Mast Cell Tumors in the Dog: A New Hope

Filed Under: Dogs, Diseases

Has your dog recently been diagnosed with a mast cell tumor?  Has your veterinarian given you a rather gloomy prognosis?  Take heart:  Pfizer Animal Health™ has a new chemotherapy drug coming out specifically for the treatment of mast cell tumors in the dog.  

Mast cell tumors, mastocytomas, mast cell sarcomas, or mastocytoses, as they are sometimes referred to, are the most common malignant or potentially malignant skin tumor occurring in the dog.  In fact, these conglomerations of mast cell sheets account for 15% to 20% of all skin tumors that occur in the dog.  Mast cell tumors may occur singly or in multiples.  They typically affect dogs around 9 years of age, but they have been seen in pets as young as 3 weeks and as old as 19 years.  Breeds that are predisposed to mast cell tumors include boxers, Boston terriers, Labrador and Golden retrievers, beagles, Shar-Peis, English bulldogs, bull terriers, fox terriers, Staffordshire terriers, dachshunds, pugs, Weimaraners, and schnauzers.  

You might ask what a mast cell is exactly, and how they evolve.  Premature mast cells develop from the bone marrow and migrate through the blood where they finally localize in connective or mucosal tissues.  Once present in connective tissues, these premature cells proliferate and differentiate into mature mast cells.  Mature mast cells serve as synthesizers, or storage facilities, for numerous inflammatory mediators.  One of the most common preformed inflammatory mediators found in a mast cell is histamine; therefore, mast cells play important roles in inflammatory and immune responses.  

Mast cell tumors may appear to be soft to solid masses, either as raised nodules or pedunculated.  These tumors range in size from a few millimeters to several centimeters or larger in diameter.  On first appearance these tumors may appear to be encapsulated, but they are not.  Mast cell tumors are actually dense aggregates of mast cells surrounded peripherally by less densely aggregated mast cells which may be misinterpreted as normal tissue. 

On pathology mast cell tumors are graded to assess their ability to metastasize.  Well-differentiated tumors carry an approximate metastatic potential of 10% (i.e. 10% of these tumors will spread to other areas), while poorly differentiated mast cell tumors have a 55%-96% rate of potential metastasis.  Mast cells may be detected in the peripheral blood and bone marrow in cases of widespread dissemination.  Shar-Peis tend to have mast cell tumors that are poorly differentiated, and they therefore typically carry a worse prognosis.  

Other commonly seen clinical signs with mast cell tumors are gastric (of the stomach) or duodenal ulcerations, which occur in 25% of all dogs having mast cell tumors.  These ulcers result from the histamine released by mast cells.  Histamine stimulates H2 gastric parietal cell receptors, which will ultimately increase hydrochloric acid secretion.  Ulceration may lead to blood loss, and in severe cases, hypotensive shock.

The initiating causative agent for mast cell development has not yet been confirmed.  In the boxer and Boston terrier, tumors have been shown to be transferable from one dog to another, which some researchers fear could signal a viral origin; however, few, if any, viral particles have been detected following such transfers.  A gene susceptibility has also been theorized to be necessary for tumor formation.

The preferred treatment for mast cell tumors is currently wide surgical resection.  Surgical margins should extend at least 3 cm in all directions including the deep margin.  Despite wide surgical excision, approximately 50% of canine mast cell tumors will recur within 4 months following surgery.  Chemotherapy is primarily used for the treatment of tumors that have spread (metastasized), are non-resectable, or are high-grade tumors that may be considered for microscopic residual disease.  Radiation is the treatment of choice for microscopic residual disease or for non-resectable tumors.  Other commonly used treatments include cryosurgery, electrosurgery, radiotherapy, and immunotherapy.  

Pfizer™ has recently announced the release of Palladia®, or toceranib phosphate.  This drug has been specifically developed for dogs to treat grade II or grade III recurrent, cutaneous mast cell tumors with or without regional lymph node involvement.  Pfizer will initially release Palladia ® to oncology specialists and hope to release the product to general practice veterinarians in 2010.  The medication will be available in tablet form and is given orally every other day.  The dose may be modified when necessary to avoid side effects.  The most common side effects of Palladia ® include diarrhea, decreased appetite, lethargy, and vomiting.  Life threatening side effects can occur but are rare.  Palladia ® should not be given to dogs used for breeding, or those who are pregnant or lactating.  Additionally, Palladia ® should not be given concurrently with corticosteroids or other non-steroidal anti-inflammatories as the risk of gastric and intestinal bleeding will increase.  Children and pregnant women should avoid direct contact with Palladia ® as well as the biological waste from dogs treated with the medication.

With affected dogs, survival time is directly related to the degree of histologic differentiation found on pathology.  Dogs with a high-grade mast cell tumor have a mean survival time of just 18 weeks following the diagnosis.  Dogs with a low-grade tumor will have an average survival time of 51 weeks.  Hopefully, with Pfizer’s™ new drugPalladia ®, the survival rates and times will greatly improve for these poor dogs.

References:

Fossum, Theresa, and Cheryl Hedlund, et al.  Small Animal Surgery.  Mosby, 2nd Edition:  2002. P. 661.

Fraser, Clarence, and Jan Bergeron, Eds., et al.  The Merck Veterinary Manual. 7th Edtion: 1991.  Pp. 862-863.

Maxie, Grant, Ed.  Pathology of Domestic Animals.  Saunders/Elsevier,  5th Edition, Vol. 1:  2007.  Pp. 771-772.

Scott, Danny, and William Miller, et al.  Muller & Kirk’s Small Animal Dermatology.  Saunders, 6th Edition:  2000. Pp. 553-556, 1320-1330.

Stanclift, Rebecca, and Stephen Gilson.  “Evaluation of Neoadjuvant Prednisone Administration and Surgical Excision in Treatment of Cutaneous Mast Cell Tumors in Dogs.”  JAVMA.  Vol. 232, No. 1:  2008.  Pp. 53-62.

 Zeltzman, Phil.  “Cancer Surgery Never as Good as First Time.  Veterinary Practice News.  March 2009. Pp. 23.

Topics: cancer, skin conditions