Allergic Dermatitis

Up to 20% of dogs will get a malignant Mast Cell Tumor (MCT) in their lifetime, making it the most common tumor we encounter in dogs. Other names for MCT are mast cell sarcoma, histiocytic mastocytoma, and mastocytosis.

This disease has a cutaneous form (skin) and a systemic form (internal organs). The cutaneous form is more prevalent, and is sometimes referred to as the “great pretender” because the skin growth appearance is so variable. What might seem like just a minor swelling or inflamed area can be a highly malignant cancer. It might also be called the “great fooler” because most people underestimate the problem.

MCTs have the potential to be highly malignant and their treatment needs to be thorough and comprehensive in order to minimize the chance of spread and premature death of your pet. In almost every case the treatment of choice is surgery to remove the tumor. After surgery additional treatment might be indicated.

This page will give detailed information on MCT in the dog since that is the primary species that gets this disease. We occasionally see MCT in cats and ferrets. MCT are second most common tumor in cats. They behave somewhat differently in our feline friends. We will go over MCT in the cat at the end of this page.

Throughout this page are links to numerous other areas on the LBAH web site to give you additional information on that specific topic.

There are some mild surgery pictures in this page showing the open skin after a MCT has been removed. They are suitable for most viewers.

Physiology

Mast cells, also known as mastocytes, originate in the bone marrow and live for weeks to months. Once produced by the bone marrow they circulate through the body ending up in large numbers in the connective tissue of the body, lymph nodes, under the skin, and in internal organs.

Mast cells surround nerves and blood vessels, and are oftentimes found at the interface between the environment and the pet. This means they tend to be found in higher numbers under the skin and the lining of the respiratory system and digestive systems. They play a role in wound healing and defense against invading bacteria, and are a big part of the immune system. They have binding sites on them for the immunoglobulin called IgE. This immunoglobulin is a big part of the immune system when it comes to allergies. You can learn more about it by linking to our allergy page.

Mast cells have the potential to release several different compounds, the most important of which are called vasoactive amines. Vasoactive amines are nitrogen-containing compounds that act on blood vessels. The more important vasoactive amines are histamine, heparin, serotonin and prostaglandin. Histamine is the most important one in relation to MCT.

Histamine goes to the stomach lining and stimulates the secretion of gastric acid. Histamine also dilates blood vessels and increases permeability of the blood vessels, leading to swelling (edema). This mechanism is part of the normal inflammatory process.

Release of large amounts of histamine from a mast cell can result in ulceration or perforation of the GI tract (stomach and intestines) causing pain, hemorrhage, delayed wound healing, shock, and dark blood in the stool (melena). A significant number of dogs with MCT that are necropsied (autopsied) after death have ulcerations in the stomach.

This release of excess histamine is called the paraneoplastic syndrome. It is serious and needs to be addressed prior to and after treatment. This is why any skin growth needs to be handled gently in case it is a MCT and histamine gets released in an excessive amount.

When excess secretion of histamine occurs and only affects the skin it is sometimes known as Darier’s sign. You will notice raised and red areas of the skin when this happens.

In young animals the disease might spontaneously resolve. This is not something you should count on though. This cancer in dogs is unpredictable and can be extremely aggressive, so waiting to see if it resolves is not a good option. Every MCT should be treated as potentially malignant. MCTs can mimic other tumors, making it impossible to identify them simply by appearance.

Tumor Behavior

As a general rule, benign MCT will be slow growing, well circumscribed (their margins are easy to feel), non-painful, not attached to the underlying tissue, and exhibit minimal inflammation. They might be irritated if your dog or cat is licking at them.

Malignant tumors tend to grow more rapidly, might be ulcerated or painful, have poor margins to determine where they begin and end, are fixed to the tissue below, and may have spread to nearby blood vessels and lymphatic tissue as evidenced by enlarged peripheral lymph nodes.

If the MCT spreads to the internal organs (called systemic mastocytosis) it usually goes to the liver, spleen, lymph nodes, or even back to the bone marrow.

In dogs most MCT are usually found on the trunk and perineum, sometimes on the limbs, and occasionally on the head or neck. MCT of the perineal and inguinal regions tend to behave more aggressively than their tumor grade would predict. Some dogs get multiple tumors.

Mast cell tumors that are large (more than 4 cm), on the face, muzzle, and oral cavity tend to have a poor prognosis.

Mast cell tumors located in the perineal region (anus, scrotum and vulva) may be may be more difficult to remove completely. They might need additional surgery or radiation and chemotherapy.

Dogs that have signs of gastrointestinal ulcers (vomiting, poor appetite, lethargy, or black stools) generally have a poor prognosis. Tumors that recur soon after surgery have a poor prognosis.

You cannot tell definitively whether any skin inflammation is a tumor or something else, and if it is a tumor, whether it is benign or malignant, just by looking at it or feeling it. Microscopic analysis by a veterinary pathologist is the only way to confirm this diagnosis. When we take a tiny sample of cells with a needle (called a fine needle aspirate- FNA) we call this cytology. When we take a large piece of tumor, or even the whole tumor, we call this histopathology.

Cause

There are several factors that contribute to this problem that include genetics, hormonal, environmental, and immune influences. There is suggestion that MCT are related to red or golden hair coats, allergies, or viruses. None of this has been proven at this time.

As is the case with many cancers it is a genetic mutation that is the originating factor. A tumor suppressant gene (called p53) can mutate and is suspected to cause MCT in 50% of the canine cases.

A gene named C-Kit can mutate, leading to excess production of a protein called Kit, which can cause excessive stimulation of mast cells.

Diagnosis

Diagnosis is made based on the Diagnostic Process we utilize in call cases. This includes:

· History- observations of the problem you make at home, along with diet, environment, medication, and past medical history

1. Signalment

MCT’s occur in both males and females, typically around 8 years of age or older, although they have been seen in dogs much younger.

This is one of the few diseases that might occur in mixed breed dogs as much as purebred dogs. Certain breeds have a higher incidence though:

In cats it is the Siamese breed that has a higher incidence. There is no difference in occurrence rates between males and females.

2. History

The most consistent symptom of pets with MCT is a growth somewhere on the skin when grooming or petting. Multiple growths are possible, but in most cases it is one skin growth that is found. It might be tiny and barely inflamed, or it might be large and firm. Some pets will be oblivious to the tumor, while others might lick or chew at it. Many MCT wax and wane, which can make pet owner’s think the growth is not important. This waxing and waning can go on for months.

Other symptoms depend on whether heparin or histamine is being released (the paraneoplastic syndrome). In this case a pet can be vomiting, have a bleeding disorder (coagulopathy), have stomach ulcers, blood in the stool (melena), poor appetite (anorexia) or no appetite, abdominal pain, or literally be in shock. Some symptoms will look as if your pet is having an allergic reaction and require immediate veterinary care. In pets that have spread of MCT to other parts of the body there might also be weight loss.

The following pictures are all MCT’s. As you will see they can vary considerably, so just looking at a skin tumor will not give you a diagnosis. Basal cell tumors, histiocytomas, soft tissue sacromas, and lipomas can all look like mast cells at times.

This large mast cell is on the back of a dog's leg seen as it is being prepped for surgery

3. Physical Exam

A complete physical exam is performed on every pet brought to us for a skin growth. There are a multitude of reasons why check other body organs and not just the skin growth you noticed at home:

· So we do not miss other skin growths that might also be present and that are small or hard to detect. These might be other MCT, lipomas, or squamous cell carcinomas, for example.

· To ascertain any spread of tumor to lymph nodes. We check the following peripheral lymph nodes during our exam:

o Submandibular

o Pre-scapular

o Axillary

o Inguinal

o Popliteal

For more information on where these lymph nodes are located and their role in the immune system follow this link. Our doctors will gladly show you how to palpate them for an in-home exam.

· To look for other problems that might be present but not obvious. Common ancillary problems in pets that get MST include dental disease, arthritis, kidney disease, liver disease, heart disease (a heart murmur might be detected), skin allergies and even obesity. It is important that we address these issues for a successful outcome when treating MST.

· To make sure the pet is ready for any anesthesia in the future

Care must be taken not to palpate a suspected tumor too vigorously because if it is a MCT it can degranulate and release histamine. At the least it might cause the skin growth to become more inflamed (Darier’s sign), and in the worst case it will cause your pet to go into an allergic reaction and shock if excess histamine is released from the MCT. This is a rare occurrence but something to keep in mind as you touch any specific growth on your pet’s skin.

4. Diagnostic Tests

Routine blood panel, urinalysis, and fecal exam are needed in every case prior to any treatment. These tests give us a detailed picture of your pets overall health status and look for other problems that are not obvious during the physical exam. Finding other problems in pets that present for just a skin growth is a situation we encounter more often than you might think. Heartworm and FeLV/FIV status needs to be know also.

The results of a normal blood panel on a dog that prior to mast cell tumor removal. Sometimes we will see anemia due to blood loss from an ulcer in the GI tract. We might also see an increase in liver enzymes if the MCT has spread to the liver, and also an increased BUN (Blood Urea Nitrogen) if there is GI bleeding.

A very important test to diagnose any skin tumor is called a final needle aspirate (FNA). In this test we take a tiny needle and syringe and obtain some cells from the mass. The test is easy to perform, feels like a pinprick, and does not require anesthesia. It is similar to giving a vaccine, but in this case we are not giving something, we are taking something.

The small number of cells obtained from an FNA are put on a microscope slide and sent to our pathologist. They know why we are sending the sample to them and they specifically look for any signs of a benign or malignant tumor. Due to the high incidence of MST they look for these cells specifically. Pathologists are experts at analyzing cells under a microscope and they will come to one of the following conclusions:

· They will tell us what cells the aspirate is made of and recommend appropriate treatment.

· They will give us an idea of what different cells might be involved but have no specific diagnosis

· They will not be able to tell us anything because of too few cells in the sample or the cells are not identifiable.

This is what a pathologist is looking for under the microscope for a FNA. The arrow points to a clump of 3 mast cells that have been stained to stand out.

Here is a typical report from a FNA on a dog with MCT

Even though no guarantee can be given to the usefulness of the FNA, it is worthwhile in almost all cases because the potential to give us useful information is high, especially when you consider the ease of obtaining the sample.

Knowing whether we are dealing with a MCT ahead of surgery is important because these tumors need aggressive surgery to be certain we remove the complete tumor. If we know going into surgery that we have a MCT we will take at least 3 cm margins around the visible mass. We will also dissect down to a deeper fascial plane to make sure no tumor remains after surgery. This type of aggressive approach is usually not needed in other skin tumor surgeries.

A pre-surgical radiograph is indicated in many cases to look at the thorax and abdomen looking for any spread of the MCT from the skin to the internal organs (systemic mastocytosis). In addition, a radiograph is indicated any time we anticipate anesthesia and surgery.

We might seen an enlarged sternal lymph node in the chest if the MCT has spread. The white arrow points to the location where the sternal lymph node resides.

This crescent shaped organ under the black arrow is a big liver, called hepatomegaly, on a radiograph. A MCT is one of several causes to an enlarged liver.

This is a large spleen, called splenomegaly, on a radiograph.

If an abnormality is found on the physical exam, or any diagnostic test, an ultrasound might also be needed. If we see an enlarged liver or spleen prior to surgery we will perform an ultrasound. This is what a spleen looks like during ultrasound

During the ultrasound we can take aspirates to determine if the mast cell has spread to one of these organs.

Here is the report on the normal appearing dog spleen above. There is no sign the MCT has spread to the liver or spleen.

DESCRIPTION:

Cellular slides consist of a heterogenous lymphoid population and a few scattered aggregates of stromal connective tissue/splenic trabeculae against a hemodiluted background. Small mature lymphocytes predominate followed by a low number of intermediate lymphocytes and large lymphoblasts. A few metarubricytes, mature plasma cells, and macrophages noted. Nor organisms or atypical cells seen.

MICROSCOPIC FINDINGS:

Spleen consistent with normal or hyperplastic lymphoid tissue

This is an enlarged spleen with nodules that could be caused by a MCT

If a regional lymph node is enlarged or draining we will perform an aspirate to determine if the tumor has spread. We can also aspirate the bone marrow looking for mast cells.

Information from all these tests is used as part of the surgical plan. It is also used to determine prognosis after surgery once the final tissue sample has been analyzed. If it looks like there has been the spread of tumor to an internal organ then chemotherapy or radiation therapy might be indicated in addition to surgical removal of the mass.

Surgical Treatment (surgery pictures in this section)

The overwhelming majority of MCT are treated with surgery. Microscopic tumor cells that are not visible or palpable can occur, so we remove a margin of 3 cm from the edge of the visible or palpable tumor. We also dissect deep down into the tissue for another 3 cm. This is problematic on tumors of the face, neck, and extremities. In those cases radiation and chemotherapy might be more appropriate.

It is not unusual to perform more than one surgery, especially if the tissue report (histopathology) reveals that we did not remove all of the tumor. This is referred to in the report as the margins not being clean. We like to have 10 mm margins to feel comfortable that we removed all of the tumor. When in doubt a second surgery is indicated to remove any suspected tumor remnant.

We use the laser for all of our MCT surgeries because of the dramatic reduction in bleeding during surgery, along with substantial reduction in swelling and pain after surgery. In the picture our surgeon is gently holding the mast cell between his fingers as he dissects with the surgical laser.

The tumor has been completely removed (notice the lack of bleeding) and what you are seeing is the fat layer under the skin. Notice how large the incision is. This is because we took 3 cm margins on all sides of the tumor, and also because the skin is under tension and spreads wide open when we remove the tumor.

In most cases we need to go deeper than this fat layer and get right down to the muscle layer. At this point we feel comfortable that we have gone 3cm deep into the tissue and have removed all of the tumor that is not visible or palpable.

MCT surgical sites sometimes heal poorly due to the disruption the cancer cells cause in the area. This fact, added to such a large incision, has the potential to heal poorly due to the tension on the skin. It is imperative that your pet wears an e-collar and you follow our postoperative instructions.

During the surgery we might also perform an aspirate or biopsy a lymph node in the region of the skin mass to look for spread of the tumor.

Gentle tissue handling is important when obtaining a fine needle aspirate and during the actual surgical procedure. Mast cells can release histamine during these times, so in addition to gentle handling we might put your pet on prednisone, Benadryl, and Pepcid AC prior to, during, and after surgery to minimize the release of histamine and its serious effects on the stomach and intestines.

In the rare cases where surgery might not be feasible, or the tumor is not completely removed, treatment can include medical therapy, radiation therapy, and chemotherapy.

Tissue Analysis and Prognosis

Analyzing the removed tumor tissue after surgery, called histopathology, is crucial to confirm the diagnosis, determine if more surgery or treatment might be needed, and to make a long term plan. The pathologist will let us know if the entire tumor was removed, what grade the tumor is, and what is the mitotic index of the tumor. This is a typical report on a dog with MCT:

Examined is a section of skin and subcutis. The section contains a moderately well-dilineated, loosely cellular, unencapsulated dermal and subcutaneous neoplasm. Neoplastic cells are generally round and characterized by round to oval nuclei with moderate variation in nuclear size and chromatin pattern, and moderate to abundant amount of pale amphophilic to deeply basophilic granular cytoplasm. These cells infiltrate between resident collagen fibers, and are accompanied by low numbers of mature eosinophils. The mitotic index is 1. There is multifocal collagenolysis and eosinophil degranulation throughout the mass.

MICROSCOPIC FINDINGS- Grade 2 mast cell tumor, well-differentiated, mitotic index 1.

COMMENTS-Local excision appears to be complete with margins of 1.3 and 1.0 cm on either side, and 0.4 cm deep. Within the sample submitted there is at least one fascial plane deep to the tumor.

Grade 1 MCT are what is called well-differentiated and are usually benign. Grade I MCT occur in 30% - 50% of dogs. Up to 90% of dogs are cured by surgery alone.

Grade 2 MCT are intermediately-differentiated and might be benign or malignant. In other words, they are unpredictable. Grade II MCT occur in 25% - 55% of dogs. Mean survival time after surgery is 28 weeks. Radiation therapy following incomplete removal can cure over 80%. Chemotherapy is sometimes used in addition to radiation therapy.

Since these tumors can go either way more information is helpful to determine the next course of therapy if at all. This is where the mitotic index comes in to play.

Grade 3 MCT are poorly differentiated and usually malignant. Grade III MCT occur in 20% - 40% of dogs. Mean survival is 18 weeks with surgery. Post-operative chemotherapy and/or radiation therapy might prolong survival.

Mitotic index is another predictor of biological behavior of MCT. Mitotic Index is an indirect measure of cell division. It is measured as the number of mitotic figures per 10 high-powered fields (a high powered field is 400x) when using a microscope.

These grading systems are the best way to determine the individual behavior of the MCT we remove from your pet and its prognosis. Nature is complicated, and unfortunately, not all MCT fit into these orderly classifications, so thoroughness of treatment and vigilance for recurrence are important.

In addition, histopathology is an art and a science, so a pathologist that might assign a specific grade to a tissue sample might not be consistent with another pathologist. Because of this no guarantee can be given to any of these prognostic indicators.

Different studies give varying statistics on prognosis. According to the Veterinary Cancer Group in Tustin, CA the prognosis is as follows:

Grade 2 tumors have a 50% chance of recurrence at 10 months. 88% of dogs with Grade 2 tumors that are incompletely excised and undergo radiation are disease free at 5 years.

Dogs with a mitotic index of 5 or less had an average survival time after surgery of over 70 months. Those with a mitotic index of greater than 5 had a survival time of less than 2 months, no matter what grade of tumor it is.

percent of dogs with Grade II and 6 percent of dogs with Grade III were living 1500 days after surgery.

In another study, 100 percent of dogs with a Grade I MCT, 44 percent of dogs with Grade II and 7 percent of dogs with Grade III were living two years after surgery.

Radiation and chemotherapy may be used following surgery. Even if the MCT is not completely removed, 90 percent of dogs that received radiation following surgery for Grades I and II MCTs survived for at least three years.

Medical Treatment

Medical treatment is usually used when surgery is not feasible. Prednisone, a very common and effective corticosteroid (cortisone), can help in some cases when used judiciously and monitored for side effects.

Chemotherapeutic drugs are sometimes used in dogs, especially if the tumor has spread. Common drugs include:

Palladia is a kinase inhibitor which blocks the excessive production of the kit protein. It is FDA approved to treat MCT in dogs and is getting lots of hype. It is not a panacea, and when it does work (around 40% of the time), the response is for around 3 months.

Use of chemotherapeutics should never be undertaken without consultation with a veterinary oncologist. These drugs are powerful and need to be monitored for potential side effects. They also cost more than the other medications we routinely use.

Additional Therapy

As is the case with every disease, proper nutrition, access to fresh water at all times, parasite control (both external parasites like fleas and internal parasites like roundworms), exercise, and lots of TLC cannot be overlooked. In our older pets particular attention needs to be paid to the debilitating effects of arthritis, dental disease, and chronic organ disease. Hill’s makes a Prescription Diet for cancer patients called n/d that nourishes the patient without nourishing the cancer cells.

Long Term Care

Even if we completely remove a MCT there is up to a 17% chance another one will appear during your dog’s lifetime. Vigilance and early detection is of importance. Run your hands over your dog’s body at least several times per week for any problems. If you find any mass or growth we need to do an immediate FNA (Fine Needle Aspirate) looking for mast cells. We will teach you how to palpate the more obvious external lymph nodes as an additional monitoring technique.

Any pet that has been previously diagnosed with a MCT should be examined every 3-6 months. This exam should also include a blood panel, urinalysis, fecal exam, radiograph, and abdominal ultrasound.

Feline Mast Cell Tumor

MCT are the second most common tumor in the cat. Even though the basics are the same, MCT’s in cats behave differently than dogs. Cats get a skin form (called cutaneous) and what is called a visceral form (internal). It is possible for a cat to get both forms. They tend to get systemic mastocytosis more commonly than dogs.

There is no correlation to FeLV or FIP in cats that develop MCT. Siamese cats might be genetically predisposed because of a greater occurrence in this breed.

In the cat the grading system used for dogs does not apply regarding prognosis. Some are benign and some are malignant, and spread of the tumor (metastasis) can occur.

Cutaneous Form

The skin form of the feline MCT occurs around the head, eyelids and neck. Lesions can look like almost any growth, although they tend to be solitary, hairless, and raised. Lesions could be multiple, although the presence of multiple lesions does not necessarily mean a poor prognosis. Cutaneous MCT in the feline is usually benign, and for the rare times it does spread, it will go to regional lymph nodes, liver, spleen, and bone marrow just like in the dog.

Visceral Form

The visceral from of MCT usually occurs in the spleen first, then less commonly in the liver or intestine. MCT is the 3^rd most common intestinal tumor in the cat after lymphoma and adenocarcinoma.

Typical symptoms in a cat with visceral MCT are vomiting, poor appetite, lethargy, and weight loss. These are the same as the dog and relate back to histamine release in excess.

During a physical exam one of our doctors might palpate an enlarged liver or spleen, abdominal fluid (ascites) or even a mass.

Treatment

Treatment of choice in both forms is surgical removal. If the pathologist report says tumor margins are not clean we can perform the surgery again or do radiation therapy.

The spleen is a common organ for visceral MCT in the cat. This is a normal spleen during surgery.

Prognosis

Prognosis of mast cell tumors of the skin is usually excellent and surgery is generally curative.

Prognosis of mast cell tumors localized to the spleen is good and many live for an additional one to two years after the spleen is removed.

Prognosis is guarded if the mast cell tumor is located in the gastrointestinal tract.

A good prognostic indicator in the cat is appetite when first examined. Those eating well tend to live much longer.

We have a case study of a cat (her name is Ruby) that had intestinal mast cell tumor. The case study covers this cat’s diagnosis and treatment from beginning to end, with pictures of surgery. Here is the link.

Cancer Specialists

When we treat a case of MCT (or any malignant tumor) we routinely refer the case to the Veterinary Cancer Group. They are experts on cancer in animals and provide the latest treatment available. Any time we diagnose and treat a dog or cat with MCT (or any malignant tumor) we recommend you go to them for a second opinion. They will review all data and set up a long-term plan. They are also able to provide chemotherapy and radiation therapy.

I just wanted to thank you for everything you've done for Bijou and me over the years. There are no words to express my gratitude to you and your staff. Bijou is still going through chemotherapy. Realistically, I know that she doesn't have very much time left, but she has more good days than bad and, thankfully, seems oblivious to the drama that surrounds her.

I'm also writing to let you know how happy we are that you led us to the Vet Cancer Group in Tustin. We are seeing Dr. Jarrod Vancil. He is an incredible vet--knowledgeable, candid, and compassionate with both dogs and their owners. I feel so fortunate to have him as our oncologist during this difficult time. At each visit, he provides chemotherapy for the dogs, but he also provides reassuring and much-needed "therapy" for me, the owner. I just wanted to pass along this information. The staff at the Vet Cancer Group is also amazing, much like the staff you have at LBAH. Bijou does not exhibit the fears and anxiety that she did when we were going to the other cancer center. The staff goes out of their way to make people and animals as comfortable as possible.

Long Beach Animal Hospital

Mast Cell Tumor (MCT)