EMPD is a rare cutaneous intraepithelial adenocarcinoma arising in apocrine gland-bearing areas, particularly the perineum, vulva, axilla, scrotum, penis and groin. PPD mostly refers to intraepithelial carcinoma within 6cm of the anus and below the dentate line . Patterns of involvement include an in situ epithelial form without associated carcinoma, an epithelial form with associated adnexal carcinoma, and association with visceral malignancy. Paget cells have the potential to invade the dermis and to metastasize. The anatomic site of the presenting EMPD is strongly related to the underlying visceral carcinoma in 86% of cases . Our patient had an intraepithelial lesion without invasion of the dermis and no associated colorectal carcinoma.
Clinical presentation is often nonspecific and the diagnosis is frequently overlooked. Patients commonly have symptoms like pruritus, irritation and rash, although pain and bleeding may occur in long-standing cases. These lesions are typically erythematous, or whitish gray, dry and raised, but may turn into eczematoid, ulcerated, nodular or papillary forms [5–10]. It is unusual to make a diagnosis of EMPD clinically, so this condition is often first treated with topical corticosteroids and antifungal agents before a diagnosis is made by biopsy.
Differential diagnoses include Bowen’s disease, contact dermatitis, lichenoid lesions, psoriasis, melanoma, perianal Crohn’s involvement, mycosis fungoides, squamous cell carcinoma and tinea cruris.
Histopathology reveals large, round, clear-staining cells with abundant pale cytoplasm confined to the epidermis. The nuclei are large and situated in the periphery of cells. In the lower epidermal layers, glandular clusters can be seen that are absent in mammary Paget’s disease. Liu et al. support the theory of two types of PPD with different immunoprofiles: primary cutaneous intraepithelial neoplasm (CK7-positive and CK20-negative), in which cells display sweat gland differentiation (gross cystic disease fluid protein 15-positive); and direct intraepithelial Pagetoid spread of anorectal adenocarcinoma (CK20-positive and CK7-negative, gross cystic disease fluid protein 15-negative). In one study, cells were androgen receptor-positive in 78% of patients and Her2/neu-positive in 52%. Coexpression, as in our patient, existed in 52% of patients .
Pathogenesis of PPD is controversial. Helwig and Graham  consider perianal and vulvar Paget’s disease to be a manifestation of a multicentric effect of an unknown carcinogenic stimulus on apocrine structures, epidermis and glandular elements of the rectum and urethra.
A patient diagnosed with EMPD needs an initial clinical assessment, evaluation of the extent of involvement of the lesion, and work-up for a possible underlying malignancy. A wide range of treatment modalities have been reported, including surgical and nonsurgical approaches. Surgical methods are still the mainstay in the management of PPD, including wide local excision with or without reconstruction and grafting, abdominoperineal resection, and Mohs micrographic surgery. Radiotherapy, chemo-radiotherapy and photodynamic therapy have been employed [6, 7, 13]. Despite varied modalities, local recurrence is a significant problem, to the extent of 33% . The major factors in relapse and chronicity of the disease are multifocal involvement and difficulty in clinical delineation of cutaneous margins.
Prognosis depends on whether the disease extends beyond the epidermis and the adnexal epithelium. If it is associated with subjacent adnexal carcinoma or regional visceral carcinoma, the prognosis is poor. Survival of patients with in situ PPD is favorable.
Long-term follow-up of patients with EMPD is required to exclude the recurrence of the disease and development of an associated cancer. Follow-up should include a punch biopsy from the margin of the old perianal lesion once a year, in addition to a colonoscopy once every two years .