Endometrial Stromal Sarcoma

Endometrial stromal sarcoma is a rare type of cancer that develops in the connective tissue of the uterine lining, affecting primarily women between ages 40 and 60.

Table of contents

• What is Endometrial Stromal Sarcoma?
• How Common is This Disease?
• Signs and Symptoms
• Risk Factors
• How is It Diagnosed?
• Treatment Options
• Outlook and Recurrence

What is Endometrial Stromal Sarcoma?

Endometrial stromal sarcoma (ESS) is a rare type of cancer that begins in the connective tissue cells found in the inner lining of the uterus, called the endometrium^[1]. It is also sometimes called uterine sarcoma^[2].

ESS is a very rare malignant tumor that makes up approximately 10% of all uterine sarcomas but only around 0.2% of all uterine malignancies^[3]. Unlike endometrial cancer, which develops from the lining cells of the uterus, ESS arises from the stroma, which is the connective tissue that supports the endometrium^[1].

Doctors classify ESS into two main types based on how the cancer cells look under a microscope and how quickly they grow^[1]:

• Low-grade ESS (LG-ESS): The cancer cells look only a little different from normal cells. This type is less aggressive, spreads slowly, and has a more favorable prognosis. The cells may grow into the uterine muscle wall and pelvic lymph nodes in a worm-like pattern^[1].
• High-grade ESS (HG-ESS): The cancer cells look very different from normal cells and have divided more quickly. This type is aggressive to treat, and individuals are often at stage 3 or 4 of the disease at the time of diagnosis^[1].

• Uterus
• Endometrium
• Myometrium
• Pelvis

How Common is This Disease?

ESS is extremely rare. There are an average of 79 cases diagnosed every year in England^[2]. The disease most commonly affects women between the ages of 40 and 60, with the median age at diagnosis being 55 years old^[2].

In comparison with other uterine cancers, uterine sarcoma makes up approximately 0.2 to 1% of all uterine cancers, occurring in 2 to 5% of all patients with uterine malignancy^[1]. The annual incidence of ESS is approximately 1 to 2 cases per million women in the general population^[6].

ESS is the second most common type of uterine sarcoma^[1]. The mean age for diagnosis ranges from 42 to 58 years, and 10 to 25% of affected women are premenopausal^[6].

Signs and Symptoms

Although less common, some people with undiagnosed ESS may not experience any symptoms. Those who do report symptoms may notice the following^[1]:

• Abnormal uterine bleeding, including bleeding between periods, more bleeding than usual during a period, or bleeding after menopause (the time when monthly periods stop)
• Pelvic pain
• Pain with urination
• Pelvic masses that seem to grow bigger
• Abnormal discharge from the vagina
• A feeling of fullness in the abdomen
• Changes in how you urinate, such as urinating more often
• Constipation

Symptoms of ESS can vary depending on the size and location of the tumor^[2]. Because the symptoms of ESS overlap with noncancerous conditions such as fibroids, adenomyosis, and endometrial polyps, doctors can often misdiagnose the condition^[1]. Spotting and bleeding changes around perimenopause can also create uncertainty.

If a person has vaginal bleeding outside of menstruation or any new or worsening vaginal bleeding, they should talk with a doctor^[1].

Risk Factors

The cause of ESS is unknown^[2]. Scientists don’t know exactly what triggers the changes in cells that lead to this cancer. The origin and biology of stromal sarcomas are poorly understood^[6].

Some research suggests a connection between ESS and the following factors^[2]:

• Hormone therapies
• Pelvic radiotherapy
• Polycystic ovary syndrome (PCOS)

It’s important to remember that the risk of developing ESS because of hormone therapy or pelvic radiotherapy is low, and doctors will always consider the benefits of treatment compared with the small risks^[2].

The only documented cause in 10% to 25% of uterine sarcomas is prior pelvic radiation therapy, which is often administered for benign uterine bleeding that began 5 to 25 years earlier^[11]. An increased incidence of uterine sarcoma has also been associated with tamoxifen in the treatment of breast cancer^[11].

Exposure to tamoxifen, unopposed estrogens, and conditions such as polycystic disease of the ovary are also implicated in the development of ESS^[6].

How is It Diagnosed?

A specialist sarcoma doctor or gynecologist will diagnose ESS through a series of tests^[2]. A proper preoperative diagnosis is difficult, and in most cases, the diagnosis is confirmed after hysterectomy for a presumed benign disease^[6].

Diagnostic testing and tissue sampling could include^[1][2]:

• Physical examination: Looking at and feeling any lump or mass in the pelvic region
• Transvaginal ultrasound: An ultrasound scan using an internal probe. Doctors gently insert an ultrasound probe into the vagina to see a clear image of the uterus
• Hysteroscopy: Doctors insert a thin tube through the vagina, cervix, and into the uterus. They can then look for any signs of ESS and can also take a biopsy if needed
• Endometrial aspiration: A sample of tissue from the uterine lining is collected for examination
• Biopsy: Taking and testing a sample of the tumor. Using this biopsy, a doctor will look to see if the tissue looks like ESS
• Other imaging scans: X-ray, CT (computed tomography), MRI (magnetic resonance imaging), or PET (positron emission tomography) scans to take pictures of the inside of the body

Endometrial sampling, ultrasound, and magnetic resonance imaging can provide diagnostic clues^[6]. Despite the rarity of the tumor, doctors need to consider the possibility of ESS in cases with presentation of rapid enlargement of a fibroid uterus^[3].

Treatment Options

First-line treatment for endometrial stromal sarcoma involves surgery to remove the uterus^[1]. Total hysterectomy with bilateral salpingo-oopherectomy (removal of the uterus, both ovaries, and both fallopian tubes) is the main line of management, and for early disease, complete cure is a reality^[6].

Surgery is the go-to treatment, but patients may need other therapies^[4]. Doctors may also recommend:

• Targeted drug therapies
• Chemotherapy: The use of drugs to kill cancer cells
• Radiation: The use of high-energy rays to kill cancer cells
• Hormone therapy: Treatment that works to change certain hormone levels in the body

Because of the proper preoperative diagnosis, doctors can plan the treatment accordingly^[3]. The optimal treatment strategies for the disease remain a matter of debate among some healthcare experts^[1].

Surgery

Surgery is the main treatment for ESS. Complete cure is possible for early-stage disease through surgery^[6]. Ovarian conservation may be possible in young women with early-stage disease, and the role of lymphadenectomy (removal of lymph nodes) is controversial^[6].

Surgical procedures for recurrent disease can include complete resections to remove all visible cancer^[20].

Hormone Therapy

Hormones like estrogen and progesterone can cause cancer cells in the uterus to grow. The goal of hormone therapy for cancer is to keep the cancer cells from getting the hormones or blocking the actions of the hormones that the cancer cells need to grow^[21].

ESS tends to respond to hormone therapy. Adjuvant hormone therapy in the form of progesterone, gonadotropin-releasing hormone analogues, and aromatase inhibitors are found to be effective in preventing recurrences^[6].

Hormone therapy options can include^[21]:

• Progestins (such as megestrol acetate and medroxyprogesterone): Pills taken every day
• Aromatase inhibitors (such as letrozole, anastrozole, and exemestane): Pills taken every day to keep estrogen from forming in people who have already gone through menopause
• Gonadotropin-releasing hormone agonists (such as goserelin and leuprolide): Injections given every 1 to 3 months to lower estrogen levels in people who have not gone through menopause

Of evaluable occasions when hormonal therapy was used for recurrent disease, disease control was achieved in a significant majority of cases^[20].

Chemotherapy and Radiation

For recurrent disease, hormone therapy, radiotherapy, and surgical excision of the metastasis are recommended^[6]. Chemotherapy combined with targeted agents like apatinib has shown promising results in some cases^[9].

Outlook and Recurrence

The prognosis for women with uterine sarcoma primarily depends on the extent of disease at the time of diagnosis^[11]. Both low-grade and high-grade ESS have a high rate of recurrence^[1].

ESS is an indolent tumor, meaning it grows slowly. Local recurrences and distant metastasis can occur even 20 years after initial diagnosis^[6]. The number of relapses can range from one to five^[20].

Low-grade ESS spreads slowly and has a more favorable prognosis compared to high-grade ESS. High-grade ESS is aggressive to treat, and individuals are often at stage 3 or 4 of the disease at the time of diagnosis^[1].

Long-term survival is possible with recurrent ESS. Complete surgical resection of recurrent tumors and hormone therapy contribute to disease control^[20]. Patients should maintain regular follow-up with their healthcare team to monitor for any signs of recurrence.