Craniopharyngioma Overview:
Example of Need for Comprehensive Long-term Management of Patients with Brain Tumors
By Patricia Donohoue, MD, Selim Firat, MD, Sachin Jogal, MD, and Marike Zwienenberg-Lee, MD
Overview
Craniopharyngioma is a histologically benign suprasellar tumor which constitutes 6 to 10 percent of intracranial tumors in children. It is thought to originate from the embryonic squamous epithelial remnants of the Rathke's pouch. In embryonic development, Rathke's pouch evolves into the anterior pituitary gland and the pituitary stalk. It is the most common tumor in the sella region in children, with peak incidence at 5 to 10 years of age. The incidence peaks again in adults at 60 to 65 years.
Although considered to be benign histologically, craniopharyngioma behaves in a clinically aggressive fashion. It tends to invade or displace surrounding critical intracranial structures such as the pituitary gland, hypothalamus, third ventricle, optic nerves and chiasm, as well as blood vessels, such as carotid arteries. (See Figure 1.) Craniopharyngioma is prone to contain solid and cystic components; these tumors may comprise of multiple cysts. Significant complications can occur as a result of uncontrolled growth of either of its components. These include visual symptoms, pituitary/hypothalamic deficiencies, hydrocephalus, increased intracranial pressure and even death. Therefore, local control of this disease is considered essential to reduce the risk of these complications. 
Therapeutic management
Surgical resection has been the main intervention in the management of this tumor. However, there continues to be a controversy regarding the optimal surgical treatment of craniopharyngioma. While most would agree that radical excision of this histologically benign tumor is desirable, this often cannot be achieved without causing significant damage to the adjacent neural and vascular structures. Either initiation or exacerbation of existing panhypopituitarism, vision loss, hypothalamic injury resulting in morbid obesity, memory and behavioral problems, disturbance of the sleep-wake cycle and temperature regulation are common complications of aggressive craniopharyngioma surgery. For this reason, a limited resection or drainage of the craniopharyngioma cyst followed by focused radiation therapy has been advocated by some as an equally effective but less morbid intervention. (See Figure 2.) To minimize the size of the radiation field, the cyst can be stereotactically drained and a cyst-catheter attached to a subcutaneous reservoir placed, allowing for intermittent percutaneous fluid drainage while the patient undergoes radiation therapy. In some cases, the tumor is confined to the Sella Turcica; endoscopic transsphenoidal resection can be considered in these patients. Other treatment strategies for local tumor growth control include intracystic radiotherapy or intracystic chemotherapy. These involve instillation of either radioactive 32P or agents such as bleomycin into the cysts of the tumors. These intracystic therapies have been considered mainly in patients who have tumors with large single cysts. Due to concern for spillage of these agents outside the tumor cyst, these treatments are not used as frequently.
The available medical evidence supporting any kind of surgical treatment consists mainly of institutional case series. In general, surgeons tend to favor a limited resection if there is hypothalamic attachment of the tumor and aggressive resection if the tumor is not attached. The postsurgical complications endocrine deficits, optic chiasm or neurovascular complications are reported to be less common with limited surgery and radiation than with aggressive total resection.
Published series using radiation for cranio-pharyngiomas have shown superior, progression-free survival rates compared to subtotal surgical resection alone. Radiation therapy seems beneficial as adjunct therapy for tumor control when patients undergo less than total resection. Given the technological advances in radiation treatment planning and delivery systems, long-term complications related to radiation therapy potentially can be reduced. Image-guided radiation therapy and intensity-modulated radiation therapy, which uses "inverse planning," are two important advances that may improve sparing of normal structures and treatment precision. In addition, CT imaging during radiation therapy provides surveillance of potential craniopharyngioma cyst growth, and this allows modification of radiation fields according to changes in target volumes. This improved precision helps to reduce the treatment volumes and to potentially reduce long-term toxicity.
Related endocrine problems
In pediatric patients with craniopharyngioma, most have signs and symptoms of endocrine dysfunction at the time of presentation. For those whose tumors are diagnosed as part of an endocrine evaluation, the most common presenting complaint is linear growth failure. In these patients, the brain imaging study obtained after the diagnosis of growth hormone (GH) deficiency is made, reveals the mass lesion. The GH deficiency can be isolated or combined with other pituitary hormone deficiencies.
In one series of 122 patients, at the time of diagnosis of the craniopharyngioma, 85 percent had one to three pituitary hormone deficiencies. In a review of a large number of studies, after treatment of the tumor, with or without radiation therapy, 54 to 100 percent had three or more hormone deficiencies. The relative prevalence of pituitary hormone deficiencies at diagnosis and after treatment is summarized in Table 1.
Another endocrine complication of treatment for craniopharyngioma is the development of hypothalamic obesity. This is associated with significant abnormalities of the hypothalamic anatomy on postsurgical imaging. This condition results from loss of satiety, reduced physical activity and lowered resting energy expenditure (REE). Possible mechanisms include disruption of leptin receptors (satiety), increased vagal tone (increased insulin secretion and calorie storage) and autonomic imbalance (decreased REE). Unfortunately, there is no specific or effective medical treatment for this condition, which causes significant morbidity and loss of quality of life. Intensive diet and activity intervention at the earliest sign of excessive weight gain is recommended. Treatment of the pituitary hormone deficiencies usually is straightforward. This consists of the appropriate combination of growth hormone, thyroid hormone, cortisol, sex steroids and vasopressin. Growth hormone treatment traditionally has been delayed until one year after the end of tumor treatment. However, GH treatment does not increase the risk of tumor recurrence in these patients. Some patients grow normally despite a confirmed diagnosis of GH deficiency. The mechanism is unknown, but it may be related to the binding of excess insulin to the IGF-1 receptor.
In summary, craniopharyngioma is a histologically benign but clinically aggressive brain tumor. Even though long-term control of the tumor usually is achieved with surgery, with or without radiation therapy, children with these tumors are at risk of or have significant long-term consequences. These patients require frequent reassessments for tumor recurrence, cyst re-accumulation and subsequent hydrocephalus. They benefit from vigilant monitoring of their growth, vision, nutrition, neuropsychological variances, neurological deficiencies and quality of life assessments. Their optimal management consists of a consistent multidisciplinary provider approach from diagnosis.
References
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Elliott RE, Hsieh K, Hochm T, Belitskaya-Levy I, Wisoff J, Wisoff JH. Efficacy and safety of radical resection of primary and recurrent craniopharyngiomas in 86 children. J Neurosurg Pediatr. 2010 Jan;5(1):30-48.
Jane JA Jr, Prevedello DM, Alden TD, Laws ER Jr. The transsphenoidal resection of pediatric craniopharyngiomas: a case series. J Neurosurg Pediatr. 2010 Jan;5(1):49-60.
Puget S, Garnett M, Wray A, Grill J, Habrand JL, Bodaert N, Zerah M, Bezerra M, Renier D, Pierre-Kahn A, Sainte-Rose C. Pediatric craniopharyngiomas: classification and treatment according to the degree of hypothalamic involvement. J Neurosurg. 2007 Jan;106(1 Suppl):3-12. Review.
Jane JA and Laws ER. Craniopharyngioma. Pituitary 9:323-326, 2006.
Karavitaki N, Cudlip S, Adams CBT, Wass JAH. Craniopharyngiomas. Endocrine Reviews 27: 371-397, 2006.
Karavitaki N, Warner JT, Marland A, Shine B, Ryan F, Arnold J, Turner HE, Wass JAH. GH replacement does not increase the risk of recurrence in craniopharyngioma. Clinical Endocrinology 64: 556-560, 2006.
Patricia Donohoue, MD, is a program director of Endocrine at Children's Hospital of Wisconsin, a professor and chief of Pediatric Endocrinology at The Medical College of Wisconsin and a member of Children's Specialty Group.
Selim Firat, MD, is a radiation oncologist at Children's Hospital of Wisconsin, an assistant professor of Radiation Oncology at The Medical College of Wisconsin and a member of Children's Specialty Group.
Sachin Jogal, MD, is a pediatric oncologist at Children's Hospital of Wisconsin, an assistant professor of Pediatrics (Hematology/ Oncology) at The Medical College of Wisconsin and a member of Children's Specialty Group.
Marike Zwienenberg-Lee, MD, is a pediatric neurosurgeon at Children's Hospital of Wisconsin, an assistant professor of Neurosurgery at The Medical College of Wisconsin and a member of Children's Specialty Group.
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