High-Grade Endometrial Stromal Sarcoma: Understanding Your Pathology Report

Section Editor: Kianoosh Keyhanian MD FRCPC
September 3, 2026

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.

What causes high-grade endometrial stromal sarcoma?

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.

YWHAE::NUTM2A/B — The first pattern recognized, and the one that originally established high-grade endometrial stromal sarcoma as a distinct diagnosis.
BCOR rearrangement — Most often a fusion between ZC3H7B and BCOR.
BCOR internal tandem duplication — A section of the BCOR gene is repeated rather than joined to another gene.

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.

What are the symptoms?

The symptoms overlap with those of much more common and less serious conditions, which is one reason the diagnosis is often unexpected.

Abnormal vaginal bleeding — The most common symptom. This may be heavy periods, bleeding between periods, or bleeding after menopause.
Pelvic pain or pressure — Often described as a dull ache or a feeling of fullness.
A mass in the uterus — Sometimes felt on examination or seen on imaging, and frequently mistaken for a fibroid beforehand.
Rapid change — Symptoms may develop or worsen over weeks to months rather than years.

How is the diagnosis made?

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.

What does high-grade endometrial stromal sarcoma look like under the microscope?

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.

Rounded or spindle-shaped tumor cells — The appearance depends on which genetic change is present. Tumors driven by the YWHAE fusion often contain sheets of round cells alongside an area of milder-looking spindle cells. Tumors driven by BCOR changes tend to be spindle-shaped with a gelatinous background.
Marked nuclear atypia — The nuclei vary considerably in size and shape. Nuclear atypia of this degree is what makes the tumor high-grade.
Frequent cell division — Many mitotic figures, meaning cells caught in the act of dividing, are present.
Necrosis — Areas of dead tumor tissue, called necrosis, are common.
Invasion into the muscle wall — The tumor grows into the muscular wall of the uterus rather than remaining within the lining.
Small blood vessels within the tumor — Delicate vessels running through the tumor are a feature of stromal tumors generally.

Immunohistochemistry

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.

Cyclin D1. Usually strongly positive. This is one of the most useful markers for this diagnosis.
BCOR. Often positive, particularly in tumors driven by a BCOR gene change.
CD10. Variable, and often only weakly or absent. This differs from the low-grade form, where CD10 is typically strongly positive throughout.
Estrogen receptor and progesterone receptor. Usually negative or only weakly positive. This result has direct treatment consequences, described in the section on how this differs from the low-grade form.
Smooth muscle markers. Usually negative. Desmin and similar markers help rule out a tumor arising from muscle, such as a leiomyosarcoma.

Molecular testing

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.

How is this different from low-grade endometrial stromal sarcoma?

The two conditions share a name but behave differently, so it is important to be clear about which one your report describes.

Appearance — Low-grade tumor cells closely resemble the normal stromal cells of the lining. High-grade tumor cells look clearly abnormal.
Growth — Low-grade tumors grow slowly, often over years. High-grade tumors grow more quickly and are more likely to have spread by the time they are found.
Genetic changes — The low-grade form typically carries a JAZF1 gene fusion. The high-grade form carries one of the three changes described above.
Hormone receptors — Low-grade tumors are usually positive for estrogen and progesterone receptors, so hormone-blocking treatment often works well. High-grade tumors are usually negative, so hormonal treatment is generally not effective, and chemotherapy is used instead.

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.

Tumor extension

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.

Margins

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.

Negative margin — No tumor cells at the cut edge. This is the goal of surgery and lowers the risk of the cancer returning in the same area.
Positive margin — Tumor cells present at the cut edge, meaning some cancer may remain. Further surgery or radiation therapy may be recommended.

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

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

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.

Pathologic stage

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 I — The tumor is confined to the uterus. Stage IA means it measures 5 cm or less, and stage IB means it measures more than 5 cm.
Stage II — The tumor has extended beyond the uterus but remains within the pelvis. Stage IIA means the ovaries or fallopian tubes are involved, and stage IIB means other pelvic tissue is involved.
Stage III — The tumor involves tissue in the abdomen or has spread to lymph nodes. Stage IIIA is a single site, stage IIIB is more than one site, and stage IIIC means spread to pelvic or abdominal lymph nodes.
Stage IV — Stage IVA means the tumor has invaded the bladder or rectum. Stage IVB means it has spread to distant organs such as the lungs.

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.

What is the prognosis?

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.

Questions to ask your doctor

Is my tumor high-grade or low-grade, and what does that mean for me?
What stage is my cancer?
Was a gene fusion identified, and which one?
Were the margins negative, and was the whole tumor removed?
Was lymphovascular invasion present?
Were lymph nodes removed, and did any contain cancer?
Did a pathologist who specializes in gynecologic cancers review my case?
Do I need chemotherapy or radiation therapy?
Would hormone-blocking treatment help in my case?
Should I be referred to a gynecologic oncologist or a sarcoma center?
Are there clinical trials I should consider?
How often will I need follow-up, and what will it involve?
What symptoms should prompt me to contact you between appointments?