eMedicine Specialties > Pediatrics: General Medicine > Oncology

Craniopharyngioma

Author: Joseph L Lasky III, MD, Clinical Assistant Professor, Department of Pediatrics, Division of Hematology and Oncology, Mattel Children's Hospital UCLA
Coauthor(s): Kathleen M Sakamoto, MD, PhD, Professor and Chief, Division of Hematology-Oncology, Vice-Chair of Research, Mattel Children's Hospital at UCLA; Department of Pathology and Laboratory Medicine, Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA and California Nanosystems Institute and Molecular Biology, UCLA; Jerry L Barker, Jr, MD, Staff Physician, Clinical Associate Professor of Radiation Oncology, Department of Radiation Oncology, University of Texas Southwestern Moncrief Cancer Center
Contributor Information and Disclosures

Updated: Dec 9, 2008

Introduction

Background

Craniopharyngiomas are histologically benign neuroepithelial tumors of the CNS that are predominately observed in children aged 5-10 years. 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. Evidence suggests that adult craniopharyngiomas are histologically and biologically different from pediatric craniopharyngiomas; however, only childhood craniopharyngiomas are discussed in this article.

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. Typically, the tumors arise within the sella or adjacent suprasellar space. Symptoms are caused by mass effects on adjacent normal intracranial structures.

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.^1,2,3 Craniopharyngiomas are the most common childhood tumor that occur in the sella-chiasmatic region.⁴

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 5.25 cases per million children reported in Japan in one series⁵ .

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%⁴ .

Presenting morbidities include the following:

• Visual loss: Anterior extension to the optic chiasm can result in a classic bitemporal hemianopsia, unilateral temporal hemianopsia, papilledema, or unilateral/bilateral decrease in visual acuity. Children are frequently inattentive to visual loss, and formal testing may be required.
• Endocrinologic derangement: This results from direct compression or destruction of the hypothalamus and pituitary stalk, leading to growth hormone deficiency (75%), thyroid-stimulating hormone deficiency (25-64%), adrenocorticotropic hormone deficiency (25-56%), and luteinizing hormone or follicle-stimulating hormone deficiency (40-44%). This can present as clinically significant short stature, hypothyroidism, and other signs of panhypopituitarism.
• Diabetes insipidus: This is reported to occur in 9-38% of patients prior to surgery and in 76-94% of patients postoperatively.²

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.

Clinical

History

Craniopharyngiomas produce symptoms by compression of adjacent neural structures. They can become quite large, obstructing cerebral spinal fluid (CSF) pathways (ie, third ventricle, Monro foramen) and causing hydrocephalus and increased intracranial pressure that leads to headaches, nausea, and projectile vomiting.

• Symptoms at presentation may include the following:
  • Headache: Headaches occur in 60-80% of children with craniopharyngioma at presentation and are usually a symptom of increased intracranial pressure or hydrocephalus.
  • Vomiting: Classic projectile vomiting (frequently without nausea) accompanies headaches as a sign of increased intracranial pressure and is reported in 35-70% of children with these tumors at presentation.
  • Vision loss: As mentioned above (see Mortality/Morbidity), children are frequently unaware of significant vision loss; nevertheless, this symptom reportedly occurs in 20-60% of pediatric patients with craniopharyngioma at presentation. Classically, vision loss starts with a superior temporal field cut. However, the eccentric growth of these tumors can result in varying patterns and severity of vision loss, including decreased acuity, diplopia, blurred vision, and subjective visual field deficits.
• The following symptoms related to endocrine dysfunction may be present:
  • Diencephalic syndrome: This term is used to describe emaciated hyperactive children who occasionally present with unusual eye movements and even blindness; these symptoms result from extrinsic compression of the hypothalamus. Conversely, damage to or invasion of the ventromedial hypothalamus can result in a dysregulation of energy balance and resultant obesity upon presentation.
  • Symptoms of growth hormone deficiency (ie, short stature): Growth hormone deficiency is the most common possible endocrinologic disturbance caused by craniopharyngiomas. One series reported that growth failure preceded the diagnosis at a mean of 4 years.
  • Symptoms of hypothyroidism
    • Weight gain
    • Lethargy
    • Fatigue
    • Cold intolerance
    • Dry skin
    • Dry brittle hair
    • Slow teething
    • Anorexia
    • Large tongue
    • Deep voice
    • Myxedema
  • Symptoms of adrenal insufficiency: Secondary adrenal insufficiency is the second most common endocrinologic disturbance caused by craniopharyngiomas.
  • Symptoms of leuteinizing hormone/follicle-stimulating hormone deficiency: Gonadotropin deficiency is the most common presenting symptom of craniopharyngioma in adults. As many as 100% of presenting adolescents may have complaints of delayed puberty.
• Mental status changes occur in as many as 25% of adults but are rare in children. Temporal lobe involvement can result in seizures, although this is rare.

Physical

Focus physical examination on the identification of neurologic and endocrine derangements.

• Papilledema: Papilledema occurs in 25-40% of children and results from increased intracranial pressure.
• Visual field deficits
  • Formal testing is generally required to identify visual field deficits in children, which likely explains the wide reported range (10-95%) of patients with craniopharyngioma.
  • Given the typical proximity of the tumor to the optic nerves, optic chiasm, and anterior optic tracts, the common discovery of visual fields defects at presentation is not surprising.
• See-saw nystagmus: Although often referred to as a classic physical examination finding among children with parasellar tumors, the literature reports an incidence rate of less than 10%.
• Cranial nerve palsy: With the notable exception of the optic nerves, cranial nerve palsies are relatively rare, with a reported incidence rate of 8% for children at time of diagnosis.
• Endocrine effects
  • Short stature or growth retardation
    • Short stature or growth retardation is the most common endocrine derangement associated with this tumor.
    • Growth retardation (as documented on formal pediatric growth charts) is reported in 86% of patients with craniopharyngioma at presentation.
  • Obesity and weight gain
    • This is the third most common endocrine abnormality associated with craniopharyngiomas.
    • Hypothyroidism, growth hormone deficiency, and direct hypothalamic injury can contribute to obesity and weight gain.
    • Obesity and weight gain are reported in 20% of presenting patients.
  • Hypothyroidism: Hypothyroidism can manifest as weight gain, dry skin, brittle hair, and bradycardia.
• Precocious or delayed puberty: Precocious or delayed puberty is the fourth most common endocrine derangement associated with craniopharyngiomas and is present at diagnosis in 10-15% of patients. This is the most common presenting sign in adolescents.
• Intellectual or emotional disturbance and somnolence: These signs are most likely the result of either hydrocephalus or thyroid dysfunction.
• Enlarging head circumference: This finding is highly suggestive of an intracranial mass or hydrocephalus, particularly when paired with papilledema.
• Ataxia: This is another sign of increased intracranial pressure or hydrocephalus, which is present in 5-10% of patients at initial evaluation.
• Seizures: These are rarely described as a presenting feature.
• Focal motor weakness: This is also rarely described as a presenting feature.

Causes

• No known environmental or infectious causes predispose to the development of craniopharyngiomas.
• Little is also 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.⁴  The significance of these findings remains to be determined.
• Craniopharyngioma studies have identified the beta-catenin pathway as playing a potential role in the pathogenesis of these tumors.¹ Beta-catenin is a downstream component of the Wnt signal transduction pathway that plays critical roles in the regulation of cellular proliferation, morphology, and development. One study showed that the accumulation of nuclear beta-catenin as measured immunohistochemically was able to help differentiate craniopharyngiomas from Rathke cleft cysts.⁶

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