Paget’s disease of the breast was first introduced by Paget. He introduced 15 patients with underlying intraductal carcinoma (
10). In 1889, Crocker introduced the first case of extramammary Paget’s with scrotal and penile involvement ( 11). In 1893, Darier and Coulillaud reported the first case of perianal Paget’s disease; cited in Vergati et al. ( 2). In 1901, the first report of vulvar Paget’s disease was reported by Dubreuilh ( 12).
Extramammary Paget’s disease is a rare neoplasm of the skin and its exact incidence is unknown. Patients are mostly white women of 50 to 80 years of age (
3). Familial incidence of the disease has been rarely reported ( 13). Most common areas affected in extramammary Paget’s are consecutively vulva, perineal regions, perianal region, scrotum and penis, and occasionally axilla, buttock, thigh, eyelid, and external auditory canal ( 1). Paget’s disease is even possible to simultaneously occur in two distinct anatomical regions ( 14).
Unlike the Paget’s disease of the breast, which is almost always associated with an underlying malignancy in the breast, extramammary Paget’s may not accompany or associate with other malignancies. However, if there is any associated internal malignancy, the location of extramammary Paget’s can be a sign of the underlying malignancy. For example, perianal Paget’s disease can be associated with gastrointestinal adenocarcinoma and the Paget’s involving the scrotum, penis, and groin can be associated with malignancy of the genitourinary system (
Perianal Paget’s disease is mainly an intraepithelial carcinoma placed at a distance of 6 cm from the anus below the dentate line. The most common symptom is itching with the prevalence of approximately 70%. Other patients’ complaints include feeling of irritation, pain, bleeding, and swelling. The disease is asymptomatic in 10% of patients (
4). Initially, the lesion is typically dry, erythematous, and raised; later, it may turn into a crusted, eczematoid, ulcerated, or papillary lesion. The lesions have sharply defined margins with plaques and also distinct erythema ( 1).
Various differential diagnoses are suggested for extramammary Paget’s disease including lichen sclerosis, seborrheic dermatitis, fungal infection, psoriasis, contact dermatitis, melanoma, anogenital intraepithelial neoplasia, mycosis fungoides, and histiocytosis (
16). Perianal and vulvar Paget’s disease may be mistaken for leukoplakia, hidradenitis suppurativa, Crohn’s disease, condylomata accuminata, squamous cell carcinoma, and basal cell carcinoma ( 17).
Most patients experience long-term use of anti-fungal treatments and local corticosteroid. Skin biopsy should be performed for such lesions that have received standard local treatment for four to six weeks without response (
3, 4, 17).
Definitive diagnosis is established by histopathologic and immunohistochemical examination of the specimen. Histopathologically, the Paget’s disease is characterized in the basal layer of the skin. Most cells are placed as single in the basal layer, which are pale, large, and vacuolated and are scattered throughout the epidermis. However, sometimes they are as glandular structures and cell-nests. The cells of extramammary Paget’s disease are large containing clear cytoplasm and sometimes with a signet ring appearance (
Immunohistochemically, extramammary Paget’s disease is positive for keratin, carcinoembryonic antigen (CEA) and epithelial membrane antigen (EMA) (
19). In addition, it is positive for CK7 and CDGFP15 and negative for CK20. However, colorectal Paget’s disease is sometimes positive for CK7, CK20, B72.3, and CD15, and is negative for CDGFP15 ( 18). Interestingly, extramammary Paget’s disease does not have estrogen and progesterone receptors, but commonly expresses androgen receptor. Histopathologic feature of extramammary Paget’s disease is being mucin-rich, although, rare variants of extramammary Paget’s disease including Bowenoid and Pigmented do not have such feature ( 20).
In the diagnosis of extramammary Paget’s disease, complete evaluation of underlying malignancy should be done. It seems that perianal Paget’s disease has stronger association with underlying malignancy than vulvar Paget’s disease does. Appropriate investigations include pelvic ultrasound scan, hysteroscopy, pelvic magnetic resonance imaging, laparoscopy, colonoscopy, cystoscopy, barium enema, mammography, intravenous pyelogram, and chest X-ray (
Various treatment methods are proposed for perianal Paget’s disease including surgical and nonsurgical treatments and these methods are used either alone or in combination with another method. These methods are wide local excision and abdominoperineal resection (
21), Mohs microscopic surgery ( 22), radiotherapy ( 23), chemoradiotherapy ( 24), photodynamic therapy, and laser therapy ( 25, 26). Shutze and Gleysteen offered a management classification for perianal Paget’s disease ( Table 1) ( 27). According to this classification, our patient was also candidate for wide local excision.
Table 1. Management classification for perianal Paget’s disease offered by Shutze and Gleysteen
Stage Description Management I Paget’s cells found in perianal epidermis and adnexae without primary carcinoma WLE IIA Cutaneous Paget’s disease with associated adnexal carcinoma WLE IIB Cutaneous Paget’s disease with associated anorectal carcinoma APR III Paget’s disease in which associated carcinoma has spread to regional nodes ILND + WLE/APR IV Paget’s disease with distant metastases of associated carcinoma CT + RT + LPM
a Abbreviations: APR, Abdominoperineal resection; CT, Chemotherapy; ILND, Inguinal lymph node dissection; LPM, Local palliative management; RT, Radiotherapy; and WLE, Wide local excision.
Anyway, surgical treatments are the main treatment methods in these patients and according to the follow-up period in different studies, best prognosis and low recurrence rates are related to the cases undergone surgical treatment (
5, 23, 27).
In conclusion, surgical treatment is still the method of choice in the treatment of this disease. Here, we reported a patient with perianal Paget’s disease who underwent wide local excision to draw attention to this uncommon disease. We recommend considering Paget’s disease as a probable diagnosis when evaluating a perianal lesion. However, further studies are needed for better understanding and management of this disease.