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

Area of Science:

• Veterinary pathology
• Oncology
• Histopathology

Background:

• The World Health Organization (WHO) established a grading system for human neuroendocrine neoplasms (NENs).
• This system utilizes proliferative indices (mitotic count, Ki67%) and immunohistochemical markers like gastrin for prognostic accuracy.
• Consistent application of this human classification in veterinary pathology is lacking.

Purpose of the Study:

• To analyze histopathologic features and gastrin expression in canine gallbladder (GB) NENs.
• To apply the human WHO histologic grading system to canine GB NENs.
• To evaluate the utility of gastrin as a prognostic marker and potential therapeutic target in canine GB NENs.

Main Methods:

• Histopathologic examination of canine GB NENs.
• Immunohistochemical staining for gastrin.
• Grading of NENs based on WHO criteria, including mitotic count and Ki67 labeling index.

Main Results:

• All gradable canine GB NENs were classified as neuroendocrine tumors (NETs), not neuroendocrine carcinomas (NECs), using the WHO system.
• Only one canine GB NET showed positive gastrin expression via immunohistochemistry.
• Canine GB NENs demonstrated lower grades compared to human counterparts and infrequent gastrin expression.

Conclusions:

• The WHO grading system, particularly proliferative indices, enhances prognostic information for canine GB NENs.
• Gastrin is unlikely to be a widely applicable therapeutic target in canine GB NENs due to limited expression.
• Standardized classification of canine NENs can improve understanding and management of these neoplasms.