Soft-Tissue Sarcomas in Dogs: A Review

Introduction

The soft-tissue sarcomas are a group of tumors with differing morphological features that share similar biological behaviors. They occur in both humans and animals and include a variety of tumor types. These tumors arise from many non-bony connective tissues and may originate in visceral and nonvisceral sites. Soft-tissue sarcomas comprise approximately 15% of all skin and subcutaneous tumors in the dog and approximately 7% of all feline skin and subcutaneous tumors.¹ Incidence estimates for soft-tissue sarcomas arising from visceral sites in both dogs and cats are less accurate.

Nomenclature given to tumors that are grouped under the soft-tissue sarcoma heading includes fibrosarcoma, hemangiopericytoma, liposarcoma, rhabdomyosarcoma, leiomyosarcoma, malignant fibrous histiocytoma, malignant nerve sheath tumors (e.g., neurofibrosarcoma, schwannoma), myxosarcoma, myxofibrosarcoma, mesenchymoma, and spindle cell tumor.^1–3 These tumors differ in histological appearance to various extents and are named after the connective (i.e., mesenchymal) tissue from which they are presumed to arise [see Table].

Despite differing histological features, soft-tissue sarcomas are grouped together because of some important features of biological behavior that are common to all of them. These features have been described by Withrow and MacEwan and include: 1) an ability to arise from any anatomical site in the body; 2) the propensity to appear as pseudoencapsulated tumours with poorly defined histological margins; 3) a tendency to infiltrate through fascial planes; 4) common local recurrence after conservative excision; 5) metastasis through hematogenous routes; and 6) a poor response to chemotherapy and radiation therapy in cases where gross tumor is present.¹ In general, these tumors share a low to moderate metastasis rate and are locally invasive.^1–3 Other tumors of connective tissue origin such as osteosarcoma, chondrosarcoma, hemangiosarcoma, lymphangiosarcoma, and synovial cell sarcoma are not usually considered to be soft-tissue sarcomas because of their higher metastasis rate.^1,2 Thus, not all tumors with the “-sarcoma” suffix are included in the soft-tissue sarcoma group.

Clinical Features

Soft-tissue sarcomas tend to occur in middle-aged to older dogs with a trend toward medium- to large-breed dogs. Soft-tissue sarcomas often present as a firm, fixed mass involving the trunk, extremities, or oral cavity. These tumors are generally slow growing, and symptoms are related to the site of involvement and degree of invasion. Soft-tissue sarcomas arising from visceral sites may induce signs of a mass involving a structure within a body cavity or may cause dysfunction of the involved organ or surrounding structures. For example, tumors in the gastrointestinal tract may cause vomiting, diarrhea, or weight loss. Oral soft-tissue sarcomas may cause halitosis, dysphagia, or anorexia. Tumors arising in the peripheral nerves (i.e., malignant nerve sheath tumors) may cause pain, lameness, or neurological impairment.

Soft-tissue sarcomas usually appear to be well-encapsulated on gross examination and palpation. This feature often misleads the uninitiated practitioner into believing that these tumors are amenable to easy resection by conservatively shelling them out with the “capsule.” In fact, the capsule-like structure (known as a pseudocapsule) is a layer of compressed tumor cells and reactive fibrovascular tissue.^1,3 Conservative excision of the mass is certain to leave microscopic bits of tumor behind, which results in local recurrence and may compromise the optimal treatment plan for the animal.

Diagnosis and Clinical Work-up

A complete physical examination should be performed, with particular attention focused on regional lymph nodes and on palpation of the mass. If regional lymph nodes are enlarged, fine-needle aspiration and cytology are indicated to determine if the tumor has spread. Thoracic radiographs (three views) are obtained to check for pulmonary metastasis. If the mass is firmly affixed to underlying bone, radiographs of the affected area are acquired to determine if there is any invasion of bone. The use of computed tomography (CT) or magnetic resonance imaging (MRI) is often necessary to image large tumors, tumors of the head or neck, or tumors within a body cavity [Figure 1].^4,5 These imaging modalities provide clearer definition of the degree of regional involvement and allow for accurate treatment planning.^4,5 Cytological examination of a fine-needle aspirate is helpful to support the diagnosis of neoplasia and to rule out other conditions or types of tumors (e.g., mast cell tumor). Soft-tissue sarcomas tend to exfoliate poorly and often contain areas of tumor necrosis and inflammation.⁶ Therefore, cytological evidence of necrosis or inflammation in the absence of neoplastic cells does not rule out a soft-tissue sarcoma. Multiple aspirates should be taken from different areas of the mass to ensure representative cytological sampling.⁶

Information obtained from the initial diagnostic work-up helps to determine the clinical stage (i.e., extent) of disease. Of particular importance to clinical stage are the tumor size, site, fixation to surrounding tissues, status of regional lymph nodes (i.e., positive or negative for tumor), and the presence of distant metastasis.^2,3 When a soft-tissue sarcoma is suspected, knowledge of the clinical stage helps guide the choice of treatment.

Definitive diagnosis of a soft-tissue sarcoma requires biopsy and histopathology. There are two approaches to tumor biopsy, namely pretreatment biopsy and posttreatment biopsy. Whenever possible, biopsy of a suspected neoplastic condition should take place before definitive excision is attempted (i.e., pretreatment biopsy).^6,7 Suitable pretreatment biopsy options include needle core biopsy (e.g., Tru-cut), wedge or incisional biopsy, or punch biopsy. These techniques are used when knowledge of the tumor type may influence the choice or extent of treatment, and they are the preferred techniques for initially diagnosing soft-tissue sarcomas.^1,6,7

Posttreatment (i.e., excisional) biopsy is done after the mass is excised. Tissue is then submitted for histopathology.⁷ This approach is attractive to many clinicians, because it allows for definitive treatment and diagnosis in one step. Unfortunately, posttreatment biopsy is often used inappropriately in the diagnosis of soft-tissue sarcomas. Because of the tendency for soft-tissue sarcomas to invade fascial planes and to have poorly defined margins, aggressive, wide excision (i.e., 2- to 3-cm margins in all planes, including under the tumor) is necessary. Failure to perform such aggressive excision during excisional biopsy often results in microscopic amounts of tumor being left at the site. Any further therapy must then be far more aggressive than would have been necessary had the clinician initially obtained wide margins. Excisional biopsy is only recommended when the tumor is located in a site where 2- to 3-cm margins in all dimensions can be easily attained.⁷ All biopsy incisions, regardless of technique, must be carefully located to allow for subsequent excision at a later time (e.g., definitive tumor removal). Care must be taken to avoid contamination of uninvolved tissue planes.^2,6,7

Treatment Options

Three forms of treatment are commonly used for soft-tissue sarcomas, including surgery, radiation therapy, and chemotherapy.^1–6 Surgery, radiation therapy, or their combination are used for local tumor control. Chemotherapy is used to control or prevent metastasis in animals at risk for systemic spread. Many treatment plans involve multiple modalities.

The mainstay of treatment for soft-tissue sarcomas is wide, aggressive excision. Advances in reconstructive techniques have significantly expanded surgical options for aggressive resection with good functional and cosmetic outcomes [Figures 2A, 2B]. Surgical therapy is involved in the treatment of nearly all cases of soft-tissue sarcomas. It is important to remove any previous biopsy incisions en bloc when the tumor is excised.⁷ Margins (including deep) of 2 to 3 cm are necessary to allow for microscopically complete excision.^2,6 In some cases, when the tumor is located in a position overlying a distinct muscle or fascial layer, it is possible to obtain clean margins by removing the muscle or fascia immediately beneath the tumor, provided the tumor has not already attached to this layer (i.e., one additional tissue plane beyond the tumor). In this situation, the margin of normal tissue obtained may be <2 to 3 cm in depth or width, but the muscle or fascial layer serves to define a normal tissue plane outside the tumor compartment and provides a barrier to further tumor invasion. If the tumor has attached to the muscle or fascial layer, the entire layer may be compromised and therefore should not be considered an adequate, clean margin. Fat and loose connective tissue do not serve as good tumor barriers, so when a soft-tissue sarcoma overlies these tissues, the 2 to 3 cm rule for surgical margins should be utilized.^1,6

Any surgical procedure involving margins <2 to 3 cm in all directions must be considered an incomplete excision even if no macroscopic tumor is evident after removal. The temptation to “peel out” the tumor should be avoided at all costs. Local recurrence is likely after conservative excision, if not inevitable. The use of preoperative biopsies is important to alert the clinician to the need for wide surgical margins. Because of the difficulties associated with a second surgical approach, the chance of increased patient morbidity, and the increased costs to the client, the first attempt at surgical excision should be as aggressive as is practical.⁶

Prior to submission for histopathology, surgical margins are clearly marked on the specimen. Pathological evaluation for completeness of excision is highly recommended. The histopathology report received from the diagnostic laboratory should include information on the tumor type and the grade and completeness of surgical margins. A histological description that includes the statement “tumor cells extend to surgical margins” means that excision was incomplete, and further surgery or adjunctive radiation therapy is warranted. A histological description that includes statements that refer to ≤1- to 2-m margins of normal tissue is suspicious of an incomplete resection.

Radiation therapy also plays an important role in the treatment of soft-tissue sarcomas.^1,2,6 Although soft-tissue sarcomas were historically considered radiation resistant when compared to other tumor types, a combination of surgery and radiation therapy or a combination of hyperthermia and radiation therapy has helped prevent local recurrence.^2,8–12 Radiation therapy seems to have the greatest efficacy when used in combination with surgical cytoreduction& of the tumor, and it is less effective for bulky disease.^8–12 The rationale for administering postoperative radiation therapy is that the radiation kills or prevents the multiplication of any microscopic tumor cells left behind. The combination of radiation therapy and surgery can be used in cases where surgical margins are known to be incomplete. Radiation therapy can also be utilized in conjunction with conservative resection when clients are unwilling to have their pet undergo a radical or disfiguring surgery or when wide surgical excision is not possible (such as with tumors of the head, neck, and extremities). For example, some owners unwilling to permit an amputation for an extremity soft-tissue sarcoma may consider conservative resection followed by radiation therapy. The combination of radiation and surgery has been effective for long-term, local control of soft-tissue sarcomas.¹ In one study, low- and intermediate-grade soft-tissue sarcomas with incomplete excision disease had a local control rate of 75% at 3 years postradiation therapy.¹¹

Radiation therapy may also be utilized preoperatively.^8,11–15 Advantages to preoperative radiation include a smaller radiation field (allowing for a smaller amount of normal tissue within the radiation treatment field) and possible consolidation or shrinkage of the tumor, which makes surgical excision with wide margins less difficult. Other advantages include an undisturbed tumor bed and blood supply, which enhances the ability of radiation to control tumor growth.¹ Disadvantages associated with preoperative radiation therapy include the possibility of poor or delayed wound healing in the irradiated field. A radiation oncologist can help the clinician to determine whether preoperative or postoperative radiation therapy will have the greatest benefit.

Adjunctive chemotherapy is also useful in the treatment of soft-tissue sarcomas.^1–3 Chemotherapy is best used when combined with radiation therapy and/or surgery. Chemotherapy alone does not seem to be effective for measurable soft-tissue sarcomas, with the exception of providing palliation in some cases. Despite the fact that, as a rule, soft-tissue sarcomas are slow to metastasize, histological features indicating aggressiveness (i.e., high histological grade) have been associated with an increased risk of metastasis and decreased survival times.^16,17 Chemotherapy may help prevent or delay such metastasis, so it is most commonly used after surgical removal of a high-grade soft-tissue sarcoma. Single-agent doxorubicin, mitoxantrone, or combination protocols (e.g., vincristine, doxorubicin, and cyclophosphamide) are used most commonly.^1,8

Treatment Planning

Multimodality treatment has improved survival times and the quality of life for many animals with soft-tissue sarcomas.^{1,8–11,14–18} Although surgery remains the cornerstone of treatment, the decision to include radiation therapy and/or chemotherapy is complex and dependent on several factors. Such factors include the tumor grade, clinical stage, the intended goal of treatment (e.g., palliation versus cure), and the ability to achieve histologically complete surgical margins.^1–3,6 An algorithm for decision-making in the treatment of soft-tissue sarcomas is provided in Figure 3.

Conclusion

Soft-tissue sarcomas are a heterogeneous group of tumor types that have similar biological behaviors. Tumor type, grade, and extent of disease should be evaluated prior to any attempt at treatment. Conservative excision almost invariably results in local recurrence. Wide excision is the cornerstone of treatment for low- and intermediate-grade tumors. Radiation therapy is used when surgical excision is incomplete, undesirable, or not possible. Chemotherapy is generally recommended for high-grade soft-tissue sarcomas because of their relatively high risk of metastasis.