Canine Mast Cell Tumors
Mast cell tumors (MCT) are cancerous proliferations of mast cells. Although they can and will spread throughout the body, the danger from mast cell tumors arises from the secondary damage caused by the release of chemicals that they produce. These chemicals can cause systemic problems that include gastric ulcers, internal bleeding, and a range of allergic manifestations. Clearly, mast cell tumors affect both lifespan and quality of life. Sometimes mast cell tumors are referred to as "the great imposters," as there is no way to definitively identify them without a biopsy and pathology report. Mast cell tumors vary widely in their size, shape, appearance, texture, and location. It can be difficult not only to recognize mast cell tumors but to predict their course. They may be relatively innocent or aggressively malignant. As mast cell tumors are very common in dogs, it is important for the regular pet owner to have at least a basic understanding of what they are and how they work.
Mast cells are specialized cells that normally are found distributed throughout the body and help an animal respond to inflammation and allergies. Mast cells can release several biologically active chemicals when stimulated, among them histamine, heparin, seratonin, prostaglandins and proteolytic enzymes. Although these chemicals are vital to normal bodily function, especially immune response, they can be very damaging to the body when released in chronic excess.
Other names: Histiocytic mastocytoma, mast cell sarcoma, mastocystosis (when there is systemic involvement).
Frequency/Location: Mast cell tumors are among the most common tumors in dogs and are the most common type of skin cancer found in dogs. Approximately 1/3 of all tumors in dogs are skin tumors, and up to 20% of those are mast cell tumors. The most common location to find mast cell tumors is, by far, the skin, followed by the spleen, liver, and bone marrow. Approximately half of all cutaneous (skin) MCTís are found on the body proper, another 40% on the extremities (most frequently the hind limbs), and the remainder on the head or neck. Approximately 11% occur in more than one location.
Causes/Predispositions: No one fully understands what causes cancer. Mast cell tumors are very common in dogs, yet they occur far less frequently in cats and very rarely in human beings. They occur in dogs of all breeds, ages, and genders and can occur anywhere on the body. There appears to be a genetic component, as certain breeds are predisposed to developing MCT. Among the most common victims are beagles, Boston terriers, boxers, bulldogs, bullmastiffs, bull terriers, dachshunds, English setters, fox terriers, golden retrievers, Labrador retrievers, schnauzers, American staffordshire terriers, and weimaraners. Boxers are at the highest risk, yet mast cell tumors are often not as aggressive in this breed. There is some suggestion that mast cell tumor development may be associated with golden/red coat color and with chronic immune over-stimulation that occurs in dogs with allergies or other inflammatory conditions. There may be environmental factors, viruses, or other undetermined contributors. Mast cell tumors, as with all cancers, tend to be associated with age. Older dogs are more likely to develop cancerous growths, with the average age of a dog with MCT being 8-9 years.
Prevention: Because the cause is unknown, there is no known way to prevent mast cell cancer. Presumably, the best one can do is to maintain their petís overall health and be alert to signs of tumor growth or ill health.
Diagnosis hopefully begins early when the alert pet-owner notices a growth on his dog. The vet may take a fine-needle aspirate from the growth to submit a sample for preliminary biopsy. The entire tumor will then need to be fully removed, if possible, and submitted for biopsy. Blood tests may include a complete blood count, serum chemistry profile, and buffy coat. The CBC may reflect low or high white blood cell count, low platelet count, elevated mast cell counts. The buffy coat is diagnostic (although subject to false-positives) and reflects mast cells circulating in the bloodstream where they are ordinarily not found in large numbers. A positive buffy coat suggests bone marrow involvement. Other tests may include urinalysis, lymph node aspirate, bone marrow aspirate, x-rays, and ultrasound. The pathologist assigns a "grade" to the tumor, a somewhat subjective assessment of how well differentiated the cells are and therefore how aggressively malignant the cancer appears to be. The practicing veterinarian and/or oncologist assigns a "stage" to the cancer, as well. The supplemental lab work gives an estimate of how great a foothold the cancer has, and this is reflected in the staging.
Histiologic Grade: The pathologist will apply specialized stains to the tumor sample and microscopically examine it in order to determine its grade. AgNOR staining appears to be the most conclusive prognosticator for mast cell tumors. Tumor grade is associated with the degree of differentiation of the mast cells. The majority of MCT are Grade 1 tumors and are well differentiated and appear to have a very good prognosis with no treatment beyond complete surgical removal. Grade 2 tumors are moderately differentiated, and the prognosis and treatment options are perhaps most complicated and difficult to predict. Grade 3 tumors are poorly differentiated, very aggressive, and most likely to rapidly metastasize. They carry the poorest prognosis but are fortunately the least common. Histiologic grade is most predictive of prognosis.
Stage: Staging refers to degree to which the cancer has already spread at the time of diagnosis. Tumors caught early - before they have invaded other tissues or caused signs of systemic disease - logically carry the most optimistic prognosis. MCT most commonly metastasizes to lymph nodes, bone marrow, liver and spleen, so much of the lab work focuses on these areas to detect and assess abnormalities. It is unusual for MCT to spread to the lungs, as is so common with many cancers. In simplest terms, Stage 1 refers to a single tumor with clean margins and no signs of spreading. Stage 2 and Stage 3 show progressively greater signs of invasion, perhaps to local lymph nodes, demonstrating dirty margins, or presenting as multiple tumors. Stage 4 involves systemic metastasis and carries a grave prognosis.
Local symptoms: The most obvious sign of mast cell cancer is likely to be a tumor of some sort. Mast cell tumors can appear singly, in groups, lie on the surface of the skin or underneath it, crop up anywhere on the body, and defy easy description. You just donít know itís a MCT by looking at it. Most (at least half of) mast cell tumors are found in or under the skin on the trunk of the body itself, and the vast majority of the remainder are found on the extremities, especially the hind limbs. They are less commonly found on the head and neck, and less commonly still arise from tissues other than the skin. If they are very swollen or ulcerated, there may be pain, but most MCTís are unlikely to be painful. It has been observed that higher-grade tumors may be more likely to be ulcerated in appearance and cause local irritation.
One characteristic quirk of mast cell tumors is the tendency for them to change in size, even on a daily basis. A tumor that gets bigger and smaller, seemingly on a whim, may be a MCT. Another idiosyncrasy is the potential of the tumor to produce "Darierís sign" if poked and prodded. Handling these tumors - even a routine veterinary palpation or needle aspirate - can cause a heavy release of histamine that results in swelling, redness, itchiness, hives (wheal formation).
Systemic symptoms: Symptoms are variable, depending on the location of the tumor and the degree to which is has developed and/or spread. Signs of systemic involvement may include: loss of appetite, vomiting, bloody vomit, diarrhea, abdominal pain, dark or black feces, itchiness, lethargy, anorexia, irregular heart rhythm and blood pressure, coughing, labored breathing, various bleeding disorders, delayed wound healing, enlarged lymph nodes.
Treatment for mast cell tumors almost always first involves surgically removing the entire tumor, if that is possible. It is particularly important to remove a wide margin or large area of healthy tissue (2-3 cm in each direction) around the perimeter of the tumor. The idea is to capture any stray cancerous cells that arenít immediately obvious. In some areas, such as a leg or paw, it is virtually impossible to remove sufficient tissue to satisfy this 2-3 cm oncological rule. The tumor is then submitted to a laboratory for biopsy, and a pathology report is generated. Very important is the determination of whether or not the margins of the submitted tissue removal are clean (showing no signs of cancerous cells) or dirty (showing invasion of cancerous cells). If the margins are dirty, further surgery or radiation may be indicated to attempt to remove or kill any remaining cancerous cells. Nonetheless, a significant proportion of tumors that are incompletely excised (i.e., dirty margins) do not return.
Beyond complete surgical excision, treatment options depend on factors that suggest the aggressiveness and status of the cancer. Low-grade tumors are generally treated locally with surgery, with or without radiation. High-grade tumors may be treated systemically with prednisone and/or other chemotherapy. Sometimes the only "treatment" is supportive care intended not to extend the dogís life but to make what remains of it as comfortable as possible.
Local treatments: Surgery is used to remove local cancerous tissue when possible. Sometimes surgical sites for MCTs are resistant to healing. Radiation may be used afterwards to locally kill off remaining cancerous cells. Sometimes radiation is used in place of surgery to shrink tumors that cannot be easily operated on. Radiation is highly effective in controlling mast cell cancer, yet radiation is not for everyone. Dogs treated for mast cell tumors may have 3-5 radiation sessions per week for 3-5 weeks and must be anesthetized for each treatment. This may cost several thousand dollars, may require travel and/or boarding during the treatment period, and may have short or long-term side effects that owners find objectionable.
Systemic treatments: Prednisone (a corticosteroid) appears to be the drug of choice in treating mast cell cancer, so much so that many veterinarians will routinely prescribe several weeks or months of prednisone subsequent to surgical removal of any mast cell tumor. In the great scheme of things, prednisone is inexpensive and safe. Side effects include increased drinking, urination, and appetite and potential gastrointestinal upset. If a tumor has a reasonably high metastatic potential, or if it has already metastasized, prednisone is likely to be prescribed.
Sometimes other chemotheraputic drugs are used in combination with prednisone if the mast cell cancer appears to have metastasized. These may include: CCNU (lomustine), vinblastine, vincristine, doxorubicin, mitoxantrone, cyclophosphamide (cytoxan), and L-asparginase. These are all heavy-duty drugs with potential side-effects that include severe immunosuppression, vomiting, diarrhea, liver damage. Several studies seem to demonstrate their limited efficacy in conjunction with surgery, but in and of itself, chemotherapy is no match for inoperable or metastatic mast cell cancer. Responses to chemotherapy are minimal in cases of MCT.
Palliative treatment (supportive care): Sometimes one cannot do anything more than offer supportive care to a dog with mast cell cancer. The cancer may have spread too far. The dog may be old or have other health impairments. The owners may object to more aggressive treatment. It is the inability to manage such things as vomiting/diarrhea from gastric ulceration that typically marks the end of quality of life for the dog with mast cell cancer. Thus, controlling symptoms may be more important than battling the cancer, per se.
Various drugs are used to prevent or manage potential problems caused by the chemicals that mast cells release. In effect, one isnít addressing the cancer itself. One is simply trying to maintain quality of life by fighting the deleterious effects of the chemicals secreted by the mast cells. Corticosteroids like prednisone, antihistamines like benadryl, and antacids like tagamet, zantac or pepcid are often used as a matter of course after surgery and/or radiation and are routinely used to maintain comfort in dogs where the cancer cannot otherwise be treated or has spread. Sucralfate may be helpful with dogs that have bleeding ulcers, as it coats the surface of the ulcer to protect it and allow for healing. Further, there are now special foods available for dogs with cancer - like Hills Prescription Diet n/d - which are intended to preferentially nourish the patient but not the cancer itself, thereby increasing both quality and length of life.
Recurrence: Dogs who have had mast cell tumors are more likely to develop more mast cell tumors. 50% of surgically removed mast cell tumors will re-grow in the same area.
Prognosis: Prognosis is highly variable and dependent on many factors including tumor location, histiologic grade and clinical stage. One statistic suggests that approximately half of all MCTís are curable with complete surgical removal and prednisone treatment. Dogs that are tumor-free after 6 months are considered unlikely to have a recurrence. Primary tumors that originate in areas other than the skin tend to be more aggressive than cutaneous tumors. MCT in preputial (sheath), perineal (groin), subungual (nail bed), and oral regions areas are generally the most malignant. MCT of bone marrow or visceral tissue is particularly grave. The higher the grade or stage, the worse the prognosis. Boxers are especially at risk for developing mast cell tumors, yet they tend to have less aggressive (lower grade) MCT than other breeds. Dogs showing systemic signs and dogs whose tumors return after surgical removal have poorer prognosis. Similarly, the faster the growth of the tumor, the worse the prognosis. One study found that dogs with tumors that grow more than 1cm per week have only a 25% chance of surviving 30 weeks. MCT's that exist locally for several months without showing signs of rapid growth tend to be benign.
Prognosis/Grade-1 MCT: A grade 1, stage 1 cutaneous MCT is likely to never return after surgical removal. The estimated long-term survival rate for dogs with such tumors is over 90%.
Prognosis/Grade-2 MCT: It is reported that 50-75% of dogs with Grade 2 MCT survive long-term (beyond 35 weeks). Another study concluded that 44% of dogs with Grade 2 MCT survived long-term (over 4 years) after nothing more than complete surgical removal of their tumors. Yet another author reports a 45% mortality rate.
Prognosis with radiation: Radiation may increase survival. One study concluded that 86% of its subjects, dogs with Grade 2 MCT, survived long-term (over 5 years) with a combination of surgery and radiation (compare that to the 44% mentioned in the previous paragraph). Another author cited a 48-77% remission rate for treatment plans that included radiation. Yet another study reported a 94% disease-free rate at one year in dogs with Grade 2 MCT (dirty margins) after surgery and radiation, and an 86% disease-free rate after 5 years. And another study still reflects a 75% survival rate two years after radiation and prednisone treatment. As with anything, any research results need to be taken with a grain of salt unless the entire research protocol is examined. These are merely statistics that one can readily discover in various citations online and in books. Nonetheless, they all appear to suggest that radiation after complete surgical removal is statistically the most effective way to combat (primarily Grade 2) MCT.
Prognosis with prednisone: Prednisone, with or without other chemotherapy, is estimated to induce partial or complete remission in approximately 20% of canine patients with MCT. The reason for prednisoneís effectiveness is not fully understood, yet its use is pervasive in treating this condition.
Prognosis/Grade-3 MCT or metastasis: Only 15% of dogs with Grade 3 MCT will be alive 7 months after surgery, and only 6% will be alive after 2 years. Once mast cell cancer has metastasized, dogs tend to die within 6 months as the symptoms of systemic illness (e.g., gastric ulcers) can no longer be managed and the animal loses its quality of life.
Bottom line: Mast cell tumors occur frequently in dogs. They are well documented and well understood in some respects, yet they are unpredictable in appearance and behavior. No one knows what causes mast cell cancer, nor how to cure it with certainty once it has metastasized. The best one can do as a pet owner is be attentive to the general health of oneís dog and get all unusual lumps and bumps examined carefully to rule out MCT or to catch it in the earliest stages. MCT can be lethal, but it is not necessarily so. If youíd like to send me the details of your experience with mast cell cancer in your dog, Iíd be fascinated to read it. Perhaps I can compile a section with this information at some point in the future.
Disclaimer: I am not a veterinarian, nor do I have any particular veterinary/scientific/medical training or knowledge. I donít even play a vet on tv. This article represents my understanding, as a layperson, and is intended merely as a starting point for the fellow layperson/pet-owner. I assume no responsibility for inaccuracies. As always, consult with a qualified veterinary professional to assess and manage your petís health. Please notify me if you encounter factual errors or would like to further my understanding of the above condition.
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