Do Canine Pancreatic Neuroendocrine Neoplasms Resemble Human Pancreatic Neuroendocrine Tumours? A Comparative Morphological and Immunohistochemical Investigation. (November 2020)

• Record Type: Journal Article
• Authors: de Vries, Cynthia; Konukiewitz, Björn; Weichert, Wilko; Klöppel, Günter; Aupperle-Lellbach, Heike; Steiger, Katja
• Is Part Of: Journal of comparative pathology. Volume 181(2020)
• Page Start: 73
• Page End: 85
• Publication Date: 2020-11
• Subjects: canine insulinoma -- Ki-67 index -- pancreatic neuroendocrine tumours -- SSTR2A; Veterinary pathology -- Periodicals; Veterinary therapeutics -- Periodicals; Pathology, Comparative -- Periodicals; Therapeutics -- Periodicals; Pathology, Veterinary -- Periodicals; 636.089607
• DOI: 10.1016/j.jcpa.2020.10.001
• Languages: English
• ISSNs: 0021-9975

Abstract

Summary: Although canine pancreatic neuroendocrine neoplasms (PanNENs) have been proposed as a model for the counterpart human neoplasms, the type or grade of human PanNEN that they resemble is unclear. PanNENs in animals are classified as adenoma or carcinoma, whereas in humans they are classified as pancreatic neuroendocrine tumour (PanNET) if well-differentiated, or as pancreatic neuroendocrine carcinoma (PanNEC) if poorly differentiated. We evaluated 16 canine primary PanNENs and two metastases histologically and immunohistochemically, and graded them using the animal and human grading systems. All neoplasms had local or vascular invasion and were classified as pancreatic islet cell carcinomas according to the current WHO classification. The Ki-67 index was low in all cases (0.01–1.50%). All had cytoplasmic expression of synaptophysin and insulin but were immunonegative for glucagon, confirming a functional diagnosis of canine insulinoma. Membranous expression of SSTR2A and nuclear expression of ATRX, but no p53 expression, was found in all neoplasms. One primary tumour was diagnosed as a mixed neuroendocrine-non-neuroendocrine neoplasm, which is the first report of this neoplasm in dogs. The other 15 primary tumours and both metastatic tumours were graded as PanNET G1, according to the human WHO classification. We conclude that canine PanNENs share well-differentiated histomorphology, SSTR2A expression and absence of nuclear p53 immunolabelling with human PanNETs G1. However, they differ in ATRX gene expression and functionality, and seem to have a worse prognosis than human PanNETs G1, although their generally low Ki-67 index precludes more precise assessment of prognosis. Membranous SSTR2A expression renders canine PanNENs potentially amenable to treatment with somatostatin analogues or SSTR targeted in-vivo imaging methods. Graphical abstract: Image 1 Canine pancreatic neuroendocrine neoplasm macrotrabecular growth patten (1; HE), showing cytoplasmic immunohistochemical labelling for synaptophysin (2) and insulin (3). Moderate membranous expression of somatostatin receptor 2A (4) could be confirmed, making these tumours amenable to treatment with somatostatin analogues. All pictures: ×20 magnification, scale bar: 50 μm.