Cutaneous Mast Cell Tumors in Dogs
Signs and Symptoms
Cutaneous mast cell tumors (Mastocytomas, Mast Cell Sarcomas) are a form of skin cancer and the most common cancer occurring in dogs. While only 20% of the skin tumors seen in dogs are malignant or have the potential to become malignant, cutaneous mast cell tumors are particularly dangerous due to the unpredictable nature of this cancer. Mast cell cancer is extremely rare in humans, and very little research had been done until recently on canine mast cell tumors. Increasing numbers of research studies are currently being run by the scientific community exploring the causes of mast cell tumors, the effect this form of cancer has upon dogs, and the most effective treatment methods.
Most skin growths or lumps that you may find on your dog are benign and will not require any intervention at all. Following is a list of the most common forms of benign skin growths in dogs:
Cysts – Very common, and can develop anywhere on a dog’s body. Sebaceous cysts are small benign growths forming in the hair follicle that are filled with keratin, a cheese-like substance. Sebaceous cysts should be removed or drained to prevent infection.
Hematomas or bruises – A collection of blood beneath the skin or within a muscle that is caused by an injury, and will usually resolve without intervention. Ear flap hematomas are the result of severe head shaking in due to intense itching from ear infection or ear mites. Large hematomas should be drained and the underlying cause treated.
Histiocytomas – Develops on the feet, face, and ears of young dogs. They are dome-shaped, appear irritated, and are painful to the touch. Some histiocytomas will resolve on their own, while others may need to be removed.
Lipomas – Benign fatty tumors that grow beneath the skin or within a muscle, and are most commonly seen in overweight female dogs. These tumors are enclosed within a thick, fibrous covering, and are usually small, round, and smooth. They are not painful but can grow very large and infringe upon joint movement or internal organs, requiring removal.
Papillomas – Has the appearance of a piece of chewing gum stuck on the surface of the skin, or a skin tag. They are benign, but should be removed if they become irritated or start to bleed. Warts can develop in older dogs, and usually will not cause any problems unless the dog worries them and causes them to start bleeding.
A mastocytoma is a collection of normal mast cells that resembles a neoplasm, which is any abnormal growth of tissue that has no function. Mastocytomas may be either benign or malignant.
Approximately 20% of all skin tumors or growths occurring in dogs are malignant mast cell tumors. The most common sites that mast cell tumors are found are the limbs, abdomen, chest, and genital area. If the mast cell tumor is located on back, this is usually a more aggressive form of cancer. These tumors can develop anywhere on the body: on the surface of or below the skin, on internal organs, within muscles, lymph nodes, bone marrow, or leukemia.
Mast cell tumors can be multiple, single, smooth, nodular, raised, bumpy, and may ulcerate. The masses can feel either soft or solid to touch, and may actually change in size; growing larger then shrinking again. Mast cell tumors may seem to have distinct margins, but usually do not, since the main tumor is surrounded by many microscopic mast cells having the appearance of normal skin.
Small mast cell tumors can remain unchanged for long periods of time then quickly become aggressive. Due to the large variety presentation of mast cell cancer, it is best to treat all new or unusual growths as potential malignancies, and have them checked by your veterinarian.
Diagnosis of mast cell cancer will begin with a physical exam of your dog by your veterinarian, followed by questions to determine if your pet is exhibiting any signs and symptoms of cancer. A blood panel and urinalysis will be ordered to determine the overall health of your dog. The blood will be examined for the presence of mast cells, which are not normally found in the bloodstream.
Part of the blood sample will be placed into either a test tube or capillary tube and centrifuged to separate the red and white blood cells. The white blood cell layer that floats above the red blood cell layer is called the buffy coat. The layer of white blood cells is then smeared onto a slide and checked with a microscope for mast cells; if present, mast cells in the bloodstream indicates the presence of mast cell cancer within the bone marrow. A bone marrow biopsy may be done to determine the presence and/or amount of malignant mast cells in the bone marrow.
A radiograph (X-ray), or abdominal ultrasound will be done to measure the size of spleen, which is part of the lymph system, to check the size and number of lymph nodes affected in the chest and abdomen, and to also measure the size of the liver. An ultrasound will be used if a biopsy of an internal organ or fine-needle aspiration of lymph nodes is to be done. Mast cell cancer usually will not spread to the lungs, but it is important to see how much of the lymph system is affected.
A biopsy of the tumor is very important, and should be done prior to its removal or the beginning of any other treatment. To perform a cytologic evaluation, or cell examination, a small amount of tissue is removed from the tumor with a very fine needle, the cells are smeared onto a slide and Wright-stain is applied. Malignant mast cells are identified by the take up of the stain in a distinctive and unmistakable manner.
Histopathology, where the tumor cells are examined under a microscope by a pathologist, should then be done to determine the margins and grade of the cancer in order to determine a prognosis. It is very important that histological diagnosis is done, since cytological evaluation alone does not provide a completely accurate diagnosis and definitive prognosis.
All of the above tests should be completed prior to surgery to remove the mast cell tumor. If the tumor is diagnosed as mast cell cancer, a large amount of surrounding tissue and skin must be removed to ensure complete removal of all malignant mast cells, and it is best to attempt to get all of the cancer during the first surgery, and avoid repeat surgery or recurrence of the cancer.
Mast cell tumors are graded as to how likely they are to be malignant:
Grade I Tumors – Found 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 Tumors – Extend below the skin. The cells appear abnormal, indicating malignancy, and their response to treatment can be unpredictable.
Grade III Tumors – Invade areas deep below the skin, possibly into the chest and abdomen, are malignant and very aggressive and invasive in their growth, require more involved treatment, and response to treatment is not good.
Staging of the mast cell tumor is also done, which measures how much the cancer has spread throughout the dog’s body. A tumor is staged after it is surgically removed along with local lymph nodes, and examined microscopically. Staging is based on the number of tumors, how many lymph nodes are involved, and whether or not the entire tumor was removed.
Stage I: One tumor in the skin, with no lymph node involvement.
Stage II: One tumor in the skin with local lymph node involvement
Stage III: Multiple large, deep tumors, with or without lymph node involvement
Stage IV: One or more tumors with metastasis with lymph node involvement, or tumor recurrence with metastasis following previous treatment.
Substage A: Negative for other clinical signs
Substage B: Positive for some other clinical signs
The location of the tumor, its grade and stage, and the symptoms your dog is exhibiting will provide the clearest picture of the severity of the cancer, the best treatment plan, and the prognosis.
Pathophysiology and Psychology
Mast cells are large tissue cells that are found throughout the body in connective tissues; but are found in the largest numbers below the skin and mucous membranes lining the digestive and respiratory tracts. Mast cells are essential for normal local immune response to allergens; they release histamine, prostaglandins, leukotrienes, and proteinases (enzymes that break down proteins) within the cell in response to allergens. Another chemical released by malignant mast cells is heparin, which affects how well the dog’s blood will clot.
The immediate hypersensitivity reaction from the above chemicals causes hives, redness, itching, and swelling as a normal and necessary response to a foreign substance. However, malignant mast cell tumors release large amounts of these vasoactive chemicals, which cause unpredictable allergic-reaction type responses throughout the dog’s body. Extremely large amounts can be released when the mast cells are damaged or removed, or with no stimulation at all. Histamine, specifically, affects heart rate and blood pressure, can cause vomiting, bloody stools, abnormal blood clotting, and duodenal ulcers.
Mast cell tumors can become ulcerated, and when surgically removed the site may not heal in up to 10% of cases; becoming a major problem. Mast cell tumors can be very aggressive and invasive in their growth, and commonly spread to the lymph nodes, liver, spleen, and bone marrow.
Most dog cancers occur in later age; about 80 percent of all older dogs will develop cancer. While the cause of mast cell tumors is unknown, there is most likely an environment factor involved. Just as with humans, everything a dog is exposed to – whether it is in food, water, air, or other environmental carcinogens, which includes naturally-occurring or man-made chemicals, heavy metals, and secondhand smoke.
Mast cell tumors can develop in dogs of any age and breed, but 8-10 year old dogs have the highest incidence of the cancer. Normal cell division becomes less precise as a dog ages, with increased chances of cell mutation and the subsequent development of many different forms of cancer. A less severe form of mast cell cancer usually occurs in young dogs.
There may be a hereditary factor, since multiple mast cells tumors are most frequently seen in Boxers and Pugs; while Boston Terriers and Rhodesian Ridgebacks are also predisposed to developing mast cell tumors. Some dogs have a decreased ability to detoxify carcinogens and repair cell damage; they may even respond less well to certain compounds due to hereditary factors.
One controversial theory has hypothesized a possible viral cause for the development of mast cell tumors, but there is little supporting scientific evidence.
Treatment of mast cell cancer depends on clinical grade and stage, and the aggressiveness of the cancer. The best prognosis when the mast cell tumor is located on a dog’s limbs; a poorer prognosis if the tumor is located on a dog’s nail bed, genital areas, muzzle and mouth; with the least favorable prognosis if the cancer has invaded internal organs, spleen, or bone marrow.
Surgery is the treatment of choice for mast cell tumors, and will usually cure Grade I and Grade II cancers. Since mast cells invade surrounding healthy tissue, at least 3 cm of healthy tissue must be removed surrounding the tumor on all sides and below. During the surgery, cell samples should be examined for mast cells, and tissue should be removed until the skin is found to be completely free of mast cells. In some cases surgical removal may not be an option, depending upon where the tumor is located. In up to 50% of dogs, the tumor may reoccur with surgical removal alone. If microscopic histologic evaluation of cell biopsy discovers that tumor extends beyond the surgical margins after surgery, another surgery should be done to remove the affected tissue.
Mast cells are sensitive to radiation, which is commonly used to treat mast cell cancer. Radiation therapy done either during surgery or as follow-up treatment may be effective if the remaining tumor is small or can only be seen microscopically, and has not metastasized. Radiation therapy after surgical removal appears to be beneficial and may reduce the incidence of reoccurrence and increase survival rates. While radiation therapy itself is not painful, some side effects can occur and usually begin after a number of treatments. Side effects include hair loss, skin burn similar to sunburn and occasionally ulcerated areas, and generally subside around two weeks after treatment ends.
Chemotherapy may also be used along with surgery and radiation using the a drug such as vinblastine, vincristine, and lomustine, along with corticosteroids. Prednisone and vinblastine are used as chemotherapy when surgical removal of the tumor is incomplete, and have shown to increase survival time up to two years for dogs with Stage III tumors. One side effect of chemotherapy is neutropenia, which usually occurs seven days after the treatment and predisposes a dog to developing an infection.
Currently, there is no standardized treatment for Stage II through IV mast cell tumors. Treatment of Stage II tumors is surgical removal of the tumor and all affected lymph nodes, prednisolone, and radiation therapy. Treatment of Stage III or Stage IV tumors is generally palliative; aimed at reducing the effects of the vasoactive chemicals and aimed at making your dog comfortable. One recommended therapy is prednisolone or injections of triamcinolone directly into the tumor. One current study has found that vinblastine and prednisone is the treatment of choice for Grade III MCTs following surgical removal of the tumor.
Pre- and post-operative treatment with steroids and H1-blockers or antihistamines such as Benadryl, and H2-blockers, such as Pepcid, may be used for dogs with systemic disease or clinical signs of histamine release. Histamine blockers can decrease the affects of the inflammatory response, thereby treating the secondary effects of the tumor.
Prognosis for completely removed Grade I and II mast cell tumors is excellent, and the prognosis for incompletely removed tumors with follow-up radiation treatment is almost as good. The prognosis for Grade III mast cell tumors is guarded due to the high rate of recurrence; most likely chemotherapy will be used. While only 5% of mast cell tumors are visceral, occurring within the abdomen, most of these are fatal.
There have been increasing numbers of scientific studies being conducted over the past few years, researching all aspects of canine malignant mast cell cancer, the causes, better diagnostic testing, and appropriate treatments. Scientific research is currently being conducted on recombinant gene therapy for the treatment of mast cell cancer, as well as many other cancers affecting dogs. Retinoids, derived from vitamin A, have been found to be effective in reducing the amount of cell growth causing the malignant mast cell to die. Specialized cell markers, called proliferation markers, are being studied as a better method for determining a dog’s prognosis.
It is a very good idea to give your dog a mini-exam for skin cancer once a month. First thoroughly inspect your dog’s skin for any changes in color or texture; then run your hands over her body feeling for any new growths or swellings. There is also one simple diagnostic test, called Darier’s sign, that you can perform at home if you find a suspicious-looking growth on your dog’s skin. Rub your thumb quickly and firmly across the growth a number of times; if there are malignant mast cells present the area will redden and swell into a wheal (hive), and become itchy from the release of histamine. While not a definitive test for mast cell cancer, this is a step along the diagnostic journey, and another sign and symptom you can report to your veterinarian.
When dealing with mast cell tumors with the large variety of presentations, and the oftentimes unpredictable response of some dogs to treatment, it is important to remember that each animal should be evaluated and treated individually. Prompt recognition and treatment is the most important factor in obtaining the best possible outcome for your dog.
For Additional Information: Common Signs of Cancer in Dogs
Vitamins & Dietary Supplements can boost your dog’s immune system and help prevent the development of cancer. If your dog has been diagnosed with cancer, the following products can provide nutritional support to assist them in their fight against the disease: