Pediatric Neurosurgery
12 
Craniopharyngiomas
GREG JAMES, KRISTIAN AQUILINA
CLINICAL PEARLS
• Craniopharyngioma is a histologically benign tumor, which
presents special challenges to the neurosurgeon due to a
combination of its highly eloquent location and locally
recurrent nature.
• Craniopharyngioma can present with visual, neurologic, or
endocrine symptoms. Neurosurgeons managing
craniopharyngioma are strongly advised to work within a
multidisciplinary team that includes neuro-ophthalmologists,
endocrinologists, and oncologists.
• The “traditional” strategy for surgical management of
craniopharyngioma was radical resection. However, there is
increasing evidence that aggressive surgical treatment causes
severe long-term sequelae, related to pituitary and (especially)
hypothalamic dysfunction. Therefore many surgeons now
Introduction
Craniopharyngioma is a rare but important intracranial tumor
that presents a unique challenge to the neurosurgeon. It has
often been described as a histologically benign tumor that
behaves in a malignant manner. This “malignancy” is due
to a combination of its predilection for arising within and
being closely apposed to exquisitely eloquent brain structures,
its unpredictable biologic behavior, and its high local recur-
rence rates. Arising from the remnants of the Rathke pouch,
the tumor itself—and attempts to treat it, either surgically
or nonsurgically—can cause significant visual, endocrine,
and neurocognitive morbidity. The challenges arising from
this situation have long been recognized, and perhaps no
other intracranial neoplasm has seen such dramatic changes
in accepted treatment protocols over the decades. There have
been changes in suggested management stratagems—from
maximal resection based on achieving a radiologic cure, to
more minimal procedures, often in combination with adju-
vant therapies, focused on preserving function and minimiz-
ing the risk of recurrence. What has become increasingly
clear is that there is no “one size fits all” approach for these
complex entities, and each individual case must be assessed
204
Downloaded for andromeda masako (andromeda72@yahoo.com) at University of Sumatera Utara from ClinicalKey.com by Elsevier on September 02, 2019.
For personal use only. No other uses without permission. Copyright ©2019. Elsevier Inc. All rights reserved.
advocate more limited surgical approaches such as cyst
drainage or subtotal resection, followed by adjuvant (usually
radiation) therapy.
• Multiple surgical approaches have been described for
craniopharyngioma, including an increasing interest in
endoscopic transsphenoidal surgery. The choice of approach
should be based on a three-dimensional understanding of the
topography of the tumor, with particular emphasis on avoiding
hypothalamic, optic, and vascular injury.
• Adjuvant therapies are important in managing
craniopharyngioma—including more novel techniques such as
proton beam therapy, stereotactic radiosurgery, and
intracavitary therapy—and their use should be considered in
both primary and recurrent disease.
on its merits by a multidisciplinary team to achieve the
best possible outcome. Despite the increasingly multidisci-
plinary management of craniopharyngioma, the neurosur-
geon still plays the central role in decision making for affected
patients.
Epidemiology
Craniopharyngioma is a rare tumor. Its incidence has been
estimated at 1.3 cases per million people per year1 with the
highest incidence in Japan and West Africa, particularly in
Nigeria. Across all ages, craniopharyngiomas constitute only
around 1% of all the new central nervous system tumors found
per year, although this rises to 4% in the pediatric age group.2
There is a well-recognized bimodal age distribution, with the
first peak occurring at school age (5–14) and a second occur-
ring in middle to late adulthood (45–65). There is no gender
predilection. The histologic diagnosis also varies with age, with
the papillary form of craniopharyngioma being seen almost
exclusively in the adult group, whereas adamantinomatous
tumors can be found in both groups. No environmental or
genetic risk factors have been identified, and craniopharyngi-
oma is best thought of as a sporadic condition.

Embryology
Craniopharyngioma pathogenesis is believed to result from
the unique embryology of the anterior pituitary gland. During
development of the fetus, a pocket of epithelial ectoderm (the
Rathke pouch), in the roof of the pharynx, extends superi-
orly to meet the neurectoderm of the developing brain. A
temporary connection between the two ectodermal layers—
the craniopharyngeal duct—thus forms. This then involutes,
leaving glandular tissue to form the normal adenohypophy-
sis or anterior pituitary gland.3 Adamantinomatous cranio-
pharyngioma is thought to arise when, during this process,
incomplete or erroneous involution of the Rathke pouch and
craniopharyngeal duct occurs, leaving “nests” of epithelial
rest cells that go on to undergo neoplastic change.3,4 Papil-
lary tumors are postulated to form from metaplasia in the
mature adult pituitary gland, with conversion of normal pitui-
cytes into epithelial nests containing abnormal epithelial cells.
These differing theories may explain the temporal distribu-
tion of the two craniopharyngioma types, as metaplasia is a
slowly occurring process and it takes many years to generate
the nests.5
Anatomy
The anatomy of the sellar region is complex, and a neurosur-
geon intending to operate on a craniopharyngioma must have
a good three-dimensional grasp on the important osseous,
arterial, venous, and neural relationships to the tumor. Within
the suprasellar space, craniopharyngiomas are intimately
related to the circle of Willis and its branches. The most impor-
tant anatomic distinction is whether the tumor arises from
above or below the sellar diaphragm, which dictates its rela-
tionship with surrounding anatomy as it grows.6 An apprecia-
tion of the premorbid arrangement of the optic chiasm—the
so-called normal (above the midpoint of the sella), “prefixed”
(above the tuberculum sellae) and “postfixed” (above the
dorsum sellae) positions—is also essential when planning a
surgical approach.
Tumors arising below the diaphragm (infradiaphragmatic
craniopharyngioma) will push the sellar diaphragm and con-
tents upward as they grow, eventually causing compression and
upward displacement of the chiasm and third ventricle. Ana-
tomically, their behavior is similar to that of an enlarging
pituitary adenoma.
Craniopharyngiomas arising from above the sellar dia-
phragm (supradiaphragmatic) can be further divided depend-
ing on their point of origin—the pituitary stalk or the
hypothalamic infundibulum. Those arising from the pituitary
stalk will enlarge into the subarachnoid space below the chiasm
and third ventricular floor, usually extending anteriorly into
the region between the optic nerves (except in the rare case of
a prefixed chiasm, where they may be entirely retrochiasmatic).
These tumors are sometimes designated as suprasellar extraven­
tricular craniopharyngiomas (SECs).
Craniopharyngiomas arising from the infundibulum tend
to grow in both extra- and intraventricular fashion and are
Downloaded for andromeda masako (andromeda72@yahoo.com) at University of Sumatera Utara from ClinicalKey.com by Elsevier on September 02, 2019.
For personal use only. No other uses without permission. Copyright ©2019. Elsevier Inc. All rights reserved.
CHAPTER 12  Craniopharyngiomas 205
sometimes therefore called intraventricular and extraventricular
craniopharyngiomas (IEVCs); this is the most commonly seen
configuration.6 They are thought to grow in a retrochiasmatic
manner and to erode and cross the floor of the third ventricle
relatively early. This leads to a lower component extending in
the suprasellar cistern and an upper part growing into the
cavity of the third ventricle. IEVCs are almost always entirely
retrochiasmatic, except in cases of a postfixed chiasm where
some of the tumor may extend below the chiasm or even grow
between the optic nerves.
A true “pure” intraventricular craniopharyngioma is a rare
entity, with the majority of tumors thought to be exclusively
enclosed within an intact third ventricle having some extension
into the suprasellar space on close radiologic or surgical exami-
nation. Cases, however, have been described.7–9
Ectopic craniopharyngiomas, occurring in locations other
than the sellar region or even outside of the central nervous
system, have been described but are exceedingly rare. “Seeding”
of craniopharyngioma cells, causing distant recurrence adja-
cent to a surgical track or craniotomy used to resect a sellar
lesion, is a rare but well-described occurrence.10–12 Primary
“true” ectopic lesions are rarer still but have been described in
central nervous system (CNS) locations such as the cerebel-
lopontine angle,13,14 corpus callosum,15 and fourth ventricle16
and even extradurally in the ethmoid17 and sphenoid18 air
sinuses.
Pathology
Craniopharyngioma, according to the 2007 World Health
Organization (WHO) definition, is a “benign, partially cystic
epithelial tumor of the sellar region, presumably derived from
Rathke pouch epithelium” and is designated as a grade I tumor
of the central nervous system.
Gross pathologic examination of craniopharyngiomas dif-
ferentiates them into cystic (50%), mixed cystic-solid (35%),
and solid (15%). They are typically described as lobulated
masses with evidence of adherence to and disruption of sur-
rounding structures such as the hypothalamus, infundibulum,
blood vessels, or cranial nerves. On section, cysts are found
to contain fluid that has a brownish color often described
as “machine oil,” which on examination contains cholesterol
crystals. In addition, calcification is frequently identified
within the specimen. This classic macroscopic description is
typical of the adamantinomatous subtype, with the papillary
type more commonly solid without “machine oil” fluid or
calcification.
The two subtypes are quite distinct on histologic examina-
tion. Adamantinomatous tumors are formed of “nests” of epi-
thelium within gliotic neural stroma. Rows of tumor cell
nuclei, or “palisading” nuclei, are often seen associated with
stellate reticulum formed of loosely arranged epithelial cells.
Mitotic figures are rare in keeping with the benign histologic
grade. The histologic hallmark of craniopharyngioma is “wet
keratin,” stacked arrays of plump, eosinophilic keratinized
cells.
206 PART 2 Pediatric Neurosurgery
Papillary tumors, in contrast, are formed of bland stratified
squamous epithelium with foci of fibrovascular tissue, without
palisading or stellate reticulum. Keratinized cells are sometimes
seen but not wet keratin.
Due to their characteristic histology, immunohistochemis-
try is not usually necessary to confirm diagnosis but is occa-
sionally helpful. Both subtypes stain strongly for epithelial
membrane antigen and cytokeratin. They are negative for
“pituitary” markers such as prolactin and adrenocorticotropic
hormone (ACTH).
Understanding of the molecular pathways involved in cra-
niopharyngioma is incomplete, but many studies are ongoing.
Mutations of the CTNNB1 gene, encoding β-catenin, have
been described in adamantinomatous craniopharyngioma;
accumulations of nuclear β-catenin, consistent with acti-
vation of the Wnt pathway, are identified in scattered cells
within this craniopharyngioma type.19,20 By contrast, the
BRAF C600E mutation is found in up to 100% of papillary
craniopharyngiomas.21
Radiology
The most useful imaging modality for assessing craniopharyn-
gioma is magnetic resonance imaging (MRI), although com-
puted tomography (CT) still has a role, particularly for assessing
calcification (which can reliably differentiate craniopharyngi-
oma from other suprasellar pathologies) and for detailed assess-
ment of skull base anatomy for surgical planning. Plain skull
radiography has been superseded by MRI and CT, whereas
formal catheter angiography is only rarely indicated—to aid
presurgical planning in large tumors that appear on MRI to
have close relationships to the circle of Willis or if a giant
suprasellar aneurysm is a differential diagnosis. Both MRI and
CT demonstrate obstruction to cerebrospinal fluid (CSF) flow
and hydrocephalus related to filling or distortion of the third
ventricle, usually by a craniopharyngioma cyst.
MRI of craniopharyngioma usually demonstrates a hetero-
geneous mass. Solid components are usually T1 isointense and
enhance with gadolinium contrast. Cystic components often
demonstrate ring enhancement, whereas the cyst contents may
vary in appearance depending on the protein or blood break-
down products contained therein. There may even be fluid-
fluid levels within individual cysts or heterogeneity in signal
characteristics between different cysts in the same tumor. MRI,
ideally reviewed in three planes, identifies the topography of
the tumor and can be used to divide craniopharyngiomas into
infra- and supradiaphragmatic as described earlier. The former
are usually associated with enlargement of the sella in a similar
manner to pituitary adenoma. The latter group can be subdi-
vided into SECs and IEVCs radiologically, using the anatomic
criteria described previously.
An assessment of the position of the optic chiasm in relation
to the tumor can usually be made accurately on MRI scan. If
the chiasm itself cannot be directly visualized, the anterior
communicating artery is a reliable marker of its position, this
artery being usually apposed to the chiasm’s upper posterior
surface.
Downloaded for andromeda masako (andromeda72@yahoo.com) at University of Sumatera Utara from ClinicalKey.com by Elsevier on September 02, 2019.
For personal use only. No other uses without permission. Copyright ©2019. Elsevier Inc. All rights reserved.
The differential diagnosis for sellar region lesions is wide
and includes the Rathke cleft cyst, optic pathway glioma,
hypothalamic hamartoma, metastasis, and others. CT can be
useful in differentiating craniopharyngioma from these other
differentials by demonstrating evidence of calcification; this is
seen in 85% to 90% of childhood craniopharyngioma and
around 40% to 50% of adult tumors. The relatively lower rate
in adults can be explained by the presence of the papillary
histologic subtype in that age group, as papillary craniopha-
ryngiomas do not calcify. A note of caution here is that the
only other lesion that may show similar rim or “eggshell”
calcification is an aneurysm. Vascular imaging (CT, MRI, or
catheter angiography) is indicated prior to surgical exploration
if concern persists.
Decision making about the feasibility and extent of surgery
is informed by close analysis of the preoperative MRI scan. The
Paris group has published a system based on presurgical
involvement of the hypothalamus to guide surgical decision
making. The Paris classification is as follows: grade 0, no hypo-
thalamic involvement; grade 1, the tumor abutting or displac-
ing the hypothalamus; and grade 2, hypothalamic involvement
(the hypothalamus is no longer identifiable).22 The implica-
tions of this presurgical radiologic grading system on operative
results and outcome are discussed next.
Presentation
Craniopharyngioma can present with a wide variety of clinical
symptoms and signs; all can be predicted by the relations of
the suprasellar tumor to the critical surrounding structures.
Symptoms can be visual (due to compression or injury to the
optic apparatus), endocrine (hypothalamic-pituitary axis),
neurocognitive (mammillary bodies, hypothalamus, and asso-
ciated limbic tracts), and those of obstructive hydrocephalus
(third ventricle). Patterns of initial presenting symptomatology
differ between age groups, with endocrinopathies and hydro-
cephalus more common in children and visual impairment and
neurocognitive changes more frequent in adults.
Visual impairment can take several forms, including field
deficits and reduced acuity. The nature of the field deficit
depends on the anatomic configuration of the tumor but
can include bitemporal hemianopia, homonymous hemiano-
pia, concentric field constriction, and central or paracentral
scotoma, of which an asymmetric bitemporal hemianopia is
the most common type. Field deficits are usually due to direct
compression of the relevant part of the optic pathway by
the enlarging craniopharyngioma but can represent ischemia
caused by involvement of perforating arteries by the tumor.
Reduced acuity is most commonly due to prolonged raised
intracranial pressure such as that seen secondary to obstructive
hydrocephalus, but it can be a late effect of prolonged compres-
sion. Children often do not report visual symptoms or impair-
ment until they are profound, and it is sadly not uncommon
for young patients to be functionally blind at first presentation.
Endocrinopathies are often insidious in their onset, and
both children and adults often miss the symptoms. Children
may show restricted growth or delayed onset of puberty. Adults

may experience decreased libido and erectile dysfunction (men)
or amenorrhea (in women). Diabetes insipidus and obesity
may occur at any age. The presence of obesity suggests hypo-
thalamic involvement.
Obstructive hydrocephalus causes the typical symptoms of
raised intracranial pressure—namely, headache, nausea, drows-
iness, and visual deterioration due to papilledema (and even-
tual optic atrophy). This presentation is much more common
in the pediatric age group, presumably as adults will notice and
report more subtle symptoms such as field deficits or neuro-
cognitive impairment more readily than children.
In adults, neurocognitive symptoms can be the presenting
feature, with memory impairment more common than person-
ality change. These symptoms are thought to result from injury
to the mammillary bodies or their connections with the hip-
pocampus, fornix, and mammillary-thalamic tract caused by
the expanding tumor.
Endocrine Assessment
It is essential that an appropriately trained and experi-
enced endocrinologist is part of the multidisciplinary team
caring for children and adults with craniopharyngioma.
Endocrinopathies—resulting either from the effect of the
tumor itself, at presentation or after multiple episodes of tumor
progression, or as a result of treatment, surgical or otherwise—
cause significant impairment of patients’ quality of life and
can be life threatening. Indeed, recognition of the importance
of steroid replacement and endocrine expertise was one of
the significant contributions to the reduction in perioperative
mortality of craniopharyngioma surgery seen in the mid-20th
century.
Although clinically under-recognized, 85% of patients have
hypopituitarism at presentation,23 with growth hormone (GH)
being the most common hormone affected, followed by lutein-
izing hormone/follicle-stimulating hormone (LH/FSH), with
sequentially lesser rates of corticotropin (ACTH) and thyroid-
stimulating hormone (TSH) deficiency. These deficiencies may
be detected biochemically or be symptomatic, with the usual
features evident clinically. Diabetes insipidus (DI), due to defi-
ciency of antidiuretic hormone (ADH), has been reported in
around a quarter of patients at diagnosis.
In addition to deficiencies of pituitary hormones, systemic
symptoms may arise from hypothalamic dysfunction caused by
tumor invasion or (more frequently) surgical disruption of
this critical homeostatic structure. The typical hypothalamic
symptom seen in craniopharyngioma (either pre- or postopera-
tively) is obesity resulting from injury to the satiety center
located in the ventromedial nucleus, close to the floor of the
third ventricle anterior to the mammillary bodies and therefore
often involved in craniopharyngiomas. This hyperphagia and
obesity often are accompanied by deterioration in behavior and
school performance in children. Other hypothalamic symp-
toms are less frequent but can occur, including temperature
dysregulation, disordered sleep, and deficient thirst.
All new cases of craniopharyngioma should have a full clini-
cal and biochemical endocrine assessment at presentation and
Downloaded for andromeda masako (andromeda72@yahoo.com) at University of Sumatera Utara from ClinicalKey.com by Elsevier on September 02, 2019.
For personal use only. No other uses without permission. Copyright ©2019. Elsevier Inc. All rights reserved.
CHAPTER 12  Craniopharyngiomas 207
definitely prior to any surgical procedure. This should consist
of a detailed clinical examination, including measurement of
body mass index (BMI) and an assessment of intravascular
volume status. The exact schedule of biochemical investigation
will vary between institutions, dependent on the experience
and preferences of the endocrine and laboratory services, but
should include a full assessment, including dynamic testing if
required, of the adrenal, thyroid, and gonadal axes, as well as
GH, prolactin, and ADH function.
Management of both pre- and postoperative endocrinopa-
thies involves exogenous replacement of deficient hormones.
The most critical, and first to be replaced, are glucocorticoids.
The administration of thyroxine, for example, in an untreated
or undertreated steroid-deficient patient can precipitate acute
adrenal crisis. When planning surgery, a plan for stress dosing
(extra administration), intra- and postoperatively, should be
made and requires close teamwork among the neurosurgical,
anesthetic, and endocrine teams.
In the postoperative period, diabetes insipidus can be a
feature, including the so-called triphasic response of initial
polyuria, followed by oliguria and water retention, followed
subsequently by a return of polyuria. Frequent monitoring of
both serum and urine sodium, as well as osmolality, is manda-
tory, with the administration of ADH analogues when indi-
cated. Although a transient diabetes insipidus–like condition
is seen frequently in many postoperative craniopharyngioma
patients, a subset will have long-term ADH replacement
requirements.24
Over time and multiple treatment modalities, pituitary defi-
ciencies are ubiquitous in patients with craniopharyngioma,
necessitating lifelong follow-up and, in children, careful tran-
sitional arrangements to appropriate adult expertise.
Neuro-Ophthalmologic Assessment
Detailed pre- and postoperative neuro-ophthalmologic exami-
nation is critical to objectively record visual impairment related
to the tumor and the response (if any) to surgical treatment.
It also establishes a baseline for subsequent follow-up. Exami-
nation should include funduscopy (ideally with photography
of the fundus and optical coherence tomography) and perim-
etry (such as Goldmann or Humphrey testing) as well the usual
documentation of visual acuity.
Fundal examination may reveal papilledema, almost exclu-
sively seen in tumors presenting with hydrocephalus and its
associated raised intracranial pressure, or optic atrophy, which
may be a late result of either direct chiasmal compression or
long-term, untreated raised intracranial pressure.
Field examination most typically reveals an asymmetrical
bitemporal hemianopia, but more posterior lesions (or sellar
lesions growing behind a prefixed chiasm) may cause a hom-
onymous hemianopia. This homonymous hemianopia is
incongruous and nonmacular sparing (so-called optic tract
syndrome), differentiating it from the field cut seen with an
occipitopolar lesion.
In children, strabismus may be a presenting feature.25 This
strabismus is most frequently due to compensation for field
208 PART 2 Pediatric Neurosurgery
loss and only rarely to involvement of the cranial nerves con-
trolling ocular motility.
Treatment Planning
Perhaps no other tumor in neurosurgical practice polarizes
opinion in its treatment to such an extent as craniopharyngi-
oma. Although for other intracranial tumors there is broad
consensus on optimal surgical management, whether that is
aggressive total resection (ependymoma) or avoidance of
surgery as first-line treatment (optic pathway glioma), two
schools of thought have developed in craniopharyngioma man-
agement: radical resection versus intentional incomplete resec-
tion with radiotherapy.
The attraction of radical surgery is that, because this is a
histologically benign tumor, the recurrence rate after gross total
resection is low, although still reported in the region of around
30% on long-term follow-up.26–28 The potential risk, as argued
by adherents of the more conservative approach, is the higher
rate of hypothalamic injury, pituitary insufficiency, neurocog-
nitive disability, and impaired quality of life in patients treated
radically.29–34
Radiotherapy has been proved to be efficacious in reducing
recurrence in both radical and limited surgery35–37 but can itself
have long-term deleterious effects, particularly in younger chil-
dren. There has been much interest in the use of newer radio-
therapy techniques, such as proton beam and stereotactic
radiosurgery, to reduce the dosing of normal neural tissue.38,39
Although surgical resection (either radical or limited)
and radiotherapy form the mainstays of definitive treat-
ment of craniopharyngioma, other modalities, usually used
in combination with those described, exist. Surgically, these
include operations to drain tumor cysts, such as placement
of catheters connected to subcutaneous reservoirs that can be
aspirated as required, or wide endoscopic cyst fenestration.
Other adjuvant therapies include intracavitary treatments,
using catheters in cysts to deliver various agents, or systemic
chemotherapy.
Ultimately, the decision on which modality to use for each
patient will depend on the experience and resources available
to the treating team, in combination with close examination
of the preoperative MRI images and an understanding of the
endocrine and neuro-ophthalmologic status. As alluded to
earlier in the radiology section, the Paris group has developed
a protocol for guiding management based on scrutiny of the
preoperative scan.22 After decompression, in the acute phase,
of large cysts to alleviate hydrocephalus and protect vision,
surgical decision making is guided by this classification; com-
plete resection is the goal for grade 0 and 1 tumors, and
intentional limited resection with hypothalamic preservation
(followed by radiotherapy) for grade 2 tumors. By comparing
a retrospective cohort, treated with intention of complete
resection prior to the introduction of this system, to a prospec-
tive cohort treated following introduction of this protocol, the
group saw a significant improvement in postoperative quality
of life, with no hypopituitarism or clinical hypothalamic dys-
function in the prospective group.22
Downloaded for andromeda masako (andromeda72@yahoo.com) at University of Sumatera Utara from ClinicalKey.com by Elsevier on September 02, 2019.
For personal use only. No other uses without permission. Copyright ©2019. Elsevier Inc. All rights reserved.
Although this system has by no means been universally
adopted, it does supply some useful clinical evidence to inform
decision making in craniopharyngioma management. Not all
surgeons agree with the grading system, and it is open to a
degree of neuroradiologic uncertainty. Moreover, surgical
results are dependent on the surgeon’s experience and the
tumor volume of the institution. The basic principle—of
radical resection of tumors not involving the hypothalamus,
and appropriate caution and judicious use of adjuvant treat-
ments of those that do—remains a good tenet for guiding
treatment decisions in this complex group of patients.
Surgical Techniques
As well as a preoperative decision about the goal of surgery
(radical vs limited resection), consideration must be given on
the optimum approach to the tumor. Approaches from all
angles have been described for craniopharyngioma.40–48 Selec-
tion of the optimum approach is based on traditional neuro-
surgical principles, a route that affords good access for resection,
avoids transgression of critical structures, and has an acceptable
risk profile for postoperative complications such as CSF leak.
In this section, surgical approaches are discussed for each of
the topographic types of tumors. Many craniopharyngiomas
involve the hypothalamus and can transgress anatomic bound-
aries (Fig. 12.1).
Infradiaphragmatic Craniopharyngioma
Purely intrasellar lesions are optimally approached via the trans-
sphenoidal route, which affords access to the tumor and identi-
fication (and therefore, in most cases, preservation) of the intact
pituitary gland. Intrasellar lesions with suprasellar extension, of
favorable size and topography, may also be managed effectively
with transsphenoidal surgery. Transsphenoidal surgery can be
microscopic or, increasingly, endoscopic, and extended tech-
niques have been used to access infradiaphragmatic craniopha-
ryngioma with extensive suprasellar extension.45 Regardless of
the exact technique used to approach the tumor, the principles
of intraoperative dissection remain identical. Once the bony
sella has been opened and the dura incised, efforts are made to
identify the normal pituitary tissue and protect it, usually by
manipulating it to one side. The capsule of the craniopharyn-
gioma is identified and dissected from surrounding structures.
The capsule is often densely adherent to surrounding tissue,
and intraoperative decisions need to be made on the nature of
the adhesion and the importance of the attached structure. For
example, a portion of capsule densely adherent to the infun-
dibulum may well be left in place rather than risk damaging
this essential structure. Care must also be taken when handling
flakes of calcification, as these may have sharp edges that can
injure local tissues.
Suprasellar Extraventricular Craniopharyngioma
These lesions are best approached via a supratentorial crani-
otomy; the decision of which particular craniotomy to use
 CHAPTER 12  Craniopharyngiomas 209

A B

C [F] D
• Figure 12.1  Cystic craniopharyngiomas with hypothalamic involvement. Postgadolinium T1 sagittal (A)
and T2 axial (B) MRI scans showing a suprasellar cystic craniopharyngioma, with two separate cystic
compartments. Only the posterior cyst contained typical thick brown craniopharyngioma fluid; the cysts
involve and obliterate the floor of the third ventricle posterior to the mammillary bodies. Postgadolinium
T1 sagittal (C) and T2 coronal (D) MRI scans showing a complex cystic and solid craniopharyngioma,
with extensive involvement of the hypothalamus and third ventricle; it is also causing obstructive hydro-
cephalus, with dilatation of the lateral ventricles.

depends on the relationship of the tumor mass to the optic
chiasm. For those (more common) tumors displacing the
chiasm upward or extending into the prechiasmatic space, the
subfrontal approach offers good access through the prechias-
matic and opticocarotid spaces. For those rarer suprasellar
extraventricular lesions situated entirely posterior to the optic
chiasm, a pterional approach is preferred to avoid injury to
interposing hypothalamic structures. Each approach should be
tailored to the individual tumor anatomy—for example, use
of the orbitozygomatic approach or a bifrontal craniotomy for
inferiorly located or giant tumors, respectively. A frontal inter-
hemispheric approach, with division of the superior sagittal
sinus, is also useful for large suprasellar tumors with retrosellar
extension. Some large tumors may require staged resection
from different approaches (Fig. 12.2).
For both subfrontal and pterional approaches, the choice of
which side to use is based primarily on the topography of the
tumor mass. For tumors where there is equipoise, the non-
dominant side is preferred. Patients are placed in a supine
position on the operating table with the neck rotated away
from the side of the craniotomy. Skull fixation with pins and
a clamp is used for most patients, with the exception of very
small children where a “horseshoe” headrest can be substituted.
Image guidance is extremely useful and should now be consid-
ered routine for these cases. Following registration of image
guidance, skin preparation, and draping, a curvilinear

Downloaded for andromeda masako (andromeda72@yahoo.com) at University of Sumatera Utara from ClinicalKey.com by Elsevier on September 02, 2019.
For personal use only. No other uses without permission. Copyright ©2019. Elsevier Inc. All rights reserved.
210 PART 2 Pediatric Neurosurgery

A B

C D
• Figure 12.2  Large craniopharyngioma treated by staged transventricular endoscopic and microsurgi-
cal resection. T1 postgadolinium sagittal (A) and coronal (B) MRI scans of a predominantly cystic supra-
sellar craniopharyngioma in an 8-year-old child presenting with bitemporal hemianopia. The optic chiasm
is elevated and stretched at the waist of the lesion. The tumor fills the third ventricle and causes obstructive
hydrocephalus. Initial transventricular endoscopic decompresses the cyst within the third ventricle and
relieves the hydrocephalus (C). The tumor is anterior to the hypothalamus and is resected through an
anterior interhemispheric approach (D).

frontotemporal scalp incision is used just behind the anterior
hairline from just over the midline to the root of the zygomatic
process. A standard frontal or pterional craniotomy is then
fashioned, with repair of the frontal air sinus if opened. An
arcuate durotomy is performed followed by patient CSF drain-
age to allow brain relaxation, reducing the need for retraction.
Gentle retraction of the frontal lobe permits subfrontal access,
with further drainage of the arachnoid cisterns, including the
medial part of the Sylvian fissure, en route to the tumor. Once
the tumor has been visualized, dissection begins by opening
and drainage of cystic components, minimizing spillage of
contents into the CSF circulation. The tumor capsule is then
identified and removal proceeds in a piecemeal fashion, with
care taken to protect surrounding critical structures. Cranio-
pharyngioma may adhere to vessels, particularly in areas of
calcification, and blend in to neural structures such as the
infundibulum and hypothalamus. In addition, many critical
perforators are at risk during capsule dissection. No vessel

Downloaded for andromeda masako (andromeda72@yahoo.com) at University of Sumatera Utara from ClinicalKey.com by Elsevier on September 02, 2019.
For personal use only. No other uses without permission. Copyright ©2019. Elsevier Inc. All rights reserved.

should be sacrificed without a thorough inspection of its course
to ensure that it does not supply a neural structure, particularly
important as many vessels supplying the tumor in an en passant
fashion may also go on to enter, for example, the hypothalamus
or optic chiasm. If portions of the tumor are densely adherent
to, or indistinguishable from, the hypothalamus, the authors’
practice is to leave this untouched for adjuvant treatment
thereafter with the aim of preserving endocrine and (especially)
hypothalamic function as previously described. Once maximal
safe resection has been achieved, repair of the dura, fixation of
the bone flap, and scalp closure are achieved using standard
methods. We do not routinely use external lumbar drainage
except in procedures where concern about postoperative CSF
leak is high, such as in some revisional or postradiotherapy
cases.
Intraventricular and Extraventricular
Craniopharyngiomas
For these tumors, planning of approach is based again on the
location of the remnant hypothalamic tissue, which is usually
situated around the midpoint of the craniopharyngioma.
Therefore these are best approached anteriorly via the lamina
terminalis of the third ventricle following a subfrontal approach.
In fact, the lamina terminalis so encountered usually consists
of the anterior tumor capsule. Opening the space between the
anterior communicating complex and the optic chiasm affords
good access for piecemeal debulking of these craniopharyngio-
mas. An exception may be larger tumors with extension into
the superoposterior segment of the third ventricle, which may
be insufficiently visualized with approaches via the lamina
terminalis. An alternative in these cases may be a transcallosal
approach. An advantage of this approach is that it allows the
surgeon to begin tumor dissection at the superior pole of the
tumor, which is usually “free” within the enlarged foramen of
Munro and not attached to surrounding neural structures. For
very large tumors that obliterate the floor of the anterior third
ventricle, the transcallosal approach can be used to reach the
suprasellar components. It is important to remember, however,
that this is primarily a midline approach and its lateral reach
remains limited.
Intraventricular Craniopharyngiomas
As described previously, pure intraventricular craniopharyn-
gioma is rare. As it sits entirely above the thinned hypothala-
mus, approaches from below are contraindicated. Access is
afforded via either the lamina terminalis or the foramen of
Munro based on the individual topography of the tumor.
Cystic Craniopharyngioma
Predominantly cystic craniopharyngioma, typically seen in
children,49 may be managed by insertion of a drainage catheter,
attached to a subcutaneous reservoir (such as an Ommaya),
into the tumor cyst (Fig. 12.3). Cyst drainage procedures may
need to be undertaken acutely to control hydrocephalus and
Downloaded for andromeda masako (andromeda72@yahoo.com) at University of Sumatera Utara from ClinicalKey.com by Elsevier on September 02, 2019.
For personal use only. No other uses without permission. Copyright ©2019. Elsevier Inc. All rights reserved.
CHAPTER 12  Craniopharyngiomas 211
preserve vision. They can be performed purely stereotactically,
using a frame or frameless techniques, or with endoscopic
assistance. If the cyst presents within the third ventricle, and
the lateral ventricles are large enough, endoscopic fenestration,
with placement of a catheter under direct vision, is the method
of choice. This has also been described in the context of small
ventricles, using image guidance to facilitate optimal ventricu-
lar entry and dilatation of the ventricles using small volumes
of saline.50 The cyst wall is often thick and firm and not easily
punctured, particularly in a blind, image-guided technique,
and care must be taken to ensure that the catheter does not
slide off the wall and end in a suboptimal position. Cranio-
pharyngioma fluid is usually viscous, and a large bore catheter
with large side holes is preferred to avoid blockage. Potential
risks of this technique include hardware infection or blockage,
and strict aseptic technique must be employed whenever the
reservoir is tapped. Occasionally, the cyst may be multilocu-
lated without communication between the locules of fluid. In
these cases, it is usually preferable to create communication
using endoscopic techniques, allowing drainage through a
single catheter and reservoir. If this is not possible, rarely,
multiple catheters may be required.
Aspiration of large craniopharyngioma cysts often changes
the anatomic relationships of the tumor with surrounding
structures. Reimaging after aspiration allows reevaluation of
hypothalamic involvement, and tumors previously deemed
inoperable may then appear separate from the hypothalamus
and therefore resectable51 (Fig. 12.4).
Appropriate placement of a catheter within a cyst also allows
aspiration during radiotherapy, when cysts often expand. This
can be done with stereotactic guidance, but it is often more
straightforward to do using endoscopic visualization (Fig.
12.5). It also permits the use of intracystic therapy, usually at
a later stage.52,53
Perioperative Management and
Potential Complications
Some postprocedural risks are general to all surgical approaches
to craniopharyngioma, particularly endocrine complications
such as hypopituitarism and diabetes insipidus, whereas some
are associated with specific techniques. Optimal perioperative
management involves recognizing these risks and minimizing
them with judicious use of appropriate strategies.
Infection
Like all invasive procedures, surgery for craniopharyngioma
introduces the risk of bacterial contamination with resulting
surgical site infection or meningitis. Preoperatively, swabs
should be taken of skin and nasal mucosa to identify carriage
of resistant organisms such as methicillin-resistant Staphylo­
coccus aureus (MRSA), and decolonization should be carried
out if feasible within the urgency of surgery. It is now routine
to use systemic (intravenous) antibiotics at the onset of all
types of neurosurgical procedures; the exact agent chosen will
212 PART 2 Pediatric Neurosurgery

[H]

A B

C D
• Figure 12.3  Mixed solid-cystic craniopharyngioma treated by catheter drainage followed by proton
radiotherapy. (A–B) T2 sagittal and coronal MRI scans showing a solid-cystic craniopharyngioma extend-
ing from the suprasellar region into the floor of the third ventricle. (C–D) Sagittal and coronal T1 MRI scans
showing the lesion after insertion of the catheter (white arrow in part D). Hypothalamic involvement by
the solid component is more clearly evident after cyst drainage.

depend on a combination of local protocols and results of
preoperative swabs. If a patient is carrying an organism resis-
tant to standard prophylaxis, a different antibiotic must be
employed. Most units carrying out transsphenoidal, especially
extended endoscopic resection, institute a prolonged prophy-
laxis of up to 5 to 7 days of antibiotic administration. In fact,
with use of appropriate pre-, intra-, and postoperative precau-
tions, infection rates with extended endoscopic transsphenoidal
techniques are no higher than that for transcranial surgery.45,54
Neurovascular
The location of craniopharyngioma in the suprasellar region,
often encroaching on or even adherent to the circle of Willis,
means that the resection risks vasospasm, thrombosis, or direct
injury, which can lead to cerebral ischemia or infarction.
Reducing the risk of this devastating complication starts in the
preoperative planning stage, with recognition of possible vessel
involvement, and, if indicated, vascular imaging to delineate
vessel position to predict areas of dissection that are at particu-
larly high risk. Intraoperatively, micro-Doppler probes may
help to detect vessels during dissection. It is usually prudent
to leave portions of tumor highly adherent to vessel walls in
situ to be dealt with by adjuvant treatment rather than to
attempt complete removal with injury to the adventitia. Post-
operatively, a neurologic examination should be carried out as
soon as possible after recovery from general anesthesia to assess
any potential neurologic deficit. If any concerns are identified,

Downloaded for andromeda masako (andromeda72@yahoo.com) at University of Sumatera Utara from ClinicalKey.com by Elsevier on September 02, 2019.
For personal use only. No other uses without permission. Copyright ©2019. Elsevier Inc. All rights reserved.
 CHAPTER 12  Craniopharyngiomas 213

[H]

A B

C D
• Figure 12.4  Large craniopharyngioma treated by catheter drainage followed by microsurgical resec-
tion. (A) Sagittal fluid-attenuated inversion recovery (FLAIR) MRI scan showing a large cystic suprasellar
craniopharyngioma. (B) Following image-guided insertion of a catheter, the cyst is smaller on postgado-
linium T1 MRI scan. The white arrow points to the catheter. The black arrow points to the decompressed
hypothalamus and floor of the third ventricle. (C) A computed tomography scan showing the catheter
(white arrow) within the decompressed cyst; the margins of the cyst are defined by the calcified rim. (D)
A postgadolinium sagittal T1 MRI scan after resection of the craniopharyngioma through an anterior
interhemispheric and subfrontal approach. The floor of the third ventricle appears intact (black arrow).

prompt neuroradiologic examination with CT is indicated.
Neurovascular injury causing ischemic stroke has been reported
in 2.9% of transcranial series and 2.7% of endoscopic trans-
sphenoidal series.46 In addition to direct intraoperative injury,
postoperative fusiform dilatation55 and vasospasm56 have been
reported. Although the former appears to be primarily a radio-
logic phenomenon without clinical sequelae, vasospasm can
potentially be a source of delayed ischemic neurologic deficit.
If suspected, appropriate perfusion imaging (CT or MR)
should be performed, and if vasospasm is confirmed, treatment
with hypervolemia and hypertension should be instituted,
which has been shown to be effective in postcraniopharyngi-
oma surgery vasospasm.57
Ophthalmic
Many patients with craniopharyngioma present with signifi-
cant visual impairment and established optic neuropathy. This

Downloaded for andromeda masako (andromeda72@yahoo.com) at University of Sumatera Utara from ClinicalKey.com by Elsevier on September 02, 2019.
For personal use only. No other uses without permission. Copyright ©2019. Elsevier Inc. All rights reserved.
214 PART 2 Pediatric Neurosurgery

A B

C D
• Figure 12.5  Transventricular endoscopic drainage of craniopharyngioma cyst. (A) Postgadolinium T1
sagittal MRI scan showing a cystic craniopharyngioma arising from the suprasellar region and filling the
cavity of the third ventricle. (B) The view from the endoscope at the foramen of Monro, with the cranio-
pharyngioma cyst (arrow) appearing through the floor of the third ventricle. (C) The catheter (arrow) has
been inserted under direct vision into the cyst and decompressing it. (D) The decompressed cyst capsule
is evident on a postgadolinium T1 sagittal MRI scan.

tenuous condition places them at high risk of further injury,
with resulting postoperative visual loss, during surgical
approaches to craniopharyngioma. As outlined earlier, all
patients should have a detailed ophthalmic examination,
including formal perimetry, documented prior to surgery.
Intraoperatively, efforts should be made to avoid retraction or
cautery on the optic apparatus itself. Great care should also be
taken to preserve arteries supplying the chiasm, which may
be at risk during dissection, such as the paired superior
hypophyseal arteries and the pial network of vessels found on
the superior aspect of the structure. Approaches that transgress
the lamina terminalis may have higher risks of chiasmal infarc-
tion than those that use an inferior corridor such as the trans-
sphenoidal route, where direct decompression of the optic
apparatus from below precedes surgical manipulation of the
capsule above. A large meta-analysis of craniopharyngioma
surgical series41 found a rate of around 13% of postprocedural
visual deterioration due to reduced acuity or field deficit,

Downloaded for andromeda masako (andromeda72@yahoo.com) at University of Sumatera Utara from ClinicalKey.com by Elsevier on September 02, 2019.
For personal use only. No other uses without permission. Copyright ©2019. Elsevier Inc. All rights reserved.

compared to an improvement in almost 50% in patients with
a preexisting deficit. Ophthalmoplegia due to injury to cranial
nerves running in the adjacent cavernous sinus is also a poten-
tial complication, but most series agree that this is much rarer
than field or acuity problems, with a rate of less than 1%.
Postoperatively, patients should have a repeat ophthalmic
assessment to allow comparison to the preoperative baseline.
Acute visual loss in the immediate postoperative period sug-
gests the possibility of a mass lesion such as a hematoma and
should trigger urgent radiologic examination and surgical
reexploration.
Endocrine
Key structures for neuroendocrine function are at risk in any
craniopharyngioma operation, including the hypothalamus,
infundibulum, stalk, and both anterior and posterior pituitary
glands. As discussed earlier, preoperative assessment by an
endocrinologist is mandatory to detect and document preexist-
ing deficits. Attempting to preserve endocrine function begins
at the preoperative stage with a close examination of the radio-
logic imaging to assess involvement of the hypothalamopitu-
itary axis and review of the endocrine work-up. As most
patients already demonstrate endocrine deficits at presentation,
and considering that multiple deficits are almost always accrued
throughout the course of this chronic disease, sacrifice of resid-
ual endocrine function, usually related to expected operative
damage of an adherent and atrophic pituitary stalk, may be
acceptable if complete resection of the tumor can be achieved
without hypothalamic injury. Hormone replacement does not,
however, restore normal quality of life if the hypothalamus is
injured. Intraoperatively, sharp dissection is preferred when
removing tumor from midline structures, with minimal (ideally
no) traction or electrocautery. The transsphenoidal route can
still be used when the pituitary gland is ventral or anterior to
the craniopharyngioma, as mobilization of the gland or a verti-
cal incision within it is still associated with good preservation
of endocrine function.58
Injury to the anterior pituitary gland can result in deficiency
of one or more of the hormones produced therein, up to and
including complete panhypopituitarism. Rates of the latter can
be as high as 50% in some series, and they appear to be higher
following transcranial rather than transsphenoidal approaches.46
Levels of LH/FSH appear to be most commonly deficient after
surgery (a reduction in up to 90% of patients), followed by
prolactin, ACTH and TSH (all reduced in about 50%).59
Perioperative management is undertaken in close collaboration
with endocrinologists, but most patients will receive supple-
mentary exogenous steroids at induction of anesthesia and in
the early postoperative period, at least until confirmation of
endogenous steroid production by an early morning, predose
serum cortisol level on the second postoperative day. After the
patient has fully recovered from surgery, the endocrinology
team usually electively undertakes a complete assessment of all
anterior pituitary hormonal function.
Posterior pituitary injury can result in diabetes insipidus
(DI) due to a deficiency of ADH. The reported incidence
Downloaded for andromeda masako (andromeda72@yahoo.com) at University of Sumatera Utara from ClinicalKey.com by Elsevier on September 02, 2019.
For personal use only. No other uses without permission. Copyright ©2019. Elsevier Inc. All rights reserved.
CHAPTER 12  Craniopharyngiomas 215
of postcraniopharyngioma surgery DI varies widely, presum-
ably due to differing definitions, with rates as low as 4%
and as high as 100% described in the literature.41,46,60 Most
neurosurgical units have their own protocols for monitoring
patients following surgery where DI is a common risk, but
all involve careful measurement of fluid balance (often using
an indwelling urinary catheter) along with recording of urine
specific gravity or osmolality in combination with frequent
blood sampling for sodium and osmolality. Exogenous desmo-
pressin is administered only when certain criteria are reached,
usually evidence of biochemical dehydration with elevated
serum sodium/osmolality in combination with inappropri-
ately dilute urine. In general, although many patients require
desmopressin in the early postoperative period, long-term
rates of desmopressin-dependent DI have been estimated at
around 70% (transcranial surgery) and 24% (transsphenoidal
surgery).41
Hypothalamic injury has been recognized as a major deter-
minant of poor outcome and can result in a number of clinical
symptoms, classically obesity, hyperphagia, and behavioral dis-
turbance (such as rage), but also memory impairment, loss of
temperature homeostasis, and disturbance of the normal sleep-
wake cycle.22,30 Profound metabolic alterations occur, with
rapid weight gain over the first postoperative year, abnormal
energy management, and increased lipogenesis. This is poorly
responsive to diet, physical activity, and pharmacologic thera-
pies.61,62 About a third of children with craniopharyngiomas
demonstrate hypothalamic disturbance at presentation.63 The
highest risks to operative hypothalamic injury include hypo-
thalamic symptoms at presentation, large tumor size, involve-
ment of the third ventricle, obstructive hydrocephalus, the
pursuit of radical resection in tumors adherent to the hypo-
thalamus, and surgery posterior to the mammillary bodies.30,64,65
Due to the somewhat nebulous nature of some of these symp-
toms, rates of hypothalamic dysfunction can be difficult to
obtain but have been estimated at between 30% and 60%,
with no differences observed between transcranial and trans-
sphenoidal approaches.22,30,41,66 If a hypothalamus-preserving
strategy of planned subtotal resection is adopted, the rate
of hypothalamic morbidity is significantly reduced; when
combined with adjuvant radiotherapy, tumor control is not
compromised.22,49,67
Cerebrospinal Fluid–Related Complications
Rates of hydrocephalus at presentation vary from 5% to 40%
(Elliott) and are usually related to large tumor components
within the third ventricle. Tumor resection or cyst drainage
usually resolves hydrocephalus, but around 10% to 15% of
patients still have postoperative hydrocephalus requiring CSF
diversion surgery.68 The incidence of CSF leak seen after trans-
sphenoidal, particularly extended endoscopic, surgery has been
a concern, particularly due to high rates reported in initial
experience with the technique. However, with improvements
in anterior skull base reconstruction such as the use of vascular-
ized nasoseptal flaps, rates of postoperative CSF rhinorrhea
have been reduced to 5% or lower.46,69,70
216 PART 2 Pediatric Neurosurgery
Adjuvant and Novel Therapies
Traditionally, adjuvant therapies (predominantly radiation
therapy) were viewed as second-line treatment for residual or
recurrent craniopharyngiomas not amenable to surgical resec-
tion. As the philosophy of managing this disease has evolved,
in conjunction with technical advances allowing more confor-
mal radiation delivery techniques reducing irradiation to
neural structures (such as stereotactic radiosurgery and proton
beam therapy), radiation therapy has been used more fre-
quently as an upfront treatment option following, for example,
intentional partial resection or cyst drainage. There has also
been increased interest in the use of intracavitary agents,
instilled directly into the craniopharyngioma cyst. Early expe-
rience was with brachytherapy with radioisotopes, although
recently chemotherapeutics such as bleomycin and interferon
have been used.
Conventional Radiotherapy
Conventional radiotherapy uses fractionation to deliver a
therapeutic dose to the target while attempting to minimize
irradiation to surrounding tissues. Modern techniques utilize
mask-based immobilization and computer-assisted, image-
guided planning. Dosing for craniopharyngioma is usually
in the region of 50 to 60 Gray, which is fractionated in 25
to 30 separate treatments. The irradiated volume typically
includes an additional 5 mm to the gross tumor volume,
to constitute the clinical target volume. Co-registration of
MRI and CT scans ensures that any residual calcification is
incorporated within the gross tumor volume. Regular surveil-
lance imaging and planning modifications are necessary to
ensure that any cyst enlargement, well known to occur during
the course of radiotherapy, is included within the irradiated
volume.71
There is good evidence that doses of >50 Gray are reliable
in achieving tumor control in the majority of patients.72–76 The
major potential complication of treatment is injury to the optic
apparatus, which is usually quoted as having a tolerance of 8
to 12 Gray. Other risks include radionecrosis, swelling, endo-
crine dysfunction, and deleterious effects on cognition. The
latter complication is exacerbated by young age at time of
treatment, particularly relevant due to relative frequency of
craniopharyngioma in childhood.
Intensity modulated radiotherapy (IMRT) is frequently
used for craniopharyngiomas. The technique involves “sculpt-
ing” of the high-dose radiation exposure to the target by the
use of multiple small beams from different directions, delivered
by a multileaf collimator. This reduces irradiation to adjacent
structures such as the hippocampus, brainstem, optic appara-
tus, and cochlea.
Stereotactic Radiosurgery
Stereotactic radiosurgery (such as Leksell Gamma Knife) is
capable of delivering high-dose radiation to a precisely confor-
mal target in a single fraction with only minimal radiation
Downloaded for andromeda masako (andromeda72@yahoo.com) at University of Sumatera Utara from ClinicalKey.com by Elsevier on September 02, 2019.
For personal use only. No other uses without permission. Copyright ©2019. Elsevier Inc. All rights reserved.
exposure to surrounding neural tissue. It achieves this using
frame-based stereotaxy and computer-aided dose planning.
The predominant drawback is the lack of suitability for larger
(>3.5 cm diameter) lesions due to the loss of conformality. It
has been used with some success in appropriately selected
craniopharyngioma.77
Proton Beam Therapy
Proton beam therapy (PBT) delivers positively charged protons
to the target. Although the efficacy and dose of treatment are
similar to conventional radiotherapy, PBT has the advantage
of using the physical characteristics of charged particles—a
sharp drop-off in dose called the Bragg peak just before they
stop, to greatly improve conformality and reduce the irradia-
tion of critical surrounding structures. As protons stop abruptly
after the Bragg peak, the exit dose, which conventional radio-
therapy delivers as the beam exits the body beyond the target,
is reduced. A range of protons with varying energy ensures that
all of the dose is deposited within the tumor tissue, over a
spread-out Bragg peak. The literature suggests craniopharyn-
gioma control rates of 90% or better with PBT,39,78 although
the relative novelty of the technology means that long-term
follow-up is awaited.
Intracavitary Therapy
Due to the cystic nature of the majority of craniopharyngio-
mas, there has been long-standing interest in the instillation of
various agents into the cystic cavity to reduce or control tumor
growth. Intracavitary therapy is reserved for tumors that are
monocystic or have a large dominant cyst. The cavity is accessed
using a catheter connected to a reservoir (such as an Ommaya
reservoir), which can be placed using open, endoscopic, or
stereotactic (frame-based or frameless) techniques. Once the
catheter has been sited, a “leak” test, performed by instillation
of a contrast agent followed by imaging (usually CT), is per-
formed to ensure that the cyst is isolated from the subarach-
noid space and that treating agent will not spill into the CSF
or brain parenchyma.
Agents that have been used for intracavitary therapy can
be divided into radioactive isotopes and chemotherapeu-
tics. Radioisotopes have included phosphorus-32 (32P),
yttrium-90 (90Y), and rhenium-186 (186Re). The chemo-
therapeutic agents that have been described are bleomycin and
interferon-α. There are case series reporting efficacy for all of
these agents in controlling craniopharyngioma, but concerns
about toxicity persist, and level 1 evidence is not available to
make strong recommendations regarding treatment.79,80 It is
likely that, at least for the moment, intracavitary therapies
will remain a second-line treatment for recurrent or inoper-
able cystic lesions. Interferon-alpha 2b is currently considered
a safe option with minimal neurologic risk. Typically, patients
receive 3 million international units of interferon-alpha 2b
three times a week for 4 weeks. Each administration is pre-
ceded by aspiration of the cyst fluid. In the largest series of
its use in pediatric craniopharyngioma published to date, 60
 CHAPTER 12  Craniopharyngiomas 217

A [FP] B

C D
• Figure 12.6  Intracystic interferon treatment for recurrent craniopharyngioma. (A) A T1 sagittal MRI
scan showing a recurrent cystic craniopharyngioma, several years after subtotal resection and radio-
therapy. The white arrow points to a catheter inserted into the cyst. (B) Radio-opaque contrast medium
has been injected into the reservoir and cyst catheter, outlining the cyst on this plain lateral skull radio-
graph. The black arrow points to the ventriculoperitoneal shunt. (C) A reconstructed sagittal CT scan
demonstrating the cyst full of contrast medium; the absence of contrast spillage into the subarachnoid
space confirms that the catheter is effectively sealed within the cyst (white arrow). (D) A postgadolinium
sagittal T1 MRI scan showing the smaller cyst 8 weeks after completion of a 4-week course of intracystic
interferon therapy.

children demonstrated a reduction in mean cyst volume from
27.7 mL to 9.6 mL52 (Fig. 12.6).
Long-Term Outcomes
As discussed earlier, the benign histologic nature of craniopha-
ryngioma is not reflected in its clinical behavior, and it is
increasingly realized that patients treated successfully on neu-
rosurgical or oncologic criteria go on to lead lives impaired by
endocrinologic, hypothalamic, and intellectual dysfunction.81
The main predictor of poor outcome in terms of quality of life
is hypothalamic involvement. The extent of resection and age
at diagnosis, perhaps counterintuitively, do not predict long-
term quality-of-life outcomes. It is the nature of these long-
term results that has caused neurosurgical and oncologic
communities to reevaluate management strategies in this group
of patients.
The extent of tumor control after various interventions,
particularly combinations of surgery and radiotherapy, has
received attention. In a review from the Surveillance,

Downloaded for andromeda masako (andromeda72@yahoo.com) at University of Sumatera Utara from ClinicalKey.com by Elsevier on September 02, 2019.
For personal use only. No other uses without permission. Copyright ©2019. Elsevier Inc. All rights reserved.
218 PART 2 Pediatric Neurosurgery
Epidemiology, and End Result Program database, overall sur-
vival (OS) at 1 and 3 years for a cohort of 644 patients with
craniopharyngioma recruited between 2004 and 2008 were
91.5% and 86.2%, respectively.82 In a large meta-analysis
reviewing 442 patients, adults and children, 2- and 5-year
progression-free survival (PFS) in those who underwent gross
total resection (GTR) (81% and 67%) and subtotal resection
(STR) with radiotherapy (91% and 66%) were similar, as were
the 5- and 10-year OS rates (98% and 98%, and 99% and
95%, respectively).37
Another study reviewing 109 children also found no differ-
ence between GTR and STR with radiotherapy, with 5-year
PFS at 77% and 73%, respectively; STR alone was, however,
significantly worse than STR with radiotherapy, with 5-year
PFS at 73% and 43%, respectively.35 A prospective surgical
multicenter study that recruited pediatric patients from central
Europe reported a 3-year PFS of 46%; however, children who
also underwent radiotherapy during the period improved this
result to 88%.83 This study also demonstrated that children
recruited from the second half of the study, when surgeons
were clearly less aggressive, showed a reduced rate of hypotha-
lamic complications from 35% to 13%.32
Recurrence
Management of recurrence remains a major issue in craniopha-
ryngioma. Just as primary management is controversial, there
is even less evidence to guide decision making in recurrent
lesions. There is disagreement in the literature about predictors
of recurrence. Although some have shown that recurrence is
predicted by extent of resection,84 other studies have not dem-
onstrated a clear relation85 There is also evidence that radio-
therapy reduces recurrence risk.86
Recurrence is detected by a combination of clinical and
radiologic follow-up. Most units mandate regular ophthalmic
and endocrine reviews and a schedule of MRI scanning for at
least 5 to 10 years after diagnosis. Much later recurrences have
been reported,87 and many advocate lifelong follow-up for
patients, particularly those with known residual lesions.
When recurrence does occur, management strategies echo
those of primary tumors; surgical resection is the preferred
option, particularly if the tumor is solid, with the aim of
maximal tumor removal while preserving hypothalamic func-
tion (if present). In a study evaluating 18 out of 97 patients
whose tumors progressed after limited surgery and radiother-
apy, the authors concluded that decompression of new cysts
alone had a low rate of long-term success and optimal manage-
ment was an attempt at GTR at first recurrence.88 Radio-
therapy and intracavitary treatments are reserved for tumors
Downloaded for andromeda masako (andromeda72@yahoo.com) at University of Sumatera Utara from ClinicalKey.com by Elsevier on September 02, 2019.
For personal use only. No other uses without permission. Copyright ©2019. Elsevier Inc. All rights reserved.
that are not fully resected surgically. Small recurrent cranio-
pharyngiomas have been considered an appropriate target for
stereotactic radiosurgery89; in a large series involving 137
patients, 54% showed shrinkage of the tumor, 16.5% showed
continued tumor growth, and in 8% the cysts enlarged.38
Conclusion
Craniopharyngioma remains a rare but uniquely challenging
tumor to treat. Optimal management requires multidisci-
plinary teams composed of the neurosurgeon, oncologist, oph-
thalmologist, and endocrinologist, among others. Increasing
realization of the dismal long-term quality of life suffered by
patients treated with aggressive early surgery has caused the
pendulum to swing back toward more limited surgery that
spares the hypothalamus, with adjuvant radiotherapy in many
units. Consensus on the best strategies of management for both
primary and recurrent craniopharyngioma has not been
reached and the ideal approach remains controversial.
Selected Key References
Cavalheiro S, Di Rocco C, Valenzuela S, et al. Craniopharyngiomas:
intratumoral chemotherapy with interferon-alpha: a multicenter pre-
liminary study with 60 cases. Neurosurg Focus. 2010;28:E12.
Clark AJ, Cage TA, Aranda D, et al. Treatment-related morbidity and
the management of pediatric craniopharyngioma: a systematic review.
J Neurosurg Pediatr. 2012;10:293-301.
Clark AJ, Cage TA, Aranda D, et al. A systematic review of the results
of surgery and radiotherapy on tumor control for pediatric cranio-
pharyngioma. Childs Nerv Syst. 2013;29:231-238.
Elliott RE, Jane JAJ, Wisoff JH. Surgical management of craniopharyn-
giomas in children: meta-analysis and comparison of transcranial and
transsphenoidal approaches. Neurosurgery. 2011;69:630-643, discus-
sion 643.
Hasegawa T, Kobayashi T, Kida Y. Tolerance of the optic apparatus in
single-fraction irradiation using stereotactic radiosurgery: evaluation
in 100 patients with craniopharyngioma. Neurosurgery. 2010;66:
688-694, discussion 694–5.
Leng LZ, Greenfield JP, Souweidane MM, et al. Endoscopic, endonasal
resection of craniopharyngiomas: analysis of outcome including
extent of resection, cerebrospinal fluid leak, return to preoperative
productivity, and body mass index. Neurosurgery. 2012;70:110-123,
discussion 123–4.
Puget S, Garnett M, Wray A, et al. Pediatric craniopharyngiomas: clas-
sification and treatment according to the degree of hypothalamic
involvement. J Neurosurg. 2007;106:3-12.
Thompson D, Phipps K, Hayward R. Craniopharyngioma in childhood:
our evidence-based approach to management. Childs Nerv Syst.
2005;21:660-668.
Please go to ExpertConsult.com to view the complete list of references.

References
1. Nielsen EH, Feldt-Rasmussen U, Poulsgaard L, et al. Incidence of
craniopharyngioma in Denmark (n = 189) and estimated world inci-
dence of craniopharyngioma in children and adults. J Neurooncol.
2011;104:755-763.
2. Dolecek TA, Propp JM, Stroup NE, et al. CBTRUS Statisti-
cal Report: Primary Brain and Central Nervous System Tumors
Diagnosed in the United States in 2005-2009. Neuro Oncol.
2012;14:v1-v49.
3. Prabhu VC, Brown HG. The pathogenesis of craniopharyngiomas.
Childs Nerv Syst. 2005;21:622-627.
4. Senthilvel HNP, Krishnan SS, Vasudevan MC. Extracranial infrasel-
lar craniopharyngioma. Neurol India. 2014;62:100-103.
5. Larkin SJ, Ansorge O. Pathology and pathogenesis of craniopharyn-
giomas. Pituitary. 2013;16:9-17.
6. Šteňo J, Malacek M, Bízik I. Tumor-third ventricular relationships
in supradiaphragmatic craniopharyngiomas: correlation of morpho-
logical, magnetic resonance imaging, and operative findings. Neuro­
surgery. 2004;54:1051-1058, discussion 1058–60.
7. Cashion EL, Young JM. Intraventricular craniopharyngioma. Report
of two cases. J Neurosurg. 1971;34:84-87.
8. Fukushima T, Hirakawa K, Kimura M, et al. Intraventricular cra-
niopharyngioma: its characteristics in magnetic resonance imaging
and successful total removal. Surg Neurol. 1990;33:22-27.
9. Migliore A, Calzolari F, Marzola A, et al. Intrinsic III ventricle
craniopharyngioma. Childs Nerv Syst. 1992;8:56-58.
10. Lee JH, Kim CY, Kim DG, et al. Postoperative ectopic seeding
of craniopharyngioma. Case illustration. J Neurosurg. 1999;90:
796.
11. Novegno F, Di Rocco F, Colosimo C Jr, et al. Ectopic recurrences
of craniopharyngioma. Childs Nerv Syst. 2002;18:468-473.
12. Ragoowansi AT, Piepgras DG. Postoperative ectopic craniopharyn-
gioma. Case report. J Neurosurg. 1991;74:653-655.
13. Bozbuga M, Turan Suslu H, Hicdonmez T, et al. Primary cerebel-
lopontine angle craniopharyngioma in a patient with Gardner syn-
drome. J Clin Neurosci. 2011;18:300-301.
14. Kim MS, Kim YS, Lee HK, et al. Primary intracranial ectopic cra-
niopharyngioma in a patient with probable Gardner’s syndrome. J
Neurosurg. 2014;120:337-341.
15. Sangiovanni G, Tancioni F, Tartara F, et al. Ectopic craniopharyn-
gioma: presentation of a case arising from the corpus callosum. Acta
Neurochir. 1997;139:379-380.
16. Shah GB, Bhaduri AS, Misra BK. Ectopic craniopharyngioma of the
fourth ventricle: case report. Surg Neurol. 2007;68:96-98.
17. Deutsch H, Kothbauer K, Persky M, et al. Infrasellar craniopha-
ryngiomas: case report and review of the literature. Skull Base.
2001;11:121-128.
18. Nourbakhsh A, Brown B, Vannemreddy P, et al. Extracranial infra-
sellar ectopic craniopharyngioma: a case report and review of the
literature. Skull Base. 2010;20:475-480.
19. Hölsken A, Kreutzer J, Hofmann BM, et al. Target Gene Activation
of the Wnt Signaling Pathway in Nuclear β-Catenin Accumulat-
ing Cells of Adamantinomatous Craniopharyngiomas. Brain Pathol.
2009;19:357-364.
20. Sekine S, Shibata T, Kokubu A, et al. Craniopharyngiomas of Ada-
mantinomatous Type Harbor β-Catenin Gene Mutations. Am J
Pathol. 2010;161:1997-2001.
21. Hölsken A, Sill M, Merkle J, et al. Adamantinomatous and papil-
lary craniopharyngiomas are characterized by distinct epigenomic
as well as mutational and transcriptomic profiles. Acta Neuropathol
Commun. 2016;4:20.
Downloaded for andromeda masako (andromeda72@yahoo.com) at University of Sumatera Utara from ClinicalKey.com by Elsevier on September 02, 2019.
For personal use only. No other uses without permission. Copyright ©2019. Elsevier Inc. All rights reserved.
CHAPTER 12  Craniopharyngiomas 218.e1
22. Puget S, Garnett M, Wray A, et al. Pediatric craniopharyngiomas:
classification and treatment according to the degree of hypothalamic
involvement. J Neurosurg. 2007;106:3-12.
23. Van Effenterre R, Boch A-L. Craniopharyngioma in adults and
children: a study of 122 surgical cases. J Neurosurg. 2002;97:3-11.
24. Pratheesh R, Swallow DMA, Rajaratnam S, et al. Incidence, predic-
tors and early post-operative course of diabetes insipidus in paediat-
ric craniopharyngioma: a comparison with adults. Childs Nerv Syst.
2013;29:941-949.
25. Kennedy HB, Smith RJ. Eye signs in craniopharyngioma. Br J
Ophthalmol. 1975;59:689-695.
26. Hoffman HJ, De Silva M, Humphreys RP, et al. Aggressive surgi-
cal management of craniopharyngiomas in children. J Neurosurg.
1992;76:47-52.
27. Müller HL. Childhood craniopharyngioma—current con-
cepts in diagnosis, therapy and follow-up. Nat. Rev. Endocrinol.
2010;6:609-618.
28. Sainte-Rose C, Puget S, Wray A, et al. Craniopharyngioma: the pen-
dulum of surgical management. Childs Nerv Syst. 2005;21:691-695.
29. Caldarelli M, Massimi L, Tamburrini G, et al. Long-term results of
the surgical treatment of craniopharyngioma: the experience at the
Policlinico Gemelli, Catholic University, Rome. Childs Nerv Syst.
2005;21:747-757.
30. De Vile CJ, Grant DB, Kendall BE, et al. Management of child-
hood craniopharyngioma: can the morbidity of radical surgery be
predicted? J Neurosurg. 1996;85:73-81.
31. Fischer EG, Welch K, Shillito JJ, et al. Craniopharyngiomas in
children. Long-term effects of conservative surgical procedures com-
bined with radiation therapy. J Neurosurg. 1990;73:534-540.
32. Hoffmann A, Warmth-Metz M, Gebhardt U, et al. Childhood cra-
niopharyngioma - changes of treatment strategies in the trials KRA-
NIOPHARYNGEOM 2000/2007. Klin Padiatr. 2014;226:161-168.
33. Weiner HL, Wisoff JH, Rosenberg ME, et al. Craniopharyngiomas:
a clinicopathological analysis of factors predictive of recurrence and
functional outcome. Neurosurgery. 1994;35:1001-1010, discussion
1010–1.
34. Yasargil MG, Curcic M, Kis M, et al. Total removal of craniopha-
ryngiomas. Approaches and long-term results in 144 patients. J
Neurosurg. 1990;73:3-11.
35. Clark AJ, Cage TA, Aranda D, et al. A systematic review of the
results of surgery and radiotherapy on tumor control for pediatric
craniopharyngioma. Childs Nerv Syst. 2013;29:231-238.
36. Iannalfi A, Fragkandrea I, Brock J, et al. Radiotherapy in craniopha-
ryngiomas. Clin Oncol (R Coll Radiol). 2013;25:654-667.
37. Yang I, Sughrue ME, Rutkowski MJ, et al. Craniopharyngioma:
a comparison of tumor control with various treatment strategies.
Neurosurg Focus. 2010;28:E5.
38. Lee C-C, Yang H-C, Chen C-J, et al. Gamma Knife surgery for
craniopharyngioma: report on a 20-year experience. J Neurosurg.
2014;121(suppl):167-178.
39. Luu QT, Loredo LN, Archambeau JO, et al. Fractionated proton
radiation treatment for pediatric craniopharyngioma: preliminary
report. Cancer J. 2006;12:155-159.
40. Chamoun R, Couldwell WT. Transcortical-transforaminal micro-
scopic approach for purely intraventricular craniopharyngioma.
Neurosurg Focus. 2013;34:Video 4.
41. Elliott RE, Jane JAJ, Wisoff JH. Surgical management of craniopha-
ryngiomas in children: meta-analysis and comparison of transcranial
and transsphenoidal approaches. Neurosurgery. 2011;69:630-643,
discussion 643.
42. Fahlbusch R, Hofmann BM. Surgical management of giant cranio-
pharyngiomas. Acta Neurochir. 2008;150:1213-1226.
218.e2 PART 2 Pediatric Neurosurgery
43. Gerganov V, Metwali H, Samii A, et al. Microsurgical resection of
extensive craniopharyngiomas using a frontolateral approach: opera-
tive technique and outcome. J Neurosurg. 2014;120:559-570.
44. Ikeda H, Gotoh H, Watanabe K. Outcome of endoscopy-assisted
microscopic extended transsphenoidal surgery for suprasellar adult
craniopharyngiomas. Front Endocrinol (Lausanne). 2012;3:25.
45. Kassam AB, Gardner PA, Snyderman CH, et al. Expanded endona-
sal approach, a fully endoscopic transnasal approach for the resec-
tion of midline suprasellar craniopharyngiomas: a new classification
based on the infundibulum. J Neurosurg. 2008;108:715-728.
46. Komotar RJ, Starke RM, Raper DMS, et al. Endoscopic endo-
nasal compared with microscopic transsphenoidal and open
transcranial resection of craniopharyngiomas. World Neurosurg.
2012;77:329-341.
47. Laws ERJ. Craniopharyngioma: transsphenoidal surgery. Curr Ther
Endocrinol Metab. 1997;6:35-38.
48. Milligan BD, Meyer FB. Morbidity of transcallosal and transcortical
approaches to lesions in and around the lateral and third ventricles:
a single-institution experience. Neurosurgery. 2010;67:1483-1496,
discussion 1496.
49. Thompson D, Phipps K, Hayward R. Craniopharyngioma in child-
hood: our evidence-based approach to management. Childs Nerv
Syst. 2005;21:660-668.
50. Margetis K, Souweidane MM. Endoscopic resection of colloid cyst
in normal-sized ventricular system. Neurosurg Focus. 2013;34:Video
8.
51. Mallucci C, Pizer B, Blair J, et al. Management of craniopharyn-
gioma: the Liverpool experience following the introduction of
the CCLG guidelines. Introducing a new risk assessment grading
system. Childs Nerv Syst. 2012;28:1181-1192.
52. Cavalheiro S, Di Rocco C, Valenzuela S, et al. Craniopharyngiomas:
intratumoral chemotherapy with interferon-alpha: a multicenter
preliminary study with 60 cases. Neurosurg Focus. 2010;28:E12.
53. Pettorini BL, Tamburrini G, Massimi L, et al. Endoscopic trans-
ventricular positioning of intracystic catheter for treatment of
craniopharyngioma. Technical note. J Neurosurg Pediatr. 2009;4:245-
248.
54. Kono Y, Prevedello DM, Snyderman CH, et al. One thousand
endoscopic skull base surgical procedures demystifying the infection
potential: incidence and description of postoperative meningitis and
brain abscesses. Infect Control Hosp Epidemiol. 2011;32:77-83.
55. Sutton LN. Vascular complications of surgery for craniopharyn-
gioma and hypothalamic glioma. Pediatr Neurosurg. 1994;21(suppl
1):124-128.
56. Salunke P, Sodhi HBS, Aggarwal A, et al. Delayed cerebral vaso-
spasm following surgery for craniopharyngioma. J Neurosci Rural
Pract. 2013;4:107-109.
57. Deshaies EM, Boulos AS, Popp AJ. Peri-operative medical manage-
ment of cerebral vasospasm. Neurol Res. 2009;31:644-650.
58. Maira G, Anile C, Albanese A, et al. The role of transsphenoidal
surgery in the treatment of craniopharyngiomas. J Neurosurg.
2004;100:445-451.
59. Honegger J, Buchfelder M, Fahlbusch R. Surgical treatment
of craniopharyngiomas: endocrinological results. J Neurosurg.
1999;90:251-257.
60. Fatemi N, Dusick JR, de Paiva Neto MA, et al. Endonasal versus
supraorbital keyhole removal of craniopharyngiomas and tubercu-
lum sellae meningiomas. Neurosurgery. 2009;64:269-284, discussion
284–6.
61. Müller HL. Childhood craniopharyngioma: current controversies
on management in diagnostics, treatment and follow-up. Expert Rev
Neurother. 2014;10:515-524.
Downloaded for andromeda masako (andromeda72@yahoo.com) at University of Sumatera Utara from ClinicalKey.com by Elsevier on September 02, 2019.
For personal use only. No other uses without permission. Copyright ©2019. Elsevier Inc. All rights reserved.
62. Müller HL. Childhood Craniopharyngioma. Horm Res Paediatr.
2008;69:193-202.
63. Elliott RE, Hsieh K, Hochm T, et al. Efficacy and safety of radical
resection of primary and recurrent craniopharyngiomas in 86 chil-
dren. J Neurosurg Pediatr. 2010;5:30-48.
64. Curtis J, Daneman D, Hoffman HJ, et al. The endocrine outcome
after surgical removal of craniopharyngiomas. Pediatr Neurosurg.
1994;21(suppl 1):24-27.
65. Müller HL. Craniopharyngioma and hypothalamic injury: latest
insights into consequent eating disorders and obesity. Curr Opin
Endocrinol Diabetes Obes. 2016;23:81-89.
66. Katz EL. Late results of radical excision of craniopharyngiomas in
children. J Neurosurg. 1975;42:86-93.
67. Clark AJ, Cage TA, Aranda D, et al. Treatment-related morbidity
and the management of pediatric craniopharyngioma: a systematic
review. J Neurosurg Pediatr. 2012;10:293-301.
68. Komotar RJ, Starke RM, Raper DMS, et al. Endoscopic skull
base surgery: a comprehensive comparison with open transcranial
approaches. Br J Neurosurg. 2012;26:637-648.
69. Jane JAJ, Kiehna E, Payne SC, et al. Early outcomes of endoscopic
transsphenoidal surgery for adult craniopharyngiomas. Neurosurg
Focus. 2010;28:E9.
70. Leng LZ, Greenfield JP, Souweidane MM, et al. Endoscopic, endo-
nasal resection of craniopharyngiomas: analysis of outcome including
extent of resection, cerebrospinal fluid leak, return to preoperative
productivity, and body mass index. Neurosurgery. 2012;70:110-123,
discussion 123–4.
71. Winkfield KM, Linsenmeier C, Yock TI, et al. Surveillance of cra-
niopharyngioma cyst growth in children treated with proton radio-
therapy. Int J Radiat Oncol Biol Phys. 2009;73:716-721.
72. Combs SE, Thilmann C, Huber PE, et al. Achievement of long-term
local control in patients with craniopharyngiomas using high preci-
sion stereotactic radiotherapy. Cancer. 2007;109:2308-2314.
73. Merchant TE, Kiehna EN, Kun LE, et al. Phase II trial of conformal
radiation therapy for pediatric patients with craniopharyngioma and
correlation of surgical factors and radiation dosimetry with change
in cognitive function. J Neurosurg. 2006;104:94-102.
74. Merchant TE, Kiehna EN, Sanford RA, et al. Craniopharyngioma:
the St. Jude Children’s Research Hospital experience 1984-2001. Int
J Radiat Oncol Biol Phys. 2002;53:533-542.
75. Minniti G, Saran F, Traish D, et al. Fractionated stereotactic con-
formal radiotherapy following conservative surgery in the control of
craniopharyngiomas. Radiother Oncol. 2007;82:90-95.
76. Rajan B, Ashley S, Gorman C, et al. Craniopharyngioma–a long-
term results following limited surgery and radiotherapy. Radiother
Oncol. 1993;26:1-10.
77. Hasegawa T, Kobayashi T, Kida Y. Tolerance of the optic appa-
ratus in single-fraction irradiation using stereotactic radiosurgery:
evaluation in 100 patients with craniopharyngioma. Neurosurgery.
2010;66:688-694, discussion 694–5.
78. Winkfield KM, Tsai HK, Yao X, et al. Long-term clinical outcomes
following treatment of childhood craniopharyngioma. Pediatr Blood
Cancer. 2010;56:1120-1126.
79. Kilday J-P, Caldarelli M, Massimi L, et al. Intracystic interferon-
alpha in pediatric craniopharyngioma patients: an international
multicenter assessment on behalf of SIOPE and ISPN. Neuro Oncol.
2017.
80. Zhang S, Fang Y, Cai BW, et al. Intracystic bleomycin for cystic
craniopharyngiomas in children. Cochrane Database Syst Rev.
2016;(7):CD008890.
81. Sterkenburg AS, Hoffmann A, Gebhardt U, et al. Survival, hypo-
thalamic obesity, and neuropsychological/psychosocial status after
 CHAPTER 12  Craniopharyngiomas 218.e3

childhood-onset craniopharyngioma: newly reported long-term out-
comes. Neuro Oncol. 2015;17:1029-1038.
82. Zacharia BE, Bruce SS, Goldstein H, et al. Incidence, treatment and
survival of patients with craniopharyngioma in the surveillance, epide-
miology and end results program. Neuro Oncol. 2012;14:1070-1078.
83. Müller HL, Gebhardt U, Schröder S, et al. Analyses of treatment
variables for patients with childhood craniopharyngioma—results of
the multicenter prospective trial KRANIOPHARYNGEOM 2000
after three years of follow-up. Horm Res Paediatr. 2010;73:175-180.
84. Liubinas SV, Munshey AS, Kaye AH. Management of recurrent
craniopharyngioma. J Clin Neurosci. 2011;18:451-457.
85. Tan TSE, Patel L, Gopal-Kothandapani JS, et al. The neuroendo-
crine sequelae of paediatric craniopharyngioma: a 40-year meta-data
analysis of 185 cases from three UK centres. Eur J Endocrinol.
2017;176:359-369.
86. Gupta DK, Ojha BK, Sarkar C, et al. Recurrence in craniopharyn-
giomas: analysis of clinical and histological features. J Clin Neurosci.
2006;13:438-442.
87. de Blank PM, Minturn JE. A rare case of ectopic recurrence of a
craniopharyngioma diagnosed 17 years after initial presentation. J
Pediatr Hematol Oncol. 2011;33:392-397.
88. Klimo PJ, Venable GT, Boop FA, et al. Recurrent craniopharyn-
gioma after conformal radiation in children and the burden of
treatment. J Neurosurg Pediatr. 2015;15:499-505.
89. Murphy ES, Chao ST, Angelov L, et al. Radiosurgery for Pediatric
Brain Tumors. Pediatr Blood Cancer. 2016;63:398-405.

Downloaded for andromeda masako (andromeda72@yahoo.com) at University of Sumatera Utara from ClinicalKey.com by Elsevier on September 02, 2019.
For personal use only. No other uses without permission. Copyright ©2019. Elsevier Inc. All rights reserved.