Practice Essentials
Craniopharyngiomas are benign, extra-axial, slow-growing tumors that arise from the anterior margin of the sella turcica and predominantly involve the sella and suprasellar space. [1, 2, 3, 4] They rarely metastasize but are locally invasive (typically the hypothalamus), and treatment, particularly surgical attempts at total resection, can result in significant morbidity.
As craniopharyngiomas grow, they can cause significant neurologic complications, including visual loss, pituitary insufficiency, and hypothalamic damage, and recurrence, both local and meningeal, is often seen and adds to patient morbidity. Malignant transformation of craniopharyngiomas is rare but has been reported after multiple recurrences and after radiation.
The first description of a craniopharyngioma is credited to Zenker, who made this observation in 1857. Following this, Mott and Barrett, in 1899, documented the occurrence of these tumors and postulated that they arose from the hypophyseal duct or Rathke pouch. This was subsequently partially confirmed in 1904, when Erdheim described the tumors histologically and suggested that they arose from remnants of the Rathke duct. Finally, in 1932, Cushing introduced the term craniopharyngioma, which came to be widely used thereafter.
Evolution of surgical treatment for craniopharyngiomas is closely related to development of the surgical techniques of sella turcica. The first surgical techniques for craniopharyngioma originated in 1891 with the first trepanation done by Selke, followed in 1907 by the first successful transcranial approach performed by Horsley.
The progress of the surgical techniques continued with the first successful resection of craniopharyngioma through a transsphenoidal approach by Eiselsberg in 1910, which was improved by Halstead as a sublabial transsphenoidal resection in the same year. Cushing created the foundations of craniopharyngioma patient treatment with hormone replacement therapy, but also, in 1919, he developed and performed the first successful resection through the trans–lamina terminalis approach of a retrochiasmatic craniopharyngioma. Later, in 1924, he performed a transcallosal resection of a craniopharyngioma. [5]
As technology in diagnostic imaging has improved, so has the surgical treatment of craniopharyngioma. (See Treatment.) Surgical treatment is indicated in most cases, but surgeons have often approached this tumor with either an aggressive attempt at gross total resection of the tumor or a more conservative approach with a planned subtotal removal of the tumor followed by radiation therapy. The decision for either approach should take into consideration the following characteristics of the tumor:
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Its anatomic location
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Its size
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The extent to which it is invading nearby structures
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Its nature
See Brain Lesions: 9 Cases to Test Your Management Skills, a Critical Images slideshow, to review cases including meningiomas, glioblastomas and craniopharyngiomas, and to determine the best treatment options based on the case history and images.
Anatomy
In surgical terms, craniopharyngiomas have been divided into the following three groups:
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Sellar
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Prechiasmatic
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Retrochiasmatic
Sellar-located tumors may be further subdivided as follows:
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Suprasellar (75%)
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Infrasellar (21%)
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Intrasellar (4%)
These tumors occasionally grow into the third ventricle, causing hydrocephalus. The arterial supply is usually from the anterior cerebral artery (ACA) and the anterior communicating artery or from the internal carotid artery (ICA) and the posterior communicating artery.
Craniopharyngiomas are usually avascular on angiography but may encase or displace vessels that form the circle of Willis. Usually, the ICA is displaced laterally, the ACA is displaced anteriorly, and the basilar artery is displaced posteriorly.
A craniopharyngioma does not receive blood supply from the posterior circulation, unless it is parasitized from the floor of the third ventricle. As these tumors enlarge, they may elevate and infiltrate the optic chiasm as well as the hypothalamic region. Occasionally, they extend into the pituitary fossa or posteriorly to the ventral pons, and rarely, they invade the basal ganglia or the brain parenchyma.
When predominantly in the sella, these tumors erode the bony floor and enlarge the sella.
Pathophysiology
In the World Health Organization (WHO) classification, craniopharyngiomas are divided into the following two groups:
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Adamantinomatous
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Papillary
These two groups do not appear to differ significantly from each other with respect to prognosis, surgical resection, radiosensitivity, or life expectancy. [6, 7]
Etiology
Although the histologic description of craniopharyngiomas was first presetned more than a century ago, considerable debate still exists. Currently, the following three theories, from which three histologic variants have been derived, are widely accepted.
The first theory, the embryogenetic theory, suggests that the adamantinomatous type (so-called adamantinoma) arises from epithelial remnants of the Rathke pouch or the craniopharyngeal duct (the embryonal structure along which the eventual adenohypophysis and infundibulum migrate). Tumors can occur anywhere along the course of this duct, from the pharynx to the sella turcica and third ventricle, which partially explains the location of the tumor.
The second theory, the metaplastic theory, suggests that the squamous papillary type results because of metaplasia of squamous epithelial cell nests that arise from squamous cell nests normally found at the junction of the pituitary stalk and pars distalis.
The third theory postulates that this tumor is a midline congenital tumor not fundamentally different from an epidermoid cyst.
Epidemiology
The incidence of newly diagnosed craniopharyngiomas is 0.13-2 persons per 100,000 population per year. In some regions, such as Japan and parts of Africa, craniopharyngiomas appear with a higher incidence. [8, 9]
In the United States, approximately 350 new cases of craniopharyngioma are diagnosed every year. Distribution by age is bimodal: Tumors tend to be found in two age groups, children younger than 15 years and adults older than 45 years. Craniopharyngiomas represent 2-5% of all primary brain tumors and 5-10% of all childhood brain tumors. [10, 11, 12]
No sex predilection exists, and craniopharyngiomas occur with equal frequency in males and females. No genetic relation has been conclusively established; however, a few familial cases have been reported in the literature. [13, 14] Craniopharyngiomas are more common in African-American patients. [10]
Prognosis
Total resection affords the best chance for cure, though some series have reported good results with subtotal resection and fractionated radiation therapy. Small residual tumors, confirmed on postoperative magnetic resonance imaging (MRI), are generally treated with external beam radiotherapy; however, stereotactic radiosurgery has also been used. The use of proton beam radiotherapy for residual disease is being investigated. Although the amount of radiation is limited by the proximity to the optic chiasm, good long-term results are being reported after radiosurgery. [15, 16, 17, 18, 19]
Adverse effects of radiation therapy include endocrine dysfunction, optic neuritis, dementia, and radiation necrosis. In addition, radiation can induce tumors such as meningiomas, sarcomas, and gliomas. In pediatric cases, radiation is postponed to minimize its effects on intelligence quotient and growth. Survival rates for patients with surgery and radiation are better than with surgery alone because radiation helps deter regrowth when residual tumor is present. [20]
Brachytherapy has also been used to treat cystic craniopharyngiomas. Radioisotopes are placed into the cystic portions of the craniopharyngioma. Phosphorus-32 (32P), colloidal gold-198, colloidal yttrium-91, and bleomycin have all been used. Bleomycin causes shrinkage of the cyst but is highly toxic to neural structures.
In a review of brachytherapy for craniopharyngiomas, Van den Berge followed 31 patients for an average of 41 months. [21] Of the 31, 29% showed improvement of visual acuity, 13% had stable visual acuity, and 58% deteriorated. Similarly, 28% showed improvement of their visual fields, 20% showed no change, and 52% deteriorated.
Overall surgical mortality is lower than 5%, mostly from hypothalamic injury. Bilateral hypothalamic injuries lead to hyperthermia and somnolence. The 10-year survival rate, excluding non-tumor-related deaths, is 90%. [12]
The recurrence of craniopharyngiomas is reported to be up to 24% with approximately a 7-year follow-up. The main risk factor for recurrence is the presence of the residual tumor. Tumor recurrence is higher in the first 3 years after surgery. [22]
In patients with gross total removal of a craniopharyngioma, the 5-year recurrence-free rate is 84.9%, compared with 48.3% in patients with subtotal removal. [22, 23] Morbidity and mortality are higher with recurrence and mainly present as visual deficits, endocrine abnormalities, hypothalamic injury, and neurocognitive and neurobehavioral deficits. [23] The visual impairment can be caused by direct damage during surgery or from a daily dose higher than 2 Gy. The cumulative probability for visual deficits after surgery/radiation is reported to be 36-48% with a 10-year follow-up. [23, 24]
Endocrine abnormality is commonly seen in postoperative patients with craniopharyngioma. It presents as hypopituitarism and is reported with deficiencies of at least three pituitary hormones in 54-100%. [23, 24] Preoperative endocrine deficits are not alleviated after surgery, though patients with diabetes insipidus may improve. [23] Hypothalamic dysfunction after surgery may present as obesity because of hyperphagia, water balance impairment, loss of temperature control, sleep disorders, and neurocognitive disorders. Hypothalamic damage may result from tumor invasion, direct surgical injury from the resection of adherent tumor, tumor recurrence, and radiation. [23, 25]
Hoffman followed 50 children with craniopharyngiomas, [26] of whom 90% had total excision and 34% experienced tumor recurrence. At follow-up, 56% of the 50 were leading normal or nearly normal lives, often requiring endocrine replacement; 24% were able to function reasonably well and to attend school despite intellectual, visual, or weight problems; 8% were significantly handicapped; and 6% had died.
Van Effenterre et al reported that failure to achieve an independent living function with poor integration and performance at work or school was seen in 16% of adults and 26% of children. [27] Data from the literature show the importance of preoperative planning with a reasonable decision in terms of maximal safe tumor resection and the avoidance of complications.
A 40-year metadata analysis by Tan et al, including 185 cases of mediatric craniopharyngioma, found that the shift away from complete resection toward hypothalamic-sparing conservative surgery with adjuvant radiotherapy reduced the prevalence of hormone deficiencies but did not achieve comparable reductions in the occurrence of hypothalamic and visual morbidities. [28]
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Coronal MRI shows a craniopharyngioma in the suprasellar space that causes compression of the optic nerves and chiasm.
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Sagittal MRI shows a cystic craniopharyngioma in the suprasellar space with extension into the third ventricle.
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Axial MRI shows a craniopharyngioma cyst that contains proteinaceous fluid in the third ventricle. The cyst fluid appears hyperintense.
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Dissection of craniopharyngioma cyst with aspiration.
