Soft-Tissue Sarcoma
World Small Animal Veterinary Association World Congress Proceedings, 2013
Jonathan Bray, MVSc, MANZCVSc, CertSAS, MRCVS, DECVS
Massey University, Auckland, New Zealand

Introduction

Soft-tissue sarcomas are a large group of tumours of mesenchymal origin that have similar biological behaviours. They are relatively common in the dog and compromise approximately 15% of all skin and subcutaneous neoplasms. Annual incidence rates of soft-tissue sarcoma have been estimated to be 35–142 per 100,000 dogs at risk. Compared to the dog, soft-tissue sarcomas are much less common in the cat. However, the cat appears to be particularly susceptible to an inducible form of sarcoma that can arise at sites of injection. Whilst vaccination sites are more commonly associated with this form of tumour, they have also been reported with microchips, flea treatments and other depot injections. The incidence of these cancers is thought to be somewhere between 1/1000 to 1/10000 'injections.'

Soft-tissue sarcoma can present the clinician with significant challenges with respect to management, but when treated appropriately, clinical cure is possible.

Animals with a soft-tissue sarcoma usually present with a mass, which has recently been noticed by the owner. Although some masses have probably been present for many months, some large masses may arise quickly and then maintain a stable size.

Depending on the location of the mass, other signs may predominate (e.g., lameness, vomiting, difficulty urinating, etc.) with the mass itself being occult on routine physical examination. This can often cause a delay in diagnosis of the tumour, which may increase the potential for local and distant spread by the tumour.

Nomenclature

Soft-tissue sarcomas arise from mesodermal tissues. Although many soft-tissue sarcomas are histologically distinct, they are usually classified together because of their similar biological behaviour. They include fibrosarcoma, perivascular wall tumours, leiomyosarcoma, liposarcoma, malignant fibrous histiocytoma, mesenchymoma, myxosarcoma, nerve sheath tumours (previously called neurofibrosarcoma, schwannoma, haemangiopericytoma), rhabdomyosarcoma, and undifferentiated sarcoma. The terms spindle-cell tumour and sarcoma are often used interchangeably due to the microscopic appearance of neoplastic mesenchymal cells.

The term soft-tissue sarcoma excludes tumours of lymphoid, haemopoetic, or bony origin, and also generally excludes synovial-cell sarcoma, lymphangiosarcoma and oral fibrosarcoma that are atypical in their behaviour, with a different distribution and higher rate of metastases.

Comparative Aspects

Soft-tissue sarcomas are less common in humans, representing less than 1% of all tumours. The biologic behaviour is very similar to that of the dog (although more low-grade tumours develop in the dog), with rates of local recurrence and metastatic disease influencing management decisions. Controversies on margins, the extent of resection required, and the role of adjuvant therapies are also a feature of human soft-tissue sarcoma, and the results of translation research will likely assist both populations.

Treatment Guidelines

Surgery remains the mainstay for the treatment of soft-tissue sarcomas. Although aggressive surgical resection (3-cm margins and a deep fascial plane) is traditionally recommended, several recent studies have challenged this generic advice, with no obvious survival advantage evident when patients are stratified by the extent of surgical excision performed. However, the potential for local recurrence (even with aggressive surgery) remains a concern.

Soft-tissue sarcoma may arise anywhere in the body. When a tumour has arisen in close proximity to a vital organ or anatomical structure, careful surgical planning is necessary to fully evaluate the consequences of surgery on the patient. Often, a sacrifice is necessary but it is important this sacrifice is justified in terms of long-term outcome and tumour control. Although utilising wide or radical excision margins for all soft-tissue sarcoma will undoubtedly cure the majority of patients, many patients will be drastically overtreated whilst a proportion of patients will continue to experience local recurrence, and some patients (possibly up to 40% with high-grade lesions) will die from metastatic disease. It is also important to realize that some patients will die with their disease rather than because of their disease.

Despite recent papers suggesting reasonable tumour control is possible with more conservative margins, it is important that we do not recalibrate our surgical margins too quickly. It remains a fundamental truism of oncologic surgery that the first surgical intervention is optimal for the successful management of all tumours. An inappropriately conservative resection may prove detrimental to the patient and can make a subsequent curative resection impossible. It is possible that successful management of some sarcoma may require a different surgical strategy. Histological studies of tumour margins in soft-tissue sarcoma suggest there can be variable extent of local invasion, with a "tumour-permissive" microenvironment extending some distance beyond the tumour edge. In some cases, discrete microscopic areas of tumour may be found several centimeters from the primary mass. Therefore, whenever it is achievable, a compartmental excision - e.g., resection of an entire muscular unit containing the tumour - is preferable to an 'en bloc'-wide excision, as this ensures the tumour and its associated environment are removed completely.

Predicting Surgical Dose

Achieving a 'clean' histological margin following resection of soft-tissue sarcoma is usually associated with successful local control. Given the uncertainties and dilemma associated with the extent of surgical margins, the challenge now is predicting which tumour is most likely to recur (or metastasise) and titrating treatment strategies accordingly. Much work remains to be done before these questions can be answered with certainty for every tumour, but several indicators exist that may alert the surgeon to the invasive potential of an individual tumour.

Palpation and Clinical Characteristics

The mass is usually readily palpable and may appear discrete and encapsulated. Most tumours are quite firm, but some (particularly haemangiopericytoma) may be multilobulated and soft, and have palpable features more typical of benign lipoma. Although the superficial aspects of the mass may appear quite mobile, the base can be indistinct and potentially attached to underlying bone or fascia. The mobility of the tumour may be significant in terms of prognosis. In a recent study, tumours that felt more 'fixed' to underlying tissues were significantly associated with decreased disease-free intervals (P < 0.0001) and survival times (P = 0.007).

Other clinical features that may suggest a more aggressive tumour include tumour > 5 cm (golf-ball sized), a history of sudden or rapid growth, ulceration and recurrence following a previous surgery.

Biopsy

Knowledge of the tumour type and histologic grade can be very helpful to guide management of the soft-tissue sarcoma, particularly when the tumour is located in a location where adherence to conventional margins is likely to be difficult (e.g., distal limb or adjacent to vital structure). In 2009, McSporran showed that histologic grade is a strong predictor for recurrence of marginally excised subcutaneous soft-tissue sarcomas, with 7, 34 and 75 percent recurrence rates for low-, intermediate- and high-grade tumours, respectively.

Cytology is often unrewarding for soft-tissue sarcoma, as mesenchymal cells do not exfoliate readily during fine-needle aspiration, and the cytological appearance of reactive or inflammatory tissue may be very similar. For these reasons, incisional biopsy is essential for definitive diagnosis of all suspected soft-tissue sarcoma. Automated Tru-Cut biopsies can usually be obtained from most soft-tissue sarcomas under local anaesthesia only. Because of the small size of Tru-Cut biopsies, multiple samples (at least 6) should be obtained. As always, good biopsy principles should be followed to ensure the subsequent curative resection is not compromised by contaminated biopsy tracts.

Imaging

In human musculoskeletal tumour surgery, the Enneking staging system has been used for many years to assist with surgical planning and prognostication of mesenchymal tumours affecting the limb. This staging system takes into account not only the histologic features of the tumour but also the clinical and radiographic features of the tumour. Coaxial imaging is utilized to determine whether the lesion is anatomically confined to well-delineated surgical compartments, or has spread beyond such compartments into ill-defined fascial planes and spaces. High-grade lesions are more likely to invade surrounding host tissue, which places the patient at greater risk of local recurrence and metastasis. In veterinary surgery, the Enneking system has not been validated but numerous anecdotal examples suggest that coaxial imaging can greatly assist surgical planning, especially for large (> 5 cm) lesions. Coaxial imaging allows the relationship of the tumour and the surrounding normal muscular compartment to be evaluated prior to surgery being performed. This enables surgical margins to be determined, and which body structures may need to be sacrificed to permit 'safe' tumour removal.

Adjuvant Treatments

Radiotherapy or chemotherapy as sole therapies are generally ineffective in the treatment of soft-tissue sarcoma. However, both modalities have potential roles in either the neoadjuvant or adjuvant setting. The role of chemotherapy in soft-tissue sarcoma is unclear, with most human and veterinary studies failing to demonstrate a survival advantage. Currently, it is recommended for higher grade tumours only, but large, low-grade tumours may still metastasise. 'Continuous low-dose' (metronomic) chemotherapy is considered to offer benefits over conventional chemotherapy, possibly by disrupting vascular development by the tumour.

Prognosis

The prognosis for the majority of cats and dogs with soft-tissue sarcoma is generally good, provided a complete resection has been achieved. However, local recurrence can develop in up to 30% of dogs. Rates of metastasis are less well-defined, but may also develop in 30–40% of cases. Overall, about 20–30% of dogs will ultimately die of their disease, and continued efforts to improve management options and to recognize those dogs with 'bad disease' remains important.

References

1.  Bray J, Polton G, Whitbread T. Outcome of 490 cases of soft tissue sarcoma managed in first opinion practice. (Abstract) European Society Veterinary Oncology Annual Congress, Glasgow, UK; 2011.

2.  Chase D, Bray J, Ide A, et al. Outcome following removal of canine spindle cell tumours in first opinion practice: 104 cases. J Small Anim Pract. 2009;50(11):568–574.

3.  Enneking WF, Spanier SS, Goodman MA. A system for the surgical staging of musculoskeletal sarcoma. Clin Orthop Relat Res. 2003;415:4–18.

4.  Kamstock DA, Ehrhart EJ, Getzy DM, et al. Recommended guidelines for submission, trimming, margin evaluation, and reporting of tumor biopsy specimens in veterinary surgical pathology. Vet Pathol. 48(1):19–31.

5.  Kuntz CA, Dernell WS, Powers BE, et al. Prognostic factors for surgical treatment of soft-tissue sarcomas in dogs: 75 cases (1986–1996). J Am Vet Med Assoc. 1997;211(9):1147–1151.

6.  McSporran KD. Histologic grade predicts recurrence for marginally excised canine subcutaneous soft tissue sarcomas. Vet Pathol. 2009;46(5):928–933.

7.  Stefanello D, Morello E, Roccabianca P, et al. Marginal excision of low-grade spindle cell sarcoma of canine extremities: 35 dogs (1996–2006). Vet Surg. 2008;37(5):461–465.

  

Speaker Information
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Jonathan Bray, MVSc, MANZCVSc, CertSAS, DECVS, MRCVS
Massey University
Auckland, New Zealand


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