A review of extramammary paget’s disease: Clinical presentation, diagnosis, management and prognosis

Paget’s disease is considered to be an intraepithelial adenocarcinoma, whose first case was described by James Paget in 1874 as a breast lesion. Since then, it has been surrounded by controversy, speculation and much interest on the part of surgeons, pathologists and dermatologists. Due to its rare incidence, no clear diagnostic and treatment guidelines are available yet (Siesling et al., 2007). The lesions are primarily found along the “milk line”, where the sites of involvement are anywhere apocrine exhibiting that type of glandular secretion in which the free end of the secreting cell is cast off along with the secretory products accumulated therein (e.g., mammary and sweat glands).

A Paget-like lesion identified in another site is called Extramammary Paget’s Disease (EMPD), whose first case was described in 1889 by Crocker. EMPD can generate from all areas characterized by a high density of apocrine glands, as the axilla, the anus and perianal region, the vulva in women, the penis and the scrotum in men. Vulvar EMPD accounts for the majority of EMPD findings (76%) (Pierie et al., 2003), although vulvar EMPD remains a rare neoplastic finding, representing less than 1% of the vulvar neoplasms (Fanning et al., 1999).

On the other hand, interesting is the case of an EMPD presenting as alopecia neoplastica and described in 2008 by an American team as a poorly circumscribed erythematous plaque with patchy alopecia of the scalp. Histology of this lesion showed pagetoid infiltration of the epidermis by atypical single and nested cells, which resulted to be positive for the markers common to Paget cells (Iwenofu et al., 2008).

Epidemiologically, Paget’s disease is essentially a disease of postmenopausal Caucasian women, with a mean age at the diagnosis of about 70 years, as many studies have documented (Banerjee et al., 2005; Shaco- Levy et al., 2010). 

The prevalence of invasive disease is reported to occur in 5-25% of patients (Awtrey et al., 2003; Hoffman and Cavanagh, 1997). The average interval between the diagnosis of intraepithelial vulvar EMPD and its sequential progression to invasive carcinoma amounts approximatively to 11 years (Hart and Millman, 1977).

Between 17% and 30% of the patients with EMPD may have an underlying adenocarcinoma (Parker et al., 2000). A higher rate of underlying adenocarcinoma was found in patients with perianal involvement and palpable masses in the vulvar region (Berardi et al., 1988). For example, vulvar EMPD can also be extended to the upper vaginal mucosa and cervix, as in a reported case of an elderly woman who had EMPD associated with vulvar adenocarcinoma and a uterine prolapse (Lloyd et al., 1999). In 10-20% of cases EMPD is associated to coexisting malignancies at other sites, as the breast, the skin basal cells, the rectum, the genitourinary tract and the cervix (Hoffman and Cavanagh, 1997; Parker et al., 2000; Tebes et al., 2002).

About that, a Spanish study suggests a relationship between the site of EMPD and the probability to find an adenocarcinoma of cutaneous adnexal structures or an internal malignancy. More in detail, this study reports that vulvar EMPD was associated with adnexal adenocarcinoma in 4% of cases and with a distant malignancy in 20%, while perianal EMPD was associated with adnexal adenocarcinoma in 7% of cases and with an internal malignancy in 14% (Pascual et al., 2008).

Many studies report cases of EMPD associated with internal malignancies. For example, a recent Korean study has documented an association with gastrointestinal neoplasms, intended as both a gastrointestinal malignancy and a colorectal adenoma. This study also reported that this association with gastrointestinal neoplasm was stronger when a EMPD was found in male patients (Yoon et al., 2008). These results are also supported by an American article, presenting the case of a synchronous primary perianal Paget’s disease and a rectal adenocarcinoma (Shi and Argani, 2009).

Moreover, a recent Taiwanese study has reported an unusual case of EMPD of the scrotum associated with hepatocellular carcinoma (HCC). The EMPD was diagnosed one year after the appearance of a scrotal erythematous plaque, and a HCC nineteen months later (Li et al., 2009). Again, an American study reports a rare collision of EMPD and malignant melanoma, by describing the case of a 78 years-old woman with a pigmented vulvar mass, which the biopsy turned out to be a malignant melanoma. Peripheral to the main mass, erythematous and thickened plaques were described, which resulted to be histologically an EMPD (Hill et al., 2008). A Danish study cites the association of EMPD and an underlying prostate carcinoma (Hammer et al., 2008).

In any case, due to the high incidence of coexisting malignancies at other sites, EMPD diagnose should not leave out to take into consideration additional controls as mammography, colonscopy, colposcopy and cervical cytology with Papanicolau staining (Dimitroulas and Settas, 2009; Minicozzi et al., 2010).