Mast Cell Tumor Rev01302018

MAST CELL TUMORS & CANCER –A DEADLLY TRICKSTER!

By Alice Villalobos, DVM, FNAP

Pawspice and Animal Oncology Consultation Service

Introduction

Mast cell tumors are ranked as the most deadly of skin tumors in dogs. One in five skin and subcutaneous tumors in dogs may be a tricky mast cell tumor that might transition into a deadly cancer. It is rare in humans, common in dogs and seldom seen in cats. Boxer and Bulldog breeds are at greatest risk; however, mast cell tumors are found in almost any breed. Mast cells are normally present in all tissues of the body and function in allergic reactions.  Higher numbers of mast cells are found in mucus membranes, axillary and groin region, in airways and around body openings. If your dog or cat has been diagnosed with mast cell tumors or mast cell cancer, we will do everything possible to maintain quality of life while helping to achieve remission and hopefully a cure.

Background on Mast Cells

Normal mast cells contain approximately 1,000 storage granules in their cytoplasm. When activated by an insect bite, normal mast cells release several chemicals from their storage granules by a process called degranulation. These chemicals are active in causing the effects we see in most allergic reactions. The main mast cell-released chemical is histamine, which causes inflammation, itching and gastrointestinal ulcers. One in three pets that have mast cell cancer are found at post mortem to have ulcers in the intestinal tract that caused mild to severe bleeding. Occasionally hemorrhaging from the gut causes an oncologic emergency and fatality. Other chemicals that can be released by mast cells have a heparin like action and cause local bleeding. We see this if the mast cell tumors are pinched or scratched by the pet. Certain factors, even a change in temperature, can cause the mast cells to release their vasoactive chemicals.

Biologic Behavior of Mast Cell Tumors

The behavior of mast cell tumors is variable in that some are rapidly fatal, some will smolder along while others are benign. One in eleven canine cases will appear as multiple nodules involving all the skin. I like to refer to mast cell tumors “tricksters” because they can’t be trusted to behave according to their classification.

Most pathologists will report them as Grade II, which means they don’t know how they’ll behave. The Grade III cases are biologically aggressive and almost always fatal. Some mast cell tumors will appear rapidly on the face, feet, groin or armpit (axilla). Some mast cell tumors may confuse pet carers and their veterinarians because they may resemble insect bites. Some mast cells tumors appear inflamed and hairless and may appear like pink raspberries.

Is the Location of Mast Cell Tumors a Problem?

Although it is controversial, in my opinion, Mast Cell Tumors that appear near the groin, axilla, and mammary chain or have a rapid growth rate have a poorer prognosis (less than six months). Unfortunately, no matter what Grade or Stage the pathologist originally established, some mast cell tumors might behave treacherously, especially if they originate in the “private parts” of a dog’s skin.

Diagnosis of Mast Cell Tumors

It is best to know in advance what cell type we are dealing with before excisional surgery for any lump in the skin. 

Your veterinarian can distinguish mast cell tumors that may feel like and appear like benign fatty tumors with FNA (Fine Needle Aspiration). The granules in mast cells are easily identified by cellular stains. FNA and the examination of the cells with special stain (cytology), harvested from a fine-needle aspirate of the suspicious mass, is the best way to quickly make the diagnosis without a surgical biopsy. It is excellent practice to perform FNA cytology to identify mast cell tumors before surgical excision. This is important for any and all skin and subcutaneous tumors that are not obviously warts.

If surgeons know in advance that they are dealing with a mast cell tumor, they will plan for the widest margins possible at the first surgery, which gives the patient the best opportunity for a complete excision.    

I like to use New Methylene Blue stain on all my FNA cytology specimens. The dark blue storage granules of mast cells are easy to see under microscopic examination of the stained aspirate. Early FNA diagnosis and aggressive treatment are most effective against this potentially fatal cancer.

Occasionally, some mast cell tumors do not contain the typical granules that are so characteristic for their diagnosis. These mast cell tumors are called “agranulocytic”, meaning “without granules” and they are very dangerous because they are growing so fast, they are not differentiating enough to make granules.   

Surgery for Mast Cell Tumors

Half of all mast cell tumors are considered malignant and 50% recur after surgery because of incomplete excision. If cytology shows that the mass is mast cell tumor, it is wise to take wide margins of at least the size of the mass itself or, whenever possible, to gain a 3 cm margin around the mass at the first surgery.  High Grade II or any Grade III Mast cell cancer with “dirty” or narrow surgical margins contain residual malignant cells that will cause trouble. Pathologists have developed several additional tests to try to predict the behavior of mast cell tumors. However, none of these newer and more costly Mast Cell Tumor Panels are fool proof. Most pathologists try to help veterinarians predict the behavior of mast cell tumors by classifying them as low or high Grade II.

Some veterinarians and pet carers feel that surgery may even stimulate the residual mast cells to behave more aggressively. Therefore, that dirty or narrow margin surgery site should be revisited with definitive intention to clear the tumor bed of residual malignant mast cells.

Several options are appropriate to deal with residual mast cells after a first surgery. The tumor bed may be excised (re-operated). The patient may treated with chemotherapy. The patient may be given radiation therapy to the residual cancer cells and a local lymph node. This precaution is considered a good option to offset the notorious potential behavior of mast cell tumors to act as if they were actually stimulated by the initial surgery. There are other option for those who cannot afford radiation therapy or if the tumor bed is difficult to excise. The administration of intralesional injections of various steroids may achieve permanent resolution of residual mast cells.

We may also use cryotherapy to freeze small mast cell tumors in selected senior patients who have multiple small nodule disease. Pretreatment with antihistamines and steroids is a must. Mast cell may release the contents of their granules (degranulation) during cell death after any procedure such as: intralesional injections, electroporation or cryotherapy. These less invasive techniques are attractive to clients who have older pets or pets with multiple mast cell tumors. Some clients fear or decline anesthesia for surgery and electroporation; however, they will elect cryosurgery, intralesional injections and chemotherapy, which may successfully manage the disease.

If the suture line of any excised mast cell tumor is red, swollen or won’t heal in two weeks, we need to suspect residual disease. This situation can be verified with multiple Fine Needle Aspiration (FNA) cytology samples from around the wound. 

Electroporation (EP) or Electrochemotherapy (ECT)

A newer option for mast cell tumors, especially multiple or recurrent tumors, is the use of electroporation (EP) also known as electrochemotherapy (ECT). EP is delivered under anesthesia without the need to surgically remove smaller tumors. EP can also bypass the need to surgically remove residual tumor bed tissue. EP causes the mast cells and other cancer cells to selectively open their cell surface pores and absorb the special drug, bleomycin, up to 1,000 times greater than normal. This results in selective cancer cell death, tumor site necrosis (manifested as an open sore) and healing over a period of 2-6 weeks.   

Chemotherapy for Mast Cell Tumors

Chemoreduction (making the mass smaller with chemotherapy) or radiation prior to surgery may be of value for large mast cell tumors, especially if they appear on the ventral surface of the body (ventrum). Debulking large mast cell tumors followed by electroporation is also an option that may be more affordable than pre or postoperative radiation therapy.

Chemotherapy using prednisone, vinblastine or vincristine, Chlorambucil and Lomustine along with Pepcid and Benadryl can be very helpful to shrink mast cell tumors and to prevent spread (metastasis), especially if local lymph nodes or internal organs are involved.

We may deliver intra-tumor injections into tumor beds or into non operated mast cell tumors on a weekly or every 2-3 week basis depending on the drug used. We evaluate the reduction in size of non-operated mast cell tumors.

The introduction of new targeted drugs such as Palladia (Toceranib) and Masivet (Kinavet or Masitinib) have created excellent responses in many cases in clinical studies. These new targeted drugs, initially released for mast cell cancer, have revolutionized some of our previous prognostic predictions.

Radiation Therapy

Post-surgical radiation therapy to the mast cell tumor bed has been shown to prevent recurrence in over 90% of cases that were staged as local before treatment. We Stage mast cell cancer by a process that includes aspiration of the local lymph nodes, the bone marrow and the spleen and liver. Staging is not perfect but it is worthwhile if one is about to embark on a course of radiation therapy for local control. One study reported that only two dogs of 45 staged cases broke down with metastasis after staging and radiation therapy.

Some mast cell tumors may be candidates for palliative radiation therapy, which delivers fewer but higher doses of radiation per treatment. It is aimed to slow things down and not aimed at cure. Stereotactic radiation therapy delivers targeted high doses of radiation therapy in fewer dose with the goal to cure. It is more costly. 

Staging of Mast Cell Tumors

Staging is the process of identifying where the cancer is located. It is most valuable if the patient is going to have radiation therapy, which is focused on the lesion. Previously, the value of a test called the buffy coat smear was over rated. Buffy coat smears were overused until found to be almost always negative in early cases.

If we are going to stage a dog to plan for radiation therapy, the splenic, liver and bone marrow aspirate upstages the buffy coat smear in my opinion. If I’m going to treat a dog with chemotherapy vs. radiation, I prefer that our clients spend their money on therapy rather than extensive staging or a buffy coat smear because staging does not change our approach with the mast cell chemotherapy protocols.  

In summary: for the best outcome, the war against mast cell cancer must be declared and planned prior to the first surgery! If dirty or narrow margins occur, or if it has spread, our team will do all we can to retain quality of life and seek remission and hopefully cure.

REV01302018

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