Rodney C. Straw, BVSc, DACVS
Soft Tissue Sarcomas (STS) are tumors of mesenchymal tissue. Most STS arise from the skin, subcutaneous tissue, or palate, and represent malignant or transformed mesenchymal cells.
The etiology is generally not known with some notable exceptions such as those associated with infestations with the parasite Spirocerca lupi, those induced by the feline sarcoma virus and those thought to be associated with feline vaccinations (Vaccine Associated Sarcomas, VAS). Sarcomas can also be induced by ionizing radiation and high grade STS are rare, serious, late complications of radiation therapy.
Although STS develop from a variety of mesenchymal tissues we usually consider them as a group for two main reasons. One is that pathologists often disagree about the histiogenesis (fibrosarcoma vs. neurofibrosarcoma vs. hemangiopericytoma) and secondly, the biological behaviour of most solitary canine STS shares many common features.
Biological Behavior
They may arise from any anatomic site in the body. They tend to appear as pseudoencapsulated fleshy tumors but have poorly defined histological margins and can infiltrate facial planes. Local recurrence after conservative surgical excision is common. STS tend to metastasize via the hematogenous route although the rate is low (10-25%). They generally have a poor response to systemically administered chemotherapy or radiation therapy for clinically detectable disease.
Diagnosis
Fine needle cytology is an extremely valuable, easily performed, screening test to rule out common differential diagnoses such as lipoma, mast cell tumor, abscess etc. For definitive diagnoses a carefully procured and prepared biopsy for histopathology is essential. Care must be taken to place the biopsy in location so the entire biopsy tract can be removed with definitive surgery or included in a radiation field. The biopsy therefore should be performed atraumatically, aseptically with excellent hemostasis and preferably by the same surgeon who is to perform the definitive surgery. Biopsy wounds should not be drained and seromas avoided by following good surgical technique.
If the mass is fixed to bone, regional radiographs must be performed. Computerized tomography or magnetic resonance imaging may also be useful to help accurate local staging especially for tumors especially those located on the head and pelvis.
Thoracic radiography is important for clinical staging. Serum biochemistry, hematology, and urinalysis are useful for overall health evaluation but may not lend diagnostic information. Some dogs with STS are hyperglycemic (intra-abdominal leiomyosarcoma).
Tumor size, fixation, site, status of the regional lymph node and detectable metastases form the basis for clinical staging.
Treatment
All too commonly inadequate surgical excision is performed. These tumors are often loosely separated from adjacent structures by a pseudocapsule which deceives the surgeon into electing this margin for resection. The result is a marginal resection.
The pseudocapsule is made up of viable tumor cells and is not a fibrous response by host cells. The viable tumor cells project from the pseudocapsule into surrounding tissue and these cells are left behind by marginal resection. The result is a very high probability of local tumor recurrence, usually within 6 months.
After subsequent marginal or intralesional resections, the probability and rate of recurrence increases and often the recurring tumor is of higher histological grade than the original lesion. The risk of metastasis is, therefore also increased. Cure rests with accurate preoperative diagnosis and staging and the performance of complete tumor removal by properly performed first time surgery. Excision with wide (2 to 3 cm margins) or radical margins is the treatment of choice.
Biopsy tracts must be excised in continuity with the mass. Any areas of fixation including bone and fascia must be excised en bloc with the mass. A recurrence free survival rate of approximately 90% can be achieved at 12 months with complete surgical resection. The margins of the resected specimen should be carefully evaluated by the pathologist because dogs with STS removed with incomplete margins are over ten times more likely to suffer recurrence than dogs with completely excised tumors. Histological grade is also of prognostic significance.
Radiation therapy alone is generally not considered optimal treatment for dogs with STS but marginal resection in conjunction with megavoltage radiation therapy results in a local recurrence rate of approximately 20-30%. Where wide surgical margins cannot be achieved, adjuvant radiation therapy may be considered.
A phase I/II clinical study investigating a biodegradable polymer delivery system containing cisplatin implanted into wounds after marginal STS removal in dogs resulted in local control rates similar to those for dogs treated with marginal surgery and megavoltage radiation therapy. Unfortunately this drug delivery system is not available commercially.
Systemically administered chemotherapy rarely controls measurable clinical disease but has been advocated in patients with high grade lesions removed at surgery. Doxorubicin based protocols are most commonly used.
Cats are similar to dogs when it comes to STS except for the fact that nerve sheath tumors and synovial cell sarcomas are extremely rare in cats compared to dogs. There are also several unique fibrosarcoma settings in cats. Cats have been reported to suffer from a virally induced multicentric fibrosarcoma; they can develop a vaccine associated fibrosarcoma; and there have been reports of fibrosarcoma developing in the orbit of cats with phthisis bulbi, ocular trauma or ocular foreign bodies.
The cause of nonvirally induced, non-vaccine associated and non-ocular fibrosarcomas is generally not known. These tumors are seen in cats 8 to 12 years of age with no sex or breed predilection. Over 50% of these fibrosarcomas occur on the limbs making limb salvage curative surgery very difficult. These solitary STS's are slow growing, low grade and can be permanently controlled with properly performed surgery. Wide or radical surgical margins are indicated for the management of these tumors in cats. There are no large studies reporting the efficacy of surgery with adjuvant radiation therapy for these types of STS in cats.
Sarcomas following ocular trauma occur most often in cats 7 to 15 years of age and the latency following trauma averages 5 years. Damage to lens and chronic uveitis may be risk factors. These tumors are often advanced by the time they are diagnosed with extension into the bone of the orbit and the optic nerve. Therefore I recommend removal of the phthisical feline eye or cat eyes that are blind and have been severely traumatized or chronically inflamed.
Feline sarcoma viruses (FeSV) are true hybrids and result from the rare recombination of feline leukemia virus (FeLV) DNA provirus with cat proto-oncogenes. Cats that have FeSV are always FeLV positive. It is thought that only 2% of fibrosarcoma of cats are virally induced. The FeSV-induced tumors are multicentric and mostly found in young cats. These tumors are generally very fast growing with metastatic rates reported of 30% or so. Prognosis is very poor in these cats. Although some authors indicate chemotherapy with radiation therapy may be tried, recurrences and progressive disease usually ensues.
Vaccine-associated sarcomas consist of cells that are morphologically and immunohistochemically compatible with fibroblasts and myofibroblasts. The precise pathogenesis of vaccine-associated sarcomas is unknown but may involve stimulation of these cells by highly immunogenic and persistent adjuvants or other vaccine components resulting in inflammation that alone or in association with unidentified carcinogens or oncogenes leads to neoplastic transformation and tumor development. Transition zones from inflammatory granuloma to sarcoma have been identified and strongly suggest that the inflammatory response to vaccination is antecedent to sarcoma development in cats.
Vaccine-associated feline sarcomas are highly invasive and, often, rapidly growing neoplasms that require aggressive treatment, which may include a combination of surgery, radiation therapy, and chemotherapy. Metastases may develop, and the metastatic rate increases with survival time. Because vaccine-associated sarcomas often mimic benign postvaccinal injection site granulomas, differentiating these lesions is critical.
Readers are directed to the Feline Vaccine Associated Sarcoma Task Force (VAFSTF) web page for more information on this important cancer of cats: http://www.avma.org/vafstf/default.asp.