Low-grade endometrial stromal sarcoma is an uncommon cancer that starts in the supporting tissue of the lining of the uterus. That supporting tissue is called stroma, and it is the material that normally surrounds the glands of the endometrium. A sarcoma is a cancer arising from connective or supporting tissue rather than from the lining cells that give rise to most cancers of the uterus.
The words “low-grade” mean the tumor cells closely resemble the normal stromal cells of the lining and grow slowly. This is a cancer, but a slow-moving one, and most people diagnosed with it do well. It is most often found in the years before and around menopause, at an average age in the mid-forties.
Two features shape everything about this diagnosis. The tumor grows slowly but can come back many years later, so follow-up continues for a long time. And it depends on estrogen to grow, which opens up treatment options and makes certain medications unsafe. Both are covered below.
The cause is not known, but the genetic event inside the tumor cells is well described. In most cases, two genes that are normally separate join together, creating a fusion gene that drives the cells to grow.
The most common is a fusion between JAZF1 and SUZ12, found in roughly half of these tumors. Other tumors carry fusions involving a gene called PHF1. These changes arise within the tumor during a person’s life. They are not inherited and are not passed to children.
Some factors have been associated with a higher risk, though none is established as a direct cause.
The symptoms overlap with those of much more common and less serious conditions, which is why many of these tumors are thought to be fibroids before surgery.
Tissue is obtained by an endometrial biopsy, a dilation and curettage, or surgery to remove the uterus. A pathologist then examines the tissue under a microscope.
A biopsy is often not enough for this diagnosis, and the reason is specific. The tumor cells look much like normal stromal cells, so what identifies the tumor as a cancer is not the cells themselves but how they grow. They push into the surrounding muscle wall in finger-like extensions, and they enter blood vessels. Those growth patterns can only be seen at the edge of the tumor, which a small biopsy usually does not capture.
This is also what separates the diagnosis from an endometrial stromal nodule, a benign tumor made of the same cells. A nodule has a smooth, well-defined edge and does not invade or enter vessels. The distinction rests entirely on the border, so it can be made only after removing the tumor.
Imaging cannot make this diagnosis, and many of these tumors are thought to be fibroids beforehand.
Low-grade endometrial stromal sarcoma is a cancer made of cells that closely resemble the normal stromal cells of the uterine lining. Under the microscope, the pathologist looks for the following features.
Immunohistochemistry is a laboratory test that uses antibodies to detect specific proteins inside cells. Here it confirms that the tumor comes from stromal tissue and separates it from tumors arising from muscle, which can look similar.
Testing for the JAZF1-SUZ12 fusion or a PHF1 rearrangement may be performed when the diagnosis is unclear from the appearance and stains alone. Your report may describe fluorescence in situ hybridization, which looks for a break in a specific gene, or a sequencing test that identifies the two joined genes.
A positive result supports the diagnosis. A negative result does not exclude it, since not every tumor carries one of the recognized fusions.
The two share a name but are separate diagnoses with different treatments and different outlooks.
The uterus has three layers: the endometrium lining the inside, the myometrium forming the muscular wall, and the serosa covering the outside. Tumor extension describes how far the cancer has grown through these layers.
Low-grade endometrial stromal sarcoma begins in the lining and characteristically grows into the myometrium. It may reach or pass through the serosa into surrounding pelvic tissue, and in advanced cases it involves nearby organs such as the ovaries, fallopian tubes, bladder, or rectum. How far the tumor has extended is one of the main factors determining the stage.
A margin is the edge of the tissue removed during surgery. The pathologist examines the margins to determine whether the whole tumor was taken out. Margins are assessed only after surgery that removes the tumor, not after a biopsy.
The margins examined depend on the operation performed. They may include the cervix where it joins the uterus, the outer surface of the cervix, and the connective tissue on either side of the uterus. The upper vagina is included if part of it was removed.
Lymphovascular invasion means tumor cells have entered small blood vessels or lymphatic channels near the tumor. These vessels can carry cells to lymph nodes or to other parts of the body.
This finding is especially common in low-grade endometrial stromal sarcoma, and growth inside vessels is one of the features that defines the diagnosis. Its presence here is expected, not a sign that something has changed for the worse. Your report will describe it as present or absent.
Lymph nodes are small immune organs found throughout the body. Cancer cells can travel to them and form a metastasis, meaning a deposit of cancer in a new location.
Lymph nodes are not routinely removed during surgery for this diagnosis, because spread to nodes is uncommon and removing them has not been shown to improve outcomes. When nodes are removed, the report states how many were examined and how many contained cancer.
Stage describes how far the cancer has spread. Two systems are used for uterine sarcomas, and they align closely. The International Federation of Gynecology and Obstetrics system uses Roman numerals. The American Joint Committee on Cancer system describes the tumor, nodes, and distant spread separately as T, N, and M.
Most of these tumors are found at stage I. Stage is the strongest predictor of outcome.
Surgery is the main treatment, and the fact that these tumors depend on estrogen shapes much of what follows.
One point deserves particular attention. Because these tumors are stimulated by estrogen, estrogen-containing hormone replacement therapy and tamoxifen are generally considered unsafe after this diagnosis. If you are taking either, tell the team managing this cancer. Stopping them has been reported to stabilize disease in some cases. If you were prescribed tamoxifen for breast cancer, this needs a joint discussion between your teams rather than a decision by either alone.
The outlook is generally good, particularly for tumors confined to the uterus. Reported five-year survival is above 90 out of 100 for stage I and stage II disease. For tumors that have spread beyond the uterus, the figure is closer to 50 out of 100, though hormone-blocking treatment can control the disease for long periods even then.
Recurrence is the main long-term concern, and it behaves differently here than in most cancers. It can happen slowly and late, sometimes more than a decade after treatment, and most often appears in the pelvis, the abdomen, or the lungs. A recurrence is usually treatable, often with further surgery and hormone-blocking medication.
Because these tumors are uncommon, published figures come from small groups of patients and vary between studies. They do not account for your stage, the completeness of your surgery, or the treatment you receive. Your own team is best placed to explain what the outlook means for you.