Alveolar Soft Part Sarcoma (ASPS)
Alveolar Soft Part Sarcoma (ASPS)
Alveolar soft part sarcoma is a very rare, slow growing, highly angiogenic (vessel-forming) tumor that can occur in any age group. It is most frequently found in young adults and teenagers and often begins in the lower extremities.
A recent analysis of the MD Anderson Cancer Center’s institutional database, which may overrepresent incidence as a tertiary care center for rare tumors, estimated 90 total new cases of ASPS in the United States in 2004; it predicted that about half of the patients would fall between the ages of 15 and 29 years (Herzog 2005).
Alveolar soft part sarcoma is characterized by a translocation between the ASPL locus on chromosome 17 and the TFE3 locus on the X chromosome (der(17)t(X;17)(p11q25))
Most patients with alveolar soft part sarcoma probably have had the cancer for some time before they come to medical attention. The reason is that the tumor grows so slowly that it at first causes few symptoms and does not form a large mass. By the time the tumor is big enough that the patient feels a lump from the primary lesion and seeks out a physician for help, the tumor has frequently spread, establishing small metastatic colonies throughout the body, frequently found in the lungs and even the brain. It grows even more slowly than clear cell sarcoma, but is definitely a malignant tumor that tends to spread inexorably if not completely removed by surgery. Many patients can live with disease for years and even decades (Pappo, Parham et al. 1996). Although most patients with alveolar soft part sarcoma can never be rid of their cancer completely, many can undergo repeated surgery over the years to keep it somewhat at bay (Weis and Goldblum 2001).
Distinct Clinical Features
Alveolar soft part sarcoma gets the “alveolar” part of its name from the arrangement of cells seen under the microscope by the pathologist (Weis and Goldblum 2001). Alveoli are a small air sacks deep within the lung where oxygen is absorbed into the body, and this cancer has an appearance similar to these air sacks. On gross pathological inspection, meaning on visual inspection without the aid of a microscope, of the tumor after it has been cut out, alveolar soft part sarcoma has numerous blood vessels, reflecting its angiogenic nature. The increased blood flow can even cause an audible noise from blood rushing through the tumor – known in medical terms as a bruit (Pappo, Parham et al. 1996). They must be distinguished from vascular malformations (collections of blood vessels that have grown out of control but they are generally not malignant and will not spread like alveolar soft part sarcoma).
Treatment and Follow-up for Localized Disease
The prognosis of alveolar soft part sarcoma is most influenced by its stage. For patients with tumors that are localized at diagnosis, 87% will remain alive five years later; only 20% of those with metastases at diagnosis will live five years. (Portera, 2001) However, even patients with metastases can have indolent courses, and are likely to have a longer life expectancy than a patient with comparable extent of another soft tissue sarcoma.
Most series reported also suggest that alveolar soft part sarcoma does not respond to chemotherapy, and that surgical therapy should be the mainstay of therapy and is associated with a chance for a long term survival (Pappo, Parham et al. 1996; van Ruth, van Coevorden et al. 2002).
Patients treated for alveolar soft part sarcoma should be followed for many years by an experienced oncologist, both for the risk of recurrence and for the risk of side effects from therapy. Even many years out from diagnosis, and even in the cases where surgery has rendered the patient apparently “disease free”, these indolent cancers can recur or grow for decades, distinctly longer than the risk period of most other soft tissue sarcomas This is particularly true for alveolar soft part sarcoma. Because late recurrences can occur, and recurrences can be treated with further benefit, long term follow-up including evaluation of the original sites of disease and the lungs is advisable. The individual recommendations for the schedule and type of surveillance scans will vary according to the patient and should consider the small but not negligible risks of repeated exposure to radiation. While there are few treatments that are curative for these tumors if they come back, it is possible that future recurrences will be amenable to surgery and it is also possible that research will uncover new therapies in the future to treat a recurrence.
Treatment and Follow-up for Metastatic Disease
Surgical resection of progressive metastases- even scores of lung metastases- should be considered on a case by case basis. Some studies suggest that, particularly in adults, for tumors that cannot be completely resected but do not have evidence of spread beyond the local area where they have occurred, radiation therapy to the tumor bed may be associated with a lower chance for recurrence (Sherman, Vavilala et al. 1994). As children may have a better chance for cure with aggressive surgery and are more likely to suffer from growth disturbance or second malignancies after radiation therapy, the indications for radiation therapy in the child with locally unresectable but non-metastatic disease are not so clear (Pappo, Parham et al. 1996). While there have been no formal studies regarding the use of anti-angiogenic agents in the treatment of patients with alveolar soft part sarcoma, the well characterized ability of this slow growing tumor to both mimic vascular malformations on clinical exam and control blood flow pathologically suggest that blocking the blood supply of this tumor may result in tumor shrinkage.
There are occasional reports of a response to interferon in alveolar soft part sarcoma patients. Interferon is a cytokine that may act to inhibit blood vessel formation in tumors but may also act to recruit the immune system to attack the tumor (Kuriyama, Todo et al. 2001; Roozendaal, de Valk et al. 2003). Another possible approach to therapy for these tumors is to block angiogenesis, or new blood vessel formation.