Mast Cell Tumors In Dogs – The Complete Dog Owners Guide

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If you are reading this, chances are your dog has a diagnosis of mast cell cancer. As a dog owner, this condition is particularly vexing because not only are you left devastated by the diagnosis, but what you read leaves you bewildered and frightened.

While I cannot change the diagnosis, as a Veterinarian of 30 years, I can explain the implications and therapy options, and help you see that perhaps there is hope after all.

Confusion and Unpredictability

When you hear your pet has cancer, what you want is a plan of action and a definite strategy to get your pet well again. Unfortunately, the only certainty about mast cell tumors in dogs is they are unpredictable and there is no ‘one size fits all’ treatment. All of which adds to your confusion and anxiety, especially when your veterinarian then suggests radical surgery.

It is natural to ask yourself questions such as:

• How much surgery should I put my dog through?
• What happens if I do nothing?
• What hope do new ‘designer’ drugs offer?

However, by understanding why mast cell tumors are so challenging, and by understanding the recent advances in therapy, you can ask the right questions to your veterinarian about the best way forward for your pet.

OK, let’s start at the beginning and meet our foe, the mast cell.

What Is The Mast Cell In Dogs?

Hard as it is might be to hear right now, mast cells aren’t all bad. In fact, in the right place and in the right quantities they’re actually rather a good thing.

Mast cells form part of a dog’s immune system by helping other cells get to where they’re needed to fight infection. To do this mast cells lie in wait, scattered throughout the skin and other tissues, ready for the call to action [SOURCE].

One of the most significant things about mast cells is they contain histamine. Once activated, mast cells release histamine which causes tissue swelling. If you are wondering why this is a good thing, the answer is it increases tissue permeability (or leakiness) which allows the white cells to travel through tissue to reach those pockets of infection.

However, too much histamine is unpleasant, which is why hay fever sufferers take anti-histamine tablets during the pollen season. But in the case of mast cell cancer the excessive amounts of histamine released are potentially dangerous. (More of this later.)

What is Mast Cell Cancer?

This is a cancer where the numbers of mast cells multiply out of control–a classic case of too much of a good thing. The cancer usually forms of lumps, or tumors, most commonly in the skin or just under the surface. (Mast cell tumors can develop in other body tissue but this is rare.)

Why My Dog?

It is not your fault your dog has cancer. Neither is it your fault the dog has a mast cell tumor. In fact, mast cell tumors are the most commonly diagnosed skin tumor in dogs with around 20-25% of the skin tumors seen in first opinion practice being mast cells tumors

Like so many cancers no one really knows what triggers a cell to mutate and become cancerous, and mast cell cancer is no different. However, some breeds are more likely to develop this cancer than others are, and a hereditary component seems likely.

Those breeds who sadly are at increased risk include the Boston terrier, Boxer, English Bulldog, Bullmastiff, Labrador retriever, Golden retriever, Staffordshire bull terriers and other bull breeds, and the Weimaraner. [3]

One of the cruel things about mast cell cancer is that it is no respecter of age and can affect both young and old. The condition is most likely in middle-aged dogs, around 8.5years old, but I’ve certainly seen cases in dogs as young as 18 months.

Signs and Symptoms of Mast Cell Tumors

A skin lump.

That’s it. Potentially any skin lump may be a mast cell tumor; hence their nickname in veterinary circles as “the great pretender”. If your pet pops up a skin lump, get it checked by your veterinarian.

In some cases a simple test called a fine needle aspirate (no anesthetic or sedation needed) may give a quick answer about what you are dealing with.

A red, itchy, rapidly growing skin lump

OK, as you will learn, some mast cell tumors are relatively harmless (but should still be removed…just in case) while others are more worrying. The later tend to look angry and red, they are often itchy (because of all the histamine they contain) and bruise easily. These signs, along with swelling around the area, are a definite red flag that should have you picking up the phone to the vet.

Vomiting and poor appetite

Now these signs may seem unrelated to the skin, but they can be a sign of mast cell cancer. The reason is histamine released from the tumor can cause stomach ulcers, which literally makes the dog sick.

My Dog has a Mast Cell Tumor Diagnosis: What Happens Next?

Surgical removal cures most mast cells tumors. Let’s look at the stats…

Surgical removal cures 100% of Grade I and 75% of Grade II mast cell tumors. But… and it’s a big but… the average survival time for a dog with a Grade III mast cell tumor is just six months [SOURCE]. This means that for most dogs, their best chance of a recovery is surgical excision (with wide margins) of the lump. However, this simple answer belies the complex nature of the condition.

• Grade I (Low risk) – Surgical excision is curative for that particular lump
• Grade II (Intermediate risk) – 75% are cured by surgery, 25% are still at risk
• Grade III (High risk) – Surgery associated with dangerous complications, and unlikely to be curative. ‘Designer’ drugs are the best option.

The first problem is that it takes a lot of tests to find out what grade the tumor is. The second problem is the tests results only predict that tumors behaviour, some lumps don’t behave as expected. The third problem is most lumps are grade II, which means that whilst three in four dogs are cured, one in four dogs may still have a serious problem – but we can’t predict which those are.

And just when you thought you couldn’t take more bad news, it keeps coming. A dog that grows one lump is likely to pop up others further down the line, and just because the first tumor was grade I is no guarantee the next lump will be the same.

One Step at a Time: Grading the Cancer

How does the laboratory know what grade my dog’s tumor is?

An excellent question. The lab gets clues by looking at how active the cells in the lump are (something called the mitotic index). Inactive, sleepy cells indicate grade I, whilst hyperactive cells are grade III. But you guessed it, most cells lie in between and are grade II. For decades this method was the only way of identifying how worrying a tumor was, but new tests are coming on stream to help with the decision making. [6] [2]

Ki-67: This test looks for additional markers in the cells of grade II tumors which help predict if it is going to be aggressive

C-Kit: This test looks for a receptor on the cell surface and helps predict which tumors are vulnerable to the new ‘designer’ drugs.

What does this mean for my dog?

OK, if your dog’s tumor is grade I, then surgical removal gets rid of that particular tumor. End of that scare.
If your dog’s tumor is grade III, ask your vet to run a C-Kit test. This predicts if the tumor will respond to new designer drugs and is the dog’s best treatment choice

For grade II tumors, surgical removal is still the best option. A low Ki-76 result is reassuring that this is the end of that lump, whereas a high Ki-67 is a warning that further vigilance is needed.

Should My Dog See a Specialist?

Grade I Tumors

The easiest answer is for those dogs with a straight forward grade I tumor. Check with your veterinarian and ask the following questions:

• Is the tumor grade I?
• Was the lump completely removed and with wide margins? (The histology report gives this information)

If the answer to both questions is “yes”, then there is no point seeing a specialist. Your dog is cancer free.

The Grade is Not Known

Fine needle aspirates can tell your veterinarian the dog has a mast cell tumor, but knowing more is impossible with this test alone. Therefore, whether to see a specialist depends on where the lump is and the surgical skills of your veterinarian.

For example, if the lump is small and in a place where there is plenty of skin, such as the dog’s flank, then your veterinarian is fully able to remove the whole lump. But if the lump is large, angry looking, and on a leg (there’s no spare skin), complete removal is difficult and you would do well to see a specialist.

The specialist may then suggest a strategy such as:

• Using drugs to shrink the lump prior to surgery
• Radiotherapy to shrink the lump
• Radical surgery such as limb amputation (if the suspicion of an aggressive tumor in an tricky place is high)

The other advantage of referral is access to specialist surgeons familiar with advanced techniques such as skin grafting, in order to facilitate complete removal.

Grade III or for Peace of Mind

While your veterinarian is able to prescribe the newer drugs, it is unlikely they deal with them every day. A specialist has in depth knowledge of the different medications and is best placed to decide on the best drug for your dog, or even if radiotherapy is an option.

Also, for whatever reason you prefer to get an expert opinion, this is absolutely fine. Just ask your first opinion vet and they can arrange referral for your dog.

What Happens if I Take No Further Action?

It might be your dog has a problem, such as heart or kidney disease, which makes repeated anesthetics dangerous and unadvisable. Or perhaps you don’t want to put your pet through the pain of surgery, or you have financial restrictions, or lack access to a specialist. Indeed, you may have ethical issues about giving your dog drugs. All of which make it important to know: What happens if I do nothing?

Part of the cruelty of this condition is that it’s hard to predict what the future holds. One example is a patient of mine who popped up new grade II mast cells as regular as clockwork. For years we diligently removed each new lump as it appeared, with the dog the canine equivalent of a patchwork quilt.

However, when that dog developed kidney disease, and the owner made the sensible decision to treat the renal problems but not put her through further surgery. Indeed, that dog did develop further lumps but it was kidney failure that eventually ended her life.

Contrast this with another patient of mine who developed a lump on his nose. It was a tricky place for surgery and the owner’s finances meant radiotherapy wasn’t an option. Four months later that dog came in with a chest full of blood (another unfortunate consequence of mast cells tumors is bleeding problems) and sadly he had to be euthanized on humane grounds.

The long and short of it is that the full spectrum of outcomes is possible. Some dogs grow one harmless lump which never causes a problem. Others grow multiple harmless mast cell tumors that are ugly, but not life threatening. Unfortunately, other dogs grow mast cell tumors that grow quickly, break open and become infected. Others die from complications such as histamine-induced stomach ulcers, or clotting disorders as a direct result of their mast cell tumor.

So you see the difficulty in doing nothing. You are balancing risk against likely outcome, and how comfortable you are with this depends how much of a gambler you are.

Treatment Options For Mast Cell Tumors In Dogs

I want the best treatment for my dog and cost is not a factor. What are the options?

In simple terms the treatment options for mast cell cancer are:

• Surgery
• Radiotherapy
• Chemotherapy
• ‘Designer’ drugs

Each of these has advantages and disadvantages, and only when you have all the facts to hand can you make a fully informed decision. This is why seeing a specialist is great news, because they can assess your dog and weigh up which is the best choice for that individual pet.

However, even when you see a specialist, in the stress of the circumstances it’s easy for information to fly over your head. To help, let’s look at each option in more detail.

Surgery

For the vast majority of dogs with a mast cell tumor, surgical removal remains the first and best choice. Statistically, the chances of a ‘cure’ are high for low grade lump removals.

What Does the Surgery Involve?

The surgeon removes the lump but takes wide skin margins and a layer of tissue from beneath it. This is to catch any tentacles of cancerous spread in the surrounding area. For non-aggressive lumps this gets rid of the whole lump and no further action is necessary.

While the dog is under anesthetic the surgeon may also take a sample from the nearest lymph node. This is not always done, but can be a useful check to see if any cells have broken off and spread to the draining lymph node.

When Is Surgery NOT the Best Answer?

Removing the whole lump effectively depends on there being plenty of skin to fill the hole. Places like a paw, leg, or nose don’t offer the luxury of this spare skin, which means there’s a greater risk of leaving some cancer behind. In these cases the veterinarian might consider using drugs to shrink the tumor and ‘buy’ more room, or radiotherapy (to shrink the tumor), or referring to a specialist surgeon for a skin graft.

One option when an aggressive mast cell tumor grows on a paw but finances do not allow referral, is amputation. While this sounds harsh, sacrificing the leg may be what it takes to stop the cancer spreading and save the pet and many pets are able to live a high quality of life for many years after amputation.

‘De Novo’ Lumps

Remember my dog from earlier, the patchwork quilt dog from so many surgeries? Well, the lumps she popped up were new or ‘de novo’ lumps. These tumors do not represent spread of a previous tumor, but lumps grown anew spontaneously. [£] These may make it appear the first operation was not a success, whereas the surgery worked for that particular lump, but the dog was incredibly unlucky and grew new ones.

Radiotherapy

Radiotherapy uses high-energy beams of radiation to target cancer cells and kill them. This procedure is done at a specialist center and under general anesthetic. A typical treatment regime would be four sessions once a week for four weeks. (One factor to consider is how good a traveller your dog is, if the specialist center isn’t near your home.)

Radiation works best on small lumps in places where surgery is difficult, such as a leg or nose. Indeed, some cases are cured by radiotherapy. Another use is when a lump was removed, but traces of cancer were left behind. Radiotherapy targeted at the healed operation site is a good way of killing those residual cancer cells.

However, the specialist will give careful thought to using radiation on a large lump. This is because of complications such as a massive release of histamine from all those dying cells can cause a serious, shock type reaction in the patient which can be life-threatening.

Chemotherapy

Until recently, the only drugs that helped against mast cell cancer were traditional chemotherapy agents. (These are different to the so-called ‘designer’ drugs discussed in the next section). Surgery or radiotherapy are better options than chemotherapy, although it does have its place.

These drugs are used for the following reasons:

• To decrease the swelling around a mast cell tumor
• To decrease the size of a tumor
• To kill cancer cells that have spread to other parts of the body
• To help dogs who grow many tumors at one time and for whom surgery is not appropriate
• Large, high grade, aggressive tumors

The drugs most commonly used are prednisolone, vinblastine, or lomustine. If chemotherapy is required, your clinician is best placed to select the right protocol for your dog, but here is some information on each drug.

Prednisolone: This is a corticosteroid widely used in veterinary practice. In this case, the steroid helps decrease the growth rate of abnormal cells and reduces inflammation. Side effects of steroids include increased thirst and appetite, and high doses for long period of time can induce problems such as Cushing’s disease or diabetes mellitus.

Vinblastine: This drug stops cancer cells reproducing and kills them. It is given intravenously and traces of the drug are passed in the dog’s saliva, urine and feces, and therefore you should be careful to avoid direct contact with these substances. Vinblastine can cause bone marrow suppression, stomach upsets, and stomatitis (inflamed membranes in the mouth).

Lomustine: Lomustine damages the DNA of cancer cells. In common with many chemotherapy drugs it may cause bone marrow suppression or liver damage.

Designer Drugs

The new drugs are exciting because in some cases they offer hope where once there was none. Indeed, there are reports of around 10% of dogs with multiple, grade 3 tumors going into full remission and their lumps ‘disappearing’ altogether. Sadly, these are the ‘best case’ scenarios, with on average a 50% (*) response rate (the dogs improved) and 10% doing really well. So, what are these drugs and how do they work?

Why “Designer” Drug?

The label “designer” reflects the sophistication of these drugs which are designed to target specific mutations in cancer cells. This makes their effect very specific (on the cancer cells) rather than the more general actions of chemotherapy agents. Think of this as gaining entry by using the correct key for that door, rather than by bulldozing the house.

A more correct name for these drugs is “tyrosine kinase inhibitors” or TKIS. There are currently two TKIS available, masitinib (Masivet) and toceranib phosphate (Palladia).

How Do TKIS Work?

Cancerous mast cells have a specific mutation that affects a receptor, called a c-kit, on the cell wall. This receptor codes for cell growth, and in the cancerous cell is permanently switched to the ‘on’ position, which creates the cancer. TKIS attach to the c-kit receptor and switch them ‘off’, and turning off the cancer process.

Do you remember in the diagnosis section, how we mentioned testing for c-kit? Well, this is where it pays off, because the test helps predict those cancers which will respond to TKIS and those that don’t.

Masivet vs Palladia: Is There a Difference?

The two drugs work slightly differently. Masivet is more highly targeted to mast cells, and has fewer side effects. Palladia is less highly targeted but this may be beneficial in some circumstances (such as fighting cancer that has spread) but also has more side effects. All in all, your specialist is best placed to decide on the best drug for your dog’s particular needs.

How are TKIS Given?

Both Masivet and Palladia are an oral medication, given in tablet form. They are a long term medication, so once started you can expect the dog to remain on treatment for the rest of their life.

What are the Side Effects?

Any drug can potentially have side effects, and TKIS are no different. The complications vary between the two drugs, so let’s take a look at each separately.

Masivet – Mild tummy upsets are common but settle down without specific treatment. However, little over one-in-ten patients have more serious side effects which included protein loss, anemia, or severe gastric upsets that were potentially life-threatening. [2]

Palladiav – Here the statistics show a higher number, around 34% of cases developed serious side effects, mainly because of gut ulceration. Sadly, around 14% either died or had to be euthanized because of these complications. [2]

I Still Don’t Know What to Do

Confusion goes with the territory when your pet is diagnosed with mast cell cancer. There are so many unpredictable factors that go with this condition that it’s easy to get lost when trying to decide what’s best for your pet.

However, if your pet’s lump is slow growing, and suspected grade 1 or 2, then surgery is streets ahead the best option.

If the lump is highly aggressive, especially if it is in a place where it cannot be removed, then TKIS offer new hope for previously hopeless cases.

For those cases that fall between these clearer cut boundaries then radiation therapy or chemotherapy can help shrink a tumor or reduce the risk of spread, and make that lump a better candidate for surgical removal.

But most important of all is to make decisions based on your own pet and what’s best for them. Remember, life is about quality, not quantity. For example, if your pet is a poor traveller, then spending his last weeks or months traveling long distances for radiotherapy, may not be the wisest way to spend that precious time…Always put your pet’s needs first and keep their welfare uppermost in your mind when making decisions.

Special Notes:

(*) The response rate varies according to different sources. These figures are consistent across clinical trials for Palladia. However, there are differences when it comes to Masivet, with some trials indicating much better results than others. Indeed, independent trials of Masivet suggest a 79% remission rate for even the most aggressive tumors.)

References:

• 1. Mast Cell Tumors.Dr Susan North BSc PhD, DVM. Oncology specialist. BSAVA lecture April 2014
• 2. Mast Cell Tumors: A Modern Approach. Gerry Poulton. MA vetMB MSc (Oncology) DipECVIM (Onc) MRCVS
• 3. Selected Neoplasms in Dogs and Cats. Small Animal Internal Medicine. Nelson & Couto. Publisher: Mosby
• 4. Mast Cell Tumours: Current Thoughts. Lecture notes by Dr Susan North BSc PhD, DVM. Oncology specialist. October 2014.
• 5. Canine Cutaneous Mast Cell Morphologic Grading and Survival in 83 Dogs. Patnaik et el. Veterinary Pathology. 21 (469-474)
• 6. Mast Cell Tumors: Investigation and Treatment Options. From BSAVA lecture notes by Susan North, BSc (Hons) PhD, DVM, MRCVS, Oncology specialist.