High-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 and holds together the glands of the endometrium. A sarcoma is a cancer that arises from connective or supporting tissue rather than from the lining cells that give rise to most cancers of the uterus.
The term “high-grade” means the tumor cells look very abnormal under the microscope and divide frequently. They are also more likely to grow beyond the uterus than the cells of a low-grade endometrial stromal sarcoma. These are separate diagnoses with different treatments and outlooks, and the distinction matters.
This article will help you understand what this diagnosis means on your pathology report, what each section of the report describes, and why it matters for your care.
The cause is not known. What is understood is the genetic event inside the tumor cells that drives it. In most cases, two genes that are normally separate become joined together, creating a fusion gene that behaves abnormally and pushes the cells to grow.
Three fusion patterns define this diagnosis, and your report may name one of them.
These changes arise within the tumor itself during a person’s life. They are not inherited and are not passed to children. Unlike the low-grade form, no clear risk factors have been established for this diagnosis.
The symptoms overlap with those of much more common and less serious conditions, which is one reason the diagnosis is often unexpected.
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 can raise the possibility of this diagnosis, but it is rarely enough on its own. These tumors often contain more than one pattern, and the biopsy sample may not represent the whole tumor. Doctors usually make the final diagnosis only after removing the tumor and examining it completely.
Imaging cannot make this diagnosis. Many of these tumors are thought to be fibroids before surgery, so learning the diagnosis afterward often comes as a surprise. Additional laboratory tests almost always confirm it, as described in the two sections below.
High-grade endometrial stromal sarcoma is a cancer of the uterus’s supporting tissue, made of cells that look clearly abnormal and divide frequently. Under the microscope, the pathologist looks for the following features.
Immunohistochemistry is a laboratory test that uses antibodies to detect specific proteins inside cells. It is used here to confirm that the tumor comes from stromal tissue and to separate it from other uterine cancers that can look similar. Your report lists protein names and whether each is present.
Because the three genetic changes define this diagnosis, testing for them is often performed. 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 genes joined together.
A positive result confirms the diagnosis. A negative result does not exclude it, since not every case carries one of the recognized changes. Molecular testing is most valuable in cases that are difficult to classify by appearance alone, which is a substantial proportion of cases.
The two conditions share a name but behave differently, so it is important to be clear about which one your report describes.
There is also a third, separate diagnosis called undifferentiated uterine sarcoma, in which the tumor cells no longer resemble stromal cells at all. The high-grade form sits between the low-grade form and that diagnosis in terms of behaviors.
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.
High-grade endometrial stromal sarcoma begins in the lining and typically grows into the myometrium. It may reach or pass through the serosa into the 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.
Your report will describe this as present or absent. When present, the risk of the cancer spreading beyond the uterus is higher, and your team may recommend additional treatment. Lymphovascular invasion is common in this type of tumor.
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 always removed during surgery for this diagnosis, because spread to lymph nodes is less common in sarcomas than in cancers arising from lining cells. 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.
Stage is the single strongest predictor of outcome, and it can only be determined after surgery and, in some cases, after imaging of the rest of the body.
The outlook depends most on the stage at diagnosis. Tumors confined to the uterus have a considerably better outlook than those that have spread, which is the same pattern seen in most cancers.
Compared with the low-grade form, this diagnosis carries a higher chance of the cancer returning and of it spreading to distant organs. Recurrences also tend to happen earlier, often within the first few years. Compared with undifferentiated uterine sarcoma, the outlook is better. This diagnosis sits between the two.
Because these tumors are uncommon, the published numbers come from small groups of patients and vary widely between studies. Figures found online may not reflect your situation, and they do not account for the stage, the completeness of surgery, or the treatment you receive. Your own team is in a far better position to discuss what the outlook means for you.
Treatment usually begins with surgery to remove the uterus, and often the fallopian tubes and ovaries. Chemotherapy is commonly recommended afterward, and radiation therapy is used in some situations. Hormone-blocking treatment, which works well for the low-grade form, is generally not effective here because these tumors lack hormone receptors.