You are in: eMedicine Specialties > Radiology > BRAIN/SPINE CraniopharyngiomaArticle Last Updated: Jun 11, 2008AUTHOR AND EDITOR INFORMATIONAuthor: Jeffrey R Wasserman, DO, Diagnostic Radiologist, Manatee Memorial Hospital and Lakewood Ranch Medical Center Jeffrey R Wasserman is a member of the following medical societies: American Medical Association Coauthor(s): Robert A Koenigsberg, DO, MSc, FAOCR, Director of Neuroradiology, Professor, Department of Radiology, Drexel University College of Medicine; Kiran Batra, MD, DNB, Neuroradiology Fellow, Radiology Resident, Drexel University College of Medicine; Christopher P Gange Jr, BS, Drexel University College of Medicine Editors: Mahesh R Patel, MD, Chief of MRI, Department of Radiology, Santa Clara Valley Medical Center; Bernard D Coombs, MB, ChB, PhD, Consulting Staff, Department of Specialist Rehabilitation Services, Hutt Valley District Health Board, New Zealand; Robert L DeLaPaz, MD, Director, Professor, Department of Radiology, Division of Neuroradiology, Columbia University; Robert M Krasny, MD, Consulting Staff, Department of Radiology, The Angeles Clinic and Research Institute; James G Smirniotopoulos, MD, Professor of Radiology, Neurology, and Biomedical Informatics, Chairman, Department of Radiology and Radiological Sciences, Uniformed Services University of the Health Sciences Author and Editor Disclosure Synonyms and related keywords: Rathke pouch tumor, craniopharyngeal duct tumor, hemangioblastoma, ameloblastoma, adamantinoma, dysodontogenic epithelial tumor, adamantinomatous tumor, papillary tumor, sellar craniopharyngioma, prechiasmatic craniopharyngioma, retrochiasmatic craniopharyngioma INTRODUCTIONBackgroundCraniopharyngioma is a histologically benign, extra-axial, slow-growing tumor that predominantly involves the sella and suprasellar space. Despite its histologic appearance, craniopharyngiomas occasionally behave like malignant tumors. They can metastasize, and patients can have severe symptoms that usually require surgery and/or radiation therapy (with intracystic chemotherapy in some pediatric patients). Recurrences, both local and along surgical tracts, have been reported, as has meningeal seeding. Characteristic radiographic findings help in differentiating craniopharyngiomas from other tumors that can occur in the same anatomic region. Zenker first described craniopharyngioma in 1857.1, 2, 3, 4, 5 PathophysiologyCraniopharyngiomas are dysodontogenic epithelial tumors derived from the Rathke cleft, which is the embryonal precursor to the adenohypophysis. The craniopharyngeal duct is 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,1 which partially explains the location of the tumor (see Anatomy). The trigger for tumor growth is not clear. Three distinct subtypes have been distinguished on the basis of histologic appearance: adamantinomatous, papillary, and mixed. Regarding adamantinomatous tumor (pediatric type), the classic and most common appearance is that of a cystic tumor, usually with a solid component. These tumors occur in a wide range of sizes. The cyst contains fluid that can vary in color, but it usually has a tan appearance similar to that of motor oil. The color is the result of suspended blood products, protein contents, and cholesterol crystals within the cyst fluid; the color may be the result of repeated hemorrhage within the cystic cavity. Histologically, the cyst has a multistratified squamous epithelium with nuclear palisade. The solid component demonstrates clumps of wet keratin, dystrophic calcifications, trabeculae, nests, and squamous or columnar epithelium. Extensive fibrosis and inflammation (which is considerably more severe with recurrent tumors than with others) are also observed. These findings may result in dense adhesion to adjacent structures and vessels, which accounts for the difficulty in resecting craniopharyngiomas. Intimate interdigitation of the tumor tissue and encasement of the vasculature of the circle of Willis are often present. Gliosis can make the differentiation of these tumors from a primary glial tumor difficult. Tumoral interdigitation also accounts for the frequency of recurrence of tumor in cases in which the tumor appears to have been totally resected on intraoperative visual inspection and despite the fact that these tumors are histologically benign. The classic appearance of the papillary variant (adult type) is different from that of the other forms and involves only a solid component, which is typically seen without calcifications. The papillary type is frequently located in the third ventricle. These tumors are usually more encapsulated than the others and are therefore more amenable to surgical resection. They demonstrate extensive squamous differentiation with the formation of pseudopapillae.6, 7 Unless otherwise indicated, the more common adamantinomatous type is the subtype referred to in this article. FrequencyUnited StatesCraniopharyngioma represents approximately 3-5% of intracranial tumors and 6-10% of pediatric brain tumors. In pediatric patients, craniopharyngiomas represent the most common intracranial tumor of nonglial origin; they account for approximately 54% of all sellar and prechiasmatic tumors.4, 8, 9 InternationalThe international frequency is identical to that reported in the United States. Mortality/MorbidityIn children, the 5-year survival rate is more than 80% after treatment with surgery and radiation. The overall 10-year survival rate is 64-96%.8, 9
RaceNo racial predominance is recognized. SexThe male-to-female ratio is equal. AgeA bimodal age distribution is seen, with the first peak occurring in childhood and early adolescence, predominately at age 5-10 years. The second peak (for papillary types) occurs at age 40-60 years. A nearly even distribution in incidences is observed between both age groups.4 AnatomyWith regard to surgery, craniopharyngiomas are classified into 3 groups: sellar, prechiasmatic, and retrochiasmatic. The tumors occur in suprasellar (75%), suprasellar and infrasellar (21%), or entirely intrasellar (4%) locations. Adamantinomatous-type tumors commonly occur entirely within the sella, the third ventricle, and the sphenoid sinus; they rarely occur within the nasal cavity. Craniopharyngiomas are usually avascular on angiography and may encase or displace vessels forming the circle of Willis. The internal carotid artery (ICA) is displaced laterally, the anterior cerebral artery (ACA) is displaced anteriorly, and the basilar artery is displaced posteriorly. Three specific growth categories have been determined on the basis of the relationship of the tumor to the vascular structures and the optic chiasm: type A, type B, and type C. In type A, the anterior communicating artery and the A1 segment of the anterior cerebral artery are not disturbed. Tumors of this type have little or no suprasellar bulge (ie, they are contained almost entirely within the sella). In type B tumors, the anterior communicating artery and the A1 segment of the anterior cerebral artery are elevated, but no posterior displacement of the basilar artery is observed. The tumor protrudes anteriorly between the optic nerves and pushes the optic chiasm posteriorly. In type C, the anterior communicating artery and the A1 segment of the anterior cerebral artery are elevated, with posterior displacement of the basilar artery and stretching of the posterior communicating arteries. The tumor protrudes posteriorly, pushing the chiasm forward and causing it to abut the tuberculum sellae. These tumors typically obstruct the third ventricle and cause hydrocephalus. Clinical DetailsThe range of clinical presentations of patients with craniopharyngioma is broad; patients may be asymptomatic, or they may have endocrine, visual, or psychological disorders. Many patients remain asymptomatic; in others, however, the disease follows a progressively deteriorating clinical course. Because of the associated and frequent endocrine dysfunction, a complete endocrine pretreatment workup is frequently performed. The most common presenting symptoms are headache, nausea, vomiting, and visual disturbances. The most common visual disturbances are bitemporal hemianopsia, homonomous hemianopsia, and amblyopia. Other common findings include oculomotor palsies, bizarre scotomas, blindness, asymmetric acuity deficiencies, and optic atrophy. Hydrocephalus may result from a tumor that obstructs the third ventricle. Papilledema frequently occurs. Visual disturbances usually improve after treatment, whereas most endocrine dysfunctions do not. Growth failure and headaches are part of the most common presentation of pediatric patients with craniopharyngioma; for children, the median age at presentation is 5 years. Other presenting symptoms are those of pituitary and adrenal hypofunction, diabetes insipidus, obesity, weakness, ataxia, coma, chemical meningitis (from rupture of cyst contents into subarachnoid space), and seizures. In particular, children can present with growth failure, obesity (one third to one half), and hypothyroidism (two thirds). Precocious puberty has been reported, as has diabetes insipidus (which affects up to one fifth of patients). Poor school performance is also common, as are psychological problems. In patients with tumors larger than 5 cm, postoperative recurrence and morbidity rates are higher than in patients with smaller tumors.11 Preferred ExaminationCT and MRI are the complementary examinations of choice. Today, the best imaging tool is MRI, both with and without contrast enhancement. CT can clearly demonstrate the characteristic calcifications and size of the tumor, whereas MRI exquisitely demonstrates the size and extent of the tumor and involvement of the third ventricle. MRI results can confirm cystic features of the tumor. Sequences such as fluid-attenuated inversion recovery (FLAIR), gradient-echo (GRE) imaging, and diffusion-weighted imaging, as well as MR spectroscopy, can be used to make a confident and correct diagnosis. Plain radiography may show abnormalities; however, CT or MRI is still needed regardless of the plain radiographic findings. CT and MRI have supplanted angiography as the primary diagnostic modality; today, magnetic resonance angiography (MRA) or CT angiography (CTA) may be helpful in differentiating the tumor from an aneurysm of the anterior communicating artery. In the later postoperative period, CT can be performed to establish the baseline for future follow-up scans and to determine the number and size of residual flecks of calcification. In the immediate postoperative period (first 48 h) and later, gadolinium-enhanced MRI may be performed to establish a baseline appearance and to determine whether residual tumor is present.8, 12, 13, 14, 15, 16, 17, 18, 19, 20 Gadolinium-based contrast agents (gadopentetate dimeglumine [Magnevist], gadobenate dimeglumine [MultiHance], gadodiamide [Omniscan], gadoversetamide [OptiMARK], gadoteridol [ProHance]) have recently been linked to the development of nephrogenic systemic fibrosis (NSF) or nephrogenic fibrosing dermopathy (NFD). For more information, see the eMedicine topic Nephrogenic Fibrosing Dermopathy. The disease has occurred in patients with moderate to end-stage renal disease after being given a gadolinium-based contrast agent to enhance MRI or MRA scans. Limitations of TechniquesNonenhanced CT may be required to detect calcifications if typical MRI findings are absent. A papillary-type lesion can be missed on MRI or CT when no characteristic cystic component is present or when lesions are not enhanced after the administration of intravenous (IV) contrast material (as occurs in approximately 10% of patients). MRI cannot be used in patients with pacemakers or implanted ferromagnetic metallic objects or in those with metallic foreign bodies in the brain, spinal cord, or soft tissues near important vascular structures. The use of MRI also is limited in patients with claustrophobia and in those who are unable to remain stationary for the required time. Both CT and MRI evaluations require IV contrast enhancement; therefore, IV access is needed. DIFFERENTIALSArachnoid Cyst Astrocytoma, Brain Epidermoid, Brain Meningioma, Brain Pituitary Adenoma Rathke Cleft Cyst Other Problems to Be ConsideredAneurysm
RADIOGRAPHFindingsA lateral radiogram of the skull may demonstrate calcifications in either the sella turcica or suprasellar space (see Image 7), or it may demonstrate sellar expansion or erosion of clinoid process or dorsum sella (see Image 10). These calcifications can be confused with curvilinear calcifications observed with large aneurysms (occasionally referred to as eggshell calcifications). An aneurysm may be differentiated on contrast-enhanced CT, which demonstrates characteristic enhancement of the remainder of the lumen of the aneurysm, and on MRI, which shows heterogeneity of signal intensity and misregistration artifact from turbulent or pulsatile flow in the aneurysm. MRA further helps to elucidate the diagnosis in questionable cases.2, 12, 13, 14, 16, 21 Degree of ConfidenceThe degree of confidence for a negative result is low because small calcifications can be missed easily. When observed, calcifications are a nonspecific finding. Soft tissue visualization on plain radiography is poor; therefore, differentiation of the type of tumor present is not possible without further imaging. False Positives/NegativesThe rate of false-negative results is high because calcified lesions can be missed easily. CT SCANFindingsOn CT, the adamantinomatous-type tumor appears as a predominately cystic mass (see Image 8) with a solid component (>90%). The solid component appears isoattenuating and usually contains calcifications (>80%). The sella may be expansile, and hydrocephalus may be present, depending on the exact location of the tumor (see Anatomy). Tumors of the papillary type are usually solid and isoattenuating; they are rarely calcified. Occasionally, craniopharyngioma may appear as an intraventricular, homogeneous soft tissue mass without calcifications but possibly with hypoattenuating regions; this is observed in the papillary subtype.14 The location of the adamantinomatous subtype is characteristic because most are located in the sella or suprasellar region. Contrast enhancement is characteristic of the solid component (see Image 9) and cyst wall (90% cases), and an enhanced study may demonstrate displacement of the A1 segment of the anterior cerebral artery (see Image 12). Displacement of the optic chiasm also may be observed. On CT, the cystic component of the tumor extends anteriorly and/or laterally and typically wraps around the solid component. Conversely, the solid component characteristically extends posteriorly and laterally. Degree of ConfidenceThe degree of confidence is high because CT is sensitive for calcifications and for visualizing the cystic nature of masses. False Positives/NegativesAs with MRI, the noncalcified, papillary variant may sometimes be missed. A Rathke cleft cyst is rarely calcified, whereas more than 90% of craniopharyngiomas are calcified. Please refer to specific findings in the MRI section below for other differential diagnostic findings. MRIFindingsOn MRI, the more common adamantinomatous subtype appears as a predominately cystic suprasellar mass with a solid component (see Image 1). Characteristic calcifications may not be discernible, though gradient-echo (GRE) images may show susceptibility effects from calcified components. Cystic areas appear hyperintense on T2-weighted and fluid-attenuated inversion recovery (FLAIR) images with heterogeneous isointense to hypointense solid components.12, 14, 16, 18, 22, 23 Changes in signal intensity vary on T1-weighted images, depending on the cystic contents, which can appear hyperintense if they have a high protein, blood product, and/or cholesterol content in the classic adamantinomatous type. In the papillary variety, solid components appear isointense on T1-weighted images. Magnetic resonance (MR) spectroscopy shows a prominent lipid spectrum (around 1 ppm) in terms of the cystic contents. Diffusion-weighted images demonstrate variable signal intensity, which reflects the cystic contents. The sella may be expansile, and hydrocephalus may be present, depending on the exact location of the tumor (see Anatomy). Compression of the third ventricle may occur; when present, such compression helps in distinguishing craniopharyingioma from Rathke's cleft cyst or pituitary adenoma. Occasionally, craniopharyngiomas appear as intraventricular, homogeneous, soft tissue masses without calcifications. They may contain regions of low signal intensity; this is observed in the papillary subtype. Some craniopharyingiomas can be both intrasellar and suprasellar, having a "snowman" appearance.23 The location of the adamantinomatous subtype is characteristic, with most tumors located in the sellar or suprasellar region (see Images 13-15). Contrast enhancement is characteristic (see Images 2, 6). MR angiography may demonstrate displacement of the A1 segment of the anterior cerebral artery; displacement of the optic chiasm may also be observed. On MRI, the cystic component of the tumor extends anteriorly and/or laterally and typically wraps around the solid component (see Images 4-5). Conversely, the solid component of the tumor characteristically extends posteriorly and laterally (see Image 3). Adjacent brain parenchyma may show hyperintensity on T2-weighted or FLAIR images, which indicates edema from compression of optic chiasm and/or tracts, gliosis, or tumor invasion. Recurrence in both the local tumor bed and along surgical tracts may the result of implantation of craniopharyngioma tissue. Therefore, post-treatment MRI has been recommended, even in patients whose primary tumor was resected completely.18, 23 Degree of ConfidenceThe degree of confidence is high. Although MRI without a GRE sequence can be insensitive for calcifications, it is sensitive for determining the fluid or soft tissue content of a given area. False Positives/NegativesFalse-positive results may occur as a result of misidentification of a similar lesion in the differential diagnosis. A Rathke cleft cyst (RCC) can usually be differentiated because it is rarely calcified, whereas 64-92% of craniopharyngiomas are calcified. An RCC is also usually associated with anterior infundibular displacement and does not have a solid component. In addition, it shows contrast enhancement less frequently than other tumors do. Small RCCs may be indistinguishable from the rare intrasellar craniopharyngiomas. A suprasellar arachnoid cyst has angular margins and is entirely cystic, with no solid component or enhancement. Hypothalamic or chiasmatic astrocytomas arise at their respective locations and appear solid with areas of necrosis. The pilocytic variety may show cystic changes; however, calcification is less common with this tumor than with others. A moderate degree of enhancement may be seen. Meningiomas demonstrate the dural tail sign, which is absent with craniopharyngiomas. Meningiomas also have a wide dural base and densely adhere to the dura. A craniopharyngioma can grow to more than 5 cm, but most are smaller. Conversely, a germinoma is almost always large, and its signal intensity and enhancement are homogeneous. A cystic component rarely is observed, and a pineal satellite lesion may be present. Pituitary adenoma is rare in children; it is mostly intrasellar in the microadenoma variety. Macroadenomas may have suprasellar components with cystic, hemorrhagic, and enhancing areas; findings closely mimic those of a craniopharyngioma. However, calcification is rare. Teratomas contain mixed solid and cystic components, as do craniopharyngiomas, but teratomas typically contain some fat. Epidermoids can be distinguished by their characteristic scalloped margins and by the fact that, with epidermoids, there is minimal or no peripheral enhancement. Epidermoids are typically strongly hyperintense on diffusion-weighted images. Dermoids also contain a fatty component. ULTRASOUNDFindingsA few case reports have described the use of ultrasonography with color Doppler imaging in the antenatal diagnosis of fetal craniopharyngiomas. Adult craniopharyngiomas have also been evaluated with the use of color Doppler and ultrasonographic contrast agents.14, 16, 19 Degree of ConfidenceUltrasonography may be useful for prenatal imaging; however, the modality is operator dependent, it can be limited because of beam attenuation by the bony skull vault, and lesions may be missed. With the wide availability and documented accuracy of CT and MRI, ultrasonography has not been accepted as a universal tool for the evaluation of pituitary masses. NUCLEAR MEDICINEFindingsAlthough evidence of increased metabolic activity in the tumor mass and surrounding brain has been observed, nuclear evaluation is not preferred for the diagnosis of craniopharyngioma. ANGIOGRAPHYFindingsMost of the findings relate to displacement of the cerebral vasculature secondary to mass effect. Specifically, the position of the anterior cerebral artery is well correlated with the location of the tumor. When the A1 segment of the anterior cerebral artery and the anterior communicating artery are in the usual position, the tumor is contained entirely or almost entirely within the sella. When the A1 segment and the anterior communicating artery are elevated (see Image 11) but the basilar artery is in the usual position, the tumor protrudes anteriorly and projects between the optic nerves, deviating the chiasm posteriorly. When the A1 segment and the anterior communicating artery are elevated and the basilar artery is displaced posteriorly, the tumor protrudes posteriorly and pushes the chiasm anteriorly. Stretching of the posterior communicating arteries also may be noted. An unreliable finding is a small, vascular blush in the region of the tumor. CTA and MRA have supplanted angiography as the primary diagnostic techniques, and angiography is now rarely needed to differentiate the tumor from an aneurysm of the anterior communicating artery. Degree of ConfidenceAngiography findings are nonspecific. False Positives/NegativesOther tumors can produce similar angiographic findings. INTERVENTIONPrimary treatments include radical surgery or limited surgery, such as subtotal resection and radiation therapy. Surgery has been associated with a high risk of hypothalamic injury and visual impairment. Some success has been observed with intracystic chemotherapeutic (bleomycin) injection, which is effective in treating the cystic component; it is also used as an adjuvant therapy and in stereotactic radiotherapy.5, 7, 15, 16, 20, 24, 25, 26, 27 Medical/Legal Pitfalls
See also the Medscape topic Medical Malpractice and Legal Issues. MULTIMEDIA
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