Contemporary Biological Insights and Clinical Management of Craniopharyngioma

Craniopharyngiomas are clinically aggressive tumours due to their invasive behaviour and recalcitrant tendency to recur after therapy. There are two types based on their distinct histology and molecular features: The papillary craniopharyngioma (PCP), which is associated with BRAF-V600E mutations and the adamantinomatous craniopharyngioma (ACP), characterised by mutations in CTNNB1 (encoding β-catenin). Patients with craniopharyngioma show symptoms linked to the location of the tumour close to the optic pathways, hypothalamus and pituitary gland, such as increased intracranial pressure, endocrine deficiencies and visual defects. Treatment is not specific and mostly non-curative, and frequently includes surgery, which may achieve gross-total or partial resection, followed by radiotherapy. In cystic tumours, frequent drainage is often required and intracystic instillation of drugs has been used to help manage cyst refilling. More recently targeted therapies have been used, particularly in papillary craniopharyngioma, but also now in adamantinomatous craniopharyngioma and clinical trials are underway or in development. Although patient survival is high, the consequences of the tumour and its treatment can lead to severe comorbidities resulting in poor quality of life, in particular for those patients that bear tumours with hypothalamic involvement. Accordingly, in these patients at risk for the development of a hypothalamic syndrome hypothalamus-sparing treatment strategies such as limited resection followed by irradiation are recommended. In this review, we provide an update on various aspects of craniopharyngioma, with emphasis on recent advances in the understanding of tumour pathogenesis, clinical consequences, management and therapies.