Prognostic Value of a Histopathological Scoring System and the Ki67 Proliferation Index in Dogs With Phaeochromocytoma

Abstract

Canine phaeochromocytomas (PCCs) are neuroendocrine tumours with malignant potential. Metastatic disease remains the sole definitive evidence of malignancy. Histopathological criteria to predict long-term survival have not been established in dogs. This study evaluated the reproducibility and prognostic value of histopathological parameters derived from human scoring systems, along with the Ki67 proliferation index (PI), in dogs after adrenalectomy for PCC. Tumour samples from 41 dogs were assessed by a veterinary pathologist and pathology resident. Of 10 histopathological parameters examined, only necrosis, tumour cell spindling, and extension into adipose tissue achieved sufficient inter- and intra-observer agreement (≥ 0.40) for inclusion in survival analyses, while Ki67 PI demonstrated excellent reproducibility (≥ 0.95). A composite histopathological score was generated by summing these three parameters and a dichotomised Ki67 PI (optimal cutoff 18%), as determined by ROC analysis. Among the 41 dogs, eight died within 2 weeks postoperatively, leaving 33 long-term survivors with four tumour-related events. Kaplan-Meier analysis showed significantly poorer survival (p < 0.001) in dogs with a high Ki67 PI (≥ 18%), whereas the composite score showed a borderline significant association with outcome in Cox regression (p = 0.056; hazard ratio 2.80). Overall, dogs surviving the immediate postoperative period demonstrated a favourable prognosis (mean overall survival of 2456 days). These findings suggest that, in this cohort with few tumour-related events, the dichotomised Ki67 PI alone may serve as a clinically applicable prognosticator for canine PCC. However, further research in larger populations is needed to determine whether a composite score adds prognostic value and guides postoperative management.