Abstract: Background – Canine mast cell tumors (MCTs) demonstrate variable biological behavior. Although histologic grading is used for prognostication, standardized criteria for subcutaneous MCTs (scMCTs) are lacking, and comparative clinical data remain limited. Hypothesis/Objectives – To compare clinical behavior and prognostic indicators of cutaneous MCTs (cMCTs) and scMCTs, focusing on histological grade, Ki67 index, and response to tyrosine kinase inhibitors (TKIs). Animals – Eleven dogs with 17 MCT lesions (cMCTs, n = 11; scMCTs, n = 6) from a veterinary teaching hospital. Methods – Medical records were retrospectively reviewed for signalment, stage, and treatment. Tumors were graded using Kiupel and Patnaik systems. Ki67 index and KIT expression patterns were evaluated. Therapeutic outcomes, adverse events, and recurrence-free intervals were assessed. Results – In cMCTs, six achieved complete remission (CR), whereas two developed local recurrence following complete excision. Recurrent cMCTs showed discordant biological profiles, including one low-grade tumor with low Ki67 (6.2) and one high-grade tumor with high Ki67 (182) and aberrant KIT expression. In dogs with scMCTs, clinical behavior was similarly heterogeneous. Two aggressive cases exhibited high-risk features (mitotic count ≥ 9/10 HPF; Ki67 ≥ 25%). Intra-patient heterogeneity was observed in one dog with concurrent high-grade metastatic and low-grade scMCTs. Clinical outcomes ranged from sustained CR to late recurrence after TKI discontinuation. Conclusions and Clinical Importance – Canine MCTs exhibit substantial biological heterogeneity regardless of location or histologic grade. Individual lesions should be evaluated independently, particularly in multifocal cases. Although TKIs can achieve durable responses, long-term surveillance is necessary following treatment cessation.
