Regular articleLow-grade endometrial stromal sarcoma: hormonal aspects☆☆
Introduction
Endometrial stromal tumors are rare uterine neoplasms, accounting for approximately 0.2% of all genital tract malignancies [1]. Their incidence is approximately 2 per million women. In turn, the incidence of endometrial cancer is 700 per million women [2]. Histologically, endometrial stromal neoplasms are divided into three groups: endometrial stromal nodules, low-grade endometrial stromal sarcomas, and high-grade endometrial stromal sarcomas [3]. Low-grade endometrial stromal sarcoma is the common form, representing approximately 80% of stromal neoplasms [4]. In contrast to the readily discernible features of high-grade endometrial stromal sarcoma, characterized by moderate to marked cytologic atypia and 10 or more mitotic figures per 10 high-power fields, the histologic appearances of benign stromal nodules and low-grade stromal sarcomas are similar, both having fewer than 10 mitotic figures per 10 high-power fields[4]. Low-grade endometrial stromal sarcomas are often distinguishable from endometrial stromal nodules by the identification of infiltrating borders [4].
Because of the rarity of the disease and the fact that the majority of women with this condition are not diagnosed until they have undergone a hysterectomy, the only consistent approach to treatment in the literature is that the patients undergo a hysterectomy. The role for bilateral oophorectomy, surgical staging, and posttreatment avoidance of estrogen replacement therapy (ERT) has yet to be determined in women with low-grade endometrial stromal sarcomas. Recurrences develop in one-third to one-half of patients with low-grade endometrial stromal sarcoma and can appear as long as 30 years after therapy [4]. Case reports and several small series have shown that low grade endometrial stromal sarcomas can express estrogen receptors (ER) and progestin receptors (PR) and advanced-stage disease may be controlled with progestin therapy [5], [6], [7], [8], [9], [10], [11].
The stimulus that led to this study was based on the senior author’s (P.E.S) observation that two women previously diagnosed to have low-grade endometrial stromal sarcoma recurred while receiving ERT [12]. This observation had not to our knowledge been previously reported. In this study, we assess the clinical impact of steroid hormones on women diagnosed with low-grade endometrial stromal sarcomas, specifically ERT, retained ovarian tissue, and progestin treatment, and their association with the development of recurrent disease. In addition, we evaluate whether the expression of ER and PR may be used as a predictive factor in hormonal treatment and response.
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Materials and methods
We obtained institutional review board approval for this study. Twenty-two consecutive patients with low-grade endometrial stromal sarcoma who were diagnosed and treated at Yale University School of Medicine-affiliated hospitals over the last 25 years were reviewed. These cases were identified through the institutional tumor registry and their histories were ascertained from divisional records and pathology reports. All cases were re-reviewed by a gynecologic pathologist (VP) to confirm the
Results
Four Stage I patients who underwent total abdominal hysterectomy (TAH) and bilateral salpingo-oophorectomy (BSO) received postoperative ERT. Three of these four recurred 4, 8, and 12 years after initial diagnosis. One patient with Stage III disease received megestrol acetate compliantly for 1 year and intermittently for a second year after diagnosis followed by estrogen alone after experiencing severe side effects from the progestin. The latter patient developed widespread intraabdominal
Discussion
We must emphasize that our series is small. Low-grade endometrial stromal sarcoma is a rare tumor that is not routinely diagnosed prior to surgery as was true in 16 of our 22 cases. This series emphasizes the difficulty in differentiating endometrial stromal nodule from low-grade stromal sarcoma. One case was not recognized as low-grade stromal sarcomas until it recurred. Almost half of the patients in our series recurred, which is consistent with most reported series [5], [7], [19], [20].
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This work was in part supported by National Institutes of Health Grants RO1 HD37137-01A2 and RO1-CA92435-01