Elsevier

Gynecologic Oncology

Volume 110, Issue 3, September 2008, Pages 336-344
Gynecologic Oncology

Prognostic implication of endometriosis in clear cell carcinoma of the ovary

https://doi.org/10.1016/j.ygyno.2008.05.025Get rights and content

Abstract

Objective

The aim of this study is to investigate whether the presence of endometriosis is a prognostic factor in patients diagnosed with clear cell carcinoma (CCC) of the ovary.

Methods

Retrospective chart review was performed to all patients diagnosed with CCC and endometriosis between 1975 and 2002. All pathology reports were reviewed and slides were reviewed when available. Cox regression analysis and Kaplan–Meier test were used to calculate survival prognostic factors. The level of significance was set at 0.05.

Results

Eighty-four patients with CCC were identified with a 49% rate of coexisting endometriosis. Patients with tumors arising in endometriosis (n = 15), with endometriosis found elsewhere in the specimen (n = 26), and those without endometriosis (n = 43) were analyzed comparatively. Patients with CCCs arising in endometriosis were 10 years younger (95% C.I. 0.6–18 years) than those with CCC not arising in endometriosis (P < 0.05). Patients with endometriosis anywhere in the surgical specimen presented at early stage 66% of the times versus 42% for patients without endometriosis (P < 0.05). Median overall survival (OS) for patients with endometriosis was 196 months (95% C.I. 28–363) versus 34 months (95% C.I. 13–55) for patients without endometriosis (P = 0.01). Advanced tumor stage at diagnosis (HR 13, 95% C.I. 5–29, P = 0.001) and absence of endometriosis (HR 2, 95% C.I. 1–3.9, P = 0.03) were the only significant prognostic factors associated with poor survival. Disease recurrence or death among optimally and completely cytoreduced patients was 31% and 59% for those with and without endometriosis respectively (P > 0.05).

Conclusions

Our study suggests that the presence of endometriosis in patients with CCC of the ovary is associated with progression free and OS advantages with no difference in initial resectability.

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.

Section snippets

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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