Canine soft-tissue sarcomas

Soft-tissue sarcomas (STS) are common for a practitioner to see as they compromise up to 15 percent of all skin tumors in dogs. The terms spindle-cell tumors and mesenchymal tumors have also been used to describe these tumors. STS are considered to be a family of tumors given that they are all derived from connective tissues and have a similar biologic behavior regardless of the histologic type (see Table 1). Histiocytic sarcomas, oral sarcomas, hemangiosarcoma and synovial cell sarcoma are generally not included given that these tumors have a different biologic behavior.

Table 1

Biologic behavior

These tumors are considered to be locally invasive tumors that will grow along tissue planes. Invasion into bone is uncommon. The potential for metastasis depends on the grade of the tumor with low- to intermediate-grade tumors having a metastatic rate of less than 15 percent and high-grade tumors having a metastatic rate of up to 45 percent (Kuntz 1997, Selting 2005). The most common site of metastasis is the lung followed by lymph node.

Presentation

Most dogs are older to middle-aged with no sex or breed predilection. These tumors present as solitary masses in the subcutaneous tissues and can occur anywhere on the body (Figure 1). In some cases, these tumors have been present for a prolonged period of time without changing but some can grow rapidly, particularly if they are high-grade tumors. Typically these tumors are solid but some can have a fluid component (i.e. myxosarcomas).

Figure 1 Typical appearance of soft-tissue sarcoma in a dog.

Initial therapeutic plan

Initial evaluation should include an aspirate of the mass, thoracic radiographs (three views) and an aspirate of the draining lymph node if indicated. Radiographs should not be taken under anesthesia if possible as atelectasis of the lung may prevent identification of smaller lesions. Sarcomas may not exfoliate well, so it is possible for an aspirate to be non-diagnostic. On cytology, the cells appear as elongated, spindle-shaped cells with indistinct margins and occur singly (Figure 2). If a sarcoma is suspected but not confirmed on cytology, an excisional or incisional biopsy is indicated. An incisional biopsy is recommended if the tumor cannot be easily excised with a wide margin.

Figure 2 Cytologic appearance of a soft-tissue sarcoma. Cells are spindle shaped with indistinct margins.

Surgery

Given that the majority of these tumors are locally invasive with low rates of metastasis, surgical excision is the first line of treatment. The likelihood of complete excision depends on several factors including the location, size of the tumor, previous surgical attempts and biologic behavior of the tumor. Pre-operatively, the surgeon should determine how best to obtain a 2-3 cm margin in all planes around the tumor while maintaining the ability to close the surgical wound. If there is a question regarding the ability to excise a tumor given the location or size, an MRI or CT scan for surgical planning is advised (Figure 3). This allows the surgeon to determine if the tumor is even resectable and if so, the best surgical approach to maximize the success of the surgery.

Figure 3 CT of dog with a nerve-sheath tumor in the right axilla. Lateral margin of the tumor is the skin surface. Medial margin of the tumor extends into the thorax. Given the CT images, surgery was not considered an option for this dog.

It also allows the surgeon to advise the client of the extent of the surgery, potential complications and the need for possible follow-up therapy (i.e. radiation therapy) prior to making a commitment to surgery.

Surgical oncology can be different from other types of surgery, and there are several important principles. It is important to keep in mind that the best chance for a surgical cure is on the first attempt. The tumor should be removed en-bloc, and if an incisional biopsy has been done, the entire scar from the biopsy should be excised. Many of these tumors have a pseudocapsule so it can appear that these tumors "shell out" (Figure 4). However, the pseudocapsule is not considered a barrier to invasion into the surrounding tissue and a 2 to 3 cm margin should be taken around the pseudocapsule. One intact fascial plane below the tumor should be included in the resection if it is not possible to obtain a 2 to 3 cm deep margin.

Figure 4 Histology section of a tumor demonstrating a thin pseudocapsule around the tumor. The pseudocapsule is mostly made of compressed tumor cells and does not provide a barrier to tumor invasion.

In some cases, the success of radiation therapy following surgery can be influenced by surgical technique. If the scar is oriented in an unusual direction, it may not be possible to treat the scar appropriately with radiation therapy. If a drain is required, care should be taken to place the drain in, including ensuring the entire drain tract can be included in the radiation field. If there is any question about the best surgical approach for a patient that is likely to need radiation therapy, it is recommended that the surgeon contact a radiation oncologist for recommendations prior to surgery.

Table 2 Soft-tissue sarcoma grading system (Kuntz 1997)

Histopathology grade

For soft-tissue sarcomas, it is important that a microscopic description be requested along with a diagnosis as this information is used to assign the tumor a grade. Tumors can be divided into low-, intermediate- and high-grade tumors based on histologic features such as the degree of differentiation, percentage of necrosis and mitotic index (Table 2). Poorly differentiated tumors, tumors with significant regions of necrosis and/or a high mitotic index are likely to be classified as high-grade tumors. The most reliable feature is the mitotic index that is defined as the number of mitosis seen per 10/hpfs. Early reports indicated that a mitotic index of ≥ 9 was associated with a more aggressive behavior (Bostock 1980) while recent publications found that dogs with tumors that have a mitotic index ≥20 are more likely to die of tumor-related causes (Kuntz 1997).

Figure 5: Davidson Marking System.

Margins

Appropriate submission of the sample is important to margin analysis. The entire surgical specimen should be submitted intact, and, if possible, the surgical margins marked with either India ink or a multi-colored margin marking system, such as the Davidson Marking System (Figures 5, 6 and 7).

Figure 6 Two soft-tissue sarcomas that have been marked using the Davidson Marking System. Note that each margin is marked using a different color. A color diagram is provided along with the specimen to allow for proper orientation.

This will allow the pathologist to give the surgeon a more accurate analysis of the margins. Factors such as tumor location, size, grade and extent of the surgery need to be taken into account when deciding whether or not a given margin is adequate.

Figure 7 Histopathologic appearance of inked margin.

Radiation therapy

The inability to completely excise a tumor often will result in local recurrence. A wider re-excision of the scar may be one option of preventing recurrence but may not be feasible due to tumor location. Adjuvant radiation therapy is another means of preventing local recurrence of these tumors when they have been reduced to a microscopic level of disease. With the combination of surgery and radiation therapy, control rates of anywhere from 50-90 percent at three to five years have been reported (McKnight 2000, Forrest 2000). In most cases, post-operative radiation therapy is preferred and would commence once surgical healing was complete (i.e. two to four weeks post-operatively). The details of the treatment protocol may vary among institutions, but typically anywhere from 15 to 20 treatments of radiation therapy are given over a three- to six-week period of time.

Radiation therapy can be considered when a tumor cannot be excised, but local control rates are significantly lower as gross disease considered to be radio-resistant. With gross disease, median control times are approximately one year (McChesney 1989).

Chemotherapy

Chemotherapy would be recommended for those dogs that have high-grade tumors, non-resectable tumors or metastatic disease. The most commonly used protocols are those that include doxorubicin but other drugs, such as ifosfamide and dacarbazine, also have been used. Similar to radiation therapy, chemotherapy is more effective when used to treat microscopic disease. In general, chemotherapy is well tolerated by veterinary patients and the risk of serious side effects is low. Potential side effects would include gastrointestinal toxicity, myelosuppression, hemorrhagic cystitis (secondary to cyclophosphamide) and cardiomyopathy (with cumulative doses of doxorubicin). The efficacy of adjuvant chemotherapy in the treatment of high-grade tumors has not been fully evaluated, but there are reports that suggest the use of chemotherapy does increase survival times. When used in patients with metastatic disease or non-resectable tumors, chemotherapy is considered to be palliative.

Prognosis

The most significant factors that determine the prognosis of dogs with STS are the ability to obtain adequate local control and tumor grade. For low- or intermediate-grade tumors, the most important prognostic factor is the ability to achieve local control with either surgery alone or surgery and adjuvant radiation therapy. The prognosis is considered to be good when local control can be achieved. The prognosis for high-grade tumors is more guarded due to the potential for metastatic disease although many of these patients benefit from an aggressive treatment plan that includes surgery +/- radiation therapy and adjuvant chemotherapy.

Dr. Cronin earned her DVM degree from Cornell University in 1990. She completed an internship at the Animal Medical Center in New York and a medical oncology residency at North Carolina State University. She is a diplomate of the American College of Veterinary Internal Medicine in the specialty of oncology. After completing her residency, she was lecturer at the University of Pennsylvania Veterinary Teaching Hospital and a medical oncologist at Angell Memorial Animal Hospital in Boston. In 2001, she co-founded the New England Veterinary Oncology Group in Waltham, Mass.