Abstract and Introduction
Abstract
Craniopharyngioma has long been considered a benign tumor because of its pathological aspect. This primordial view of craniopharyngioma fit with the primitive treatment attempts based on blind resection of the tumor each time it recurred. The limits of this management strategy were proven early by the high morbidity related to the resection and recurrence risk despite radical lesion removal. Nowadays, craniopharyngioma must be considered a complex molecular disease, and a detailed explanation of the mechanisms underlying its aggressive biological and clinical behavior, despite some benign pathological features, would be the first step toward defining the best management of craniopharyngioma. Indeed, advances in the knowledge of the molecular mechanisms at the base of craniopharyngioma oncogenesis will lead to comprehension of the critical checkpoints involved in neoplastic transformation. The final research target will be the definition of new biological agents able to reverse the neoplastic process by acting on these critical checkpoints. This biological approach will lead to a refined therapy combining higher efficacy and safety with lower morbidity. In this paper the authors reveal state-of-the-art comprehension of the molecular biology of craniopharyngioma and the consequent therapeutic implications.
Introduction
Craniopharyngioma accounts for 5–10% of childhood tumors. Two histological variants are known: adamantinomatous, typically occurring in the pediatric population, and the squamous papillary form, frequent in adults. These histological forms differ in pathological features, reflecting a distinct oncogenetic origin. Adamantinomatous craniopharyngiomas arise from a neoplastic transformation of the epithelial remnants of the craniopharyngeal duct, involuting during embryological development of the adenohypophysis. The squamous papillary variant arises from a metaplastic process involving the adenohypophyseal cells in the pars tuberalis, leading to the formation of squamous cell nests.
Although a purely surgical approach aimed at total resection has been advocated to cure craniopharyngiomas, this management strategy is often burdened by high morbidity because of the critical relationships of this tumor with neighboring vascular and nervous structures. The identification of new therapies would help to comprehend the molecular mechanisms underlying the clinically aggressive behavior of these lesions. Although recent studies have been aimed at clarifying some aspect of neoplastic cell transformation, the molecular pathogenesis of craniopharyngiomas has not been systematically examined in literature. In this paper we attempted to critically review the recent literature on the oncogenetic mechanisms of craniopharyngiomas and their therapeutic implications.