Undifferentiated Sarcoma
Undifferentiated sarcoma is a rare type of cancer that develops in the body’s connective tissues, often affecting the arms, legs, or abdomen. This aggressive disease requires prompt diagnosis and a combination of treatments to give patients the best chance of recovery.
Table of contents
- What is Undifferentiated Sarcoma?
- Other Names for This Disease
- Types of Undifferentiated Sarcoma
- Signs and Symptoms
- Causes and Risk Factors
- How Doctors Diagnose Undifferentiated Sarcoma
- Treatment Options
- Outlook and Prognosis
What is Undifferentiated Sarcoma?
Undifferentiated sarcoma is a group of cancers that begin in the body’s connective tissues, which are the structures that connect, support, and surround other body parts[3]. These cancers are called “undifferentiated” because when doctors look at the cancer cells under a microscope, they don’t look like the normal tissues where they started growing[1]. The term pleomorphic (plee-o-MOR-fik) means the cells grow in multiple shapes and sizes[1].
Undifferentiated sarcoma typically develops in the soft tissues of the body, including muscles, fat, fibrous tissue, blood vessels, and nerves[3]. The cancer most commonly appears in the deep soft tissues of the arms and legs, especially the thigh, though it can also develop in the trunk or the area behind the abdominal organs called the retroperitoneum[4]. In very rare cases, undifferentiated sarcoma can affect bones[2].
This is a rare condition, affecting fewer than 5,000 people in the United States each year[2]. However, undifferentiated pleomorphic sarcoma is one of the three most common soft tissue sarcomas in adults, along with liposarcoma and leiomyosarcoma[2]. It accounts for approximately 5% to 10% of all soft tissue sarcomas[4].
Undifferentiated sarcoma is typically aggressive, meaning it can spread quickly to other areas of the body, usually to the lungs or lymph nodes[2]. This high-grade malignancy is marked by a high propensity for local recurrence and distant metastasis, which means the cancer can come back in the same area or spread to distant parts of the body[4].
malignant fibrous histiocytoma, undifferentiated pleomorphic sarcoma, UPS
Other Names for This Disease
Undifferentiated sarcoma used to be called malignant fibrous histiocytoma[1][2]. Researchers originally thought this type of cancer formed in specialized immune cells called histiocytes, but later research suggested it likely starts in mesenchymal cells that form connective tissue[2]. When the cancer affects soft tissue specifically, it may be called undifferentiated pleomorphic sarcoma or UPS[7].
Types of Undifferentiated Sarcoma
Undifferentiated sarcoma includes several subtypes based on how the cells appear under a microscope. These subtypes include spindle cell sarcoma, pleomorphic sarcoma, and round cell sarcoma[7]. Each type is named for the shape and characteristics of the cancer cells.
One specific type is pleomorphic dermal sarcoma, also known as PDS, which occurs on the surface of sun-damaged skin in older people[20]. This distinguishes it from other forms that develop deeper within the body.
Signs and Symptoms
The symptoms of undifferentiated sarcoma vary depending on where the cancer develops in the body[1]. Most commonly, people notice a growing lump or area of swelling[1]. This lump is often painless and may or may not move when touched[2].
When undifferentiated sarcoma occurs in an arm or leg, there may be swelling in the hand or foot of the affected limb[1]. If the tumor grows very large, it may cause pain, tingling, and numbness[1]. This happens when the lump pushes on nearby nerves[2].
If the cancer occurs in the abdomen, symptoms may include pain, loss of appetite, and constipation[1]. When the tumor gets large enough, it may press on other organs and cause blockage[3]. For example, a sarcoma in the lungs may cause breathing difficulty[3].
Some people may also experience fever and weight loss[1]. However, undifferentiated pleomorphic sarcoma doesn’t always cause noticeable symptoms and is most often painless without any skin changes over the top[2].
Causes and Risk Factors
Experts aren’t entirely sure what causes undifferentiated sarcoma. They know it happens when healthy cells develop changes in their DNA, which contains the instructions that tell a cell what to do[2][6]. These changes tell the cell to multiply rapidly, creating a mass of abnormal cells[6]. However, doctors don’t know what causes these DNA changes in the first place[2].
The molecular pathogenesis, or how the disease develops at the cellular level, remains poorly defined. Undifferentiated pleomorphic sarcoma involves highly complex and disorganized cell structures without consistent genetic alterations that could be targeted by specific treatments[4].
Several risk factors may increase the chances of developing undifferentiated sarcoma. Being male, particularly white males, poses the highest risk[2]. Being over the age of 50 is another significant risk factor, as this cancer typically affects people between ages 50 and 70, though it can develop at any age[2][9].
Certain diseases increase risk, including neurofibromatosis and Paget’s disease of bone[2]. Some genetic disorders, such as Li-Fraumeni syndrome, also raise the risk[2]. Exposure to certain chemicals like arsenic or vinyl chloride has been linked to undifferentiated sarcoma[2].
History of radiation therapy to the affected area or occupational radiation exposure are known risk factors[2]. At least 25% of radiation-associated soft tissue sarcomas are undifferentiated[7]. However, most people who develop undifferentiated sarcoma don’t have any known risk factors[2].
How Doctors Diagnose Undifferentiated Sarcoma
Diagnosis of undifferentiated sarcoma usually begins with a review of symptoms and a physical examination[10]. The doctor will ask questions about when symptoms started and whether they’ve changed over time[2]. During the physical exam, the doctor will check the size of the lump, feel its location, and assess how hard it is[2][10].
Several imaging tests help doctors see inside the body and understand more about the condition. These typically include X-rays, ultrasound, CT scans, MRI, and positron emission tomography (PET) scans[2][10]. These tests create pictures of the affected area to determine the size and extent of the tumor[3].
To make a definitive diagnosis, doctors perform a biopsy, which means taking a sample of the tumor tissue and sending it to a lab for testing[2][10]. The tissue sample may be collected with a needle inserted through the skin or during an operation, depending on the situation[10]. This is a surgical procedure done under general anesthesia so the patient is not conscious and will not feel any pain[3].
In the lab, doctors called pathologists who are trained in analyzing body tissues examine the sample under a microscope[10]. They look at the sample to determine the types of cells involved and whether the cells are likely to be aggressive[10]. Undifferentiated sarcoma is a “diagnosis of exclusion,” meaning doctors diagnose it only after ruling out other specific types of sarcoma[20].
Additional tests may be performed to see if the disease has spread. These can include X-rays of the bones, radioisotope scans, CT scans, MRI, bone marrow aspirate and biopsy, and sentinel node biopsy[3].
Treatment Options
Treatment for undifferentiated sarcoma depends on several factors, including the location of the cancer, the size of the tumor, and whether the cancer has spread[1][2]. A combination of surgery, radiation, and in some situations chemotherapy is most often used[3].
Surgery
Surgery is the first and main treatment for undifferentiated sarcoma[2][20]. The surgeon removes the tumor and aims to take out an area of normal tissue around it, which is known as “taking a margin”[20]. This helps make sure all of the cancer has been removed.
When undifferentiated sarcoma affects the arms and legs, surgeons perform limb-sparing surgery so that the limb can continue to work well[20]. Although very rare, if the cancer has spread throughout the limb, surgeons may have to perform a partial or full amputation to stop the cancer[20].
Radiation Therapy
Radiation therapy uses high-energy radiation to destroy cancer cells[20]. It can be used either before or after surgery[3][20]. When used before surgery, radiation aims to make the tumor smaller so it can be more easily removed[20]. When used after surgery, radiation aims to kill off any remaining cancer cells that were not removed by surgery[20].
In some situations, doctors may recommend proton therapy instead of traditional radiation therapy[3]. Proton therapy targets the tumor while avoiding organs and healthy tissue, which means fewer short-term side effects and long-term complications from radiation[3].
Chemotherapy
Chemotherapy uses anti-cancer drugs to destroy cancer cells[20]. It is sometimes used in patients who have a high risk of the cancer coming back or if it has spread to other parts of the body, a condition known as metastasis[20].
Immunotherapy and Targeted Therapies
Researchers have been learning more about treatments known as targeted therapies and immunotherapies for undifferentiated sarcoma[20]. Targeted therapy is a treatment that targets specific characteristics within cancer cells to stop them from growing and spreading[20]. Immunotherapy is a treatment that helps the person’s own immune system fight and kill cancer cells[20].
Some patients with undifferentiated pleomorphic sarcoma have shown responsiveness to immunotherapy treatment[14]. One case report documented successful continuous immunotherapy for metastatic undifferentiated pleomorphic sarcoma over 6.5 years and 109 cycles, showing that prolonged treatment can be tolerated without adverse effects[14].
Planning Treatment
The treatment plan will be based on specific characteristics of the cancer, the location of the tumor, whether the tumor has spread, and whether the tumor was completely removed by surgery[3]. Determining the type of biopsy needed and the specifics of how treatments should be performed requires careful planning by the medical team[10].
Outlook and Prognosis
The prognosis for undifferentiated sarcoma is determined by several factors, including tumor size, depth, anatomic site, and histologic grade, which describes how abnormal the cancer cells look under a microscope[4]. High-grade, deep, and large tumors show an elevated risk of distant metastasis, most commonly to the lungs, followed by lymph nodes, bone, and liver[4].
Because undifferentiated pleomorphic sarcoma is an aggressive malignancy, it is marked by a high propensity for local recurrence and distant metastasis[4]. Early detection and treatment are key to improving outcomes[2].
People should make an appointment with a doctor if they develop any persistent signs or symptoms that worry them[1]. For this reason, patients should ask their doctor for a referral to a team of experts with extensive experience in treating soft tissue sarcoma[10].
