Information on the following diseases can be found in the Related Disorders section of this report:

• None

The symptoms of a leiomyosarcoma vary depending upon the exact location, size, and spread of the tumor. A leiomyosarcoma, especially in the early stages, may not be associated with any obvious symptoms (asyptomatic). General symptoms associated with cancer may occur including fatigue, fever, weight loss, a general feeling of ill health (malaise), and nausea and vomiting.

Pain may occur in the affected area because of compression of the adjacent nerves. Swelling may also occur. A mass may be detectable in some cases. Additional symptoms are specific to the exact location of the tumor. The two most common sites affected are the gastrointestinal tract and the uterus. A leiomyosarcoma of the gastrointestinal tract may cause black, tarry, foul-smelling stools (melena), abdominal discomfort, bleeding in the bowels, and vomiting up of blood (hematemesis). A leiomyosarcoma of the uterus may cause abnormal bleeding for the uterus and vagina, pelvis or stomach, abnormal vaginal discharge, and a change in bladder or bowel habits.

Most forms of leiomyosarcoma are aggressive tumors that may spread (metastasize) to other areas of the body such as the lungs or liver, potentially causing life-threatening complications. Leiomyosarcoma also has a high risk of recurring even after treatment.

The exact cause of leiomyosarcoma is unknown. Researchers speculate that genetic and immunologic abnormalities, environmental factors (e.g., exposure to ultraviolet rays, certain chemicals, ionizing radiation), diet, stress, and/or other factors may play contributing roles in causing specific types of cancer. Investigators are conducting ongoing basic research to learn more about the many factors that may result in cancer.

In individuals with cancer, including leiomyosarcoma, malignancies may develop due to abnormal changes in the structure and orientation of certain cells known as oncogenes or tumor suppressor genes. Oncogenes control cell growth; tumor suppressor genes control cell division and ensure that cells die at the proper time. The specific cause of changes to these genes is unknown. However, current research suggests that abnormalities of DNA (deoxyribonucleic acid), which is the carrier of the body's genetic code, are the underlying basis of cellular malignant transformation. These abnormal genetic changes may occur spontaneously for unknown reasons or, more rarely, may be inherited.

Leiomyosarcomas are associated with specific genetic and environmental risk factors. Certain inherited conditions that run in families may increase the risk of developing a leiomyosarcoma. These disorders include Gardner syndrome, Li-Fraumeni syndrome, Werner syndrome, neurofibromatosis and several immune deficiency syndromes. The exact association between leiomyosarcomas and these disorders is not understood. (For more information on these disorders, choose the specific disorder name as your search term in the Rare Disease Database.)

Individuals exposed to high dose radiation may have a higher than normal risk of developing a leiomyosarcoma. Researchers have speculated that exposure to certain chemicals (e.g., herbicides) may also be linked to an increased risk of developing a leiomyosarcoma.

Leiomyosarcomas affect both males and females. Leiomyosarcoma is a form of soft tissue sarcoma. According to the American Cancer Society, 9,530 new cases of soft tissue sarcoma will occur in the United States in 2006. Soft tissue sarcomas affect men slightly more often than women and occur more often in adults than children or adolescents. Soft tissue sarcomas account for 1 percent of all adult cancers in the United States.

According to one estimate, leiomyosarcomas account for 7-11 percent of all cases of soft tissue sarcomas. Certain types of leiomyosarcoma (e.g., retroperitoneal and interior vena cava) occur more often in women.

Symptoms of the following disorders can be similar to those of a leiomyosarcoma. Comparisons may be useful for a differential diagnosis.

Leiomyomas are benign tumors arising from the smooth muscle. The uterus and the gastrointestinal tract are the most common locations for this tumor. In some cases, multiple leiomyomas form. Leiomyomas often do not cause symptoms (asymptomatic). In some cases they may be associated with pain or swelling in the affected area. Leiomyomas may grow large enough to compress nearby structures causing a variety of symptoms and necessitating surgical removal. In extremely rare cases, leiomyomas may progress to become cancerous (malignant transformation). The exact cause of leiomyomas is unknown. (For more information on this condition, choose "leiomyoma" as your search term in the Rare Disease Database.)

Gastrointestinal stromal tumors (GIST) belong to a group of cancers known as soft tissue sarcomas. Tumors usually arise from the intestinal tract with the most common site being the stomach, followed by the small intestine, and the colon/rectum with rare cases arising in the esophagus. There are also tumors that appear to arise in the membranous tissue lining the wall of the stomach (peritoneum) or in a fold of such membranous tissue (the omentum). There are also case reports of tumors arising in the appendix and/or pancreas. These tumors most commonly present with abdominal pain, bleeding or signs of intestinal obstruction. They spread most commonly to sites within the abdominal cavity and to the liver, although there are rare cases of spread to the lungs and bone. GIST results from a change in one of two genes, KIT or PDGFR, which leads to continued growth and division of tumor cells. There are a few reported cases of families in which a gene mutation is inherited; however, the majority of tumors are sporadic and not inherited. Treatment is with surgery. In individuals in whom the disease has spread, treatment may include surgery when possible and the administration of imatinib mesylate (Gleevec, Glivec), a tyrosine kinase inhibitor that inhibits the KIT or PDGFR responsible for tumor growth. Ongoing studies are testing to see whether imatinib mesylate can delay or prevent recurrence of GIST after the tumor has been removed (resection). Standard chemotherapy is not effective for this type of sarcoma, with a less than 5% response rate. The role of imatinib mesylate in pediatric GIST is being studied at this time. (For more information on this disorder, choose "GIST" as your search term in the Rare Disease Database.)

Diagnosis
A diagnosis of a leiomyosarcoma may be made based upon a detailed patient history, a thorough clinical evaluation and a variety of tests including blood tests, surgical removal and microscopic examination of tissue (biopsies) and various imaging techniques. In some cases, individuals may notice a painful lump or mass in the affected area. A key diagnostic aspect is distinguishing malignant leiomyosarcoma from its benign counterpart, the leiomyoma.

To confirm a diagnosis of leiomyosarcoma a fine-needle aspiration may be performed. Fine-need aspiration (FNA) is a diagnostic technique in which a thin, hollow needle is passed though the skin and inserted into the nodule or mass to withdraw small samples of tissue. The collected tissue is then studied under a microscope. In some cases, FNA may prove inconclusive and physicians may perform an incisional biopsy. During an incisional biopsy, a small sample tissue is surgically removed and sent to a pathology laboratory where it is processed and studied to determine its microscopic structure and makeup (histopathology).

Specialized imaging techniques may be used to help evaluate the size, placement, and extension of the tumor and to serve as an aid for future surgical procedures, among individuals with leiomyosarcomas. Such imaging techniques may include computerized tomography (CT) scanning, magnetic resonance imaging (MRI) and ultrasound. During CT scanning, a computer and x-rays are used to create a film showing cross-sectional images of certain tissue structures. An MRI uses a magnetic field and radio waves to produce cross-sectional images of particular organs and bodily tissues. During an ultrasound reflected sound waves create an image of internal organs and other structures within the body.

Laboratory tests and specialized imaging tests may also be conducted to determine possible infiltration of regional lymph nodes and the presence of distant metastases.

Treatment
The therapeutic management of individuals with a leiomyosarcoma may require the coordinated efforts of a team of medical professionals, such as physicians who specialize in the diagnosis and treatment of cancer (medical oncologists), specialists in the use of radiation to treat cancer (radiation oncologists), surgeons, oncology nurses, and other specialists.

Specific therapeutic procedures and interventions may vary, depending upon numerous factors, such as primary tumor location, extent of the primary tumor (stage), and degree of malignancy (grade); whether the tumor has spread to lymph nodes or distant sites; an individual's age and general health; and/or other elements. Decisions concerning the use of particular interventions should be made by physicians and other members of the health care team in careful consultation with the patient, based upon the specifics of the case; a thorough discussion of the potential benefits and risks; patient preference; and other appropriate factors.

The main form of treatment for leiomyosarcomas is surgical excision and removal of the entire tumor and surrounding tissue (resection). Depending upon the location of the primary tumor, surgical procedures may also include the use of certain reconstructive techniques. If the lymph nodes are affected, they will be removed as well. Surgical options are dictated by the size, location and spread of a tumor.

In addition, based upon primary tumor site, size, and other factors, recommended standard therapy may often include postoperative radiation to help treat known or possible residual disease. If initial surgery is not an option due to the specific location and/or progression of the malignancy, therapy may include radiation alone. Radiation therapy preferentially destroys or injures rapidly dividing cells, primarily cancerous cells. However, some healthy cells (e.g., hair follicles, bone marrow, etc.) may also be damaged, leading to certain side effects. Thus, during such therapy, the radiation is passed through diseased tissue in carefully calculated dosages to destroy cancer cells while minimizing exposure and damage to normal cells. Radiation therapy works to destroy cancer cells by depositing energy that damages their genetic material, preventing or slowing their growth and replication.

For some affected individuals, particularly those who have locally advanced, metastatic, or recurrent disease, therapy with certain anticancer drugs (chemotherapy) may also be recommended, possibly in combination with surgical procedures and/or radiation; physicians may recommend combination therapy with multiple chemotherapeutic drugs that have different modes of action in destroying tumor cells and/or preventing them from multiplying.

In most cases, however, chemotherapy and radiation therapy have had only limited success in slowing or stopping progression of leiomyosarcomas. Because of the rarity of leiomyosarcomas no standard or overall effective type of chemotherapy or radiation therapy has been identified. The use of chemotherapy and radiation therapy for the treatment of leiomyosarcomas remains under investigation. (Please see the "Investigational Therapies" section below.)

Medical centers and hospitals that specialize in sarcomas (sarcoma centers) are conducting research into new treatments for individuals with soft tissue sarcomas including new chemotherapeutic drugs, new combinations of chemotherapeutic drugs, angiogenesis inhibitors that prevent the formation of new blood vessels needed to supply blood tumors, and various biologic therapies that involve the immune system in fighting cancer. (For information on sarcoma centers, contact the sarcoma specific nonprofit organizations listed in the Resources section of this report.)

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com

TEXTBOOKS
De Vita Jr Vt, Hellman S, Rosenburg SA. Eds. Cancer: Principles and Practice on Oncology. 5th ed. J.B. Lippincott Company. Philadelphia, PA; 1997:1748-9.

JOURNAL ARTICLES
Suppiah R, Wood L, Elson P, Budd GT. Phase I/II study docetaxel, ifosfamide, and doxorubicin in advanced, recurrent, or metastatic soft tissue sarcomas (STS). Invest New Drugs. 2006;21[Epub ahead of print].

Bay JO, Ray-Coquard I, Fayette J, et al., Docetaxel and gemcitabine combination in 133 advanced soft tissue sarcomas: a retrospective analysis. Int J Cancer. 2006;119:706-11.

Garcia del Muro X, Lopez-Pousa A, Martin J, et al., A phase II trial of temozolomide as a 6-week, continuous, oral schedule in patients with advanced soft tissue sarcoma: a study by the Spanish Group for Research on Sarcomas. Cancer. 2005;104:1706-12.

Shmulevich I, Hunt K, El-Naggar A, et al., Tumor specific gene expression profiles in human leiomyosarcoma. An evaluation of intratumor heterogeneity. Cancer. 2002;94:2069-75.

ON THE INTERNET
Mayo Foundation for Medical Education and Research. Thyroid Cancer. Soft Tissue Sarcomas. Sept. 15, 2005. Available at: http://www.mayoclinic.com/health/soft-tissue-sarcoma/DS00601 Accessed On: 7/20/2006.

American Cancer Society. Detailed Guide: Sarcoma – Adult Soft Tissue Cancer. Last Update: 3/10/2006. Available at: http://www.cancer.org/docroot/cri/cri_2_3x.asp?dt=38 Accessed On: 7/20/2006.

Martinez GE. Intestinal Leiomyosarcoma. eMedicine Journal. Last Update:12/29/2004:10pp. Available at: http://www.emedicine.com/med/topic1180.htm Accessed On:7/29/2006.

Children's Hospital Boston. Leiomyosarcoma. Copyright 2005-2006. Available at: http://www.childrenshospital.org/az/Site1098/mainpageS1098P0.html Accessed On: 7/12/2006.