Last updated:
5/21/2025
Years published: 2002, 2017, 2021, 2025
NORD gratefully acknowledges Omar Jaber, MD, Department of Pathology, University of Iowa Hospitals and Clinics and Andrew S. Brohl, MD, Sarcoma Department, Moffitt Cancer Center, for assistance in the preparation of this report.
Summary
Alveolar soft part sarcoma (ASPS) is a rare, slow growing soft tissue tumor with an unclear cause. It is among the least common sarcomas, representing 0.2-1 percent of soft tissue sarcomas, which is an uncommon type of cancer. ASPS is characterized by a mass that is usually painless and usually arises in the leg or buttock, with a particular affinity to travel to the lungs as multiple nodules, often while the sarcoma is still small.
This cancer is very rare in part because it requires a very specific genetic event to occur that involves a breaking and joining event between two chromosomes, called an “unbalanced translocation”. This finding is observed in essentially all tumors diagnosed as ASPS examined so far. This genetic finding cannot be passed on to children, however, because it occurs only in the tumor cells, not in the non-cancerous body cells. In addition, there are no families in which multiple family members have the disorder. ASPS tends to occur more often in younger people, specifically adolescents and young adults.
Treatment is with surgery for the primary place where the sarcoma arises. Radiation therapy is sometimes considered as an adjunct to surgery depending on the tumor characteristics (size, location, microscopic appearance). For disease that spreads to the lungs, sometimes surgery is possible to remove nodules, but often systemic therapy is the only option for treatment. This tumor tends to be resistant to traditional chemotherapy; however newer approaches utilizing so called “targeted” chemotherapy drugs as well as “immunotherapy” have emerged as more promising and now standard treatment strategies for patients that have advanced disease, such as those that are inoperable or those that have metastasized.
Introduction
ASPS 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, nerves, tendons and blood and lymph vessels.
The typical clinical findings are 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. These masses are usually soft and slow growing. In children, these masses most often occur in the head and neck, most commonly the tongue and the eye socket (orbit). In adults, the thighs and buttocks are most often affected.
Although ASPS is a slow growing tumor, it can spread (metastasize) to other areas of the body. Sometimes there is a delay of years after surgery to remove the tumor before sites of spread (metastases) are detectable. The lungs, brain and bone are most frequently affected when the cancer spreads. In the advanced stages, when nodules are found in the lungs, the tumor nodules can cause cough, sharp chest pain, or fluid collections around the lungs (pleural effusions). Some people develop headaches associated with metastases to the brain, or a fracture from metastases to the bones. The involvement of the lungs or brain in ASPS are potentially life-threatening complications but people can live for years despite lung nodules, since the nodules grow very slowly in most people.
ASPS is caused by two chromosomes that break and rejoin is a certain way (unbalanced translocation) and bring together two genes, normally separated on chromosome X (the sex chromosome) and chromosome 17.
Chromosomes are in the nucleus of human cells and carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes numbered from 1 through 22 are called autosomes and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome, and females have two X chromosomes. Each chromosome has a short arm designated “p” and a long arm designated “q”. Chromosomes are further sub-divided into many bands that are numbered. The numbered bands specify the location of the thousands of genes that are present on each chromosome.
The two genes involved in ASPS are the ASPSCR1 gene on chromosome 17 and the TFE3 gene on chromosome X. In an unbalanced translocation, one chromosome ends up with extra material while the other chromosome is missing material. In ASPS, the TFE3 gene breaks off from the X chromosome and attaches onto the ASPSCR1 gene on chromosome 17. This unbalanced translocation creates a new so-called “fusion” gene known as ASPSCR1-TFE3. This fusion gene creates an abnormal protein. Researchers think this abnormal protein plays a significant role in the development of ASPS. However, more research is necessary to determine how this abnormal protein functions.
There is no exposure or infection that is known to predispose someone to develop ASPS.
ASPS tends to affect younger people, especially those between 15 and 35 years of age. It is rare in children under 5 and adults over 50. More females than males are affected, especially under age 25. There does not appear to be a higher risk in any ethnic groups. ASPS accounts for about 0.2-1% of all soft tissue sarcomas. Soft tissue sarcomas account for approximately 1% of all cancers.
Biopsy is the fastest way to diagnose a soft-tissue sarcoma. A biopsy involves taking a small sample of affected tissue and examining it under a microscope. There are more than 50 different types of sarcomas, of which ASPS is only one rare subtype. Often, 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.
Doctors can use a biopsy sample to check the cells to see if the characteristic chromosome change (unbalanced translocation involving chromosomes 17 and X, resulting in the formation of the fusion gene, ASPSCR1-TFE3) is present. Detection of this fusion gene confirms a diagnosis of ASPS.
Because the tumor grows slowly and usually does not cause any pronounced symptoms, affected individuals can have ASPS for years before a diagnosis is made.
Typically, people will also have specialized imaging techniques such as computed tomography (CT) scans or magnetic resonance imaging (MRI) scans of the primary tumor site to determine if the mass is removable. A CT scan of the chest is typically performed to determine if there is disease in the lungs. Additional scans may also be considered to assess for the spread of cancer to other areas of the body. ASPS generally does not spread to lymph nodes but rather travels via the blood to get to the lungs or other parts of the body.
The therapeutic management of individuals with ASPS may require the coordinated efforts of a team of medical professionals, such as physicians who specialize in diagnosis (pathologists) and treatment of cancer (medical oncologists), specialists in the use of radiation to treat cancer (radiation oncologists), surgeons, oncology nurses and other specialists (depending upon the area(s) of tumor involvement). Given the rarity of this disease, it is recommended that patients be treated at a high-volume referral center for sarcomas.
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 distant sites, individual’s age and general health and/or other elements. Decisions concerning the use of 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 their case, a thorough discussion of the potential benefits and risks, patient preference and other appropriate factors.
Surgery is a standard treatment option for ASPS that has not metastasized to other areas of the body and the only known potentially curative treatment. The prognosis is best if the tumor is small and localized (i.e. has not moved elsewhere in the body, such as the lungs) and can be completely removed by surgery. 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 U.S. 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 another site) does not work well anymore.
Often and particularly for larger tumors, 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 directing a radiation beam at the tumor (external beam radiation or some variant of that) or can be achieved by placing temporary tubes (catheters) in the area where the tumor was removed. 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 typically considered when the tumor is 5cm (approximately 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 generally not recommended. There is no evidence that chemotherapy for ASPS after surgery (and radiation for some people) will decrease the risk of the tumor coming back.
If the tumor is advanced and has traveled elsewhere (metastasized) or recurred, surgery is still sometimes considered depending on the extent of disease, particularly the number of sites affected. For patients in whom surgery is not an appropriate option, systemic therapy (i.e. something delivered to the whole body via pill or IV infusion) is the main consideration for therapy. However, traditional chemotherapies for metastatic disease have generally been ineffective. Standard drugs for sarcoma include doxorubicin and ifosfamide but do not work particularly well for ASPS. Few people have a shrinking of tumor, and chemotherapy will not be curative if the tumor has spread beyond the tumor’s starting place.
Fortunately, there have been several advances in the systemic treatment options for ASPS beyond traditional chemotherapies. Most commonly, advanced ASPS that require systemic treatment are treated with “targeted” therapies or “immunotherapies.” Targeted therapies, also sometimes called tyrosine kinase inhibitors, are designed to target a specific protein or set of proteins that make a cancer grow and spread. In theory, targeted therapies tend to have less severe side effects than traditional chemotherapy because the drugs ‘target’ specific genes or proteins that are more specific to cancer cells than non-cancerous cells, whereas traditional chemotherapy targets any rapidly dividing and growing cells in the body, even healthy ones. Several targeted therapies have been evaluated in ASPS and are now in routine use including sunitinib, pazopanib, cabozantinib and axitinib.
In addition to “targeted therapies” to treat ASPS, there has been recent enthusiasm for treatment with immune-based therapeutics particularly a class of medication called “checkpoint inhibitors” or PD1/PDL1 inhibitors. These medications are designed to increase the body’s immune response against the cancer. For ASPS, clinical trials have now demonstrated ASPS to be among the most likely sarcomas to respond well to treatment with checkpoint inhibitors such as atezolizumab or pembrolizumab.
In people with brain metastases, surgery and radiation are the major ways to control the tumor and the side effects they cause in the brain.
Despite the improved treatment options for advanced ASPS with the availability of immunotherapy and targeted therapy options, more study is needed to help optimize these current options as well as continue to develop additional treatments.
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:
Toll-free: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
Some current clinical trials also are posted on the following page on the NORD website:
https://rarediseases.org/living-with-a-rare-disease/find-clinical-trials/
For information about clinical trials sponsored by private sources, contact: www.centerwatch.com
For more information about clinical trials conducted in Europe, contact: https://www.clinicaltrialsregister.eu/
JOURNAL ARTICLES
Wilky BA, Trucco MM, Subhawong TK, et al. Axitinib plus pembrolizumab in patients with advanced sarcomas including alveolar soft-part sarcoma: a single-centre, single-arm, phase 2 trial. Lancet Oncol. 2019 Jun;20(6):837-848. https://pubmed.ncbi.nlm.nih.gov/31078463/
Gronchi A, Maki RG, Jones RL. Treatment of soft tissue sarcoma: a focus on earlier stages. Future Oncol. 2017;13:13-21. https://www.ncbi.nlm.nih.gov/pubmed/27918202
Von Mehren M, Randall RL, Benjamin RS, et al. Soft tissue sarcoma, version 2.2016 NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2016;14:758-786. https://www.ncbi.nlm.nih.gov/pubmed/27283169
Jaber OI, Kirby PA. Alveolar soft part sarcoma. Arch Pathol Lab Med. 2015;139:1459-1462. https://www.ncbi.nlm.nih.gov/pubmed/26516944
Reis H, Hager T, Wohlschlaeger J, et al. Mammalian target of rapamycin pathway activity in alveolar soft part sarcoma. Hum Pathol. 2013;44:2266-2274. https://www.ncbi.nlm.nih.gov/pubmed/23871289
Stockwin LH, Vistica DT, Kenney S, et al. Gene expression profiling of alveolar soft-part sarcoma (ASPS). BMC Cancer. 2009;9:22. https://www.ncbi.nlm.nih.gov/pubmed/19146682
Folpe AL, Deyrup AT. Alveolar soft-part sarcoma: a review and update. J Clin Pathol. 2006;59:1127-1132. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1860509/
Ladanyi M, Lui MY, Antonescu CR, et al. The der(17)t(X.17)(p11;q25) of human alveolar soft part sarcoma fuses the TFE3 transcription factor gene to ASPL, a novel gene at 17q25. Oncogene. 2001;20:48-57. https://www.ncbi.nlm.nih.gov/pubmed/11244503
Portera CA Jr, Ho V, Patel SR, et al. Alveolar soft part sarcoma: clinical course and patterns of metastasis in 70 patients treated at a single institution. Cancer. 2001; 91: 585-591. https://www.ncbi.nlm.nih.gov/pubmed/11169942
Casanova M, Ferrari A, Bisogno G, et al. Alveolar soft part sarcoma in children and adolescents: A report from the Soft-Tissue Sarcoma Italian Cooperative Group. Ann Oncol. 2000;11:1445-1449. https://www.ncbi.nlm.nih.gov/pubmed/11142485
Wilky BA, Trucco MM, Kolonias D, et al. A phase II trial of axitinib plus pembrolizumab for patients with advanced alveolar soft part sarcoma (ASPS) and other soft tissue sarcomas (STS). Lancet Oncol. 2019; 20(6):837-848. https://pubmed.ncbi.nlm.nih.gov/31078463/
Lieberman PH, Brennan MF, Kimmel M, et al. Alveolar soft-part sarcoma. A clinico-pathologic study of half a century. Cancer. 1989; 63: 1-13. https://www.ncbi.nlm.nih.gov/pubmed/2642727
INTERNET
National Cancer Institute. Targeted Cancer Therapies. May 31, 2022. Available at: https://www.cancer.gov/about-cancer/treatment/types/targeted-therapies/targeted-therapies-fact-sheet Accessed May 14, 2025.
McKusick VA., ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University; Entry No:606243; Last Update:04/12/2012. Available at: https://omim.org/entry/606243 Accessed May 14, 2025.
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