Exploratory analysis of perioperative plasma histamine concentrations in dogs with mast cell tumours

In this exploratory study, we investigated plasma histamine concentration as a perioperative prognostic marker in dogs with mast cell tumours. Mast cell tumours exhibit marked heterogeneity in biological behaviour, and histological grading is widely used for prognostication; however, grading alone does not directly reflect tumour burden or residual disease following surgery. Histamine has a short half-life in the circulation, and persistently elevated plasma histamine levels may reflect continuous release from neoplastic mast cells. Although plasma histamine concentration has been proposed as a marker of prognosis and residual disease, its clinical relevance and optimal interpretation remain incompletely defined. Twenty-seven dogs that underwent surgical excision of mast cell tumours (29 surgeries) during a 28-month study period were included. Associations between plasma histamine concentration and survival outcomes were evaluated using Kaplan-Meier survival analyses. Multivariable analyses were performed to explore factors associated with preoperative and postoperative plasma histamine concentration.

Dogs with elevated preoperative plasma histamine concentration (>1.0 ng/mL) had significantly shorter progression-free intervals (PFIs) than those with low preoperative plasma histamine concentration (≤1.0 ng/mL). However, in multivariable analyses restricted to dogs with cutaneous mast cell tumours, preoperative plasma histamine concentration was confounded by tumour volume and was not an independent prognostic factor following adjustment. Postoperative plasma histamine concentration values were elevated in only a few cases, limiting formal survival analyses; nonetheless, multivariable analyses demonstrated a significant association between postoperative plasma histamine concentration and gross residual disease, suggesting that postoperative plasma histamine concentration may reflect macroscopic residual tumour but may lack sensitivity for microscopic disease.

The findings suggest that preoperative plasma histamine concentration primarily reflects tumour burden in dogs with cutaneous mast cell tumours, whereas postoperative plasma histamine concentration is associated with macroscopic residual disease and may be less informative for detecting microscopic residual or metastatic disease. Plasma histamine concentration may serve as an adjunctive perioperative biomarker when interpreted in conjunction with established clinicopathological factors. Larger prospective studies are warranted to validate assay performance, refine cut-off values, and determine the clinical utility of plasma histamine concentration in canine mast cell tumours.