History

The first pathologic description was from an autopsy performed in 1857, when Zenker reported a suprasellar lesion with cholesterol crystals and squamous epithelial cells. The first accurate pathologic description was by Erdheim² in 1904. Frazier and Alpers in 1931 and Cushing in 1932 first used the term craniopharyngioma.¹ In 1909 Halstead³ was the first to successfully remove a craniopharyngioma using the transsphenoidal route. A child operated on by Cushing in 1923 survived for more than 50 years.⁴ In 1899 Mont and Barrett suggested that these tumors arise from the hypophysial duct (Rathke’s pouch).⁵ The hypophysial duct is actually an invagination of the primitive stomodeum, not of the pharynx, making craniopharyngioma a misnomer.⁶ Rathke’s pouch forms the pars tuberalis in the development of the anterior lobe of the pituitary gland. This embryologic origin becomes important when viewing magnetic resonance imaging (MRI) scans because it is extremely uncommon not to have a portion of the tumor located within the sella turcica.

Rathke’s cleft cysts also arise from Rathke’s pouch, which is normally reduced to a neural cleft by the sixth week of embryonic life. When a Rathke’s cleft cyst persists, it has the potential to become pathologic, progressively enlarging and filling with mucoid material. Rathke’s cleft cysts and craniopharyngiomas may represent a continuum from the simplest form of Rathke’s cleft cyst to a more complex form of craniopharyngioma.⁷ Other entities found in this area are epithelial, epidermoid, and dermoid cysts.

Histology

There are three histologic types of craniopharyngioma: adenomatous, squamous papillary, and mixed. The adenomatous variety, which is the histologic pattern most common in the pediatric population, resembles tumors of tooth-forming tissue, having a varied histologic pattern of sheet-like epithelium, lobules, anastomosing trabeculae, cysts, and cloverleaves. The distinctive feature is a palisading layer of small cells enclosing a loose stellate reticular zone with alternating, compactly arranged squamous cells that have a tendency to whorl. The epithelium is a wet keratin, differing from the flaky keratin of epidermoid cysts, and is the hallmark of this tumor subtype. Dystrophic calcification, fibrosis, chronic inflammation, and cholesterol clefts are also prominent features.⁶ The squamous papillary type is rare in children but makes up approximately one third of the adult variety.⁸ These tumors tend to be solid rather than cystic and may occur within the third ventricle.⁹ They are less likely to develop calcification and do not form keratin nodules, leading to no evidence of calcification on computed tomography (CT), which is important in the differential diagnosis in adult patients. Mixed tumors contain separate foci with histologic features of both adenomatous and squamous papillary types.⁹

Adenomatous craniopharyngiomas tend to have finger-like projections that invade the hypothalamus. Therefore, it is common to find small foci of normal brain tissue within resected craniopharyngioma specimens.^7–9 This histologic finding is not readily appreciable under the operating microscope, where the tumor capsule may seem to be distinct from the adjacent neural tissue. It is well established that the squamous papillary type, which does not have these microscopic projections, has a better clinical outcome and a lower rate of recurrence with gross total surgical removal than the adenomatous type.^8,10 Other authors contend that this histologic difference is not predictive of outcome.^9–11 A fibrillary gliotic reaction in the brain immediately adjacent to a craniopharyngioma may create a cleavage plane that actually aids in tumor removal.^12–16 Again, there is a difference of opinion; other authors think this dense adherence makes separation from normal brain more difficult.^17,18

Epidemiology

Craniopharyngiomas are the most common intracranial pediatric tumors of nonglial origin; they constitute 1.2% to 4% of all brain tumors and 6% to 9% of all pediatric brain tumors.¹⁷ There are approximately 0.5 to 2 new cases per million people per year.¹⁷ In childhood, approximately 54% of tumors in the sella-chiasmatic region are craniopharyngiomas.²⁰ These tumors can present at any age, but there is a bimodal age distribution, with peak incidence rates in children aged 5 to 15 years and adults aged 40 to 70 years (Fig. 198-1).²¹ In the United States, 338 cases are expected to occur annually, with 96 patients presenting at an age younger than 14 years. Although classically thought to be more common in males, there has been no obvious gender difference in large population-based studies.²¹ The peak incidence in the pediatric age group is 5 to 10 years, but craniopharyngioma can occur at any age. There are no known associated genetic abnormalities or risk factors.⁸

FIGURE 198-1 Age of presentation in a series of 109 patients with craniopharyngioma.

(Adapted from data in Sung DI, Chang CH, Carmel PW, et al. Treatment results of craniopharyngioma. Cancer. 1981;47: 847-852.)

Clinical Presentation

Craniopharyngiomas are slow-growing extra-axial tumors and frequently become quite large before they become symptomatic. Children present with three major clinical syndromes: increased intracranial pressure, visual impairment, and endocrine dysfunction. When the child comes to medical attention, it is common for all three components to be present; however, usually the symptoms of increased intracranial pressure, including headache, lethargy, and vomiting, bring the child to the physician.

Increased intracranial pressure may be due to the actual size of the tumor but is more often caused by obstructive hydrocephalus as the tumor blocks cerebrospinal fluid at the foramen of Monro or the third ventricle.

Visual impairment is common, and tumors are occasionally discovered when visual screening or parental observation results in ophthalmologic referral. One should note that very large tumors may cause minimal to no visual defects. Visual defects often go undetected until severe visual impairment and optic atrophy are present.¹⁹ Visual disturbance is noted in 37% to 68% of children at presentation.^13,21–30 A formal neuro-ophthalmologic examination should be obtained preoperatively whenever possible.

Endocrine dysfunction is very common, occurring in 66% to 90% of new pediatric patients. However, it is rare for a child to be brought to medical attention specifically for an endocrine-related complaint. Short stature (defined as height less than the 3rd percentile), diabetes insipidus (7.5% to 24% of patients), and hypothyroidism (12% to 25% of patients) have been reported.^{6–9,11,30,31} Endocrine testing reveals deficiencies of growth hormone in up to 75% of patients, luteinizing hormone and follicle-simulating hormone in 40% of patients, adrenocorticotropic hormone (ACTH) in 25%, and thyroid-stimulating hormone in 25%. Less common presenting features are elevation of prolactin (20%), morbid obesity (11% to 18%), diplopia (8% to 11%), and disturbance of mentation.^{6–8,11,30,31} It should be noted that it is rare for a child with a craniopharyngioma to have clinically significant diabetes insipidus at presentation.

Imaging

Historically, skull radiographs were very important in the diagnosis of craniopharyngioma because they demonstrated sellar enlargement and suprasellar calcification, but they are unnecessary in the modern era. MRI is required in the diagnostic evaluation and is necessary for adequate surgical planning and postoperative evaluation. Because CT scans show calcification, which occurs in 51% to 90% of pediatric craniopharyngiomas,^32,33 this modality remains a useful and important part of the preoperative evaluation. CT is also superior in demonstrating the anatomy and size of the sphenoid sinus when the transsphenoidal surgical route is anticipated. The calcifications have a craggy, popcorn-like appearance, with fine eggshell lines (Fig. 198-2A to C).³⁴ Coronal CT can facilitate the detection of intrasellar ossification.

FIGURE 198-2 A, Computed tomography (CT) demonstrates calcification within the sella. B, CT shows calcification within the cyst wall. C, CT depicts hydrocephalus. D, T1-weighted magnetic resonance imaging (MRI) shows a large cyst. E, T1-weighted MRI shows the dome of the cyst and acute hydrocephalus. F, T2-weighted MRI shows the dome of the cyst and acute hydrocephalus. G, CT scan, with a catheter in the cyst, shows relief of hydrocephalus after the removal of cyst fluid. H, CT scan, with a catheter in the cyst, shows cyst reduction, but the calcified wall restricts further reduction.

MRI, with and without gadolinium enhancement, is critical for demonstrating the tumor’s relationship to the optic chiasm, infundibulum, hypothalamus, and major vessels (Fig. 198-3C, E, and F). The T1-weighted images should be in the axial, coronal, and sagittal planes. The postcontrast sagittal images are most useful in assessing the relationship of the tumor to the hypothalamus, providing critical information for later decisions regarding treatment options.^35,36 If a patient has a cystic, enhancing suprasellar mass with calcifications, it is almost certainly an adamantinomatous type of craniopharyngioma (see Figs. 198-2 and 198-3).³³

FIGURE 198-3 A, Sagittal T1-weighted magnetic resonance imaging (MRI) without contrast. B, Sagittal T1-weighted MRI with gadolinium shows patchy enhancement with multiple small cysts. C, Axial T2-weighted MRI demonstrates a solid tumor portion and a cyst. D, Coronal T1-weighted MRI with gadolinium demonstrates a partially enhancing tumor and cyst. E and F, T1-weighted MRI without contrast demonstrates the optic tract and nerve. G, T1-weighted MRI with gadolinium shows patchy enhancement.

Craniopharyngiomas are typically 2- to 4-cm lesions in 58% to 76% of cases,^37,38 although very large tumors have been reported.^39,40 The most common morphologic finding is a predominantly cystic type of tumor in 46% to 64% of cases.^30,38,41 The predominantly solid type is seen in 18% to 39% of cases, and mixed solid and cystic tumors are seen in 8% to 36% of cases.^29,41 On MRI the solid portion of the tumor typically appears mottled, an indirect effect of signal dampening due to tumor calcification.⁴² Gadolinium produces heterogeneous enhancement of the solid tumor (see Fig. 198-3B and G). The signal intensity of cystic fluid on T1-weighted images may range from low to high. This variation and degree of intensity is the result of different protein concentrations, free methemoglobin, and cholesterol crystals.⁴³ The walls of the cystic portions of the tumor almost always enhance with contrast (Table 198-1; see Fig. 198-3B).⁴⁴

TABLE 198-1 Magnetic Resonance Imaging Characteristics of the Cystic and Solid Portions of Craniopharyngioma

* Acute, subacute, or chronic hemorrhage; protein density; and cholesterol deposition may alter cystic imaging characteristics.

Cerebral angiography provides the best demonstration of the displacement of major vessels by tumor, but it has largely been supplanted by magnetic resonance angiography. When planning a radical surgical removal of recurrent craniopharyngioma, invasive angiography may be useful to delineate constriction of the carotid, middle, or anterior cerebral arteries and facilitate tumor dissection. Fusiform dilation of the carotid artery has been reported after radical tumor resection, and it potentially increases the risk during reoperation.^35,45 Because craniopharyngiomas are relatively avascular, even modern angiography may not demonstrate the small nutrient vessels.¹⁹

There are many postoperative and intraoperative options for the follow-up of patients with craniopharyngioma. We recommend that MRI be obtained within 48 hours after surgery to document the presence or absence of residual tumor and the size of residual cysts and to minimize confusion when interpreting postsurgical changes (see Fig. 198-2G and H). If complete surgical removal is attempted, an additional CT scan is necessary because a small fleck of calcification may mean that the resection was incomplete, portending recurrent tumor growth in the follow-up period.

Differential Diagnosis

The differential diagnosis of suprasellar-sellar masses includes chiasmatic-hypothalamic glioma, germinoma, Rathke’s cleft cyst, hypothalamic hamartoma, arachnoid cyst, pituitary adenoma, and meningioma; the last two are rare in children.²⁷ The presence of calcification on CT virtually eliminates all these diagnoses except meningioma. In children whose tumors are predominantly adamantinomatous, calcification occurs more than 90% of the time.^33,34 The next most common tumor in this area is the chiasmatic-hypothalamic glioma, which does not have an intrasellar component and does not commonly calcify.

Rathke’s cleft cysts are an important diagnostic challenge because they rarely need to be resected. Although the cyst wall may enhance with gadolinium, there is no solid component and no calcification.

Hypothalamic hamartoma does not enhance, does not have calcification, and does not progress with serial observation.

Some craniopharyngiomas are suprasellar with no intrasellar component, but the characteristic cyst and calcification virtually assure the preoperative diagnosis on the basis of imaging alone. Because the neurosurgeon can be relatively confident of the diagnosis preoperatively, it allows a frank discussion of treatment options with the family before surgical intervention.

Endocrine Evaluation

Management Controversy

Although there is much debate over the proper management of patients with craniopharyngiomas, the treatment must focus on relief of symptoms, cure of disease, and quality of life of the patient. In reaching these goals, the surgeon must choose the treatment strategy that causes the least harm and delivers the most benefit to the patient. The continuum of treatment ranges from radical resection with the avoidance of radiation to limited surgery followed by radiotherapy. The role of other treatment modalities such as intracystic therapy (P-32, bleomycin) or the Gamma Knife is discussed later, but they are usually just adjuncts to one of the major treatment approaches. In expert hands, cure rates using either surgical approach are nearly identical.^16,49–52 One certainty is that attempts at gross total resection of large solid tumors have a significantly negative effect on quality of life.^{17,34,50,51,53–55} As such, the surgeon must look closely at his or her own results in terms of cure of disease and harm from treatment and make the best treatment decision for each patient. A survey of neurosurgeons demonstrated that surgeons who operated on one or fewer craniopharyngiomas per year could not expect the results of radical surgery quoted in the literature with regard to cure rate or complication rate.⁵⁶

Because the diagnosis is 99% assured after neuroimaging, it allows the surgeon to discuss with the family and the patient the various treatment options. Failure to provide full informed consent is unethical and unwise in our present age of universal access to medical information.

Radical Resection Versus Limited Surgery Plus Radiotherapy