Olya A. Smrkovski, DVM, DACVIM (oncology)
Dr. Olya A. Smrkovski
Mast cell tumors comprise 16% to 21% of all skin tumors and represent the most common cutaneous neoplasm in dogs (Figure 1).1 Predisposed breeds include boxers, Boston terriers, Labrador retrievers, beagles, and schnauzers.1 Metastatic rates vary but tend to be correlated with the histologic grade of the primary tumor. Low-grade cutaneous mast cell tumors have a metastatic rate of 10% to 15%, whereas high-grade cutaneous mast cell tumors have metastatic rates > 50%.1 Common sites of metastasis include regional lymph nodes, the liver, and the spleen. A mast cell tumor can be definitively diagnosed on cytologic examination of a fine-needle aspirate, while histopathologic examination of an excised tumor or biopsy sample provides tumor grade and margin assessment.
1. The gross appearance of a mast cell tumor at the base of the caudal pinna in a dog.
A 6-year-old 57.6 lb (26.2 kg) spayed female boxer was presented to The University of Tennessee Veterinary Medical Center for staging and treatment of multifocal cutaneous masses on its left ear. On physical examination, three alopecic, ulcerated nodules were found on the left pinna. Two of the nodules (5 x 3 x 2.5 cm and 0.5 x 0.5 x 0.5 cm) were located at the base of the lateral aspect of the pinna, and the third nodule (5.2 x 3.2 x 2 cm) was near the tip of the ear.
Cytologic examination of fine-needle aspirates obtained from each nodule was diagnostic for mast cell tumor. No abnormalities were found on bloodwork, thoracic and abdominal radiographic examinations, or abdominal ultrasonographic examination. No evidence of metastasis was found on cytologic examination of fine-needle aspirates of the left mandibular lymph node, liver, and spleen. Thus, surgical excision of the tumors was recommended.
A left pinnectomy was performed, including 3-cm margins around the two tumors at the base of the ear pinna and about one-third of the vertical ear canal. Histologic evaluation of the resected tissue indicated completely excised grade III mast cell tumors with 12 mitotic figures in 10 high-power fields.
Adjuvant chemotherapy was recommended because of the high tumor grade, and 14 days after the surgery a vinblastine and prednisone chemotherapy protocol (Table 1) was initiated.2
Table 1: Protocol for Using Vinblastine and Prednisone to Treat Mast Cell Tumors in Dogs
Six weeks later, while still receiving vinblastine and prednisone, the dog developed another mast cell tumor on its left lip. In addition, an enlarged left prescapular lymph node was noted on physical examination. Cytologic examination of an aspirate obtained from the lymph node was consistent with metastatic mast cell tumor. The left mandibular lymph node was not enlarged on physical examination and did not contain cytologic evidence of metastatic mast cell tumor. Chemotherapy with vinblastine and prednisone was discontinued, and chemotherapy with masitinib mesylate (Kinavet-CA1—AB Science) (12.5 mg/kg orally every 24 hours),3 diphenhydramine (2 mg/kg orally every 8 hours), and famotidine (0.5 mg/kg orally every 12 hours) was initiated.
Follow-up and further developments
At a recheck appointment one month after masitinib treatment was initiated, the dog's disease was stable. No side effects from the masitinib were noted. At the two-month recheck, the left prescapular lymph node and the mast cell tumor on the left lip remained unchanged in size; however, a new cutaneous mass (3.5 x 1.8 x 0.5 cm) was found in the left axilla. Cytologic examination of a fine-needle aspirate of this mass was diagnostic for mast cell tumor.
Additional chemotherapy. Because masitinib had not prevented tumor progression, the owners were offered treatment with either lomustine or toceranib phosphate (Palladia—Pfizer Animal Health).4,5 They elected to treat the dog with toceranib (2.75 mg/kg orally every 48 hours). The dog was concurrently treated with famotidine, maropitant citrate (Cerenia—Pfizer Animal Health), metronidazole, and sucralfate because of a reported high incidence of gastrointestinal toxicity of toceranib phosphate.5
Two weeks later, the dog became lethargic and anorectic and developed three new mast cell tumors. Additionally, the mast cell tumor on the left lip had grown in size by about 30%.
Toceranib was discontinued, and treatment with lomustine (70 mg/m2) and concurrent high-dose vitamin C (250 mg/kg orally every 24 hours) was started. It is important to point out that there is no literature supporting the use of high-dose vitamin C for the treatment of canine mast cell tumors but that therapy was initiated based on anecdotal clinical observations of response of gross mast cell tumors to this form of therapy by one of the attending clinicians.6 The lomustine proved to be ineffective since two weeks later two new mast cell tumors were found, and the tumor on the left lip had grown larger.
Masitinib reinstituted. Because of the lack of better treatment options, masitinib therapy (12.5 mg/kg orally every 24 hours) was reinstituted, since the dog had its longest interval of stable disease (about two months) while receiving this drug. Two weeks after masitinib treatment was reinstituted, the owners reported resolution of the dog's anorexia and lethargy. The high-dose vitamin C was discontinued. The dog was reevaluated four weeks after restarting on masitinib, and complete resolution of all gross mast cell tumors was noted on physical examination. Masitinib therapy was continued in an effort to prevent recurrence of mast cell tumor formation.
Seven months after masitinib treatment was reinstituted, the dog developed a mild neutropenia (1,900/μl), so the drug's frequency was decreased to every 48 hours. The dog subsequently developed a mast cell tumor on its chin, however, so the masitinib frequency was increased to every 24 hours after resolution of the neutropenia.
Case outcome. Two years later, the dog is in complete remission while remaining on masitinib therapy. The dog currently has no evidence of macroscopic mast cell tumors and is monitored every two months for neutropenia, increases in liver enzyme activities, and proteinuria, which are the reported side effects of masitinib.3