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Gynaecological Cancer

Hormonal Treatment of Metastatic Endometrial Stromal Sarcomas Jonathan M Kitayama,1

David Shimizu2 and Keith Y Terada3

1. Pathology Resident, University of Hawaii Pathology Residency Program; 2. Assistant Professor, Department of Pathology, University of Hawaii, John A Burns School of Medicine; 3. Associate Professor, Department of Obstetrics and Gynecology, and Director, Gynecologic Oncology, University of Hawaii, John A Burns School of Medicine


Endometrial sarcomas account for 10–15% of all uterine sarcomas. These tumours are composed of uniform cells that resemble the stromal cells of proliferative endometrium. As endometrial sarcomas are rare, accounting for less than 1% of all gynaecological malignancies, there is an absence of clinical trials and treatment guidelines do not exist. It is well-known that low-grade endometrial stromal sarcomas (LGESS) are often oestrogen-receptor- (OR) and progesterone-receptor- (PR) positive. This provides a potential target for treatment, similar to other hormonally sensitive tumours. This article reviews the literature in terms of current management strategies for LGESS, particularly the data in terms of hormonal therapy.

Keywords Endometrial stromal sarcoma, uterine sarcoma, mesenchymal tumours, hormone therapy, progestins

Disclosure: The authors have no conflicts of interest to declare. Received: 16 March 2010 Accepted: 24 September 2010 Citation: European Oncology & Haematology, 2011;7(2):116–8 Correspondence: Keith Y Terada, Queen’s Physician Office Buildings II, 1329 Lusitana Street, Suite 803, Honolulu, HI 96813, US. E:

Endometrial sarcomas account for 10–15% of all uterine sarcomas. They make up fewer than 1% of all gynaecological malignancies.1,2,5,6

cases per million women in the US.6,7

Uterine sarcomas in general are rare: they account for 4% of all uterine malignancies.1–4

The reported incidence is approximately one to two Women often present with an

enlarged uterus or have complaints of heavy menstrual bleeding. Occasionally, the diagnosis is established by endometrial biopsy or diagnostic curettage. Most often, however, the diagnosis is not recognised until the time of hysterectomy. Generally, these women are pre- or peri-menopausal at the time of diagnosis.5

Endometrial stromal tumours are composed of cells that resemble the stromal cells of proliferating endometrium.1

Previously, endometrial

sarcomas were divided into low-grade endometrial stromal sarcomas (LGESS) and high-grade endometrial stromal sarcomas, as originally described by Norris and Taylor.2

Current terminology substitutes the

term undifferentiated endometrial sarcoma for high-grade endometrial sarcoma because of the pleomorphic nature of the tumour and the lack of endometrial stromal differentiation histologically. The World Health Organization (WHO) classifies endometrial sarcomas as LGESS and undifferentiated endometrial sarcoma.5

Endometrial stromal nodule, a benign tumour and LGESS recapitulate the endometrial stroma of proliferative endometrium. How they differ is based on the growth pattern: endometrial stromal nodules are circumscribed; LGESS are characterised by infiltrative tongues of tissue, generally low mitotic activity (<10 mitotic figures/10hpf), mild cytological atypia and a generally indolent behaviour. Undifferentiated endometrial sarcomas have a pleomorphic appearance, marked cytological atypia and high mitotic activity (>10 mitotic figures/10hpf) with atypical mitotic figures.8–11

They tend to grow rapidly and metastasise early, and are 116

generally fatal. Disease-free survival and prognosis are substantially better for low-grade versus undifferentiated sarcomas.2,7,8,12 recur, local/regional sites are more common than distant sites.8


Post-operatively, various treatment strategies have been reported, utilising radiation therapy, chemotherapy or hormonal therapy. However, for patients with localised disease, studies demonstrate no difference in survival comparing patients who receive adjuvant therapy versus those who do not.5,13


chemotherapy regimens have been reported in the adjuvant setting, but to date there are no convincing data to support routine use. Radiation therapy has been shown to prevent local recurrence but not distant metastases.5,9,14

Recent studies have examined hormone therapy based on the observation that LGESS express oestrogen (OR) and progesterone receptors (PRs), making this a potential target for treatment. Studies have shown success with the use of high-dose progestin therapy. Furthermore, the use of hormonal therapy has expanded to the use of other agents such as gonadotropin-releasing hormone (GnRH) analogues and aromatase inhibitors.7

This article will review current

recommendations and recent studies investigating the role of hormones in treating metastatic LGESS.


The standard of care and primary treatment for LGESS is surgery, which is the only potentially curative procedure. When surgery is performed, it is customary to perform a total hysterectomy. Bilateral salpingo-oophorectomy is often performed since the ovaries are a common site of metastases and also a source of oestrogens. However, there are conflicting reports to support this practice; some authors report that the recurrence rates are the same in patients who have their ovaries compared with those without.8

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