Canine cutaneous mast cell tumors

Mast cell tumors are the most common tumors of the skin in dogs. Whilst many mast cell tumors can be cured by appropriate management, dogs that get one mast cell tumor may develop other separate mast cell tumors elsewhere on their skin at other times in their life.

© Glen Cousquer

Mast cell tumors arise from a special type of cell that is typically found in the skin. These cells are normally involved in inflammatory reactions. Therefore, mast cell tumors can show any of the changes typically associated with inflammation like swelling, bleeding, itchiness and redness. In fact, it is common for owners to notice that the lump of a mast cell tumor has been fluctuating in size.

There is marked variation in the behavior of mast cell tumors and for this reason tumor grading schemes are used. These schemes categorize mast cell tumors into:

• EITHER three groups:
  • Grades 1-3.
  • OR low/well-differentiated, intermediately differentiated and high-grade/poorly differentiated.
• OR, two groups:
  • Low-grade.
  • High-grade.

The tumor grade significantly influences the treatment decision-making process. Generally, the higher grade the tumor is the more likely it is to spread and/or grow back. Many of these tumors can be cured but only by appropriate intervention and there is merit in finding out what grade a mast cell tumor is before definitive treatment is planned.

The higher grade a tumor is, the more likely it is to infiltrate into the normal body tissues around it and the more likely it is to spread through the body via the blood or lymph systems.

Additional factors are used by clinicians to characterize mast cell tumors, such as proliferations markers and mutation status. These help to narrow down the level of aggressiveness of mast cell tumors and help to plan treatment accordingly. The higher the proliferations markers are, the faster mast cell tumors may grow, recur, and/or spread to distant sites. Mast cell tumors may also carry a special mutation (Kit mutation) in their DNA which causes fast proliferation of the cells and is associated with higher level of spread. This mutation can be searched for upon tissue or cell samples but this test result may take few weeks.

Mast cell tumors do not have a typical appearance and so any lump in or under the skin should be viewed with suspicion. High-grade mast cell tumors tend to look bad from the start. They can be big, red, itchy and frequently discharging serum or blood with no apparent border between the normal and the cancerous tissues.

Diagnosis is typically made by fine needle aspirate, where a needle is placed into the lump and a tiny number of cells withdrawn. These cells are then examined under a microscope. Sedation is rarely required and certain tumors, including most mast cell tumors, are very readily identified by this means.

Once a mast cell tumor has been diagnosed, a complex series of decisions needs to be made. Ideally whether the tumor is likely to have spread is determined first. This is done by doing a fine needle aspirate of the local draining lymph node. If a mast cell tumor is showing signs of being high-grade, eg large size, fast growth, ulceration, bleeding, causing vomiting, being located in an area at risk such as the prepuce or muzzle, then further tests to see if it has spread to distant sites (such a fine needle aspirates of the liver and spleen) may be advised.

Sometimes mast cell tumors are not identified until after surgery (to remove what had appeared to be an innocuous skin lump). The pathology laboratory will send a report describing the presence of a mast cell tumor and they will usually define the tumor grade and comment on the degree of invasiveness of the tumor. Under these circumstances further treatment is often necessary as the original surgery will often not have been adequate to completely remove the cancer.

Low-grade mast cell tumors can be cured in almost all cases. Surgical removal with appropriate margins of apparently normal tissue (0.5 – 1cm) is appropriate. Less than 1 in 10 dogs with low-grade mast cell tumor will suffer from tumor spread.

Intermediate grade tumors require wider margins (2-3 cm). It is important to note though that approximately 1 or 2 out of 10 of these patients will have spread of their tumor before the diagnosis is made.  The local lymph node can be removed alongside the primary tumor if tumor spread has not gone beyond.

Surgical removal of high-grade tumors requires much wider margins of normal tissue to be removed. Approximately 6 – 9 of every 10 of these tumors will have spread before the time of diagnosis and therefore the role of surgery in their management is limited.

Supportive treatment with anti-nausea drugs, anti-acid drugs for the stomach (as mast cell tumors may release a special molecule called histamine that can increase acidity in the stomach), allergy tablets (antihistamine such as chlorphenamine) is advised when dealing with high-grade mast cell tumors.

Other treatments do exist for mast cell tumors. As a rule, they are less effective than surgery in that they do not cure the disease. However, there are instances when these treatments are more appropriate.

Radiotherapy

Radiotherapy has a particular role to play in the management of mast cell tumors at sites that are not amenable to surgery, for instance the lower limb or around the face. Radiotherapy can dramatically affect the further progression of mast cell tumors, irrespective of tumor grade, with many cases failing to worsen for many months or even years after treatment. For this reason, radiotherapy is also used in the post-operative management of some mast cell tumors, when there is a strong suspicion of incomplete removal. By and large the side effects of radiotherapy are minimal; this is defined in part by the particular radiotherapy protocol used. Some animals develop reddening of the skin; others can develop skin ulceration. Skin related side effects can be irritating but tend to be short-lived. More serious effects can develop in the long-term and for this reason radiotherapy is undertaken less freely in younger patients.

Electrochemotherapy

For mast cell tumors that are not suitable for wide surgical excision, electrochemotherapy can be used alone or in conjunction with debulking surgery. This treatment is done under anesthesia and consists of applying an electric current to the tumor cells to increase intake of chemotherapy.

Local injection of tigilanol tiglate (Stelfonta)

For mast cell tumors that have not spread, are below a certain volume (10 cm3), and depending on location on the body, a drug that will cause tumor cell death can be injected directly in the mass. This treatment is done under anesthesia and may be considered when surgery is not possible. The downsides are that rapid tumor cell death cause ulceration and wound management at the site may last weeks, post injection. With this treatment, the tumor is also not sent to the laboratory for analysis and therefore information about tumor grade or whether the whole mass has been successfully treated is not available.

Chemotherapy

While there are countless descriptions of the use of chemotherapy in the management of canine cutaneous mast cell tumors in the veterinary literature, many of the successes reported have probably failed to recognize that a number of the cases described were already cured by the earlier administration of appropriate surgery. As a result, the stated responses to chemotherapy are likely to be overoptimistic. Having said that, chemotherapy may be appropriate in the management of metastatic mast cell tumors (those which have spread around the body) and favorable results can be seen. Unfortunately, the response to chemotherapy can be unpredictable. While every effort is made to control the patient’s disease, it is not controlled at the expense of quality of life. The overriding philosophy in the management of all canine cancer patients is the promotion of quality of life first and length of life second.

Steroids, such as prednisolone, are part of chemotherapy protocols for mast cell tumors. They can also be used on their own when cytotoxic drugs are declined but would have a short-lived effect in this instance.

Designer Drugs

Low molecule inhibitors, such as masitinib or toceranib, are licensed for treating mast cell tumors in dogs. These drugs are specifically designed to block proteins important in the development of a proportion of canine mast cell tumors. A special test (kit mutation status) can be done to assess the possible rate of response from mast cell tumors to these drugs, ie tumors carrying the mutation are more prone to respond to treatment. The risks associated with the use of masitinib and toceranib are limited. Dogs may develop low-grade gastrointestinal signs (vomiting and diarrhea) that rarely required treatment modification, mild reduction in their immunity, loss of protein in the urine, or increased blood pressure. The best indication for masitinib and toceranib are high-grade metastatic or multifocal mast cell tumors.

Complete removal of a mast cell tumor that has not spread from its original site will result in a cure. This is the case for nearly all grade 1 or low-grade mast cell tumors and more than three-quarters of grade 2 or intermediate grade tumors. Unfortunately, in the majority of cases with grade 3 or high-grade tumors this is not possible. In cases with high grade tumors or cancer that has spread, it is unusual that patients live more than six months from the time of diagnosis, even with treatment. We may find that this changes as we gain more experience with the new designer drugs. A specialist veterinary oncologist would be able to offer the most up to date information in this respect.