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Mast Cell

No one

Big Dog
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 mean 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.”

IgE_antibodies.gif

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). 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 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&#8221 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).
 
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No one

Big Dog
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.
 
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