Abstract
To assess the clinical relevance of transgenic and patient‐derived xenograft models of adamantinomatous craniopharyngioma (ACP) using serial magnetic resonance imaging (MRI) and high resolution post‐mortem microcomputed tomography (μ‐CT), with correlation with histology and human ACP imaging. The growth patterns and radiological features of tumors arising in Hesx1Cre/+;Ctnnb1lox(ex3)/+ transgenic mice, and of patient‐derived ACP xenografts implanted in the cerebral cortex, were monitored longitudinally in vivo with anatomical and functional MRI, and by ex vivo μ‐CT at study end. Pathological correlates with hematoxylin and eosin stained sections were investigated. Early enlargement and heterogeneity of Hesx1Cre/+;Ctnnb1lox(ex3)/+ mouse pituitaries was evident at initial imaging at 8 weeks, which was followed by enlargement of a solid tumor, and development of cysts and hemorrhage. Tumors demonstrated MRI features that recapitulated those of human ACP, specifically, T1‐weighted signal enhancement in the solid tumor component following Gd‐DTPA administration, and in some animals, hyperintense cysts on FLAIR and T1‐weighted images. Ex vivo μ‐CT correlated with MRI findings and identified smaller cysts, which were confirmed by histology. Characteristic histological features, including wet keratin and calcification, were visible on μ‐CT and verified by histological sections of patient‐derived ACP xenografts. The Hesx1Cre/+;Ctnnb1lox(ex3)/+ transgenic mouse model and cerebral patient‐derived ACP xenografts recapitulate a number of the key radiological features of the human disease and provide promising foundations for in vivo trials of novel therapeutics for the treatment of these tumors.
Highlights
Adamantinomatous craniopharyngioma (ACP) is the most common tumor of the sellar region in childhood, accounting for approximately 1.2–4% of pediatric intracranial tumors
The growth patterns and radiological features of tumors arising in Hesx1Cre/1;Ctnnb1lox(ex3)/1 transgenic mice, and of patientderived adamantinomatous craniopharyngioma (ACP) xenografts implanted in the cerebral cortex, were monitored longitudinally in vivo with anatomical and functional magnetic resonance imaging (MRI), and by ex vivo l-computed tomography (CT) at study end
MRI and m-CT imaging performed at 8 weeks of age revealed enlargement of the pituitary of Hesx1Cre/1;Ctnnb1lox(ex3)/1 mice relative to wildtype control mice (Figure 1A), consistent with the previously observed prenatal pituitary hyperplasia [11]
Summary
Adamantinomatous craniopharyngioma (ACP) is the most common tumor of the sellar region in childhood, accounting for approximately 1.2–4% of pediatric intracranial tumors. ACP is an epithelial lesion thought to arise from Rathke’s pouch, the embryonic primordium of the anterior pituitary, and is characterized by the formation of a peripheral basal layer of palisading epithelium, loose aggregates of stellate cells, nodules of “wet
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
