Pleomorphic leiomyosarcoma is a rare and aggressive form of cancer that begins in smooth muscle tissue and behaves differently from the more common types of leiomyosarcoma. Understanding this unusual variant can help patients and their families navigate the difficult journey ahead.

Understanding Pleomorphic Leiomyosarcoma

Pleomorphic leiomyosarcoma is a specific type of leiomyosarcoma, which is a cancer that starts in smooth muscles found throughout the body. Smooth muscles are involuntary muscles that help control organs like the bladder, stomach, intestines, blood vessels, and uterus. Unlike regular muscles you control when you walk or lift something, smooth muscles work automatically without you thinking about them.^[2]

The term “pleomorphic” refers to how the cancer cells look under a microscope. These cells vary greatly in size, shape, and structure, appearing very disorganized and abnormal. This disorganized appearance sets pleomorphic leiomyosarcoma apart from ordinary leiomyosarcoma, where cells look more uniform.^[1]

This variant represents only about 8.6% of all leiomyosarcoma cases, making it exceptionally rare even within an already uncommon group of cancers.^[5] Because of its rarity, many doctors may encounter it only once or twice in their careers, which is why seeking care at specialized sarcoma centers becomes especially important.

Epidemiology: Who Gets Pleomorphic Leiomyosarcoma

Leiomyosarcoma as a whole is quite rare. In the United States, approximately 15,000 people receive a diagnosis of soft tissue sarcoma each year, and leiomyosarcoma accounts for 10% to 20% of these cases. This means roughly 1 in every 100,000 people in the United States develops leiomyosarcoma.^[4]

Leiomyosarcoma can affect anyone, but certain patterns have emerged. The condition is most commonly diagnosed in females over the age of 50, though it can occur at other ages as well.^[4] When looking specifically at pleomorphic leiomyosarcoma, one case report described a 41-year-old woman who developed this variant originating from the mesenteric vein, highlighting that younger adults can also be affected.^[5]

The location where pleomorphic leiomyosarcoma develops can vary. Cases have been documented in the maxilla (upper jaw) with metastasis to the colon, in the mesenteric vein (a blood vessel in the abdomen), and in other areas where smooth muscle tissue exists.^[3][5] Vessel-derived pleomorphic leiomyosarcomas, which originate from blood vessels, are extremely rare.

Causes of Pleomorphic Leiomyosarcoma

Scientists do not know exactly what causes pleomorphic leiomyosarcoma or leiomyosarcoma in general. The disease begins when something changes the cells in smooth muscle tissue, causing them to grow and divide uncontrollably. These changes occur in the cell’s DNA, which is like an instruction manual that tells each cell what to do.^[2]

In healthy cells, DNA gives instructions for cells to grow and multiply at a controlled rate and tells them when to die. In cancer cells, the DNA changes in ways that cause cells to keep growing without stopping and to avoid dying when they should. Over time, these abnormal cells accumulate and form a tumor that can invade nearby tissues or spread to distant parts of the body.

The cause of these DNA changes remains unclear. They could be hereditary, meaning you inherited altered genes from your parents, or they could happen spontaneously during your lifetime for reasons scientists don’t fully understand.^[4]

Risk Factors

While the exact causes remain unknown, researchers have identified certain factors that may increase a person’s risk of developing leiomyosarcoma. Previous radiation therapy is a significant risk factor, particularly when radiation was given at a young age.^[11] The cancer may develop years or even decades after the radiation treatment ended.

Certain inherited genetic conditions are also associated with higher risk. These include Gardner syndrome, Gorlin syndrome, hereditary retinoblastoma, Li-Fraumeni syndrome, neurofibromatosis type 1 (NF1), tuberous sclerosis, and Werner syndrome.^[4] People with these conditions have mutations in specific genes that make their cells more prone to developing cancer.

Chronic lymphedema, which is long-term swelling caused by a buildup of lymph fluid in the tissues, is a risk factor for lymphangiosarcoma, a related type of soft tissue cancer.^[11] Exposure to certain chemicals, including thorium dioxide (also known as Thorotrast), vinyl chloride, and arsenic, has been linked to soft tissue sarcomas, particularly those affecting the liver.^[11]

It’s important to note that having one or more risk factors doesn’t mean you will definitely develop pleomorphic leiomyosarcoma. Many people with risk factors never develop the disease, and many who develop it have no known risk factors at all.

Symptoms of Pleomorphic Leiomyosarcoma

The symptoms of pleomorphic leiomyosarcoma vary greatly depending on where the tumor is located in the body. Many people don’t experience noticeable symptoms early on, which can delay diagnosis until the cancer has grown larger or spread to other areas.^[2]

One of the most common symptoms is a firm, painless lump or mass that you can feel under the skin. This lump may or may not move when you touch it. As the tumor grows, it might start causing pain, though not everyone experiences this.^[4]

General symptoms that can occur with pleomorphic leiomyosarcoma include unexplained weight loss, persistent fever, tiredness that doesn’t improve with rest, and nausea and vomiting.^[4] Some people also experience abdominal bloating, especially when the tumor is located in the abdomen.

When pleomorphic leiomyosarcoma affects the digestive system, it may cause abdominal pain, loss of appetite, black or dark stools that result from bleeding in the gastrointestinal tract, and persistent nausea or vomiting.^[4] In the case report of a 41-year-old woman with vessel-derived pleomorphic leiomyosarcoma, the patient presented with acute abdominal pain, a bulge in the left lower abdomen, loss of appetite, and anemia.^[5]

If the tumor develops in or near the uterus, symptoms might include abnormal uterine bleeding, vaginal discharge, or frequent urination caused by the tumor pressing on the bladder.^[4] Some patients experience swelling in an arm or leg, or numbness and tingling if a tumor is pressing on or involving a nerve.

Prevention

Because scientists don’t fully understand what causes pleomorphic leiomyosarcoma, there are no specific proven strategies to prevent this disease. However, there are some general approaches that may reduce your overall cancer risk.

If you have one of the genetic conditions associated with increased risk of leiomyosarcoma, regular check-ups with your doctor are important. Genetic counseling can help you understand your risks and make informed decisions about screening and monitoring.^[4]

Avoiding unnecessary exposure to radiation is wise, though sometimes radiation therapy is medically necessary and its benefits outweigh potential future risks. If you work in an environment where you might be exposed to chemicals like vinyl chloride or arsenic, following workplace safety guidelines and using proper protective equipment is important.

Maintaining overall good health through a balanced diet, regular physical activity, maintaining a healthy weight, not smoking, and limiting alcohol consumption may help reduce your general cancer risk, though these measures haven’t been proven to specifically prevent leiomyosarcoma.

Perhaps most importantly for early detection, pay attention to your body and report any unusual symptoms to your doctor promptly. While most lumps are not cancer, any new, growing, or changing lump should be evaluated, especially if it’s larger than 5 centimeters, deep in the tissues, or growing rapidly.

Pathophysiology: How Pleomorphic Leiomyosarcoma Affects the Body

Pleomorphic leiomyosarcoma disrupts normal body function in several ways. When smooth muscle cells develop the DNA changes that turn them cancerous, they begin growing and dividing much faster than normal cells. Instead of following the usual life cycle where cells grow, function, and eventually die in an orderly way, these cancer cells keep multiplying without control.

As these abnormal cells accumulate, they form a tumor that can grow quite large. Leiomyosarcoma in general is known to grow quickly and can double in size in as little as one month.^[4] The pleomorphic variant can be particularly aggressive, sometimes showing abnormal growth patterns that contribute to poor outcomes even after surgery intended to remove all the cancer.^[5]

The tumor can physically press on nearby organs, blood vessels, or nerves, causing pain, swelling, or loss of function in the affected area. For example, a tumor in the abdomen might press on the intestines or urinary system, causing digestive problems or urination difficulties. A tumor near a nerve might cause numbness, tingling, or weakness.

One of the most concerning aspects of pleomorphic leiomyosarcoma is its tendency to spread. Cancer cells can break away from the original tumor and travel through the bloodstream to distant parts of the body, a process called metastasis. Leiomyosarcoma spreads most commonly to the lungs, but it can also spread to lymph nodes, bones, liver, and other organs.^[4]

The case of a 41-year-old woman with vessel-derived pleomorphic leiomyosarcoma illustrates how aggressive this variant can be. Despite undergoing surgery that successfully removed all visible tumor, she experienced what doctors called “super-early recurrence” just two months after surgery, with the cancer returning locally and spreading to distant sites. This rapid recurrence led to disseminated intravascular coagulation, a serious condition where blood clots form throughout the small blood vessels, and generalized peritonitis, inflammation of the abdominal cavity lining.^[5]

The abnormal appearance of pleomorphic leiomyosarcoma cells under the microscope reflects the chaotic changes in their DNA. These cells show significant variation in size, shape, and appearance of their nuclei (the part of the cell that contains genetic material). This “pleomorphic” appearance is one way pathologists distinguish this variant from ordinary leiomyosarcoma.^[1]

Because of the rapid growth and high potential for spread, pleomorphic leiomyosarcoma can significantly impact a person’s overall health. The cancer may interfere with normal organ function, cause nutritional problems if it affects the digestive system, lead to bleeding or clotting problems, and cause a general decline in strength and energy levels.