Histomorphological and ultrastructural characterization of pancreatic islet intranuclear and intracytoplasmic inclusions in giant southern pouched rats ( Cricetomys ansorgei )

Abstract

Intracellular inclusions are singular structures that may occur secondary to viral infection, cytoplasmic invagination, and organelle entrapment, or due to abnormal accumulation of biological material, such as proteins. Determining the exact nature of an inclusion is crucial in diagnostic pathology, especially in the context of colony management and toxicity studies. In this case series, we identified pancreatic islet intranuclear (IN) and intracytoplasmic (IC) eosinophilic inclusions in 13 out of 21 southern giant pouched rats (Cricetomys ansorgei), a species studied for its outstanding olfactory capacities. Intranuclear inclusions were smooth, globular, and marginated the chromatin. Intracytoplasmic inclusions were either single or multiple, and polygonal to globular. Females and males were both affected, regardless of their wild-caught or inhouse-bred status. Immunohistochemistry labeling for p62 in some IN inclusions suggested a correlation with autophagy. Okajima’s stain for hemoglobin positively stained all inclusions. Periodic acid-Schiff reaction, Masson’s trichrome, Congo red, and Prussian blue were all negative, ruling out polysaccharides, β-pleated sheets, fibrin, and free iron. Ultrastructural evaluation further revealed that IN inclusions consisted of aggregated fibrillar to microtubular material and excluded a viral infection. By contrast, IC inclusions were identified as giant mitochondria with crystalline deposits and abnormal cristae. In conclusion, the frequent occurrence of either type of inclusion, irrespective of clinical health status, suggests that they are likely incidental although possibly related to autophagy. Importantly, the natural occurrence of giant mitochondria in seemingly healthy individuals is unusual. Giant pouched rats may thus represent a suitable species to deepen our understanding of these peculiar organelles.