Mast Cell Tumors in Dogs and Cats
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Article Written by Dr. Daniel A. Degner, Board-certified Veterinary Surgeon (DACVS)

Key Points

Mast cell tumors are a lot larger than they appear to the naked eye, therefore large margins of normal looking tissue must also be removed

Mast cell tumors in cats and ferrets frequently are benign

Radiation therapy is an effective means to treat mast cell tumors that cannot be surgically removed

Chemotherapy is indicated to shrink tumors down to resectable size and for patients that have high grade tumors

 


What are mast cells?

Mast cells are normally found in the tissues of the body. They release histamine when stimulated by mechanical factors (tissue injury) or chemical factors (allergies). Histamine causes signs of allergies such hives and increases production of acid in the stomach. Proteolytic enzymes released by mast cells delay healing of incisions. Heparin, a blood thinning agent also found in the mast cells, increases the bleeding into traumatized tissues. There are many other chemical messangers that are found in mast cell granules, but these will not be discussed in this article.

 

Mast cell tumors

A mast cell tumor is a mass of cancerous mast cells. These tumors are common location for mast cell tumors is in the skin. Mast cell tumors can be located in the fatty layer beneath the skin. They can form in organs such as the liver, spleen, intestines, stomach. Theses tumors may spread into lymph nodes, the blood stream, the bone marrow or the internal organs.

 

Effects of mast cell tumor degranulation

Excessive levels of histamine in the blood stream from the mast cell tumor degranulation can cause stomach ulcers to develop. Signs of stomach ulcers include vomiting blood or coffee ground-like material, black stools, decreased or loss of appetite, and stretching in a praying position (due to abdominal pain). Extensive bruising and swelling is common following fine needle aspiration of high grade tumors. Shock and death may occur due to acute degranulation of the tumor cells. Poor healing of the incision following tumor excision, especially if residual tumor is left behind.

 

Signs of a mast cell tumor

Mast cell tumors have been refered to as the "master of disguise", as they can mimick the appearance of benign tumors. The most common presentation of a mast cell tumor is a lump in the skin (so called "button tumor"); about 10% of the patients will have or will develop multiple mast cell tumors in the skin. The mass may appear as a raised pink lump (see photo below). Mast cell tumors located in the fatty tissues (subcutaneous tissues) frequently feel like an ill-defined mass; higher grade tumors tend to have a more ill-defined margins. If the lump is massaged or rubbed it may swell or form hives….called the Darier sign; this is caused by the release of histamine from the mast cells.

The photos below are from patients that had mast cell tumors.

 

Diagostic work-up

A fine needle biopsy (aspirate) and cytology (examination of cells under a microscope) is used to establish a diagnosis of a mast cell tumor. Cells of this tumor are round, have a round nucleus, and are filled with many blue granules. Eosinophils are found amongst the mast cells, and the background is invariably stipled with blue granules from ruptured mast cells. High grade mast cell tumors cells may have few or no visible granules with standard cytology stains; however, special stains will show the granules in the tumor cells. A complete cell count, chemistry profile and urinalysis results are evaluated to ensure that the pet has good internal organ health for the general anesthesia and no complicating factors from the mast cell tumor. Abdominal ultrasound is used to look for internal organ and lymph node enlargement. If abnormalities are noted, fine needle biopsy of affected organs is performed. Chest radiographs rarely show spread of mast cell tumors to the lungs; however, enlargement of lymph nodes in the chest may be found. Bone marrow biopsy is recommended for patients having a high grade tumor or those that have indicators of high malignancy on the proliferative panel.

 

 

Surgery of mast cell tumors of the skin

Benadryl should be given to the patient prior to surgery to minimize degranulation effects of the mast cell tumors during surgery; high grade tumors are more prone to degranulating and causing low blood pressure or shock during surgery than mid and low grade tumors. In dogs, 2 cm of normal looking skin surrounding the tumor and a deep layer of tissue (dense fascia or muscle) should also be removed with the mass. High grade tumors should have 3 to 4 cm side margins and a deep layer of tissue removed around the mass. The removed tissue is evaluated by a pathologist to determine tumor type, tumor grade, and completeness of tumor removal.

In cats, mast cell tumors located in the skin are commoly grade 1 tumors, therefore only a small border (0.5 to 1 cm) of normal looking skin surrounding the tumor may be needed to be removed with the mass to achieve a surgical cure.

 

 

Additional therapy

If the histopathology report indicates that the mast cell tumor has incomplete or very close surgical margins, additional surgery can be performed to remove more tissue. This should be the first choice of treatment if additional tissue can be safely removed. The tissue again is sent to a pathologist to ensure that the entire tumor has been removed.

Chemotherapy may be recommended before or after surgery. Indications for adjunctive chemotherapy includes high grade tumors, high index of cell proliferation (proliferative study), cKit mutation, and presence of metastasis to regional lymph nodes, internal organs or the bone marrow. Prednisone, which is a steroid may help to shrink the tumor size, but is effective at best in only 20% of the cases. Incomplete response is due to prednisone does not kill the tumor cells rather decreases the size of the tumor by reducing tumor-associated inflammation; a positive response is typically seen for only 1 to 2 months. Vinblastine, vincristine, lomustine (CCNU), cyclophosphamide, hydroxyurea (chemotherapy) can improve the long-term survival in some patients. Chronic treatment with benadryl has been suggested for dogs that have developed multiple mast cell tumors. Palladia is a tyrosine kinase receptor blocker; the proliferative panel is used to determine if the patient should be prescribed this medication. The tumor should be positive for cKIT mutations for this drug to be potentially effective. Ulcers of the stomach and intestine have been a common side effect of this medication, but this may be due to overdosing this medication.

Radiation therapy may be used to "clean up mast cells that are left behind" following incomplete removal of a mast cell tumor. Mast cell tumors are moderately sensitive to radiation therapy. Radiation therapy is not a good choice if the tumor has spread to the internal organs.

     

     

Prognosis in dogs

In dogs, the prognosis following treatment of mast cell tumors of the skin is directly related to the grade of the tumor as determined by the biopsy results (histopathology). If the tumor has been completely removed with surgery, then recurrence of the tumor should be low. Grade 1 tumors have a benign behavior and an excellent cure rate with surgery. Grade 2 tumors bear a moderately malignant behavior, and have a 20% recurrence rate following aggressive surgery. Grade 3 tumors are very malignant, commonly metastasize and 10% of these patients are alive at 1 year following surgery.

Some pathologists subclassify grade 2 mast cells as high grade 2 or low grade 2 mast cell tumors; high grade 2 tumors behave like grade 3 tumors and low grade 2 mast cell tumors behave like grade 1 tumors. Beware that grading mast cell tumors is very subjective. In one study, mast cell tumors were graded by a group of pathologists and they commonly disagreed upon the grade of the tumors. A much better testing method of determining the how malignant or benign a mast cell tumor will behave is a proliferative study. This includes PCNA (proliferating cell nuclear antigen), AgNOR (agyrophilc nuclear oganizing regions), and Ki67. Tyrosine kinase receptors (a receptor for mast cell growth factor) is also important and tests related to this include cKIT mutations and KIT staining patterns. All of these tests in the panel are important, however cKIT mutations are very dangerous and the Ki67 also seems to be very important. These tests are more expensive than standard testing (histopathology), but they seem to be worthwhile.

Mast cell tumors located on the muzzle and oral cavity tend to have a more malignant behavior. Mast cell tumors located in the perineal region (anus, scrotum and vulva) may not have as aggressive of behavior as previously believed, however tumor in these locations may be more difficult to remove. Dogs that have evidence of mast cells also in the internal organs, blood stream or bone marrow have a poor prognosis.

Tumors that are ulcerated may result in a poor prognosis. Dogs that have signs of gastrointestinal ulcers (vomiting, black stools) generally have a poor prognosis. Tumors that are large have a poor prognosis (larger than 4 cm). Tumors that have shown recent rapid growth have a poor prognosis. Mast cell tumors which have not changed for a period of 2 months frequently have a good prognosis.

Tumors that have recurred after surgical removal may result in a poor prognosis. Dogs living greater than 30 weeks after surgery and not having any recurrence of local or distant tumor are considered cured

 

Prognosis in cats

In cats, the prognosis following removal of mast cell tumors of the skin is usually excellent and surgery is commonly curative. The 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. Sometimes cats have multiple mast cell tumors all over their body which may spontaneously resolve or may progress with time and result in death (see photo below).

 

Frequently Asked Questions After Surgery

When should my dog have the first bowel movement after surgery?

  • Many dogs will not have a bowel movement for the first 4 to 5 days after surgery
  • Reasons that a dog will not have regular bowel movements after surgery include:
    • The dog has been fasted prior to surgery
    • Dogs do not eat well during the hospital stay
    • They frequently do not eat well when they go home
    • They are fed highly digestible food that produces little stool
    • Pain medication that contain narcotics (such as morphine, fentanyl patches, and tramadol) can be constipating
  • If a pet does not have a bowel movement on the 5th day of being home, a stool softener such as metamucil can be fed
    • Dose of metamucil is 1 tsp per 25 Kg mixed in with each meal (canned dog food); feed immediately after mixing, as the metamucil will gel the food and may make it less palatable

My pet had surgery and will not eat.  What can be done?

  • Dogs
    • Most pets will not eat their regular dog food after surgery, especially if it is kibble.
    • Offer a cooked diet having a 1:1 ratio of a protein source and carbohydrate source.  The protein source can be any meat (example: chicken breast, turkey breast, lean hamburger) that is low in fat and should be cooked (drain off all fat after the meat has been cooked).   The carbohydrate can be pasta, potato or white rice.
    • Try canned dog food; to enhance the flavor sprinkle a very small amount of garlic powder or chicken or beef broth (Chicken-in-a- MugTM or Beef-in-a-MugTM products)
    • Try Gerber strained meats for babies such as the chicken, beef, turkey, or veal
    • Try Hill's A/D diet available at most veterinary hospitals
    • Hand feeding: place a small amount of food in the mouth so that your dog gets the flavor
    • Warm the food slightly in a microwave, as the food will be more aromatic; stir the food before feeding and test the temperature on the bottom side of your wrist; it should only be luke warm.
    • Remember that most pets will not eat the first day or two after they get home from surgery
  • Cats
    • Offer smelly foods that contain fish such as tuna or smelly cat foods
    • Try Gerber strained meats for babies such as the chicken, beef, turkey or veal
    • Hand feeding:  with your finger place a small amount of food on the roof of your cat's mouth; use a syringe to get soft food into the mouth
    • Warm the food slightly in a microwave as the food will be more aromatic; remember to stir the food before feeding and test the temperature; it should be only luke-warm
    • Some cats will only eat dry food, try kibble if your cat normally has been fed that food
    • Petting and stroking your cat frequently will help to stimulate appetite
    • Remember that most pets will not eat the first day or two after they get home from surgery
    • Appetite stimulants such as cyproheptadine may be helpful
    • If your cat refuses to eat anything for 7 days a stomach tube or nasogastric tube should be placed to provide nutrition so that a serious liver problem (hepatic lipidosis) does not develop

My pet is vomiting.  What can be done?

  • The first thing for you to discern is whether your pet is vomiting or regurgitating.  Both will result in fluid or food being brought up.  Vomiting always will have heaving or retching of the abdomen prior to expulsion of the vomitus.  Regurgitation is not associated with heaving and the pet usually just opens the mouth and fluid or food will be expelled.  Usually the regurgited material will be clear or brown colored fluid. 
  • Next is to identify the cause of the vomiting or regurgitation.
  • Causes and treatment of vomiting after surgery
    • When some pets return home after a stay in the hospital they may drink excessive amounts of water at one time and then vomit; if this appears to be the case, the water should be limited to frequent smaller amounts.
    • Medications such as antibiotics, narcotics or nonsteroidal anti-inflammatory medication commonly cause vomiting after surgery.  In order to see which medication is causing the problem, the administration of each drug should be separated 2 hours apart.  Usually the pet will vomit or appear nauseated (drooling and sick look) within 1 hour of administration of the medication that they are sensitive to.  The antibiotic in some cases may be changed to a different one, or may be discontinued. 
    • Stomach upset from anesthesia is a potential cause of vomiting and will pass within a couple of days. 
    • An uncommon cause of vomiting after surgery is internal organ failure.  Blood testing will confirm this problem. For this reason vomiting should not be ignored if it persists for more than 24 hours.
    • If your pet had surgery of the bowels or stomach, vomiting is always a concern, as it may indicate that infection of the abdominal cavity, called peritonitis, is present.  Do not ignore this sign.
    • Symptomatic treatment of vomiting involves withholding food for 12 to 24 hours, then introducing small amounts of bland food such as rice and lean cooked hamburger, if your pet does not vomit after that then gradually wean him/her back onto the regular diet after 3 days.  In order to decrease the acidity of the stomach, Pepcid AC 0.5 mg/kg can be given by mouth twice daily for 5 days.  Metoclopramide and Cerenia are good anti-vomiting medications for dogs and cats.  You should always consult a veterinary healthcare professional before administering medication.
  • Causes and treatment of regurgitation after surgery
    • The most common cause of regurgitation is reflux of acid from the stomach into the esophagus while your pet is under anesthesia.  Acidic fluid from the stomach can cause a chemical burn of the esophagus and result in a bad case of heart burn, called esophagitis.  This results in poor motility of the esophagus, therefore water and food will accumulate in this structure.  In most cases, esphagitis is self-eliminating and will resolve within two or three days. 
    • If the esophagitis is severe the esophagus may develop one or more strictures.  A stricture is a narrowing or stenosis of the esophagus and does not allow passage of food down the esophagus, in regurgitation that lasts longer than one week.  This problem should be brought to the attention of your pet's doctor within the first two weeks so that it can be treated by ballooning the stricture (minimally invasive procedure, as it is done with the aide of an endoscope).  If an esophageal stricture is chronic surgery is needed.
    • Symptomatic treatment of regurgitation caused by esophagitis includes feeding bland food, and administering a coating agent (sucralfate) and an acid blocker (omeprazole or other).  Consult a veterinary health care professional if the regurgitation continues for more than a couple of days.

How do I know that my dog is in pain following surgery?

  • Signs of pain include
    • crying
    • biting if you get near the surgical site
    • grimacing (lips are pulled back and the the dog looks anxious)
    • tragic facial expression
    • panting
    • restlessness and unable to sleep; pacing
    • if abdominal surgery was done the pet will not lie down on the incision, or will continually sit up in spite of appearing very tired
    • the worst pain will be for the first 2 to 3 days after surgery

What can I do to control my dog's pain?

  • Narcotic medications that control pain: tramadol, butorphanol, Duragesic (fentanyl patch)
  • Anti-inflammatories used to control pain: Deramaxx, Rimadyl, Previcox, or Etogesic
  • If an orthopedic surgery has been done cold packing the surgical site may be helpful
    • A cold pack may be a pack of frozen peas, crushed ice in a Ziploc bag, or a cold gel pack; place a thin barrier between the skin and the cold pack.  An alternative to a cold pack is to freeze water in a styrofoam cup; after frozen cut the bottom of the styrofoam cup out. Cool the surgical site around the incision by rubbing the exposed ice directly on the skin in a circular pattern.  Cooling the surgical site helps to numb the area.

How do I know that my cat is in pain following surgery?

  • Pain is more difficult to assess in cats versus dogs, as signs can be more subtle and they usually do not vocalize when in pain
  • Signs of pain in a cat include the following:
    • biting if you get near the surgical site
    • growling or deep cry
    • not wanting to eat
    • hiding and not wanting to be near owner (remember that this could also be caused by the cat just being upset about leaving home and coming back)

What can be done for pain at home for my cat?

  • Pain medication such as buprenorphine or a Duragesic (fentanyl) patch
  • Tylenol will kill a cat as they lack abundant glutathione enzyme in the liver
  • Anti-inflammatories can be used, but the dose is much less than dogs

Is it okay for my pet to lick the incision?

  • If a dog licks the incision, the healing process may be delayed.
  • Licking can remove stitches and cause the incision to open
  • Licking can become a severe habit that is difficult to break
  • Licking can cause infection as the mouth has many bacteria
  • Dogs will frequently lick the incision when the owner is not watching such as at night time; if the skin looks red or excoriated the most common cause is from licking.
  • To stop your pet from licking the following can be tried:
    • Elizabethan collar can be placed on the neck; this will not help stop your pet from scratching at the region
    • Cervical collar (bite not collar) is a less awkward device and can be effective at stopping a pet from licking the surgical site
    • A tee shirt can be used to cover an incision on the chest or front part of the abdomen; gather the waist of the shirt up over the dog's back and wrap an elastic band around this part of the shirt.
    • A bandage or sock can be used to cover an incision on a limb; fasten the top of the sock to the dog's limb with tape.
    • Bitter apple can be applied around the incision; many dogs will continue to lick  after application of this topical
    • Bitter Apple and Liquid HeetTM (obtain this from a drugstore...it is used for sore muscles) mixed in a 2:1 ratio can be applied around the skin incision
    • Antipsychotic medication in some cases is needed

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  • Experience in the development of new surgical treatments

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