Cytologic, Clinicopathologic, and Histologic Findings in a Dog with a Gallbladder Neuroendocrine Carcinoma and Multiple Endocrinopathies

A 10-year-old spayed female Shih Tzu was evaluated for a gallbladder mass incidentally identified during a diagnostic workup for hyperadrenocorticism and persistent hypercalcemia. Diagnostic imaging revealed a vascularized intraluminal gallbladder mass, and cytologic examination showed cohesive clusters of epithelial cells with distinct intercellular junctions, magenta cytoplasmic stippling, and marked pleomorphism, raising suspicion for a neuroendocrine carcinoma. Cholecystectomy was performed with tissues submitted for histopathology and immunohistochemistry (IHC), which confirmed a diagnosis of gallbladder neuroendocrine carcinoma (GB-NEC) with hepatic and vascular invasion. The tumor exhibited diffuse positive immunolabeling for synaptophysin, chromogranin A, neuron-specific enolase, and insulinoma-associated protein 1 (INSM-1), consistent with neuroendocrine differentiation. However, no appreciable immunolabeling for gastrin, adrenocorticotropic hormone (ACTH), and parathyroid hormone (PTH) was observed. This case illustrates an uncommon cytologic presentation of GB-NEC in dogs and suggests a potential association between neuroendocrine tumors and multiple endocrinopathies. The findings support the utility of INSM-1 as a broad-spectrum marker for canine neuroendocrine tumors and underscore the need for further investigation into the hormonal activity and clinical variability of GB-NEC.