Craniopharyngioma is a rare, benign tumor of the central nervous system (CNS). It is a partly cystic embryonic malformation that can occur in the sellar/parasellar region and can produce a wide array of symptomatology such as headaches, nausea and vomiting, visual disturbances, and endocrine disturbances. It represents a special challenge for the physicians that treat it; these physicians commonly include neurosurgeons, neuro-ophthalmologists, neurologists, endocrinologists, and pediatricians. The challenge is due to the tumor's ability to adhere to the surfaces that surround it. For this reason, it is extremely difficult to control, and it is also notorious for its high rates of recurrence.
The majority of craniopharyngiomas arise in the pituitary stalk and encroach on the hypothalamus. The lesion can also extend 1) posteriorly into the third ventricle, cerebellopontine angle and posterior fossa 2) anteriorly into the prechiasmatic cistern and 3) laterally into the subtemporal area. Rarely the tumor may grow extracranially into the nasopharyngeal space.
The clinical features of craniopharyngioma depend on its location and extent of invasion of nearby organs.
There are two major theories of the development of craniopharyngioma: the embryonic theory and the metaplastic theory. These two theories correlate with the two subtypes of craniopharyngioma which are the adamantinomatous craniopharyngiomas and the papillary craniopharyngiomas.
The embryonic 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. During embryogenesis, there is an outpouching of the ectodermal roof of the stomodeum. This outpouching, known as Rathke's pouch, extends cranially towards 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. On some occasions, 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.
The metaplastic theory is related to the development of papillary craniopharyngiomas, which are believed to be the most common subtype of craniopharyngioma in adult patients. It states that adenohypophyseal cells of the pars tuberalis can undergo metaplasia and result in the formation of squamous cell nests. These nests can then proliferate and lead to a papillary craniopharyngioma.
Genomic studies remain conflicting about the presence of oncogenes.
Craniopharyngioma has an incidence of 0.5 to 2 cases per million persons per year. Almost half of these cases occur during the first two 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 five 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% five-year survival and 65% to 100% 10-year survival) but also carries similar rates of morbidity, with almost all patients developing some sequelae.
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.
Most craniopharyngiomas are supplied by blood from the anterior circulation.
Recurrence of the craniopharyngioma is most common at the primary site but occasionally metastatic foci may appear as a result of seeding during surgery.
As mentioned before, there are two subtypes of craniopharyngioma: adamantinomatous and papillary.
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 that hold an oily proteinaceous fluid along with cholesterol, piloid gliosis, granulomatous inflammation, calcification, and nodules of "wet keratin."
On the other hand, papillary craniopharyngioma is characterized as well-differentiated squamous epithelium lacking surface maturation, with occasional goblet cells and ciliated epithelium. It is not nearly as organized as the adamantinomatous subtype, and calcifications are rare.
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 tumor is very slow-growing and symptoms tend to appear when the diameter approaches 3 cm.
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.
As the tumor grows, men may complain of impotence and loss of libido and women may complain of amenorrhea.
The dysfunction of the optic pathway is present in 50-75% of patients. Unfortunately, children rarely are aware of the vision changes and consequently they develop permanent loss of vision. Severe cases may manifest with optic nerve atrophy, papilledema, and visual field deficits.
Other manifestations include changes in behavior, mood, emotional lability, and cognitive dysfunction.
Three classic syndromes associated with craniopharyngiomas include the following:
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.
If hormonal dysfunction is suspected, the patient's CBC, electrolytes, levels of growth hormone, thyroid, LH, FSH, and cortisol levels need to be measured.
If the evaluation of the specimen following surgery reveals a MIB-1 index (proliferative index) of more than 7, then chances are that the tumor may recur.
CT scan is the imaging modality of choice. Nearly 2/3rd of lesions are calcified and cystic. Calcification is most common in children compared to adults.
MRI is often done to assess local invasiveness and planning for surgery.
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.
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.
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 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.
Craniopharyngiomas have a survival rate of 80-95% at 5 years. The variation is because the prognosis is good in young individuals and poor for individuals over the age of 65. Females tend to have additional morbidity that includes stroke, adverse cardiac events, and psychosocial deficits.
The differential diagnosis for craniopharyngioma include:
Craniopharyngiomas are rare benign tumors of the central nervous system (CNS). These patients usually present to the primary care provider or nurse practitioners with a wide array of symptomatology such as headaches, nausea and vomiting, visual disturbances, and endocrine disturbances. It represents a special challenge for the physicians that treat it; these physicians commonly include neurosurgeons, neuro-ophthalmologists, neurologists, endocrinologists, and pediatricians. The challenge is due to the tumor's ability to adhere to the surfaces that surround it. For this reason, it is extremely difficult to control, and it is also notorious for its high rates of recurrence. However, the outcomes in most people are good. (Level V)
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