Soft tissue sarcomas are cancers of the supporting tissues of the body. Soft tissue tumors can occur in muscles, fat, nerves, blood vessels, tendons and other tissues that support, surround or protect body organs and joints. While most of such tumors are benign (i.e. not cancerous) and are not life-threatening, those that are malignant are called soft tissue sarcomas. Approximately 5,000 to 6,000 soft tissue sarcomas are newly-diagnosed each year in the United States. About 40% of soft tissue sarcomas occur in the legs, usually at or above the knee. 15% develop in the hands or arms, 15% in the head or neck and the remaining 30% in the shoulders, chest, abdomen or hips.
It is not clear why some people develop sarcomas, but researchers have been able to identify some common characteristics in groups with high rates of soft tissue sarcoma. Some studies have shown that people exposed to phenoxyacetic acid in herbicides and chlorophenols in wood preservative have increased risk of developing soft tissue sarcoma, and people with certain inherited diseases such as neurofibromatosis have a higher risk of developing soft tissue sarcomas. People exposed to high doses of radiation are also at a greater risk for developing soft tissue sarcoma. Researchers are also studying genetic abnormalities and chromosome mutations as possible causes of soft tissue sarcomas.
In their early stages, soft tissue sarcomas rarely display any symptoms. Because soft tissue is very elastic, tumors can grow quite large before they are felt. The first symptom is usually a painless lump. As the tumor grows and begins to press against nearby nerves and muscles, soreness or pain will be felt. Soft tissue sarcomas can only be diagnosed by a surgical biopsy procedure in which tissue from the tumor is removed for analysis under a microscope. Soft tissue sarcomas are treated using surgery, radiation therapy or chemotherapy. Depending on the size, location, extent and severity of the tumor, a combination of all or some of these treatments may be used. Biological therapy is currently being tested as a treatment in clinical trials. The most common types of soft tissue sarcomas are described below.
Descriptions of Soft Tissue Sarcomas
This cancer develops as a tumor sticking out of the skin on the back or abdomen. Dermatofibrosarcoma protuberans is uncommon, but occurs slightly more frequently in males than females. It can occur at any age, but is more likely to occur in adults. In its early stages, the tumor remains under the skin and the skin surface will appear dark red-violet. If untreated, the tumor can break through the skin and form an open wound. The cancer has a tendency to recur, buy rarely metastasizes. Treatment consists of surgical excision.
Epithelioid sarcomas typically occur in the hands or feet of young adults. They appear as small nodules, which sometimes then merge together. The sarcoma spreads to lymph nodes in approximately 20% of patients. Because of their proximity to the joints, surgical excision can be difficult.
There are three types of Extraosseous tumors that are actually bone sarcomas found in the soft tissue. They are giant cell tumors, osteosarcomas, and Ewing's sarcoma (see pages 16-18). They have very similar characteristics as their bone sarcoma variation, Extraosseous Ewing's sarcomas respond well to radiation therapy.
Fibrosarcoma (Fibrous Tissue)
Fibrosarcomas usually occur in the arms, legs or trunk, but can occur in any of the soft tissues. They can occur around scars, muscles, nerves, tendons the lining of bones. Fibrosarcomas typically invade local tissues and can spread through the bloodstream to the lungs. This cancer will spread to the lymph nodes in fewer than 5% of patients.
Gastrointestinal stromal tumor (GIST)
Gastrointestinal stromal tumor (GIST) is a very rare cancer affecting the digestive tract or nearby structures within the abdomen. GIST most commonly affects older people, usually over age of 50 years. Children are affected very rarely.
GISTs arise either from cells called Interstitial Cells of Cajal (ICCs) or from less differentiated stem cells or precursor cells that can develop into ICCs. The ICCs are known as “pacemaker cells of the gut” because they send signals to trigger peristalsis, the digestive tract’s muscular contractions that move food along its course. Primary tumors are in the original site of development, before any spread to other locations. Primary gastrointestinal stromal tumors (GISTs) may occur anywhere along the gastrointestinal tract from the esophagus to the anus tract lumen; this is sometimes called endophytic. The most frequent site for GISTs is the stomach (about 55%), followed by the duodenum and small intestine (about 30%), esophagus (about 5%), rectum (about 5%), colon (about 2%), and rare other locations.
Cancer is most threatening when it metastasizes or spreads to additional locations beyond the primary tumor site. In GIST the most common sites for metastasis are the liver and the abdominal membranes.
Note: Information on GIST above was provided by GIST Support International.
Leiomyosarcomas are cancerous tumors that originate in the smooth muscle tissue. Smooth muscle is muscle over which the brain does not have conscious control, such as muscles in the walls of blood vessels, the uterus or the gastrointestinal tract. These cancers can originate anywhere in the body, but the uterus or gastrointestinal tracts are the most common sites of origination, with over 60% of the GI tract tumors originating in the stomach. Uterine and GI leiomyosarcomas typically are accompanied by significant bleeding and pain. Metastases usually occur in the lungs or, in the case of GI tumors, in the liver. The average age of patients diagnosed with this type of sarcoma is 60 years.
Leiomyosarcomas of the retroperitoneum and the vena cava are found mostly in women. The growth of the tumors can accelerate during pregnancy. Metastases usually occur in the lungs except in GI tumors, which often metastasize in the liver. Treatment for uterine leiomyosarcoma is total abdominal hysterectomy.
Liposarcomas which arise in fat tissue and are the most commonly diagnosed soft tissue cancer. While Liposarcoma tumors can develop anywhere in the body, they most often originate in the lining in the back of the abdominal cavity. They also occur in the thigh, the groin, the gluteal area or behind the knee. Liposarcomas rarely develop from a preexisting lipoma (i.e. a no cancerous tumor). The liposarcoma tumors are usually firm and bumpy and invade surrounding tissue aggressively. In approximately 10% of patients, the liposarcoma will spread to the lymph nodes. Liposarcomas are most often found in adults between 30 and 60 years old and are slightly more common in men than in women.
Lymphangiosarcoma / Stewart-Treves Syndrome
Lymphangiosarcoma or Stewart-Treves Syndrome is a malignant tumor originating from the endothelial cells of lymphatic vessels. Most lymphangiosarcomas arise in an arm secondary to radical mastectomy but they sometimes complicate idiopathic lymphedema. The lymphedema has usually been present for 6 to 10 years before malignant changes develop.
Most cases arise from lymphedema induced by a radical mastectomy in breast cancer patients with an average onset of 5 - 15 years and an occurrence rate of <1%. The three main indications for the development of Stewart Treves in a lymphedemous limb appear to be radiation, extensive fibrosis and recurrent or chronic infection. Another cause factor may be the immunodeficient state of a lymphedemous limb.
The sarcoma first appears as a bruised area or a purplish discoloration in an extremity. The appearance of multiple "purplish" lesions, with given patient history should cause a suspicion of lymphangiosarcoma. It progresses to an ulcer with crusting and finally to an extensive necrosis involving the skin and subcutaneous tissue. There is also often development of satellite spots from the original locale. It metastasizes widely and there is no effective therapy or cure.
There is no effective treatment for the condition. Generally the affected area is excised, which includes the amputation of a limb when affected. Chemotherapy with intraarterial mitoxantrone and placitaxel with ex vivo previous sensitivity test seems a current adequate complementary approach.
Malignant fibrous histiocytoma (MFH)
MFH has become the most common malignant sarcoma of older adults (ages of 50 and 70). These sarcomas are twice as common in men as they are in women. It tends to occur in the deep soft tissue of the extremities and the retroperitoneum (the anatomical space behind the abdominal cavity). However, it has been described in nearly every organ of the body. Signs and symptoms relate directly to the location in which it arises. It is a diagnosis of exclusion; the burden of proof is upon the pathologist to do a battery of immunohistochemical studies to exclude other sarcomas such as rhabdomyosarcoma and liposarcoma.
There are four variations of MFH: storiform pleomorphic, myxoid malignant fibrous histiocytoma, malignant giant cell tumor of soft parts and inflammatory malignant fibrous histiocytoma. Storiform and myxoid types of MFH are typically fast growing and invasion tumors, while the malignant giant cell MFH and inflammatory MFH tend to be slower growing and less invasive.
Malignant Peripheral Nerve Sheath Tumor (MPNST)
The malignant peripheral nerve sheath tumor (MPNST) is the malignant counterpart to benign soft tissue tumors such as neurofibromas and schwannomas. It is most common in the deep soft tissue, usually in close proximity of a nerve trunk. The most common sites include the sciatic nerve, brachial plexus, and sarcal plexus.
The most common symptom is pain which usually prompts a biopsy. Most cases average more than 5 cm in diameter. On sections, it may have a white surface with areas of necrosis or hemorrhage. It is the most common sarcoma arising in the setting of von Recklinghausen's disease. MPNST usually occurs in persons between 20-50 years but patients with neurofibromatosis develop tumors at an earlier age. The average age is 32 years.
Mesenchymomas is as a rare soft tissue sarcoma showing two or more distinct types of malignant mesenchymal differentiation. It is generally thought that malignant mesenchymomas are high grade sarcomas with a poor prognosis. However, low grade malignant mesenchymomas have been reported which had a better prognosis. These tumors are frequently located in the trunk (for example, the chest wall and retroperitoneum) and lower extremities (usually on the thigh). Mesenchymomas mainly occurs in adults. These tumors are quite invasive, especially when they occur in the skeletal muscles. Treatment is wide excision, often combined with radiation and/or chemotherapy.
Rhabdomyosarcomas (striated muscle tumors)
Cancerous tumors in the skeletal muscles are one of the most common types of soft tissue sarcoma. They most commonly originate in the arms or legs, but can also develop in the head, neck, heart, urinary or reproductive organ areas. Over 85% of rhabdomyosarcomas occur in infants, children, and teenagers. Although most of our skeletal muscles are in our limbs and trunk, these cancers are most often found elsewhere in the body. The most common site is in the head and neck (30%-40%) where it can grow near the eye, inside the mouth or even near the spine in the neck. The next most common sites are the urinary and reproductive organs (20%-25%) where it can start in the bladder, prostate gland, or any of the female organs. The least common sites are the arms and legs (18%-20%), and trunk (7%). But these cancers can occur anywhere else in the body and not necessarily in a site that normally contains skeletal muscle. There are several different types of Rhabdomyosarcoma:
- Embryonal rhabdomyosarcoma - The most common type, embryonal rhabdomyosarcoma (ERMS) tends to occur in the head and neck area, bladder, vagina, and in or around the prostate and testes. These usually affect infants and young children under the age of 10. Cells of embryonal (embryo-like) rhabdomyosarcomas resemble the developing muscle cells of a 6- to 8-week-old fetus. Two variants of ERMS, botryoid and spindle cell rhabdomyosarcomas, tend to have a better prognosis (outlook) than the more common forms. Chemotherapy is very effusive in treating these tumors and there is a high cure rate when combination therapy (i.e. surgery and chemotherapy) is used.
- Alveolar rhabdomyosarcoma - The second main type, alveolar rhabdomyosarcoma (ARMS), occurs more often in large muscles of the trunk, arms, and legs and typically affects older children or teenagers. This type is called alveolar because the malignant cells form little hollow spaces, or alveoli. Alveolar rhabdomyosarcoma cells resemble the normal muscle cells seen in a 10-week-old fetus. This tumor is extremely aggressive and metastasizes widely at an early stage. This cancer typically occurs in adolescents and young adults.
- Plemorphic rhabdomyosarcoma - This type of sarcoma is usually found deep in the limb. Tumors can arise at many sites within the same muscle group and may grow very rapidly. The tumors generally spread through the bloodstream, although it can also spread through the lymphatic system. Unfortunately, this sarcoma is commonly spread at the time of diagnosis Treatment generally consists of surgery and chemotherapy. Plemorphic rhabdomyosarcoma occurs in people over age 30 and commonly, but not exclusively, affects males on their extremities.
- Botryoid rhabdomyosarcoma - Botryoid rhabdomyosarcoma lesions usually occur in the genital region or urinary tract where they appear as a swollen lumpy mass. This form of sarcoma typically affects children under the age of seven.
Synovial sarcomas are most commonly found in the arms or legs often next to a joint. The most common site is adjacent to the knee, although they are also commonly found near the foot, ankle or hand. These sarcomas usually occur in young adults. While synovial cells normally line the joints of the body, the name of this particular form of sarcoma is probably a misnomer as synovial sarcomas do not necessarily arise in a joint, and the cancer cells in synovial sarcoma are likely to be very different from normal joint cells. The term “synovial” was given due to the cancer cell’s similar microscopic appearance to the normal synovial cells lining joints.
Unlike other soft tissue sarcomas, synovial cell sarcomas are often painful. Treatment usually consists of radical excision with radiation and chemotherapy or amputation combined with chemotherapy.
There are a number of different forms of sarcomas grouped as vascular sarcomas or containing many blood vessels. These include:
- Angiosarcoma - account for less than 1% of all sarcomas. This rare malignancy arises from endothelial cells of either lymphatic or vascular origin. When the cell of origin can be identified as lymphatic, the lesion is termed a lymphangiosarcoma; when vascular derivation can be ascertained, the correct term is hemangiosarcoma. Often, the cell of origin cannot be determined with certainty; hence, the more general term angiosarcoma is used. Approximately half of these lesions occur in the head and neck. The scalp and face are the most common sites of involvement. Angiosarcomas typically occur in those aged 50-70 years, and males are more commonly affected than females, with a 3:1 ratio. While most patients are asymptomatic at the time of diagnosis, some have pain or bleeding at the tumor site. Conditions associated with angiosarcoma include long-standing lymphedema and prior irradiation. Exposure to vinyl chloride is associated with angiosarcomas of the liver, but this association has not been reported with head and neck angiosarcomas.
- Alveolar soft-parts sarcoma - ASPS is very rare sarcoma typically occurs in adolescent and young adult females. It is usually a slow growing tumor found in the extremities and commonly metastasizes to the lungs. Treatment generally involves a wide resection of the lesion. It is characterized by a painless mass in the leg or buttock, with a particular affinity to travel to the lungs as multiple nodules, presumably while the sarcoma itself is still small. ASPS is very rare, because it involves a specific breaking and joining event between two chromosomes, called an "unbalanced translocation". Treatment is with surgery and radiation for the primary place where the sarcoma arises. For disease that travels to the lungs, sometimes surgery is possible to remove nodules, but more typically chemotherapy is the only option for treatment.
- Hemangioendothelioma - is a very rare form of vascular tumor. Approximately 15-30% of hemangiopericytomas occur in the head and neck; the sinonasal tract is the most common site. No sex predilection exists, and 90% of hemangiopericytomas arise in persons aged 50-70 years. Approximately 10% of hemangiopericytomas occur in children; hemangiopericytomas tend to have a much more indolent course in this group. No etiologic factors are known. Complete surgical excision is the treatment of choice for patients with hemangiopericytomas. Compared with other sarcomas of the head and neck, hemangiopericytomas are associated with a better prognosis. Local recurrence rates of 10-50% have been reported; fewer than 20% of patients have local recurrence after surgical excision.
- Kaposi’s sarcoma - Kaposi’s sarcoma typically occurs in the tissues under the skin or mucous membranes that line the mouth, nose or anus. The cancer originates in multiple sites in the mid-dermis (second layer of skin) and extends to the epidermis (outer layer of skin). Some forms of Kaposi’s sarcoma look nodular or plaque-like on the skin. Radiation therapy is usually the treatment for Kaposi’s sarcoma; however, where tumors have spread to the organs, chemotherapy is may also be used. Karposi’s sarcoma typically affects three different patient groups:
- The first group of affected patients includes older men of Jewish, Italian or Mediterranean heritage. This type of Kaposi’s sarcoma usually progresses slowly over 10-15 years. Patients commonly develop a bluish lesion on the front of the lower leg, which typically spreads to multiple lesions and can also spread to other organs.
- The second distinct group of Kaposi’s sarcoma patients are persons who have received organ transplants and who have a weakened immune system as a result of the immunosuppressive treatment following the transplant.
- The third distinct patient group is AIDS patients, whose weakened immune systems make them more susceptible to the disease. Kaposi’s sarcoma in AIDS patients usually spreads more quickly and can be found in many parts of the body.
- Malignant neurolemmoma (a/k/a malignant schwannoma or neurosarcoma) - This vascular sarcoma usually develops in young to middle- age adults, most commonly in males. Tumors occur in the peripheral nerves (i.e. not brain or spinal cord nerves). Half of the persons afflicted with this disease also have Von Recklinghausen’s disease or multiple neurofibromatosis. These tumors typically spread to the surrounding soft tissue to form a nodular tumor. Metastases can occur through the bloodstream. Tumors can be painful and sometimes nerve function is affected. Treatment is generally wide resection of the nerve. Radiation therapy and chemotherapy can also be used.