Pediatric Craniopharyngioma

Updated: May 18, 2017
  • Author: Joseph L Lasky, III, MD; Chief Editor: Vikramjit S Kanwar, MBBS, MBA, MRCP(UK), FAAP  more...
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Overview

Background

Craniopharyngiomas (see the image below) are histologically benign neuroepithelial tumors of the CNS that are predominately observed in children aged 5-10 years.

This MRI sequence was obtained following the intra This MRI sequence was obtained following the intravenous administration of gadolinium contrast. Observe the relatively homogeneous and cystic mass arising from the sella turcica and extending superiorly and posteriorly with compression of normal regional structures. Note that the lesion is sharply demarcated and smoothly contoured. This fluid-filled mass is consistent with a typical craniopharyngioma.

These tumors arise from squamous cell embryologic rests found along the path of the primitive adenohypophysis and craniopharyngeal duct. Although histologically benign, these tumors frequently recur after treatment. In addition, because they originate near critical intracranial structures (eg, visual pathways, pituitary gland, hypothalamus), both the tumor and complications of curative therapy can cause significant morbidity. These characteristics have led to various treatment approaches, and disagreement continues regarding optimal treatment in children with this disease.

Adult craniopharyngiomas are histologically and biologically different from pediatric craniopharyngiomas; however, only childhood craniopharyngiomas are discussed in this article.

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Pathophysiology

Pediatric craniopharyngiomas are believed to arise from cellular remnants of the Rathke pouch, which is an embryologic structure that forms both the infundibulum and anterior lobe of the pituitary gland. Its path of development extends from the pharynx to the floor of the sella turcica; not surprisingly, these tumors have been identified extensively in suprasellar, parasellar, and ectopic locations. [1] Typically, the tumors arise within the sella or adjacent suprasellar space. Symptoms are caused by mass effects on adjacent normal intracranial structures.

Little is known regarding the genetic basis for craniopharyngiomas. Transformation of normal cells into neoplastic ones likely involves multiple genomic changes, including loss of tumor-suppressor genes, activation of oncogenes, and alterations in DNA repair and methylation mechanisms. Although these events have started to be elucidated for neuroepithelial neoplasms such as gliomas, little progress has been made in understanding these events in craniopharyngiomas. Some chromosomal abnormalities, including deletions, translocations, and increased copy numbers, have been recognized but are largely nonspecific. [2] The significance of these findings remains to be determined.

However, studies have identified the beta-catenin pathway as playing a role in the pathogenesis of these tumors in the pediatric population, as opposed to BRAF mutations which are predominantly found in adults with papillary craniopharyngioma. [3, 4] Beta-catenin is a downstream component of the Wnt signal transduction pathway that plays a critical role in the regulation of cellular proliferation, morphology, and development. The accumulation of nuclear beta-catenin as measured immunohistochemically was able to help differentiate craniopharyngiomas from Rathke cleft cysts. [5] Other molecular factors that have been identified in aggressive or recurrent craniopharyngiomas are low expression levels of macrophage-inhibiting factor (MIF) and galectins, retinoic-acid receptor levels, low cathepsin levels, and high vascular-endothelial growth factor (VEGF) levels. [6]

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Epidemiology

Frequency

United States

Craniopharyngiomas are relatively rare, representing 6-10% of intracranial malignancies in children and adolescents (approximately 2-3 cases per 1,000,000 children). A bimodal distribution peak has been reported, with one peak at age 5-14 years and the other at age 65-74 years. More than 300 cases are reported in the United States annually, and roughly one third of these involve children aged 0-14 years. [3, 7, 8] Craniopharyngiomas are the most common childhood tumor that occur in the sella-chiasmatic region. [2]

International

The Childhood Cancer Registry of Piedmont, Italy estimates an incidence of 1.4 cases per million children per year in keeping with reports from other Western countries. Higher incidence rates have been observed in Asia and Africa with about 4 cases per million children reported in Japan in one series. [9]

Mortality/Morbidity

Previous studies have shown relatively good outcomes, with 10-year overall survival rates of 86-100% among patients who underwent gross total resection. Subtotal resection or recurrence treated with surgery and radiation therapy carry 10-year overall survival rates of 57-86%. The perioperative mortality rate after primary surgical intervention has been estimated to be 1.7-5.4%. However, the mortality rate after re-resection for recurrent disease can be as high as 25%. [2]

Almost all patients with craniopharyngioma ultimately suffer from chronic morbidities. These are most commonly endocrinologic in nature but also include significant neurologic morbidities such as vision loss, ataxia, behavioral problems, cognitive disabilities, and sleep disorders (See Clinical and Complications for details).

Race

No clear racial predilection has been reported.

Sex

The most recent large series demonstrate equal sex distribution, although a slight male preponderance has been historically reported.

Age

Peak incidence of childhood craniopharyngiomas occurs in individuals aged 5-14 years. Neonatal craniopharyngiomas are rare. Of the more than 300 cases per year in the United States, approximately one third involve children aged 0-14 years. The incidence of adult craniopharyngiomas has a second peak in individuals aged 50-74 years.

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