Prognostic implication of endometriosis in clear cell carcinoma of the ovary☆
Introduction
Considered a benign, surgically diagnosed disease, endometriosis has a prevalence estimated at 10% in premenopausal women and less than 4% after menopause [1], [2], [3]. Given that an unknown proportion of affected women are asymptomatic and may not undergo abdominal exploration or biopsy procedures, the true prevalence may be higher.
Clear cell carcinoma (CCC) accounts for less than 5% of all ovarian malignancies and 3.7–12.1% of all histologic subtypes among epithelial ovarian cancers [4], [5], [6], [7]. These tumors are often present as large pelvic masses, rarely occur bilaterally, are frequently diagnosed at an early stage, and are more often accompanied by thromboembolic events, malignant hypercalcemia, and the coincident presence of endometriosis than the other common epithelial cancers of the ovary [8], [9]. Treatment of afflicted patients is challenging, given an often poor tumor response to platinum-based chemotherapy, and a worse prognosis compared to patients with more common papillary serous carcinoma.[10].
Since Sampson reported the first series of cases of ovarian cancer arising in the context of endometriosis in 1925 [11], the relationship between endometriosis and ovarian cancer has been repeatedly described in the literature [12], [13], [14], [15], [16], [17], [18]. Most of the studies addressing the relationship between these two entities, utilize Sampson's original histopathologic criteria to classify tumors as arising in endometriosis. These criteria dictates that: (1) there must be clear endometriosis in proximity to the tumor, (2) no other primary site for the tumor can be found, and (3) the presence of tissue resembling endometrial stroma surrounding epithelial glands [11]. Subsequently, Scott proposed an additional criterion requiring the demonstration of histologically-proven transition from endometriosis to cancer [19]. While these four criteria define cancer arising in endometriosis, they do not address the possibility that, in an unknown proportion of cases, the tumor might have overgrown or replaced the originating endometriotic focus or that demonstration of histological contiguity between endometriosis and cancer may be missed due to limited sampling for pathologic evaluation.
The purpose of this study was to investigate whether the presence of endometriosis in the surgical specimen is a prognostic factor in patients diagnosed with CCC of the ovary.
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Materials and methods
After protocol approval by the Institutional Review Board, using the institutional Cancer Registry, we identified all patients diagnosed with CCC of the ovary seen at Massachusetts General Hospital (MGH) between 1975 and 2002. Case selection was based on the original diagnosis rendered by the gynecologic pathologists from our institution and, when possible, re-reviews by an independent pathologist (OE and EJ).
Comprehensive review of the medical record and pathology report was performed. Data
Results
Between 1975 and 2002 we identified a total of 84 patients with CCC and defined three different groups based on histopathologic findings in the surgical specimen. See Table 1.
Fifteen tumors were classified as CCC arising in endometriosis (Figs. 1A, B and C), 26 as CCC associated with endometriosis, and 43 as CCC without endometriosis. Clinical data characterizing the three groups is summarized in Table 2.
For the total sample of 84 patients, endometriosis was found in 49% of the patients, and
Discussion
Shih and Kurman [22] recently proposed a novel dualistic model for ovarian tumorigenesis. Type I tumors correspond to low-grade carcinomas arising and progressing in a stepwise manner from a defined benign precursor lesion. Type II tumors are comprised of high-grade tumors arising from lesions not morphologically identified yet or thought to originate de novo from the surface epithelium or inclusion cysts of the ovary [23]. According to this model, most endometrioid adenocarcinomas fall into
Conflict of interest statement
MGDC is currently on the Speaker's Bureau program for Ortho-Biotech and GlaxoSmithKline. The other authors have no conflicts of interest to disclose.
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Presented at the 49th Annual Meeting of the Society of Gynecologic Oncologists, Tampa, FL, March 8–12, 2008.