Introduction

Sarcomas of soft tissues (STS) are common in companion animals and pose a therapeutic and diagnostic challenge for the practising veterinarian. STS is defined as a malignant tumour of the extraskeletal connective tissues. These tissues, all of mesoderm origin, surround, support or connect other anatomic structures and are present in any part of the body.

Because soft tissues are estimated at 40% proportional body weight, it is not surprising that numerous soft tissue tumours arise with regularity. STS form an assembly of tumours of different histogenetic origin, with ubiquitous localisation possibilities, and variation in biological behaviour. Still, STS are often grouped together because of their shared mesodermal origin, similarities in clinical presentation, and communality in diagnostic and therapeutic approach. In general, STS are fleshy (the Greek word ‘Saρκoµα’ or ‘sarkoma’ is often translated as flesh-like mass), infiltrative and locally aggressive tumours that have a variable metastatic potential. Mast cell tumours are often soft to the touch and can be either well described or ill defined.

Incidence & Clinical Signs

STS are common tumours and comprise from 15% (skin and subcutaneous tissues) to 35% (spleen) of all canine tumours, dependent on original tumour location. Cats are afflicted less frequently (7% reported for skin and subcutaneous tissues). Clinically, STS often are solid masses that seem well circumscribed and encapsulated. However, this is based upon the presence of a pseudocapsule of atrophic remains of surrounding tissue and wedged tumour cells, while infiltration through this pseudocapsule and through fascia leads to attachment to deeper structures. The annual incidence of STS in the United States is estimated to be 35/100.000 for dogs and 17/10000 for cats at risk. These data are not available for the European countries.

Pathogenesis

Little is known about the pathogenetic cause of STS in dogs and cats. Changes in genetic make-up, chronic trauma, foreign bodies, vaccinations, parasites and radiation have been associated with STS in both species. P53 mutations and MDM2 gene amplification were observed in a subgroup of canine soft tissue sarcoma; however, familial predispositions have not been reported. No sex or breed predilections have been found, although certain breeds seem to be afflicted with tumours more commonly than others. In general, most studies report medium to large breeds to be affected more commonly, with an overrepresentation of the older animal. The presence of foreign bodies or material (such as vaccinations) may induce chronic stimulation of the tissues and promote neoplastic transformation.

Classification

All soft tissues are exposed to the risk of benign or malignant tumour formation. Any classification schedule, however, is complicated by overlapping patterns of dedifferentiation or by the inability to recognize the appearance of the cell of origin. A classification by localisation, grade and tumour stage seems more logical and may prove more useful at present. Advances in histochemical, electron microscopic and biogenetic markers will improve the ease of classification in the future.

Diagnosis

The diagnostic plan for STS is not essentially different from any other tumour type. The physical appearance is noticed depending on the location of the tumour and, in general, peripherally located tumours are more easily detected and often smaller than more centrally located STS. Pain is associated with location, pressure of the tumour or tumour invasion. Some peripheral nerve sheath tumours have been reported to be sensitive to the touch. A clinical differentiation between benign and malignant is not possible, so additional diagnostics are necessary. Moreover, rate of growth of the tumour often does not predict the biologic behaviour correctly. Additional biopsy specimens should be obtained in all cases. The easiest method of biopsy is fine needle aspiration (FNAB), and this method should be used as the first step in the diagnosis. Although many STS are not  well diagnosed by FNAB because of their limited exfoliative character, many other tumour types can be excluded as well as some inflammatory processes; in particular if infection can be demonstrated while overlying skin is intact. In case of any doubt, and in particular also if cytology indicates mesenchymal proliferation in absence of an inflammatory response, this provides a solid indication for further diagnostic work-up. lncisional, excisional or thick needle core biopsy (TNCB) specimens should be obtained. TNCB is the easiest and fastest method and requires minimal sedation. Multiple core biopsies should be performed and submitted to the pathologist. Sufficient tissue, however, is often better acquired by incisional or excisional biopsies. Excisional biopsies are only advantageous when adequate margins can be obtained. In all other cases, an incisional biopsy is preferred. Normal tissue should be incorporated in the biopsy specimen to evaluate peripheral infiltration of the tumour. lncisional biopsies should always be performed in such a manner that removal of the scar is possible in future radical excisions or adjunctive radiation therapy protocols. Adjunctive diagnostic evaluations should include routine blood work, radiographs of the local tumour site for possible underlying bone infiltration, ultrasound of the tumour, radiographs of the chest for possible metastatic spread, FNAB of the regional lymph node and CT or MRI imaging techniques.

The most important factors in STS evaluation are the determination of tumour grade and tumour stage. Tumour grade is determined through histological evaluation and varies among grade I (low grade or well differentiated) to grade Ill (high grade or poorly differentiated). Tumour grade is determined by degree of differentiation, cellular pleiomorphism, cellularity and matrix formation, as well as mitotic index and amount of tumour necrosis.

In human sarcomas, the tumour grade has a major impact on tumour staging. Tumour staging is based on four parameters: histological grade (G), tumour size (T), regional lymphnodes (N), and distant metastasis (M) (Table 2). Factors reported to be of prognostic importance in canine STS are size, site, grade and presence of local or distant metastases. The prognostic effect of localisation of the tumour is most likely dependent on the difficulty of complete excision. Prognostic significance is closely correlated to tumour grade; the least differentiated tumours have the worst prognosis. Additionally, the higher the stage of the disease, the poorer the prognosis.

General Considerations

STS pose a problem to the veterinarian mainly because they tend to be locally aggressive. Complete surgical excision is often impossible because of localisation or size of the tumour. Recurrence is common after incomplete resection and is the primary reason to refer these tumours to a specialised surgical oncology service. Most recurrences will occur within 2 years after primary tumour removal. Recurrence is caused because STS tend to spread into deeper or surrounding tissues by invasion or extension next to natural anatomic structures. Cutting of the tumour mass leaves these tumour extensions in the patient. Through this, the tumour homeostasis is disrupted and fast-growing tumour cells thrive causing fast tumour regrowth. Early detection and diagnosis of the original tumor will facilitate complete removal and prevent recurrence. Shelling out the tumor is the most common cause for recurrence. Education and communication should be directed in the future to achieve these goals of early detection and complete removal.

Overall metastatic rate is estimated to be 20%. Among subtypes there exists considerable variation. In part, this appears based on a link between subtype and frequency distribution of histologic grade. Low to moderate rate of metastasis is seen in (mostly low-grade) tumours. More undifferentiated STS have a higher rate of metastasis, i.e., 40–60%. Metastatic spread by lymphatic routes and lymph node involvement is reported to be rare STS. High-grade tumours have a higher incidence of lymphatic spread especially in late stages of the disease.

Treatment

Surgery is the primary therapy of STS, with or without adjunctive therapy. The surgical goal is to completely remove the tumor and, as a result, a large margin of normal tissue is sacrificed. An example of this type of surgery is the amputation of a limb. Limb-sparing surgeries are an alternative, but can only be performed in combination with adjunctive therapy modalities such as radiotherapy, chemotherapy and immunotherapy in case of large tumor mass.

Surgery

Surgery is only successful if large margins of normal tissue are obtained, with margins of 2–3 cm normal tissue advocated. The objective local failure rate for marginal excisions (peel-out or shelling-out) in humans is 86%; however, these rates, based on large numbers, are unknown in dogs and cats. Failure rates after wide local excisions and more radical excisions (such as amputations) were 49% and 14% in humans, respectively. Extrapolation from human data is tempting, but should be interpreted with caution. Recurrence rates of 60–70% are reported in marginally excised STS. Although most STS tend to recur within a year after surgery, adequate follow-up of 2 to 3 years is necessary. Wide surgical excision is often complicated by the anatomic localisation of the tumour to important structures. In general, a repeat surgery is more complicated if the tumor has recurred and failure is more likely. The first surgery has the largest chance for complete removal. Recurrence, as of yet, is not associated with an increased risk of metastases, however. It is the author's opinion that the incidence of metastases depends more on tumour grade than on the type of surgery performed. The recurrence rate decreases when the surgery is performed by more experienced oncologic surgeon. Experience often correlates to a more radical surgery, knowledge of innovative reconstruction techniques and better understanding of the pathophysiological properties of the tumour.

References

1.  Ranieri G, Marech I, et al. In vivo model for mastocytosis: a comparative review. Crit Rev Oncol Hematol. 2015;93(3):159–169.

2.  Welle MM, Bley CR, Howard J, Rufenacht S. Canine mast cell tumours: a review of the pathogenesis, clinical features, pathology and treatment. Vet Dermatol. 2008;19(6):321–339.

3.  London CA, Seguin B. Mast cell tumors in the dog. Vet Clin North Am Small Anim Pract. 2003;33(3):473–489.