Craniopharyngioma Pathology 

Updated: Sep 03, 2013
  • Author: Abir L Mukherjee, MD; Chief Editor: Adekunle M Adesina, MD, PhD  more...
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Definition

Craniopharyngiomas are low-grade (World Health Organization [WHO] grade I) circumscribed epithelial tumors that most commonly arise in the suprasellar region.

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Epidemiology

Craniopharyngioma comprises 5%-10% of all childhood brain tumors and 1.2%-4.6% of brain tumors in adults (0.5-2.5 new cases per million population per year). [1] The reported incidence of craniopharyngioma is particularly high in Nigeria and Japan. [2, 3] The peak incidence is in children aged 5-15 15 years. A second peak occurs later in life, between ages 50 and 60 years. There is no sexual predilection. [1]

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Etiology

Craniopharyngioma comprises two clinically, histologically, and biologically distinct subtypes: adamantinomatous (most common) and papillary. [4, 5] Rare hybrid forms have also been reported. [6] Papillary craniopharyngioma occurs almost exclusively in adults, whereas adamantinomatous craniopharyngioma occurs both in adults and children. Adamantinomatous craniopharyngioma presumably arises from remnants of the Rathke pouch and the craniopharyngeal duct.

The close histopathologic and immunohistochemical resemblance among adamantinomatous craniopharyngioma, adamantinoma of the jaw, and calcifying odontogenic cyst suggests an odontogenic epithelial differentiation for these tumors. [7] Collision lesions of the sellar region, including pituitary adenoma associated with Rathke cyst and pituitary adenoma associated with craniopharyngioma, have been described. [8] Complex sellar lesions consisting of pituitary adenoma intimately admixed with Rathke cyst and metaplastic squamous epithelium have also been reported. [9]

The current hypothesis is that pituitary adenoma, adamantinomatous craniopharyngioma, and Rathke cyst share a common ancestry from involuted remnants of the Rathke pouch and the craniopharyngeal duct. In elderly persons, squamous metaplasia of adenohypophyseal cells of the pituitary stalk or gland has been postulated as a possible origin for the papillary variant of craniopharyngioma. [10]

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Location

Craniopharyngiomas most commonly arise in the suprasellar region, with a variable intrasellar component. Other rarer locations include isolated infrasellar, intraventricular (third ventricle), corpus callosal, posterior fossa, and postclival sites. [11, 12, 13, 14, 15]

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Clinical Features and Imaging

Clinical features of craniopharyngiomas may include visual disturbances (from compression of the optic chiasm and adjacent nerves and tracts), endocrine abnormalities, and signs of increased intracranial pressure. Endocrine abnormalities may take the form of hormonal deficiencies or of diabetes insipidus. Cognitive and personality changes have also been observed.

Adamantinomatous craniopharyngioma

Magnetic resonance imaging (MRI) typically shows a complex solid/cystic lesion with heterogeneous signal intensity. The cysts are often filled with fluid of high protein content (thus, they are hyperintense on T1-weighted images). Solid areas show enhancement following gadolinium administration. Peripheral calcification is often prominent on computed tomography (CT) scans.

Papillary craniopharyngioma

MRI characteristically shows an enhancing, predominantly solid, circumscribed mass without the calcification or complex cystic architecture of the adamantinomatous variant. The papillary architecture may sometimes be evident.

Although the imaging descriptions of the two morphologic variants are typically as described above, overlap and exceptions occur. In addition, there is overlap between the imaging characteristics of craniopharyngioma of both subtypes and other sellar/suprasellar mass lesions of this anatomic neighborhood; thus, tissue examination is generally required for definitive diagnosis.

Gadolinium warning

Gadolinium-based contrast agents (gadopentetate dimeglumine [Magnevist], gadobenate dimeglumine [MultiHance], gadodiamide [Omniscan], gadoversetamide [OptiMARK], gadoteridol [ProHance]) have been linked to the development of nephrogenic systemic fibrosis (NSF) or nephrogenic fibrosing dermopathy (NFD). For more information, see Nephrogenic Systemic Fibrosis. 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.

NSF/NFD is a debilitating and sometimes fatal disease. Characteristics include red or dark patches on the skin; burning, itching, swelling, hardening, and tightening of the skin; yellow spots on the whites of the eyes; joint stiffness with trouble moving or straightening the arms, hands, legs, or feet; pain deep in the hip bones or ribs; and muscle weakness.

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Gross Findings

Adamantinomatous craniopharyngioma is a partly cystic mass filled with dark greenish-brown fluid that has traditionally been compared in terms of color and consistency to "machinery oil." The characteristic white speckled appearance of "wet" keratin nodules typical of the adamantinomatous variant are frequently grossly visible and give the neurosurgeon advance notice of the diagnosis before the pathologist even sees the surgical specimen.

In contrast to the adamantinomatous variant, which tends to insinuate tongues around nerves and blood vessels, the papillary subtype is comparatively more well-circumscribed and typically lacks the complex multicystic architecture and fluid-filled spaces upon sectioning.

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Microscopic Findings

Cytopathology

The cytologic smear of adamantinomatous craniopharyngiomas show compact nodules of "wet" keratin, calcifications, macrophages, multinucleated giant cells, cholesterol crystals, and amorphous debris in the background. Cellular, cohesive sheets of epithelial cells with peripheral palisading are prominent, in addition to individual epithelial cells.

The cytologic smear of papillary craniopharyngiomas shows tissue fragments composed of benign squamoid cells, with only rare individual cells. Small cellular whorls are often seen.

Histology

With adamantinomatous craniopharyngiomas, a complex epithelial lesion with cysts and calcified "wet" keratin is seen. The epithelium has central stellate reticulum with prominent peripheral palisading. Rarely, ciliated cells and goblet cells are encountered. Even rarer are calcification and enamel formation in an abortive attempt to form "toothlike" structures. The adjacent neural parenchyma may show granulomatous reaction with cholesterol clefts. In some cases, there are perilesional piloid gliosis with Rosenthal fibers. A biopsy or frozen section sample from this area can be potentially misleading.

Adamantinomatous craniopharyngioma (low power). Adamantinomatous craniopharyngioma (low power).
Adamantinomatous craniopharyngioma (medium power) Adamantinomatous craniopharyngioma (medium power)
Adjacent gliosis with rosenthal fibers (medium pow Adjacent gliosis with rosenthal fibers (medium power)

With papillary craniopharyngiomas, an epithelial lesion composed of mature squamous epithelium without surface maturation, a keratohyaline granular layer, or keratin formation is noted. Focal tissue dehiscence with resultant pseudopapillary architecture is often present. Small whorls are frequently present, and basal peripheral palisading is also seen, but this feature is not as prominent as with the adamantinomatous variant. The most characteristic features of the adamantinomatous subtype, including nodules of "wet" keratin, "stellate reticulum," and calcification, are absent.

Papillary Craniopharyngioma (low power) Papillary Craniopharyngioma (low power)

Ultrastructure

Electron microscopic studies are virtually never needed for diagnosis of craniopharyngiomas, but, when performed, these studies show the expected ultrastructural features of epithelial differentiation, including prominent numbers of desmosomes and associated cytoplasmic tonofilaments. [16]

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Immunohistochemistry

Most adamantinomatous craniopharyngiomas show aberrant nuclear expression of beta-catenin, a feature that is not observed in papillary craniopharyngiomas. [17] Nuclear beta-catenin expression is also observed in the shadow cells of pilomatricoma and calcifying odontogenic cysts. [18] Adamantinomatous craniopharyngioma also expresses various enamel proteins, including amelogenin, enamelin, and enamelysin, supporting the postulated odontogenic differentiation. [19]

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Molecular/Genetics

Most of the adamantinomatous craniopharyngiomas harbor a mutation of the beta-catenin gene (CTNNB1). [20] Almost all mutations involve exon 3, which encodes the degradation targeting box of beta-catenin. This mutation results in nuclear accumulation of beta-catenin protein and dysregulation of the Wnt signaling pathway, with activation of downstream targets such as Axin-2. [21] Papillary craniopharyngioma and other sellar region lesions do not exhibit this mutation. Chromosomal imbalances are very rare in both the adamantinomatous and papillary subtypes. [22]

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Tumor Spread and Staging

Craniopharyngiomas are WHO grade I tumors; however, rare cases of craniopharyngioma seeding along the surgical access route and through the cerebrospinal fluid (CSF) pathways have been reported. [23, 24]

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Prognosis and Predictive Factors

Although classified as WHO grade I tumors, craniopharyngiomas often demonstrate an aggressive local behavior after therapy and may require adjuvant radiotherapy. [25] The recurrence rate is related to the extent of surgical resection and tumor size (>5 cm). [26] Some studies have shown a better prognosis for the papillary subtype, whereas other reports have failed to confirm this finding. [6] Malignant transformation into squamous cell carcinoma following irradiation has been documented both in adults and in children. [27, 28]

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Alternate Diagnoses

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