Leiomyosarcoma: Understanding Your Pathology Report

Section Editor: Bibianna Purgina MD FRCPC
September 17, 2026

Leiomyosarcoma is a cancer that develops from smooth muscle cells. Smooth muscle is the type of muscle that works without conscious control. It is found in the walls of blood vessels, the digestive tract, the uterus, and the skin. Leiomyosarcoma is a type of sarcoma, a cancer that begins in the body’s connective tissues.

Leiomyosarcoma makes up about 10% to 20% of all soft tissue sarcomas. Outside the uterus, it most often starts in the retroperitoneum, which is the space at the back of the abdomen. It can also start in the wall of a large blood vessel, in the arms or legs, or in the skin. Leiomyosarcoma usually affects adults, most often after age 50.

This article explains how leiomyosarcoma outside the uterus is diagnosed and what the grade, size, margins, and stage in your leiomyosarcoma pathology report mean. Leiomyosarcoma that starts in the uterus is staged and treated differently, as described in our article on uterine leiomyosarcoma.

What causes leiomyosarcoma?

Leiomyosarcoma develops when smooth muscle cells collect many changes in their genes and chromosomes that allow them to grow without control. Unlike some sarcomas, it does not have a single defining genetic change such as a gene fusion. Instead, the tumor cells usually have many changes, often including loss of genes that normally act as brakes on cell growth.

For most people, doctors find no cause. A small number of cases of leiomyosarcoma develop in an area treated with radiation therapy years earlier. Rarely, leiomyosarcoma occurs in people with an inherited condition that raises cancer risk, such as Li-Fraumeni syndrome or hereditary retinoblastoma.

What are the symptoms of leiomyosarcoma?

The symptoms of leiomyosarcoma depend on where the tumor starts:

Retroperitoneum. Tumors here often grow large before they cause symptoms. They may cause abdominal or back pain or fullness.
Large blood vessels. A tumor in the inferior vena cava, the large vein that returns blood from the lower body, may cause abdominal or flank pain or swelling of the legs.
Arms, legs, and trunk. The usual symptom is a lump that grows over time and may or may not be painful.
Skin. A small, firm bump in the skin that may be tender.

How is the diagnosis made?

The diagnosis of leiomyosarcoma is made after a pathologist examines a sample of the tumor under the microscope. The sample is usually obtained by a core needle biopsy, which removes small pieces of the tumor with a needle. Doctors often diagnose skin tumors after removing the entire bump.

Under the microscope, leiomyosarcoma is made of long, thin spindle cells arranged in bundles that cross each other. The cells often have long, blunt-ended nuclei that look abnormal. Pathologists separate leiomyosarcoma from a noncancerous smooth muscle tumor called a leiomyoma by looking for abnormal-looking cells, dividing cells, and dead tumor tissue called necrosis.

Additional tests may be needed to rule out similar-looking tumors. For tumors in the retroperitoneum, a test for extra copies of the MDM2 gene helps rule out a type of fat cancer called dedifferentiated liposarcoma. For tumors in the digestive tract, stains help rule out gastrointestinal stromal tumor (GIST).

Once leiomyosarcoma is confirmed, imaging tests look for spread. CT scans of the chest and abdomen are usually done because leiomyosarcoma most often spreads to the lungs and liver. The next section describes the immunohistochemistry tests used to confirm the diagnosis.

Immunohistochemistry

Immunohistochemistry uses antibodies to show which proteins tumor cells make. For leiomyosarcoma, it confirms that the tumor cells are smooth muscle cells and helps rule out other tumors. Your report may include some of the following:

SMA, desmin, and h-caldesmon. These smooth muscle proteins are usually positive in leiomyosarcoma, and most tumors are positive for at least two. Poorly differentiated tumors may lose some of these proteins.
Keratins and EMA. These proteins are normally found in epithelial cells. They can be positive in a small number of tumor cells in leiomyosarcoma, so the pathologist interprets them together with the other results.
S100 and SOX10. These proteins are negative in leiomyosarcoma. A positive result would suggest melanoma or a nerve sheath tumor instead.
CD117 and DOG1. These proteins are negative in leiomyosarcoma. A positive result would suggest GIST, which is treated very differently.
MDM2 and CDK4. These proteins are usually negative in leiomyosarcoma. A positive result would suggest dedifferentiated liposarcoma.

Not every case of leiomyosarcoma needs every stain. The pathologist chooses tests based on how the tumor looks, where it started, and which other tumors need to be ruled out.

Tumor site

The site where a leiomyosarcoma started is an important part of your report. The site affects how the tumor is staged, how it behaves, and how it is treated.

Retroperitoneum. This is the most common site of leiomyosarcoma outside the uterus. These tumors are often large when found and have a high risk of spreading to the lungs and liver.
Large blood vessels. Leiomyosarcoma is the most common cancer that starts in the wall of a large vein, most often the inferior vena cava. Surgery may require removing and rebuilding part of the vein.
Arms, legs, and trunk. These tumors usually start deep in the soft tissue, often near a blood vessel.
Skin. Smooth muscle tumors that are limited to the skin rarely spread. Current classifications call them atypical intradermal smooth muscle neoplasms rather than leiomyosarcoma. Tumors that grow into the fat under the skin are still called leiomyosarcoma.

Histologic grade

Histologic grade describes how abnormal the cells of a leiomyosarcoma look and how quickly they appear to be growing. Grade is one of the strongest predictors of whether leiomyosarcoma will spread. Pathologists grade it using the FNCLCC system, which adds together scores for three features:

Differentiation. This describes how closely the tumor cells resemble normal smooth muscle. Well-differentiated leiomyosarcoma scores 1, conventional leiomyosarcoma scores 2, and poorly differentiated or pleomorphic leiomyosarcoma scores 3.
Mitotic count. This is the number of dividing cells in 10 high-power fields, which are areas seen through the microscope at high magnification. Fewer than 10 dividing cells score 1, 10 to 19 score 2, and 20 or more score 3.
Necrosis. This is the amount of dead tumor tissue. No necrosis scores 0, less than 50% scores 1, and 50% or more scores 2.

The total score gives the final grade:

Grade 1. Total score of 2 or 3. These tumors are called low grade.
Grade 2. Total score of 4 or 5. These tumors are considered high grade.
Grade 3. Total score of 6 to 8. These tumors are also considered high grade.

Low-grade leiomyosarcoma is less likely to spread. High-grade tumors, especially grade 3 tumors, are more likely to come back after treatment and to spread to other parts of the body.

Tumor size

Tumor size is the greatest dimension of the leiomyosarcoma, measured in centimeters (cm). The final measurement comes from the tumor removed at surgery rather than from a biopsy. For most body sites, size is used to determine the tumor stage (pT). Larger tumors are associated with a higher risk of spread.

Tumor extension

Tumor extension describes whether leiomyosarcoma has grown beyond the tissue where it started into nearby structures such as organs, bone, nerves, or other blood vessels. The pathologist examines the tissue removed with the tumor and reports which structures contain tumor cells.

For tumors in the head and neck, the orbit (the space around the eye), and internal organs, growth into nearby structures raises the tumor stage. For tumors of the trunk, arms, legs, and retroperitoneum, the stage depends on size alone. Extension into nearby structures still affects how surgeons and radiation oncologists plan treatment.

Treatment effect

Some people with leiomyosarcoma receive radiation therapy, chemotherapy, or both before surgery. This is called neoadjuvant or pre-operative treatment. When this happens, the pathologist estimates what percentage of the removed tumor is non-viable (dead) and what percentage is still viable (alive).

A tumor that is 90% or more non-viable is often considered a strong response to pre-operative treatment. For soft tissue sarcomas, including leiomyosarcoma, experts have not agreed on a single cut-off that predicts outcome. Your doctors interpret the percentage together with the other findings in your report.

Treatment changes how tumor cells look under the microscope. For this reason, the grade is usually taken from the biopsy done before treatment. If no treatment was given before surgery, the report may say there was no known presurgical therapy.

Lymphovascular invasion

Lymphovascular invasion means that cells from the leiomyosarcoma are seen inside a small blood vessel or lymphatic channel. These vessels give cancer cells a route to other parts of the body. Current reports may list this finding as “lymphatic and/or vascular invasion.”

Present. Tumor cells were seen inside a vessel. This finding is associated with a higher risk of tumor spread.
Not identified. No tumor cells were seen inside vessels in the tissue examined.

Perineural invasion

Perineural invasion means tumor cells are growing around or along a nerve. It is not a standard item in soft tissue sarcoma reports, but a pathologist may mention it when it is seen in leiomyosarcoma. When present, it suggests the tumor may extend beyond its visible edge and may raise the risk of the tumor coming back in the same place.

Surgical margins

A margin is the edge of tissue cut by the surgeon to remove a leiomyosarcoma. The pathologist examines each margin to see whether tumor cells reach it. For soft tissue sarcomas, margin status is the most important predictor of whether the tumor will come back in the same place.

Negative margin. No tumor cells are seen at the cut edge. The report usually names the closest margin and gives its distance from the tumor.
Close margin. Tumor cells are near the cut edge but do not reach it. Reports often list every margin that is less than 0.5 cm from the tumor.
Positive margin. Tumor cells are present at the cut edge. This means some tumor may remain in the body and raises the risk of the tumor coming back. Further surgery or radiation therapy may be considered.

For leiomyosarcoma of a blood vessel, the report may also describe the vessel margins, which are the cut ends of the vein above and below the tumor.

Lymph nodes

Lymph nodes are small immune organs that filter fluid from the tissues. Leiomyosarcoma rarely spreads to lymph nodes. It much more often spreads through the bloodstream to the lungs and liver. For this reason, doctors usually remove lymph nodes only if they look enlarged or suspicious on imaging.

If lymph nodes are examined, the report states how many were examined and how many contain tumor cells. Tumor cells in a lymph node change the nodal stage to pN1.

Biomarker and genetic testing

Biomarker testing looks for tumor features that guide treatment, predict outcome, or point to an inherited condition. For leiomyosarcoma, no biomarker test currently selects a specific targeted drug. Treatment is chosen based on the grade, the stage, and where the tumor started.

When leiomyosarcoma returns or spreads, the tumor may be tested with a broad next-generation sequencing (NGS) panel. This test looks for changes that could make a person eligible for a clinical trial. A result that finds no targetable change is common and does not change the diagnosis.

Genetic testing for an inherited condition is a separate question from tumor testing. It may be recommended for people diagnosed with leiomyosarcoma at a young age, people who had retinoblastoma as a child, or people with a strong family history of cancer. Our article What is a hereditary cancer syndrome? explains how inherited gene changes are tested. You can learn more about tumor testing in our Biomarkers and Genetic Testing section.

Pathologic stage (pTNM)

The pathologic stage for leiomyosarcoma outside the uterus is assigned using the TNM system from the American Joint Committee on Cancer (AJCC), 8th edition. The tumor stage (pT) is based on the tissue removed at surgery, and the nodal stage (pN) describes the lymph nodes. The metastasis stage (M) is usually determined by imaging and is often not included in the pathology report.

If you received treatment before surgery, the stage may begin with the letter “y,” as in ypT2. A stage beginning with “r” describes a tumor that has come back after treatment.

The tumor stage (pT) for leiomyosarcoma depends on where the tumor started in the body.

Trunk and extremities (chest, back, abdominal wall, arms, and legs):

pT1. The tumor is 5 cm or smaller.
pT2. The tumor is larger than 5 cm but not larger than 10 cm.
pT3. The tumor is larger than 10 cm but not larger than 15 cm.
pT4. The tumor is larger than 15 cm.

Retroperitoneum (the space at the back of the abdomen):

pT1. The tumor is 5 cm or smaller.
pT2. The tumor is larger than 5 cm but not larger than 10 cm.
pT3. The tumor is larger than 10 cm but not larger than 15 cm.
pT4. The tumor is larger than 15 cm.

Head and neck:

pT1. The tumor is 2 cm or smaller.
pT2. The tumor is larger than 2 cm but not larger than 4 cm.
pT3. The tumor is larger than 4 cm.
pT4a. The tumor has grown into the eye socket, the bones of the face, or the base of the skull and its lining. It may instead involve the organs in the center of the neck or the chewing muscles called the pterygoid muscles.
pT4b. The tumor has grown into the brain, surrounds the carotid artery, or has grown into the muscles in front of the spine. A tumor that has spread along a nerve into the brain or spinal cord is also pT4b.

Abdominal and thoracic visceral organs (internal organs such as the stomach, intestines, and lungs):

pT1. The tumor is confined to the organ where it started.
pT2a. The tumor has grown into the organ’s thin outer lining.
pT2b. The tumor has grown beyond the outer lining into the surrounding tissue.
pT3. The tumor has grown into another organ or a nearby structure such as the diaphragm or abdominal wall.
pT4a. Tumor is found in 2 separate sites.
pT4b. Tumor is found in 3 to 5 separate sites.
pT4c. Tumor is found in more than 5 separate sites.

Orbit (the space around the eye):

pT1. The tumor is 2 cm or smaller.
pT2. The tumor is larger than 2 cm and has not grown into the bony walls of the orbit or the eye.
pT3. The tumor, of any size, has grown into the bony walls of the orbit.
pT4. The tumor has grown into the eye or nearby structures such as the eyelid, sinuses, or brain.

A stage of pT0 means no tumor was found in the tissue removed, which can happen after treatment before surgery. If the tumor cannot be assessed, for example because it was removed in many pieces, the report may say that pT was not assigned.

The nodal stage (pN) for leiomyosarcoma describes whether tumor cells were found in the lymph nodes:

pN0. No tumor cells were found in the lymph nodes examined.
pN1. Tumor cells were found in at least one nearby lymph node.

If no lymph nodes were removed, which is common for leiomyosarcoma, the report will usually say that pN was not assigned. Older reports may show pNX, but current reporting standards no longer use this term for soft tissue sarcomas.

What is the prognosis?

The outlook for a person with leiomyosarcoma depends mainly on the grade of the tumor, where it started, whether it has spread, and whether it can be completely removed. The main risk for most people is spread through the bloodstream to the lungs or liver, rather than the tumor coming back in the same place.

Across studies, the risk of spread within 10 years ranges from about 31% to 71%, depending on where the tumor started. For leiomyosarcoma of the inferior vena cava that is removed with negative margins, reported five-year survival ranges from about 33% to 70%. Tumors limited to the skin have an excellent outlook.

Features associated with the outcome of leiomyosarcoma include:

Histologic grade. High-grade tumors are much more likely to spread than low-grade tumors.
Spread at diagnosis. Cancer that has already spread when it is found is associated with a less favorable outcome.
Tumor site. Tumors of the retroperitoneum and large blood vessels have a higher risk of spread than tumors of the arms and legs.
Tumor size. Larger tumors are associated with a less favorable outcome.
Surgical margins. Complete removal with negative margins is associated with longer survival.

What happens after the diagnosis?

After leiomyosarcoma is confirmed, care is usually planned by a team at a center experienced in treating sarcoma. The team often includes surgeons, radiation oncologists, and medical oncologists. The findings in your report, including the grade, size, margins, and stage, help the team decide which options to consider.

Surgery. Complete removal of the tumor with negative margins is the main treatment for leiomyosarcoma that has not spread. For tumors of the inferior vena cava, surgeons may remove part of the vein and replace it.
Radiation therapy. Radiation may be given before or after surgery for tumors of the arms, legs, and trunk. Its role is more limited for retroperitoneal tumors.
Chemotherapy. Chemotherapy is used mainly when leiomyosarcoma has spread or cannot be removed. Doxorubicin is commonly used. In the LMS-04 trial, tumors shrank in 36% of people receiving doxorubicin plus trabectedin, compared with 13% with doxorubicin alone.
Other treatments. Other drugs, such as gemcitabine with docetaxel or pazopanib, may be used when the cancer grows after earlier treatment. Surgery to remove a small number of lung or liver metastases may be considered in selected people.
Clinical trials. Your oncologist may discuss clinical trials, especially if the tumor has come back or spread.

Access to these treatments differs between countries, and your care team can explain what applies where you live. After treatment, follow-up usually includes regular imaging of the chest and abdomen to look for spread.

Questions to ask your doctor

Where did my leiomyosarcoma start?
What is the grade of my tumor?
Which tests were used to rule out other tumors, such as dedifferentiated liposarcoma or GIST?
How large was the tumor, and did it grow into nearby structures?
Were all the margins negative? How close was the closest margin?
If I had treatment before surgery, what percentage of the tumor was non-viable?
What is my pathologic stage, and has the cancer spread to my lungs, liver, or elsewhere?
Will radiation therapy or chemotherapy be considered in my case?
Should I have genetic counseling or testing for an inherited condition?
Is there a clinical trial I could join?
How often will I need imaging, and for how long?