Treatment outcomes in a large cohort of patients with invasive Extramammary Paget's disease
Highlights
► The outcome of patient with EMPD is generally favorable. ► Surgery remains the therapy of choice. ► Radiotherapy is associated with worse outcomes.
Introduction
Extramammary Paget's disease (EMPD) was first described by Radcliffe Crocker in 1889. Generally considered an adenocarcinoma, EMPD is thought to originate in the skin or its underlying appendages, and shares many morphologic and histological characteristics with the more common mammary Paget's disease (MPD). The exact incidence is still a matter of debate, but it affects primarily postmenopausal Caucasian females [1].
The most common anatomic location of EMPD is the vulva, followed by the perianal skin and less frequently the scrotum, penis and axilla [[2], [3], [4], [5], [6]]. While the majority of MPD is associated with an underlying breast cancer, most cases of EMPD are intraepithelial neoplasms that are not associated with an underlying or distant carcinoma. In the case of vulvar EMPD, 4 to 17% of cases are associated with an underlying carcinoma of the vulva upon initial diagnosis. In addition, in 11 to 20% of vulvar EMPD, other malignancies involving the vagina, cervix, uterus, ovary, bladder, rectum, colon, breast, gallbladder, liver or skin have been reported [1], [7], [8]. In contrast, anorectal EMPD is more frequently associated with an underlying anorectal carcinoma or more distant colorectal, stomach or breast carcinoma [9], [10]. The presence or absence of synchronous malignancies has led some authors to sub-classify EMPD into primary, intraepithelial EMPD, and a secondary form that is associated with an underlying or distant carcinoma with direct epidermal extension or epidermal metastases [11]. The pathogenesis of invasive EMPD remains controversial. One popular theory postulates that EMPD may arise either as a primary intraepidermal neoplasm originating from the intra-epidermal portions of sweat/apocrine glands, or from primitive basal cells within the epidermis [12]. Primary EMPD may then progress from a non-invasive epidermal neoplasm to an invasive adenocarcinoma potentially metastasizing to loco-regional lymph nodes and/or distant sites.
The prognosis of patients with intraepithelial EMPD is generally better compared to patients with an underlying malignancy [1], [13]. The difference in outcome between patients with invasive EMPD and those patients with an underlying malignancy is less clear [14]. Most prior reports have been derived from limited case series and single institution experience with invasive EMPD thereby significantly limiting our insight into the exact incidence and outcome of affected patients [1]. Surgical resection of the tumor is the accepted standard treatment modality for EMPD. Due to the multicentric nature of the disease and frequent microscopic extension beyond the visible borders of the tumor recurrences remain disappointingly common even with the use of more radical procedures and intraoperative margin assessment [[2], [15], [16], [17]]. Radiotherapy for the treatment of EMPD has usually been reserved for those patients who are medically unfit, suffer from or are at high risk of a recurrence or declined surgery with variable results [1], [18], [19]. Experience with topical and systemic chemotherapy is even more limited [20], [21]. The outcome of patients with invasive EMPD is poorly characterized and based on historical case series. In the largest reported series, Chanda et al. reported that 46% of patients with EMPD associated with an underlying carcinoma succumbed to metastatic disease versus 18% of patients with non-invasive disease [1]. Using data derived from the Surveillance, Epidemiology and End Results (SEER) program, we undertook an analysis of the incidence, treatment approaches and outcome of patients with invasive Extramammary Paget's disease.
Section snippets
Methods
We evaluated patients diagnosed with invasive EMPD using data collected from the SEER program. We included patients diagnosed between 1973 and 2007 who survived for at least 2 months after their initial diagnosis and were followed up through December 31, 2007. For the survival analyses we used the SEER 17 registries database containing data from Atlanta, Connecticut, Detroit, Hawaii, Iowa, New Mexico, San Francisco–Oakland, Seattle–Puget Sound, Utah, Los Angeles, San Jose–Monterey, Rural
Incidence and patient characteristics
From 1973 to 2007, 1439 patients in the SEER registry were diagnosed with invasive EMPD among which 965 were female and 474 were male. The median age at the time of diagnosis was 72 years (range 63 to 79 years) which was not significantly different for female or male patients with a median age at diagnosis of 72 years for both. The majority of patients were Caucasian with 1144 (80.8%) patients classified as white, 13 (0.9%) as black and 259 (18.3%) classified as other. 1037 (80.4%) patients were
Discussion
Our study provides data on the incidence, treatment and outcome of the largest cohort of invasive EMDP analyzed to date. Our analysis based on the SEER program data shows that patients with invasive EMPD have a good prognosis particularly with localized disease.
Previous reports have described that invasive EMPD affects primarily elderly Caucasian females with a median age at the time of diagnosis of 72 years [6]. Our data are consistent with this observation. However, we unexpectedly noted a
Conflict of interest statement
No conflict of interest.
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