Pathology and pathogenesis of craniopharyngiomas

Abstract

Craniopharyngiomas are benign but locally invasive tumours of the sellar region that occur as two subtypes. The adamantinomatous type (aCP) occurs mainly during childhood while the papillary type (pCP) is found almost exclusively in adults. It is thought that aCPs arise from ectopic embryonic remnants of Rathke's pouch and these tumours share features with odontogenic tumours suggesting a common origin. The pathogenesis of pCPs is less understood but these tumours may arise from metaplastic transformation of anterior pituitary epithelial cells. Mutations in CTNNB1 that encodes β-catenin are found in around 70 % of aCPs. These mutations stabilise β-catenin, which evades destruction and accumulates in the nucleus and cytosol leading to constitutive activation of the Wnt signaling pathway. Expression of mutant β-catenin early in mouse pituitary development promotes the formation of tumours similar to aCPs. However, accumulation of β-catenin occurs only in small clusters of tumour cells even though the mutation is ubiquitous. These cell clusters are slow-growing and share some characteristics with pituitary stem cells. They are often present at the invading edge and express growth factors that may participate in paracrine signaling to surrounding cells. β-Catenin nuclear translocation may also occur in the absence of CTNNB1 mutations, suggesting that other genetic or epigenetic events can activate Wnt signaling in aCP. These mechanisms, as well as those underlying the molecular pathogenesis of pCPs remain to be identified.

Molecular pathology of adamantinomatous craniopharyngioma: review and opportunities for practice

“…More detailed reviews of the histopathology of ACP, specific pathways, and the lessons learnt from mouse models may be found elsewhere. 30,35,36,41 Opportunities for Practice ACP is a clinically heterogeneous disease. At presentation, tumors may be variably solid to cystic and variably invasive and destructive of neighboring structures.…”

Potential evolution of neurosurgical treatment paradigms for craniopharyngioma based on genomic and transcriptomic characteristics

“…10,11,16,41 A destruction complex restrains b-catenin within the cytosol and facilitates its ubiquitination and proteasomal degradation. 31 The Wnt protein family includes approximately 20 different proteins that bind to the Frizzled (Fz) family of receptors. When Wnt proteins bind the Fz receptors, the Wnt pathway is activated, 31 leading to an intracellular signaling cascade that ultimately prevents formation of the b-catenin destruction complex.…”

“…31 The Wnt protein family includes approximately 20 different proteins that bind to the Frizzled (Fz) family of receptors. When Wnt proteins bind the Fz receptors, the Wnt pathway is activated, 31 leading to an intracellular signaling cascade that ultimately prevents formation of the b-catenin destruction complex. 9,11,16,22,31 Without the destruction complex, b-catenin protein accumulates and ultimately translocates to the nucleus, where it facilitates transcription of b-catenin target genes and stimulates cellular proliferation and other Wnt regulated cellular processes.…”

Frontal dermoid cyst coexisting with suprasellar craniopharyngioma: a spectrum of ectodermally derived epithelial-lined cystic lesions?

“…6,15,18,19,23 Normally, the pituitary gland is formed by fusion of the ectoderm of the oral cavity stomodeum with the neuroectoderm of the diencephalon during the 3rd and 4th weeks of gestation. This fusion of the stomode- um and neuroectoderm gives rise to the adenohypophysis and neurohypophysis, respectively.…”