Low Grade Endometrial Stromal Sarcoma : Report of a Rare Uterine Malignancy

Introduction

Low-grade endometrial stromal sarcoma(LGESS), also known as endolymphatic stromal myolysis, is a rare tumor, accounting for just 0.2% of malignant uterine tumors and approximately 10% to 30% of uterine sarcomas(1–3). They resemble endometrialstromal cells in the proliferative stage. The annual incidence of endometrial stromal sarcoma(ESS) is 1-2 per million women. Compared to other uterine malignancies, ESS affects younger women and the mean age is 42-58 years(4).

Based on the mitotic state, ESS is histologically divided into two groups: high grade(HG) and low grade(LG)(5). HGESS is currently defined as an undifferentiated endometrial sarcoma(UES) characterized by more than 10 mitosis per 10 high power fields(HPFs). Additionally, this sarcoma is more aggressive and has a poor prognosis. In contrast, LGESS has fewer than 10 mitosis per 10 HPFs, and the cell nuclei are not atypical or pleomorphic(5). LGESS is relatively more common and tends to occur before menopause. LGESS exhibits a more indolent course, but has high relapse potential(6). These two entities should be treated differently.

For LGESS, hysterectomy is the cornerstone of treatment, however, the role of a bilateral salpingo-oophorectomy(BSO), as well as lymphadenectomy for complete surgical staging, is debated. Adjuvent treatment including hormonal treatment, chemotherapy and radiotherapy(7).

Recently a specific translocation t(7;17) (p15;q21) with involvement of two zinc finger genes juxtraposed with another zinc finger protein 1 and joint juxtraposed with another zinc finger protein 1 was described in most of the ESS(8). There is relation between chromosomal aberrations and endometrial sarcomas. Chromosomal deletion on 7p was the most common finding(55.6%) in ESS and may play a role in tumor development and progression(9).

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Fig. 1 A : Gross photograph showing a cut section of the uterus with a large partially circumscribed grey white tumor obliterating the endometrial cavity.

Fig. 2 B: Low power microphotograph displaying highly cellular tumor comprising of oval to spindle cells supported by rich vascular network (H & E stain X5x)

Fig. 2 C : High power microphotograph displaying tumor cells displaying mild to moderate pleomorphism having close proximity to the wall of proliferating blood vessels (H & E stain X40x)

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Case Report

A 42 years old female (para3 living3) was admitted to our hospital with complaints of menorrhagia and mild lower abdominal pain for the last 2 years. Her menstrual cycles had been normal six months back when she developed menorrhagia. She had periods at an interval of twenty five days and bleeding lasting for eight to ten days. Flow was excessive with history of passage of clots.

She was not using any contraception. There was neither history of exogenous hormone use nor history of drug intake like tamoxifen.

Physical examination showed the patient was moderately built and nourished with severe pallor. The rest of the general and systemic examination was normal. Her haemoglobin was 7 gm%.

On per abdominal examination there was suprapubic mass corresponding to twenty eight weeks size uterus. On per speculum examination cervix was healthy. On pervaginal examination uterus was uniformly enlarged to twenty eight weeks size, soft to hard in consistency and mobile. Bilateral fornices were free.

Ultrasound showed grossly enlarged uterus >25 X 10 X 15cm and multiple hypoechoic masses largest measuring 12cm in the uterus suggestive of fibroids. Our clinical diagnosis was fibroid uterus with cystic degenerative changes. Prior to surgery she was transfused with two units of blood. Total abdominal hysterectomy and bilateral salpingo-oophorectomy was performed.

Intraoperative uterus was enlarged to twenty eight weeks size with irregular surface and soft in consistency, with cervix. Bilateral ovaries were normal. Cut section of the uterus showed a mass 10X12cm a large partially circumscribed grey white tumor obliterating the endometrial cavity with fluid filled cystic spaces histopathological examination of the specimen showed low grade endometrial stromal sarcoma.

The histopathological diagnosis of LGESS was conferred for appropriate treatment. Immunohistochemical stains were not done in our case because of economic limitations. Postoperative period was uneventful. She received adjuvent pelvic radiotherapy(2DRT)with 50Gy for 25 days.

Discussion

Uterine sarcomas are rare tumours of mesoderaml origin. They constitute 2 to 6% of uterine malignancies. Of these, endometrial stromal sarcomas are very rare.

They are divided into three types depending upon mitotic activity, vascular invasion and observed differences in prognosis.

1. Endometrial stromal nodule(ESN)

2. Low grade endometrial stromal sarcoma(ESS) and

3. High grade or undifferentiated endometrial stromal sarcoma(UES)(10)

Boardman et al. differentiated low grade ESS by cellular uniformity, less frequent mitosis(<3/10 HPF versus >10/HPF), and lack of haemorrhage and necrosis(11).

Uterine sarcomas usually affect post-menopausal females. Women with LGESS are younger with a median age being 45 and 57 years. Symptoms at presentation include abnormal vaginal bleeding, menorrhagia and abdominal pain(12). The tumours have an indolent growth with a tendency for late recurrence(13). Metastasis are rarely detected before the diagnosis of the primary lesion.(14).

Grossly, low grade ESSs involve the endometrium, occasionally extensively. By definition tumours are infilterative. Rarely, the tumours manifest as polyps, usually with haemorrhage and infarction. Because of its prominent intravascular growth a soft tan to yellow cut surface and appear as cords and nodules infilterating through the uterine smooth muscle.

The histologic features recapitulate the gross appearance with cords of tumour cells infilterating between smooth muscle and within lymphatic spaces. The neoplastic stromal cells resemble those of the proliferating endometrium, are monotonous in appearance, and have relatively uniform size and shape(14). Tumour cell nuclei are round to ovoid and have fine chromatin, and small, inconspicuous nucleoli may be seen. A small amount of cytoplasm is present, and cell borders are indistinct. Mitotic activity is usually low (<10/10 HPF). It should be noted that rare causes of low-grade ESS will have a greater number of mitotic figures, although this is not associated with an adverse prognosis(15). Proliferating small vessels resembling the endometrial spiral arterioles are characteristic, and tumours can have bands of hyaline connective tissue separating islands and clusters of bland neoplastic stromal cells(16).

The differential diagnosis of LGESS includes ESN, cellular leiomyoma, cellular intravenous leiomyomatosis, cellular endometrial polyp and various soft tissue neoplasms(17)

Surgery is the final resort for primary treatment of LGESS consisting of total abdominal hysterectomy with bilateral salpingo-oophorectomy. Regardless of patient's age, preservation of ovarian tissue because of likelyhood of ovarian metastasis. In addition, since ESS has sterioid receptors the possibility exists that estrogen production by retained ovaries may stimulate any residual disease, oophorectomy is recommended. Due to high recurrence risk even with localized tumours. Many clinicians advocate use of adjuvant chemotherapy, radiation therapy and/or hormonal therapy to suppress tumour growth.

Hormoe therapy with medroxy-progesterone, tamoxifen, gonadotropin releasing hormone analogues(GnRH) and aromatase inhibitors are suggested for LGESS and for recurrent disease(¹⁸). Uterine sarcomas have a poorer prognosis and survival is much worse than that reported for endometrial adenocarcinoma, with an overall survival of less than 50% at 2 years, even when presenting at an early stage. A higher survival is reported with LGESS as compared to other uterine sarcoma(19, 20).

Conclusion

LGESS is a rare malignant tumor, presenting as abnormal uterine bleeding in perimenopausal women. The usual preoperative diagnosis is uterine leiomyoma and definitive diagnosis is achieved only after histopathology of uterus. By reporting our case, we wish to stress the necessity for a high grade suspicion to diagnose this tumor even in younger women. A prompt diagnosis and timely intervention are keys to improve patient survival.