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Canine Mast Cell Tumours
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Mast Cell Tumours
Mast Cell Tumors in Dogs
Mast Cell Tumors
Mast Cell
Tumours
Harvey Carruthers
www.shootingtimes.co.uk
Mast cell tumours
account for 25% of skin tumours in dogs. Some breeds, may inherit these
tumours. Individual lines of some breeds may be more prone to mast
cell tumours than others. The age of affected dogs varies, but the
average age is eight years old. Small tumours can be missed in dogs
with long or dense coats. Some common, benign growths can be similar
in appearance to mast cell tumours.
Mast cell tumours first appear as solitary lumps on or under a dog's skin,
and may grow over just a few days. The size of such lumps may vary
- they can get smaller and then grow again. Surrounding skin will
often be inflamed. Half of all growths tend to appear on the trunk
of the dog's body. Though cell tumours can look like many other tumours,
they can also resemble insect bites or an allergic reaction. The lymph
nodes can swell, as can the liver and spleen.
Diagnosis of mast cell tumours is done by a fine needle aspirate or biopsy,
often followed by surgery to remove the mass. X-rays and ultrasound
scans may help to find other masses around the body, with affected lymph
nodes often being removed. Chemotherapy or radiotherapy may be advised
for repeated or widespread mast cell tumours - 20% of dogs with a tumour
will later develop two or more unrelated tumours, which should be removed.
Some tumours are benign; they will not spread and can simply be removed.
Where moderately aggressive tumours are removed, no other treatment
may be needed, but often another growth will appear within 2 months. Opinions
vary widely on how well dogs with the most aggressive tumours fare. The
prognosis is poor if one spreads to other organs, as their function will
be affected. Mast cell tumours produce more widespread effects.
reprinted with kind permission from Alastair Balmain
Deputy Editor:Shooting Times
& Country Magazine
Blue Fin Building, 110 Southwark Street SE1 0SU
Tel: 020 3148 4750
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Mast Cell Tumors in Dogs
Author: Clinical Oncology Service
Affiliation: Veterinary Hospital of the University of
Pennsylvania (VHUP)
January 11, 1998
Mast cells are a special
type of blood cell that is normally involved in the body's response
to allergens and inflammation. Sometimes, these cells can become cancerous
and develop into mast cell tumors. The most common locations for these
tumors are the skin, spleen, liver and bone marrow. They are malignant
tumors that have the ability to spread to other organs. Even though we
know a lot about mast cell tumors, it can be difficult to predict how
they will behave in an individual dog.
Mast cells contain substances that could be released into the
bloodstream and potentially cause systemic problems. This would include
gastric ulceration, bleeding and allergic reactions (anything from swelling
around the tumor to life threatening shock). Therefore, we often put
our patients on antihistamines, antacids and corticosteroids as part
of their treatment.
Most of the remaining information will focus on cutaneous (skin)
mast cell tumors because they are the most common type seen in dogs.
Cutaneous Mast Cell Tumors (Skin)
The skin is the most common site for mast cell tumors in the
dog.
They are usually located in the skin of the legs or body. These
tumors are locally aggressive and can also metastasize (spread) to other
areas of the body. The most common sites of spread are the lymph nodes,
bone marrow and spleen.
The initial evaluation of a dog with a mast cell tumor includes:
biopsy, complete blood count (CBC), serum chemistry profile,
urinalysis, buffy coat (this is a special test that looks for mast
cells in the blood stream), lymph node aspirate and an abdominal ultrasound
(to look at the liver and spleen).
In some cases, we may also do a bone marrow aspirate to look
for mast cells there.
The pathologist assigns a "grade" to the tumor when he looks
at it under the microscope. We use the grade to help predict how the
tumor will behave. This influences both the prognosis (outcome) and
treatment plan. For example, low-grade tumors are unlikely to spread
so that complete surgical removal of the tumor may be the only treatment
required. High-grade tumors have a very high chance of spreading so we
look very carefully for spread and consider using systemic therapy (such
as prednisone) in addition to local therapy (such as surgery or radiation).
Treatment Options
Treatment option for cutaneous mast cell tumors include surgery,
radiation therapy, chemotherapy and supportive care.
Surgery is usually our first treatment choice. Because these
tumors are invasive, the surgeon must remove the tumor with a large
margin of normal tissue both around and underneath it to ensure complete
removal. Mast cell tumors are deceptive and sometimes what we can see
and feel represents only a small part of the tumor. Even when a large
margin is taken, sometimes tumor cells are still left behind. When this
occurs, additional treatment is needed, otherwise, there is the chance
that the tumor might return. Options include another surgery or radiation
therapy. It may not be possible to do another surgery because of the location
of the tumor (e.g. tumors on the leg are difficult to completely remove because
there is not much extra skin). In this case, radiation therapy is a good
alternative. Radiation therapy is very effective at preventing local recurrence
of these tumors.
It is important to remember that surgery and radiation therapy
are local treatments and have no effect on the spread of the tumor.
Chemotherapy can be beneficial in treating metastasis since it
is a systemic treatment. In the case of mast cell tumors, prednisone
(a corticosteroid or "cortisone") is one of the most effective chemotherapy
agents available. We will prescribe prednisone if we either find metastasis
or if there is a high likelihood of metastasis.
Most dogs are kept on prednisone for a 6-month period. If there
is no evidence of metastasis or recurrence by that time, the prednisone
is discontinued. There are some situations where we will recommend prednisone
for a longer period of time. The most common side effects of prednisone
include increased thirst, urination, appetite and panting. Prednisone
can also cause gastrointestinal upset and rarely, gastric ulcers. However,
we use a gradually decreasing ("tapering") dose of prednisone to try
to minimize these side effects. We may also recommend other chemotherapy
drugs on an individual basis. Unfortunately, there are no other chemotherapy
drugs that are highly effective against these tumors.
As mentioned above, we prescribe additional medications to prevent
tumor related side effects. These include an antihistamine (Benadryl)
and an antacid (usually Tagamet). We also ask that you watch your pet
closely for any problems such as vomiting (especially if there is fresh
blood), diarrhoea, loss of appetite or a very dark or black stool (this
is a sign of digested blood). If any of these signs occur, we ask that
you contact either VHUP or your local veterinarian.
The prognosis (outcome) for cutaneous mast cell tumors depends
upon several things including the "grade" of the tumor, the location
of the tumor and the presence of metastasis. Many of these tumors are successfully
treated if there is no evidence of spread at the start of treatment.
Any future "lumps" and "bumps" should be evaluated with an aspirate because
dogs that have had one mast cell tumor are at greater risk for the development
of additional mast cell tumors. Early detection of these tumors will increase
the likelihood of successful treatment.
For those tumors that have already spread or that occur in locations
other than the skin (e.g. the spleen), the prognosis is guarded. The
goal of treatment for these patients is to maintain a good quality of
life for as long as we can by controlling symptoms caused by the presence
of mast cells in the body. Symptoms can include vomiting, diarrhoea,
anorexia (loss of appetite) and lethargy (tiredness).
Unfortunately, most of these dogs will die within 6 months because
we can no longer control these symptoms.
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THE PET HEALTH LIBRARY
Mast Cell Tumors
What Is a Mast Cell?
A normal mast
cell is part of our immunologic defense systems against invading organisms.
Mast cells are
meant to participate in the war against parasites (as opposed
to the war against bacterial or viral invaders). They are bound within
tissues that interface with the external world such as the skin, respiratory
or intestinal tract. They do not circulate through the body.
The mast cell possesses within itself granules of especially inflammatory
biochemicals meant for use against invading parasites. (Think of these
as small bombs that can be released). The mast cell has binding sites
on its surface for a special type of antibody
called IgE. IgE is produced in response to exposure to antigens
typical of parasites normal mast
cell-note the
(i.e., worm skin proteins, or similarly shaped proteins).
IgE antibodies find their way
dark purple staining
to a tissue mast cell and perch there. With enough exposure
to the antigen in question, granular
structure
the mast cell may be covered with IgE antibodies like the
fluff of a dandelion. The mast
cell is said, at this point, to be sensitized.
The IgE antibodies are Y-shaped. Their foot is planted in the mast
cell while their arms lift up hoping to capture their antigen. When the
antigen comes by and is grasped by the IgE antibodies, this should indicate
that a parasite is near and the mast cell, like a land mine, degranulates
releasing its toxic biochemical weapons. These chemicals are harmful
to the parasite plus serve as signals to other immune cells that a battle
is in progress and for them to come and join in.
At least this is what is supposed to happen.
We live in a clean world without a lot of parasites. What unfortunately
tends to happen is that the IgE/mast cell system is stimulated with other
antigens that are of similar shape or size as parasitic antigens. These
next best antigens are usually pollen proteins and the result is an allergy.
Instead of killing the invading parasite, the mast cell biochemicals produce
local redness, itch, swelling, and other symptoms we associate with allergic
reactions.
And the Mast Cell Tumor?
As if the mast cell isn't enough of a troublemaker in this regard,
the mast cell can form a tumor made of many mast cells. When this happens,
the cells of the tumor are unstable. This means they release their toxic
granules with simple contact or even at random creating allergic symptoms
that do not correlate with exposure to any particular antigen.
Mast cell tumors are notoriously invasive and difficult to treat.
Canine
Mast cell tumors are especially common in dogs accounting for approximately
one skin tumor in every five. The Boxer is at an especially high risk,
as are related breeds: English Bulldog, Boston Terrier. Also at higher
than average risk are the Shar pei, Labrador Retriever, Golden Retriever,
Schnauzer, and Cocker Spaniel. Most mast cell tumors arise in the skin
but technically they can arise anywhere that mast cells are found. The
mast cell tumor does not have a characteristic appearance though because
of the tumor's ability to cause swelling through the release of granules,
it is not unusual for the owner to notice a sudden change in the size of
the growth or, for that matter, that the growth is itchy or bothersome to
the patient.
Diagnosis can often be made with a needle aspirate, which collects
some cells of the tumor with a needle, and the cells are examined under
the microscope. The granules have distinct staining characteristics leading
to their recognition. An actual tissue biopsy, however, is needed to grade
the tumor and grading of the tumor is crucial to determining prognosis.
Grading the Mast Cell Tumor
The pathologist grades mast cell tumors when the biopsy sample
is read. The grade is a reflection of the malignant characteristics of
the cells under the microscope (which of course generally correlates to
the behavior of the tumor) with Grade I being benign, Grade III being
malignant, and Grade II having some ability to go either way.
Grade I Tumors
This is the best type of mast cell tumor to have. While it may
tend to be larger and more locally invasive than may be visually apparent,
it tends not to spread beyond its place in the skin. Surgery should be curative.
If the original biopsy sample shows that the tumor has only narrowly been
removed or that the tumor extends to the margins of the sample, a second
surgery should promptly be done to get the rest of the tumor if at all
possible. If the grade I mast cell tumor is incompletely excised it will
grow back in time; it is best to get it all and be done with it as quickly
as possible. About half of all mast cell tumors are Grade 1 tumors and
can be cured with surgery alone.
Grade III Tumors
This is the worst type of mast cell tumor to have. Grade III tumors
account for approximately 25% of all mast cell tumors and they behave
very invasively and aggressively. If only surgical excision is attempted
without supplementary chemotherapy, a mean survival time of 18 weeks (4-5
months) can be expected.
Grade II Tumors
This type of tumor is somewhat unpredictable in its behavior. Recent
studies have shown that radiation therapy administered to the site of
the tumor can cure greater than 80% of patients as long as the tumor has
not already shown distant spread.
Staging The Mast Cell Tumor
In order for a rational therapeutic plan to be devised, the extent
of tumor spread (or stage of the tumor) must be determined. Between the
stage and the grade, a plan can be devised. The tumor is staged 0 through
IV as described below:
Stage 0: one tumor but incompletely excised from the skin
Stage I: one tumor confined to the skin with no regional
lymph node involvement
Stage II: one tumor confined to the skin but with regional
lymph node involvement present
Stage III: many tumors or large deeply infiltrating tumors,
with or without lymph node involvement
Stage IV: any tumor with distant spread evident (this stage
is further divided into substage a (no clinical signs of illness) and
substage b (with clinical signs of illness). In order to determine the
tumor stage some probing of other lymphoid organs must be performed.
Your veterinarian may recommend the following tests:
Basic Blood Work
A basic blood panel is part of this evaluation process and should
be obtained at this point if it has not already been obtained. This testing
will help show any factors that limit kidney or liver function and thus
determine what drugs of chemotherapy can or cannot be used. It also will
show if there are circulating mast cells in the blood (a very bad sign)
or if anemia (low red blood cell count) is present which might be related
to the tumor.
Buffy Coat Smear/Bone Marrow Tap
The buffy coat is the small layer of white blood cells that floats
atop the layer of red blood cells when a capillary tube of the patient's
blood has been centrifuged. This layer of cells can be smeared onto a
microscope slide and checked for circulating mast cells. This process
was once considered an important method of evaluating mast cell spread
in dogs but has more recently been found not very helpful. This test is
still of use for cats but has been supplanted by an actual bone marrow
tap for dogs. The idea behind both of these tests was to determine the
presence of malignant mast cells in the bone marrow (malignant cells circulating
in the blood/found in the buffy coat would indicate malignant cells in the
marrow).
Local Lymph Node Aspiration
The lymph nodes local to the site of the tumor should be aspirated
(if they can be found) to see if the tumor has spread there.
Aspiration of the Spleen/Radiographs
The size of the spleen can be evaluated with radiographs but ultrasound
guidance is generally needed to withdraw some cells for testing. The spleen
is an organ of the lymph system and the presence of tumor in the deeper
lymph organs such as the spleen and abdominal lymph nodes should be assessed.
While the mast cell tumor does not spread to lungs the way other tumors
do, there are many lymph nodes in the chest and it is helpful to radiograph
the chest to assess the size of these lymph nodes and thus help determine
the extent of tumor spread.
Other Factors In Prognosis
As if grade and stage do not pose enough food for thought, other
factors add in to the prognosis.
Anatomic Location: Mast cell tumors arising in the following
areas tend to be the most malignant: nail bed, genital areas, muzzle,
and oral cavity. Mast cell tumors that originate in deeper tissues such
as the liver or spleen carry a particularly grave prognosis.
Growth Rate Of Tumor: Tumors that have been present for months
or years tend to be more benign.
Argyrophilic Nuclear Staining Organizing Regions (AgNORs):
The pathologist can use a special silver stain on the tumor sample.
The uptake of this stain correlates to the rapidity with which the tumor
cells proliferate. The higher the AgNOR count, the more malignant the
tumor.
There are other testing features that can be applied to the sample
but, in general, the grade, stage, location and symptoms of the patient
help point to therapy.
Therapy
Therapy for mast cell tumors consists of surgery, radiation therapy,
and chemotherapy (as is the case for almost all types of cancer). What
combination of the above is chosen depends on the extent of spread and
malignant characteristics of the tumor.
Surgery
If the tumor can be cured with one or even two surgeries, this
is ideal. Mast cell tumors are highly invasive and very deep and extensive
margins (at least 3 cm in all directions) are needed. If for some reason,
a grade I or II tumor cannot be completely excised, radiation therapy makes
an excellent supplement.
Radiation Therapy
While radiation therapy tends to be expensive, the potential to
permanently cure a grade I or II mast cell tumor is likely worth it. Radiation
is a therapy most appropriate for localized disease. If the tumor stages
so as to show more distant spread, radiation becomes less helpful and medications
(chemotherapy), which can be delivered to the tumor through the patient's
own vasculature becomes needed.
In January 2004, Hahn, King and Carreras published a study where
radiation therapy was used to treat incompletely removed Grade III mast
cell tumors. They studied 31 dogs with Grade III mast cell tumors that
did not show evidence of distant spread beyond the external area where
the tumor was first detected. They treated these dogs with radiation
sessions given three days a week for a total of 18 sessions. Approximately
65% of dogs achieved remission and 71% were alive one year after treatment.
The median remission time was approximately 28 months, with dogs having
ear, or genital tumors doing better than dogs with tumors in other locations,
Dogs with tumors less than or equal to 3 cm in diameter prior to surgery
had a median survival time of 31 months. These are optimistic findings for
the Grade III mast cell tumor, even though radiotherapy is an expensive
treatment method.
Chemotherapy
Currently three anti-cancer drugs have been particularly helpful
in combating mast cell disease: Corticosteroids (such as prednisone),
Lomustine, and Vinblastine.
Corticosteroids seem to be directly toxic to mast cells
and can lead to a brief remission even when used alone. They are particularly
inexpensive treatments and definitely worth trying should more powerful
chemotherapy drugs be considered too expensive or troublesome.
At this time, statistics for survival and disease-free interval
with this type of combination therapy are not available. An oncologist
should be consulted for details.
The mast cell tumor releases histamine-containing granules that
lead to inflammation and increased stomach acid secretion.
These unpleasant symptoms may be alleviated with the use of H1
blockers (antihistamines such as Benadryl® and others) as well as
H2 blockers (antihistamines such as Pepcid AC® and others).
These medications help palliate the inflammatory effects of the
spreading malignant mast cell tumor.
Feline
The mast cell tumor situation is slightly different for cats though
most of the same concepts hold true (so if you skipped the canine section
to read the feline information it would be best to go back and read the
canine section at this point). Mast cell tumors classically affect
older cats; in one study the average age was 10 years. Pathologists
divide mast cell tumors into two forms: Well Differentiated and Poorly
Differentiated. The well differentiated tumor is generally more benign
in its behavior while the poorly differentiated tumor behaves more malignantly.
But mast cell tumors in cats are also classified by their location into
two forms: cutaneous (located in the skin) and visceral (located internally).
A very unlucky cat may have both.
Cutaneous Forms
The skin form of the feline mast cell tumor classically arises
around the head and neck. Lesions may be solitary or multiple with the
presence of multiple lesions not necessarily boding poorly (though if
there are many mast cell tumors present, that would constitute rather
a lot of inflammatory biochemicals about and more symptoms for the cat).
Treatment of choice would be surgical excision. If surgical excision
is incomplete, radiation therapy as a follow-up is generally successful
at "cleaning up" any leftover cells still present.
Visceral Form
As one might surmise, mast cell tumors located internally are more
serious than those in the skin. The most common organs involved are
spleen, liver, and intestine. Vomiting, appetite loss, and weight
loss are the most common symptoms. As with the cutaneous form (but not
as easily accomplished), surgery is the treatment of choice; no single
chemotherapy protocol has emerged as being particularly successful above
the others. Unlike the canine situation, it is not all that helpful
to stage the disease with buffy coat smears and bone marrow taps (though
localizing the disease to the spleen with a splenic aspirate might be particularly
useful - see below) as presence of tumor cells in these locations has not
altered prognosis for this disease. The most telling piece of information
for prognosis actually comes from the history: appetite. Cats that are
eating decently at the time they are first brought to the veterinarian
have a median survival of 19 months, while cats that are not eating have
a median survival of 8 weeks.
Splenic Mast Cell Tumor
Luckily, the spleen can be removed leading to a a rapid recovery.
The median survival after splenectomy is 14 months (vs. 4-6 months if
the spleen is left in place). This is not to say that the cat is cured with
splenectomy, but removing the spleen frees the cat from the bulk of the
mast cells quickly and it takes time for the tumor to regrow.
After diagnosis of mast cell tumor has been made, consider consultation
with an oncologist for the most up to date information on chemotherapy
or other adjunctive treatment.
Date
Published: 12/28/2003 12:04:00 PM
Date Reviewed/Revised:
04/17/2006
Copyright
2006 - 2007 by the Veterinary Information Network, Inc. All rights reserved.
This work was originally published by Veterinary Information
Network, Inc. (VIN) and is republished with VIN's permission.
The above information is simply informational.
It's intent is not to replace the advice of a veterinarian nor to assist
you in making a diagnosis of your pet. Please consult with your own veterinarian
for confirmation of any diagnosis. Your pets life may depend on it.
