Mast Cell Tumors in Dogs
What are mast cell tumors?
Mast cells are present in most tissues, and are especially prominent in the skin, lining of the lungs and digestive tract,
mouth and nose. They are an important component of the immune system, with functions in inflammation and allergy
reactions. Mast cell tumors (MCTs) are formed by the abnormal proliferation of mast cells, and when the entire body is
affected, the disease is referred to as mastocytosis. Mast cells can release several biologically active chemicals such as
histamine and heparin, which can be very damaging to the body when released in excess by the tumor cells.

The behavior or skin mast cell tumors ranges from being benign (non-cancerous) to highly malignant (cancerous). There
is a wide variation in the histological pattern of MCTs and the tumor grade (level of aggressiveness) is a strong predictor of
how well the dog will do. The metastatic potential (ability to spread to other organs) is not known for MCTs. It is estimated
that well-differentiated tumor cells (those that still resemble mast cells) have a low-to-moderate risk of
metastasis but
undifferentiated tumor cells (those that no longer resemble mast cells) have a high metastatic potential. Most of these
tumors spread first to regional lymph nodes and then mainly to the spleen and liver.

How common are mast cell tumors in dogs?
Skin MCTs are the most common type of mast cell tumors, accounting for 16%-21% of all skin tumors in the dog. The
average age at diagnosis is 8 years but puppies as young as 4 months have been reported. There is some evidence that
certain breeds may be at higher risk of developing skin mast cell tumors, including boxers, bulldog breeds, bullmastiffs,
Boston terriers, Staffordshire, Rhodesian ridgbacks, pugs, Labradors retrievers, golden retrievers, weimaraners, and
beagles. Although mast cells are also present in the lung and gastrointestinal tract, the development of tumors in these
sites is not as common as for the skin. Skin MCTs are most commonly found on the trunk (50-60%) and the limbs (25%).  
MCTs that are located underneath the skin appear as soft nodules and can be misdiagnosed as lipoma. Although boxers,
bulldogs and pugs are at increased risk of developing skin mast cell tumors, they tend to have less aggressive tumors.
Labrador retrievers tend to have more aggressive tumors and golden retrievers tend to have multiple tumors.

What are the symptoms of mast cell tumors in dogs?
Skin MCTs are usually detected by owners as raised lumps on the skin which can have a wide range of appearance, from
a wart-like nodule (mass) to a soft subcutaneous lump to an ulcerated skin mass. MCTs that are located underneath the
skin appear as soft nodules and can be misdiagnosed as
lipoma.

Most tumors are solitary (single mass) but 11-14% of dogs can have multiple tumors. The appearance of these tumors
depends on how differentiated the tumor cells are (how much their appearance still resembles mast cells). Tumors that are
composed of cells that resemble mast cells under the microscope are usually slow growing and not ulcerated, although the
hair may be lost in the area. Tumors that are composed of cells that no longer resemble mast cells are typically rapidly
growing and ulcerated. Surrounding tissues may become inflamed and edematous (swollen due to fluid accumulation), with
small nodules forming nearby. The clinical symptoms of dogs with MCTs may be complicated due to the release of
chemicals by the tumor cells, which can cause gastrointestinal ulceration (open sores). In this case, the dogs may
experience vomiting, anorexia, dark feces and abdominal pain.















How is the diagnosis made?
The World Health Organization has developed a clinical staging system for canine mast cell tumors, reflecting the natural
progression of the disease. This system is by no means absolute and serves only as a guide.








Mast cell tumors are initially diagnosed by
fine-needle aspriation (FNA) cytology. While FNA is useful, it does not provide
any information about the tumor's grade (level of aggressiveness), and
biopsy is therefore recommended. Additional
diagnostic steps will vary depending on the tumor's location, size and initial findings. If the tumor is located at a site easily
accessible for surgical removal, and no obvious negative prognostic factors are present, the tumor is usually surgically
removed and the sample sent to pathology lab for evaluation. If the tumor develops at a site where complete surgical
removal is not possible and/or if additional negative prognostic factors are present, further
diagnostic tests are done prior
to initiating treatment. The veterinarian will typically examine the regional lymph nodes to check for
metastasis (spread of
cancer cells), do blood test to check for overall health of the pet, buffy coat smear to check for circulating mast cell tumor
cells throughout the body, abdominal ultrasound to check for metastasis to the spleen or liver, chest X-rays to check for
metastasis to the lungs and fluid accumulation in the chest, and bone marrow aspiration to check for MCT dissemination
(spread).
Advanced imaging such as CT (computed tomography) can be a very useful diagnostic tool that can evaluate
the extent of the disease in more detail and can aid the oncologist in planning an appropriate treatment strategy.

Does cancer cause pain in pets?
Pain is common in pets with cancer, with some tumors causing more pain than others. In addition to pain caused by the
actual tumors, pets will also experience pain associated with cancer treatments such as surgery, radiation therapy or
chemotherapy. Untreated pain decreases the pet's quality of life, and prolongs recovery from the illness, treatment or
injury. It is, therefore, essential that veterinary teams that are taking care of pets with cancer should also play a vital role in
educating pet owners about recognizing and managing pain in their pets. The best way to manage cancer pain in pets is to
prevent it, a term referred to as preemptive pain management. This strategy anticipates pain ahead of time and
administers pain medication before the pet actually experiences pain, thus ensuring the pet's maximum comfort.

To learn more about which tumors are likely to cause a lot of pain, how to recognize pain in pets with cancer and what
cancer pain management options are available for your pet, please visit the
Cancer Pain Management section.

Is nutritional support important for pets with cancer?
Cancer cachexia (a term referring to progressive severe weight loss) is frequently observed in pets with cancer. Pets with
cancer lose weight partly because of lack of appetite and partly because of cancer-induced altered metabolism. Some of
the causes for decreased appetite are related to the cancer itself (for example, tumors may physically interfere with food
chewing, swallowing, and digestion process) and some may be related to the side effects of cancer treatment (for example,
some chemotherapy drugs cause nausea and vomiting, and radiation therapy can cause mouth inflammation).

Proper nutrition while undergoing cancer treatment is essential to maintain your pet's strength, improve survival times,
quality of life and maximize response to therapy. Adequate nutritional support was shown to decrease the duration of
hospitalization, reduce post-surgery complications and enhance the healing process. Additionally, pets with cancer need to
be fed diets specifically designed to provide maximum benefit and nutritional support for the patient. To learn more, please
visit the
Cancer Nutrition section.

What are the treatment options for dogs with mast cell tumors?
Treatment strategies will largely depend on the tumor's grade (level of aggressiveness) and how advanced the disease is.
In addition to treating the tumor itself, some cases may also require treatment with anti-histamine medication and/or drugs
to relieve gastrointestinal ulceration associated with MCTs.

Low or intermediate grade (mildly aggressive) MCT easily accessible for complete surgical removal
For easily accessible MCTs, surgical removal is the treatment choice, followed up by histologic evaluation to ensure
completeness of surgery. The surgery will typically remove not only the tumor itself but also normal tissue surrounding the
tumor to ensure that no cancer cells are left behind. If the histologic evaluation confirms that no cancer cells were present
in the healthy tissues, then the dogs should either come for routine check ups on regular basis to monitor possible tumor
recurrence/metastasis or the pet owners can agree to
chemotherapy. In this setting, the goal of chemotherapy would be to
prevent or minimize the risk of
metastasis (cancer spread) and/or local tumor recurrence. Because of the lack of adequate
studies, veterinary oncologists seem to disagree on the potential benefit of chemotherapy in this particular scenario. If the
histologic evaluation confirms the presence of cancer cells in the healthy tissues, then additional treatments are necessary
to prevent the tumor from growing back and spreading to distant sites. These will typically include either additional surgery
that will remove larger area around the tumor and/or
radiation therapy and/or chemotherapy. Recently, the arsenal of anti-
cancer therapies for canine mast cell tumors included targeted therapies as summarized in more detail in the next section.

Low or intermediate grade (mildy aggressive) MCT not easily accessible for complete surgical removal
For tumors that are not easily accessible for complete surgical removal such as distal extremities (eg paws), it is usually
recommended that an incisional
biopsy is done prior to deciding on a definitive treatment plan. In this case, three main
treatment options exist: amputation,
radiation therapy and combination of surgery with radiation therapy. Amputation is an
aggressive treatment option with the best chance of controlling the tumor but it will also affect the dog's function. Radiation
therapy alone has had varying degrees of success. Combining radiation with surgery offers an attractive alternative to limb
amputation, in which the surgery removes as much of the mass as possible and the radiation beam kills any remaining
cancer cells left behind. Alternative treatments may include surgical removal followed by
chemotherapy or chemotherapy
alone but the benefit of these treatments is not established. Regardless of the procedure chosen, the dogs should be
evaluated on regular basis to monitor for local tumor recurrence and possible metastasis. Recently, the arsenal of anti-
cancer therapies for canine mast cell tumors included
targeted therapies as summarized in more detail in the next section.

High grade (highly aggressive) MCT easily accessible for complete surgical removal
For easily accessible MCTs, complete surgical removal is the treatment of choice, followed up by histologic evaluation to
ensure completeness of
surgery. The surgery will typically remove not only the tumor itself but also surrounding normal
tissue to ensure that no cancer cells are left behind. If the histologic evaluation confirms that no cancer cells were present
in the healthy tissues, then
chemotherapy is used to try to kill any circulating tumor cells that are likely to be present due to
the aggressive behavior of high grade tumors. The dogs are then followed up on regular basis for any signs of local
recurrence and/or
metastasis development. If the histologic evaluation confirmed the presence of cancer cells in the
healthy tissues, then either another surgery is attempted that will excise a larger region around the tumor or the area can
be subjected to
radiation therapy, followed by chemotherapy.

High grade (highly aggressive) MCT not easily accessible for complete surgical removal
For tumors that are not easily accessible for complete surgical removal such as distal extremities (eg paws), several
options are available:
  • surgical removal combined with radiation therapy (including regional lymph nodes) and chemotherapy
  • amputation combined with chemotherapy
  • surgical removal combined with chemotherapy
  • chemotherapy alone
  • radiation therapy combined with chemotherapy
  • radiation therapy alone

Several chemotherapy drugs have been evaluated for their efficacy. There is accumulating evidence in both human and
veterinary oncology that certain combination of different classes of chemotherapy drugs may offer the best chance of
controlling the spread of the tumor throughout the body compared to single drugs. The following table summarizes the
response to commonly used chemotherapy drugs in the setting of mast cell tumors:

















Source: Withrow Stephen J, and David M. Vail. Small Animal Clinical Oncology. St Louis: Saunders Elsevier, 2007.

Targeted therapies for Grade II/III mast cell cell tumors
Advances in scientists' understanding of cancer has led to the development of two targeted therapies for dogs with mast
cell tumors: Palladia by Pfizer Animal Health and Masivet (Europe)/Kinavet (U.S.) by AB Science.

Palladia (toceranib phosphate, Pfizer Animal Health)
Palladia specifically inhibits several molecular targets: proteins called c-KIT, vascular endothelial growth factor receptor-2
(VEGFR-2), and platelet-derived growth factor receptor (PDGFR-beta), which are known to play a role in cancer. Palladia
was evaluated in a multi-center, randomized, placebo-controlled clinical trial in 153 dogs with mast cell tumors that recurred
(came back) after surgery. In this study, dogs were randomized to either receive Palladia (given orally at 3.25 mg/kg dose)
or placebo (inactive substance serving as a control) every other day for six weeks. During this time, neither the veterinary
oncologist nor the owner knew which pill was administered (Palladia or placebo) - a term known as blinded study - to
ensure that no bias is introduced and the study is well controlled. The results showed that 32 of 86 dogs (37.2%) who
received Palladia responded to treatment, with seven dogs achieving complete response and 25 dogs achieving partial
response. In contrast, only five of 63 dogs (7.9%) treated with placebo achieved partial responses. This difference in
response between Palladia and placebo was statistically significant. The median time to progression was longer for dogs
treated with Palladia compared to those treated with placebo (>6 weeks versus 3 weeks, respectively); and more dogs
progressed on placebo versus Palladia during the 6-week blinded phase of the study (66.7% vs. 34.9%, respectively).
Dogs with c-Kit mutations were more likely to respond to Palladia compared to dogs with no c-Kit mutation (60% vs. 31.3%,
respectively). Dogs who were in the placebo group could receive Palladia after the blinded phase of the study ended,
making the total number of dogs treated with Palladia 145. Of these 145 Palladia-treated dogs, 42.8% responded to
treatment (21 dogs achieved complete response and 41 dogs achieved partial response). Among the 62 dogs who
responded to therapy, median duration of  response was 12 weeks and time to tumor progression was 18.1 weeks. Side
effects (any severity) that occurred more frequently in dogs receiving Palladia compared to placebo included diarrhea
(46% vs 26.6%), bloody stool (12.6% vs. 3.1%), weight loss (14.9% vs. 3.1%), and neutrophil toxicity (46% vs. 6.3%). The
full clinical trial results were published in a research journal (
London, Clin Cancer Res, 2009), and can be accessed by
clicking on the link.

Client information sheet about Palladia's safety and efficacy can be found
here.

Masitinib (AB Science)
Masitinib is currently available in Europe under the name Masivet, and in the United Sates under the name Kinavet.
Masitinib specifically inhibits several molecular targets: c-Kit, PDGFR alpha and beta, and Lyn.  In a clinical trial with 202
dogs of different breeds, dogs with mast cell tumors were randomized to either receive the drug (12.5 mg/kg) or placebo
(inactive control). The results of the study showed that masitinib was safe and effective in dogs with Grade II/III skin mast
cell tumors. In dogs whose mast cell tumors could not be removed by surgery, masitinib was better than placebo in
delaying the time it took for the tumor to progress. Median time to tumor progression for masitinib was 173 days compared
to 75 days for dogs treated with placebo. This result was statistically significant (p=0.001). Masitinib also showed a trend
toward improving overall survival (617 days for dogs treated with masitinib versus 322 days for dogs treated with placebo;
p=0.078), but this result did not reach statistical significance (a statistical significance is usually considered at p value of <0.
05). For dogs with tumors harboring a mutation in c-KIT tyrosine kinase receptor, the efficacy of masitinib was even greater
compared to placebo in terms of prolonging time to tumor progression (230 days for masitinib versus 42 days for placebo,
p=0.006), and median overall survival time (160 days for masitinib versus 62 days for placebo, p=0.025).

The most common side effects of masitinib are gastrointestinal reactions (diarrhea and vomiting), which are usually mild to
moderate and temporary, although a few may last for up to four weeks. Dogs who receive masitinib should be monitored
for side effects by their veterinarian at least once monthly, and if side effects do occur, the veterinarian may either lower
the dose or decide to discontinue the treatment. Masitinib cannot be used in dogs with certain liver and kidney conditions,
or anemia (low red blood cel count) or neutropenia (low white blood cell count). Additionally, masatinib cannot be used in
dogs <6 months old or less than 4kg in weight, or pregnant or nursing female dogs.  

For more information about masitinib from AB Science, please visit
www.masivet.com

How do I find a qualified veterinary oncologist?
To locate a qualified veterinary oncologist worldwide who can discuss with you appropriate cancer treatment plan for your
pet's cancer condition, please visit the "
Locate a veterinary oncologist" section.  

Are there any clinical trials investigating new treatments for mast cell tumors in dogs?
There are some clinical trials ongoing for dogs with mast cell tumors in dogs, which are partially funded by the institutions.
To learn more about these trials, please visit the
Clinical Trials for Mast Cell Tumors in Dogs section.

Additionally, there are several clinical trials available for cats and dogs with any tumor type for which your pet may qualify.
To learn more these trials (which are partially or fully funded by the institutions), please visit the
Dog Clinical Trials (any
tumor type) or Cat Clinical Trials (any tumor type) section.  

To learn more about veterinary clinical trials in general, please visit the
Pet Clinical Trials section.

What is the prognosis of mast cell tumors in dogs?
The prognosis for dogs with MCTs is dependent on a variety of different factors such as the tumor's size, location, grade
(level of aggressiveness), age, or symptoms. Tumor grade appears to be the most consistent prognostic factor for dogs
with MCTs and the survival times associated with specific tumor grades are summarized the following table. High grade,
undifferentiated tumor corresponds to a highly aggressive tumor and most dogs die within 1 year after surgery as a result
of local recurrence or
metastasis.

.


























Source: Withrow Stephen J, and David M. Vail. Small Animal Clinical Oncology. St Louis: Saunders Elsevier, 2007.

Dogs diagnosed with visceral MCTs (tumors in their internal organs) face poorer prognosis compared to those in the skin.
These dogs may show symptoms such as anorexia, vomiting, dark feces, wide-spread inflammation, and edema due to the
release of substances from the tumor mast cells.  One study showed that only 40% of dogs with gastrointestinal MCTs
were alive 30 days after diagnosis and less than 10% were alive at 6 months. Therefore, an aggressive treatment is
warranted upon the initial diagnosis to improve the pet's long-term prognosis.

Additional online resources about mast cell tumors:

Sources:
  • Withrow Stephen J, and David M. Vail. Small Animal Clinical Oncology. St Louis: Saunders Elsevier, 2007.
  • Morrison Wallace B. Cancer in Dogs and Cats: Medical and Surgical Management. Baltimore: Williams&Wilkins,
    1998.
Tumor Grade
Number of dogs
Percent alive months after surgery
Study #1
   
Low grade MCT
39 dogs
79% alive 7 months post-surgery
Intermediate grade MCT
30 dogs
37% alive 7 months post-surgery
High grade MCT
45 dogs
15% alive 7 months post-surgery
Study #2
   
Low grade MCT
30 dogs
83% alive 48 months post-surgery
Intermediate grade MCT
36 dogs
44% alive 48 months post-surgery
High grade MCT
17 dogs
6% alive 48 months post-surgery
Study #3
   
Low grade MCT
19 dogs
90% alive (months not reported)
Intermediate grade MCT
16 dogs
75% alive (months not reported)
High grade MCT
15dogs
27% alive (months not reported)
Study #4
   
Low grade MCT
87 dogs
100% alive 12 months post-surgery
Intermediate grade MCT
199 dogs
92% alive 12 months post-surgery
High grade MCT
54 dogs
46% alive 12 months post-surgery
Study #5
   
Low grade MCT
33 dogs
91% alive 20 months post-surgery
Intermediate grade MCT
35 dogs
71% alive 20 months post-surgery
High grade MCT
19 dogs
42% alive 20 months post-surgery
Chemotherapy drug
Number of
dogs treated
Complete
response
Partial
response
Overall
response
Median response
duration
Prednisone
25
4%
16%
20%
Not reported
Vincristine
27
0%
7%
7%
Not reported
CCNU (lomustine)
21
6%
38%
44%
79 days
Prednisone/
vinblastine
17
33%
13%
47%
157 days
Prednisone/      
cyclophosphamide/
vinblastine
21
0%
78%
78%
Not reported
Cyclophosphamide/
vincristine/prednisone/hyd
roxyurea
17
23%
35%
58%
53 days
PET CANCER CENTER
Comprehensive guide to cancer diagnosis and treatment in cats and dogs
© 2007 Pet Cancer Center. ALL RIGHTS RESERVED.
Last updated 4/10/13
Clinical stage
 
Grade I
One skin tumor with no spread to lymph nodes
Grade II
One skin tumor with spread to lymph nodes
Grade III
Multiple skin tumors or large infiltrative tumor with or without spread to lymph nodes
Grade IV
Skin tumors with metastasis (spread) to other body sites
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