PCM-02: A GENETICALLY ENGINEERED MOUSE MODEL RECAPITULATES RADIOLOGICAL FEATURES OF HUMAN ADAMANTINOMATOUS CRANIOPHARYNGIOMA

Adamantinomatous craniopharyngiomas (ACPs) are histologically benign but clinically aggressive pituitary tumours mostly affecting children. ACPs present as mixed lesions with cystic and solid components, and are treated with surgery, radiotherapy and cystic drainage, but no specific chemotherapeutics exist. Mutations in CTNNB1, which encodes β-catenin, resulting in over-activation of the Wnt pathway are present in most human ACPs. Expression of oncogenic β-catenin in the developing pituitary in Hesx1^Cre/+; Ctnnb1^lox(ex3)/+ mice results in tumours resembling human ACP at the histological and molecular levels. However, no radiological studies had previously been executed in this model. T₂-weighted MRI performed from approximately 7 weeks demonstrated enlargement and increased heterogeneity of the pituitary in Hesx1^Cre/+;Ctnnb1^lox(ex3)/+ mice compared to controls. The imaging phenotype remained stable prior to the development of cysts and enlargement of a solid portion of the tumour (median age 15.7 weeks, range 8.3-35.3 weeks; n = 14). Cystic regions presented as hyperintense areas on T₂-weighted images; in some animals cysts were also hyperintense on T₁-weighted MRI and fluid attenuated inversion recovery (FLAIR) images, which is observed clinically and attributed to high cystic protein and cholesterol levels. Calcification of cystic fluid is also evident by CT in patients. The solid components showed heterogeneous enhancement on T₁-weighted images following gadolinium contrast agent administration, again recapitulating the human phenotype. Unlike ACP patients, mice presented with significant haemorrhagic regions, which, in combination with cystic volume, was likely the cause of morbidity. The Hesx1^Cre/+; Ctnnb1^lox(ex3)/+ model provides a promising foundation for imaging embedded in vivo trials of promising therapeutics for the treatment of ACP.