Sarcomas, soft-tissue

Also known as: Rhabdomyosarcoma, leiomyosarcoma, hemangiosarcoma, Kaposi sarcoma, lymphangiosarcoma, synovial sarcoma, neurofibrosarcoma, liposarcoma, fibrosarcoma

Related conditions: Osteosarcoma, bone cancer

Definition: Sarcomas are divided into two categories: sarcomas of bone and sarcomas of soft tissue. Soft-tissue sarcomas describe a class of malignant tumors that develop from connective tissue, which usually derives from an embryonic layer called mesoderm, is involved in structural support, and is found in linings or coverings of muscle, organs, nerves, and joints. These sarcomas can develop in any part of the body. However, more than half arise in the arms or legs, while about 20 percent are found in the chest and abdomen and about 10 percent in the head and neck.

Risk factors: The cause of most soft-tissue sarcomas is unknown; however, for some, there may be an association with heredity, radiation therapy, immune disorders, or environmental factors. For example, sarcomas may follow radiation therapy used in treating thyroid disease, breast cancer, lymphoma, or tuberculosis of the skin.

For some soft-tissue sarcomas, there is an inherited component. About 5 percent of patients stricken with neurofibromatosis, a benign but often disfiguring condition of the nerves, develop malignant sarcomas. Additionally, there is an increased sarcoma risk associated with inherited diseases such as Gardner syndrome, Li-Fraumeni syndrome (LFS), Werner's syndrome, tuberous sclerosis, basal cell nevus syndrome, and retinoblastoma. Genetic testing has linked soft-tissue sarcoma with a mutated tumor-suppressor gene in some cases and heritable chromosome rearrangement in others.

Some investigators have named vinyl chloride, dioxin, and herbicides containing the chemical phenoxyacetic acid as causative agents for other soft-tissue sarcomas, but the association is weak.

Viruses are the cause of Kaposi sarcoma in people with defective immune systems. Kaposi sarcoma usually involves the skin but may affect other areas as well.

Etiology and the disease process: Whatever its origin or cause, a sarcoma begins as a solid mass that grows from a central point outward with the least mature elements on the periphery. Surrounding the mass is a pseudocapsule, which is composed of compressed tumor cells bordered by inflammatory cells and fibrous components. The degree of pseudocapsule containment may have important implications on the progress of the tumor and the prognosis of the disease. Sarcomas generally are contained within anatomical borders such as muscle sheaths, but as the disease progresses, these borders are challenged and the tumor grows into new compartments until these are also breached. Compartmental breakdown poses special challenges for the surgeon and radiologist.

Incidence: Soft-tissue sarcoma is a relatively uncommon malignancy representing about 1 percent of all cancers. It has an annual incidence in the United States of approximately twelve thousand cases as of 2014, with women affected slightly less than men. Approximately 4,740 people were estimated to die of soft-tissue sarcoma in the United States in 2014. The most prevalent forms are fibrous histiocytoma, liposarcoma, and leiomyosarcoma.

Symptoms: Symptoms will vary with the location, size, and type of the soft-tissue sarcoma. For example, a sarcoma may appear as a seemingly harmless lump under the skin or as an abdominal growth that exhibits symptoms only after it becomes quite large. As the sarcoma grows and presses on nearby organs, nerves, muscles, or blood vessels, symptoms will correspond to the degree of interference with those tissues. For example, pressure on the nerves may result in pain or paralysis, while interference with the blood supply may cause an accumulation of fluid in the surrounding tissue spaces (edema). Similarly, restriction in mobility follows joint involvement, and internal growths may cause obstructions of the bowel, urinary tract, or chest cavity. As the tumor progresses, signs such as weight loss, fever, and fatigue may become apparent. Additionally, specific endocrine gland involvement may cause goiter, hypoglycemia, or pituitary dysfunction.

Screening and diagnosis: Early detection brings the most favorable result. However, the tumor is usually painless and often will grow unobserved. Once a tumor is suspected, imaging tests such as computed tomography (CT) or magnetic resonance imaging (MRI), radioisotope studies, and tissue biopsy will help define its aggressiveness and characteristics. Additionally, arteriograms are useful in defining the extent of tumor growth and in outlining the irregularity of the vascular network. Chest films using CT scans are essential in evaluating metastatic spread to the lungs.

The pathologist examining the biopsy tissue pays close attention to how fast the cells are dividing and compares the tissue’s structure to the surrounding normal tissue. The information from the biopsy report allows for formal grading and staging of the sarcoma. All the information from the biopsy, imaging, staging, and past experience sets the best course of treatment and gives an estimate of the patient’s prognosis.

The pathologist grades the sarcoma according to the degree of new blood vessels supplying the tumor, how far it has reached into surrounding tissues, how fast the cells are dividing (mitosis), and their degree of structural abnormality. The grading systems vary somewhat according to the parameters set by the Musculoskeletal Tumor Society (MTS) or the American Joint Committee (AJC), but both are a measure of the tumor’s aggressiveness.

Staging further defines the tumor by characterizing its aggressiveness and anatomic profile. The designation T1 indicates a tumor less than 5 centimeters (cm), T2 more than 5 cm, and T3 signifies the invasion of major blood vessels, nerves, or bones. The letter N describes the presence or absence of metastasis to the local lymph nodes and respectively receives an N1 or N0 description. Similarly, M1 or M0 represents the presence or absence, respectively, of metastasis to distant areas. The sarcoma is staged from IA through IVB depending on severity. For example, at the lower end of the system the tumor might receive the most favorable grade (G) of 1A and its GTNM parameters might look like this: G1, T1, N0, M0. At the opposite extreme, the GTNM description would have this designation: G3, T3, N1, M1.

Treatment and therapy: The staging system combined with tumor location sets the course of treatment. The treatment decisions incorporate surgery, radiation therapy, and possibly chemotherapy in a multidisciplinary approach. Typically, surgery alone is reserved for grade 1 tumors, where the surgeon is able to incise the tissue using wide margins. Generally, however, surgery alone invites recurrence. Combining surgery with radiation allows for less radical surgery and may eliminate the need for such debilitating outcomes as amputation.

Soft-tissue sarcomas are not always what they seem. They may appear well encapsulated, but there is no true capsule, and the surgeon must resect the tumor beyond its apparent margins. This requires using wide or even radical incisions when extracting the tumor and may include limb amputation. In the past, less aggressive surgical removal resulted in a high rate of recurrence, increasing the likelihood of metastasis. Conversely, aggressive surgery combined with radiation therapy and possibly chemotherapy results in relatively low recurrence rates.

Like surgery, radiation therapy usually targets a larger area than seems affected. Past experience with sarcomas dictates the total destruction of the primary tumor, as any recurrence is associated with metastasis and a poor prognosis. Because of this, maintaining function or anatomical form is an important but secondary consideration. Soft-tissue sarcomas tend to grow along fascial planes, which are the connective tissue surrounding muscles, bones, organs, nerves, blood vessels, and other structures, and accordingly, this is factored in during treatment. Radiation therapy may be used before or after surgery, and there are advantages and disadvantages to each, but the effectiveness is the same.

Beyond traditional radiation therapy, techniques using intraoperative irradiation and interstitial implantation are coming into use. Intraoperative radiation therapy ( IORT) sends a concentrated beam of radiation directly into the exposed sarcoma during surgery. This technique allows doctors to administer high doses of radiation to tumors without exposing nearby healthy organs to radiation. Interstitial implantation is a radiotherapeutic technique in which the physician implants radioactive isotopes directly into tissue.

Chemotherapy is another treatment option, either as a primary method or with surgery. Some of the drugs used against soft-tissue sarcomas include vincristine, doxorubicin (Adriamycin), dacarbazine (DTIC), methotrexate, ifosfamide, and cisplatin, and they may be given individually or in combinations. Although chemotherapy results in mixed outcomes, it has found a place when used for limb salvage together with surgery and irradiation.

Prognosis, prevention, and outcomes: Prognosis depends on the health of the patient; the size, location, type, grade, and stage of the tumor; and whether the tumor has recurred. For example, sarcomas of the arms or legs respond better than those of other locations, and older patients generally have a poorer result. When the tumor is still small and localized (Stage I), the five-year survival rate is about 90 percent. As the tumor becomes more aggressive, survival becomes increasingly difficult. Location of the tumor is critical. When tumors arise in the extremities, they are usually noticed earlier, are easier to remove surgically, and are more amenable to radiation therapy. Conversely, tumors in the pelvis, chest, paraspinal region, neck, and abdomen pose greater barriers to complete resection and effective radiation therapy. Specific types of soft-tissue sarcoma, such as Kaposi sarcoma, have a worse prognosis than other forms. In general, lymph node metastasis is uncommon.

According to the National Cancer Institute (NCI), the five-year survival rate for sarcomas as a group is about 50 percent. Included in the overall picture is a five-year survival rate of 83 percent for localized sarcomas; 54 percent for regional stage sarcomas; and 16 percent for sarcomas with distant spread.

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