The Dog Cancer Survival Guide (95 page)

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Authors: Susan Ettinger Demian Dressler

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Which Dogs Are at Risk for Mast Cell Tumors?

The cause of MCT is not known, although we do know a few things about what can predispose a dog to developing it. Dogs of any age, and either gender, can develop MCT; we see it more commonly in the following breeds: Boxers, Boston Terriers, Labradors, Golden Retrievers, Pugs and Staffordshire Bull Terriers. Boxers tend to develop low and intermediate grade tumors.

Chronic inflammation of the skin may predispose dogs to develop MCT, as can repeated application of skin irritants. Also, about one-third of dogs with MCT have a genetic mutation in a protein called the c-kit oncogene.

Although we tend to associate skin cancer in humans with sun exposure, studies have found no link between sun exposure and MCT in dogs.

What are the Signs of Mast Cell Tumors?

Most dogs do not seem sick when they are diagnosed with MCT. They usually have a lump, or mass, on or just under the skin. These lumps are often found by the owner, and sometimes by the vet, during a routine exam.

MCT tumors usually look like raised, hairless, pink bumps – and their appearance can vary widely. Because of this, MCT is called “the great impersonator.” Tumors can look like benign skin tags or harmless lipomas. Some are mistaken for insect bites because they get bigger and smaller on their own (this is due to the cyclical building up of and subsequent releasing of histamine, which causes inflammation and swelling and then a reduction). The tumor can be ulcerated (an open sore), swollen and inflamed or relatively benign looking. Tumors can be found anywhere, the trunk and the limbs being the most common locations.

Some tumors are present for months or even years, with little change in growth or appearance; others appear suddenly and grow very rapidly.

Some MCT masses itch and dogs may scratch or lick them to relieve the sensation. If your dog chews, scratches, or bangs the tumor against the ground, it can open up and release inflammatory chemicals from the granules. This is called degranulation, and the release of histamine can cause a localized swelling that looks like a hive. Massive degranulation can also provoke system-wide symptoms, like full-body swelling or, in very severe cases, anaphylaxis (shock).

Because of the wide variation in the appearance of MCT, I strongly advocate that every skin mass be aspirated for microscopic evaluation as soon as it is found (see below). With this evaluation, MCT might be caught early.

If MCT has spread to the internal organs, symptoms other than skin masses can occur. For example, internal tumors can release histamine into the bloodstream and cause the stomach to produce excess acid. The resulting stomach irritation and ulceration can lead to a decrease in appetite, vomiting with a small amount of blood, dark tarry stools and weight loss. Massive degranulation of internal tumors can also produce low blood pressure. Dogs with MCT of every grade tend to experience delayed wound healing because of the excess histamines and other chemical substances in the MCT granules.

How Are Mast Cell Tumors Diagnosed?

MCT are typically diagnosed with a fine needle aspirate, which has proven very reliable in confirming their presence. No one – not even experienced oncologists – can be sure that a suspicious lump is benign just by feeling it, which is why every skin mass (and those just below the skin) must be aspirated. The results allow your vet to then formulate an accurate treatment plan.

The most important factor in treating MCT is the grade of the tumor, which cannot be discovered via aspirate. Once the malignancy of your dog’s MCT is found, your vet will likely want to do a surgical biopsy before planning curative surgery or other treatments. Let’s look at how to grade MCT.

Grading MCT

If possible, the entire visible tumor is removed, along with a wide margin of surrounding normal tissue, because it may be possible to “get it all out” with the biopsy. (Wide margins in these tumors are two to three centimeters on all sides and a layer of tissue underneath.) These margins are not always achieved, of course, and must be confirmed with the pathologist’s report.

If there is more than one tumor, it is recommended to biopsy each one, because each separate tumor could be of a different grade and need a different course of treatment. If there are many tumors – more than four or five – I will often biopsy the two largest or the ones which have grown most quickly, depending upon the specific case, the location and size of the tumors, and my own discernment.

The pathologist will look at several criteria to grade MCT (see below) and assign one of three grades to each biopsied tumor: grade I, II or III, according to what is called the Patnaik grading system.

Grade I tumors are the easiest MCT to deal with, and account for 33-50% of all MCT cases. These tumors are also referred to as low grade. They do not invade surrounding tissues, are well differentiated and they rarely metastasize. If your dog has a single Grade I tumor, further staging before surgery is probably not necessary.

Further Staging for MCT

In all other cases – two or more tumors of any grade, a Grade II or III tumor, a recurrent MCT tumor, or lymph node metastasis – further staging is necessary before deciding upon a course of treatment. For these tumors, staging will include, at minimum, an aspirate of lymph nodes in the region of the tumor or tumors (even if they are of normal size) and an abdominal ultrasound to check for internal metastasis. A bone marrow aspirate may also be needed.

Vets often perform lymph node aspirates first, because they are minimally invasive, do not require sedation and are relatively inexpensive. If cancer cells are found in the aspirate, even when they are not numerous enough to confirm actual metastasis, a lymph node biopsy will be done (usually the entire lymph node will be removed). If either the aspirate or the lymph node biopsy is positive, local metastasis has already occurred and the lymph node(s) will be scheduled for removal or radiation. Meanwhile, the internal organs will be checked before the first surgery is scheduled.

If no cancer cells are found in regional lymph nodes, it is probably safe to go ahead with surgery to remove the primary tumor, and wait to do the ultrasound (and maybe a bone marrow aspirate) later. This holds true only if there is enough room around the tumor for a wide excision (two to three centimeters) of normal-seeming flesh and if the tumor is not in a location with a higher risk of metastasis (see the prognosis section below). The advantage of going ahead with a surgery at this point and leaving further staging for later is that the tumor is excised sooner and its biopsy can provide useful information about the cancer’s grade.

In addition to spreading to the draining lymph nodes, MCT tends to spread to the liver, spleen and, sometimes, internal lymph nodes; an abdominal ultrasound will reveal suspicious lesions or enlarged, infiltrated organs. If these are found, it does not necessarily mean that there is metastasis; the organs must be aspirated to confirm the situation. In most dogs, these aspirates can be done without sedation, using ultrasound as for guidance.

 

New Grading System for MCT

Currently, we are still using the Patnaik grading system, but that may change soon because of studies conducted by Michigan State University. According to those studies, twenty-eight different pathologists who separately examined the same ninety-five MCT tumors didn’t classify their grades consistently.

For example, 75% of the pathologists agreed on which tumors were grade III, but only 63% agreed about which tumors were grade I and II, which means that pathologists may not be classifying tumors in real life in a consistent fashion. If this is true, their assessments based on grade may be less reliable in determining prognosis.

The study also revealed a tendency to grade tumors on the borderline between I and II as grade II. This makes a grade II tumor assessment less valuable as a prognostic factor.

This inconsistency matches my clinical experience, and is why I generally recommend getting a second opinion on MCT biopsies. The study has also prompted the creation of a new system for grading MCT.

In the new system, there would be two, rather than three, grades, and it would be based on the mitotic index (how much replication is going on), the presence of bizarre or multiple nuclei cells, or karyomegaly (which is increased nuclear size). Tumors would be classified as either low-grade (longer time until metastasis, and more than two years median survival time) or high-grade (shorter time until metastasis, higher death rates due to the MCT, and median survival times of less than four months).

This streamlined system is still quite new and being validated, but it would not surprise me if it is adopted in the future.

 

Before aspirating internal organs, a blood-clotting test will be performed, and if the blood is not clotting properly, steps will be taken to boost clotting for the aspirate. I have heard vets express concern that aspirating internal organs suspected for MCT can cause bleeding problems; this very rarely happens in my experience. Because mast cells contain granules filled with heparin, which is a blood thinner, their concern is that a sudden release of this chemical into the body could keep the blood from clotting properly. While this is true, there typically is not enough heparin to cause an issue, so the actual risk is low. Information is power when it comes to this unpredictable cancer – and with each case being so very different, the information gained by aspirating these organs is valuable, necessary, and worth the slight risk involved.

In addition to lymph node aspirates/biopsies and abdominal ultrasounds, I often recommend a bone marrow aspirate. I always recommend this test for Grade III MCT, and sometimes for Grade II tumors, or recurrent tumors. This procedure requires sedation, so I usually perform it while the dog is already under anesthesia for a biopsy or curative surgery. It is also an additional expense, so I usually discuss its inclusion with owners before scheduling it for Grade II tumors.

Every removed tumor should be submitted for a post-surgical biopsy. In addition to looking for clean margins (clean margins usually indicate that future recurrence is less likely), the pathologist can find more definitive information to make a prognosis.

For example, the pathologist will look at the mitotic index, or how many MCT cells are dividing. In a recent study, it was shown that the higher the mitotic index, the poorer the prognosis: if the score is over five on the mitotic index, the median survival time was only two months, regardless of grade. If the score was under five, however, the median survival time was seventy months (over five years), regardless of grade. Other studies put the bar higher, even up to a score of ten, and the new grading system discussed in the sidebar on
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uses a score of seven as the bar. As we continue to use this score to evaluate MCT tumors, I expect we will come to a firmer consensus. For now, knowing the mitotic index can really assist your oncologist to plan treatments, and formulate a prognosis.

The pathologist can also discover other information that may be helpful. There are certain markers, which help to evaluate cancer proliferation and cell division: AgNOR, PCNA, Ki-67, c-Kit and c-Kit mutation status. Only a handful of laboratories have the special stains and expertise needed to analyze these markers, so I recommend consulting with your oncologist to see if this information is necessary before adding these expensive tests to the biopsy. I find this panel especially informative for Grade II and grade III tumors, so if budget is a concern, this may be more helpful than a bone marrow aspirate when dealing with Grade II.

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