Endometrial stromal sarcoma is a rare type of cancer that grows in the inner lining of the uterus, specifically in the connective tissue that supports the endometrium. While most uterine cancers are more common types, this particular sarcoma affects only a small number of people each year, mostly during or after their reproductive years.

Understanding Endometrial Stromal Sarcoma

Endometrial stromal sarcoma, often shortened to ESS, develops in a layer of tissue called the stroma, which is the connective tissue found in the lining of the uterus. This cancer is quite uncommon, making up only about 0.2% of all uterine cancers. To put this in perspective, uterine sarcomas as a whole account for just 2 to 5% of all cancers that form in the uterus, and ESS represents roughly 10% of those rare uterine sarcomas.^[1][3]

When doctors classify ESS, they look at how the cancer cells appear under a microscope and how quickly they are likely to grow and spread. This leads to two main categories: low-grade ESS and high-grade ESS. Low-grade ESS is less aggressive, meaning the cancer cells look somewhat similar to normal cells and tend to grow slowly. High-grade ESS is more aggressive, with cancer cells that look very different from normal cells and may grow and spread more quickly. Patients with high-grade ESS are often diagnosed when the disease has already reached stage 3 or 4.^[1][2]

ESS can remain confined to the uterus, or it may spread to nearby areas such as the pelvis, or even to more distant parts of the body. The cancer may grow into the muscular wall of the uterus or reach pelvic lymph nodes. In some cases, it can spread to organs far from the uterus, including the lungs or abdomen.^[2]

How Common Is This Cancer?

Endometrial stromal sarcoma is extremely rare. In England, an average of 79 cases are diagnosed each year. The median age at diagnosis is 55 years, though the disease can occur in anyone with a uterus at any age. Most cases are found in people between 40 and 60 years old, with the mean age ranging from 42 to 58 years in different studies.^[2][6]

The annual incidence of ESS is approximately one to two cases per million women in the general population. Between 10 and 25% of people diagnosed with ESS are premenopausal, meaning they have not yet gone through menopause. This cancer affects younger individuals compared to other types of uterine malignancies.^[6]

ESS is the second most common type of uterine sarcoma. However, because uterine sarcomas themselves are so rare, ESS remains an uncommon diagnosis overall.^[1]

What Causes Endometrial Stromal Sarcoma?

The exact cause of endometrial stromal sarcoma is not well understood. Scientists know that the cancer develops when cells in the uterine stroma undergo genetic mutations that cause them to grow out of control. However, what triggers these DNA changes remains unknown.^[4]

The origin and biology of stromal sarcomas are still being studied. Researchers have identified a specific genetic change called a translocation, labeled t(7;17), which involves two zinc finger genes. This genetic alteration has been found in most cases of ESS. There is also evidence that chromosomal deletion on chromosome 7 may play a role in tumor development and progression, as this finding appears in more than half of ESS cases.^[6]

The genetic makeup of these tumors shows they are typically diploid, meaning they have a normal number of chromosomes, and they have a low rate of cell division, which is measured as the S-phase fraction.^[6]

Risk Factors for Developing ESS

While the direct causes of endometrial stromal sarcoma are unclear, several risk factors have been identified that may increase a person’s chance of developing this cancer. It is important to remember that having one or more risk factors does not mean a person will definitely develop ESS, but awareness of these factors can help with early detection.

One of the documented risk factors is previous pelvic radiation therapy. This treatment, often given for other cancers or sometimes for benign conditions like abnormal uterine bleeding, can increase the risk of developing uterine sarcoma. Sarcomas related to radiation typically appear five to 25 years after the therapy was completed. However, this is a rare occurrence, affecting only 10 to 25% of people with uterine sarcoma.^[4][11]

Long-term use of tamoxifen, a medication used to treat or prevent breast cancer, has also been linked to an increased risk of uterine sarcoma. Tamoxifen has estrogenic effects on the uterus, meaning it can stimulate the uterine lining in ways similar to the hormone estrogen. This stimulation may contribute to the development of abnormal growths.^[4][11]

Some research suggests a connection between ESS and exposure to unopposed estrogens, which means estrogen without the balancing effects of progesterone. Conditions such as polycystic ovary syndrome (PCOS), a hormonal disorder that can cause irregular periods and other symptoms, have also been implicated in a possible link to ESS.^[2][6]

Genetic factors also play a role. Having the gene that causes retinoblastoma, a type of eye cancer, increases the risk of developing some types of uterine sarcoma. Additionally, a rare family cancer syndrome called hereditary leiomyomatosis and renal cell cancer (HLRCC) is linked to uterine sarcomas.^[4]

Black women are twice as likely as white women to develop uterine sarcomas, though researchers do not yet understand why race is a risk factor for this cancer.^[4]

Recognizing the Symptoms

Symptoms of endometrial stromal sarcoma can vary depending on the size and location of the tumor. Some people may experience all, some, or none of the typical symptoms. In less common cases, people with undiagnosed ESS may not notice any symptoms at all until the disease has progressed.^[1][2]

The most common symptom is abnormal vaginal bleeding. This may include bleeding between periods, heavier bleeding than usual during a period, or bleeding after menopause. Any unusual vaginal bleeding should be discussed with a doctor, as it can be a sign of ESS or other conditions.^[2][4]

Pelvic pain is another frequent symptom. Some people describe this as a persistent discomfort or cramping in the lower abdomen or pelvic region. In one reported case, a person experienced intense cramps that they knew were not normal period cramps, which led them to seek medical attention.^[3]

A noticeable lump or mass in the pelvic or stomach area may also be present. This mass might grow larger over time, and in some cases, it can be felt during a physical examination. A feeling of fullness in the abdomen is another related symptom.^[2][4]

Other symptoms include abnormal vaginal discharge, pain with urination, changes in urinary habits such as needing to urinate more often, and constipation. Some people may also experience a prolonged period that lasts for more than a month.^[1][2]

Because the symptoms of ESS overlap significantly with noncancerous conditions such as fibroids, adenomyosis, and endometrial polyps, doctors can sometimes misdiagnose the condition initially. Spotting and bleeding changes around perimenopause can also create uncertainty. This makes it essential to discuss any new or worsening vaginal bleeding with a healthcare provider to rule out ESS.^[1]

How to Prevent Endometrial Stromal Sarcoma

Because the exact causes of endometrial stromal sarcoma are not fully understood, there are no guaranteed ways to prevent this cancer. However, being aware of risk factors and taking steps to manage them may help reduce the chances of developing ESS.

For people taking tamoxifen for breast cancer treatment or prevention, it is crucial to have regular follow-up pelvic examinations. Any abnormal uterine bleeding should be reported immediately, and an endometrial biopsy should be performed if needed. This vigilance allows for early detection if any uterine changes occur.^[11]

Individuals who have undergone pelvic radiation therapy should also be monitored closely over the long term. Since sarcomas can develop years or even decades after radiation treatment, maintaining regular check-ups with a healthcare provider is important.

Genetic counseling, risk assessment, and testing may be beneficial for people with a family history of certain cancers, such as retinoblastoma or hereditary leiomyomatosis and renal cell cancer. Understanding whether you carry genes linked to a higher risk can help guide preventive measures and screening strategies.^[4]

Maintaining overall uterine health through regular gynecological check-ups is another important step. While these visits cannot prevent ESS, they can help detect any abnormalities early, when treatment is most effective.

What Happens in the Body: Pathophysiology

Endometrial stromal sarcoma develops when the normal connective tissue cells in the endometrial stroma begin to change and grow abnormally. These cells, which normally support the lining of the uterus, undergo genetic mutations that cause them to multiply uncontrollably and form a tumor.

In low-grade ESS, the cancer cells still resemble normal stromal cells fairly closely. They tend to grow slowly and may take years to spread beyond the uterus. The worm-like appearance of these cells under a microscope is a characteristic feature. Low-grade ESS may infiltrate the muscular wall of the uterus, known as the myometrium, and can spread to pelvic lymph nodes.^[1]

In high-grade ESS, the cancer cells look significantly different from normal cells. They divide more rapidly and are more likely to have already spread outside the uterus by the time of diagnosis. High-grade ESS is more aggressive and harder to treat, often presenting at advanced stages.^[1]

ESS can spread through several pathways. It may grow directly into surrounding tissues, such as the myometrium or the parametrium, which is the connective tissue surrounding the uterus. It can also spread through the lymphatic system to lymph nodes or through the bloodstream to distant organs like the lungs, liver, or abdomen.^[2]

One unique feature of ESS is its indolent, or slow-growing, nature, particularly in low-grade cases. Local recurrences and distant metastases can occur even 20 years after the initial diagnosis, making long-term follow-up essential.^[6]

ESS tumors often express receptors for hormones like estrogen and progesterone, meaning the cancer cells can respond to these hormones. This is why hormone-blocking therapies can sometimes be effective in treating ESS. The tumors may grow or spread in response to hormonal stimulation, which is why treatments that reduce or block estrogen and progesterone are used in managing this cancer.^[6]