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Canine mast cell tumors account for up to 20% of all skin tumors in dogs. While they often appear small and somewhat insignificant, they can be a very serious form of cancer in the dog. Some mast cell tumors are easily removed without the development of any further problems and others can lead to a life threatening disease. Proper identification and treatment are very important in controlling these tumors.

What are mast cells?

Mast cells are cells that normally occur in the skin and other tissues, such as the intestines and respiratory tract. They are part of the immune system (defense mechanism) of the body. They contain large amounts of histamine, heparin, and proteolytic enzymes (enzymes which break down protein). These can be toxic to foreign invaders, such as parasites, and are released when the mast cell is triggered by the immune system.

A mast cell tumor is formed from many of these mast cells. Because of the histamine, heparin, and enzymes present in mast cell tumors, they can create problems when damaged or removed. Large amounts of these substances can be released into the body and have significant effects on heart rate, blood pressure, and other body functions. Sites where the tumors are removed can sometimes refuse to heal and can become difficult to manage.

Which dogs are at risk for developing mast cell tumors?

Mast cell tumors can develop in all ages and breeds of dogs. They are rare in cats and humans. There appears to be a hereditary factor to these tumors as shown by some strong breed predilections. They are most common in Boxers, Boston Terriers, Pugs, English Bulldogs, and other brachiocephalic breeds (those having a short, wide head). Golden Retrievers may also be at increased risk. Most mast cell tumors develop in older dogs, usually those 8.5 - 9.5 years of age.

The exact cause of mast cell tumors is still speculative. A viral source has been mentioned, as well as hereditary and environmental factors. It is quite possible that there are a variety of different causes for the development of this tumor. Because this tumor is not found in humans, there has not been as much research and information available for the veterinarian as there are for tumors that are found in both humans and animals.

What are the symptoms of mast cell tumors?

The appearance of mast cell tumors can be widely variable. They can be either benign or malignant and can be found on any part of the body. They are found most commonly on the trunk, limbs, and perineal (genital) area. Tumors can be found on the skin or in the underlying or subcutaneous tissue. They can be single or multiple and can be smooth, bumpy, or even ulcerated.

Systemic signs, such as vomiting, duodenal ulcers, blood in the stool, and abnormalities in blood clotting occur in some dogs with mast cell tumors. These signs result from the release of histamine, etc. from the active mast cell tumors.

How are mast cell tumors diagnosed?

Since they occur in a variety of shapes and locations, a biopsy or needle aspirate (collecting some tumor cells through a needle and examining them under the microscope) is necessary to properly identify a growth as a mast cell tumor.

Mast cell tumors are commonly graded and staged, meaning classified as to how they are expected to behave. This is performed by examining the tumor after it has been removed. The grading and staging help determine what type of further treatment may be necessary and the prognosis.

Grading Mast Cell Tumors

Mast cell tumors are "graded" as to how likely they are to be malignant. The higher the grade, the more serious the tumor.

• Grade I: Occur in the skin and are considered benign. Although they may be large and difficult to remove, they tend to not spread to other areas of the body. Most mast cell tumors are Grade I.
• Grade II: Extend below the skin into the subcutaneous tissues. Their cells show some characteristics of malignancy and their response to treatment can be unpredictable.
• Grade III: Invade areas deep below the skin, are very aggressive, and require more involved treatment.

Staging Mast Cell Tumors

In addition to grading mast cell tumors, they are also staged, which is a measurement of how they have spread in the body. A tumor is staged after it is surgically removed and examined, along with the neighboring lymph nodes. Staging is based on how many tumors were present, the lymph node involvement, and if all of the tumor was removed.

• Stage 0: One tumor in the skin incompletely removed, with no lymph node involvement.
• Stage I: One tumor in the skin, with no lymph node involvement.
• Stage II: One tumor in the skin with lymph node involvement
• Stage III: Multiple large, deep skin tumors, with or without lymph node involvement
• Stage IV: One or more tumors with metastasis in the skin with lymph node involvement. This stage is subdivided into those that have no other signs (substage a) and those that do have some other clinical signs (substage b).

How are mast cell tumors treated?

In determining the appropriate therapy for mast cell tumors and their wide variety of forms, it is important to remember that each animal needs to be evaluated and treated individually.

Surgical Removal

Mast cell tumors are usually treated by surgical removal. This is the treatment of choice, and if performed correctly, will usually cure Grade I and Grade II tumors. It is important that the tumor is carefully removed and a large area of 'healthy' tissue around the tumor is also removed. It is sometimes difficult to determine exactly where the tumor begins and healthy tissue starts, so a wide margin (large portion of healthy tissue around the tumor, at least one inch) should be removed along with the tumor.

Radiation

In some cases, surgical removal may not be an option, or it may not be possible to remove enough margin around a tumor. In these instances, radiation is recommended. Radiation therapy after surgical removal appears to be beneficial and may reduce the incidence of reoccurrence and increase survival rates. Radiation is most useful when the tumors have not spread to multiple areas of the body.

Chemotherapy

If the mast cell tumors have spread to multiple areas, a combination of anti-cancer drugs are commonly used along with surgery and radiation. These include vinblastine, lomustine, and corticosteroids, such as prednisolone. Unfortunately, mast cell tumors do not respond well to these drugs.

There is a new weapon available in the fight against canine mast cell tumors. This medication is a tyrosine kinase inhibitor called toceranib phosphate. This drug is marketed by Pfizer Animal Health under the trade name Palladia. Palladia is a prescription medication designed to treat grade II-III, recurrent, mast cell tumors of the skin. It is given orally and works in two ways: it attacks and kills the tumor cells and it cuts off the blood supply to the tumor. There are some strict warnings and handling instructions with this medication so Palladia should only be administered to dogs that are under a veterinarian's care.

What is the prognosis for dogs with mast cell tumors?

The prognosis depends primarily upon the grade and stage of the tumor. The lower the grade, the better prognosis. In addition, dogs with Stage I tumors have the best prognosis, compared to those staged higher. The location of the tumor also plays a role. Dogs with tumors on the limbs appear to have the best prognosis. Those with tumors in the nail bed, genital areas, muzzle, and mouth have a poorer prognosis. Dogs with mast cell tumors in the internal organs, such as the spleen or bone marrow, have the least favorable prognosis.

Conclusion

Mast cell tumors can present in a wide variety of ways and can have an equally varied set of symptoms and outcomes. Because it is difficult to diagnose a mast cell tumor by visual inspection, it is important that all suspicious-looking skin tumors be examined by a veterinarian and followed up with diagnostic testing and identification. Treatment consists of surgical removal and radiation, and possibly chemotherapy. As with all tumors, prompt recognition and treatment is very important in obtaining the best possible outcome.

In veterinary medicine, radiation therapy was first attempted at the beginning of the twentieth century. During the last 50 years, large advances have been made. The use of histopathology, MRI, and CAT scans has resulted in accurate diagnosis of the type and location of tumors. New technology has increased the effectiveness and decreased the side effects and risks of radiation therapy.

Under what conditions is radiation therapy used?

Radiation therapy can be used in combination with surgery and/or chemotherapy to provide permanent control or death of a tumor. It is used for tumors that have not spread to other sites in the body and offers a potential cure for some localized tumors. In other cases, radiation therapy can be used for its palliative effect (relieving the signs of disease). Even if the tumor can not be destroyed, at least shrinking the tumor may improve the quality of life of the animal by reducing pressure, bleeding, or pain.

Which tumors are commonly treated with radiation therapy?

Oral tumors and tumors within the nasal cavity often respond well to radiation therapy. Brain tumors have been successfully treated, as have small skin tumors, including some mast cell tumors and squamous cell carcinomas. Lymphoma in both cats and dogs has responded to radiation therapy, and it is often used in conjunction with chemotherapy. The management of bone tumors, including osteosarcoma, has used radiation therapy as part of the regimen.

In considering good candidates for radiation therapy, issues that must be included in the decision-making process include:

• The owner's wishes, commitment, time, and financial resources
• The pet's overall health and presence of any other disease conditions
• The probability of control of the tumor, which must take into account its size, type, location, and any metastasis
• Availability of other treatments, e.g.; surgery, chemotherapy
• Predicted outcome of radiation and other treatments in relation to cosmetic effects and function

How does radiation therapy work?

Using radiation therapy, beams of photons, electrons, or gamma rays are focused on the tumor. When the photon, electron, or wave hits the nucleus of a cell, it alters it, destroying the ability of the cell to divide and grow. The slower growth rate and ultimate death of the cancer cells causes the tumor to shrink over time. Radiation affects both normal and cancer cells, but the radiation treatment is designed to produce the maximum effect on the tumor and minimize the effect on normal tissue.

What are the types of radiation therapy?

There are many types of radiation therapy. Some radioactive particles can be injected into the body and localize in specific tissues. Radiation therapy using iodine, which collects in the thyroid gland, has been used to treat thyroid disease, such as hyperthyroidism in cats.

"Brachytherapy" is the term used to describe the radiation therapy that is administered through radioactive implants. Implants of iridium-192 are the most commonly used. Radioactive wire containing iridium-192 can be placed using a large needle, or through minor surgery. This type of therapy has been used to treat nasal tumors in dogs and fibrosarcomas in cats.

Beams of radiation are the type of therapy most people are familiar with. A linear accelerator can be programmed to produce varying levels of photon or electron beams that are focused on a certain area on or within the body. Large orthovoltage machines, which are very large x-ray machines, form beams of electrons. Cobalt-60 machines produce gamma electromagnetic waves. These beams, or waves, are focused on the tumor, and when the actual burst of radiation therapy is over, no radioactivity remains in the body.

How is beam radiation therapy administered?

During the treatment, the animal will need to be anesthetized because he cannot move during the procedure. During the first session, the animal is placed on the table. Using radiographs (x-rays), MRIs, and CAT scans, the exact location of the tumor is located. Using mathematical formulas and mapping techniques, the machine is programmed and positioned to focus the beam on the tumor. Various points on the animal's skin may be marked to provide "landmarks" for subsequent treatments. This machine setup usually requires 30-60 minutes. The actual treatment time during the following sessions is very short, and the animal is usually anesthetized for only 10-15 minutes.

How often is radiation therapy administered?

When administered with curative intent, radiation therapy is given in small fractions over 2-5 weeks, depending on the size and location of the cancer, the pet's general health, and the type of cancer they have. For palliative effects, radiation therapy is given in large fractions, usually once weekly for three weeks.

What are the risks and side effects of radiation therapy?

Severe toxic effects of radiation therapy in pet animals are rare, and occur in less than 5% of the animals treated. Because the radiation affects all cells, some normal cells with be killed. Side effects of radiation therapy occur more often with curative attempts, and can be categorized into acute and chronic problems. Acute injuries begin during or shortly after the completion of therapy. They arise in tissues within the radiation therapy field that are growing and dividing rapidly. The most common acute effects are skin problems that mimic a severe sunburn, which sometimes causes the animal to scratch. Since the scratching will further traumatize the skin, medications may be prescribed to reduce the itchiness. Hair loss often occurs at the area where the beam penetrates and leaves the body. The hair will grow back with time, but may be darker or lighter.

Oral and nasal tumors may develop a foul odor as they die.

Chronic side effects arise from damage to tissues that slowly replace old, dying, or damaged cells (i.e., bone, retina, brain). Because these cells reproduce slowly, it takes a longer period of time for them to be replaced. Clinical syndromes such as the formation of bony sequestra, retinal lesions, and neurologic signs may appear, depending upon the area of the body being treated. If the eye is near the radiation field, a loss of tears (keratoconjunctivitis sicca) or vision may occur. Chronic side effects are dose limiting, meaning the dose of radiation may need to be limited if chronic side effects are observed. Veterinary radiation therapy protocols are designed to minimize long-term problems.

There is always a slight risk associated with general anesthesia, but the pet is monitored carefully while it is anesthetized, and the duration of anesthesia is generally short. Prior to radiation therapy, each animal is assessed through laboratory tests and a physical examination.

Radiation therapy in pets usually does NOT cause systemic side effects (tiredness, loss of appetite, nausea).

How much does radiation therapy cost?

Depending on the type and number of treatments, radiation therapy may cost $900 - $3,500. The cost is a result of the expensive and complex equipment needed, anesthetic and laboratory costs, and the expertise of the many veterinary health care professionals involved.