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Pediatric Craniopharyngioma

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Last Update: April 3, 2019.

Introduction

Pediatric craniopharyngioma could be considered one of the most complex neurosurgical pathologies in the pediatric population. The tumor's proximity to essential neural structures poses is challenging to manage in both pediatric and adult populations. In pediatric populations, these structures are still maturing and are extremely sensitive, both to the craniopharyngioma and the treatments that might be employed against it making treatment decisions difficult. This article reviews the most important aspects of this pathology in the pediatric population.

Etiology

Craniopharyngioma is a benign tumor of the central nervous system (CNS); however, malignant cases have been reported. It is a partly cystic embryonic malformation of the sellar/parasellar region. There are 2 types of craniopharyngioma, each with distinct histopathology. These are the adamantinomatous craniopharyngioma and the papillary squamous craniopharyngioma. Two theories attempt to explain the etiology of craniopharyngioma. These are the embryo-genetic and the metaplastic theories, which propose a mechanism for the development of pediatric and adult craniopharyngioma, respectively. This article only reviews the embryo-genetic theory.

The embryo-genetic theory is related to the development of adamantinomatous craniopharyngiomas, which are believed to be the most common subtype of craniopharyngioma that occurs in the pediatric population. It is important to note that despite the adamantinomatous subtype being the most commonly seen in the pediatric population, there have been cases reported in the literature of papillary squamous and mixed subtypes presenting in children. During embryogenesis, there is an outpouching of the ectodermal roof of the stomodeum. This outpouching, known as Rathke's pouch, extends cranially toward the floor of the diencephalon to later form the adenohypophysis or anterior pituitary gland. While migrating cranially, its extension forms the craniopharyngeal duct which later involutes. In some circumstances, involution is not total, and remnants of ectodermal cells can be present. These embryonic cells can proliferate around the extension of the craniopharyngeal duct and develop into a craniopharyngioma.

Epidemiology

Craniopharyngioma has an incidence of 0.5 to 2 cases per million persons per year. Almost half of these cases occur during the first 2 decades of life. It represents 1.2% to 4% of all childhood intracranial tumors. It has a classical bimodal distribution of incidence with increased incidence rates in patients aged 5 to 14 years and 50 to 74 years. No statistically significant differences have been described regarding demographic characteristics such as age, gender, race, and geographical location. Interesting instances of craniopharyngioma have been reported, including craniopharyngiomas of the cerebellopontine angle, malignant transformation of craniopharyngiomas and familial cases of craniopharyngiomas.

Craniopharyngioma has a very high recurrence rate, with reported rates as high as 50%. It also has high survival rates (83% to 96% 5-year survival and 65% to 100% 10-year survival) but also carries similar rates of morbidity, with almost all patients developing some sequelae. This is particularly relevant for the pediatric population as they have longer survival rates than adult patients and have to live their lives with sequelae of treatment.

Pathophysiology

The most common location of craniopharyngioma is the sellar/suprasellar region, with 95% of craniopharyngiomas having a suprasellar component. Its location defines its pathophysiology. Craniopharyngiomas can compress normal pituitary tissue and result in pituitary deficiencies, particularly of the anterior pituitary hormones. It can also compress the optic chiasm and/or optic nerves and cause different degrees and types of visual disturbances, from blurry vision to blindness. It can also present with hydrocephalus secondary to third ventricle compression. In cases of significant suprasellar extension, non-specific symptoms of intracranial hypertension such as a headache, nausea, and vomiting can also occur. Cases of isolated oculomotor nerve and abducens nerve palsies have been described.

Histopathology

As mentioned before, there are two subtypes of craniopharyngioma: adamantinomatous and papillary. For purposes of this discussion, we will discuss the histopathology of the most common subtype of craniopharyngioma in children, which is the adamantinomatous craniopharyngioma.

Adamantinomatous craniopharyngioma is characterized by dense nodules and trabeculae of squamous epithelium bordered by a palisade of columnar epithelium sometimes referred to as a "picket fence." These nests of squamous epithelium are surrounded by loose aggregates of squamous epithelium known as stellate reticulum. Spread between the mix, one can find cystic cavities which hold an oily proteinaceous fluid along with cholesterol, piloid gliosis, granulomatous inflammation, calcification, and nodules of "wet keratin" which is abrupt keratinization of cells into stacks of large flat plates. [1] These tumors frequently calcify.

History and Physical

Craniopharyngioma most commonly manifests with signs of increased intracranial pressure (ICP) including a headache and nausea and vomiting along with visual and endocrine disturbances (62% to 84% and 52% to 87%, respectively). The most common visual disturbance encountered is temporal hemianopsia due to optic chiasm compression. The onset of blindness is considered a neurosurgical emergency. At the time of presentation, around 40% to 87% of patients present with at least one hormonal deficit. The hormonal deficiency is secondary to normal pituitary compression, particularly of the anterior pituitary. In some cases, posterior pituitary hormonal deficiencies can be seen, particularly diabetes insipidus. In children, failure to thrive and decreased growth rate can be the initial presentation as growth hormone is the most commonly affected hormone.

Evaluation

Any presentation with a combination of a headache, visual disturbance, and endocrine disturbance should have a pituitary region lesion in the differential diagnosis.

Visual exam, including acuity and visual fields, can suggest a visual disturbance and visual fields can be used to confirm it. In terms of hormonal deficiencies, laboratory tests for hormone level measurement or stimulation of hormone production can be used to confirm a suspected hormonal deficiency.

Treatment / Management

Multiple modalities can be implemented in the management of craniopharyngioma, including neurological surgery, radiotherapy, and instillation of sclerosing substances. There is no consensus on the best treatment regimen. The types of modalities chosen depend on neurosurgeon judgment and experience.

Neurosurgery

The most common surgical approaches include pterional, subfrontal, and transsphenoidal. Transcallosal approaches for craniopharyngiomas with third ventricle extension, retrosigmoid approaches for posterior fossa craniopharyngiomas and transorbital approaches have also been described. Extension of resection is a matter of debate. Gross total resection has been associated with increased incidence of post-surgical deficits, with no clear benefits in regards to recurrence rates. Unless the tumor is clearly visualized and with no extension into neural structures including the hypothalamus, optic nerves, optic chiasm, and/or carotids, most neurosurgeons will favor a partial resection. These partial resections can be accompanied by adjuvant methods including radiotherapy and instillation of sclerosing substances. For the later, in cases of cystic tumors, the surgeon can introduce a catheter into the tumor and connect it to a reservoir. The reservoir then permits instillation of substances into the tumor as well as aspiration of cystic fluid, which can be performed as an outpatient procedure.

Radiotherapy

Radiation therapy includes various modalities: conventional external radiotherapy, proton beam therapy, stereotactic radiotherapy, radiosurgery, and brachytherapy. The goal of radiotherapy is to decrease tumor burden while protecting essential neural structures. Specific Gy doses have been designated for every radiation modality. Multiple reports have suggested decreased mortality with slightly reduced morbidity following radiation therapy. Despite this, radiation therapy has not been proven to reduce the recurrence rate. Therefore, it continues to be an adjuvant modality to neurosurgical intervention.

Instillation of Sclerosing Substances

This method consists of instillation of different toxic substances with the endpoint of producing tumor fibrosis and sclerosis, for example, radioactive isotopes, bleomycin, interferon alpha. This method has been reported to produce significant cyst shrinkage, but prospective data are still missing, making it a promising option. A disadvantage of this option is that severe neurotoxicity can occur in some cases due to cystic leakage of the sclerosing substance. [2]

In pediatric cases, there has recently been a trend toward favoring a subtotal resection followed by adjuvant radiotherapy. The basis for this decision as that there is evidence indicating that gross total resection, although associated with a lower rate of recurrence, is associated with morbidity related to damage of involved structures. Pediatric patients are particularly more sensitive to damage of these structures and have to live their lives impaired from this morbidity. For this reason, most neurosurgeons would employ a treatment plan where they attempt to debulk as much tumor as possible while protecting intervening structures in an attempt to avoid morbidity and then can subject the patient to radiotherapy for tumor control. [3] In the long run, there is evidence suggesting that this method is as effective or even more effective than pursuing a total resection and may be associated with less morbidity. It is important to keep in mind that radiotherapy can also be morbid, and this will depend on the dosage administered and the extent of tumor involvement. [4]

Differential Diagnosis

The differential diagnosis for craniopharyngioma include [5]:

Other tumors: Pituitary adenomas, primitive neuroectodermal tumors, hypothalamic hamartoma, germ cell tumor, epidermoid or dermoid tumor, meningioma, medulloblastoma, brainstem glioma and lymphoma

Other congenital conditions: Rathke's cleft cyst and arachnoid cysts

Inflammatory conditions: Pituitary abscess, lymphocytic hypophysitis, infundibulitis, histiocytosis, sarcoidosis, tuberculosis, and syphilis

Vascular malformations: Giant suprasellar carotid aneurysm, cavernous sinus hemangioma, and carotid-cavernous fistula

Enhancing Healthcare Team Outcomes

The management of craniopharyngioma is complex and usually requires a multidisciplinary team that includes a specialty trained nurse, oncologist, radiologist, radiotherapy specialist, neurologist, ophthalmologist and an endocrinologist. Once the patient is treated, the follow up is usually by the nurse practitioner and primary care provider. Depending on the type of tumor, the patient may develop a hormonal deficiency. 

The outcomes for microadenomas are excellent but patients with macroadenomas may be left with residual visual, metabolic or neurological deficits following treatment.[6][7][8][9] (Level V)

Questions

To access free multiple choice questions on this topic, click here.

References

1.
Miller DC. Pathology of craniopharyngiomas: clinical import of pathological findings. Pediatr Neurosurg. 1994;21 Suppl 1:11-7. [PubMed: 7841069]
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Mrowczynski OD, Langan ST, Rizk EB. Craniopharyngiomas: A systematic review and evaluation of the current intratumoral treatment landscape. Clin Neurol Neurosurg. 2018 Mar;166:124-130. [PubMed: 29408768]
3.
Weiner HL, Wisoff JH, Rosenberg ME, Kupersmith MJ, Cohen H, Zagzag D, Shiminski-Maher T, Flamm ES, Epstein FJ, Miller DC. Craniopharyngiomas: a clinicopathological analysis of factors predictive of recurrence and functional outcome. Neurosurgery. 1994 Dec;35(6):1001-10; discussion 1010-1. [PubMed: 7885544]
4.
Webb SM. Clinical outcomes of childhood craniopharyngioma: can we do better? Endocrine. 2018 Oct;62(1):1-2. [PubMed: 29934877]
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Fenstermaker R, Abad A. Imaging of Pituitary and Parasellar Disorders. Continuum (Minneap Minn). 2016 Oct;22(5, Neuroimaging):1574-1594. [PubMed: 27740989]
6.
Hill TK, Baine MJ, Verma V, Alam M, Lyden ER, Lin C, Connolly EP, Zhang C. Patterns of Care in Pediatric Craniopharyngioma: Outcomes Following Definitive Radiotherapy. Anticancer Res. 2019 Feb;39(2):803-807. [PubMed: 30711960]
7.
Willard VW, Berlin KS, Conklin HM, Merchant TE. Trajectories of psychosocial and cognitive functioning in pediatric patients with brain tumors treated with radiation therapy. Neuro-oncology. 2019 Jan 08; [PMC free article: PMC6502488] [PubMed: 30624746]
8.
Lesueur P, Calugaru V, Nauraye C, Stefan D, Cao K, Emery E, Reznik Y, Habrand JL, Tessonnier T, Chaikh A, Balosso J, Thariat J. Proton therapy for treatment of intracranial benign tumors in adults: A systematic review. Cancer Treat. Rev. 2019 Jan;72:56-64. [PubMed: 30530009]
9.
Li X, Wu W, Miao Q, He M, Zhang S, Zhang Z, Lu B, Yang Y, Shou X, Li Y, Wang Y, Ye H. Endocrine and Metabolic Outcomes After Transcranial and Endoscopic Endonasal Approaches for Primary Resection of Craniopharyngiomas. World Neurosurg. 2019 Jan;121:e8-e14. [PubMed: 30266691]
Copyright © 2019, StatPearls Publishing LLC.

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Bookshelf ID: NBK519027PMID: 30085569

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