Case Report - 5 Year Old FS Boxer with Severe Mast Cell Disease

Zachary M. Wright DVM, DACVIM (oncology)

History:

Maddi originally presented to my oncology service with a 6 month history of a mass on the right flank. The mass was eventually completely excised by the referring veterinarian and diagnosed as a grade II mast cell tumor. Maddi did very well post-operatively. 1 month prior to the oncology referral, the owner noticed multiple skin growths on her forehead and inner thighs. Every day had resulted in more noticeable masses and progression of the original tumors. At the time of presentation, Maddi was on routine hydroxyzine and Tramadol for discomfort.

Assessment:

T- 102.6 HR- 110 RR-panting Wt- 57.8lbs.

Maddi was bright and alert. Her heart and lungs ausculted within normal limits. Her abdomen was soft and non painful. All of her peripheral lymph nodes palpated within normal limits. She had approximately 300 dermal masses throughout her entire body (see photos). The lesions were red, raised, and of varying sizes. The remainder of her physical exam was unremarkable.

Cytology of multiple, randomly picked masses were all consistent with well granulated mast cell tumors.

Recommendations:

The treatment of choice for all mast cell disease is surgical removal with wide (2cm) surgical margins. However, in Maddi’s presentation, the number of masses was so extensive that surgical removal was unrealistic. Thus, Maddi’s disease should be treated as a systemic illness since the entirety of her skin is involved.

The standard chemotherapy options for stage III or IV mast cell disease is a combination of vinblastine, lomustine and prednisone. However, the recent advancement of tyrosine kinase inhibitors (TKI) as a treatment for mast cell tumors has just recently landed on the veterinary market. C-kit (CD117) is a tyrosine kinase receptor (TKR) that is both mutated and over-expressed in many canine mast cell tumors. Some laboratories (Michigan State University) can evaluate histopathologic samples for these mutations and over expressions. These changes in c-kit will lead to increase cell cycle replication and more aggressive mast cell tumors.

Palladia (Pfizer) is the first veterinary approved tyrosine kinase inhibitor for the treatment of canine cancers. While it blocks a variety of different TKR, it is specifically created to block c-kit and thus has its greatest efficacy against canine mast cell disease.

Due to financial restraints, additional diagnostics (including c-kit evaluation and routine mast cell tumor staging) could not be performed and the owner elected to try the more experimental Palladia therapy instead of conventional chemotherapy.

Maddi was started on 3.0mg/kg of Palladia every other day. She was also started on standard dosages of Benadryl and Pepcid AC. Due to significant gastrointestinal toxicity associated with Palladia, it is recommended to put all naïve patients on daily sucralfate as well.

Follow-Up:

Maddi presented for a recheck exam 7 days after initiation of therapy. No Palladia toxicity was reported by the owner. Her physical exam noted dramatic reduction in most of her masses (see photos). The remainder of her physical exam was unremarkable.

She had a mild neutropenia (2000) on a CBC

which is anticipated with Palladia therapy. Treatment was continued at the previously prescribed frequencies and dosages.

Maddi again presented for a recheck exam 3 weeks later. There was still no clinical signs associated Palladia toxicity. On physical exam, her masses had almost completely resolved. However, in areas where masses were no longer palpated, Maddi had developed depigmentation in the areas of previous mast cell tumors. Her neutropenia remained but was stable.

Maddi continued to do well on the Palladia treatment protocol for another 3 months. At that time, her masses developed a resistance to the treatment and progressed rapidly causing significant pruritus and a general decline in overall quality of life. At that time, the owners elected for humane euthanasia.