The clinician should be aware that tumour location affects tumour behaviour and prognosis (see ‘Prognostic factors’ below). A thorough search of the animal for multiple cutaneous masses should be performed and any new lump found should undergo FNA cytology. If multiple cutaneous MCT are found, the approach to treatment is often different from that for a single MCT.

The majority of MCT can be identified on FNA. They appear as small-to-medium round cells, usually abundant and with uniform cytoplasmic granules that stain purple-red (metachromatically) (Figure 19.4). However, grade cannot be determined by cytology and it is important to remember that not all MCT stain with Romanovsky-type stains, giving them an epithelial or macrophage-like appearance on the slide. In such cases, histology and possibly immunohistochemistry are required for diagnosis. In some cases FNA of an MCT will only yield blood.

Prior to surgery it is important to assess the extent of the local tumour. In some cases this can be very difficult when the tumour is fluctuant and does not appear to have defined margins. It can also be difficult in those tumours that constantly wax and wane. Whenever an MCT undergoes a local inflammatory response resulting in a transient increase in size, it must be assumed that tumour cells extend into the affected area. Therefore, the presurgical use of steroids to reduce tumour size results in underestimation of the size of the tumour and potentially incomplete resection. Shrinkage of a tumour before surgery with radiotherapy, however, is completely different in that the edges have been truly sterilized.

The extent of the tumour can be estimated by physical examination, radiographs, ultrasound or computed tomography (CT) scan. Interestingly, in one study, dogs with cutaneous MCT had the extent of the margin upgraded in 19% of cases using ultrasound and 65% of cases using CT (Hahn et al 1990). This is important for planning surgery and radiotherapy. What additional tests are required to establish the extent of the tumour depends on its location and whether a wide excision will be simple or difficult.

The more information that is obtained, the more accurate the predictions as to prognosis. In terms of treatment this means that the most appropriate course of treatment can be determined. It is also important to understand the relevance of normal responses in the body that may account for the presence of mast cells. Interestingly, MCT do not metastasize or originate in the lungs.

Additional presurgical diagnostics include the following.

One approach is this:

This is strongly predictive of outcome (Thamm et al 2006). In spite of some ‘greyness’ in defining histological grade, it is highly predictive for overall survival time, providing appropriate therapy is given from the beginning. The vast majority of dogs with well-differentiated tumours (80–90%) and 60–75% of moderately differentiated tumours experience long-term survival following surgical excision ± radiotherapy. Dogs with undifferentiated (high-grade) tumours treated surgically frequently die of their disease within 12 months due to local recurrence or metastasis.

Individual histological criteria such as invasiveness and the number of mitotic figures were prognostic in one study. These parameters may be more reliable than the Patnaik grading system, which is influenced by more subjective observations such as tumour heterogeneity, cellular differentiation and nuclear morphology (Preziosi et al 2007).

In combination with histological grade, stage is predictive of long-term prognosis (see Table 19.1). Patients with stage 0-I disease confined to the skin without local lymph node involvement or distant metastasis have a better prognosis than patients with stage III–IV disease. At least one study has suggested that there is no difference in outcome between patients with a single MCT and those with multiple cutaneous MCT (Mullins et al 2006, Simoes et al 1994, Thamm et al 2006).

In general, our ability to recognize MCT earlier and combine better surgical approaches with radiotherapy has resulted in overall better survival times for patients with MCT. However, certain locations may still warrant a more guarded long-term prognosis; in particular, aural (early metastasis to regional lymph nodes), subungual, perianal, oral and other mucocutaneous sites are associated with more undifferentiated tumours and a poorer prognosis, with metastasis earlier in the course of their disease (Cahalane et al 2004, Sfiligoi et al 2005, Thamm et al 2006). Any MCT at a mucocutaneous site is considered grade III disease (due to metastatic potential) no matter what grading they are given by the pathologist. Visceral disease carries a grave prognosis (O’Keefe 1990, Ozaki et al 2002).

This is determined by tumour volume/number of weeks the tumour was present. Low-grade MCT tend to have a long, stable history. Some MCT will remain sessile for weeks, months or even years before entering a phase of rapid growth; the biological trigger is unknown.

Any growing MCT should be removed immediately, as should any ‘quiescent’ MCT located in an area where growth would compromise surgical margins, e.g. distal extremity or face. Rapid growth is a negative prognostic indicator and the faster an MCT is growing, the sooner it should be addressed. Best practice is to diagnose and treat as early as possible. A ‘wait and see’ approach is potentially detrimental to the patient.

Vomiting, melaena, anorexia, or widespread erythema and oedema due to massive mast cell degranulation are more often associated with large cutaneous MCT or disseminated disease (Mullins et al 2006, O’Keefe 1990, Pollack et al 1991). In 16 cases of visceral MCT, the median survival time (MST) was 90 days and all dogs died of MCT (O’Keefe 1990).

Recurrence following surgical excision is thought to carry a more guarded prognosis (Thamm et al 2006).

Boxers usually have well-differentiated tumours and therefore a better prognosis (Bostock 1986). Other breeds that have a predisposition to develop more biologically aggressive MCT include Bernese Mountain Dogs (BMD), Shar Pei and Bull Mastiff. Multiple cutaneous MCT are seen most frequently in Boxers, Golden Retrievers, Labrador Retrievers and Weimaraners.

For tumours localized to the skin or subcutaneous tissues in areas amenable to wide excision, surgery is the treatment of choice.

The surgeon should include a 3 cm margin of surrounding normal tissue. However, margins of 2 cm may be sufficient for low- and intermediate-grade MCT (Simpson et al 2004) (Figure 19.5). Wide margins are deep as well as lateral, and for a deep margin a fascial plane is required to ensure adequate excision (see Chapter 5). Histological assessment of margins is important. If planned curative surgery has not been achieved, then further local therapy may be warranted. This may entail a second excision with additional wide margins or adjuvant radiation therapy depending on MCT location. Not all incompletely resected MCT will recur, especially if low–intermediate grade and the possibility of normal mast cells at tissue margins may cause some confusion (Séguin et al 2006). However, if the resection is incomplete and recurrence would be difficult to deal with (distal extremity or face), adjuvant therapy is indicated.

Wide margins to ensure adequate excision of MCT mean that in many cases flaps are required (Figure 19.6). It is important that before a flap is attempted the surgeon is entirely confident that this will result in complete excision. If not, it is better for the patient to do a marginal excision and refer for radiotherapy. There is nothing worse than putting a patient through the long process of recovering from extensive surgery and then not having a margin, because at that point the radiation oncologist has to assume potential recurrence in any region of the flap. It also makes the whole process more expensive for the client than it needed to be.

For many patients the long-term prognosis with surgery alone is good. Patnaik et al (1984), in a large retrospective study, showed that 1550 days after surgery 93% of dogs with well-differentiated MCT were alive, compared with 44% with intermediate-grade tumours and only 6% with poorly differentiated tumours. A number of studies since then have come to similar conclusions concerning prognosis (Murphy et al 2004, Séguin et al 2006, Sfiligoi et al 2005).

MCT often arise in areas where it is not possible to achieve adequate surgical margins, e.g. the head and distal extremities. In the case of a MCT on a distal extremity, amputation of the leg is an option and in some cases can be the treatment of choice, especially if the tumour has extended 360 degrees around either the carpus or the tarsus. Usually, however, amputation is seen as a salvage procedure and in most cases the goal is to preserve the limb.

In veterinary medicine the most frequent application of radiotherapy is in the control of incompletely resected MCT. Radiotherapy should be considered in all patients where an MCT has been incompletely resected and where no further surgery can be carried out to obtain surgical margins. This means that the majority of patients eligible for radiotherapy have had MCT on the head/muzzle region or a distal extremity (Figure 19.7).

The decision as to the value of radiotherapy in an individual patient depends on the experience of the radiation oncologist. The rule of thumb used by the authors is that any fast-growing/aggressive MCT in an area of the body that would be difficult to re-excise should it regrow should receive radiation. Any MCT that has shown invasion onto tendons etc. should also be irradiated, irrespective of grade. MCT that may be best monitored are those of lower grade, less invasive or in areas that should there be recurrence, good options for further treatment are available.

Age and breed can also influence treatment decisions. The younger the patient, the better it is to avoid radiotherapy for MCT, if possible, because of the potential for long-term side effects of treatment (see Chapter 7).

A number of treatment protocols are available in the literature but all give good long-term control for stage 0 tumours of low to intermediate grade (median 2-year control rates of 85–90%). Radiotherapy is equally successful in local control of high-grade MCT but unfortunately these patients fail early due to metastatic disease.

Radiotherapy can also be used to shrink tumours before surgery and actually sterilizes the margins so that these are not underestimated at the time of surgical excision.

Radiotherapy can be used as the sole treatment in the management of MCT. In this scenario, it should be considered palliative therapy and is most often applied to MCT located on the muzzle not amenable to surgery or the client declines surgery due to the potential cosmetic appearance, e.g. MCT of the distal extremities that are not amenable to surgery and the client declines amputation. The major concern in irradiating bulky MCT is mast cell degranulation and the resulting consequences of acute hyperhistaminaemia.

Large MCT can be considered for radiotherapy to shrink them down to improve quality of life. However, the potential for complications, as above, is high, and such patients require hospitalization after treatment.

The role of chemotherapy remains an area of discussion in veterinary medicine. The primary treatment modalities are undoubtedly surgery and radiotherapy. However, in patients with metastatic disease (Figure 19.8) or multiple cutaneous MCT, surgery and radiotherapy may not be appropriate. In general, for multiple cutaneous MCT, multiple marginal excisions are combined with adjuvant chemotherapy.