Dr. Gail Mason, DVM, MA, DACVIM
Kathi L. Smith, RVT
Mast cell tumors (MCTs) are fairly common tumors in dogs. They are most frequently found in the superficial layers of the skin, on any part of the body. Frequently, there will be ulceration over the area of the tumor, and the dog may scratch or bite at the affected area. The appearance of the tumor does not reveal its potential for spread or recurrence with any certainty. The tumors are usually singular, but dogs may present with multiple nodules, or recurrent ones. Some nodules occasionally enlarge and then regress in size on their own, due to swelling within the tumor itself. This should always raise the suspicion of the presence of an MCT.
Diagnosis of Mast Cell Tumors
Mast cell tumors do not have a specific appearance. However, they are fairly easily detected by a "needle aspirate and cytology." Insertion of a small needle into the tumor (virtually painless) area is followed by examination of the cells under a microscope. Mast cells are large, round cells that usually have dark granules in them. The granules contain substances which, when released, cause swelling, itching, and redness. Infrequently, when a large number of granules spontaneously discharge their chemical contents into the bloodstream, vomiting, stomach ulcers, shock and even death may result.
Mast Cell Tumor Staging
Mast cell tumors can be somewhat unpredictable in their behavior, relative to other types of tumors in dogs. Because of this, care is taken to "grade" the tumors that are discovered. The grade reflects the degree to which the malignant mast cells differ from normal, non-malignant mast cells. The stage can generally be correlated with tumor behavior, tumor recurrence, and survival of the patient. Mast cell tumors affecting the limbs, head, or neck tend to correlate with a more favorable prognosis than those found on the trunk or groin. Multiple mast cell tumors or those exhibiting rapid growth tend to have a more guarded prognosis. A pathologist determines the tissue grade of the tumor after the tumor is biopsied or removed.
*Grade I: well-differentiated-25% recurrence rate post-surgery
*Grade II: moderately differentiated-44% recurrence rate post-surgery
*Grade III: poorly differentiated-76% recurrence rate post-surgery
Treatment for Mast Cell Tumors
Treatment for mast cell tumors may involve surgery (the mainstay), chemotherapy, and/or radiation therapy. Recommendations for treatment are based on the type and grade of the tumor, surgical feasibility, and the presence or absence of spread (dissemination) of malignant mast cells throughout the body. Your veterinarian will usually submit blood tests and request abdominal ultrasound or radiographs (x-rays) to determine the likelihood of malignant mast cells elsewhere in the dog's body. Bone marrow biopsies are no longer routinely done, as they have not shown to have high predictive value for tumor staging.
For single mast cell tumors, a surgical procedure known as a "wide resection" by an experienced surgeon is performed. This means aggressively excavating the tumor and surrounding tissues so that at least 2-3 cm of normal tissue in all directions is removed. This must include a "deep margin" which involves removing tissue below the tumor. The margins of the removed tissue are marked and examined by a pathologist to determine the presence of any lingering malignant cells. If negative, we refer to it as "clean margins". If the pathologist suspects the presence of mast cells in the remaining tissues of the surgery site, we refer to it as "dirty margins". If the remaining, malignant cells are less than 2 cm from the edge of the biopsy specimen, it is referred to as "close margins".
An aggressive surgery early in the course of mast cell tumor disease is associated with the best overall prognosis. A grade I or II tumor that has been completely removed usually requires no other immediate therapy. A grade III tumor, multiple tumors, recurrent tumors, or tumors with dirty margins (those which for anatomical reasons could not be subjected to further surgery) often require follow-up or "adjunct" therapy.
Radiation therapy is an option for dogs whose mast cells tumors are localized, but too large for a clean resection or in an area difficult to resect such as tissues of the facial region, or as follow-up therapy for tumors with dirty margins. Dogs tolerate radiation therapy well, and it can offer long-term control for these tumors. Radiation therapy would not be appropriate for dogs with multiple tumors or those with evidence of disease throughout the body since the radiation beam treats only a single focus of disease. Radiation treatment can be accessed at New England Veterinary Oncology Group (NEVOG) in Waltham MA., Angell Memorial Animal Hospital in Boston, MA. and Tufts University School of Veterinary Medicine in Grafton, MA. This is a highly specialized form of therapy and we are pleased to refer your pet to these centers if need arises.
Chemotherapy denotes the administration of certain anti-cancer drugs in order to delay/prevent tumor growth or spread. It may be used before or after surgery, or alone.
Prednisone (a cortisone) is the most commonly used drug for therapy of mast cell tumors. It is well tolerated by dogs and is usually employed for a minimum of six months. If no new tumors appear within that time, your doctor may wean your dog off the prednisone completely. The side effects of prednisone include weight gain, increased appetite and thirst, bladder or skin infections, and panting. Occasionally, stomach irritation or ulcers can occur, or inflammation of the pancreas. Most of the time, the drug dose can be titrated to the patient to minimize any overt symptoms. If the tumor type is determined to be aggressive, additional drugs such as stomach protectants may be prescribed to guard against untoward tumor effects. By itself, prednisone is considered to have only mild anti-cancer effects on MCTS.
If your pet is deemed to have an increased risk of tumor recurrence, we may recommend combination oral therapy with prednisone and chlorambucil (Leukeran¨). Chlorambucil is a chemotherapy drug that is extremely well tolerated in most patients and yet offers more tumor protection than prednisone alone. This drug is usually administered twice weekly and requires that your pet be monitored at least every 6-8 weeks. The minimum treatment period is 6 months.
For recurrent or multiple tumors, and for those tumors that cannot be surgically removed, combination chemotherapy can be effective in controlling tumor growth and spread for weeks to months or more. A cure per se is generally not realistic, but many dogs tolerate therapy extremely well. The six-month protocol involves:
Prednisone: high dose at first, then taper over 4 months
Vinblastine: an outpatient injection, given once every 21 days
Cyclophosphamide (Cytoxan¨): an oral chemotherapy drug, given by the owners on days 8,9,10, and 11 of a 21-day cycle.
This protocol has produced a 1 and 2 year survival rate for grade 2 tumors of 91%. For patients with grade 3 tumors, the 1-year survival rate is 66%.
The side effects of prednisone are discussed above. Vinblastine and Cytoxan have the ability to cause nausea and or vomiting, though this is not usual. The most important possible side effects are lowering the body's defenses so that infections occurs, or (rarely) causing many mast cells to release their contents at once. Both situations can be life threatening. However, these are NOT common, and the risk of these is significantly lower than the risk of untreated mast cell disease. You will be given instructions on what to do if any side effects occur, so do not hesitate to contact us.
CeeNu is a potent oral chemotherapy drug that can be used once every three weeks in patients who MCTs have become resistant to other treatments. It is very well tolerated in general. However, because it can increase the risk of infection (especially seven days after it is given), any noted fever, depression, weakness, or refusal to eat should be reported to us or your veterinarian, or an emergency hospital immediately. Infection is almost always completely reversible. This drug is more potent than Cytoxan¨ and maybe substituted for it if indicated. Occasionally, this drug may decrease patient blood cell counts, which requires a dose reduction or discontinuance.
The factors that are known to influence patient outcome are grade of tumor (I is best, III is most dangerous), completeness of surgical removal (clean margins), and tumor location. Dogs with high-grade tumors, multiple or recurrent tumors, or evidence of spread to the bloodstream or other organs have a much more guarded prognosis for a lengthy survival.
Close patient monitoring is essential in dogs with a history of mast cell tumors. As with many tumors, early detection and treatment increases the chances of successful treatment. You may be asked to have your dog examined and monitored every 6-8 weeks following surgery, or every 21 days during chemotherapy. Blood tests and/or needle aspirates are often requested to assess tumor control. Any time you suspect a new or recurrent tumor, or that your dog is physically ill, contact us immediately. We welcome the opportunity to help you and your dog in any manner we can.
Reference: Mast cell tumors in dogs; In: Managing The Veterinary Cancer Patient; Ogilvie, OK and Moore, As. © 1995 Veterinary Learning Systems. Trenton, NJ. *Based on protocol published by Elmslie, Robin; published in the Veterinary Cancer Newsletter.