Histologic grading of canine cutaneous mast cell tumors (cMCTs) has prognostic and therapeutic implications, yet validation for subcutaneous MCTs (scMCTs) is lacking. For scMCTs with or without dermal invasion, determining their biological behavior remains poorly standardized and sometimes sparks controversy. This prospective study aimed to assess the prognostic utility of the 2-tier histologic grading system in MCTs with different growth models (GMs) and explore the prognostic impact of the GM itself. We assessed 6 histologic GM categories: solely cMCT (C-SC₀), cMCT with superficial (C-SC₁) or deep subcutaneous (C-SC₂) involvement, solely scMCT (SC-C₀), and scMCT with deep (SC-C₁) or superficial (SC-C₂) infiltration of the dermis. Ninety-one MCTs from 76 dogs undergoing excision and regional/sentinel lymphadenectomy were examined. GM classification identified 11 (12%) C-SC₀ tumors, 12 (13%) C-SC₁, 15 (16%) C-SC₂, 21 (23%) SC-C₀, 15 (16%) SC-C₁, and 17 (19%) SC-C₂. Mitotic count, 2-tier grade, nodal involvement, surgical margins, and outcome were stratified according to GM. scMCTs lacking dermal invasion, historically associated with a benign clinical course, had a poor prognosis in 10% of cases. cMCTs exhibiting deep subcutaneous involvement included the largest percentage of high-grade tumors (33%), had the highest occurrence of overt nodal metastases (33%), and had the lowest 1-year survival rate (86%). Histologic grade was confirmed as a relevant prognostic factor, surpassing nodal involvement and histologic margin status. The 2-tier histologic grading enabled the identification of all MCTs with aggressive biological behavior, regardless of their cutaneous or subcutaneous location.

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