What are the other Names for this Condition? (Also known as/Synonyms)

• ESS (Endometrial Stromal Sarcoma)

What is Endometrial Stromal Sarcoma? (Definition/Background Information)

• Endometrial Stromal Sarcoma (ESS) comprise of a rare group of malignant uterine tumors that include the following types:
  • Low-grade endometrial stromal sarcoma (LG-ESS)
  • High-grade endometrial stromal sarcoma (HG-ESS)
  • Undifferentiated uterine sarcoma (UUS)
• Endometrial Stromal Sarcoma is mostly present in adult women, and both pre- and post- menopausal women may be affected. The tumors are known to be caused by genetic mutations and chromosomal aberrations
• The signs and symptoms of Endometrial Stromal Sarcoma include unusual vaginal bleeding, abdominal pain, and sensation of pressure in the pelvic area. The complications are dependent upon the stage of the cancer and the method of treatment employed. Advanced stage tumors are observed to metastasize to various organs
• Treatment for the malignancy is mainly through surgery and supplementary treatment measures that include radiation therapy and chemotherapy. The prognosis of Endometrial Stromal Sarcoma mostly depends on the type of ESS and the cancer stage. In many cases, the prognosis is guarded, due to metastasis at the time of diagnosis

Who gets Endometrial Stromal Sarcoma? (Age and Sex Distribution)

• Endometrial Stromal Sarcoma may be present in adult women of any age
• Women may be affected both before and after menopause; 10-25% tumors are seen in premenopausal women
• There is no geographical, racial, or ethnic preference observed
• ESS form less than 0.5% of all cancers found in the uterine corpus. The incidence rate is approximately 1-2 women per million population

What are the Risk Factors for Endometrial Stromal Sarcoma? (Predisposing Factors)

The following are the potential risk factors for Endometrial Stromal Sarcoma:

• Tamoxifen therapy
• Long-term estrogen therapy (stimulation)
• Radiation to the pelvic region
• Polycystic ovarian syndrome (PCOS)

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Endometrial Stromal Sarcoma? (Etiology)

The cause of development of Endometrial Stromal Sarcoma is related to genetic abnormalities. The chromosomes and genes involved depend upon the subtype of ESS. Currently, studies indicate defects in the following genes:

• Low-grade endometrial stromal sarcoma:
  • JAZF1-SUZ12(JJAZ1) fusion gene due to t(7;17)(p21;q15)
  • EPC1-PHF1 gene fusion
• High-grade endometrial stromal sarcoma:
  • Fusion of genes YWHAE and FAM22, due to chromosomal translocation, namely t(10;17)(q22;p13)
• Undifferentiated uterine sarcoma:
  • Gains on chromosomes involving 2q, 4q, 6q, 7p, 9q, and 20q
  • Losses on chromosomes involving 3p, 10p, and 14q

What are the Signs and Symptoms of Endometrial Stromal Sarcoma?

Approximately, 1 in 4 women may not show any signs and symptoms. In others, the signs and symptoms of Endometrial Stromal Sarcoma may include:

• The presence of a solitary infiltrating tumor
• The majority of ESS tumors are between 5-10 cm in size, while undifferentiated sarcomas generally grow over 10 cm
• Most tumors have poorly-defined boundaries
• Sensation of pelvic mass or enlarged uterus
• Most of the tumors are located intramurally (i.e., found within the uterine walls) and may be polypoidal
• Heavy or abnormal bleeding from the uterus and abdominal pain are common symptoms in women with ESS
• Signs and symptoms may also occur from large-sized tumors causing compression of adjoining uterine structures including frequent urination and lower back pain
• Tumor necrosis and hemorrhage is observed in many cases
• The tumors can invade into the myometrium and lymphovascular spaces
• Pain during sexual intercourse
• Weight loss, weakness, and lethargy

How is Endometrial Stromal Sarcoma Diagnosed?

The diagnosis of Endometrial Stromal Sarcoma may involve:

• Complete physical examination with thorough evaluation of medical history
• Ultrasound scan of the abdomen and pelvis: It is a noninvasive procedure that uses high frequency sound waves to produce real-time images. An ultrasound exam may not always be accurate in suspecting the diagnosis, since the following may have similar features on an USG exam
  • Endometrial stromal sarcoma
  • Adenomyosis (a benign condition)
  • Uterine fibroids (benign tumors)
• Abdominal and pelvic CT scan: It is a noninvasive procedure that provides more details of soft tissues, blood vessels, and internal organs
• Pelvic MRI scan: It is a noninvasive medical test that uses a powerful magnetic field to produce images of soft tissues, bones, organs, and all other internal structures of the abdomen and pelvis
• Blood tests that include:
  • Complete blood count (CBC) to detect the cause of anemia
  • Determination of estrogen/progesterone levels in blood
• Hysteroscopy: This procedure involves placing a probe through the cervix to examine the cavity of the uterus. This exam is helpful in detecting submucosal tumors
• Hysterosalpingography: It is usually performed in individuals with infertility. In this procedure, the structure of the uterus and fallopian tubes are studied by using a dye and X-ray images
• Needle biopsy of tumor: A needle biopsy may not be helpful, because one may not be able to visualize the different morphological areas of the tumor. Hence, a needle biopsy as a diagnostic tool has certain limitations, and an open surgical biopsy is preferred
• Open biopsy of tumor: A tissue biopsy is performed and sent to a laboratory for a pathological examination, who examines the biopsy under a microscope. After putting together clinical findings, special studies on tissues (if needed) and with microscope findings, the pathologist arrives at a definitive diagnosis
• Dilation and curettage (D&C) of the uterus or an endometrial biopsy: These are not helpful in establishing a proper classification of ES tumors such as low-grade and high-grade endometrial stromal sarcomas
• Endometrial curettage or biopsy: It is important to note that even though, in some individuals, endometrial curettage is an important diagnostic tool, the result may appear negative for malignancy, despite the presence of the tumor
• In case of a hysterectomy, extensive sampling of the removed uterus during a pathological examination is necessary, before arriving at a definitive diagnosis of ESS

A differential diagnosis to eliminate the following tumor types is considered, before arriving at a definitive diagnosis of ESS:

• Adenomyosis
• Cellular endometrial polyp
• Cellular leiomyoma
• Low-grade mullerian-adenosarcoma
• The following tumors may be confused with metastatic endometrial stromal sarcoma occurring outside the genital tract (known as extragenital ESS):
  • Gastrointestinal stromal tumor (GIST)
  • Hemangiopericytoma
  • Lymphangiomyomatosis
  • Mesenchymal cystic hamartoma of the lung

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Endometrial Stromal Sarcoma?

The possible complications of Endometrial Stromal Sarcoma include:

• Stress and anxiety due to cancer of the uterus
• Infertility
• Heavy and prolonged menstrual bleeding may result in anemia
• Polypoid tumors may undergo mechanical injury, such as torsion or twisting, which can result in excruciating pain
• Such polyp-shaped tumors are known to cause cervical prolapse, in some cases
• Some tumors may grow to large sizes, and even grow out of the uterus affecting adjoining reproductive organs
• Spread of tumor to various local and regional sites: In many cases, ESS tumors are diagnosed during advanced stages, when it has already metastasized (such as to the lungs or ovary)
• Recurrence of the tumor due to its partial or incomplete surgical removal
• Side effects of chemotherapy (such as toxicity) and radiation
• Sexual dysfunction can take place as a side effect of surgery, chemotherapy, or radiation therapy

How is Endometrial Stromal Sarcoma Treated?

Once a diagnosis of cancer of the uterus has been made, the extent to which the tumor has spread is assessed. This is called staging.

Following is the staging protocol for uterine cancer, according to the American Joint Committee on Cancer (AJCC), updated July 2016:

Stage I uterine cancer: The cancer is found in the uterus only. Stage I is divided into stages IA and IB, based on how far the cancer has spread.

• Stage IA: The cancer is in the endometrium only or less than halfway through the myometrium (muscle layer of the uterus).
• Stage IB: The cancer has spread halfway or more into the myometrium.

Stage II uterine cancer: The cancer has spread into connective tissue of the cervix, but has not spread outside the uterus.

Stage III uterine cancer: The cancer has spread beyond the uterus and cervix, but has not spread beyond the pelvis. Stage III is divided into stages IIIA, IIIB, and IIIC, based on how far the cancer has spread within the pelvis.

• Stage IIIA: The cancer has spread to the outer layer of the uterus and/or to the fallopian tubes, ovaries, and ligaments of the uterus.
• Stage IIIB: The cancer has spread to the vagina and/or to the parametrium (connective tissue and fat around the uterus).
• Stage IIIC: The cancer has spread to lymph nodes in the pelvis and/or around the aorta (largest artery in the body, which carries blood away from the heart).

Stage IV uterine cancer: The cancer has spread beyond the pelvis. Stage IV is divided into stages IVA and IVB, based on how far the cancer has spread.

• Stage IVA: The cancer has spread to the bladder and/or bowel wall.
• Stage IVB: The cancer has spread to other parts of the body beyond the pelvis, including the abdomen and/or lymph nodes in the groin.

(Source: Stages of Uterine Cancer, July 2016, provided by the National Cancer Institute at the National Institutes of Health; U.S. Department of Health and Human Services)

The following treatment measures may be considered for Endometrial Stromal Sarcoma:

Surgery: In younger women, who have only early-stage disease, appropriate surgical treatment with ovarian conservation may be an option.

• Hysterectomy: A hysterectomy, or removal of the uterus, is the most common treatment procedure for localized (non-metastasized) cancer. In this procedure, the uterus and cervix are removed. This is done by making an incision on the abdomen (termed abdominal hysterectomy), or through the vagina (termed vaginal hysterectomy), or by using a laparoscope (termed laparoscopic hysterectomy). Surgery is performed under general or epidural anesthesia, though the ability to have children is lost. Complications, such as bleeding, infection, or damage to the urinary tract, or the intestinal system may occur in rare cases
• Radical hysterectomy: A radical hysterectomy, removal of the uterus and tissues surrounding it, may be performed. But, this is typically more suited for tumors that have spread beyond the uterus. The uterus, cervix, the upper part of the vagina and tissues, next to the uterus are removed. Additionally, some pelvic lymph nodes may also be surgically taken out. The surgery is performed under anesthesia and may be carried out, via an incision made on the abdomen or by using laparoscopy. With this invasive procedure, the ability to have children is lost. Rarely, complications such as bleeding, infection, or damage to the urinary tract or the intestinal system, may occur. Removal of lymph nodes may lead to swelling of legs (lymphedema)
• Pelvic exenteration: The uterus, tissues surrounding the uterus, cervix, pelvic lymph nodes, and the upper part of the vagina, are removed. In addition, depending on the tumor spread, the remainder of the vagina, the bladder, rectum, and a part of the colon, may also be removed. Recovery from this surgery takes a long period
• Arterial embolization may be used to provide temporary relief from the symptoms, and reduce blood loss during a surgical procedure
• Post-operative care is important: One must maintain minimum activity levels, until the surgical wound heals

Chemotherapy:

• Medications are used to kill the tumor cells, which may be given as oral pills or injected into veins
• A combination of chemotherapy medications may be used

Radiation therapy:

• This procedure uses high-energy beams to kill the cancer cells
• These beams may be delivered from outside the body (external beam radiation therapy) or the radioactive material maybe placed inside the vagina or the uterus (internal radiation therapy or brachytherapy)

Hormone therapy:

• Hormonal therapy is a medical treatment used for women with advanced Endometrial Stromal Sarcomas that have metastasized beyond the uterus. It can also help in preventing or reducing the risk of recurrences
• The treatment options include taking the following medications that affect the hormone levels in the body:
  • Synthetic progestin: Synthetic progestin, a type of hormone progesterone, may help prevent the development and progression of endometrial cancer cells
  • Luteinizing hormone (LH): Also called lutropin, this hormone therapy drug helps lower an individual’s estrogen level in the body, or decrease the body’s ability to use the available estrogen. Endometrial cancer cells rely on estrogen (the primary female sex hormone) to proliferate, and thus, administering LH drugs may cause the cancer cells to die out

In addition to traditional adjuvant therapies, the following techniques are being investigated for cancers of the uterus, in general:

• Immunotherapy aims to stimulate the patient’s immune system to recognize and destroy the cancer cells. It includes:
  • Antigen vaccines
  • DNA vaccines
  • Viral therapy
  • Gene therapy
• Currently, clinical trials on adjuvant chemotherapy and combinational chemotherapy, as secondary treatment to hysterectomy, are showing promising results on reducing the risk of relapse

Advanced stage tumors with metastasis may be treated on a case-by-case basis; often symptomatic treatment with radiation and/or chemotherapy is attempted. Many patients with metastatic or locally advanced tumors may be referred for clinical trials for experimental treatment options.

Once treatment is complete, it is recommended that the patient schedule regular check-ups (and for a long duration of time), based on the recommendation of the specialist treating them. Close monitoring is necessary, since the tumor can recur locally or with distant metastasis, even 20 years following its initial diagnosis.

How can Endometrial Stromal Sarcoma be Prevented?

Current medical research has not established a method of preventing Endometrial Stromal Sarcoma. However, the following general factors may be considered to reduce the risk for tumor development:

• Address any condition causing hormonal imbalance in the body
• Maintain weight through proper diet modification and physical exercises, if you are overweight/obese
• Avoid alcohol consumption or limit its intake
• Have a balanced diet that is not high in meat and low in vegetables; a balanced diet can also help avoid any mineral or vitamin deficiencies in the body
• Regular medical screening at periodic intervals with blood tests, radiological scans, and physical examinations are mandatory, due to risk of recurrence and metastasizing potential of the tumor. Often several years of active vigilance may be necessary

What is the Prognosis of Endometrial Stromal Sarcoma? (Outcomes/Resolutions)

• The prognosis of Endometrial Stromal Sarcoma mainly depends upon the subtype of ESS and the stage of the tumor. An early diagnosis and prompt treatment of low-grade tumors can result in a good prognosis
• However, in many cases, ESS tumors are diagnosed during advanced stages, and so, the prognosis is typically guarded. It is estimated that approximately 30-50% women with ESS have tumor spread beyond the uterus, at the time of diagnosis
• In general, the prognosis depends upon a set of several factors that include:
  • The size of the tumor and the extent of its invasion: Individuals with small-sized tumors fare better than those with large-sized tumors
  • Stage of cancer: With lower-stage tumors, when the tumor is confined to site of origin, the prognosis is usually excellent with appropriate therapy. In higher-stage tumors, such as tumors with metastasis, the prognosis is poor
  • Cell growth rate of the cancer: A high mitotic count, more than 5 per 10 high-power fields, is an unfavorable prognostic factor
  • Overall health of the individual: Individuals with overall excellent health have better prognosis compared with those with poor health
  • Age of the individual: Older individuals (over 50 years) generally have poorer prognosis than younger individuals
  • Ethnicity of the individual: Generally, dark-skinned women have a poorer prognosis than fair-skinned individuals
  • CD10 negative or low expression of CD10 on immunohistochemical studies is associated with poorer prognosis
  • Lack of estrogen and progesterone receptors are independent prognostic factors for poor survival
  • Individuals with bulky disease have a poorer prognosis
  • Involvement of the regional lymph nodes, which can adversely affect the prognosis. Individuals with nodal metastasis have generally poorer outcomes
  • Involvement of vital organs may complicate the condition
  • The surgical respectability of the tumor (meaning, if the tumor can be removed completely): A lack of primary surgery (due to various reasons) is a poor prognostic indicator
  • Whether the tumor is occurring for the first time, or is a recurrent tumor. Recurring tumors have worse prognosis compared to tumors that do not recur
  • Response to treatment: Tumors that respond to treatment have better prognosis compared to tumors that do not respond to treatment
  • Progression of the condition makes the outcome worse
• The combination chemotherapy drugs used, may have some severe side effects (like cardio-toxicity). This chiefly impacts the elderly adults, or those who are already affected by other medical conditions. Individuals, who tolerate chemotherapy sessions better, generally have better outcomes

Additional and Relevant Useful Information for Endometrial Stromal Sarcoma:

• Removal of the uterus will cause the regular menstrual bleeding to stop. This also means that a woman may not have children after uterus removal; though, sexual intercourse is still possible 
• Hysterectomy is a surgical procedure characterized by the surgical removal of the uterus

The following link will help you understand hysterectomy surgical procedure:

http://www.dovemed.com/common-procedures/procedures-surgical/hysterectomy-abdominal-with-salpingo-oophorectomy/