Pediatric Craniopharyngioma

Craniopharyngiomas (see image below) are histologically benign neuroepithelial tumors of the CNS that are predominantly observed in children aged 5-10 years.

This MRI sequence was obtained following the intravenous administration of gadolinium contrast. Observe the relatively homogeneous and cystic mass arising from the sella turcica and extending superiorly and posteriorly with compression of normal regional structures. Note that the lesion is sharply demarcated and smoothly contoured. This fluid-filled mass is consistent with a typical craniopharyngioma.

These tumors arise from squamous cell embryologic rests found along the path of the primitive adenohypophysis and craniopharyngeal duct. Although histologically benign, these tumors frequently recur after treatment. In addition, because they originate near critical intracranial structures (eg, visual pathways, pituitary gland, hypothalamus), both the tumor and complications of curative therapy can cause significant morbidity.

We discuss childhood craniopharyngioma in this article. 

Pediatric craniopharyngiomas are believed to arise from cellular remnants of the Rathke pouch, which is an embryologic structure that forms both the infundibulum and anterior lobe of the pituitary gland. Its path of development extends from the pharynx to the floor of the sella turcica; not surprisingly, these tumors have been identified extensively in suprasellar, parasellar, and ectopic locations.[1] Typically, the tumors arise within the sella or adjacent suprasellar space.

The WHO classification of central nervous system tumors divides craniopharyngiomas into three histologic subtypes: adamantinomatous, found in children, papillary, found in adults, and mixed.[2]

Recent studies have demonstrated that the histologic subtypes of craniopharyngioma have distinct molecular signatures that play a role in tumorigenesis.[3] Mutations in the beta-catenin pathway, i.e. CTNNB1, have been found in adamantinomatous craniopharyngioma in the pediatric population, and BRAF mutations have been identified in papillary craniopharyngioma in adults.[4, 5] Beta-catenin is a downstream component of the Wnt signal transduction pathway. Intranuclear accumulation of beta-catenin results in enhanced expression of target genes that play a critical role in cellular proliferation and differentiation. The accumulation of nuclear beta-catenin can also be used diagnostically to help distinguish Rathke cleft cysts from adamantinomatous or papillary craniopharyngiomas on immunohistochemistry.[6, 7] Investigations are ongoing to harness the therapeutic implications of these mutations.

Paracrine signaling mechanisms resulting in a pro-inflammatory tumor microenvironment have also been hypothesized to drive adamantinomatous tumor behavior.[8] Additional molecular factors have been implicated in aggressive or recurrent craniopharyngiomas, including low expression levels of macrophage-inhibiting factor (MIF), galectins, retinoic-acid receptors isotypes,  and cathepsins, and high levels of vascular-endothelial growth factor (VEGF) levels, however additional studies are needed to elucidate the clinical implications of these findings.[9, 10]

Frequency

United States

Craniopharyngiomas are relatively rare, representing 6-10% of intracranial malignancies in children and adolescents (approximately 2-3 cases per 1,000,000 children). A bimodal distribution peak has been reported, with one peak at age 5-14 years and the other at age 65-74 years. More than 300 cases are reported in the United States annually, and roughly one third of these involve children aged 0-14 years.[4, 11, 12] Craniopharyngiomas are the most common childhood tumor that occur in the sella-chiasmatic region.[13]

International

The Childhood Cancer Registry of Piedmont, Italy estimates an incidence of 1.4 cases per million children per year in keeping with reports from other Western countries. Higher incidence rates have been observed in Asia and Africa with about 4 cases per million children reported in Japan in one series.[14]

Mortality/Morbidity

Previous studies have shown relatively good outcomes, with 10-year overall survival rates of 86-100% among patients who underwent gross total resection. Subtotal resection or recurrence treated with surgery and radiation therapy carry 10-year overall survival rates of 57-86%. The perioperative mortality rate after primary surgical intervention has been estimated to be 1.7-5.4%. However, the mortality rate after re-resection for recurrent disease can be as high as 25%.[13]

Almost all patients with craniopharyngioma ultimately suffer from chronic morbidities. These are most commonly endocrinologic in nature but also include significant neurologic morbidities such as vision loss, ataxia, behavioral problems, cognitive disabilities, and sleep disorders (See Clinical and Complications for details).

Race

No clear racial predilection has been reported.

Sex

The most recent large series demonstrate equal sex distribution, although a slight male preponderance has been historically reported.

Age

Peak incidence of childhood craniopharyngiomas occurs in individuals aged 5-14 years. Neonatal craniopharyngiomas are rare. Of the more than 300 cases per year in the United States, approximately one third involve children aged 0-14 years. The incidence of adult craniopharyngiomas has a second peak in individuals aged 50-74 years.

Symptoms of craniopharyngioma can be present for years before diagnosis.  Craniopharyngiomas produce symptoms by compression of adjacent neural structures most importantly the optic pathways and hypothalamus and pituitary stalk. They can become quite large, obstructing cerebral spinal fluid (CSF) pathways (i.e. third ventricle or the foramen of Monro) and causing hydrocephalus and increased intracranial pressure that leads to headaches, nausea, and projectile vomiting. 

• Headache: Headaches occur in 60-80% of children with craniopharyngioma at presentation and are usually a symptom of increased intracranial pressure or hydrocephalus.

• Vomiting: Classic projectile vomiting (frequently without nausea) accompanies headaches as a sign of increased intracranial pressure and is reported in 35-70% of children with these tumors at presentation.

• Vision loss

  • Children are frequently unaware of significant vision loss; nevertheless, this symptom reportedly occurs in 20-60% of pediatric patients with craniopharyngioma at presentation.

  • Anterior extension to the optic chiasm can result in a classic bitemporal hemianopsia, unilateral temporal hemianopsia, papilledema, or unilateral/bilateral decrease in visual acuity. Classically, vision loss starts with a superior temporal field cut. However, the eccentric growth of these tumors can result in varying patterns and severity of vision loss, including decreased acuity, diplopia, blurred vision, and subjective visual field deficits. Children are frequently inattentive to visual loss, and formal testing may be required.

• Endocrine dysfunction: This results from direct compression or destruction of the hypothalamus and pituitary stalk. At the time of diagnosis, 40-85% of patients present with at least one hormonal deficit. ^[11]

  See the list below:

  • Growth hormone deficiency is the most common deficit in children occurring in 35-95%. This can result in short stature. One series reported that growth failure preceded diagnosis of craniopharyngioma by a mean of 4 years.
  • Gonadotropin deficiency (LH and FSH) is the most common deficit in adolescents occurring in up to 40% of patients resulting in delayed puberty, erectile dysfunction, and amenorrhea.
  • Secondary hypothyroidism (TSH deficiency) is present in 21-42% of cases and include weight gain, lethargy, fatigue, cold intolerance, dry skin, dry brittle hair, slow teething, anorexia, large tongue, deep voice, and myxedema.
  • Secondary adrenal insufficiency (ACTH deficiency) occurs in 25% of patients and can present with fatigue, myalgias, arthralgias, weakness, and hypoglycemia due to glucocorticoid deficiency.
  • Diabetes insipidus (ADH deficiency) occurs in 17-28% of patients and may present with polydipsia and polyuria.

• Diencephalic syndrome: This term is used to describe emaciated hyperactive children who occasionally present with unusual eye movements and even blindness. These symptoms result from extrinsic compression of the hypothalamus. Conversely, damage to or invasion of the ventromedial hypothalamus can result in a dysregulation of energy balance and resultant obesity upon presentation.

• Mental status changes occur in as many as 25% of adults, but are rare in children. Temporal lobe involvement can rarely result in seizures.

Focus physical examination on the identification of neurologic and endocrine derangements.

Neurologic Examination

See the list below:

• Enlarging head circumference: this finding is highly suggestive of an intracranial mass or hydrocephalus, particularly when paired with papilledema.
• Papilledema: occurs in 25-40% of children and results from increased intracranial pressure.
• Visual field deficits

  • Formal testing is generally required to identify visual field deficits in children, which likely explains the wide reported range (10-95%) of patients with craniopharyngioma.
  • Given the typical proximity of the tumor to the optic nerves, optic chiasm, and anterior optic tracts, the common discovery of visual fields defects at presentation is not surprising.
• See-saw nystagmus: although often referred to as a classic physical examination finding among children with parasellar tumors, the literature reports an incidence rate of less than 10%.
• Cranial nerve palsy: with the notable exception of the optic nerves, cranial nerve palsies are relatively rare, with a reported incidence rate of 8% for children at time of diagnosis.
• Ataxia: this is another sign of increased intracranial pressure or hydrocephalus, which is present in 5-10% of patients at initial evaluation.
• Seizure: rarely described as a presenting feature
• Focal motor weakness: rarely described as a presenting feature
• Intellectual disturbance or somnolence: most likely to be due to hypothyroidism or hydrocephalus

Endocrinologic Evaluation

See the list below:

• Short stature or growth retardation is the most common endocrine derangement associated with this tumor. Growth retardation (as documented on formal pediatric growth charts) is reported in 86% of patients with craniopharyngioma at presentation.
• Obesity and weight gain is the third most common endocrine abnormality associated with craniopharyngiomas. Hypothyroidism, growth hormone deficiency, and direct hypothalamic injury can contribute to obesity and weight gain. Obesity and weight gain are reported in 20% of presenting patients.
• Hypothyroidism can manifest as weight gain, dry skin, brittle hair, and bradycardia.
• Precocious or delayed puberty is the fourth most common endocrine derangement associated with craniopharyngiomas and is present at diagnosis in 10-15% of patients. This is the most common presenting sign in adolescents.

No known environmental or infectious causes predispose to the development of craniopharyngiomas.

The following laboratory measurements are indicated in patients with craniopharyngiomas:

Serum electrolytes levels establish readiness for surgery. Importantly, the endocrine dysfunction frequently associated can cause abnormalities in several of these test findings.

Intracranial germ cell tumors can also primarily occur in the suprasellar region. Therefore, serum beta-HCG and alpha-fetoprotein (AFP) measurements should be considered to help narrow the differential diagnosis prior to definitive biopsy.

Growth hormone levels, including thyroid-stimulating hormone/thyroid hormone levels, steroid hormone levels (cortisol), follicle-stimulating hormone/luteinizing hormone levels should be obtained preoperatively as a baseline. Obtain tests to allow for perioperative hormone replacement as necessary.

Skull Radiography

Approximately 85% of craniopharyngiomas have calcifications above or within the pituitary fossa on plain radiographs of the skull.

Enlargement of the sella turcica can also be reliably identified.

If hydrocephalus is associated with a tumor in a young patient, split sutures may be observed.

Head CT

This may be the only preoperative radiographic study needed because craniopharyngiomas are observed with mixed solid and cystic components, and the solid component is enhanced following the administration of intravenous contrast.

CT scanning is better than MRI at revealing the common tumor-associated calcifications.

Peritumoral edema is rare.

Hydrocephalus is identified and readily characterized.

Non-contrast Head CT with peripheral calcifications around a bi-lobed craniopharyngioma.

Brain MRI

MRI is better than CT scan at determining the relationship of the tumor to adjacent normal structures.

As with CT scanning, mixed solid and cystic components are identifiable, and multiple cysts are common.

Craniopharyngiomas are usually sharply demarcated and smoothly marginated (see the image below).

This MRI sequence was obtained following the intravenous administration of gadolinium contrast. Observe the relatively homogeneous and cystic mass arising from the sella turcica and extending superiorly and posteriorly with compression of normal regional structures. Note that the lesion is sharply demarcated and smoothly contoured. This fluid-filled mass is consistent with a typical craniopharyngioma.

The solid component of the lesion frequently enhances following intravenous contrast administration, and a smooth ring of enhancement of the cyst wall can also be present (see the image below).

This axial CT scan image demonstrates a cystic lesion in the typical location of a craniopharyngioma. Although most of the lesion is fluid filled, a rim of enhancing soft tissue is observed following the administration of intravenous contrast.

Distortion or obliteration of the third ventricle is common.

Frequent involvement of the optic chiasm is found.

Obtaining postoperative imaging within 48 hours after surgery to best distinguish residual tumor from postsurgical changes is important.

Preoperative intellectual or psychological assessment may be useful as a baseline examination prior to undertaking curative therapies.

Angiography: Cerebral angiography can be useful in planning the surgical approach, although it has been largely replaced by MRI/magnetic resonance angiography (MRA) in most centers. A vascular blush can be observed, although the tumor is not visible.

Craniopharyngiomas can be histologically classified into 3 types: adamantinomatous, papillary, and mixed. The adamantinomatous type is by far the most common in children (92-96%). Grossly, these tumors usually have both solid and cystic components. The fluid within the cysts has been historically described as "crankcase oil" because of its frequently dark and oily intraoperative appearance. Upon microscopic examination, the fluid contains abundant lipids with birefringent cholesterol crystals. Clinically, spillage of the cyst fluid into the subarachnoid space can cause severe chemical arachnoiditis.

Microscopic examination of the solid components reveals an epithelial tumor with angulated columnar cells resting on a collagen basement membrane. Papillary structures are common, and calcification is nearly universal. Large tumors may induce an intense glial reaction and intensely adhere to the underlying normal brain.

Preoperative and postoperative MRIs of the brain are adequate staging modalities for most children with craniopharyngioma. The postoperative scan is important in assessing residual disease. Neuraxis dissemination does not occur; thus, full spinal evaluation is unnecessary in an asymptomatic patient.

A large study out of China looked at 226 pediatric and adult cases of craniopharyngioma and subdivided them into 3 anatomical growth patterns: infradiaphragmatic (Id-CP) (referring to the diaphragm sellae), suprasellar subarachnoid extraventricular (Sa-CP), and suprasellar subpial ventricular (Sp-CP). The authors went on to demonstrate that the Id-CP tumors were much more common in children and tended to have more invasive growth patterns than the other 2 sub-types. In addition, the surgical approached differed for the different anatomic sub-types as well, suggesting that pre-operative MRI categorization of these tumors may help in surgical planning.[15]

The optimal treatment for craniopharyngiomas remains controversial.  Decisions regarding the care of a patient with craniopharyngioma should be made in a multidisciplinary setting that includes neurosurgery, neuro-oncology, radiation oncology, ophthalmology, and endocrinology.

Medical management can be divided into two components: achieving tumor control and management of treatment complications.

Tumor Control

The utility of pharmacologic agents in the management of pediatric craniopharyngioma remains controversial and randomized controlled trials are needed.

The evidence for administration of systemic agents in pediatric craniopharyngioma is limited, however, some data suggests it may be useful in progressive or recurrent craniopharyngioma patients who are not candidates for resection or radiation therapy. Interferon alpha-2a, chosen for its efficacy in cancers with a similar epithelial origin, was administered in a phase II trial in recurrent or progressive pediatric craniopharyngioma.[16] Although an objective radiographic response was seen in only 3 of 12 patients who were able to be evaluated, the time until radiation therapy was required was delayed in those patients. However, 60% experienced moderately severe toxicities (eg, hepatic, neurologic, cutaneous), but these were all reversible with discontinuation or dose reduction. The same group more recently administered pegylated interferon-alpha-2b in a small series of 5 patients demonstrating the feasibility of this approach, however larger, more robust investigations are clearly needed.[17]

Intracystic or intratumoral administration has demonstrated some benefit.[18] Bleomycin, an antibiotic that induces DNA strand breaks and acts as an antineoplastic agent, has been successfully administered by an Ommaya-type catheter into the cyst with subsequent regression of cystic cavities in many patients.[19] However, in a large meta-analysis, no definitive conclusions could be made about the effectiveness of intratumoral Bleomycin in the treatment of pediatric craniopharyngioma.[20]  Intratumoral interferon alpha has also been administered with similar results.[21] Complications from intratumoral administration, including those from inappropriate intratumoral catheter placement and leak of the pharmacologic agent outside of the cyst, have been described. One report described the use of carmustine (BCNU)–impregnated wafers (Gliadel: Guilford Pharmaceuticals, Inc; Baltimore, Maryland) in a patient with recurrent craniopharyngioma.[22]

Management of Treatment Complications

Long-term hormone replacement is the primary medical treatment associated with childhood craniopharyngiomas and includes the administration of intranasal vasopressin (desmopressin acetate [DDAVP]), corticosteroids, thyroid hormones, growth hormones, and sex hormones.

Perioperative care includes attention to frequently associated multiple hormone deficiencies.

Frequently, perioperative corticosteroid administration (stress doses) is required.

Surgical management when feasible is the treatment of choice in pediatric craniopharyngioma.  Surgical options include radical surgery or  conservative surgery with postoperative radiotherapy.

Radical Surgery

Radical surgery with gross total resection was historically the preferred surgical approach.  However, due to the significant morbidity and lack of evidence to suggest a lower recurrence rate, radical surgery is now only recommended when the tumor is favorably localized and does not intimately involve the hypothalamic or optic regions.

Both transcranial and transsphenoidal approaches have been described.  No surgical technique has been identified as superior in the pediatric population. Transsphenoidal approaches were more commonly associated with nonendocrine complications in 7-12 year olds in one analysis.[23] Another study comparing transcranial and transsphenoidal approaches in 314 pediatric craniopharyngioma patients found that transsphenoidal surgery was associated with a higher incidence of cerebrospinal fluid leak, but shorter length of stay.[24]

True complete resection of these tumors is challenging, even for experienced neurosurgeons who operate on several children with craniopharyngiomas each year.[25, 26] Frequently, these tumors densely adhere to the optic chiasm, pituitary stalk, and internal carotid artery and often invade the region of the third ventricle; therefore, not surprisingly, radical surgery frequently causes significant morbidity including panhypopituitarism, neurologic deficits (cranial nerve palsies, hemiparesis, aphasia), and visual field deficits or blindness. Recently, the perioperative mortality rate has been reported as low as 3%; however, perioperative morbidity remains an issue, ranging from 8-14%.[27, 28]

In addition, gross total resection does not prevent recurrence. Following radical resection, local relapses have been described in 10-50% of patients. One series reported that complete excision was achieved in only 63% of patients treated with radical surgery, and one half of the tumors believed to be completely excised subsequently recurred.[29]

Conservative Surgery Alone

Morbidity and mortality associated with radical surgery led neurosurgeons to attempt lesser resections; unfortunately, limited surgery alone resulted in worse local control with rates of local progression as high as 75-90%, and even greater morbidity due to repeated resections after recurrences.

Conservative Surgery and Postoperative Radiotherapy

Because both radical and conservative surgical approaches have limitations, postoperative external-beam radiotherapy has been added to limited surgery in an effort to improve local control. The literature seems to support this approach, with a reported long-term control of approximately 80-95% at 5-20 years and a low risk of long-term morbidity.[30]

Some advocate postoperative radiation even after gross total resections, particularly if residual calcifications are noted on postoperative imaging studies since this portends a poor prognosis.

In general, radiotherapy is administered using field arrangements similar to those used for pituitary adenomas (>2 fields, narrow margin around gross tumor volume). A dose response for craniopharyngiomas has been reported; thus, the total tumor dose is generally 5000-5500 cGy in 25-30 fractions.

Radiation therapy may also be of benefit as a salvage therapy in patients with failed surgical resection or progressive or recurrent craniopharyngioma.[31] Radiosurgery has also been used in pediatric craniopharyngioma both as an adjunct in postoperative residual disease and as salvage for recurrent or progressive disease.[32] Intracavitary irradiation (brachytherapy) has also been attempted in patients with recurrent craniopharyngioma. The local radiation doses ranged from 200-267 Gy, and complete or partial cyst resolution was seen in 71-88% of cases. However, the appropriate isotope to use and whether intracavitary brachytherapy has any impact on overall outcome remains unclear.[13]

Children younger than 3 years may not be candidates for such radiotherapy because they can develop unusually severe long-term adverse effects.

Risk of parenchymal brain injury or second malignancy caused by radiation therapy is estimated to be less than 1-2%.

Obtain consultations from the following:

• Pediatric neurosurgeon

• Radiation oncologist

• Pediatric endocrinologist

• Pediatric hematologist/oncologist

Attention to special neurologic and endocrinologic concerns is prudent. Weight gain can be dramatic and a significant long-term problem. Nutritional consultation can be helpful.

Drug therapy currently is not usually a component of standard care for craniopharyngioma. However, altered CNS hormone regulation may result following treatment with surgery and radiation, requiring long-term hormonal therapy. Endocrinologic consultation is recommended.

Class Summary

Immunostimulatory therapies with interferon and intracystic/intratumoral injection of chemotherapeutic agents (eg, bleomycin) are occasionally used in cases of recurrent disease.

Bleomycin (Blenoxane)

Peptide antibiotic that acts to inhibit DNA, RNA, and protein synthesis through the induction of DNA strand breaks.

Peginterferon alfa-2b (PEG Intron, PegIntron Redipen, Sylatron)

Naturally occurring interferon alpha is normally secreted by B cells and T cells in response to viral or bacterial infection. The manufactured form (ie, interferon alpha) is a protein product manufactured using recombinant DNA technology. Mechanism of antitumor activity is not clearly understood; however, direct antiproliferative effects against malignant cells and modulation of host immune response may play important roles.

Endocrine

Close monitoring of growth, pubertal development, and any known hormone abnormalities is essential in patients with craniopharyngioma.

Oncologic

Routine neuroimaging is the mainstay of follow-up assessment.

The expert consensus recommends brain MRI every 3 months for 1 year, followed by MRI every 6 months for 1 year, and then annual MRI until year 5. If they received radiation therapy, an MRI annually or every other year for life is recommended due to the potential risk for second malignancies.

Ophthalmologic

Routine ophthalmology evaluations are recommended. In particular, new visual field deficits may hallmark disease progression.

Neuropsychiatric

Periodic formal assessment can be useful when monitoring the long-term sequelae of surgery or radiotherapy.

In formal assessment, include comparison with preoperative and postoperative evaluations.

Long-term hormone supplementation is the primary medical treatment associated with childhood craniopharyngiomas and includes the following:

• Intranasal vasopressin

• Corticosteroids

• Thyroid hormones

• Growth hormones

• Sex hormones

A meta-analysis confirmed the high rates of endocrine, vascular, neurologic, and visual morbidities experienced by the patients posttherapy. Although the study was retrospective and had limitations, they concluded that, at least for some patients, less aggressive surgery followed by radiation therapy might result in less morbidity.[30] Further details regarding complications are below.

Endocrine Morbidity

The need for hormone replacement is common (approximately 80%) following therapy for craniopharyngiomas. Individual hormone deficits manifest with rates of 88-100% for GH, 55-88% for ACTH, 39-95% for TSH, 80-95% for FSH/LH, and 25-86% for ADH.

There have been concerns regarding the use of supplemental human growth hormone therapy for short stature in these children. Many pre-clinical brain tumor studies have demonstrated tumor growth after administration of growth hormone.[33] However, more recently, several large observational series have been unable to find an association between inferior tumor outcomes and use of growth hormone replacement. Current practice centers around continuing use of physiologic growth hormone replacement, with close imaging follow-up of these patients to monitor for tumor growth/recurrence.[34, 35, 36]

Diabetes insipidus is one of the most serious endocrinologic disturbances. Children with diabetes insipidus can become dehydrated during episodes of illness, and their summer activity must frequently be curtailed; in addition, vasopressin administration can be expensive.

Hypothyroidism, growth hormone deficiencies, steroid hormone deficiencies, and delayed or precocious puberty have also been reported. Pay particular attention to these children when they develop significant systemic illnesses; stress doses of steroids may be required.

Obesity and obesity-related complications are also well described morbidities for these patients. Hypothalamic damage, changes in metabolic expenditures, and decreased physical activity are some reasons for these often difficult to manage problems.[12]

Severe endocrine abnormalities are associated almost exclusively with radical surgery.

Ophthalmologic Morbidity

More than 50% of patients present with visual impairment at diagnosis.  40-50% of patients experience some post-surgical improvement of vision. Patients at risk for post-surgical visual impairment are those with a prechiasmatic tumor location or severe pre-surgical visual deficits.  The transsphenoidal approach has been associated with improved opthhalmological outcomes.  

Neurologic Morbidity

This is also frequently associated with attempts at radical tumor resection, visual loss, and hypothalamic injury (morbid obesity, hypersomnolence), which may develop following therapy for craniopharyngiomas. Sleep dysfunction has also become increasingly recognized as a complication of craniopharyngioma diagnosis and management, with almost two thirds of patients reporting sleep problems in one series.[37]

Neuropsychological Morbidity

Memory loss, behavior changes, and academic decline can result directly from neurologic damage. These neuropsychological changes can also occur indirectly as a result of other complications of therapy (eg, endocrinologic derangement).

Thrombophilia

Deep vein thromboses (DVT) have been well described as a complication postoperatively for patients with craniopharyngioma. Inadequate control of serum sodium and hormonal changes have been hypothesized as contributing to an increased risk for DVT in these patients.

One series evaluated concomitant risk factors for DVT in a small series of patients with craniopharyngioma and identified some inherited risk factors that might further increase the risk for DVT in these patients including increased factor VIII and von Willebrand factor (vWF) levels, MTHFR mutations, and mutations in plasminogen activator inhibitor-1(PAI-1).[38]

Consequences of Radiation Therapy

Although it is now more commonly used in the management of craniopharyngiomas, even for children, late effects of radiation therapy are becoming increasingly recognized.

Endocrinopathies, vasculopathies (as high as 21%), and second malignancies (1.9% at 10 years) are now being seen following radiation therapy for these tumors.[39]

Transformation of low-grade craniopharyngiomas into high-grade epithelial carcinomas has also been observed. Generally this is in association with prior radiation therapy, although 1 of 3 cases from 1 series did not have prior radiation.[40]

Previous studies have shown relatively good outcomes, with 10-year overall survival rates of 86-100% among patients who underwent gross total resection. Subtotal resection or recurrence treated with surgery and radiation therapy carry 10-year overall survival rates of 57-86%. More recently, the surgical mortality rate after primary surgical intervention has been reported to be 1.7-5.4%. However, mortality rate after re-resection can be as high as 25%. Gross total resection carries a greater risk of long-term neurologic and endocrinologic morbidity.

Yosef and colleagues recently looked at the impact of initial tumor size on outcomes. They looked at tumors less than 4.5 cm maximum diameter versus tumors greater than 4.5 cm in diameter. They termed the large craniopharyngiomas, “giant” craniopharyngiomas and found them to be associated with greater residual post-operative tumor and significantly decreased 2 and 5 year PFS versus smaller tumors (33.3 vs. 73.3% and 33.3 vs. 53.3% respectively).[41]

For additional information, see the People Living With Cancer article on craniopharyngioma.