Introduction
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 12,000 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
Types of Soft Tissue Sarcoma (and the tissue it arises from)
Clear Cell Sarcoma
Clear cell sarcoma is a rare soft tissue cancer that most often develops in tendons of the arms or legs of young adults. Under the microscope, it has some features of malignant melanoma, a type of skin cancer, hence the reference of malignant melanoma of soft parts. It is an aggressive cancer that has a propensity for lymph node metastases.
Dermatofibrosarcoma Protuberans (DFSP)
This cancer develops as a tumor sticking out of the skin, most commonly 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, but rarely metastasizes. Treatment consists of surgical excision. If DFSP metastasizes, the use of a tyrosine kinase inhibitor such as imatinib can be effective at helping to control the tumor.
Desmoplastic Small Round Cell Tumor
Desmoplastic small round cell tumors are a soft tissue sarcoma that typically begins in the abdomen. These tumors occur most often in young men and boys, though they can occur at any age and can also affect females. Desmoplastic small round cell tumors often form as multiple tumors in the tissue (peritoneum) that lines the inside of the abdomen and pelvis and can quickly spread to other structures within the abdomen. Treatment for desmoplastic small round cell tumors typically involves a combination of surgery, chemotherapy and radiation therapy.
Epithelioid Sarcoma
Epithelioid sarcoma typically occurs in the hands or feet of young adults. It appears in the form of small nodules, which sometimes merge together. This sarcoma spreads to lymph nodes in approximately 20% of patients. Because of the nodules’ proximity to the joints, surgical excision can be difficult.
Extraosseous Tumors
There are three types of extraosseous tumors, which are actually bone sarcomas found in the soft tissue: (1) mesenchymal chondrosarcoma; (2) extraskeletal osteosarcoma; and (3) Ewing's sarcoma (see pages 16-19). Chondrosarcomas and osteosarcomas may not be treated in exactly the same way as their bone varieties, but extraosseous Ewing's sarcomas are treated similarly and 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, and the lining of bones. Fibrosarcomas typically invade local tissues and can spread through the bloodstream to the lungs.
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 the age of 50 years. Children are affected very rarely, and their disease is different than that in adults.
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 the “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 GISTs may occur anywhere along the gastrointestinal tract from the esophagus to the anus. 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.
In GIST, the most common sites for metastasis are the liver and the abdominal membranes. Systemic treatment options include the use of tyrosine kinase inhibitors: imatinib, sunitinib, and regorafenib, as well as others.
Note: Information on GIST, above, was provided by GIST Support International.
Leiomyosarcoma
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 muscle 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 tumors can accelerate during pregnancy. Treatment for uterine leiomyosarcoma is total abdominal hysterectomy.
You can read more information on Leiomyosarcoma. A new chemotherapy option for Leiomyosarcoma was approved in October of 2015.
Liposarcoma
Liposarcomas arise in fat tissue and are the most commonly diagnosed soft tissue cancers. 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, and behind the knee. Liposarcomas rarely develop from a pre-existing lipoma (for example, a non-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. There are several types of liposarcoma: atypical lipomatous tumor, myxoid liposarcoma, pleomorphic liposarcoma and dedifferentiated liposarcoma.
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 a lymphedematous arm secondary to radical mastectomy, but they sometimes complicate idiopathic lymphedema. The lymphedema has usually been present for 6-10 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 less than 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.
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 also is often development of satellite spots from the original location. It metastasizes widely and there is no effective therapy or cure. Generally the affected area is excised, which includes the amputation of a limb when affected.
Malignant Fibrous Histiocytoma (MFH)/Undifferentiated Pleomorphic Sarcoma
MFH has become the most common malignant sarcoma of older adults (age 50-70). This category of tumors has been renamed Undifferentiated Pleomorphic Sarcoma (UPS) by the World Health Organization (WHO). However, an MFH diagnosis is still commonly used by pathologists. These sarcomas are twice as common in men as they are in women. They tend to occur in the soft tissue of the extremities and the retroperitoneum (the anatomical space behind the abdominal cavity). However, it has been identified 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, and usually a battery of immunohistochemical studies must be done 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 invasive 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, Malignant Schwannoma or Neurofibrosarcoma) is the malignant counterpart to benign soft tissue tumors such as neurofibromas and schwannomas. It accounts for 5-10% of soft tissue sarcomas. It is most common in the deep soft tissue, usually in close proximity to 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 tumors are more than 5 cm in diameter. MPNST is seen among patients with Type 1 Neurofibromatosis, or von Recklinghausen's disease. It usually occurs in people 20-50 years old, but patients with neurofibromatosis develop tumors at an earlier age.
These tumors typically spread to the surrounding soft tissue to form a nodular tumor. Metastasis 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.
Mesenchymomas
Mesenchymoma is 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 and have 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 found in children. 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 in the body, and not necessarily in a site that normally contains skeletal muscle. There are several different types of rhabdomyosarcoma:
Rhabdomyosarcomas (Striated Muscle Tumors)
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 six- to eight-week-old fetus. Two variants of ERMS, botryoid and spindle cell, tend to have a better prognosis or outlook. Chemotherapy is very commonly used in treating these tumors, and there is a high cure rate when combination therapy (i.e. surgery and chemotherapy) is used. When there is a tumor seen at the surgical margin, radiotherapy is often added. 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.
Rhabdomyosarcomas (Striated Muscle Tumors)
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. This tumor is extremely aggressive and metastasizes widely at an early stage.
Pleomorphic 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 they can also spread through the lymphatic system. Unfortunately, this sarcoma has usually spread by the time of diagnosis. Treatment generally consists of surgery and chemotherapy. Pleomorphic rhabdomyosarcoma occurs in people over age 30 and commonly, but not exclusively, affects males on their extremities.
Synovial Sarcoma
Primary synovial sarcomas are most common in the soft tissue near the large joints of the arm and leg but have been documented in most human tissues and organs, including the brain, prostate and heart. The most common site is adjacent to the knee, although they are also often 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 chosen due to the cancer cell’s similarity, under a microscopic, to the normal synovial cells lining joints; however, the actual cells from which the tumor develops are unknown and not necessarily synovial.
Synovial sarcoma occurs most commonly in the young, representing about 8% of all soft tissue sarcomas but about 15-20% of cases in adolescents and young adults. The peak of incidence is before the 30th birthday and males are affected more often than females (ratio around 1.2:1).
Symptoms
Synovial sarcoma usually presents with an otherwise asymptomatic swelling or mass, although general symptoms related to malignancies can be reported such as fatigue. Unlike other soft tissue sarcomas, synovial sarcomas are often painful from the outset.
Treatment
Treatment usually involves:
Surgery, to remove the tumor and a safety margin of healthy tissue. This is the mainstay of synovial sarcoma treatment and is curative in approximately 20-70% of patients,depending on the particular study being quoted.
Conventional chemotherapy, (for example, doxorubicin hydrochloride and ifosfamide), to reduce the number of remaining microscopic cancer cells. The benefit of chemotherapy in synovial sarcoma to overall survival remains unclear, although a recent study has shown that survival of patients with advanced, poorly differentiated disease marginally improves with doxorubicin/ifosfamide treatment.
Radiotherapy to reduce the chance of local recurrence. The benefit of radiotherapy in this disease is less clear than for chemotherapy.
Vascular Sarcomas
Vascular sarcomas are so named because they contain many blood vessels. There are different forms of vascular sarcomas, including:
Angiosarcoma
Angiosarcomas account for less than 2% 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 determined, 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 between 50 and 70 years old, and males are more commonly affected than females by 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.
Hemangiopericytoma/Solitary Fibrous Tumor (SFT)
Hemangiopericytoma is a very rare form of a 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 people 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. Most pathologists prefer to use the term “SFT”, rather than “hemangiopericytoma.” 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 in the mucous membranes that line the mouth, nose, and 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, when tumors have spread to the organs, chemotherapy 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 group of Kaposi’s sarcoma patients consists of people who have received organ transplants and have a weakened immune system as a result of the immunosuppressive treatment following the transplant.
The third patient group is made up of AIDS patients, whose weakened immune systems make them more susceptible to the disease. Kaposi’s sarcoma in AIDS patients usually spreads quickly and can be found in many parts of the body.
References:
- American Academy of Orthopaedic Surgeons. (Nov. 2014). Soft Tissue Sarcomas. Retrieved on January 28, 2016 at http://www.orthoinfo.org/topic.cfm?topic=A00508
- American Cancer Society. (2015). What is a soft tissue sarcoma? Retrieved on January 28, 2016 at http://www.cancer.org/cancer/sarcoma-adultsofttissuecancer/detailedguide/sarcoma-adult-soft-tissue-cancer-soft-tissue-sarcoma
- Amschwand Sarcoma Cancer Foundation
- Cancer Information Network. Aug. 2000.
- Cheng, Edward Y. M.D., Maheshwari, Aditya V. MD. Ewing’s Sarcoma Family of Tumors (EWST). Journal of the American Academy of Orthopedic Surgeons, February 2010. http://journals.lww.com/jaaos/Fulltext/2010/02000/Ewing_Sarcoma_Family_of_Tumors.4.aspx
- Cheng, M.D., Edward Y., Department of Orthopaedic Surgery, University of Minnesota Masonic Cancer Center Newsletter, Summer 2008.
- DeVita, Vincent T. , et al., eds. Cancer: Principles and Practice of Oncology. Philadelphia, PA: Lippincott-Raven, 1997.
- GIST Support International. What is GIST?. (2011). Retrieved 2015 at http://www.gistsupport.org/about-gist/
- Mayo Clinic. (2014). Diseases and Conditions: Desmoplastic small round cell tumors. Retrieved January 28, 2016 from http://www.mayoclinic.org/diseases-conditions/desmoplastic-tumors/basics/definition/con-20035314
- Pisters M.D., Peter W. T., Casper M.D., Ephraim S. and Soffen M.D., Edward M. "Soft tissue Sarcomas." Cancer Management: A Multidisciplinary Approach. Ed. PRR Inc. Aug. 2000.
- The Doctor’s Doctor Web site
- The Sarcoma Alliance. Retrieved January 28, 2016 from http://sarcomaalliance.org/what-you-need-to-know/what-is-sarcoma/