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New outlook on the diagnosis, treatment and follow-up of childhood-onset craniopharyngioma

Key Points

  • The clinical, neuroradiological and surgical definition of hypothalamic involvement is a fundamental factor related to poor postoperative outcome, progressive obesity and neuropsychological impairment in children after surgical removal of craniopharyngioma

  • The previously assumed 'gold-standard' objective of a primary radical removal of the lesion in all cases needs to be replaced with the new paradigm of a limited resection plus focused radiotherapy in patients with craniopharyngioma and hypothalamic lesions

  • Hypothalamic involvement and treatment-related hypothalamic lesions are associated with the highest risk of postoperative sequelae and impaired quality of survival

  • 3D intensity-modulated proton beam radiotherapy has potential advantages over photon beam methods to focus and limit the radiation effects to optic and hypothalamic structures

  • Preclinical, in vivo mouse models can be used to investigate the pathogenesis of adamantinomatous craniopharyngioma and to test novel treatments

Abstract

Childhood-onset craniopharyngiomas are rare embryonic tumours of low-grade histological malignancy. Novel insights into the molecular pathogenesis of human adamantinomatous craniopharyngioma have started to unveil the possibility of testing novel treatments targeting pathogenic pathways. Hypothalamic involvement and/or treatment-related lesions result in impaired physical and social functionality and in severe neuroendocrine sequelae. Quality of survival in patients with craniopharyngioma with hypothalamic involvement is impaired by severe obesity, physical fatigue and non-optimal psychosocial development. Patients with craniopharyngioma involving hypothalamic structures have reduced 20-year overall survival, but overall and progression-free survival are not related to the degree of surgical resection. Irradiation is effective in the prevention of tumour progression and recurrence. For favourably localized craniopharyngiomas, the preferred treatment of choice is to attempt complete resection with preservation of visual, hypothalamic and pituitary function. For unfavourably localized tumours in close proximity to optic and/or hypothalamic structures, a radical neurosurgical strategy attempting complete resection is not recommended owing to potential severe sequelae. As expertise has been shown to have an impact on post-treatment morbidity, medical societies should establish criteria for adequate professional expertise for the treatment of craniopharyngioma. On the basis of these criteria, health authorities should organize the certification of centres of excellence that are authorized to treat and care for patients with this chronic disease.

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Figure 1: Molecular pathways involved in human adamantinomatous craniopharyngioma.
Figure 2: Paracrine model for the involvement of pituitary stem cells in tumorigenesis.
Figure 3: Childhood craniopharyngioma.
Figure 4: Survival of patients with childhood-onset craniopharyngioma.
Figure 5: MRI of childhood craniopharyngioma.

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Acknowledgements

H.L.M. acknowledges support from the German Childhood Cancer Foundation, Bonn, Germany.

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H.L.M., T.E.M., S.P. and J.-P.M.-B. researched data for the article, made substantial contributions to discussions of the content, wrote the article and reviewed and/or edited the manuscript before submission.

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Correspondence to Hermann L. Müller.

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Müller, H., Merchant, T., Puget, S. et al. New outlook on the diagnosis, treatment and follow-up of childhood-onset craniopharyngioma. Nat Rev Endocrinol 13, 299–312 (2017). https://doi.org/10.1038/nrendo.2016.217

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