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Canine Mast Cell Tumors

Mast cell tumors (MCT) in dogs are very common, accounting for approximately 20% of all skin tumors in dogs.

For most dogs, the underlying cause promoting the development of the tumor is not known. Mast cells are specialized cells derived from stem cells in the bone marrow and play an important role in helping an animal respond to inflammation and allergies. They are found distributed throughout the body, predominantly near blood vessels, nerves, and beneath the skin. Mast cells become activated when antigens bind to receptors on their surface and subsequently release several biologically active chemicals stored in their granules when stimulated including histamine, heparin, serotonin, prostaglandins, proteolytic enzymes, and other pro-inflammatory molecules. Although these chemicals are vital to normal bodily function, they can be very damaging to the body when released in chronic excess. These chemicals can cause systemic problems that include gastric ulcers, internal bleeding, and a range of allergic manifestations.

Mast cell tumors can arise from any skin site on the body and can have a variety of appearances. MCT most commonly are seen as solitary lumps or masses in or underneath the skin; occasional dogs can have multiple masses. MCT can look like just about anything ranging from benign-appearing lumps, to more angry or ulcerated lumps, masses with a stalk, or focal thickenings in the skin. MCT may change quickly in size because of reactions around the mass and release of their vasoactive compounds. In most cases, evidence of an MCT is easily generated by examination of a fine-needle aspirate of the suspect mass, and aspiration is advised before removal of a mass to determine if it is an MCT, a finding that would demand a more aggressive surgical removal than for other more benign skin masses. Often, obtaining blood for a complete blood count and biochemical profile, buffy coat analysis, and a urinalysis will be advised as these can help assess overall health and provide information that potentially influences treatment recommendations. The CBC may reflect low or high white blood cell count, low platelet count, and/or 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 lymph node aspirate, bone marrow aspirate, x-rays, and ultrasound evaluation.

As mentioned previously, canine mast cell tumors are among the most common skin tumors, which occur in dogs. Boxers, Rhodesian ridgebacks, Pugs, Boston terriers, Pit-bull terriers, and Weimaraners are at high risk (4 to 8 times more than the population) for developing MCT. Shar-Peis, particularly young dogs, are predisposed to developing MCT, and these tumors are often poorly differentiated and act more aggressively biologically than in other breeds.

One characteristic 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, maybe an MCT. Another idiosyncrasy is the potential of the tumor to produce “Dariers 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, and/or hives. Symptoms are variable, depending on the location of the tumor and the degree to which it 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.

Most mast cell tumors are considered locally invasive and can be difficult to remove completely because of the extent of local spread. The behavior of mast cell tumors is a reflection of their grade. When evaluating the tissue sample obtained from surgical removal of the mast cell tumor, the diagnosis of mast cell tumor will be confirmed, the mast cell tumor will be staged, and the width of the tissue margins, which are free of tumor will be measured. Staging and the width of the tissue margins which are free of tumor cells together with the location of the mass, the health of the dog, and the grade of the mast cell tumor will determine whether further treatment with radiation therapy or chemotherapy will be recommended.

Mast cell tumors have 3 grades. Tumor grade is associated with the degree of differentiation of the mast cells. Grade I tumors are well differentiated and are the least aggressive and least likely to metastasize (spread to other organs). Complete surgical excision of Grade 1 MCT is usually curative. Grade 2 tumors are moderately differentiated and the prognosis and treatment options are perhaps the most complicated and difficult to predict. Grade 3 tumors are poorly differentiated, very aggressive with a high likelihood of metastasis. They carry the poorest prognosis but are fortunately the least common grade encountered. Mast cell tumors show a predilection to spread to regional lymph nodes, liver, spleen, and bone marrow.

Grading of mast cell tumors, however, is very subjective. In one study, mast cell tumors were graded by a group of pathologists, and frequently, there was disagreement regarding the grade even amongst board-certified pathologists. In many cases, perhaps a better method of determining how malignant or benign a mast cell tumor will behave is to have a proliferative study performed. This includes PCNA (proliferating cell nuclear antigen), AgNOR (agyrophilc nuclear organizing regions), and Ki67. Tyrosine kinase receptors (a receptor for mast cell growth factor) are also important and tests related to this include cKIT mutations and KIT staining patterns.

Because mast cell tumors prefer to metastasize the above-mentioned sites, staging a dog with a mast cell tumor entails collecting cells from the regional lymph nodes for microscopic examination, imaging the thorax and abdomen (radiographs, abdominal ultrasound, ) for evidence of enlargement of the mesenteric lymph nodes, liver or spleen, and an assessment of potential bone marrow involvement, either via a bone marrow aspirate for microscopic examination, or examination of the white blood cells for circulating mast cells.

Surgical removal is the mainstay of treatment of canine mast cell tumors. Presurgical treatment with histamine blockers and/or steroids is recommended to prevent complications of mast cell degranulation during manipulation of the tumor mass for the duration of its removal. Because of their locally invasive behavior, wide margins of what appears to be normal tissue around the tumor needs to be removed to increase the likelihood that the tumor has been completely removed. Approximately 2-3 cm margins and one fascial plane of depth are attempted as surgical margins.  Recent research has shown that 1-2 cm clean margins of a grade 1 or 2 mast cell tumor can be curative.  For mast cell tumors that were not or because of location could not be completely removed with wide surgical margins, radiation therapy is often the best treatment for residual disease. 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. Radiation therapy, however, is expensive and there may not be a facility able to offer this option within a convenient distance in many locations. Chemotherapy is sometimes used to treat mast cell tumors, but chemotherapy is usually reserved for dogs with grade 3 tumors. Mast cell tumors are notoriously unpredictable tumors with regards to response to chemotherapy, and chemotherapy for metastatic mast cell neoplasia does not offer consistent results. If the mast cell tumors have spread to multiple areas, combinations of anti-cancer drugs are commonly used along with surgery and radiation. These include vinblastine, lomustine, vincristine, doxorubicin, mitoxantrone, cyclophosphamide, and L-asparginase. These are all heavy-duty chemotherapy drugs with potential side-effects that include severe immunosuppression, vomiting, diarrhea, and/or liver damage. Palladia is a tyrosine kinase receptor blocker; the proliferative panel may be helpful to determine if the patient will respond to this type of medication. The tumor should be positive for cKIT mutations for this drug to be potentially effective. Unfortunately, mast cell tumors do not respond well to these drugs and several recent studies seem to demonstrate very limited efficacy in conjunction with surgery. It is important to remember that, while radiotherapy and chemotherapy are potentially useful adjuvant forms of therapy, aggressive surgery remains the mainstay of treatment for canine MCT and is sufficient to successfully treat the majority of MCT encountered in practice.

In addition to surgery, radiation therapy, and/or chemotherapy management of the tumors, many dogs will benefit from the administration of medications that tend to help fight the secondary local and systemic effects of the tumor. These usually include steroidal drugs like prednisone, and anti-histamines like Benadryl, Pepcid, or Zantac. These medications prevent the undue side-effects of histamine release commonly encountered in dogs with MCT.

Several prognostic factors (in addition to grade or stage) have been identified. Boxers have a higher percentage of low-grade tumors compared to most other breeds (It is important to recognize, though, that a high-grade mast cell tumor will behave just as aggressively in a boxer as in any other breed.) Smaller tumors and tumors that remain relatively static in size for prolonged periods (months or years) carry a better prognosis. Tumors that remain confined to the skin without metastasis to regional lymph nodes or distant sites carry a better prognosis. The presence of multiple cutaneous tumors does not affect long-term prognosis. Systemic illness (anorexia, vomiting, melena, gastrointestinal ulceration) is usually a reflection of a larger tumor burden and therefore carries a worse prognosis. Tumors located on the muzzle have a higher rate of spread to regional lymph nodes and therefore carry a more guarded prognosis. Historically, it has been suggested that tumors located in the inguinal area, perineum, and scrotum carry a more guarded prognosis, but this is based solely on anecdotal evidence, and two recent studies have refuted this claim.

The prognosis for completely removed grade I and grade II tumors is excellent. Even with complete surgical removal, however, because of the tendency of MCT to exhibit multicentric origination, new lesions may appear elsewhere, which are not the result of actual metastatic spread. For this reason, multiple surgeries over time may be necessary to control the disease process. The prognosis for incompletely removed grade I and II tumors treated with radiation therapy after surgery is also excellent with approximately 90-95% of dogs having no recurrence of tumor within 3 years of receiving radiation therapy. The prognosis for dogs with grade III tumors is considered guarded as local recurrence and/or spread is likely in most dogs. If your dog is diagnosed with a grade III MCT, most likely chemotherapy will be recommended as at least part of the protocol and a guarded prognosis is warranted.

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