbilicus.3,4 This disease sometimes accompanies an internal or underlying adnexal malignancy.5–7 Histopath- ological analysis indicates that EMPD can also invade the dermis to increase the number of Paget’s cells typically found within the epidermis and eccrine apparatus. Surgi- cal procedures, such as conventional radical excision and Mohs micrographic surgery (MMS), are the only thera- pies to eradicate EMPD, but there are issues with recur- rence and grave outcomes.
There have been few documented multicenter studies of EMPD in Korea compared with the number that have been conducted in Western populations. The aim of this study was to investigate the epidemiology, clinical and histopathological features, associated internal malignan- cies, treatments, and clinical outcomes of Korean EMPD patients. These studies are required to establish safer and more effective management guidelines for Korean EMPD patients.
Materials and methods
This retrospective study was based on a review of 194 EMPD patient cases. The cases were taken from 16 university hospitals from all over Korea over a five-year period from January 2002 to December 2006. Clinical data for each patient included gender, age, duration of illness, location, clinical presentation, symptoms, presence of underlying non-malignant disease, presence of other internal malignancies from medical records, and other information obtained via telephone contact if applicable. An internal malignancy was considered to be genuinely associated with EMPD if the two malignancies occurred within the same five-year period. If the interval between diagnosis of EMPD and diagnosis of malignancy was greater than five years, we determined whether the malignancy was genuinely associated, either by using anatomical correlations between the two diseases or by assessing for the presence of immunohistochemical CK20-positive Paget’s cells. Histological sections were stained with hematoxylin and eosin(H&E), in addition to several other immunohistochemical stains. The staining was reviewed by a researcher from each hospital included in the study. The layer in which Paget’s cells resided was evaluated by the presence and depth of dermal invasion and the presence of epidermal changes. The type of therapy (i.e. excisional surgery, MMS, radiation, or other local therapy) and the clinical course (i.e. recurrence and follow-up data) were also assessed. Follow-up results were used to divide patients into six groups: alive with no evidence of disease (ANED); alive with disease (AWD); dead of EMPD (DOD); dead of associated cancer (DOAC); dead of unrelated disease (DOUD); and follow- up loss (FUL). For some cases, multiple checks were permitted for the predilection site, clinical presentation, symptoms, and treatment modality. These studies were performed in collaboration with the Korean Society for Skin Cancers and the Korean Dermatopathology Research Group.
Results
Clinical data
The majority of the 194 patients were male (154 male patients vs. 40 female patients; ratio: 3.9 : 1). Their mean age at diagnosis was 67.5 years (range: 23–94 years). According to the age distribution, most patients were aged 60–69 years (77 cases, 39.7%), followed by 70– 79 years (68 cases, 35.1%), and 50–59 years (30 cases, 15.5%). The mean duration of the disease was 4.5 years. Predilection sites included the scrotum (129 cases, 66.5%), penile shaft (81 cases, 41.8%), pubic area (48 cases, 24.7%), vulva (34 cases, 17.5%), and groin (21 cases, 10.8%). Less common sites included the anus (3.6%), perineum (2.6%), axilla (1.5%), glans penis (1.5%), and thigh (0.5%). The disease frequently pre- sented as erythematous patches (175 cases, 90.2%) and oozing eczematous patches (116 cases, 59.8%), and less frequently as erosions/ulcers (54 cases, 33.0%), gray- white patches (30 cases, 15.5%), and hypopigmented patches (12 cases, 6.2%) (Fig. 1). The most common symptoms were itching (124 cases, 63.9%), burning (50 cases, 25.8%), pain (38 cases, 19.6%), tenderness (five cases, 2.6%), and anesthesia (two cases, 1.0%). Some patients had an underlying disease, such as hypertension (44 cases, 22.7%), diabetes mellitus (22 cases, 11.3%), or tuberculosis (13 cases, 6.7%). Twenty-seven cases of associated malignancies were identified in 26 patients (of 181, 14.4%); one patient had two malignant cancers (stomach and rectal cancer) simultaneously (Table 1). The associated internal malignancies included stomach cancer (six cases), rectal cancer (three cases), colon cancer (three cases), anal cancer (two cases), pancreatic cancer (two cases), and liver cancer. In addition, associated malignan- cies were observed in the kidney, ovary, cervix, prostate, bladder, bile duct, lung, and undesignated sites, and included thyroid cancer and leiomyosarcoma (Table 1). There were no cases of accompanying mammary Paget’s disease.