Mast Cell Tumors – From Benign to Malignant to Somewhere In-between
Mast cell tumors are the most common cancerous skin tumor seen in dogs. Mast cell tumors are tumors of the mast cells, which are immune cells normally functioning in allergic reactions. Mast cells contain various chemical mediators that are released upon some sort of external stimulation. I typically use the example of a mosquito bite on your skin: Mast cells release chemicals in response to the substance injected by the mosquito, and this causes the development of a pesky, itchy red bump.
Mast cells are also involved in anaphylactic reactions to things like peanuts or shellfish. In these instances, mast cells are releasing their chemicals on a more “global” scale in the body, causing swelling of the airways and lowering blood pressure, which can even lead to death.
Cutaneous mast cell tumors in dogs can be extremely challenging as it seems no two tumors behave alike, even in the same dog. Some dogs develop a single tumor during their lifetime and never have any evidence of recurrence or spread after it has been surgically removed. Other dogs develop multiple tumors in their skin at the same time, or develop one tumor every year like clockwork. Some others may experience regrowth of a tumor soon after surgery, which can then spread malignantly through the body at a rapid rate.
Among many variables, the biggest predictor of the behavior of a cutaneous mast cell tumor in a dog is something called the histological grade. The grade of a cutaneous mast cell tumor can ONLY be determined through a biopsy. There are currently several grading schemes for mast cell tumors; the most commonly used is the 3 tier Patnaik scale, which designates tumors as grade 1, grade 2, or grade 3.
Grade 1 tumors are invariably benign in their behavior, and are generally considered cured following surgery.
On the other end of the spectrum are grade 3 tumors, which are considered invariably malignant. They tend to recur following surgery, spreading to regional lymph nodes and internal organs with a high frequency that can be rapidly fatal.
Grade 2 tumors fall in the middle, which can be a diagnostic and therapeutic challenge for oncologists. Most grade 2 tumors behave like grade 1 tumors. However, some grade 2 tumors behave in a very aggressive fashion. As a veterinary oncologist, these are my most difficult cases as it can be very hard to predict which grade 2 tumors will “behave badly.”
A new and exciting anti-cancer treatment option has recently been made available to veterinary oncologists in the United States for the treatment of cutaneous mast cell tumors in dogs. Two new oral chemotherapy drugs in the family of receptor tyrosine kinase inhibitors (TKI’s) are currently licensed for use in dogs: Palladia (toceranib phosphate) was the first drug to be approved by the FDA for treating cancer in animals, and approval of Kinavet (masitinib) soon followed.
Receptor tyrosine kinase inhibitors (TKIs) are targeted anti-cancer therapies. This class of drugs has caused significant excitement in the human cancer field. The most widely known receptor TKI for people is Gleevec (imatinib mesylate), a drug that has revolutionized the successful treatment of human gastrointestinal stromal tumors and chronic myelogenous leukemia. Both Palladia and Kinavet are multi-receptor TKIs, similar to Gleevec, that target mutated receptors involved in both cellular proliferation and tumor angiogenesis (blood vessel growth) pathways.
Specifically, mutations in the receptor tyrosine kinase, or KIT, occur in 20-30% of grade 2 and 3 canine mast cell tumors. Palladia and Kinavet successfully target mutated KIT receptors in mast cell tumors. Palladia is indicated for the treatment of grade 2 and 3 recurrent mast cell tumors, with or without lymph node metastasis. Kinavet is licensed for the treatment of recurrent (post-surgery) or nonresectable Grade II or III cutaneous mast cell tumors in dogs with no previous treatment with radiation therapy and/or chemotherapy except corticosteroids.
Exciting information from preliminary clinical trials indicate Palladia may also have activity against cancers other than mast cell tumors, making this drug an option for patients who previously may have had little or no opportunity for treatment. Published information is not currently available about the use of Palladia in cats. However, preliminary studies indicate this drug is safe to administer to cats, and we have personally successfully used Palladia to control a variety of cancers in our feline patients as well.
TKIs are a unique form of anti-cancer therapy for animals. They are available as oral tablets designed to be administered either daily or every other day at home by the owners, rather than being given intravenously at the veterinarian’s office as we do for most other chemotherapy drugs.
Initially, patients receiving these drugs are scheduled for monthly rechecks with comprehensive physical exams and labwork for the first 6 months of therapy. Rechecks are sometimes reduced to an every-other-month basis, depending on the patient’s status. Treatment is continued for 12 months or longer, depending on tumor control. The major toxicities seen with TKIs are adverse gastrointestinal signs rather than hematological toxicity as seen with other traditional chemotherapy agents.
If you or your veterinarian feel that your dog could benefit from treatment with a TKI, please consider referral to a veterinary oncologist to discuss the pros and cons of treating your pet with this family of drugs so that further diagnostic and therapeutic options can be discussed.
Dr. Joanne Intile