Pleomorphic Leiomyosarcoma

Pleomorphic leiomyosarcoma is a rare and aggressive form of cancer that develops in smooth muscle tissue, characterized by cancer cells that vary greatly in size and shape, making it particularly challenging to diagnose and treat.

Table of contents

• What is Pleomorphic Leiomyosarcoma?
• Where It Occurs in the Body
• Signs and Symptoms
• Causes and Risk Factors
• How It Is Diagnosed
• Treatment Approaches
• Outlook and Prognosis

What is Pleomorphic Leiomyosarcoma?

Pleomorphic leiomyosarcoma is a specific type of leiomyosarcoma, which is a rare cancer that starts in smooth muscles. Smooth muscles are involuntary muscles found in various parts of your body, including your bladder, blood vessels, intestines, stomach, and uterus^[1][2].

The term “pleomorphic” means that the cancer cells vary greatly in size, shape, or the structure that contains chromosomes (called the nucleus). These cells grow in a very disorganized way^[1]. Pleomorphic leiomyosarcoma was recently described as a specific variant of leiomyosarcoma and accounts for approximately 8.6% of all leiomyosarcomas^[5].

This type of cancer is particularly aggressive, meaning it grows and spreads quickly. It is considered to have a more dismal prognosis compared to ordinary leiomyosarcoma^[5]. Leiomyosarcoma itself is a type of soft tissue sarcoma, which is a broad group of cancers that begin in the tissues that connect, support, and surround other body structures^[2].

In the United States, about 15,000 people receive a soft tissue sarcoma diagnosis every year, and leiomyosarcoma accounts for 10% to 20% of those cases. About 1 in every 100,000 people in the U.S. develops leiomyosarcoma^[4].

Where It Occurs in the Body

Pleomorphic leiomyosarcoma can develop in several locations throughout the body. It most commonly affects smooth muscle tissue in hollow organs and blood vessels^[1][2].

Cases have been reported originating from the mesenteric vein, which is a blood vessel in the abdomen^[5]. One documented case involved a pleomorphic leiomyosarcoma of the maxilla (upper jaw bone) that later spread to the colon^[3].

When leiomyosarcoma originates from blood vessels, it is called leiomyosarcoma of vascular origin. This is the rarest form of leiomyosarcoma and typically forms in major blood vessels like the pulmonary arteries, inferior vena cava, or peripheral arteries^[4].

The location where the cancer develops affects both the symptoms experienced and the overall prognosis for the patient^[5].

Signs and Symptoms

Symptoms of pleomorphic leiomyosarcoma depend on the tumor’s size and location. Many people don’t experience symptoms early on, which can delay diagnosis^[2][4].

As the tumor grows, general symptoms may include:

• A firm, usually painless lump or mass under the skin
• Pain in the affected area
• Weight loss without trying
• Nausea and vomiting
• Fever
• Tiredness
• Abdominal bloating^[2][4]

When the cancer affects the digestive system, additional symptoms may include abdominal pain, black stools from blood in the stool, and loss of appetite^[4].

In one reported case, a patient with pleomorphic leiomyosarcoma originating from the mesenteric vein experienced acute abdominal pain, a bulge in the left lower abdomen, loss of appetite, and anemia^[5].

If uterine tissue is involved, symptoms might include abnormal uterine bleeding, frequent urination, or vaginal discharge^[4].

Causes and Risk Factors

Experts are not exactly sure what causes pleomorphic leiomyosarcoma. The cancer happens when something changes the cells in smooth muscles. In healthy cells, DNA (the cell’s instruction manual) tells the cells to grow and multiply at a set rate and to die at a set time. In cancer cells, the DNA changes cause cells to grow out of control^[2][4].

The cause of these DNA changes could be hereditary, meaning you inherited altered genes from your parents, or it could be because your own genes changed for unknown reasons^[4].

Several factors may increase the risk of developing leiomyosarcoma:

Genetic conditions: Researchers have found links between leiomyosarcoma and certain inherited syndromes, including:

• Gardner syndrome
• Gorlin syndrome
• Hereditary retinoblastoma
• Li-Fraumeni syndrome
• Neurofibromatosis type 1 (NF1)
• Tuberous sclerosis
• Werner syndrome^[4]

Previous radiation exposure: A history of radiation therapy or occupational radiation exposure increases risk^[4].

Chemical exposure: Exposure to certain chemicals like arsenic or vinyl chloride may increase risk^[4].

Leiomyosarcoma can affect anyone but is most common in females over age 50^[4].

How It Is Diagnosed

Diagnosing pleomorphic leiomyosarcoma requires careful evaluation by healthcare professionals, preferably at specialized sarcoma centers^[4].

Physical examination: A healthcare provider will perform a physical examination and ask about your symptoms, including when they started and whether they’ve changed over time. They will check the size, location, and firmness of any lumps^[4].

Imaging tests: Several imaging tests help create pictures of the affected area to understand the tumor’s size and location:

• X-rays: Basic imaging that can show abnormalities
• Computed tomography (CT) scans: Creates detailed cross-sectional images
• Magnetic resonance imaging (MRI): Provides detailed images of soft tissues. In one case, MRI showed a large tumor with low intensity on one type of image and high intensity on another^[5]
• Ultrasound: Uses sound waves to create images
• PET scan: Can help identify cancer spread^[4]

Biopsy: To make a definitive diagnosis, a healthcare provider must collect a sample of the tumor tissue and send it to a laboratory for testing. This is typically done through a core needle biopsy, where tissue is removed using a needle inserted through the skin^[4].

In the laboratory, doctors called pathologists examine the sample under a microscope. They look at the types of cells present and whether the cells appear aggressive. On histopathological analysis (examination of tissue under a microscope), pleomorphic leiomyosarcoma shows high-grade pleomorphic spindle cells characteristic of this cancer type^[1][5].

Getting a second opinion from a sarcoma specialist at a high-volume sarcoma center is highly recommended, as these rare cancers require specialized expertise for accurate diagnosis^[4].

Treatment Approaches

Treatment for pleomorphic leiomyosarcoma depends on several factors, including the tumor’s size, location, whether it has spread, and the patient’s overall health^[4].

Surgery: Surgery is the most important and effective treatment for leiomyosarcoma when the tumor can be removed. The goal is to remove the entire tumor with clear margins (removing some normal tissue around the tumor to ensure all cancer cells are gone)^[4][8].

In one documented case, a patient underwent extensive surgery including left hemicolectomy (removal of part of the colon) and partial resection of the small intestine because the tumor had invaded these organs^[5]. Another case involved a 14-hour surgery to successfully remove a large pleomorphic leiomyosarcoma tumor^[5].

Chemotherapy: Chemotherapy uses drugs to kill cancer cells. Several chemotherapy regimens are used for leiomyosarcoma:

• First-line therapy for advanced leiomyosarcoma typically includes anthracycline-based regimens (such as doxorubicin) or gemcitabine-based combinations (such as gemcitabine with docetaxel)^[8]
• Other chemotherapy drugs used include ifosfamide^[8]
• These treatments provide a median progression-free survival time of about 5 months and overall survival time between 14-16 months^[8]

Unfortunately, in some cases, pleomorphic leiomyosarcoma may not respond well to chemotherapy. In one reported case, the tumor continued to grow despite multiple chemotherapy regimens^[5].

Radiation therapy: Radiation therapy uses high-energy beams to kill cancer cells. It may be used before surgery to shrink the tumor or after surgery to kill any remaining cancer cells^[4][5].

Targeted therapy: Newer treatment approaches target specific abnormalities in cancer cells. Research is ongoing to develop more effective targeted therapies for leiomyosarcoma, including approaches that target DNA damage repair pathways and abnormal metabolism associated with cancer growth^[8].

Clinical trials: Because pleomorphic leiomyosarcoma is rare and aggressive, participation in clinical trials should be considered. Many trials combine older chemotherapies with new drugs, so it’s important to consider trials first, before standard treatments, as previous chemotherapy may disqualify patients from some trials^[8].

An interdisciplinary approach involving surgical oncologists, medical oncologists, and radiation oncologists is essential for optimal treatment planning^[4].

Outlook and Prognosis

Pleomorphic leiomyosarcoma is known to have an aggressive malignant potential with a generally poor prognosis^[5].

Several factors affect prognosis:

• Tumor location: Where the cancer develops affects outcomes
• Tumor size: Larger tumors generally have worse outcomes
• Tumor grade: High-grade tumors grow and spread more quickly
• Whether cancer has spread: Tumors that have spread to other parts of the body have worse outcomes^[4][5]

Risk factors for poor outcomes include incomplete tumor removal (R1 resection), older age, large tumor size, invasion into other organs, and the histologic type^[5].

The cancer grows quickly and can spread through the bloodstream to any soft tissue in the body. Leiomyosarcoma can double in size in as little as one month^[4]. The most common site of spread is the lungs^[4].

In one documented case, despite curative-intent surgery to completely remove a vessel-derived pleomorphic leiomyosarcoma, the patient experienced super-early local recurrence (cancer came back very quickly) and died two months after surgery due to complications^[5].

However, when detected and treated early, outcomes can be more favorable^[4]. Regular monitoring with scans is essential because leiomyosarcoma can recur many years after being in remission or showing no evidence of disease^[4].

Because vessel-derived pleomorphic leiomyosarcoma is extremely rare, more research is needed to determine its specific characteristics and develop better treatment strategies to improve long-term survival^[5].