Tania Ann Banks,     Gatton, Australia

Julius M. Liptak,     Ottawa, Canada

Terminology

Sarcoma is a broad term for malignant tumors of mesenchymal origin. Soft tissue sarcomas (STSs) are a particular subgroup of this larger sarcoma family. Names that pathologists often ascribe to these tumors include malignant peripheral nerve sheath tumor, hemangiopericytoma, malignant schwannoma, neurofibrosarcoma, fibrosarcoma, undifferentiated sarcoma, liposarcoma, leiomyosarcoma, myxosarcoma, myxofibrosarcoma, and rhabdomyosarcoma. They are grouped together because they possess similar biologic behavior and histologic features. The behaviors common to all STSs are the following:

Some sarcomas are not included in the traditional STS classification because of more aggressive biologic behavior (e.g., higher metastatic rates) and different histologic features. These include osteosarcoma, chondrosarcoma, hemangiosarcoma (HSA), synovial cell sarcoma, histiocytic sarcoma, mesothelioma, and lymphangiosarcoma.

Canine hemangiopericytoma (HEP) may be a nonspecific term, encompassing several neoplasms of different histologic origin. Canine perivascular wall tumors (c-PWT) have been described as a mixed group of distinct biologic entities comprising hemangiopericytomas, angioleiomyomas, myopericytomas, and most likely angiomyofibroblastomas and angiofibromas. PWT are distinguished from HEP on the basis of specific histologic growth patterns, cell shape, and immunohistochemistry (Avallone et al, 2007). In humans this is important because myopericytoma is generally benign compared with mostly malignant HEP. However, it is not yet clear whether this distinction between HEP and PWT is clinically important in dogs.

Incidence and Risk Factors

STSs account for 15% and 7% of all skin and subcutaneous tissues in the dog and cat, respectively. The annual incidence of STS is 35 per 100,000 dogs and 17 per 100,000 cats. The etiology is generally unknown; however, in dogs sarcomas have been associated with radiation, trauma, foreign bodies, orthopedic implants, and the parasite Spirocerca lupi. In cats, sarcomas have been associated with feline sarcoma virus, vaccines and other subcutaneous injections, and trauma (e.g., intraocular sarcoma). This discussion is limited to spontaneous, non–vaccine-associated STSs in dogs and cats.

Clinical Features

Most STSs are solitary and occur in middle-aged to older dogs and cats. They are more common in medium- to large-breed dogs but can occur in any age or breed. STSs often are a soft to firm, spherical, nonpainful subcutaneous mass over the trunk or extremities and can be fixed to the underlying tissue. They can originate in visceral and nonvisceral sites. They are generally slow growing, and clinical signs are related to the site of involvement and the degree of invasion.

Diagnosis and Clinical Workup

The mass is palpated to give an idea of site, size, fixation to underlying or adjacent structures, and an initial assessment of the extent of local disease. The regional lymph nodes also should be palpated for enlargement and fixation to underlying tissues.

Fine-needle aspirates (FNAs) are recommended to exclude other differential diagnoses but are often insufficient for obtaining a definitive diagnosis of STS. In one study in which FNAs were performed on STS from 40 dogs, 15% were diagnosed incorrectly, a further 23% were nondiagnostic, and only 62% were diagnosed correctly (Baker-Gabb et al, 2003). In another study of 44 dogs with STS, FNAs incorrectly diagnosed four cases as benign masses (Mallik et al, 2010). The difficulty in cytologic diagnosis of STS may be due to poor exfoliation, high degree of necrosis resulting in false negatives, and nonmalignant disease showing similar results.

A definitive preoperative diagnosis of STSs requires a needle core, punch, or incisional biopsy. The biopsy should be planned so that the biopsy tract can be included in the curative-intent treatment, whether it be surgery and/or radiation therapy (RT), without increasing the surgical dose or size of the radiation field. Excisional biopsies are not recommended because they are rarely curative, and subsequent surgery required to achieve complete histologic margins is often more aggressive than surgery after core or incisional biopsies, resulting in additional morbidity and expense.

Histopathologic grading (low, intermediate, high, or I, II, III) is ascertained from large biopsy specimens and always should be requested from the pathologist. One recent study compared histologic grading from pretreatment biopsies with definitive surgical samples. The two methods correlated 59% of the time, with pretreatment biopsies tending to underestimate grade. Additionally, the method of pretreatment biopsy (14-gauge needle-core, 4- to 8-mm punch, or a wedge biopsy with a mean sample width of 0.5 cm) did not significantly affect grade concordance (Perry et al, 2005). Tumor grade is predictive of behavior and prognosis and is critical to treatment planning. Less than 10% of grade I, 20% of grade II, and 50% of grade III STSs metastasize to the regional lymph node and lung. Higher grade lesions also tend to grow more rapidly and are more locally invasive.

The tests performed for workup and clinical staging are dependent on the type and location of the STS, especially if atypical (e.g., HSA, histiocytic sarcoma, lymphangiosarcoma, and synovial cell sarcoma), but usually involves routine hematologic and serum biochemical blood tests, urinalysis, three-view thoracic radiographs, and potentially regional imaging of the STS. Blood tests are usually within the normal reference range for most dogs with STS; however, anemia and thrombocytopenia are relatively common in dogs with disseminated histiocytic sarcoma and HSA. Paraneoplastic hypoglycemia has been reported with intraabdominal leiomyosarcomas or leiomyomas.

Further imaging of the local tumor may be required for planning the surgical approach or RT if the mass is very large, within a body cavity, fixed to underlying bone, or impinging on or in close proximity to vital structures. Three-dimensional imaging techniques, such as computed tomography (CT) and magnetic resonance imaging (MRI) scans, are particularly useful for staging the local tumor. The surgeon then may better assess the feasibility and more accurately plan an aggressive surgical resection.

The most important diagnostic test for staging of metastatic disease is three-view thoracic radiographs because the lungs are the most common metastatic site for typical STS. Lymph node metastasis is uncommon with typical STS. Fine-needle aspiration or biopsy of regional lymph nodes should be performed in dogs with clinically abnormal lymph nodes or atypical STS with a high rate of metastasis to regional lymph nodes, such as HSA, histiocytic sarcoma, lymphangiosarcoma, synovial cell sarcoma, leiomyosarcoma, and possibly rhabdomyosarcoma. Abdominal imaging (e.g., ultrasonography or advanced imaging) also may be employed to assist in further staging in selected cases.

Treatment Options

Treatment options are considered once clinical staging is complete. For nonmetastatic STS, local tumor control is the most important consideration for optimal management because of locally aggressive behavior.

On gross examination, STSs appear to be well encapsulated. This is not the case because microscopically the pseudocapsule is composed of compressed tumor cells. These peripheral cells are thought to be more aggressive and responsible for the invasion into adjacent normal tissues. Shelling out the tumor leaves behind the potentially more aggressive subpopulation of peripheral, invasive cells. Consequently, recurrent lesions are often behaviorally more aggressive or of a higher grade than the initial lesion and may compromise the optimal treatment and long-term outcome for the animal.

Incomplete surgical excision for canine STS has been reported to result in a probability of local recurrence of 60% within the first 12 months, increasing in subsequent years. In a study comparing local recurrence rates for canine STS treated with a variety of surgical margins, local recurrence occurred in 60% of cases overall, 100% of cases with dirty margins, 80% of cases with close margins, and 22% of cases with clean margins over a 24-month follow-up period (Scarpa et al, 2012). Margin classification was a significant predictor of the recurrence-free interval, and was 87% accurate. In another study, geriatric dogs (median age 10 years) treated in first opinion practice with a variety of surgeries (marginal to radical) to remove STS were followed for a median of 875.5 days postoperatively. Local tumor recurrence occurred in 28% overall, in 13 of 45 dogs with marginal resection, in 3 of 18 dogs with narrow resection, in 1 of 5 dogs with wide resection, and in no dogs treated with radical excision. Additionally, 22% of dogs in this study died as a result of their STS. This study again indicates the importance of wide clean margins in preventing local and distant tumor recurrence. In another study, 28% of dogs with incomplete surgical margins had local recurrence and were more than 10 times more likely to have local recurrence than dogs with completely excised STS. In a study of 55 c-PWT in which more than 90% of tumors were of low or intermediate grade in various locations, resection was performed with either clean (13%), clean but close (27%), or dirty (60%) margins (Stefanello et al, 2011). The overall tumor recurrence rate was 22% (20% local recurrence and 4% distant recurrence), with an average follow-up time of 665 days. These results compare similarly with the previously reported local recurrence rates for the larger STS classification group of low-to-intermediate grade treated with incomplete resection.

Low-grade STS of the extremities in 35 dogs were treated by marginal excision in another study, resulting in an 11% local tumor recurrence rate, and 6% of these dogs died of tumor-related causes. The median age at diagnosis was 11 years and the median time to recurrence was 522 days. This study highlights that marginal resection of an extremity low-grade STS is a valid treatment option in a geriatric dog because the median time to recurrence is prolonged and many dogs (37%) ultimately died of unrelated causes. However, in a younger cohort of dogs, the median time to recurrence is more likely to be reached, warranting a more curative-intent initial treatment approach. Dogs with higher-grade tumors also warrant a more curative-intent treatment approach, as local recurrence rates for STS were shown to be grade dependent in another study, with recurrence rates of 7%, 35%, and 75% for grade I, II, and III tumors, respectively.

In dogs with incompletely resected STS, treatment options include observation (particularly for a grade I STS), staging recut, wide surgical excision, and adjuvant therapies such as RT, conventional chemotherapy, metronomic chemotherapy, and electrochemotherapy.

In one study of 39 dogs with incompletely resected STS, early reexcision of the surgical scar with widest surgical margins possible (0.5 to 3.5 cm) resulted in 15% local recurrence and 10% distant metastatic rates, with a median follow-up time of 816 days. This study again highlights the importance of attaining clean histologic margins to prevent local recurrence.