Craniopharyngiomas: Clinic Al Pearls

Pediatric Neurosurgery
12
Craniopharyngiomas
GREG JAMES, KRISTIAN AQUILINA
CLINICAL PEARLS
• Craniopharyngioma is a histologically benign tumor, which advocate more limited surgical approaches such as cyst
presents special challenges to the neurosurgeon due to a drainage or subtotal resection, followed by adjuvant (usually
combination of its highly eloquent location and locally radiation) therapy.
recurrent nature. • Multiple surgical approaches have been described for
• Craniopharyngioma can present with visual, neurologic, or craniopharyngioma, including an increasing interest in
endocrine symptoms. Neurosurgeons managing endoscopic transsphenoidal surgery. The choice of approach
craniopharyngioma are strongly advised to work within a should be based on a three-dimensional understanding of the
multidisciplinary team that includes neuro-ophthalmologists, topography of the tumor, with particular emphasis on avoiding
endocrinologists, and oncologists. hypothalamic, optic, and vascular injury.
• The “traditional” strategy for surgical management of • Adjuvant therapies are important in managing
craniopharyngioma was radical resection. However, there is craniopharyngioma—including more novel techniques such as
increasing evidence that aggressive surgical treatment causes proton beam therapy, stereotactic radiosurgery, and
severe long-term sequelae, related to pituitary and (especially) intracavitary therapy—and their use should be considered in
hypothalamic dysfunction. Therefore many surgeons now both primary and recurrent disease.
Introduction on its merits by a multidisciplinary team to achieve the

best possible outcome. Despite the increasingly multidisci-
Craniopharyngioma is a rare but important intracranial tumor plinary management of craniopharyngioma, the neurosur-
that presents a unique challenge to the neurosurgeon. It has geon still plays the central role in decision making for affected
often been described as a histologically benign tumor that patients.
behaves in a malignant manner. This “malignancy” is due
to a combination of its predilection for arising within and Epidemiology
being closely apposed to exquisitely eloquent brain structures,
its unpredictable biologic behavior, and its high local recur- Craniopharyngioma is a rare tumor. Its incidence has been
rence rates. Arising from the remnants of the Rathke pouch, estimated at 1.3 cases per million people per year1 with the
the tumor itself—and attempts to treat it, either surgically highest incidence in Japan and West Africa, particularly in
or nonsurgically—can cause significant visual, endocrine, Nigeria. Across all ages, craniopharyngiomas constitute only
and neurocognitive morbidity. The challenges arising from around 1% of all the new central nervous system tumors found
this situation have long been recognized, and perhaps no per year, although this rises to 4% in the pediatric age group.2
other intracranial neoplasm has seen such dramatic changes There is a well-recognized bimodal age distribution, with the
in accepted treatment protocols over the decades. There have first peak occurring at school age (5–14) and a second occur-
been changes in suggested management stratagems—from ring in middle to late adulthood (45–65). There is no gender
maximal resection based on achieving a radiologic cure, to predilection. The histologic diagnosis also varies with age, with
more minimal procedures, often in combination with adju- the papillary form of craniopharyngioma being seen almost
vant therapies, focused on preserving function and minimiz- exclusively in the adult group, whereas adamantinomatous
ing the risk of recurrence. What has become increasingly tumors can be found in both groups. No environmental or
clear is that there is no “one size fits all” approach for these genetic risk factors have been identified, and craniopharyngi-
complex entities, and each individual case must be assessed oma is best thought of as a sporadic condition.
204
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CHAPTER 12 Craniopharyngiomas 205
Embryology sometimes therefore called intraventricular and extraventricular

craniopharyngiomas (IEVCs); this is the most commonly seen
Craniopharyngioma pathogenesis is believed to result from configuration.6 They are thought to grow in a retrochiasmatic
the unique embryology of the anterior pituitary gland. During manner and to erode and cross the floor of the third ventricle
development of the fetus, a pocket of epithelial ectoderm (the relatively early. This leads to a lower component extending in
Rathke pouch), in the roof of the pharynx, extends superi- the suprasellar cistern and an upper part growing into the
orly to meet the neurectoderm of the developing brain. A cavity of the third ventricle. IEVCs are almost always entirely
temporary connection between the two ectodermal layers— retrochiasmatic, except in cases of a postfixed chiasm where
the craniopharyngeal duct—thus forms. This then involutes, some of the tumor may extend below the chiasm or even grow
leaving glandular tissue to form the normal adenohypophy- between the optic nerves.
sis or anterior pituitary gland.3 Adamantinomatous cranio- A true “pure” intraventricular craniopharyngioma is a rare
pharyngioma is thought to arise when, during this process, entity, with the majority of tumors thought to be exclusively
incomplete or erroneous involution of the Rathke pouch and enclosed within an intact third ventricle having some extension
craniopharyngeal duct occurs, leaving “nests” of epithelial into the suprasellar space on close radiologic or surgical exami-
rest cells that go on to undergo neoplastic change.3,4 Papil- nation. Cases, however, have been described.7–9
lary tumors are postulated to form from metaplasia in the Ectopic craniopharyngiomas, occurring in locations other
mature adult pituitary gland, with conversion of normal pitui- than the sellar region or even outside of the central nervous
cytes into epithelial nests containing abnormal epithelial cells. system, have been described but are exceedingly rare. “Seeding”
These differing theories may explain the temporal distribu- of craniopharyngioma cells, causing distant recurrence adja-
tion of the two craniopharyngioma types, as metaplasia is a cent to a surgical track or craniotomy used to resect a sellar
slowly occurring process and it takes many years to generate lesion, is a rare but well-described occurrence.10–12 Primary
the nests.5 “true” ectopic lesions are rarer still but have been described in
central nervous system (CNS) locations such as the cerebel-
Anatomy lopontine angle,13,14 corpus callosum,15 and fourth ventricle16
and even extradurally in the ethmoid17 and sphenoid18 air
The anatomy of the sellar region is complex, and a neurosur- sinuses.
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 Pathology
the suprasellar space, craniopharyngiomas are intimately
related to the circle of Willis and its branches. The most impor- Craniopharyngioma, according to the 2007 World Health
tant anatomic distinction is whether the tumor arises from Organization (WHO) definition, is a “benign, partially cystic
above or below the sellar diaphragm, which dictates its rela- epithelial tumor of the sellar region, presumably derived from
tionship with surrounding anatomy as it grows.6 An apprecia- Rathke pouch epithelium” and is designated as a grade I tumor
tion of the premorbid arrangement of the optic chiasm—the of the central nervous system.
so-called normal (above the midpoint of the sella), “prefixed” Gross pathologic examination of craniopharyngiomas dif-
(above the tuberculum sellae) and “postfixed” (above the ferentiates them into cystic (50%), mixed cystic-solid (35%),
dorsum sellae) positions—is also essential when planning a and solid (15%). They are typically described as lobulated
surgical approach. masses with evidence of adherence to and disruption of sur-
Tumors arising below the diaphragm (infradiaphragmatic rounding structures such as the hypothalamus, infundibulum,
craniopharyngioma) will push the sellar diaphragm and con- blood vessels, or cranial nerves. On section, cysts are found
tents upward as they grow, eventually causing compression and to contain fluid that has a brownish color often described
upward displacement of the chiasm and third ventricle. Ana- as “machine oil,” which on examination contains cholesterol
tomically, their behavior is similar to that of an enlarging crystals. In addition, calcification is frequently identified
pituitary adenoma. within the specimen. This classic macroscopic description is
Craniopharyngiomas arising from above the sellar dia- typical of the adamantinomatous subtype, with the papillary
phragm (supradiaphragmatic) can be further divided depend- type more commonly solid without “machine oil” fluid or
ing on their point of origin—the pituitary stalk or the calcification.
hypothalamic infundibulum. Those arising from the pituitary The two subtypes are quite distinct on histologic examina-
stalk will enlarge into the subarachnoid space below the chiasm tion. Adamantinomatous tumors are formed of “nests” of epi-
and third ventricular floor, usually extending anteriorly into thelium within gliotic neural stroma. Rows of tumor cell
the region between the optic nerves (except in the rare case of nuclei, or “palisading” nuclei, are often seen associated with
a prefixed chiasm, where they may be entirely retrochiasmatic). stellate reticulum formed of loosely arranged epithelial cells.
These tumors are sometimes designated as suprasellar extraven Mitotic figures are rare in keeping with the benign histologic
tricular craniopharyngiomas (SECs). grade. The histologic hallmark of craniopharyngioma is “wet
Craniopharyngiomas arising from the infundibulum tend keratin,” stacked arrays of plump, eosinophilic keratinized
to grow in both extra- and intraventricular fashion and are cells.
206 PART 2 Pediatric Neurosurgery
Papillary tumors, in contrast, are formed of bland stratified The differential diagnosis for sellar region lesions is wide
squamous epithelium with foci of fibrovascular tissue, without and includes the Rathke cleft cyst, optic pathway glioma,
palisading or stellate reticulum. Keratinized cells are sometimes hypothalamic hamartoma, metastasis, and others. CT can be
seen but not wet keratin. useful in differentiating craniopharyngioma from these other
Due to their characteristic histology, immunohistochemis- differentials by demonstrating evidence of calcification; this is
try is not usually necessary to confirm diagnosis but is occa- seen in 85% to 90% of childhood craniopharyngioma and
sionally helpful. Both subtypes stain strongly for epithelial around 40% to 50% of adult tumors. The relatively lower rate
membrane antigen and cytokeratin. They are negative for in adults can be explained by the presence of the papillary
“pituitary” markers such as prolactin and adrenocorticotropic histologic subtype in that age group, as papillary craniopha-
hormone (ACTH). ryngiomas do not calcify. A note of caution here is that the
Understanding of the molecular pathways involved in cra- only other lesion that may show similar rim or “eggshell”
niopharyngioma is incomplete, but many studies are ongoing. calcification is an aneurysm. Vascular imaging (CT, MRI, or
Mutations of the CTNNB1 gene, encoding β-catenin, have catheter angiography) is indicated prior to surgical exploration
been described in adamantinomatous craniopharyngioma; if concern persists.
accumulations of nuclear β-catenin, consistent with acti- Decision making about the feasibility and extent of surgery
vation of the Wnt pathway, are identified in scattered cells is informed by close analysis of the preoperative MRI scan. The
within this craniopharyngioma type.19,20 By contrast, the Paris group has published a system based on presurgical
BRAF C600E mutation is found in up to 100% of papillary involvement of the hypothalamus to guide surgical decision
craniopharyngiomas.21 making. The Paris classification is as follows: grade 0, no hypo-
thalamic involvement; grade 1, the tumor abutting or displac-
Radiology ing the hypothalamus; and grade 2, hypothalamic involvement
(the hypothalamus is no longer identifiable).22 The implica-
The most useful imaging modality for assessing craniopharyn- tions of this presurgical radiologic grading system on operative
gioma is magnetic resonance imaging (MRI), although com- results and outcome are discussed next.
puted tomography (CT) still has a role, particularly for assessing
calcification (which can reliably differentiate craniopharyngi- Presentation
oma from other suprasellar pathologies) and for detailed assess-
ment of skull base anatomy for surgical planning. Plain skull Craniopharyngioma can present with a wide variety of clinical
radiography has been superseded by MRI and CT, whereas symptoms and signs; all can be predicted by the relations of
formal catheter angiography is only rarely indicated—to aid the suprasellar tumor to the critical surrounding structures.
presurgical planning in large tumors that appear on MRI to Symptoms can be visual (due to compression or injury to the
have close relationships to the circle of Willis or if a giant optic apparatus), endocrine (hypothalamic-pituitary axis),
suprasellar aneurysm is a differential diagnosis. Both MRI and neurocognitive (mammillary bodies, hypothalamus, and asso-
CT demonstrate obstruction to cerebrospinal fluid (CSF) flow ciated limbic tracts), and those of obstructive hydrocephalus
and hydrocephalus related to filling or distortion of the third (third ventricle). Patterns of initial presenting symptomatology
ventricle, usually by a craniopharyngioma cyst. differ between age groups, with endocrinopathies and hydro-
MRI of craniopharyngioma usually demonstrates a hetero- cephalus more common in children and visual impairment and
geneous mass. Solid components are usually T1 isointense and neurocognitive changes more frequent in adults.
enhance with gadolinium contrast. Cystic components often Visual impairment can take several forms, including field
demonstrate ring enhancement, whereas the cyst contents may deficits and reduced acuity. The nature of the field deficit
vary in appearance depending on the protein or blood break- depends on the anatomic configuration of the tumor but
down products contained therein. There may even be fluid- can include bitemporal hemianopia, homonymous hemiano-
fluid levels within individual cysts or heterogeneity in signal pia, concentric field constriction, and central or paracentral
characteristics between different cysts in the same tumor. MRI, scotoma, of which an asymmetric bitemporal hemianopia is
ideally reviewed in three planes, identifies the topography of the most common type. Field deficits are usually due to direct
the tumor and can be used to divide craniopharyngiomas into compression of the relevant part of the optic pathway by
infra- and supradiaphragmatic as described earlier. The former the enlarging craniopharyngioma but can represent ischemia
are usually associated with enlargement of the sella in a similar caused by involvement of perforating arteries by the tumor.
manner to pituitary adenoma. The latter group can be subdi- Reduced acuity is most commonly due to prolonged raised
vided into SECs and IEVCs radiologically, using the anatomic intracranial pressure such as that seen secondary to obstructive
criteria described previously. hydrocephalus, but it can be a late effect of prolonged compres-
An assessment of the position of the optic chiasm in relation sion. Children often do not report visual symptoms or impair-
to the tumor can usually be made accurately on MRI scan. If ment until they are profound, and it is sadly not uncommon
the chiasm itself cannot be directly visualized, the anterior for young patients to be functionally blind at first presentation.
communicating artery is a reliable marker of its position, this Endocrinopathies are often insidious in their onset, and
artery being usually apposed to the chiasm’s upper posterior both children and adults often miss the symptoms. Children
surface. may show restricted growth or delayed onset of puberty. Adults
may experience decreased libido and erectile dysfunction (men) definitely prior to any surgical procedure. This should consist
or amenorrhea (in women). Diabetes insipidus and obesity of a detailed clinical examination, including measurement of
may occur at any age. The presence of obesity suggests hypo- body mass index (BMI) and an assessment of intravascular
thalamic involvement. volume status. The exact schedule of biochemical investigation
Obstructive hydrocephalus causes the typical symptoms of will vary between institutions, dependent on the experience
raised intracranial pressure—namely, headache, nausea, drows- and preferences of the endocrine and laboratory services, but
iness, and visual deterioration due to papilledema (and even- should include a full assessment, including dynamic testing if
tual optic atrophy). This presentation is much more common required, of the adrenal, thyroid, and gonadal axes, as well as
in the pediatric age group, presumably as adults will notice and GH, prolactin, and ADH function.
report more subtle symptoms such as field deficits or neuro- Management of both pre- and postoperative endocrinopa-
cognitive impairment more readily than children. thies involves exogenous replacement of deficient hormones.
In adults, neurocognitive symptoms can be the presenting The most critical, and first to be replaced, are glucocorticoids.
feature, with memory impairment more common than person- The administration of thyroxine, for example, in an untreated
ality change. These symptoms are thought to result from injury or undertreated steroid-deficient patient can precipitate acute
to the mammillary bodies or their connections with the hip- adrenal crisis. When planning surgery, a plan for stress dosing
pocampus, fornix, and mammillary-thalamic tract caused by (extra administration), intra- and postoperatively, should be
the expanding tumor. made and requires close teamwork among the neurosurgical,
anesthetic, and endocrine teams.
Endocrine Assessment In the postoperative period, diabetes insipidus can be a
feature, including the so-called triphasic response of initial
It is essential that an appropriately trained and experi- polyuria, followed by oliguria and water retention, followed
enced endocrinologist is part of the multidisciplinary team subsequently by a return of polyuria. Frequent monitoring of
caring for children and adults with craniopharyngioma. both serum and urine sodium, as well as osmolality, is manda-
Endocrinopathies—resulting either from the effect of the tory, with the administration of ADH analogues when indi-
tumor itself, at presentation or after multiple episodes of tumor cated. Although a transient diabetes insipidus–like condition
progression, or as a result of treatment, surgical or otherwise— is seen frequently in many postoperative craniopharyngioma
cause significant impairment of patients’ quality of life and patients, a subset will have long-term ADH replacement
can be life threatening. Indeed, recognition of the importance requirements.24
of steroid replacement and endocrine expertise was one of Over time and multiple treatment modalities, pituitary defi-
the significant contributions to the reduction in perioperative ciencies are ubiquitous in patients with craniopharyngioma,
mortality of craniopharyngioma surgery seen in the mid-20th necessitating lifelong follow-up and, in children, careful tran-
century. sitional arrangements to appropriate adult expertise.
Although clinically under-recognized, 85% of patients have
hypopituitarism at presentation,23 with growth hormone (GH) Neuro-Ophthalmologic Assessment
being the most common hormone affected, followed by lutein-
izing hormone/follicle-stimulating hormone (LH/FSH), with Detailed pre- and postoperative neuro-ophthalmologic exami-
sequentially lesser rates of corticotropin (ACTH) and thyroid- nation is critical to objectively record visual impairment related
stimulating hormone (TSH) deficiency. These deficiencies may to the tumor and the response (if any) to surgical treatment.
be detected biochemically or be symptomatic, with the usual It also establishes a baseline for subsequent follow-up. Exami-
features evident clinically. Diabetes insipidus (DI), due to defi- nation should include funduscopy (ideally with photography
ciency of antidiuretic hormone (ADH), has been reported in of the fundus and optical coherence tomography) and perim-
around a quarter of patients at diagnosis. etry (such as Goldmann or Humphrey testing) as well the usual
In addition to deficiencies of pituitary hormones, systemic documentation of visual acuity.
symptoms may arise from hypothalamic dysfunction caused by Fundal examination may reveal papilledema, almost exclu-
tumor invasion or (more frequently) surgical disruption of sively seen in tumors presenting with hydrocephalus and its
this critical homeostatic structure. The typical hypothalamic associated raised intracranial pressure, or optic atrophy, which
symptom seen in craniopharyngioma (either pre- or postopera- may be a late result of either direct chiasmal compression or
tively) is obesity resulting from injury to the satiety center long-term, untreated raised intracranial pressure.
located in the ventromedial nucleus, close to the floor of the Field examination most typically reveals an asymmetrical
third ventricle anterior to the mammillary bodies and therefore bitemporal hemianopia, but more posterior lesions (or sellar
often involved in craniopharyngiomas. This hyperphagia and lesions growing behind a prefixed chiasm) may cause a hom-
obesity often are accompanied by deterioration in behavior and onymous hemianopia. This homonymous hemianopia is
school performance in children. Other hypothalamic symp- incongruous and nonmacular sparing (so-called optic tract
toms are less frequent but can occur, including temperature syndrome), differentiating it from the field cut seen with an
dysregulation, disordered sleep, and deficient thirst. occipitopolar lesion.
All new cases of craniopharyngioma should have a full clini- In children, strabismus may be a presenting feature.25 This
cal and biochemical endocrine assessment at presentation and strabismus is most frequently due to compensation for field
loss and only rarely to involvement of the cranial nerves con- Although this system has by no means been universally
trolling ocular motility. adopted, it does supply some useful clinical evidence to inform
decision making in craniopharyngioma management. Not all
Treatment Planning surgeons agree with the grading system, and it is open to a
degree of neuroradiologic uncertainty. Moreover, surgical
Perhaps no other tumor in neurosurgical practice polarizes results are dependent on the surgeon’s experience and the
opinion in its treatment to such an extent as craniopharyngi- tumor volume of the institution. The basic principle—of
oma. Although for other intracranial tumors there is broad radical resection of tumors not involving the hypothalamus,
consensus on optimal surgical management, whether that is and appropriate caution and judicious use of adjuvant treat-
aggressive total resection (ependymoma) or avoidance of ments of those that do—remains a good tenet for guiding
surgery as first-line treatment (optic pathway glioma), two treatment decisions in this complex group of patients.
schools of thought have developed in craniopharyngioma man-
agement: radical resection versus intentional incomplete resec- Surgical Techniques
tion with radiotherapy.
The attraction of radical surgery is that, because this is a As well as a preoperative decision about the goal of surgery
histologically benign tumor, the recurrence rate after gross total (radical vs limited resection), consideration must be given on
resection is low, although still reported in the region of around the optimum approach to the tumor. Approaches from all
30% on long-term follow-up.26–28 The potential risk, as argued angles have been described for craniopharyngioma.40–48 Selec-
by adherents of the more conservative approach, is the higher tion of the optimum approach is based on traditional neuro-
rate of hypothalamic injury, pituitary insufficiency, neurocog- surgical principles, a route that affords good access for resection,
nitive disability, and impaired quality of life in patients treated avoids transgression of critical structures, and has an acceptable
radically.29–34 risk profile for postoperative complications such as CSF leak.
Radiotherapy has been proved to be efficacious in reducing In this section, surgical approaches are discussed for each of
recurrence in both radical and limited surgery35–37 but can itself the topographic types of tumors. Many craniopharyngiomas
have long-term deleterious effects, particularly in younger chil- involve the hypothalamus and can transgress anatomic bound-
dren. There has been much interest in the use of newer radio- aries (Fig. 12.1).
therapy techniques, such as proton beam and stereotactic
radiosurgery, to reduce the dosing of normal neural tissue.38,39 Infradiaphragmatic Craniopharyngioma
Although surgical resection (either radical or limited)
and radiotherapy form the mainstays of definitive treat- Purely intrasellar lesions are optimally approached via the trans-
ment of craniopharyngioma, other modalities, usually used sphenoidal route, which affords access to the tumor and identi-
in combination with those described, exist. Surgically, these fication (and therefore, in most cases, preservation) of the intact
include operations to drain tumor cysts, such as placement pituitary gland. Intrasellar lesions with suprasellar extension, of
of catheters connected to subcutaneous reservoirs that can be favorable size and topography, may also be managed effectively
aspirated as required, or wide endoscopic cyst fenestration. with transsphenoidal surgery. Transsphenoidal surgery can be
Other adjuvant therapies include intracavitary treatments, microscopic or, increasingly, endoscopic, and extended tech-
using catheters in cysts to deliver various agents, or systemic niques have been used to access infradiaphragmatic craniopha-
chemotherapy. ryngioma with extensive suprasellar extension.45 Regardless of
Ultimately, the decision on which modality to use for each the exact technique used to approach the tumor, the principles
patient will depend on the experience and resources available of intraoperative dissection remain identical. Once the bony
to the treating team, in combination with close examination sella has been opened and the dura incised, efforts are made to
of the preoperative MRI images and an understanding of the identify the normal pituitary tissue and protect it, usually by
endocrine and neuro-ophthalmologic status. As alluded to manipulating it to one side. The capsule of the craniopharyn-
earlier in the radiology section, the Paris group has developed gioma is identified and dissected from surrounding structures.
a protocol for guiding management based on scrutiny of the The capsule is often densely adherent to surrounding tissue,
preoperative scan.22 After decompression, in the acute phase, and intraoperative decisions need to be made on the nature of
of large cysts to alleviate hydrocephalus and protect vision, the adhesion and the importance of the attached structure. For
surgical decision making is guided by this classification; com- example, a portion of capsule densely adherent to the infun-
plete resection is the goal for grade 0 and 1 tumors, and dibulum may well be left in place rather than risk damaging
intentional limited resection with hypothalamic preservation this essential structure. Care must also be taken when handling
(followed by radiotherapy) for grade 2 tumors. By comparing flakes of calcification, as these may have sharp edges that can
a retrospective cohort, treated with intention of complete injure local tissues.
resection prior to the introduction of this system, to a prospec-
tive cohort treated following introduction of this protocol, the Suprasellar Extraventricular Craniopharyngioma
group saw a significant improvement in postoperative quality
of life, with no hypopituitarism or clinical hypothalamic dys- These lesions are best approached via a supratentorial crani-
function in the prospective group.22 otomy; the decision of which particular craniotomy to use
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 extension. Some large tumors may require staged resection
chiasm. For those (more common) tumors displacing the from different approaches (Fig. 12.2).
chiasm upward or extending into the prechiasmatic space, the For both subfrontal and pterional approaches, the choice of
subfrontal approach offers good access through the prechias- which side to use is based primarily on the topography of the
matic and opticocarotid spaces. For those rarer suprasellar tumor mass. For tumors where there is equipoise, the non-
extraventricular lesions situated entirely posterior to the optic dominant side is preferred. Patients are placed in a supine
chiasm, a pterional approach is preferred to avoid injury to position on the operating table with the neck rotated away
interposing hypothalamic structures. Each approach should be from the side of the craniotomy. Skull fixation with pins and
tailored to the individual tumor anatomy—for example, use a clamp is used for most patients, with the exception of very
of the orbitozygomatic approach or a bifrontal craniotomy for small children where a “horseshoe” headrest can be substituted.
inferiorly located or giant tumors, respectively. A frontal inter- Image guidance is extremely useful and should now be consid-
hemispheric approach, with division of the superior sagittal ered routine for these cases. Following registration of image
sinus, is also useful for large suprasellar tumors with retrosellar guidance, skin preparation, and draping, a curvilinear
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 the tumor has been visualized, dissection begins by opening
hairline from just over the midline to the root of the zygomatic and drainage of cystic components, minimizing spillage of
process. A standard frontal or pterional craniotomy is then contents into the CSF circulation. The tumor capsule is then
fashioned, with repair of the frontal air sinus if opened. An identified and removal proceeds in a piecemeal fashion, with
arcuate durotomy is performed followed by patient CSF drain- care taken to protect surrounding critical structures. Cranio-
age to allow brain relaxation, reducing the need for retraction. pharyngioma may adhere to vessels, particularly in areas of
Gentle retraction of the frontal lobe permits subfrontal access, calcification, and blend in to neural structures such as the
with further drainage of the arachnoid cisterns, including the infundibulum and hypothalamus. In addition, many critical
medial part of the Sylvian fissure, en route to the tumor. Once perforators are at risk during capsule dissection. No vessel
should be sacrificed without a thorough inspection of its course preserve vision. They can be performed purely stereotactically,
to ensure that it does not supply a neural structure, particularly using a frame or frameless techniques, or with endoscopic
important as many vessels supplying the tumor in an en passant assistance. If the cyst presents within the third ventricle, and
fashion may also go on to enter, for example, the hypothalamus the lateral ventricles are large enough, endoscopic fenestration,
or optic chiasm. If portions of the tumor are densely adherent with placement of a catheter under direct vision, is the method
to, or indistinguishable from, the hypothalamus, the authors’ of choice. This has also been described in the context of small
practice is to leave this untouched for adjuvant treatment ventricles, using image guidance to facilitate optimal ventricu-
thereafter with the aim of preserving endocrine and (especially) lar entry and dilatation of the ventricles using small volumes
hypothalamic function as previously described. Once maximal of saline.50 The cyst wall is often thick and firm and not easily
safe resection has been achieved, repair of the dura, fixation of punctured, particularly in a blind, image-guided technique,
the bone flap, and scalp closure are achieved using standard and care must be taken to ensure that the catheter does not
methods. We do not routinely use external lumbar drainage slide off the wall and end in a suboptimal position. Cranio-
except in procedures where concern about postoperative CSF pharyngioma fluid is usually viscous, and a large bore catheter
leak is high, such as in some revisional or postradiotherapy with large side holes is preferred to avoid blockage. Potential
cases. risks of this technique include hardware infection or blockage,
and strict aseptic technique must be employed whenever the
Intraventricular and Extraventricular reservoir is tapped. Occasionally, the cyst may be multilocu-
Craniopharyngiomas lated without communication between the locules of fluid. In
these cases, it is usually preferable to create communication
For these tumors, planning of approach is based again on the using endoscopic techniques, allowing drainage through a
location of the remnant hypothalamic tissue, which is usually single catheter and reservoir. If this is not possible, rarely,
situated around the midpoint of the craniopharyngioma. multiple catheters may be required.
Therefore these are best approached anteriorly via the lamina Aspiration of large craniopharyngioma cysts often changes
terminalis of the third ventricle following a subfrontal approach. the anatomic relationships of the tumor with surrounding
In fact, the lamina terminalis so encountered usually consists structures. Reimaging after aspiration allows reevaluation of
of the anterior tumor capsule. Opening the space between the hypothalamic involvement, and tumors previously deemed
anterior communicating complex and the optic chiasm affords inoperable may then appear separate from the hypothalamus
good access for piecemeal debulking of these craniopharyngio- and therefore resectable51 (Fig. 12.4).
mas. An exception may be larger tumors with extension into Appropriate placement of a catheter within a cyst also allows
the superoposterior segment of the third ventricle, which may aspiration during radiotherapy, when cysts often expand. This
be insufficiently visualized with approaches via the lamina can be done with stereotactic guidance, but it is often more
terminalis. An alternative in these cases may be a transcallosal straightforward to do using endoscopic visualization (Fig.
approach. An advantage of this approach is that it allows the 12.5). It also permits the use of intracystic therapy, usually at
surgeon to begin tumor dissection at the superior pole of the a later stage.52,53
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 Perioperative Management and
ventricle, the transcallosal approach can be used to reach the Potential Complications
suprasellar components. It is important to remember, however,
that this is primarily a midline approach and its lateral reach Some postprocedural risks are general to all surgical approaches
remains limited. to craniopharyngioma, particularly endocrine complications
such as hypopituitarism and diabetes insipidus, whereas some
Intraventricular Craniopharyngiomas are associated with specific techniques. Optimal perioperative
management involves recognizing these risks and minimizing
As described previously, pure intraventricular craniopharyn- them with judicious use of appropriate strategies.
gioma is rare. As it sits entirely above the thinned hypothala-
mus, approaches from below are contraindicated. Access is Infection
afforded via either the lamina terminalis or the foramen of
Munro based on the individual topography of the tumor. Like all invasive procedures, surgery for craniopharyngioma
introduces the risk of bacterial contamination with resulting
Cystic Craniopharyngioma surgical site infection or meningitis. Preoperatively, swabs
should be taken of skin and nasal mucosa to identify carriage
Predominantly cystic craniopharyngioma, typically seen in of resistant organisms such as methicillin-resistant Staphylo
children,49 may be managed by insertion of a drainage catheter, coccus aureus (MRSA), and decolonization should be carried
attached to a subcutaneous reservoir (such as an Ommaya), out if feasible within the urgency of surgery. It is now routine
into the tumor cyst (Fig. 12.3). Cyst drainage procedures may to use systemic (intravenous) antibiotics at the onset of all
need to be undertaken acutely to control hydrocephalus and types of neurosurgical procedures; the exact agent chosen will
[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 means that the resection risks vasospasm, thrombosis, or direct
preoperative swabs. If a patient is carrying an organism resis- injury, which can lead to cerebral ischemia or infarction.
tant to standard prophylaxis, a different antibiotic must be Reducing the risk of this devastating complication starts in the
employed. Most units carrying out transsphenoidal, especially preoperative planning stage, with recognition of possible vessel
extended endoscopic resection, institute a prolonged prophy- involvement, and, if indicated, vascular imaging to delineate
laxis of up to 5 to 7 days of antibiotic administration. In fact, vessel position to predict areas of dissection that are at particu-
with use of appropriate pre-, intra-, and postoperative precau- larly high risk. Intraoperatively, micro-Doppler probes may
tions, infection rates with extended endoscopic transsphenoidal help to detect vessels during dissection. It is usually prudent
techniques are no higher than that for transcranial surgery.45,54 to leave portions of tumor highly adherent to vessel walls in
situ to be dealt with by adjuvant treatment rather than to
Neurovascular attempt complete removal with injury to the adventitia. Post-
operatively, a neurologic examination should be carried out as
The location of craniopharyngioma in the suprasellar region, soon as possible after recovery from general anesthesia to assess
often encroaching on or even adherent to the circle of Willis, any potential neurologic deficit. If any concerns are identified,
[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. should be performed, and if vasospasm is confirmed, treatment
Neurovascular injury causing ischemic stroke has been reported with hypervolemia and hypertension should be instituted,
in 2.9% of transcranial series and 2.7% of endoscopic trans- which has been shown to be effective in postcraniopharyngi-
sphenoidal series.46 In addition to direct intraoperative injury, oma surgery vasospasm.57
postoperative fusiform dilatation55 and vasospasm56 have been
reported. Although the former appears to be primarily a radio- Ophthalmic
logic phenomenon without clinical sequelae, vasospasm can
potentially be a source of delayed ischemic neurologic deficit. Many patients with craniopharyngioma present with signifi-
If suspected, appropriate perfusion imaging (CT or MR) cant visual impairment and established optic neuropathy. This
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, hypophyseal arteries and the pial network of vessels found on
with resulting postoperative visual loss, during surgical the superior aspect of the structure. Approaches that transgress
approaches to craniopharyngioma. As outlined earlier, all the lamina terminalis may have higher risks of chiasmal infarc-
patients should have a detailed ophthalmic examination, tion than those that use an inferior corridor such as the trans-
including formal perimetry, documented prior to surgery. sphenoidal route, where direct decompression of the optic
Intraoperatively, efforts should be made to avoid retraction or apparatus from below precedes surgical manipulation of the
cautery on the optic apparatus itself. Great care should also be capsule above. A large meta-analysis of craniopharyngioma
taken to preserve arteries supplying the chiasm, which may surgical series41 found a rate of around 13% of postprocedural
be at risk during dissection, such as the paired superior visual deterioration due to reduced acuity or field deficit,
compared to an improvement in almost 50% in patients with of postcraniopharyngioma surgery DI varies widely, presum-
a preexisting deficit. Ophthalmoplegia due to injury to cranial ably due to differing definitions, with rates as low as 4%
nerves running in the adjacent cavernous sinus is also a poten- and as high as 100% described in the literature.41,46,60 Most
tial complication, but most series agree that this is much rarer neurosurgical units have their own protocols for monitoring
than field or acuity problems, with a rate of less than 1%. patients following surgery where DI is a common risk, but
Postoperatively, patients should have a repeat ophthalmic all involve careful measurement of fluid balance (often using
assessment to allow comparison to the preoperative baseline. an indwelling urinary catheter) along with recording of urine
Acute visual loss in the immediate postoperative period sug- specific gravity or osmolality in combination with frequent
gests the possibility of a mass lesion such as a hematoma and blood sampling for sodium and osmolality. Exogenous desmo-
should trigger urgent radiologic examination and surgical pressin is administered only when certain criteria are reached,
reexploration. usually evidence of biochemical dehydration with elevated
serum sodium/osmolality in combination with inappropri-
Endocrine ately dilute urine. In general, although many patients require
desmopressin in the early postoperative period, long-term
Key structures for neuroendocrine function are at risk in any rates of desmopressin-dependent DI have been estimated at
craniopharyngioma operation, including the hypothalamus, around 70% (transcranial surgery) and 24% (transsphenoidal
infundibulum, stalk, and both anterior and posterior pituitary surgery).41
glands. As discussed earlier, preoperative assessment by an Hypothalamic injury has been recognized as a major deter-
endocrinologist is mandatory to detect and document preexist- minant of poor outcome and can result in a number of clinical
ing deficits. Attempting to preserve endocrine function begins symptoms, classically obesity, hyperphagia, and behavioral dis-
at the preoperative stage with a close examination of the radio- turbance (such as rage), but also memory impairment, loss of
logic imaging to assess involvement of the hypothalamopitu- temperature homeostasis, and disturbance of the normal sleep-
itary axis and review of the endocrine work-up. As most wake cycle.22,30 Profound metabolic alterations occur, with
patients already demonstrate endocrine deficits at presentation, rapid weight gain over the first postoperative year, abnormal
and considering that multiple deficits are almost always accrued energy management, and increased lipogenesis. This is poorly
throughout the course of this chronic disease, sacrifice of resid- responsive to diet, physical activity, and pharmacologic thera-
ual endocrine function, usually related to expected operative pies.61,62 About a third of children with craniopharyngiomas
damage of an adherent and atrophic pituitary stalk, may be demonstrate hypothalamic disturbance at presentation.63 The
acceptable if complete resection of the tumor can be achieved highest risks to operative hypothalamic injury include hypo-
without hypothalamic injury. Hormone replacement does not, thalamic symptoms at presentation, large tumor size, involve-
however, restore normal quality of life if the hypothalamus is ment of the third ventricle, obstructive hydrocephalus, the
injured. Intraoperatively, sharp dissection is preferred when pursuit of radical resection in tumors adherent to the hypo-
removing tumor from midline structures, with minimal (ideally thalamus, and surgery posterior to the mammillary bodies.30,64,65
no) traction or electrocautery. The transsphenoidal route can Due to the somewhat nebulous nature of some of these symp-
still be used when the pituitary gland is ventral or anterior to toms, rates of hypothalamic dysfunction can be difficult to
the craniopharyngioma, as mobilization of the gland or a verti- obtain but have been estimated at between 30% and 60%,
cal incision within it is still associated with good preservation with no differences observed between transcranial and trans-
of endocrine function.58 sphenoidal approaches.22,30,41,66 If a hypothalamus-preserving
Injury to the anterior pituitary gland can result in deficiency strategy of planned subtotal resection is adopted, the rate
of one or more of the hormones produced therein, up to and of hypothalamic morbidity is significantly reduced; when
including complete panhypopituitarism. Rates of the latter can combined with adjuvant radiotherapy, tumor control is not
be as high as 50% in some series, and they appear to be higher compromised.22,49,67
following transcranial rather than transsphenoidal approaches.46
Levels of LH/FSH appear to be most commonly deficient after Cerebrospinal Fluid–Related Complications
surgery (a reduction in up to 90% of patients), followed by
prolactin, ACTH and TSH (all reduced in about 50%).59 Rates of hydrocephalus at presentation vary from 5% to 40%
Perioperative management is undertaken in close collaboration (Elliott) and are usually related to large tumor components
with endocrinologists, but most patients will receive supple- within the third ventricle. Tumor resection or cyst drainage
mentary exogenous steroids at induction of anesthesia and in usually resolves hydrocephalus, but around 10% to 15% of
the early postoperative period, at least until confirmation of patients still have postoperative hydrocephalus requiring CSF
endogenous steroid production by an early morning, predose diversion surgery.68 The incidence of CSF leak seen after trans-
serum cortisol level on the second postoperative day. After the sphenoidal, particularly extended endoscopic, surgery has been
patient has fully recovered from surgery, the endocrinology a concern, particularly due to high rates reported in initial
team usually electively undertakes a complete assessment of all experience with the technique. However, with improvements
anterior pituitary hormonal function. in anterior skull base reconstruction such as the use of vascular-
Posterior pituitary injury can result in diabetes insipidus ized nasoseptal flaps, rates of postoperative CSF rhinorrhea
(DI) due to a deficiency of ADH. The reported incidence have been reduced to 5% or lower.46,69,70
Adjuvant and Novel Therapies exposure to surrounding neural tissue. It achieves this using
frame-based stereotaxy and computer-aided dose planning.
Traditionally, adjuvant therapies (predominantly radiation The predominant drawback is the lack of suitability for larger
therapy) were viewed as second-line treatment for residual or (>3.5 cm diameter) lesions due to the loss of conformality. It
recurrent craniopharyngiomas not amenable to surgical resec- has been used with some success in appropriately selected
tion. As the philosophy of managing this disease has evolved, craniopharyngioma.77
in conjunction with technical advances allowing more confor-
mal radiation delivery techniques reducing irradiation to Proton Beam Therapy
neural structures (such as stereotactic radiosurgery and proton
beam therapy), radiation therapy has been used more fre- Proton beam therapy (PBT) delivers positively charged protons
quently as an upfront treatment option following, for example, to the target. Although the efficacy and dose of treatment are
intentional partial resection or cyst drainage. There has also similar to conventional radiotherapy, PBT has the advantage
been increased interest in the use of intracavitary agents, of using the physical characteristics of charged particles—a
instilled directly into the craniopharyngioma cyst. Early expe- sharp drop-off in dose called the Bragg peak just before they
rience was with brachytherapy with radioisotopes, although stop, to greatly improve conformality and reduce the irradia-
recently chemotherapeutics such as bleomycin and interferon tion of critical surrounding structures. As protons stop abruptly
have been used. after the Bragg peak, the exit dose, which conventional radio-
therapy delivers as the beam exits the body beyond the target,
Conventional Radiotherapy is reduced. A range of protons with varying energy ensures that
all of the dose is deposited within the tumor tissue, over a
Conventional radiotherapy uses fractionation to deliver a spread-out Bragg peak. The literature suggests craniopharyn-
therapeutic dose to the target while attempting to minimize gioma control rates of 90% or better with PBT,39,78 although
irradiation to surrounding tissues. Modern techniques utilize the relative novelty of the technology means that long-term
mask-based immobilization and computer-assisted, image- follow-up is awaited.
guided planning. Dosing for craniopharyngioma is usually
in the region of 50 to 60 Gray, which is fractionated in 25 Intracavitary Therapy
to 30 separate treatments. The irradiated volume typically
includes an additional 5 mm to the gross tumor volume, Due to the cystic nature of the majority of craniopharyngio-
to constitute the clinical target volume. Co-registration of mas, there has been long-standing interest in the instillation of
MRI and CT scans ensures that any residual calcification is various agents into the cystic cavity to reduce or control tumor
incorporated within the gross tumor volume. Regular surveil- growth. Intracavitary therapy is reserved for tumors that are
lance imaging and planning modifications are necessary to monocystic or have a large dominant cyst. The cavity is accessed
ensure that any cyst enlargement, well known to occur during using a catheter connected to a reservoir (such as an Ommaya
the course of radiotherapy, is included within the irradiated reservoir), which can be placed using open, endoscopic, or
volume.71 stereotactic (frame-based or frameless) techniques. Once the
There is good evidence that doses of >50 Gray are reliable catheter has been sited, a “leak” test, performed by instillation
in achieving tumor control in the majority of patients.72–76 The of a contrast agent followed by imaging (usually CT), is per-
major potential complication of treatment is injury to the optic formed to ensure that the cyst is isolated from the subarach-
apparatus, which is usually quoted as having a tolerance of 8 noid space and that treating agent will not spill into the CSF
to 12 Gray. Other risks include radionecrosis, swelling, endo- or brain parenchyma.
crine dysfunction, and deleterious effects on cognition. The Agents that have been used for intracavitary therapy can
latter complication is exacerbated by young age at time of be divided into radioactive isotopes and chemotherapeu-
treatment, particularly relevant due to relative frequency of tics. Radioisotopes have included phosphorus-32 (32P),
craniopharyngioma in childhood. yttrium-90 (90Y), and rhenium-186 (186Re). The chemo-
Intensity modulated radiotherapy (IMRT) is frequently therapeutic agents that have been described are bleomycin and
used for craniopharyngiomas. The technique involves “sculpt- interferon-α. There are case series reporting efficacy for all of
ing” of the high-dose radiation exposure to the target by the these agents in controlling craniopharyngioma, but concerns
use of multiple small beams from different directions, delivered about toxicity persist, and level 1 evidence is not available to
by a multileaf collimator. This reduces irradiation to adjacent make strong recommendations regarding treatment.79,80 It is
structures such as the hippocampus, brainstem, optic appara- likely that, at least for the moment, intracavitary therapies
tus, and cochlea. will remain a second-line treatment for recurrent or inoper-
able cystic lesions. Interferon-alpha 2b is currently considered
Stereotactic Radiosurgery a safe option with minimal neurologic risk. Typically, patients
receive 3 million international units of interferon-alpha 2b
Stereotactic radiosurgery (such as Leksell Gamma Knife) is three times a week for 4 weeks. Each administration is pre-
capable of delivering high-dose radiation to a precisely confor- ceded by aspiration of the cyst fluid. In the largest series of
mal target in a single fraction with only minimal radiation its use in pediatric craniopharyngioma published to date, 60
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 The main predictor of poor outcome in terms of quality of life
27.7 mL to 9.6 mL52 (Fig. 12.6). is hypothalamic involvement. The extent of resection and age
at diagnosis, perhaps counterintuitively, do not predict long-
Long-Term Outcomes term quality-of-life outcomes. It is the nature of these long-
term results that has caused neurosurgical and oncologic
As discussed earlier, the benign histologic nature of craniopha- communities to reevaluate management strategies in this group
ryngioma is not reflected in its clinical behavior, and it is of patients.
increasingly realized that patients treated successfully on neu- The extent of tumor control after various interventions,
rosurgical or oncologic criteria go on to lead lives impaired by particularly combinations of surgery and radiotherapy, has
endocrinologic, hypothalamic, and intellectual dysfunction.81 received attention. In a review from the Surveillance,
Epidemiology, and End Result Program database, overall sur- that are not fully resected surgically. Small recurrent cranio-
vival (OS) at 1 and 3 years for a cohort of 644 patients with pharyngiomas have been considered an appropriate target for
craniopharyngioma recruited between 2004 and 2008 were stereotactic radiosurgery89; in a large series involving 137
91.5% and 86.2%, respectively.82 In a large meta-analysis patients, 54% showed shrinkage of the tumor, 16.5% showed
reviewing 442 patients, adults and children, 2- and 5-year continued tumor growth, and in 8% the cysts enlarged.38
progression-free survival (PFS) in those who underwent gross
total resection (GTR) (81% and 67%) and subtotal resection Conclusion
(STR) with radiotherapy (91% and 66%) were similar, as were
the 5- and 10-year OS rates (98% and 98%, and 99% and Craniopharyngioma remains a rare but uniquely challenging
95%, respectively).37 tumor to treat. Optimal management requires multidisci-
Another study reviewing 109 children also found no differ- plinary teams composed of the neurosurgeon, oncologist, oph-
ence between GTR and STR with radiotherapy, with 5-year thalmologist, and endocrinologist, among others. Increasing
PFS at 77% and 73%, respectively; STR alone was, however, realization of the dismal long-term quality of life suffered by
significantly worse than STR with radiotherapy, with 5-year patients treated with aggressive early surgery has caused the
PFS at 73% and 43%, respectively.35 A prospective surgical pendulum to swing back toward more limited surgery that
multicenter study that recruited pediatric patients from central spares the hypothalamus, with adjuvant radiotherapy in many
Europe reported a 3-year PFS of 46%; however, children who units. Consensus on the best strategies of management for both
also underwent radiotherapy during the period improved this primary and recurrent craniopharyngioma has not been
result to 88%.83 This study also demonstrated that children reached and the ideal approach remains controversial.
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 Selected Key References
Cavalheiro S, Di Rocco C, Valenzuela S, et al. Craniopharyngiomas:
Recurrence intratumoral chemotherapy with interferon-alpha: a multicenter pre-
liminary study with 60 cases. Neurosurg Focus. 2010;28:E12.
Management of recurrence remains a major issue in craniopha- Clark AJ, Cage TA, Aranda D, et al. Treatment-related morbidity and
ryngioma. Just as primary management is controversial, there the management of pediatric craniopharyngioma: a systematic review.
is even less evidence to guide decision making in recurrent J Neurosurg Pediatr. 2012;10:293-301.
lesions. There is disagreement in the literature about predictors Clark AJ, Cage TA, Aranda D, et al. A systematic review of the results
of recurrence. Although some have shown that recurrence is of surgery and radiotherapy on tumor control for pediatric cranio-
predicted by extent of resection,84 other studies have not dem- pharyngioma. Childs Nerv Syst. 2013;29:231-238.
Elliott RE, Jane JAJ, Wisoff JH. Surgical management of craniopharyn-
onstrated a clear relation85 There is also evidence that radio-
giomas in children: meta-analysis and comparison of transcranial and
therapy reduces recurrence risk.86 transsphenoidal approaches. Neurosurgery. 2011;69:630-643, discus-
Recurrence is detected by a combination of clinical and sion 643.
radiologic follow-up. Most units mandate regular ophthalmic Hasegawa T, Kobayashi T, Kida Y. Tolerance of the optic apparatus in
and endocrine reviews and a schedule of MRI scanning for at single-fraction irradiation using stereotactic radiosurgery: evaluation
least 5 to 10 years after diagnosis. Much later recurrences have in 100 patients with craniopharyngioma. Neurosurgery. 2010;66:
been reported,87 and many advocate lifelong follow-up for 688-694, discussion 694–5.
patients, particularly those with known residual lesions. Leng LZ, Greenfield JP, Souweidane MM, et al. Endoscopic, endonasal
When recurrence does occur, management strategies echo resection of craniopharyngiomas: analysis of outcome including
those of primary tumors; surgical resection is the preferred extent of resection, cerebrospinal fluid leak, return to preoperative
option, particularly if the tumor is solid, with the aim of productivity, and body mass index. Neurosurgery. 2012;70:110-123,
discussion 123–4.
maximal tumor removal while preserving hypothalamic func-
Puget S, Garnett M, Wray A, et al. Pediatric craniopharyngiomas: clas-
tion (if present). In a study evaluating 18 out of 97 patients sification and treatment according to the degree of hypothalamic
whose tumors progressed after limited surgery and radiother- involvement. J Neurosurg. 2007;106:3-12.
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alone had a low rate of long-term success and optimal manage- our evidence-based approach to management. Childs Nerv Syst.
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CHAPTER 12 Craniopharyngiomas 218.e1
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Craniopharyngiomas: Clinic Al Pearls

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Craniopharyngiomas: Clinic Al Pearls

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Pediatric Neurosurgery

Introduction on its merits by a multidisciplinary team to achieve the

Embryology sometimes therefore called intraventricular and extraventricular

References 22. Puget S, Garnett M, Wray A, et al. Pediatric craniopharyngiomas:

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Craniopharyngiomas: Clinic Al Pearls

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Craniopharyngiomas: Clinic Al Pearls

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Craniopharyngiomas: Clinic Al Pearls

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Pediatric Neurosurgery

Introduction on its merits by a multidisciplinary team to achieve the

Embryology sometimes therefore called intraventricular and extraventricular

References 22. Puget S, Garnett M, Wray A, et al. Pediatric craniopharyngiomas:

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References 22. Puget S, Garnett M, Wray A, et al. Pediatric craniopharyngiomas: