Soft Tissue Sarcomas in Dogs

Quick Facts at a Glance

•  15% of all skin/subcutaneous (under the skin) tumors

•  Soft tissue sarcoma (STS) of the trunk and extremities (legs) are very invasive into surrounding tissue with a generally low metastatic (spread) rate

•  Malignant peripheral nerve sheath tumor is most common STS

•  Complete, wide surgical resection, confirmed histologically (biopsy), is highly predictive of local tumor cure

•  These tumors are not encapsulated but have a “pseudocapsule” comprised of compressed tumor cells

•  70% of grade 3 tumors will metastasize (spread)

Terminology

Veterinary oncologic pathologists have amended the term used to describe tumors that were previously referred to as schwannoma, neurofibrosarcoma or hemangiopericytoma. In veterinary medicine, these tumors are all believed to originate from the same cell type and are therefore now categorized as malignant peripheral nerve sheath tumors (MPNST).

Soft tissue sarcomas make up a large category of tumors that arise from connective tissue. This category includes tumors of fibrous tissue, fat, smooth muscle, nerves and lymphatic vessels. Histologic diagnoses include fibrosacoma, MPNST, malignant fibrous histiocytoma, myxosarcoma, liposarcoma, lymphangiosarcoma and undifferentiated sarcoma. The most common STS in dogs is the malignant peripheral nerve sheath tumor. Tumors such as hemangiosarcoma, osteosarcoma, chondrosarcoma, rhabdomyosarcoma and synovial cell sarcoma are often classified as soft tissue sarcomas. However, their behavior is not consistent with that of the more common STS and they are therefore considered separately in veterinary medicine.

Tumor location plays an important role in the behavior of STS. STS of the oral cavity or brachial plexus are more aggressive than STS of the trunk and extremities.

How do these tumors behave?

STS of the trunk and extremities behave similarly in that they are very invasive into surrounding tissue, often extending far beyond gross margins. Gross evaluation of these tumors at the time of surgery can be deceptive as “pseudocapsule” comprised of compressed tumor cells allows the surgeon to “peel” the main body of the tumor away from the deeper microscopic tumor base.

In general, the metastatic rate of these tumors is low. Metastases occur in 5% or less in patients with grade 1 and 2 tumors.

Is an incisional biopsy helpful?

Grading of STS is now widely acceptable as a standardized practice amongst veterinary oncologic pathologists. This grading scheme is adopted from grading of human soft tissue sarcomas and uses mitotic index, percent tumor necrosis and degree of histologic differentiation. If a tumor scores high in all 3 of these categories it is characterized as a grade 3 STS, which correlates well with an aggressive biologic behavior. Tumor grade is highly predictive of biologic behavior, both for degree of local tumor invasion and metastasis. Metastasis occurs in approximately 70% of dogs with grade 3 STS. The extent of the surgery required and need for follow-up therapy can be predicted once the results of the incisional biopsy are available.

Treatment of choice

Wide surgical excision without disrupting the pseudocapsule is always the treatment of choice when feasible. The pathologist determines the completeness of resection by histologically examining all surgical margins. Whenever possible, the entire tumor should be submitted so that all margins can be reviewed. The margins should be marked so that the pathologist can easily orient the tissue and precisely identify which margins are not sufficient to prevent recurrence. (i.e. which areas were not completely removed). This will increase the success of a second surgery if indicated as we would know where we need to take more tissue. Recurrence of the tumor is 10 times more likely in patients with histologically incomplete surgical margins than in patients undergoing wide surgical resection with adequate margins.

Radiation therapy

Time to recurrence is variable, dependent on tumor grade and degree of residual tumor burden (amount of tumor left behind). Radiation therapy is very effective at preventing tumor recurrence when performed following incomplete resection of low to intermediate grade STS, particularly those of the extremities. Local control of 5 years or longer can be achieved in many cases. Radiation therapy alone (without surgery) is less effective for treating gross disease.

When is chemotherapy indicated?

Intravenous chemotherapy is not effective for local tumor control; however, chemotherapy does appear to be of benefit in 2 situations: used prior to surgery to help shrink high grade 2 or grade 3 tumors, or following complete resection of a high-grade 2 or grade 3 STS to prevent metastasis. Doxorubicin (adriamycin) alone or doxorubicin-based multi-drug protocols appear to be the most effective in both veterinary and human medicine.

What's on the horizon?

The importance of angiogenesis (blood vessel growth) for the development of the primary tumor and distant metastatic disease is well understood for all cancers including STS. Evolution of treatments to inhibit angiogenesis is ongoing.

We currently have a study for dogs with soft tissue sarcoma, either recurring or without viable surgical options. Patients are treated with a vaccine against vascular endothelial growth factor (VEGF). A total of 8 vaccines are administered intradermally (into the skin) over a period of 18 weeks. Patients with stable disease or tumor regression at the end of 18 weeks remain in the study for one year. All diagnostic and treatment costs are covered by the study once the patient is entered. Entry criteria are: histologically confirmed diagnosis of soft tissue sarcoma, tumor is accessible for measurement and serial biopsies, no prior treatment with radiation therapy or angiogenesis inhibitors, no concurrent illness, patient may be on non-steroidal anti-inflammatory drugs if started more than 3 weeks prior to entry, no steroids or concurrent chemotherapy.