Alveolar Soft Part Sarcoma (ASPS) is a rare cancer that originates in soft tissues like muscle and fat. It accounts for less than 1% of all soft tissue sarcomas and is known for its slow growth, which can delay diagnosis. While it can develop at any age, ASPS most frequently appears in adolescents and young adults. The name is derived from the tumor’s microscopic appearance, where cells form a pattern resembling the small air sacs, or alveoli, of the lungs.
Symptoms and Common Locations
The most common initial sign of Alveolar Soft Part Sarcoma is a mass or lump that is often painless and grows slowly. This slow growth can delay diagnosis, as the tumor may be present for a long time before it is discovered. Symptoms like soreness or reduced motion often appear only after the tumor is large enough to compress nearby nerves or muscles.
These tumors most often arise in the deep soft tissues of the extremities. The legs, particularly the thigh, are the most frequent location, followed by the buttocks and arms. ASPS can also develop in the trunk of the body. In children, it is more commonly found in the head and neck region, including the tongue and the orbit, which is the skull cavity containing the eye. A tumor in the orbit may cause localized symptoms such as vision changes or a bulging eye.
The Diagnostic Process
Diagnosing ASPS involves imaging tests and a laboratory analysis of the tumor tissue. A physician will use imaging, such as Magnetic Resonance Imaging (MRI), to visualize the mass. An MRI shows the tumor’s exact size, location, and relationship to nearby structures. Computed Tomography (CT) scans may also be used to get a clear picture of the tumor and to check if the cancer has spread.
While imaging provides valuable information, a biopsy is required for a definitive diagnosis. During a biopsy, a surgeon removes a small tissue sample from the mass, which is then examined by a pathologist. The pathologist looks for the characteristic alveolar pattern of the cells and for unique crystalline structures within them. These are known as PAS-positive, diastase-resistant crystals, and their identification is a classic hallmark of ASPS.
The final step is molecular testing of the tumor cells to detect a specific genetic abnormality unique to ASPS. The presence of this distinct genetic marker provides definitive confirmation of the diagnosis and is important for determining the most appropriate course of treatment.
Underlying Genetic Factors
The development of Alveolar Soft Part Sarcoma is driven by a specific genetic alteration. This change is a “somatic” mutation, meaning it is not inherited but occurs in the body’s cells after birth and is only found within the tumor. No known environmental factors or infections have been linked to causing this genetic event.
The specific event is a chromosomal rearrangement called a translocation between the X chromosome and chromosome 17. During this process, a piece of chromosome X breaks off and fuses with a piece of chromosome 17. This creates the ASPSCR1-TFE3 fusion gene.
This fusion gene acts as the engine for the cancer. It contains instructions for producing a fusion protein not found in healthy cells. This abnormal protein drives the uncontrolled growth and survival of the cancer cells, leading to the formation and progression of the tumor.
Primary Treatment Approaches
The primary treatment for a localized ASPS is surgery to completely remove the tumor. The standard procedure is a wide local excision, where the surgeon removes the tumor along with a surrounding border, or “margin,” of healthy tissue. Achieving clear margins is important to reduce the risk of the cancer returning at the original site.
Radiation therapy may be used with surgery to improve outcomes. It can be administered either before surgery (neoadjuvant) to shrink the tumor or after surgery (adjuvant) to destroy any remaining microscopic cancer cells. This lowers the risk of local recurrence.
The decision to use radiation depends on the tumor’s size, location, and proximity to important structures. For instance, if a tumor is very large or in an area where achieving wide surgical margins is difficult, such as the head and neck, radiation may be recommended. The strategy is tailored to each individual to maximize the chances of controlling the tumor.
Managing Metastatic and Recurrent Disease
ASPS has a tendency to metastasize, or spread, to distant parts of the body. This can occur years after the initial tumor is removed, so long-term monitoring with imaging tests is necessary. The most common sites for metastasis are the lungs, brain, and bones.
Traditional chemotherapy has limited effectiveness against ASPS. Because of this resistance, treatment for metastatic disease focuses on other systemic therapies. One of the main strategies is targeted therapy with drugs known as anti-angiogenic inhibitors, which block the formation of new blood vessels that tumors need to grow. Drugs like sunitinib, pazopanib, and cediranib are standard options for patients with advanced ASPS.
Another approach is immunotherapy, which uses the body’s immune system to fight cancer. Immune checkpoint inhibitors can help immune cells recognize and attack tumor cells more effectively. For disease that has spread to specific locations, more specialized treatments may be used. For example, stereotactic radiosurgery, a highly focused form of radiation, can be an effective option for treating metastases in the brain.