Proliferation-Based WHO Grading and Heterogeneous Gastrin Expression in Canine Gallbladder Neuroendocrine Tumors

Efforts by the World Health Organization (WHO) have clarified the descriptive nomenclature and histologic grading of neuroendocrine neoplasms (NENs) in human medicine. Employing a standardized stratification scheme in conjunction with specific immunohistochemical markers, such as gastrin, enhances prognostic accuracy and guides treatment recommendations. Yet, this classification system has yet to be applied consistently in veterinary pathology. Histopathologic features and gastrin expression were analyzed in a group of canine gallbladder (GB) NENs. Based on the human WHO histologic system, which stratifies grade based on proliferative indices (mitotic count and Ki67%), all gradable GB NENs were classified as neuroendocrine tumors (NETs) rather than neuroendocrine carcinomas (NECs). Only one GB NET was positive for gastrin using immunohistochemical staining. Collectively, our data suggest that canine GB NENs have a lower grade than most human GB NENs and rarely express gastrin. The use of proliferative indices in the histologic characterization of canine GB NENs is likely to improve prognostic information. Given the limited expression of gastrin in these neoplasms in dogs, this marker is unlikely to be widely applicable as a druggable target.