dos Santos Horta, Rodrigo, Lavalle, Gleidice Eunice, de Pádua Costa, Mariana, Carneiro, Rubens Antônio, de Olveira Paes, Paulo Ricardo, and de Araújo, Roberto Baracat
Background: The proliferative disorders of mast cells include, in addition to mast cell tumor, systemic mastocytosis and myeloid leukemia of mast cells. Surgery is the treatment of choice for tumors in the skin, in regions which allow wide excision but adjuvant treatments should be performed in selected patients. However, the use of adjuvant chemotherapy remains empirical, due to the absence of controlled studies. Despite the relevance of the use of tyrosine kinase inhibitors for the treatment of mast cell tumors, studies with these drugs have focused primarily on neoadjuvant scenery. Case: A 13-year-old male Poodle dog, weighing 4.6 kg, was presented with bilateral increase in inguinal lymph nodes and a vesicular cutaneous lesion, in the inguinal region, 75 days after surgery for the removal of a scrotum grade II mast cell tumor. Patient was admitted for surgery and the tissues removed were sent for pathological examination that allowed the diagnosis of grade II mast cell tumor and metastasis in all inguinal lymph nodes. The immunohistochemical study for CD117 revealed an aberrant expression of KIT receptor (KIT II), while the PCR for mutations in exon 11 of c-KIT gene revealed internal tandem duplications. The patient underwent a session of chemotherapy with lomustine, however it had serious side effects that resulted in discontinuation of treatment, opting for utilization of masitinib mesylate at a dose of 12.5 mg/m2 once daily. One hundred and fifty days after the start of masitinib and 198 days after surgery, multiple lesions, similar to pustules, were observed in the skin whose cytology revealed that it was moderately differentiated mast cell tumors. The disease-free interval was therefore 198 days. Fifteen days later blood count revealed mild anemia and severe thrombocytopenia and two mast cells were identified in the differential count of leukocytes. The cytological examination of bone marrow allowed the identification of 1% of mast cells in nucleated cells, that diagnosed the mast cell leukemia. The patient was in the final stage and thus, were euthanized, resulting in an overall survival of 213 days and 165 days of treatment with masitinib without major side effects. Discussion: Although no metastases were observed in abdominal organs, the patient was classified as stage III, due to lymph node involvement and the presence of skin lesions distant from the surgical scar, but close to the inguinal lymph nodes. This injury may be considered a satellite metastasis, probably related to tumor dissemination by lymphatic vessels in skin. Once the patient did not tolerate the standard protocol of chemotherapy used in the institution, for the mastocytoma scrotum in advanced stage, and presented the mutational status of the c-KIT, it was chosen to use masitinib, with the goal of delaying the appearance of metastases in distant organs. The patient was considered a candidate for treatment with the target molecular masitinib, since this tyrosine kinase inhibitor reaches a limited number of protein kinases, including KIT receptor being indicated for the treatment of mast cell tumors with aberrant expression of this receptor, with better outcomes in patients with functional mutations (exon 11) in c-KIT. Disease progression, as evidenced 198 days after surgery, could be related to resistance to tyrosine kinase inhibitors, after a favorable initial response. Patients with mast cell tumor and lymph node metastasis, receiving no treatment, have a mean survival of 42 days while those treated with surgery alone have median survival of 132 days. The survival of 213 days, in this case, can be attributed mainly to the use of masitinib as adjunctive therapy. [ABSTRACT FROM AUTHOR]