NORD gratefully acknowledges William B. Laskin, MD, Associate Professor of Pathology, Feinberg School of Medicine, Northwestern University; Head of Surgical Pathology, Northwestern Memorial Hospital, for assistance in the preparation of this report.
Leiomyosarcoma of the inferior vena cava is an extremely rare malignant (cancerous) tumor arising from the smooth muscle lining the walls of the large vein that carries blood from the lower body to the heart (inferior vena cava). There are essentially two types of muscles in the body - voluntary and involuntary. Smooth muscles are involuntary muscles - the brain has no conscious control over them. Smooth muscles react involuntarily in response to various stimuli. For example, the smooth muscle in walls of blood vessels contracts to help regulate blood flow.
Leiomyosarcomas are a form of cancer. The term "cancer" refers to a group of diseases characterized by abnormal, uncontrolled cellular growth that invades surrounding tissues and may spread (metastasize) to distant bodily tissues or organs via the bloodstream, the lymphatic system, or other means. Different forms of cancer, including leiomyosarcomas, are graded according to certain histological parameters evaluated microscopically and this grade (low, intermediate, or high) gives the clinician an indication of the potential clinical aggressiveness of the tumor.
Leiomyosarcoma is classified as a soft tissue sarcoma. Sarcomas are malignant tumors that arise from the connective tissue, which connects, supports and surrounds various structures and organs in the body. Soft tissue includes fat, muscle, nerve, tendons, tissue surrounding the joints (synovial tissue), and blood and lymph vessels. The exact cause of sarcomas including leiomyosarcomas is unknown.
The symptoms associated with a leiomyosarcoma of the IVC vary greatly from case to case. The exact location and size of the tumor within the vena cava determines the specific symptoms that occur and whether or not the tumor can be removed surgically. The inferior vena cava runs from the pelvis to the thoracic cavity, emptying into the heart. The inferior vena cava is connected to numerous veins including the main vein of the liver (hepatic vein) and the main vein of the kidneys (renal vein). Most tumors occur in the middle portion of the IVC (i.e., between the hepatic and renal veins or the lower portion of the IVC (i.e., below the renal vein). Less often, a leiomyosarcoma develops within the upper portion of the IVC (i.e., above the hepatic vein).
Many individuals with a leiomyosarcoma of the inferior vena cava do not exhibit any symptoms (asymptomatic). The tumor may grow and spread without any apparent signs. Eventually, some individuals may develop a palpable mass in the stomach. Vague, general symptoms may occur including abdominal pain, fever, weakness, weight loss, vomiting, difficulty breathing (dyspnea), and night sweats.
A leiomyosarcoma’s location within the IVC may be associated with additional symptoms specific to that area. Tumors in the lower portion of the inferior vena cava may be associated with lower back pain and generalized swelling due to the abnormal accumulation of fluid (edema), especially in the legs and around the eyes. A leiomyosarcoma of the middle portion may cause narrowing or blockage (occlusion) of the renal vein resulting in nephrotic syndrome – a kidney condition characterized by protein in the urine, low blood protein levels, and edema affecting the limbs and the area around the eyes.
A leiomyosarcoma of the upper segment may cause the development of Budd-Chiari syndrome and, in extremely rare cases, irregular heartbeat rhythms (arrhythmia). (For more information on this disorder, see the Related Disorders section of this report.)
Another complication associated with a leiomyosarcoma of the IVC is deep vein thrombosis (DVT), a condition characterized by blood clots (thrombosis) in the deep veins of the lower legs or thigh that often hamper circulation. A piece of the blood clot can potentially break off and travel to another area of the body (embolize) where it lodges in a vein or artery cutting off blood flow to a vital organ such as the brain or lungs.
The exact cause of leiomyosarcomas of the IVC is unknown. They often occur spontaneously, for no apparent reason. 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.
Malignancies, including leiomyosarcoma, 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 leiomyosarcomas. Researchers have speculated that exposure to certain chemicals (e.g., herbicides) may also be linked to an increased risk of developing leiomyosarcomas.
Leiomyosarcomas of the IVC affect females more often than males. Most cases are diagnosed in adult women in the fifth or sixth decade of life. Leiomyosarcoma of the IVC was first identified by a German doctor in 1871. However, as of 2006, fewer than 300 cases had been reported in the medical literature. Although extremely rare, it is the most common primary malignancy of the inferior vena cava.
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 and adolescents.
A tumor affecting the inferior vena cava is often found incidentally on routine imaging exams. Various 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.
Surgical removal and microscopic evaluation of affected tissue may confirm a diagnosis of a leiomyosarcoma. However, because of the location of the inferior vena cava, it may be difficult to perform a biopsy. In some cases, a CT-guided biopsy may be used to obtain a tissue sample and confirm a diagnosis of leiomyosarcoma.
A procedure known as an angiography is sometimes used to aid in the diagnosis of leiomyosarcoma of the IVC. During an angiography, a special fluid known as contrast dye is injected into the body. This fluid is visible upon x-rays and allows for examination of blood vessels. X-rays of blood vessels taken using an angiography are called angiograms.
Laboratory tests and specialized imaging tests may also be conducted to determine possible infiltration of regional lymph nodes and the presence of distant metastases.
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), oncological surgeons, oncology nurses, and other healthcare 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 a leiomyosarcoma of the IVC is surgical excision and removal of the entire tumor and surrounding tissue (resection). Surgery is the mainstay of treatment for leiomyosarcoma and should be performed by experienced oncological surgeons (and not general surgeons unfamiliar with the surgical approach). In some cases only a portion of the tumor can be safely removed. Depending upon the location of the primary tumor, surgical procedures may also include the use of certain reconstructive techniques.
Although radiation therapy provides limited or no benefit in treating most forms of soft tissue sarcoma, some reports suggest that it may be helpful for individuals with leiomyosarcomas of the IVC. 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 occurring in the IVC 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 in general 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: [email protected]
For information about clinical trials sponsored by private sources, contact:
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FROM 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.
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