Soft Tissue Sarcomas Explained

Soft tissue sarcomas are a diverse group of cancers that arise from fat, muscle, tendon, cartilage, lymphoid tissues, vessels, and so forth. There are more than 80 types of soft tissue sarcoma. Although most sarcomas are soft tissue sarcomas, they can also affect bone.

The diagnosis and treatment of soft tissue sarcomas are involved and multidisciplinary, requiring the input of oncologists, surgical oncologists, radiologists, interventional radiologists, and more. Treatment includes surgery, radiotherapy, and, in some cases, chemotherapy.

What Are Soft Tissue Sarcomas?

Soft tissue sarcomas are a rare type of neoplasm and account for less than 1% of cancers in adults. The American Cancer Society estimated that 13,460 new cases of soft tissue sarcoma would be diagnosed in 2021 (7,720 cases in men and 5,740 cases in women). In children, soft tissue sarcomas represent 15% of cancers.

The exact cause of most soft tissue sarcomas is unknown, and these lesions typically occur for no apparent reason. There are several genetic cancer syndromes that predispose someone to different types of soft tissue sarcomas. However, in some cases of soft tissue sarcoma, DNA mutations acquired after birth and secondary to radiation or carcinogen exposure may play a role in pathogenesis.

The most common soft tissue sarcomas in adults are undifferentiated pleomorphic sarcoma (previously called malignant fibrous histiocytoma), liposarcoma, and leiomyosarcoma. Liposarcomas and undifferentiated pleomorphic sarcomas most often present in the legs, and leiomyosarcomas are the most common abdominal sarcomas.

In children, the most common type of soft tissue sarcoma is rhabdomyosarcoma, which affects skeletal muscle.

Soft tissue sarcomas can be life-threatening, with only 50% to 60% of people alive five years after they were first diagnosed or treated—a measure called the five-year survival rate. Among those people who die of soft tissue sarcoma, metastasis—or spread—to the lungs is the most common cause of death. In 80% of affected patients, these life-threatening lung metastases occur between two and three years after initial diagnosis.

Clinical Presentation of Soft Tissue Sarcomas

Typically, a soft tissue sarcoma appears as a mass that doesn’t cause symptoms (i.e., it is asymptomatic). It can resemble a lipoma, or a benign tumor made of fat. In fact, lipomas are 100 times more common than soft tissue sarcomas and should be considered part of the differential diagnosis. In other words, a skin lump located on your arm or leg is much more likely to be a benign lipoma than a soft tissue sarcoma.

About two-thirds of soft tissue sarcomas arise on the arms and legs. The other one-third arise in the head, abdomen, trunk, neck, and retroperitoneum. The retroperitoneum is a space located behind the abdominal wall that contains the kidneys and pancreas as well as part of the aorta and inferior vena cava.

Because soft tissue sarcomas often cause no symptoms, they are usually noticed only incidentally after a traumatic event that requires medical attention brings a person to the hospital. Soft tissue sarcomas of the distal extremities (the parts of the arm and leg farthest from the torso) are often smaller when diagnosed. Soft tissue sarcomas that occur in either the retroperitoneum or proximal portions of the extremities (those closest to the torso) can grow quite large before being noticed.

If a soft tissue sarcoma becomes big enough, it can impinge on surrounding structures such as bone, nerves, and blood vessels, and cause symptoms including pain, swelling, and edema. Depending on location, larger sarcomas can obstruct the gastrointestinal tract and cause gastrointestinal symptoms such as cramps, constipation, and loss of appetite. Larger sarcomas can also impinge on the lumbar and pelvic nerves, thus resulting in neurological problems. Finally, sarcomas located in the extremities can present like deep venous thrombosis.

Diagnosis and Staging of Soft Tissue Sarcomas

Small soft tissue masses that are new, non-enlarging, superficial, and fewer than 5 centimeters in size can be observed by a clinician with no immediate treatment. Enlarging masses that are deeper or bigger than 5 centimeters require a full workup entailing history, imaging, and biopsy.

Before the biopsy, diagnostic testing is used to evaluate soft tissue sarcoma. Magnetic resonance imaging (MRI) is most useful when visualizing soft tissue sarcomas located in the extremities. With respect to tumors that are retroperitoneal, intra-abdominal (within the abdomen), or truncal, computed tomography (CT) is most useful. Other diagnostic modalities that can play a role in diagnosis are positron emission tomography (PET) and ultrasound. Radiography (X-rays) is not useful when diagnosing soft tissue tumors.

After diagnostic testing, a biopsy is performed to examine the microscopic anatomy of the tumor. Historically, open incisional biopsies, which are surgeries that require general anesthesia, have been the gold standard when obtaining adequate tissue samples for histological diagnosis. However, core needle biopsy, which is safer, less invasive, and more accurate and cost-effective, has become the preferred type of biopsy. Fine-needle aspiration is another biopsy option, but it is generally discouraged because it may be difficult to make an accurate primary diagnosis based on a small sample size. Finally, when a lesion is smaller and closer to the surface, an excisional biopsy can be done.

Although biopsy of more superficial tumors can be performed in an outpatient or office setting, deeper tumors need to be biopsied in the hospital by an interventional radiologist using ultrasound or CT for guidance.

Microscopic evaluation of soft tissue sarcomas is complicated, and even expert sarcoma pathologists disagree on histologic diagnosis and tumor grade at times. Nevertheless, histologic diagnosis is the most important factor when staging the tumor and determining the tumor’s aggressiveness and patient prognosis, or anticipated clinical outcome. Other factors of importance when determining a tumor’s stage are size and location. Staging is used by a specialist to plan out treatment.

With soft tissue sarcomas, metastases to lymph nodes are rare. Instead, tumors usually spread to the lungs. Other locations of metastases include the bone, liver, and brain.

Treatment of a Soft Tissue Sarcoma

Surgery to remove the tumor is the most common treatment option for soft tissue sarcomas. Sometimes, surgery is all that’s needed.

Once upon a time, amputation was frequently performed to treat sarcomas of the arms and legs. Fortunately, nowadays, limb-sparing surgery is most common.

When removing a soft tissue sarcoma, wide local excision is performed wherein the tumor along with some surrounding healthy tissue, or margin, is removed. When tumors are removed from the head, neck, abdomen, or trunk, the surgical oncologist tries to limit the size of the margins and keep as much healthy tissue intact as possible. Nevertheless, no consensus opinion exists on what the size of a “good” margin is.

In addition to surgery, radiotherapy, which uses high-energy X-rays or other forms of radiation, can be used to kill tumor cells or limit their growth. Radiotherapy is often combined with surgery and can either be given before surgery (i.e., neoadjuvant therapy) to limit the size of a tumor or after surgery (i.e., adjuvant therapy) to lower the risk of cancer recurrence. Both neoadjuvant and adjuvant therapy have their benefits and drawbacks, and there is some controversy as to the best timing to treat soft tissue sarcomas using radiotherapy.

The two main types of radiotherapy are external radiation therapy and internal radiation therapy. With external radiation therapy, a machine located outside the body delivers radiation to the tumor. With internal radiation therapy, radioactive substances sealed in wires, needles, catheters, or seeds are placed in or near the tumor.

A newer type of radiotherapy is intensity-modulated radiotherapy (IMRT). IMRT uses a computer to take pictures and reconstruct the exact shape and size of the tumor. Beams of radiation of varying intensities are then aimed at the tumor from multifarious angles. This type of radiation therapy causes less damage to surrounding healthy tissue and places the patient at lower risk for adverse effects such as dry mouth, trouble swallowing, and skin damage.

In addition to radiotherapy, chemotherapy can also be used to kill cancer cells or stop them from growing. Chemotherapy involves the administration of chemotherapeutic agents or drugs either by mouth or by vein or muscle (parenteral administration). Of note, responses to chemotherapy vary, and next-generation sequencing analysis of soft tissue sarcomas may be indicated in order to identify potential molecular targets for various tyrosine kinase inhibitors.

Various drugs are used in different types of sarcomas, in combination or alone. Examples of common drugs used include:

• Chemotherapy: doxorubicin hydrochloride (Adriamycin), dactinomycin (Cosmegen), eribulin mesylate (Halaven), trabectedin (Yondelis)
• Tyrosine kinase inhibitors: imatinib mesylate (Gleevec), pazopanib (Votrient)
• Immunotherapy: nivolumab (Opdivo)
• Anti-angiogenic agents: bevacizumab (Avastin)
• Methyl transferase inhibitors: tazemetostat (Tazverik); approved by the FDA for the treatment of locally advanced or metastatic epithelioid sarcomas in January 2020

Finally, recurrent soft tissue sarcoma is soft tissue sarcoma that returns after treatment. It may return either in the same soft tissue or in soft tissue located in another part of the body.

Bottom Line

Please keep in mind that soft tissue sarcomas are rare. All else being equal, the chance that any lump or bump on your body is cancer is low. However, you should feel free to schedule an appointment with your physician to evaluate any concerning lump or bump—especially if it’s causing pain, weakness, or so forth.

If you or a loved one has already been diagnosed with soft tissue sarcoma, please closely heed the guidance of your specialists. Although life-threatening in about half of those diagnosed, for many, soft tissue sarcomas can be treated.

Finally, newer treatments of soft tissue sarcoma are emerging. For example, regional chemotherapy, which is chemotherapy that targets specific body parts like arms or legs, is an active area of research. You or a loved one may be eligible for participation in a clinical trial. You can find clinical trials supported by the National Cancer Institute (NCI) that are near you.