Normal mast cell
-
note the dark purple staining granular
structures

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 (i.e. worm
skin proteins, or similarly shaped proteins). IgE antibodies find
their way to a tissue mast cell and perch there.  With enough
exposure to the antigen in question, 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 releases 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).

Boxer

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.

Chinese Shar
pei

Labrador
Retriever

Golden
Retriever

Miniature Schnauzer.

Cocker
Spaniel

Diagnosis can often be made by aspirating some
cells of the tumor with a needle and examining them 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

Mast cell tumors are graded by the pathologist when
the biopsy sample is read. The Grade is a reflection of the
malignant characteristics of the cells under the mircoscope (which
of course generally correlates to the behavior of the tumor) with
Grade 1 being benign, Grade 3 being malignant, and Grade 2 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 excistion 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 >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 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
basically 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
lung 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, there are other factors that 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 become 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 acheived
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 < 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, eventhough
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 to 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 which 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.

Page last updated:
6/16/05