Leiomyosarcoma

Leiomyosarcoma is a rare and aggressive cancer that develops in smooth muscles found in various organs throughout the body. While it can grow quickly and spread to other tissues, early detection and treatment offer the possibility of recovery.

Table of contents

• What is leiomyosarcoma?
• Types of leiomyosarcoma
• How common is this cancer?
• Signs and symptoms
• Possible causes and risk factors
• How doctors diagnose leiomyosarcoma
• Treatment options
• Outlook and survival

What is leiomyosarcoma?

Leiomyosarcoma (LMS) is a rare type of cancer that forms in smooth muscles, which are involuntary muscles located in various parts of the body^[1]. These muscles are found in hollow organs and blood vessels, and you cannot control them consciously—they work automatically.

This cancer is classified as a soft tissue sarcoma, which means it develops in the connective tissues of the body rather than in bones or organs themselves^[3]. Leiomyosarcoma is particularly aggressive—it grows quickly and can double in size in as little as one month^[1]. The cancer cells can travel through the bloodstream and spread to other soft tissues anywhere in the body.

• Bladder
• Blood vessels
• Large intestine
• Small intestine
• Stomach
• Uterus
• Retroperitoneum (area behind the intestines)

The most common locations where leiomyosarcoma develops are the retroperitoneum (the space in the abdomen behind the intestines), the uterus, and the extremities (arms and legs), in that order^[3].

Types of leiomyosarcoma

There are three main subtypes of leiomyosarcoma, based on where the cancer develops^[1]:

• Somatic soft tissue LMS: This affects connective tissue and is the most common form. Uterine leiomyosarcoma is one example of this type.
• Cutaneous or subcutaneous LMS: This involves muscles in the skin and eyes, specifically the piloerector muscles that give you goosebumps and make your pupils get larger or smaller.
• LMS of vascular origin: This forms in major blood vessels, such as the pulmonary arteries, inferior vena cava, or peripheral arteries. It is the rarest form of LMS.

In children, soft tissue leiomyosarcoma usually appears in the gastrointestinal tract, which includes the stomach, small intestines, colon, appendix, rectum, and anus^[6].

How common is this cancer?

Leiomyosarcoma is rare. In the United States, approximately 15,000 people receive a soft tissue sarcoma diagnosis each year, and leiomyosarcoma accounts for 10% to 20% of those cases^[1][3]. This means about 1 in every 100,000 people in the U.S. develops LMS cancer.

Leiomyosarcoma can affect anyone at any age, but it is most common in females over age 50^[1]. When it affects the uterus specifically, it occurs in approximately 6 individuals per 1 million people in the United States each year^[4].

Signs and symptoms

The symptoms of leiomyosarcoma vary greatly depending on the size and location of the tumor^[1]. Some people do not experience symptoms early on, especially because soft tissue is elastic and easily moved, allowing a tumor to exist for a long time before being discovered^[6]. However, as the tumor grows, people may notice certain signs.

General symptoms that may appear include^[1]:

• A firm, painless lump
• Abdominal bloating
• Fever
• Nausea and vomiting
• Pain
• Tiredness
• Unintentional weight loss

When leiomyosarcoma develops in the digestive system, it may cause^[1]:

• Abdominal pain
• Black stools (from blood in the stool)
• Loss of appetite
• Nausea and vomiting

Uterine leiomyosarcoma can cause^[1]:

• Abnormal uterine bleeding
• Frequent urination
• Vaginal discharge

If the cancer appears in the arms or legs, symptoms may include a painless swelling or mass, pain or soreness caused by compressed nerves or muscles, or limping or other difficulty using the affected limb^[6].

Possible causes and risk factors

Experts are not exactly sure what causes leiomyosarcoma^[1]. It could be hereditary, meaning you inherited altered genes from your parents, or it could be because your own genes changed over time, causing normal cells to grow out of control and become cancer cells.

The most significant known risk factor for soft tissue sarcomas, including leiomyosarcoma, is a history of radiation exposure or radiotherapy, particularly at a young age^[3].

Researchers have found links between leiomyosarcoma and several genetic conditions^[1][3]:

• Gardner syndrome
• Gorlin syndrome
• Hereditary retinoblastoma (caused by deletion of the RB1 gene)
• Li-Fraumeni syndrome (caused by a mutation in the TP53 gene)
• Neurofibromatosis type 1 (NF1)
• Tuberous sclerosis
• Werner syndrome

There also appears to be a connection between leiomyosarcoma and Epstein-Barr virus infection (the virus that causes mononucleosis or “mono”)^[6]. People with HIV, AIDS, or other conditions that compromise the immune system may be more vulnerable to developing leiomyosarcoma^[6].

How doctors diagnose leiomyosarcoma

To diagnose leiomyosarcoma, a healthcare provider will first perform a physical examination and ask about your symptoms^[1][10]. They will also review your medical history, including any past or current health conditions. The provider may examine your body to look for areas of swelling or lumps under the skin.

Several imaging tests are used to see inside the body and determine the size and location of the tumor^[1][10]:

• MRI (Magnetic Resonance Imaging): Uses magnets and radio waves to create detailed images
• CT scan (Computed Tomography): Creates 3D images of the body
• PET scan (Positron Emission Tomography): Shows how tissues and organs are functioning
• Angiography: Imaging of blood vessels

A biopsy is typically required for diagnosis^[1][10]. This is a procedure to remove a sample of tissue for testing in a laboratory. For leiomyosarcoma, the biopsy is often collected with a needle that is inserted through the skin to get the sample. The sample is then examined under a microscope to determine whether cancer is present.

A biopsy for leiomyosarcoma needs to be done carefully so it does not cause problems with future surgery. For this reason, it is a good idea to seek care at a medical center that sees many people with this type of cancer^[10]. Experienced healthcare teams will select the best type of biopsy for each situation.

Treatment options

Treatment of leiomyosarcoma depends on where the cancer is located, how large it is, whether it has spread to other areas of the body, your overall health, and what you want^[10]. Treatment can be complex and often requires an approach that involves multiple specialists^[3].

The main treatment options for leiomyosarcoma include^[5]:

• Surgery
• Interventional radiology
• Chemotherapy (including targeted drugs and immunotherapy)

Surgery

Surgery is the most effective treatment for leiomyosarcoma, if possible^[5][14]. The goal is to remove all of the cancer with as wide a margin of removal as possible^[4][10]. This means removing the tumor along with a portion of healthy tissue surrounding it to ensure no cancer cells are left behind. If any cancer cells remain in the body, a new tumor may begin to grow^[5].

However, complete removal might not be possible if the cancer is large or involves nearby organs. In such cases, the surgeon may remove as much of the cancer as possible^[10].

Chemotherapy

Chemotherapy uses drugs to kill cancer cells. For metastatic (spread) or unresectable (cannot be removed) leiomyosarcoma, first-line therapy includes anthracycline-based regimens (such as doxorubicin) or gemcitabine-based regimens^[13]. These treatments typically provide a median progression-free survival time of about 5 months and overall survival time between 14 and 16 months.

Recent research has shown that combining trabectedin (Yondelis) with doxorubicin as an initial treatment can help people with advanced leiomyosarcoma live longer than those treated with doxorubicin alone—a median of 33 months versus 24 months^[11].

Most sarcoma specialists do not recommend adjuvant chemotherapy (chemotherapy when there is no visible tumor) unless surgeons could not achieve clear margins around the tumor^[14].

Radiation Therapy

Radiation therapy uses high-energy beams to kill cancer cells. It is often used as an adjunct to surgery or when surgery is not possible^[3].

Targeted Therapy

Targeted therapy involves drugs that target specific pathways or molecules involved in cancer growth^[1]. This is an area of ongoing research for leiomyosarcoma treatment.

Clinical Trials

Clinical trials test new treatments and should be considered first, before agreeing to standard treatment^[14]. Many trials combine older chemotherapy drugs with new drugs. If you have already had the older chemotherapy drugs, it may disqualify you from participating in certain trials. Participating in trials also helps advance treatments for leiomyosarcoma.

Treatment at high-volume sarcoma centers is preferred and improves patient outcomes^[3].

Outlook and survival

The outlook for leiomyosarcoma is related to the tumor’s location, size, and grade^[3]. The tumor grade—which indicates how abnormal the cancer cells look and how quickly they are likely to grow—has a significant impact on overall survival. With higher-grade tumors, the rate of distant spread (metastasis) increases.

Some people do not develop symptoms until the disease reaches an advanced stage, and in these cases, leiomyosarcoma can be life-threatening^[1]. However, when it is detected and treated early, recovery is possible. The outlook is more favorable when the cancer is caught early and can be completely removed surgically.

More than half of all patients treated for leiomyosarcoma require additional treatments within 8 to 16 months after initial diagnosis^[5]. This means that ongoing monitoring through routine scans and surveillance is important, as leiomyosarcoma can recur many years after being in remission or showing no evidence of disease^[14].

Leiomyosarcomas are generally resistant cancers, meaning they are not very responsive to chemotherapy or radiation alone^[4]. The best outcomes occur when the tumor tissue can be removed surgically at an early stage while it is small and has not yet spread from the original site.

If you or a loved one has been diagnosed with leiomyosarcoma, it is important to work closely with your healthcare team and consider connecting with support groups and other resources that can help throughout the journey^[1].