Alveolar soft part sarcoma (ASPS) is a rare sarcoma (malignant tumor of connective tissue) of an unclear cause. It is among the least common sarcomas, representing 0.2-1 percent of large studies of soft tissue sarcomas. Since there are approximately 8000 soft-tissue sarcomas per year that arise in the United States, this means there are on the order of 15 to 80 cases nationwide each year. 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". This finding is observed in essentially all ASPS examined so far. This finding cannot be passed on to children, however, as the finding occurs only in the tumor, not in the normal cells, in addition, there are no families in which multiple family members have ASPS.
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. This tumor tends to be resistant to standard chemotherapy, so new treatments involving new chemotherapy drugs are also a reasonable option for treatment. Interferon-alfa showed benefit in one person from Japan with ASPS. There is little other data on possible helpful chemotherapy for this tumor.
The typical clinical findings are of a painless thigh or buttock mass, although ASPS can occur in the trunk, arm or elsewhere. Sometimes these masses cause pain by stretching of the surrounding tissues, and cause limping or other difficulty with movement.
In its advanced stages, when nodules are found in the lung, the tumor nodules can cause cough, sharp chest pain, or fluid collections around the lungs (pleural effusions). Some people will develop headaches associated with metastases to the brain, or a fracture from metastases to the bones. The involvement of the lungs or brain by ASPS is a potentially life-threatening complication, but people can live for several years despite lung nodules, since the nodules grow only very slowly for most people. In the case of brain metastases, surgery and radiation are the major ways to control the tumor and the side effects they cause in the brain.
There is no exposure or infection that is known to predispose to ASPS. It is known that two chromosomes break and rejoin is a certain way (unbalanced translocation) and bring together two genes, normally separated on chromosomes X (the sex chromosome) and 17. These genes are called ASPL on chromosome 17 and TFE3 on chromosome X. Interestingly, the exact same chromosomal changes are found in a rare form of kidney cancer, papillary renal cell carcinoma. This is a cancer of an entirely different nature. The finding of the same chromosomal breaking and rejoining in two very different forms of cancer is unprecedented in medicine, and will likely point out more about the nature of these two very rare cancers.
ASPS, tends to affect younger people, between 15 and 35 years of age. Women outnumber men, especially under age 25. There appears to be no link of this tumor to a particular ethnicity.
Biopsy is the fastest way to come to a diagnosis of soft-tissue sarcomas. There are more than 50 different types of sarcomas, of which ASPS is only one rare subtype. Often times, a core needle biopsy of the leg mass is enough to make the diagnosis. If a core needle biopsy is not diagnostic, then an incisional biopsy that obtains more tissue will make the diagnosis.
Typically, people will get CT (computed tomography) scans or MRI (magnetic resonance imaging) scans of the primary tumor site to determine if the mass is removable. A CT scan of the chest or even a simple chest X-ray will determine if there is disease in the lungs. Bone scans can sometimes show if tumors have moved to bone, even with normal findings on x-rays. ASPS, generally does not move to lymph nodes, instead preferring to travel via the blood to get to the lungs or other parts of the body.
Treatment for ASPS involves teams of doctors. For local care of the tumor, surgery and radiation are the key elements of treatment. If the tumor has traveled, chemotherapy or similar treatments that go all over the body are used.
Surgery is the only way to cure ASPS. It can only cure ASPS if the tumor is localized and has not moved elsewhere in the body, such as the lungs. It is rare for amputation to be used as a surgical technique to attempt to cure sarcomas (it occurs less than 5% of the time at most major US sarcoma centers). Typical surgery is called “limb-sparing”, trying to get around the tumor completely, without having to remove so much tissue that the limb (or other site) does not work well anymore.
Often, radiation is used before or after surgery to minimize the chance of the tumor coming back in the place where it started. This can be achieved by shining a radiation beam at the tumor (external beam radiation, or some variant of that) or can be achieved by placing temporary catheters (tubes) in the area where the tumor was resected. These tubes stick out of the skin and can have radiation seeds placed in them to deliver a high dose of radiation to the area of the tumor in a very specific manner. This technique is called brachytherapy. Either external beam radiation or brachytherapy are used, typically when the tumor is 2 inches in size or greater. For smaller tumors, it is not clear that radiation helps decrease the risk of the tumor coming back.
Without evidence of disease in the lungs, or other spread of ASPS beyond where it started, chemotherapy is not recommended. Chemotherapy for ASPS after surgery (and radiation for some people) will not decrease the risk of the tumor from coming back, like it can for breast cancer or colon cancer.
If the tumor is advanced and has traveled elsewhere (metastasized) or recurred, chemotherapy is the major option for therapy. Standard drugs for sarcoma include doxorubicin and ifosfamide, but do not work particularly well for ASPS. Few people have shrinking of tumor, and chemotherapy will not be curative if the tumor has spread beyond the tumor's starting place. As you might expect, the larger the tumor is at the time of diagnosis, the higher the risk of the tumor coming back elsewhere in the body.
Thus, since regular chemotherapy does not often work well, new treatments, known as clinical trials or research studies are appropriate for people with ASPS that has gone elsewhere in the body. There is a report of one patient responding to interferon-alfa. It is unclear why this one person has responded to such therapy, but it provides a hint that new drugs may be more successful than old ones in treating this tumor.
Large sarcoma specialty centers such as Memorial Hospital in New York, MD Anderson in Houston, and Dana-Farber in Boston, and the National Cancer Institute in Bethesda, MD are all working on new therapies for soft tissue sarcomas, of which ASPS is one of many that such centers treat. These include drugs such as: angiogenesis inhibitors to block blood vessel growth into tumors, new chemotherapy drugs, biological therapies.
Since the genes involved in this rare disease are now known, new treatments such as vaccines can also be proposed, in an attempt to teach the immune system to attack the exact protein that causes ASPS. However, such an immune response may not exist or not be of sufficient strength to recognize the cancer as it is, since people develop metastases from this tumor despite an intact immune system. Similarly, once the biochemistry of the genes involved in ASPS is known, it may point out an Achille’s heel that doctors may be able to exploit for treatment of this rare condition. It is hoped that this new knowledge will lead to more effective treatments of ASPS.
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.
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