Handbook of Pediatric Neurosurgery

computed tomography (CT) imaging has an
adjunct role in delineating tumor-associated calci-
fications and cysts, as well as the ventricular sys-
tem, serial monitoring of the tumor substance
itself preferably utilizes MRI. Imaging typically
includes the entire cerebrum as well as focused
views of the orbits to evaluate the optic nerves.
Frequently, OP-HGs are hypointense or isointense
on T1-weighted imaging and hyperintense on
T2-weighted imaging. Gadolinium contrast admin-
istration will demonstrate a variable enhancement
pattern for these tumors. A varying degree of solid
and cystic components may also be seen. Gener-
ally, OP-HGs isolated to the optic nerves will dem-
onstrate nerve expansion as well as increased
nerve tortuosity or optic nerve sheath enlarge-
ment (Fig. 15.1). Importantly, the finding of
nerve sheath enlargement in and of itself may be
present in other conditions in which elevated
intracranial pressure is present. Tumors extending
posteriorly into the optic chiasm may also demon-
strate enlargement of this structure ( Fig. 15.1).
Expansion of these neural structures is demon-
strative of the di use properties of OP-HGs;
however, in some cases, significant exophytic com-
ponents may extend into the suprasellar space,
causing obstructive hydrocephalus due to third
ventricular compression ( Fig. 15.2). In addition
to bulky exophytic lesions, tumor-associated cysts
can cause a similar obstructive process, necessitat-
ing cyst drainage and aspiration in some cases. In
some instances, especially during presurgical plan-
ning stages, vascular imaging with MR or CT
angiography can be helpful in demarcating critical
vascular structures that may be encompassed by
tumor.
Various classification system s have been used
to describe optic pathway tum ors. Although
these categorization schem es m ay be useful for
research purposes, they play less of a role in the
clinical m anagem ent and prognostication of OP-
HGs. For example, the Dodge classification sys-
tem ( Fig. 15.3) di erentiates tum ors between
three categories based on anatom ic location,
whether there is involvem ent of the optic nerve
(Dodge I), optic chiasm (Dodge II), or postchias-
m atic (Dodge III). More detailed anatom ical clas-
sification system s, such as the m odified Dodge
system , are also available.
15.4 Treatment
Unfortunately, given the lack of a well-defined nat-
ural history of OP-HGs and the heterogeneity
present within this disease process, treatment
options must be tailored to each individual patient
based on age, comorbidities, presentation, dura-
tion of symptoms, anatomy, and other factors. In
most cases, asymptomatic or incidentally discov-
ered lesions are serially monitored over time.
However, in cases with progressive symptomatol-
ogy and lesion growth, surgery, chemotherapy,
radiation therapy (RT), or a combination of
these interventions should be considered. In the
majority of cases, treating physicians are part of a
Fig. 15.1 Optic pathway tumor in a
patient with neurofibromatosis type 1
(NF1). (a,b) Axial T2-weighted mag-
netic resonance (MR) imaging dem-
onstrating right optic nerve
enlargement (arrowhead), increased
nerve tortuosity, and a dilated right
optic nerve sheath, consistent with an
optic pathway glioma. (c) Coronal
T2-weighted MR image demonstrating
expansion of the optic chiasm
(arrowhead), indicative of tumor
extension into this structure.
Tumor
108

multidisciplinary group that includes neurosur-
geons, neuro-ophthalmologists, oncologists, endo-
crinologists, and others.
15.4.1 Surgery
Compared to other neurosurgical diseases, the role
of surgery for OP-HGs is limited. For example, even
diagnostic biopsy is unnecessary when a classically
appearing lesion isolated to the optic nerve is
identified in a patient with NF1. In many such
cases, chemotherapy may be initiated in sympto-
matic patients without a tissue diagnosis. Espe-
cially relevant to the limited surgical role in this
disease are the critical surrounding structures of
these lesions. Given the critical structures sur-
rounding such tumors and the neural structures
within which they arise, the risks of surgical
intervention must be weighed strongly against
alternate treatment modalities or, simply, serial
monitoring.
As mentioned, identification of a classically
appearing OP-HG radiographically may not neces-
sitate tissue diagnosis with surgical biopsy. Certain
features, however, such as rapid tumor growth or
symptom progression, or worsening hydrocepha-
lus, may warrant surgical intervention. The bene-
fits of surgical debulking include facilitation of
chemotherapeutic intervention as well as relief of
obstructive hydrocephalus. Given the indolent
nature of OP-HGs, emergent intervention is rarely
necessary. In some instances, urgent CSF diversion
is needed to treat obstructive hydrocephalus, or
malfunction of already shunted patients may war-
rant immediate intervention. Other indications for
surgery include the need for a diagnosis, especially
in those with atypical imaging features or in older
children with rapid neurological decline. A tail-
ored, individualized treatment approach should be
Fig. 15.2 Suprasellar extension of
optic pathway tumor. (a) Axial and
(b) coronal T1-weighted with contrast
MR images demonstrating lobulated,
cystic suprasellar extension of an optic
pathway tumor. (c) Axial T2-weighted
MR image demonstrating loculated
cystic components of an optic pathway
tumor causing mass effect in a child
with NF1. (d) Sagittal T1-weighted MR
with contrast demonstrating suprasel-
lar extension of optic pathway tumor
causing third ventricular effacement
and obstruction.
Fig. 15.3 Dodge classification system. Illustration de-
picting optic pathways and classification zones based on
the region of tumor expansion. (Reproduced with
permission from Thieme eNeurosurgery, 2016.)
Hypothalamic and Optic Pathway Tumors
109

created for each patient. Growing, exophytic
lesions are more easily debulked than di use,
expansile lesions of the optic pathways. In children
with growing tumors isolated to an orbit in which
there is no preserved vision, surgical intervention
can prevent tum or invasion of the optic chiasm ,
which could prevent deterioration of vision in
the contralateral, functional eye. This treatm ent
plan m ay be especially relevant in patients who
have already failed a trial of chem otherapy who
also dem onstrate evidence of tum or progression
toward the chiasm . In a child w ith severely
a ected vision and an optic nerve tumor causing
pain or proptosis, surgical treatm ent m ay aid in
alleviating disfiguration and pain.
Surgical approaches include a standard pterional
craniotomy in order to obtain access to the ante-
rior skull base and orbital roof, with or without
use of an orbital unroofing procedure. The optic
nerve is rem oved close to but not directly at the
chiasm so as to not injure crossing fibers from
the contralateral eye. Alternative or ancillary
approaches include an orbital approach alone,
which may be warranted when the goal of
surgery is enucleation. As m any tum ors are infil-
trative and expansile w ithin normal neural struc-
tures, gross total resection can pose a threat to
remaining visual function and thus is not fre-
quently the surgical goal. For example, cytoreduc-
tive debulking can alleviate CSF obstruction and
restore ventricular flow. Lesions of the suprasellar
space can also be reached through a frontotempo-
ral craniotomy using a subfrontal or transsylvian
approach, as well as transcortical, transventricu-
lar, or interhemispheric approaches.
15.4.2 Chemotherapy
The current mainstay of treatment for OP-HGs is
with chemotherapy. Given the potential morbidity
of surgical intervention and the unlikelihood of
achieving total tumor extirpation without causing
visual harm or other adverse events, as well as the
unwanted risks of RT in the developing child, the
primary modality for intervention is with chemo-
therapy.
Several studies have evaluated the role of che-
motherapy in children with low-grade tumors and
OP-HGs. Packer and colleagues determined that
a combination of vincristine and carboplatin
resulted in a progression-free survival (PFS) of
around 75% at 2-year follow-up in children with
low-grade gliomas.4 Other studies evaluating plat-
inum-based therapy demonstrated good response
rates to this treatment, with toxicity occurring in
the form of transient neutropenia and thrombocy-
topenia, as well as rare allergic reactions.5,6 Other
regimens include weekly vinblastine treatment for
low-grade pediatric gliomas, with close to 95%
5-year overall survival (OS) and 53% PFS, with
treatment being well tolerated and demonstrating
increased PFS in NF1 patients compared to non-
NF1 patients.7,8 Such treatments may be especially
useful as second-line therapy after prior chemo-
therapeutic agents have been attempted.
Other studies have also compared the e ective-
ness of carboplatin and vincristine to a combina-
tion of thioguanine, procarbazine, lomustine, and
vincristine (TPCV) in pediatric low-grade gliomas,
demonstrating an OS between the groups of 86%
and similar event-free survival (EFS), but with a
trend toward improved EFS in the TPCV group.9
While the majority of chemotherapeutic interven-
tions have only a modest, if any, e ect on visual
outcomes, recent evidence has suggested that bev-
acizumab therapy may result in a more robust res-
ponse in improved visual outcomes in patients
with OP-HGs.10 Examples of targeted therapy, such
as BRAF inhibitors, have demonstrated some e -
cacy in children with low-grade gliomas, and their
utility in children with OP-HGs remains to be eval-
uated.
15.4.3 Radiation Therapy
As we have entered the chemotherapy era of treat-
ment for OP-HGs, the role of RT has been limited.
In fact, typical treatment models would attempt
various forms of chemotherapy prior to the initia-
tion of RT in an attempt to delay its potential
adverse e ects. For example, optic neuritis, vascul-
opathy, neurocognitive delay, and endocrine and
hypothalamic disturbances are all risks associated
with RT, especially in young, developing children.
Additionally, the possibility of secondary neoplasia
exists with RT, especially in NF1 patients.11
In the prechemotherapy era, RT was utilized
more frequently as an adjunct treatment for non-
resectable OP-HGs. Reported 10-year OS and PFS
vary, from 80 to 94% and 65 to 100%, respec-
tively.12,13,14 Tumor response rates varied, but a
modest probability of radiographic response (25–
50%) has been shown in the first 24 to 60 months
following RT. Although radiographic response and
some improvement in vision was demonstrated in
these studies, long-term sequelae of RT included
significant endocrine and neurological abnormal-
ities. Overall, current treatment algorithms would
Tumor
110

categorize RT as a last resort option in children
with OP-HGs, after surgical and chemotherapeutic
intervention were first attempted.
15.5 Summary
Regardless of the need for intervention, overall
outcomes for children with OP-HGs are favorable.
Higher-grade lesions arising from the optic nerves
and pathways are extremely unusual in the pedia-
tric population and, when encountered, rapid
symptom onset and progression to death occur.
Given the variability of OP-HGs of low grade, the
natural history lacks concrete definition and
thresholds for treatment vary from institution to
institution. Treatment is often initiated when there
is tumor growth and progression of visual symp-
toms. Those with NF1 tend to demonstrate
improved outcomes in comparison to their non-
NF1 counterparts. OS for OP-HGs is greater than
90%, and surgery is often well tolerated when a
judicious approach is taken so as to not harm nor-
mal neural structures.
Overall, OP-HGs represent a heterogeneous pop-
ulation of tumors occurring in both NF1 and
non-NF1 patients that require a patient-centric,
individualized management approach. A multidis-
ciplinary team should serially evaluate patients
clinically and radiographically in order to maxi-
mize neurological function, while minimizing
adverse e ects of intervention.
References
[1] Aquilina K, Daniels DJ, Spoudeas H, Phipps K, Gan HW, Boop
FA. Optic pathway glioma in children: does visual deficit
correlate with radiology in focal exophytic lesions? Childs
Nerv Syst. 2015; 31(11):2041–2049
[2] El Beltagy MA, Reda M, Enayet A, et al. Treatment and
outcome in 65 children with optic pathway gliomas. World
Neurosurg. 2016; 89:525–534
[3] Gan HW, Phipps K, Aquilina K, Gaze MN, Hayward R,
Spoudeas HA. Neuroendocrine morbidity after pediatric
optic gliomas: a longitudinal analysis of 166 children over 30
years. J Clin Endocrinol Metab. 2015; 100(10):3787–3799
[4] Packer RJ, Ater J, Allen J, et al. Carboplatin and vincristine
chemotherapy for children with newly diagnosed progressive
low-grade gliomas. J Neurosurg. 1997; 86(5):747–754
[5] Listernick R, Charrow J, Tomita T, Goldman S. Carboplatin
therapy for optic pathway tumors in children with
neurofibromatosis type-1. J Neurooncol. 1999; 45(2):185–190
[6] Mahoney DH, Jr, Cohen ME, Friedman HS, et al. Carboplatin is
e ective therapy for young children with progressive optic
pathway tumors: a Pediatric Oncology Group phase II study.
Neuro-oncol. 2000; 2(4):213–220
[7] Bou et E, Jakacki R, Goldman S, et al. Phase II study of weekly
vinblastine in recurrent or refractory pediatric low-grade
glioma. J Clin Oncol. 2012; 30(12):1358–1363
[8] Lassaletta A, Scheinemann K, Zelcer SM, et al. Phase II weekly
vinblastine for chemotherapy-naïve children with progressive
low-grade glioma: A Canadian Pediatric Brain Tumor
Consortium Study. J Clin Oncol. 2016; 34(29):3537–3543
[9] Ater JL, Zhou T, Holmes E, et al. Randomized study of two
chemotherapy regimens for treatm ent of low-grade glioma
in young children: a report from the Children’s Oncology
Group. J Clin Oncol. 2012; 30(21):2641–2647
[10] Avery RA, Hwang EI, Jakacki RI, Packer RJ. Marked recovery of
vision in children with optic pathway gliomas treated with
bevacizumab. JAMA Ophthalmol. 2014; 132(1):111–114
[11] Sharif S, Ferner R, Birch JM, et al. Second primary tumors in
neurofibromatosis 1 patients treated for optic glioma:
substantial risks after radiotherapy. J Clin Oncol. 2006; 24
(16):2570–2575
[12] Cappelli C, Grill J, Raquin M, et al. Long-term follow up of 69
patients treated for optic pathway tumours before the
chemotherapy era. Arch Dis Child. 1998; 79(4):334–338
[13] Grabenbauer GG, Schuchardt U, Buchfelder M, et al.
Radiation therapy of optico-hypothalamic gliomas (OHG)–
radiographic response, vision and late toxicity. Radiother
Oncol. 2000; 54(3):239–245
[14] Tao ML, Barnes PD, Billett AL, et al. Childhood optic chiasm
gliomas: radiographic response following radiotherapy and
long-term clinical outcome. Int J Radiat Oncol Biol Phys.
1997; 39(3):579–587
Hypothalamic and Optic Pathway Tumors
111

16 Craniopharyngiomas and Other Sellar Tumors
David S. Hersh, Rafael U. Cardenas, Nir Shimony, and Mari L. Groves
16.1 Introduction
Primary tumors of the sellar and parasellar region
constitute 10% of all primary brain tumors in chil-
dren.1,2 Craniopharyngiomas are the most common
tumor found in this region, constituting 90% of
pediatric sellar and parasellar tumors. The remain-
ing 10% are comprised mainly of Rathke’s cleft cysts
and pituitary adenomas, although, rarely, germino-
mas, hamartomas, lipomas, teratomas, dermoid
cysts, and epidermoid cysts may be found as well.3,4
16.2 Craniopharyngiomas
● Incidence: 0.5 to 2 cases per million per year.5
● Bimodal age distribution, with peaks during the
first and second decades of life (typically
between the ages of 5 and 14 years) as well as
the fifth decade of life.6,7
● Approximately 30 to 50% of craniopharyngiomas
occur in pediatric patients.
● Craniopharyngiomas comprise up to 5% of
pediatric intracranial masses and up to 10% of
pediatric brain tumors.7,8
16.3 Rathke’s Cleft Cysts
● Rathke’s cleft cysts are most commonly found as
incidental lesions, and are found in 11 to 33% of
autopsies.5,9,10
● Asymptomatic cystic sellar or parasellar lesions
are found in 1.2% of children who undergo
magnetic resonance imaging (MRI).11
● Rathke’s cleft cysts account for only 9 to 10% of
sellar lesions that require surgical treatment.12
16.4 Pituitary Adenomas
● Incidence: 0.1 cases per million children per year.6
● Pituitary adenomas account for approximately
4% of pediatric intracranial tumors.13
● Pituitary adenomas are more common in females.
● Macroadenomas occur more commonly than
microadenomas.
● Pituitary adenoma subtypes:
– Prolactinomas occur most frequently (30–50%
of pediatric pituitary adenomas), particularly
during and after puberty.
– They are followed by adrenocorticotropic
hormone (ACTH)–secreting tumors, which are
more common prior to the onset of puberty,
and growth hormone (GH)–secreting
adenomas, which comprise 10 to 15% of
pediatric adenomas and occur most commonly
in infants.
– Only about 5% of pediatric adenomas are
nonfunctioning pituitary adenomas (which, in
contrast, constitute one-third of adenomas in
the adult population).6,14
16.5 Embryology and
Pathology
Rathke’s cleft cysts and craniopharyngiomas have
been described as similarly derived lesions that
likely represent di erent ends of the spectrum of
pathological progression.2 Rathke’s cleft cysts are
nonneoplastic cystic remnants of the Rathke
pouch that form in the region of the pars interme-
dia, and are characterized by columnar or cuboidal
epithelial walls surrounding mucoid material. Cra-
niopharyngiomas, too, are nonglial, extra-axial
tumors that develop from epithelial remnants of
the Rathke pouch or the craniopharyngeal duct.
Despite benign histological features, craniophar-
yngiomas are typically aggressive tumors that
produce significant neurological morbidity.7 Cra-
niopharyngiomas are characterized by two histo-
pathological subtypes: adamantinomatous and
papillary ( Fig. 16.1).
16.5.1 Adamantinomatous
Craniopharyngiomas
● Adamantinomatous tumors are the most
common subtype, particularly in the pediatric
population.
● These tumors are characterized by keratinized
cells that face a cyst lumen, and “wet” keratin
nodules consisting of desquamated epithelial
cells. The nodules may become calcified over
time.
● The cystic regions of adamantinomatous
craniopharyngiomas contain fluid with a “motor
oil” consistency, rich in cholesterol.
112

16.6 Papillary
Craniopharyngiomas
● Squamous papillary tumors occur primarily in
adults, and are rarely found in the pediatric
population.
● These tumors are characterized by a solid,
papillary architecture with minimal cysts.4
● Papillary craniopharyngiomas rarely undergo
calcification.
16.7 Clinical Presentation
Pediatric sellar and parasellar tumors present with
symptoms that reflect their relationship to critical
surrounding structures, including the pituitary
gland, infundibulum, hypothalamus, optic path-
ways, third ventricle, and cerebral vasculature.15 As
a result, symptoms associated with the endocrine,
limbic, and visual systems tend to predominate. The
anatomical relationship between the tumor and
adjacent structures is dictated by the degree of
intrasellar and/or suprasellar involvement, which, in
turn, determines the clinical presentation.
16.8 Craniopharyngiomas
● Approxim ately 95% of craniopharyngiom as
have a suprasellar component, w hile 30% also
extend into the anterior and m iddle cranial
fossae.4
● The most common complaints related to
craniopharyngiomas are nonspecific symptoms
of intracranial hypertension, particularly
headaches and nausea.
● Visual deficits occur in over half of patients,
although this tends to be well tolerated in
children.
Fig. 16.1 (a) Adamantinomatous craniopharyngioma with a highly distinctive pattern of epithelial maturation. (b) On
low-power view, the tumor consists of both solid and cystic epithelial components associated with chronically inflamed
fibrous stroma. (c) Another characteristic feature of adamantinomatous craniopharyngioma is the presence of nodules
of plump eosinophilic keratinized cells with ghosted nuclei. (d) On higher power view, tumor cells abutting the stroma
are palisaded, whereas centrally they readily dehisce to create a loose “stellate reticulum.” (Reproduced with permission
from Couldwell W. Craniopharyngiomas. In: Bernstein M, Berger MS, eds. Neuro-oncology: The Essentials. New York, NY:
Thieme; 2015:Fig. 35.1a–d.)
Craniopharyngiomas and Other Sellar Tumors
113

● Over half of patients also have signs and
symptoms of endocrine deficiency at the time of
presentation.
– GH is most commonly a ected, with low levels
found in 75% of patients. Gonadotropins—
follicle-stimulating hormone (FSH) and
luteinizing hormone (LH)—are deficient in 40%
of patients. ACTH- and thyroid-stimulating
hormone (TSH) are a ected in 25% of
patients.6,16
– Possible findings include growth failure,
delayed puberty, weight gain, and diabetes
insipidus.
● Frontal lobe dysfunction, memory deficits, and
obstructive hydrocephalus may occur as well.
16.9 Rathke’s Cleft Cysts
● Rathke’s cleft cysts are typically intrasellar cysts,
although the majority demonstrate suprasellar
extension as well.5
● Many Rathke’s cleft cysts are asymptomatic and
present as “incidentalomas”—lesions that are
identified during imaging that is performed for
unrelated reasons.
● Symptomatic Rathke’s cleft cysts typically
present with headaches, visual loss, and/or
endocrine insu ciency due to mass e ect.17
● In the pediatric population, Rathke’s cleft cysts
may also present with a variety of endocrine
signs and symptoms including delayed or
precocious puberty, amenorrhea, galactorrhea,
hypogonadism, growth retardation, and weight
gain.18
16.10 Pituitary Adenomas
● Pituitary adenomas are predominantly
intrasellar, and typically present with endocrine
symptoms.
● The particular presentation depends on the
adenoma subtype.
● Prolactinomas:
– In females, prolactinomas commonly present
with primary or secondary amenorrhea
(depending on the age of presentation), with
or without galactorrhea.6
– In males, macroadenomas occur more
frequently, resulting in headaches and visual
deficits.
– Growth arrest may occur in children and
adolescents regardless of gender.19
● ACTH-secreting adenomas:
– Growth failure is commonly the initial
presenting symptom, often resulting in a
delayed diagnosis.6
– Other features of Cushing’s disease
subsequently appear, including facial plethora,
striae of the abdomen and extremities,
osteoporosis, and impaired carbohydrate
tolerance. Muscular weakness, hypertension,
acne, hair grow th, precocious puberty, or,
alternatively, pubertal delay may be seen as
well.6
● GH-secreting adenomas:
– Although GH-secreting adenomas typically
present with acromegaly (due to hyperostosis)
in adults, pediatric patients may present with
gigantism due to delayed epiphyseal closure.6
16.11 Examination and
Diagnostic Workup
Patients with sellar or parasellar masses should
undergo a thorough evaluation prior to surgical in-
tervention. Neuroimaging, formal ophthalmologi-
cal studies, and a complete endocrine workup are
integral for medical and operative decision-mak-
ing, as well as to serve as a baseline for postopera-
tive evaluations. In patients with suprasellar and/
or frontal lobe involvement, a preoperative neuro-
psychiatric evaluation should be considered, as
well.
16.12 Neuroimaging
● Patients should undergo a head computed
tomography (CT) without contrast to assess for
calcification within the mass. Thin slices through
the sinuses and skull base may be indicated for
surgical planning if a transsphenoidal approach
is planned (Fig. 16.2).
● A magnetic resonance imaging (MRI) of the
brain with and without gadolinium is useful for
both diagnostic purposes and assessing the
relationship of the mass to its surrounding
structures. Dedicated pituitary protocols focus
on the sellar and parasellar regions and are
helpful in providing enhanced detail
(Fig. 16.3).
● Vascular imaging (either CT angiography or MR
angiography) is particularly helpful in cases of
craniopharyngiomas in order to map their
relationship with the adjacent circle of Willis.
Tumor
114

● Imaging pearls and pitfalls:
– During the first 6 to 8 weeks of life, the
adenohypophysis is globular and hyperintense
on T1-weighted imaging. It is only
subsequently that it flattens and becomes
isointense, while the neurohypophysis
remains hyperintense on T1-weighted
imaging.4
– Physiological pituitary hyperplasia may occur,
particularly in pubertal females. During
puberty, the pituitary gland may reach 10 mm
in height.4 This should not be mistaken for a
pituitary adenoma.
– In contrast to craniopharyngiomas and
pituitary adenomas, Rathke’s cleft cysts
typically do not demonstrate enhancement.
However, pseudoenhancement may occur
secondary to the normal enhancement of the
pituitary gland when the gland is stretched
around the cyst.4,18
16.13 Ophthalmological
Evaluation
● A full ophthalmological examination, including
formal visual field testing, should be performed.
● While younger children may not complain of
gradually progressive visual deficits, subtle
findings are often found on examination.
16.14 Endocrine Workup
● Laboratory studies should include a full
endocrine panel, including serum prolactin, TSH,
free thyroxine (T4), ACTH, morning fasting
cortisol, GH, insulinlike growth factor-1, FSH/LH
in females, and free testosterone in males. A
basic metabolic panel, serum osmolarity, and
Fig. 16.2 Imaging of a 48-year-old patient who had a
subtotal resection of a craniopharyngioma at age 5
and 43 years later experienced increasing headaches
and decline in vision. Computed tomography dem-
onstrated a suprasellar lesion with a calcified rim.
(Reproduced with permission from Couldwell W.
Craniopharyngiomas. In: Bernstein M, Berger MS, eds.
Neuro-oncology: The Essentials. New York, NY:
Thieme; 2015:Fig. 35.2.)
Fig. 16.3 T1 gadolinium-enhanced MRI shows a cystic craniopharyngioma on sagittal (a), coronal (b), and axial
(c) imaging.
Craniopharyngiomas and Other Sellar Tumors
115

urine specific gravity should be sent to assess for
diabetes insipidus.20
● A diluted prolactin level should be obtained due
to the hook e ect, which produces falsely low
levels in undiluted samples.
● If the morning fasting cortisol level is elevated, a
dexamethasone suppression test should be
performed. In patients with Cushing’s syndrome,
low-dose dexamethasone administered at
midnight does not suppress the serum cortisol
concentration the next morning. High-dose
dexamethasone administered at midnight
suppresses the morning cortisol level by more
than 50% in cases of Cushing’s disease, but not in
patients with ectopic ACTH-secreting masses.
● In patients with cortisol deficiency, an ACTH
stimulation test should be performed. Following
a baseline, fasting serum cortisol level obtained
in the morning, a synthetic form of ACTH—
cosyntropin—is administered. Serum cortisol
levels are then obtained 30 and 60 minutes later.
Cortisol levels rise significantly in patients with
secondary adrenal insu ciency (i.e., a sellar
mass causing hypopituitarism), but not in
patients with primary adrenal insu ciency (i.e.,
Addison’s disease).
● In patients with elevated GH levels, an oral
glucose tolerance test may be performed. Failure
to suppress GH levels, or alternatively a further
increase in GH levels, are associated with GH-
secreting pituitary adenomas.21
16.15 Classification Systems
● Several functional classification systems have
been developed to describe patients with
craniopharyngiomas. These classification
systems may be applied both pre- and
postoperatively.
● One of the simpler systems22 classifies patients
as:
– Class I: independent, with only mild hormonal
deficiencies.
– Class II: independent, with panhypopituitarism,
mild/moderate visual compromise, mild
neurological/cranial nerve deficits, and mild
psychological dysfunction.
– Class III: partially dependent, with serious
visual compromise, serious deficits, and
learning disorders.
– Class IV: fully dependent.
● A more recent, comprehensive classification
system, the Craniopharyngioma Clinical Status
Scale, assigns a score of 1 to 4 (ranging from
normal to extremely abnormal) across five
domains: neurological status, vision, pituitary
function, hypothalamic function, and
educational status.15
16.16 Nonsurgical
Management
● Many Rathke’s cleft cysts are “incidentalomas”—
asymptomatic lesions found on imaging.
– Patients with small (less than 10 mm),
asymptomatic Rathke’s cleft cysts, a normal
visual examination, and normal endocrine
findings are typically managed nonoperatively.
Such patients undergo observation with yearly
MRIs and clinical examinations.
– In some situations, asymptomatic patients
with larger lesions (greater than 10 mm) may
also undergo close observation, including
serial visual field testing.20
– Headache in the absence of visual or endocrine
symptoms is typically not considered to be an
indication for surgical resection.18
● Prolactinomas are typically treated medically,
with therapy consisting of dopamine agonists.
– Most prolactinomas respond well to dopamine
agonists including bromocriptine and
cabergoline—prolactin levels normalize and
the tumor shrinks in response to treatment.
– Cabergoline has a longer half-life than
bromocriptine, allowing it to be administered
once a week, which is particularly useful in the
pediatric population.23
– Patients who cannot tolerate medical therapy,
or whose tumors are refractory to medication,
are subsequently referred for surgical
resection.6
● In adults with GH-secreting adenomas,
somatostatin analogues such as octreotide and
lanreotide have been applied as options for
medical therapy. However, surgical resection
remains the primary form of treatment,
particularly in children, in whom there is little
experience with somatostatin analogues.6,23
16.17 Surgical Approaches
Sellar and parasellar masses may be accessed via a
craniotomy, a transsphenoidal approach, or both.
Traditionally, the transsphenoidal approach has
been utilized for intrasellar lesions, while a cra-
niotomy is reserved for suprasellar masses. As a
Tumor
116

result, Rathke’s cleft cysts and pituitary adenomas
are typically approached via the transsphenoidal
route. Conversely, the majority of craniopharyng-
iomas arise from the tuber cinereum in the supra-
sellar region, and are therefore approached via a
craniotomy. However, up to 30% of pediatric cra-
niopharyngiomas have a sellar component, and as
many as 15% have an infradiaphragmatic intrasel-
lar origin (suggested by sellar expansion on pre-
operative imaging), with the diaphragma sellae
serving as a barrier that separates the tumor from
the overlying suprasellar structures including the
optic chiasm, hypothalamus, and circle of Willis.
Infradiaphragmatic craniopharyngiomas are there-
fore suitable for transsphenoidal resection.23,24 In
contrast, supradiaphragmatic masses, or those that
cross the diaphragma, are adherent to the adjacent
neurological structures, which increases the risks
associated with placing traction on the tumor from
below.12
However, extended transsphenoidal
approaches, such as those that involve removal of
the tuberculum sellae, are being adopted in order
to access suprasellar locations, as well.3
● The transsphenoidal route may be reached via a
sublabial or endonasal approach.
– The sublabial approach is associated with
increased patient discomfort, including upper
lip and incisor paresthesias.3
– The endonasal approach is gaining broader
acceptance, despite initial hesitation due to the
small nostril and nasal cavity size of pediatric
patients.
● Transsphenoidal surgery may be accomplished
with the operative microscope, an endoscope, or
both.
– The microscope o ers the advantage of depth
perception by providing the surgeon with a
stereoscopic three-dimensional field.3
– The endoscope, on the other hand, provides a
wider field of view. Angled endoscopes also
allow the closer examination of di cult
angles.3,23 Newer three-dimensional
endoscopes o er improvements in depth
perception, as well.
● The transsphenoidal approach has a number of
advantages, including:
– Minimal brain retraction.
– Early decompression of the optic apparatus
while avoiding manipulation of the optic
nerves and chiasm.
– Less tissue trauma, less postoperative pain, and
shorter hospital stays.
● Prior to performing a transsphenoidal resection in
a pediatric patient, the degree of pneumatization
of the sphenoid sinus should be assessed.12
● Craniopharyngiomas treated via the
transsphenoidal approach tend to be smaller
than those resected via a craniotomy.12
● Significant suprasellar calcification and tumor
extension lateral to the carotid arteries have
been suggested as relative contraindications to
the transsphenoidal approach. When the goal of
surgery is gross total resection, adhesivity to the
adjacent structures and an increased risk of
vascular injury are challenging to manage
through the limited field of view a orded by the
transsphenoidal route.12 However, micro-
Doppler probes o er some degree of protection
against vascular injury.
● The transsphenoidal approach is associated with
a higher risk of cerebrospinal fluid (CSF) leak and
meningitis postoperatively. However, the rate of
CSF leak has gradually decreased with the
development of reconstructive skull base
techniques including but not limited to
multilayered closures and pedicled flaps (both
pericranial and nasoseptal).12
16.18 Surgical Technique
16.18.1 Transsphenoidal Approach
(Fig. 16.4)3,12,20,23,24,25
● Setup and equipment:
– A right-sided approach is used for right-
handed surgeons and/or for lesions that are to
the left of the midline.
– If an endoscope is used, a table-mounted
pneumatic arm may be used to hold the scope.
– Either fluoroscopy or neuronavigation, or both,
may be used in order to assist in identifying
the sphenoid ostia and guiding the surgical
trajectory.
– Micro-Doppler probes may be used in order to
identify the carotid arteries, in order to
minimize the risk of vascular injury.
– A lumbar drain may or may not be placed
preoperatively, depending on surgeon
preference. If used, the drain is generally
removed at the end of the case if a CSF leak is
not encountered.
● The nasal cavities are prepped with Betadine.
● An area of the abdomen is prepared in the event
a fat graft is needed.
Craniopharyngiomas and Other Sellar Tumors
117

● Oxymetazoline (Afrin)-soaked cotton pledgets
are placed in the nares bilaterally for 5 to
10 minutes.
● Using a handheld pediatric intranasal speculum
and a # 2 Penfield, the middle turbinate may be
mobilized laterally. Some surgeons prefer to
resect the middle turbinate for additional
exposure.
– A more aggressive “two-nostrils-four-hands”
technique involves bilateral maxillary
antrostomy, bilateral total
sphenoethmoidectomy, a posterior partial
septectomy, and a right partial middle
turbinate resection for maximal exposure
when the pathology is suprasellar.25
● The sphenoid ostia are identified and using the
# 2 Penfield, Kerrison punches, and pituitary
rongeurs, the anterior wall of the sphenoid sinus
is opened.
● A pneum atic drill w ith a 3-m m diam ond drill
bit is used to rem ove the anterior wall of the
sellae.
– A significant amount of drilling may be
required in patients with incompletely
pneumatized sphenoid sinuses.
– An irrigating drill may be used to reduce the
risk of thermal injury to the adjacent
structures.
● Extended transsphenoidal approaches are
necessary to reach suprasellar and parasellar
pathology.
– Transtuberculum and/or transplanum
approach for suprasellar lesions.
– Transclival approach for retrosellar lesions.
● The dura is opened with an 11-blade scalpel, and
ringed curettes are used for tumor removal.
Bipolar coagulation and sharp dissection have
been described for the resection of
craniopharyngiomas, as well.
– AValsalva maneuver may be used to force
suprasellar portions of the tumor into the sella
and into the field of view.
– For Rathke’s cleft cysts, cyst drainage and
biopsy of the cyst wall is recommended, given
Fig. 16.4 Schematics of an endonasal transsphenoidal resection of a pituitary adenoma in a pediatric patient.
(Reproduced with permission from Chaichana KL, Jusue-Torres I, Jallo GI. Tumors of the skull base and orbit. In: Cohen
AR, ed. Pediatric Neurosurgery. New York, NY: Thieme; 2016.)
Tumor
118

the comparable recurrence rate and lower
morbidity compared to complete resection of
the cyst wall.5,9 Biopsy of the anterior cyst wall
should be performed before substantial
drainage has taken place. Large dural openings
may promote continued drainage and reduce
the recurrence rate of Rathke’s cleft cysts.
● Reconstruction of the skull base depends on
surgeon preference as well as the degree of
suspicion for CSF leak. Options include one or a
combination of the following: abdominal fat
grafts, dural substitutes, various forms of
biodegradable glue, bioabsorbable miniplates,
and pedicled flaps.
16.18.2 Transcranial Approach
(Fig. 16.5)23,26,27
● A pterional exposure is typically reserved for
large craniopharyngiomas and is used to access
Fig. 16.5 Pterional approach for craniopharyngiomas. (a) The head position for the pterional approach. Also seen are
the curvilinear incision (dotted line) for the classic pterional approach and the bicoronal incision (solid line) for the
craniotomy with medial extension. (b) The skin flap reflected and the pericranial dissection. (c) The temporalis muscle
cut and reflected. Also seen are burr holes and the craniotomy flap. Note the frontal burr hole placed medially in the
frontal region. (d) The bone flap elevated, the dura exposed, and the sphenoid wing being removed. (e) The dural
incision (dotted line). Note the wide space achieved at the frontal–temporal junction after drilling the sphenoid wing. (f)
The dura opened and reflected over the sylvian fissure. (g) The transsylvian approach to the craniopharyngioma through
the opticocarotid space. Note the visualization of the carotid bifurcation that is achieved after splitting the sylvian
fissure. (Reproduced with permission from Yasargil MG. Microneurosurgery. Vol 4B. New York, NY: Thieme; 1994; and
Krisht AF, Türe U. Surgical approaches to craniopharyngiomas. In: Behnam B, ed. Neurosurgical Operative Atlas: Neuro-
Oncology. New York, NY: Thieme; 2007:Fig. 2-2.)
Craniopharyngiomas and Other Sellar Tumors
119

the suprasellar region with minimal frontal and
temporal lobe retraction. This approach allows
for early visualization of the carotid arteries and
optic chiasm, facilitating the protection of these
structures.
● A frontotemporal craniotomy is performed.
– Removal of the sphenoid wing and/or orbital
rim may be used to maximize the exposure.
● The dura is opened. Mannitol, hyperventilation,
and release of CSF from the subarachnoid
cisterns may be used to facilitate brain
relaxation and minimize retraction.
● The sylvian fissure is opened widely and the
carotid arteries and optic apparatus are
identified.
● An arachnoidal plane is developed between the
tumor and the ipsilateral cerebral vasculature.
● Cystic portions of the tumor are then aspirated,
and solid components of the tumor are debulked
while preserving the tumor capsule.
– Premature aspiration of the cyst makes further
dissection of the arachnoid di cult, and
should only be performed once the vascular
anatomy has been clearly identified.
● The goal of surgery—debulking versus gross total
resection—remains controversial. The following
steps may be adapted depending on surgeon
preference.
● An arachnoidal plane is developed between the
tumor and the optic apparatus as well as the
contralateral cerebral vasculature.
● Whenever possible, the pituitary stalk is
preserved. When it is adherent to the tumor and
the surgical goal is gross total resection, the
pituitary stalk may sectioned, given the high rate
of diabetes insipidus following radical resection
regardless of whether the stalk is intact.
– The stalk should be sectioned as distally to the
hypothalamus as possible in order to prevent
traction on the hypothalamus.
● When gross total resection is desired, the tumor
is bluntly dissected away from its attachment to
the hypothalamus, which is typically located at
the tuber cinereum.
● When there is significant extension into the
third ventricle or into the retrochiasmatic space,
the lamina terminalis may be fenestrated.
● When there is extension of the tumor into the
sella, the posterior planum sphenoidale and
tuberculum sellae may be removed.
● A micromirror or an angled endoscope may be
used to inspect the surgical bed for residual
tumor.
16.18.3 Complications
The surgical complications that are encountered
depend largely on the precise location of the mass
(sellar vs. suprasellar) and whether a transsphe-
noidal approach or a craniotomy is performed.
Injury to the adjacent structures may include
hypothalam ic dam age, pituitary dysfunction,
injury to the optic apparatus, and vascular injury.
Large, invasive tum ors are naturally associated
with greater m orbidity.6 Surgical m orbidity and
patient outcom es are also dependent on surgeon
experience.28
● Hypothalamic dysfunction is associated with a
variety of signs and symptoms that have a major
impact on quality of life, including15:
– Hyperphagia and obesity.
– Memory deficits.
– Emotional lability.
– Inability to regulate body temperature.
– Disturbance of the circadian rhythm.
● Although some degree of hypothalamic
dysfunction is found in up to 35% of pediatric
patients with craniopharyngiomas, surgical
treatment has been associated with higher
postoperative rates of hypothalamic dysfunction.
– Obesity, in particular, increases during the first
6 to 12 months following treatment.16
● A grading scale was designed by De Vile et al29 to
predict hypothalamic dysfunction in order to
help guide the intended extent of surgical
resection. This remains a controversial area.
– Some surgeons propose incomplete resection
followed by radiotherapy in order to minimize
acute postoperative morbidity, while others
point to the risk of delayed hypopituitarism
associated with radiotherapy, therefore
arguing for gross total resection at the time of
initial presentation.6
● Craniopharyngioma resection is associated with
high rates of postoperative hypopituitarism and
diabetes insipidus in particular. GH deficiency is
also commonly found postoperatively, although
most patients respond well to exogenous GH.
Patients and their families should be counseled
about the risk of pituitary dysfunction and the
need for close endocrinologic follow-up and
hormone supplementation.16
– The transsphenoidal approach is associated
with a lower rate of diabetes insipidus than the
transcranial approach. This may be secondary
to superior visualization of the infundibulum.
Alternatively, intrasellar tumors involve the
infundibulum distally, while suprasellar
Tumor
120

tumors requiring a transcranial approach tend
to involve the infundibulum proximally, where
surgical manipulation is more likely to result
in diabetes insipidus.12
● Following surgical treatment of
craniopharyngiomas, vision tends to improve in
over half of cases. However, visual deterioration
does occur in some patients, although this is less
common with the transsphenoidal approach.15
16.19 Postoperative Care
Following an endonasal transsphenoidal approach,
patients should avoid inserting anything into the
nares, including nasal cannula for oxygen supple-
mentation. Straws, nasogastric tubes, oral temper-
ature probes, Valsalva’s maneuvers, and nose
blowing should be strictly avoided.
Postoperatively, a full endocrine panel should be
sent to assess for signs of new or worsening pitui-
tary dysfunction. In particular, patients should be
monitored closely for signs of diabetes insipidus. In
the setting of diabetes insipidus, patients should be
encouraged to maintain their fluid status orally if
possible; if this is not possible, intravenous supple-
mentation may be necessary. The serum sodium
level, osmolarity, and urine specific gravity should
be followed. Patients are also typically placed on
hydrocortisone postoperatively and the dose is
tapered in coordination with endocrine specialists.
16.20 Adjuvant Treatment
Given the aggressive and recurrent nature of cranio-
pharyngiomas, a variety of adjuvant treatments have
been explored, especially for patients in whom a
gross total resection cannot be achieved. Radiation
treatment, in particular, plays a prominent role in
the adjuvant treatment of craniopharyngiomas. Vari-
ous methods for delivering radiation—including frac-
tionated radiation, stereotactic radiosurgery, and
intracavitary radiation therapy—have been studied.
● Fractionated focal radiation therapy to the sellar
and parasellar region typically involves doses of
50 to 60 Gy delivered in 2-Gy fractions.7
● Following incomplete resection of a
craniopharyngioma, adjuvant radiotherapy
decreases the rate of progression from about
70–90% to about 20%.16,30
– However, those tumors that do progress
following failed radiotherapy are associated
with increased morbidity and mortality, and
are more challenging to re-resect.15
● Fractionated radiation also carries a number of
risks7:
– In a similar manner as surgical resection,
radiation-induced injury to the adjacent
structures may result in hypothalamic
dysfunction (including obesity and/or
disruption of the sleep–wake cycle),
hypopituitarism, and diabetes insipidus.
– There is a 3% risk of optic neuropathy
associated with fractionated radiation.
– Radiation may have deleterious cognitive
e ects and is associated with delayed
secondary malignancies, both of which are
particularly concerning in the pediatric
population.
● Immediate postoperative radiation and
“progression-contingent radiation” have similar
rates of overall survival, although the latter
delays the negative e ects of radiation on
neurological development.16
● Single-session stereotactic radiosurgery is
typically limited to craniopharyngiomas that are
less than or equal to 3 cm in diameter and are 3
to 5 mm away from the optic apparatus.7
– Exposure of the optic chiasm to doses higher
than 8 to 10 Gy per session results in an
elevated risk of optic neuropathy.
– Multisession stereotactic radiosurgery has
been proposed as a technique for treating
craniopharyngiomas that are even closer to
the optic nerves and chiasm.
● Cystic craniopharyngiomas may be treated via
the stereotactic placement of an intracystic
catheter with a subcutaneous reservoir.
Percutaneous decompression of the cyst may be
performed. Alternatively, the catheter may be
used to instill radioisotopes (beta emitters such
as Re-186, P-32, Au-198, or Y-90) or sclerosing
agents (e.g., bleomycin). Despite encouraging
response rates to intracavitary radiation,
neurotoxicity resulting from leakage into the CSF
remains a limiting factor.6,7,16
16.21 Outcomes
The treatment of craniopharyngiomas and other
sellar and parasellar lesions is associated with high
rates of survival (as high as 95%).5 As a result, the
success of treatment is now measured in terms of
the recurrence rate as well as by the quality of life
experienced by the patient. The latter, in particu-
lar, is critically a ected by the hypothalamic, endo-
crine, and visual function of the patient following
treatment. Several variables have been correlated
Craniopharyngiomas and Other Sellar Tumors
121

with patient outcomes—younger age at diagnosis,
larger tumor size, and worse preoperative func-
tional status are all associated with worse out-
comes, while surgeon experience is associated
with improved outcomes.15,28
16.21.1 Craniopharyngiomas
● Postoperative imaging is performed within 48
hours of craniopharyngioma resection and
residual tumor is graded by the Ho man scale,31
which ranges from grade 1 (no residual tumor or
calcification) to grade 5 (contrast enhancing
mass).1,5
● Gross total resection reduces the recurrence rate
of pediatric craniopharyngiomas by more than
half (18–28% following incomplete resection vs.
0–13% following gross total resection).24
● Although the transsphenoidal approach appears
to o er higher rates of gross total resection than
the transcranial approach, this is likely due to
selection bias—transsphenoidal resection is
typically chosen for small tumors confined to the
sella. Larger tumors are associated with lower
rates of gross total resection and higher rates of
recurrence.12
● Adjuvant radiotherapy following incomplete
surgical resection dramatically reduces the risk
for progression of a craniopharyngioma.7
● Gross total resection of a craniopharyngioma
and limited resection followed by adjuvant
radiation are both associated with similar rates
of tumor control and overall survival.
Controversy arises as to which approach a ords
a better functional outcome and higher quality
of life.15
● De Vile et al29 and Puget et al32 developed
classification systems that could be used to
predict the risk of hypothalamic dysfunction
following surgical resection of a
craniopharyngioma.
● The transsphenoidal approach is associated with
higher rates of visual improvement, and less
visual deterioration postoperatively, relative to
the transcranial approach.12
– This is most likely due to the opportunity
a orded by the transsphenoidal approach to
perform an early decompression of the optic
apparatus with minimal manipulation.
16.21.2 Rathke’s Cleft Cysts
● Headaches and visual function tend to improve
following surgical drainage.
● In general, resolution of hormonal deficits occurs
in only 14 to 20% of patients.
Hyperprolactinemia resolves in over half of
patients following drainage.18
● Recurrence occurs in 14 to 18% of patients in
spite of gross total resection of the cyst wall.
However, aggressive resection is associated with
increased morbidity, including permanent
diabetes insipidus.17,18,20
– Recurrence has been associated with the
presence of squamous metaplasia.20
● Following surgical drainage, close clinical and
radiographic follow-up is warranted for at least
5 years, followed by further imaging every 2 to 3
years for an additional 5 years.20
16.21.3 Pituitary Adenomas
● Prolactinomas: Medical therapy is widely
e ective. Those who cannot tolerate the
medication or patients in whom the tumor is
refractory to medication are referred for surgical
resection.
● Cushing’s disease: Surgical resection results in
high remission rates (70–98%) in the short term,
but many tumors recur if followed for more than
5 years.6
– Hydrocortisone replacement is typically
required for 6 to 12 months following surgery
due to transient adrenal insu ciency.
– Normal growth resumes once the cortisol level
normalizes.
– ACTH and cortisol levels may be monitored for
early signs of recurrence.
● GH-secreting adenomas: GH levels frequently
remain elevated postoperatively, and normalize
in only 60% of patients.6
16.22 Clinical Pearls
● Reconstruction is generally not performed for
Rathke’s cleft cysts in the absence of a CSF leak,
in order to facilitate continued cyst drainage.
● During craniopharyngioma resection, the
normal pituitary gland is often identified ventral
and anterior to the tumor. In order to reach the
dorsally located tumor from a transsphenoidal
approach, a vertical incision may be used to
mobilize the pituitary gland. This maneuver is
associated with low rates of iatrogenic endocrine
deficits.
● When gross total resection of a
craniopharyngioma is the goal, resection of the
diaphragma sellae may be necessary if it is
Tumor
122

adherent to the tumor capsule. A CSF leak should
be expected and careful skull base
reconstruction should be performed.
● AValsalva maneuver may be used to force
suprasellar portions of the tumor into the sella
and into the field of view.
– The right lower quadrant is not used in pediatric
patients so that the incision is not confused with
an appendectomy scar in the future.
16.23 Common Clinical
Questions
1. How do pediatric craniopharyngiomas most
commonly present?
2. How is Cushing’s disease identified
preoperatively?
3. Craniopharyngiomas in which location are most
suitable for the transsphenoidal approach?
4. Describe the options for adjuvant radiotherapy
following surgical resection of a
craniopharyngioma.
16.24 Answers to Common
Clinical Questions
1. Craniopharyngiomas most commonly present
with nonspecific symptoms of raised
intracranial pressure, such as headaches and
nausea. Many patients also have at least some
level of endocrine dysfunction at the time of
presentation. GH is most commonly a ected,
resulting in growth failure. Patients may also
show signs of delayed puberty, weight gain, and
diabetes insipidus. Visual deficits, although
frequently found in patients, tends to be well
tolerated by the pediatric population.
2. Upon identification of a sellar or parasellar mass
on neuroimaging, a full endocrine workup
should be performed. Cushing’s disease is
associated with elevated serum ACTH and
cortisol levels. Low-dose dexamethasone
administered at midnight does not suppress the
production of cortisol (measured the next
morning), although cortisol production is
indeed suppressed by high-dose
dexamethasone. In contrast, ectopic ACTH-
secreting tumors result in elevated cortisol
levels that are suppressed by neither low- nor
high-dose dexamethasone.
3. The transsphenoidal approach is most
appropriate for intrasellar pathology (unless an
extended transsphenoidal approach is utilized,
in which case the suprasellar region may be
reached as well). Craniopharyngiomas with an
infradiaphragmatic intrasellar origin may be
safely resected via the transsphenoidal
approach, as the diaphragma sellae drapes over
the tumor and separates it from suprasellar
structures such as the optic chiasm,
hypothalamus, and circle of Willis.
4. Various strategies for delivering adjuvant
radiotherapy have been described, including
fractionated radiation (50–60 Gy delivered in
2-Gy fractions), single or multi-session
stereotactic radiosurgery, and intracystic
radioisotopes delivered via a stereotactically
implanted catheter. Radiosensitivity of adjacent
structures—in particular the optic apparatus—
remains a key limiting factor in the dosing of
adjuvant radiotherapy.
References
[1] Surawicz TS, McCarthy BJ, Kupelian V, Jukich PJ, Bruner
JM, Davis FG. Descriptive epidemiology of primary brain
and CNS tumors: results from the Central Brain Tum or
Registry of the United States, 1990–1994. Neuro-oncol.
1999; 1(1):14–25
[2] Zada G, Lin N, Ojerholm E, Ramkissoon S, Laws ER.
Craniopharyngioma and other cystic epithelial lesions of the
sellar region: a review of clinical, imaging, and histopathological
relationships. Neurosurg Focus. 2010; 28(4):E4
[3] Frazier JL, Chaichana K, Jallo GI, Quiñones-Hinojosa A.
Combined endoscopic and microscopic management of
pediatric pituitary region tumors through one nostril:
technical note with case illustrations. Childs Nerv Syst. 2008;
24(12):1469–1478
[4] Schroeder JW, Vezina LG. Pediatric sellar and suprasellar
lesions. Pediatr Radiol. 2011; 41(3):287–298, quiz 404–405
[5] Müller HL, Gebhardt U, Faldum A, et al. Kraniopharyngeom
2000 Study Committee. Xanthogranuloma, Rathke’s cyst,
and childhood craniopharyngioma: results of prospective
multinational studies of children and adolescents with rare
sellar malformations. J Clin Endocrinol Metab. 2012; 97(11):
3935–3943
[6] Jagannathan J, Dumont AS, Jane JA, Jr, Laws ER, Jr. Pediatric
sellar tumors: diagnostic procedures and management.
Neurosurg Focus. 2005; 18 6A:E6
[7] Veeravagu A, Lee M, Jiang B, Chang SD. The role of radiosurgery
in the treatment of craniopharyngiomas. Neurosurg Focus.
2010; 28(4):E11
[8] Bunin GR, Surawicz TS, Witman PA, Preston-Martin S, Davis F,
Bruner JM. The descriptive epidemiology of craniopharyngioma.
JNeurosurg. 1998; 89(4):547–551
[9] Jahangiri A, Molinaro AM, Tarapore PE, et al. Rathke cleft
cysts in pediatric patients: presentation, surgical management,
and postoperative outcomes. Neurosurg Focus. 2011; 31(1):
E3
[10] Teramoto A, Hirakawa K, Sanno N, Osamura Y. Incidental
pituitary lesions in 1,000 unselected autopsy specimens.
Radiology. 1994; 193(1):161–164
Craniopharyngiomas and Other Sellar Tumors
123

[11] Takanashi J, Tada H, Barkovich AJ, Saeki N, Kohno Y. Pituitary
cysts in childhood evaluated by MR imaging. AJNR Am J
Neuroradiol. 2005; 26(8):2144–2147
[12] Elliott RE, Jane JA, Jr, Wiso JH. Surgical management
of craniopharyngiomas in children: meta-analysis and
comparison of transcranial and transsphenoidal approaches.
Neurosurgery. 2011; 69(3):630–643, discussion 643
[13] Webb C, Prayson RA. Pediatric pituitary adenomas. Arch
Pathol Lab Med. 2008; 132(1):77–80
[14] Abe T, Lüdecke DK, Saeger W. Clinically nonsecreting pituitary
adenomas in childhood and adolescence. Neurosurgery. 1998;
42(4):744–750, discussion 750–751
[15] Elliott RE, Sands SA, Strom RG, Wiso JH. Craniopharyngioma
Clinical Status Scale: a standardized metric of preoperative
function and posttreatment outcome. Neurosurg Focus. 2010;
28(4):E2
[16] Müller HL. Childhood craniopharyngioma: treatment
strategies and outcomes. Expert Rev Neurother. 2014; 14(2):
187–197
[17] Higgins DM, Van Gompel JJ, Nippoldt TB, Meyer FB.
Symptomatic Rathke cleft cysts: extent of resection and
surgical complications. Neurosurg Focus. 2011; 31(1):E2
[18] Zada G, Ditty B, McNatt SA, McComb JG, Krieger MD. Surgical
treatment of rathke cleft cysts in children. Neurosurgery.
2009; 64(6):1132–1137, author reply 1037–1038
[19] Keil MF, Stratakis CA. Pituitary tumors in childhood: update
of diagnosis, treatment and molecular genetics. Expert Rev
Neurother. 2008; 8(4):563–574
[20] Zada G. Rathke cleft cysts: a review of clinical and surgical
management. Neurosurg Focus. 2011; 31(1):E1
[21] Samii M, Tatagiba M. Craniopharyngioma. In: Kaye A, Laws E,
eds. Brain Tumors. New York, NY: Churchill Livingstone;
1995:873–94
[22] Wen BC, Hussey DH, Staples J, et al. A comparison of the roles of
surgery and radiation therapy in the management of cranio-
pharyngiomas.Int JRadiat Oncol Biol Phys.1989; 16(1):17–24
[23] Wiso J, Donahue B. Craniopharyngiomas. In: Albright A,
Pollack I, Adelson P, eds. Principles and Practice of Pediatric
Neurosurgery. New York, NY: Thieme; 2015:483–502
[24] Jane JA, Jr, Prevedello DM, Alden TD, Laws ER, Jr. The
transsphenoidal resection of pediatric craniopharyngiomas:
a case series. J Neurosurg Pediatr. 2010; 5(1):49–60
[25] Ali ZS, Lang SS, Kamat AR, et al. Suprasellar pediatric
craniopharyngioma resection via endonasal endoscopic
approach. Childs Nerv Syst. 2013; 29(11):2065–2070
[26] Elliott RE, Hsieh K, Hochm T, Belitskaya-Levy I, Wiso J,
Wiso JH. E cacy and safety of radical resection of primary
and recurrent craniopharyngiomas in 86 children. J
Neurosurg Pediatr. 2010; 5(1):30–48
[27] Sands SA, Milner JS, Goldberg J, et al. Quality of life and
behavioral follow-up study of pediatric survivors of
craniopharyngioma. J Neurosurg. 2005; 103(4) Suppl:302–311
[28] Sanford RA. Craniopharyngioma: results of survey of the
American Society of Pediatric Neurosurgery. Pediatr
Neurosurg. 1994; 21 Suppl 1:39–43
[29] De Vile CJ, Grant DB, Kendall BE, et al. Management of
childhood craniopharyngioma: can the morbidity of radical
surgery be predicted? J Neurosurg. 1996; 85(1):73–81
[30] Becker G, Kortmann RD, Skalej M, Bamberg M. The role of
radiotherapy in the treatment of craniopharyngioma–indications,
results,side e ects.Front Radiat Ther Oncol.1999; 33:100–113
[31] Ho man HJ. Craniopharyngiomas. Can J Neurol Sci. 1985; 12
(4):348–352
[32] Puget S, Garnett M, Wray A, et al. Pediatric craniopharyngiomas:
classification and treatment according to the degree of
hypothalamic involvement.JNeurosurg.2007; 106(1) Suppl:3–12
Tumor
124

17 Germ Cell Tumors
Gerald F. Tuite, Stacie Stapleton
17.1 Introduction
All germ cell tumors (GCTs) are thought to have a
common cell of origin, the primordial germ cell.
GCTs are divided into gonadal and extragonadal
tumors. Approximately half of GCTs are extragona-
dal, and most of these occur intracranially.1
GCTs account for only a small proportion of all
cancers in children, and the incidence and location
vary significantly with age and gender.
17.2 Epidemiology Factors
17.2.1 Extracranial Germ Cell
Tumors
● GCTs have a bimodal distribution: a peak in
infancy and a second peak after the onset of
puberty.2
● Newborns more commonly have teratomas and
yolk sac tumors, but tumors in the peripubertal
period have a wider range of histologies.2
● Sacrococcygeal teratomas are the most common
GCTof childhood, accounting for 40% all GCTs
and 78% of extragonadal GCTs.3 Prior to age 5,
42% of GCTs are sacrococcygeal teratomas.4
● Malignant GCTs are rarely diagnosed in early
childhood but the incidence begins to rise
during the onset of puberty in boys and girls.2
● During adolescence, GCTs make up a much
larger proportion of all cancer: for patients
younger than 15 years, GCTs make up only 2 to
4% of all cancer diagnoses, but they account for
16% of all cancers in adolescent between 15 and
19 years of age.2,5,6 Overall, there is a higher
incidence in males5; however, GCTs are more
common in females in the neonatal period and
during the peripubertal period.2,5
● Gonadal tumors are more common than
extragonadal tumors, but females have a higher
proportion of extragonadal tumors (33%) than
males (15%).2,5 In the first year of life, males have
an equal proportion of gonadal and extragonadal
tumors, but females have a higher proportion of
extragonadal tumors than ovarian tumors. Rates
of all GCTs remain low in both genders during
childhood, but the rates increase significantly in
both girls and boys with the onset of puberty. In
puberty and the peripubertal periods, rates of
extragonadal tumors increase somewhat but the
incidence of gonadal tumors has a dramatic
increase, much more so in males than females.4
17.2.2 Intracranial Germ Cell
Tumors
Overall, intracranial GCTs represent a small pro-
portion of all pediatric brain tumors.2,5 The inci-
dence varies significantly according to geography.
In western countries, intracranial GCTs represent
0.4 to 3.4% of all pediatric central nervous system
(CNS) tumors,7,8 while in Japan and other Asian
countries, intracranial GCTs represent up to 11% of
all pediatric CNS tumors.9,10
● The most common primary sites in the brain are
the pineal gland (56%) and the suprasellar region
(28%). The basal ganglia, thalamus, corpus
callosum, cerebellum, and spinal cord are much
less common.11
● CNS GCTs predominate in the young population,
with more than 90% of CNS GCTs diagnosed
before the age of 20 years,8 with the peak age at
diagnosis being 10 to 12 years.12
● Nongerminomatous germ cell tumors (NGGCTs)
predominate in younger children and
germinomas are more common in older
children.7,8
● Gender di erences are marked. In males, 70% of
GCTs occur in pineal region, and in females, 75%
of GCTs are suprasellar. For NGGCTs, the male-
to-female ratio is 3:1, but in germinomas it is
1.8:1.7,8
17.3 Predisposing Factors
17.3.1 Extracranial Germ Cell
Tumors
There has been a doubling of the worldwide rate
of testicular cancer in the past 30 years as well as a
general rise in the incidence of pediatric GCTs.2
Prenatal exposure to high levels of maternal
estrogens (diethylstilbestrol or oral contracep-
tives) may be a possible environmental cause,
which has been linked to increased GCTs in animal
experiments; however, these links have not been
125

supported in clinical epidemiological studies.2 Pre-
disposing syndromes include: cryptorchidism —
relative risk of testicular cancer of 2.1 to 17.6%13;
Turner’s syndrome (45, X, loss of X chromosome)—
increased risk of gonadoblastoma2; Klinefelter’s
syndrome (47, XXY)—increased risk of mediastinal
GCT but not increased risk of testicular cancer2;
and androgen insensitivity syndromes (X,Y)—
cryptorchid testes are at high risk for GCT.2
17.3.2 Intracranial Germ Cell
Tumors
The only known predisposing factor is Japanese or
other Asian ancestry. In western countries, intracra-
nial GCTs account for only 0.4 to 3.4% of all pediatric
CNS tumors; in Japan and other Asian countries,
intracranial GCTs account for up to 11% of all pedia-
tric CNS tumors.8 Peripubertal individuals are pre-
disposed for GCTs. Circulating gonadotropin levels
may be a factor in tumor development.14 There are
no known environmental risk factors.
17.4 Pathophysiology
GCTs arise from cells of the germline, cells that are
destined to become either the egg or the sperm.2
Di erent GCTs may represent the malignant forms
of di erent stages of normal embryonic develop-
ment. Primordial germ cells may result in germi-
nomas, embryonic di erentiation may give rise to
teratomas and embryonal carcinomas, extraem-
bryonic yolk sac cells may give rise to endodermal
sinus tumors, and derivatives of the trophoblast
may give rise to choriocarcinomas.1
There are multiple theories for the development
of GCTs in the brain:
● The “germ cell theory” states that primordial
germ cells, which normally develop from the
extraembryonic yolk sac endoderm and migrate
to the gonadal folds, have abnormal migration
and end up in brain; then, these cells undergo
malignant transformation.2,15
● The “embryonic cell theory” suggests there is
mismigration of pluripotent embryonic cells,
which give rise to GCTs.2,8
● Another theory proposes that germinomas are
the only GCTs that arise from germ cells. and
that other GCTs develop secondary to misfolding
and misplacement of embryonic cells into the
lateral mesoderm, resulting in entrapment in
di erent brain regions.8,16,17
17.5 Pathology
The pathologic classification of intracranial GCTs is
based primarily on the tumor’s histopathology and
tumor markers ( Table 17.1)
17.5.1 Germinoma (Pure
Germinoma)
● Histologically indistinguishable from tumors in
extracranial locations such as gonads or
mediastinum.
● Key features include large round blue cells, with
abundant clear cytoplasm arranged in nests
around bands of connective tissue, focal
microvilli.
● Negative for alpha-fetoprotein (AFP), may be
positive for beta-human chorionic gonadotropin
(b-HCG) if syncytiotrophoblastic cells are
present, may have elevation of placental alkaline
phosphatase (PLAP), and c-kit is typically
elevated.7,18,19
Table 17.1 Tumor markers in germ cell tumors
Type of germ cell tumor

AFP

b-HCG

PLAP

c-kit
Germinoma

–

–1

+/–

+
Embryonal carcinoma

–

–

+

–
Endodermal sinus (yolk sac) tumor + + +

–

+/–

–
Choriocarcinoma

–

+ + +

+/–

–
Mixed germ cell tumor

+ /–

+ /–

+/–

+ /–
Teratoma

–2

–2

–

–2
Abbreviations: AFP, alpha-fetoprotein; b-HCG, beta-human chorionic gonadotropin; PLAP, placental alkaline phosphatase.
Source: Data from Louis et al.18
Note: 1, positive if syncytiotrophoblastic; 2, positive if immature.
Tumor
126

17.5.2 Nongerminomatous Germ
Cell Tumors
Embryonal Carcinoma
● Cuboidal-columnar cells in sheets and cords,
large nuclei and large prominent nucleoli, very
little lymphocytic infiltration.
● PLAP positive, AFP, and b-HCG.7,18,19
Endodermal Sinus Tumor
(Yolk Sac Tumor)
● Di erentiation of yolk sac noted, Schiller–Duval
bodies are pathognomonic (glomeruloid
structures), invaginated vascular pedicle lined by
a single layer of tumor cells.
● AFP positive, PLAP may or may not be elevated.7,18,19
Choriocarcinoma
● Di erentiated trophoblasts, bilaminar
cytotrophoblasts/syncytiotrophoblasts,
hypervascular, intratumoral hemorrhage
common.
● b-HCG positive, PLAP may or may not be
elevated.7,18,19
Mixed Germ Cell Tumor
● May contain a mixture of multiple elements
including germinoma elements.
● May demonstrate any variation of tumor
markers.
Teratoma
● Key characteristic is presence of all three germ
layers.
● Immature teratoma versus mature teratoma
based on degree of di erentiation.
● Teratoma with malignant transformation is a
designation for teratomas that contain an
additional malignant component such as
sarcoma or carcinoma.20
● Solid or cystic foci of squamous epithelium,
cartilage, or glandular elements.7,18,19
● Mature teratomas are negative for tumor
markers, although immature teratomas may
have AFP or b-HCG if certain components are
present.
17.6 Molecular Biology
The molecular biology of GCTs is an evolving field
of uncertain clinical significance, and additional
work is needed in this area. Interesting data are
mentioned here:
● One study demonstrated 92% of intracranial
GCTs had an extra X chromosome and that 81%
of those were hypomethylated. In addition, 20%
had increased copy numbers of 12p.21
● Compared with astrocytomas, p53 mutation is
rare (5%) in GCTs, but mdm2 amplification (19%)
and homozygous deletion or frameshift
mutation of INK4a/ARF (71%) are frequent.22,23
● Various mutations of c-kit have been noted with
up to three di erent mutations in a single
tumor.22
17.7 Radiographic Findings of
Intracranial Germ Cell Tumors
Most intracranial GCTs originate in the vicinity of
the third ventricle, with most tumors localized to
the pineal region or the suprasellar cistern.1 Pineal
region GCTs outnumber those occurring in the
suprasellar cistern by a ratio of approximately 2:1.7
So-called synchronous GCTs, occurring in both the
pineal and suprasellar locations, occur in approxi-
mately 5 to 10% of cases.7 Germinomas more com-
monly occur in the pineal region in males, whereas
females are more likely to have lesions in the supra-
sellar region.7 GCTs have a predilection to metasta-
size along the entire neural axis but they have also
been reported to originate at various areas outside
the third ventricle, including the basal ganglia, tha-
lamus, lateral and fourth ventricles, medulla, cere-
bellum, optic nerves, and spinal cord.
MRI with and without intravenous contrast is
the imaging modality of choice, but computed
tomography (CT) scanning can help delineate the
degree of calcification. Historically, GCTs were sus-
pected when calcifications were seen in the pineal
region on skull radiographs. When a GCT is consid-
ered, brain and total spine MRI with and without
contrast are recommended to delineate the extent
of disease.8 Angiography is rarely indicated, unless
other imaging modalities suggest a primary vascu-
lar malformation.
The radiographic characteristics of all GCTs are
very similar: enhancing, sometimes calcified and/
Germ Cell Tumors
127

or cystic lesion within the pineal or suprasellar
area. Because the imaging characteristics of most
GCTs are so similar, a precise and reliable histologic
diagnosis cannot be made based on radiographs
alone.8 There is also significant overlap in the radio-
graphic characteristics of several other tumor
types that occur in these location, including pineo
blastoma, trilateral retinoblastoma, pineocytoma,
glioma, meningioma, lymphoma, cyst, and vascular
abnormalities. However, certain imaging character-
istics of GCTs tend to follow the following trends:
● Synchronous third ventricular lesions, within the
pineal and suprasellar areas, occur more often
with germinoma than with NGGCTs.8
● Germinomas tend to di usely and
homogenously enhance. NGGCTs and very large
germinomas have a more heterogeneous
enhancement pattern.1
● Choriocarcinoma is the most common GCT
associated with hemorrhage. In general, NGGCTs
are more likely to hemorrhage than
germinomas.1
● Mature teratomas have a very heterogeneous
appearance with predominant cysts and
calcifications. Immature teratomas tend to have
less cysts and calcifications.
● A calcified, benign-appearing pineal cyst seen on
CTwarrants an MRI scan to rule out tumor.24
17.8 Presenting Signs and
Symptoms
The clinical presentation of intracranial GCTs
depends on the patient age, tumor location, and
size of the tumor.
17.8.1 Suprasellar GCTs
● Rarely present with signs of raised intracranial
pressure (ICP).
● Usually present with dysfunction of the
pituitary/hypothalamic axis: diabetes insipidus,
delayed sexual development, hypopituitarism,
isolated grow th hormone deficiency, precocious
puberty.
● Ophthalmic abnormalities such as visual field
deficits or bitemporal hemianopsia.
17.8.2 Pineal GCTs
● Usually present with signs of raised ICP related
to obstructive hydrocephalus—somnolence,
vomiting, headaches.
● Ophthalmologic findings are present in 25 to
50% of patients with pineal region tumors and
include papilledema or Parinaud’s syndrome
(paralysis of upward gaze, impaired
accommodation, and convergence-retraction
nystagmus).8
● Ataxia, seizures, and behavioral changes in
approximately 25%.
● Endocrinopathies are less common than with
suprasellar tumors. However, the presence of
diabetes insipidus with a pineal region tumor,
even without radiographic abnormality in the
suprasellar area, may be an indication of
suprasellar tumor involvement.15
17.9 Laboratory Evaluation
Because radiographs are not always diagnostic,
b-HCG and AFP should be measured in the cere-
brospinal fluid (CSF) and serum. Tumor markers
may frequently be negative or only show mild lev-
els of elevation, but radiographs in combination
with tumor markers can often narrow the diagnos-
tic possibilities substantially. U.S. and European
groups have traditionally classified tumors as
“secreting” if the serum and/or CSFAFP is ≥10 ng/dL
and the b-HCG is ≥50 IU/L.15 Elevation in PLAP and
c-kit have shown association with pure germino-
mas, but these are not routinely used in diagnostic
decision-making. These tumor markers may not
always be readily available in all hospitals and may
require submission to a reference lab, which may
delay time to diagnosis.25,26
● Pure germinomas, mature teratomas, and
embryonal carcinomas typically have negative
AFP and b-HCG. However, syncytiotrophoblastic
germinomas may have modest elevations in
b-HCG of up to 50 IU/L.15
● Choriocarcinoma characteristically has a very
high b-HCG level.27
● Endodermal sinus tumors (yolk sac tumors)
typically have an isolated elevated AFP.
● Immature teratomas and mixed GCTs have
variable expressions of AFP and b-HCG.
● Pure germinomas tend to be negative for b-HCG
and AFP.
● Some patients with germinoma can have a
modest elevation of b-HCG, which can confuse
the diagnostic picture. However, current
convention has accepted levels of 50 to
100 mIU/mL for diagnosis as a pure germinoma
and higher levels to recommend diagnosis as a
mixed GCT.28,29
Tumor
128

17.10 Nonsurgical
Management
Although there is a broad di erential diagnosis for
pineal and suprasellar tumors, tissue diagnosis and/
or resection is not always necessary. Surgery is fre-
quently indicated for other reasons, such as the
presence of hydrocephalus at diagnosis, atypical/
nondiagnostic radiographs, or due to nonspecific
tumor markers. Unless otherwise indicated, tumor
biopsy may be avoided in the following situations:
● Extremely high b-HCG combined with a very
vascular suprasellar or pineal region tumor,
which suggests NGGCT, most likely
choriocarcinoma. The surgical risk is higher due
to the vascularity, and for this reason, empiric
adjuvant therapy may be advocated.
● Very high AFP with a heterogeneously
enhancing suprasellar or pineal region tumor
may suggest endodermal sinus tumor. Empiric
therapy would be considered.
● Homogenously enhancing suprasellar or pineal
region tumor with negative markers. Although
controversial, some centers are willing to treat
patients empirically based on the clinical picture
and the radiographic findings consistent with a
germinoma without histological confirmation or
elevated tumor markers.28
17.11 Surgical Indications
Unlike many other pediatric CNS tumors, there is a
limited role for complete resection in the treat-
ment of most GCTs. Gross total resection is the
treatment of choice for mature teratomas. How-
ever, the remainders of GCTs are treated with adju-
vant therapy, with subsequent surgery performed
if there is a histologic diagnostic uncertainty or if
parts of the tumor do not respond to radiation
therapy and/or chemotherapy.
The initial diagnosis of GCT can be confidently
made without biopsy if there are characteristic
clinical and radiographic findings combined with
markedly elevated tumor markers. For example,
pediatric patients presenting with enhancing
pineal masses with markedly elevated AFP (endo-
dermal sinus tumor) or b-HCG (choriocarcinoma)
can often be treated with adjuvant therapy with-
out tissue diagnosis.
However, if GCT is suspected and there are any
noncharacteristic imaging findings or if tumor
markers are only slightly elevated or in the normal
range, a tumor biopsy is usually strongly consid-
ered.8 If mature teratoma is diagnosed, gross total
resection is often attempted. In the case of all
other GCTs, adjuvant therapy is usually instituted
without an attempt at resection.
In clinical practice, the common presence of
hydrocephalus at the time of diagnosis often
necessitates urgent ventricular drainage. Because
most GCTs have an exposed surface within the
third ventricle, endoscopic biopsy can often be
readily performed at the time of ventricular access
in the treatment of hydrocephalus in cases where
the diagnosis cannot be made without histologic
confirmation. When hydrocephalus is not present,
tissue diagnosis can be made by stereotactic
biopsy or craniotomy if necessary.
17.12 Surgical Technique
Hydrocephalus is often present at the time of diag-
nosis, providing an ideal route for access to GCTs.
When biopsy is required, a combined endoscopic
third ventriculostomy (ETV) and tumor biopsy is
often the treatment of choice. When hydrocepha-
lus is not present at diagnosis, tissue can be
obtained by stereotactic biopsy, craniotomy, or
endoscopically assisted craniotomy.
17.12.1 Endoscopic Biopsy/
Endoscopic Third Ventriculostomy
● ETVand endoscopic biopsy (ENDOBX) can be
performed during a single operation, either
through a single burr hole (flexible endoscope)
or through two separate burr holes (rigid
endoscope).30,31
● ETV is usually performed prior to ENDOBX
because bleeding from biopsy may obscure view
for ETV.
● ETV success rate for treatment of hydrocephalus
is high, approximately 68 to 89%.10,30,31,32,33
17.12.2 Stereotactic Biopsy
● More likely to be performed in a pineal region
tumor than a suprasellar tumor because of
surrounding vasculature.
● Frame or frameless biopsy.
● Need to carefully plan trajectory to avoid
important vasculature.
Germ Cell Tumors
129

17.12.3 Craniotomy
● Usually the initial approach of choice
when a m ature teratom a is strongly
suspected or if hydrocephalus is not present
at diagnosis.
● May be considered even when hydrocephalus is
present at the time of diagnosis if the lesion is
not accessible endoscopically or if the tumor is
felt to be excessively vascular for an endoscopic
biopsy.
● An endoscopically assisted craniotomy may be
considered in certain situations in order to
minimize exposure.34
● For pineal region tumors:
– Midline infratentorial supracerebellar
approach is the most commonly utilized.
– Occipital transtentorial.
– Transventricular.
– Transcallosal.
● Suprasellar region tumors:
– Pterional.
– Subfrontal.
17.12.4 Ventricular Shunting
● Usually reserved for cases where ETV is either
not technically possible or unsuccessful.
17.13 Postoperative Care
Postoperative care is similar to that rendered after
typical ETV, endoscopic biopsy, or craniotomy.
● Steroids are often used on a limited basis before
and after surgery.
● External ventricular drainage is often performed
after ETV/biopsy. Proceed to clamping and drain
removal depending on surgeon preference, the
degree of bleeding after biopsy, and clinical
status.
● Com m on neurologic sequelae include
Parinaud’s syndrom e, convergence nystagm us,
and other focal neurologic deficits related to
hem orrhage.
17.14 Surgical Complications
17.14.1 Lack of Diagnosis
● A large multi-institutional study of 293 patients
found endoscopic biopsy diagnostic 90% of the
time.32
17.14.2 Sampling Error
● A large study showed that 27% of patients who
underwent endoscopic biopsy eventually also
had an open procedure. In this subset of
patients, pathology was found to be discordant
between endoscopic and open surgery 18% of
the time. This discordant pathology only
changed management 11% of the time.32
17.14.3 CSF Dissemination
● There is some concern that combined ETV plus
endoscopic biopsy might lead to greater CSF
dissemination of GCTs.
● Most studies show no increased risk of
dissemination with endoscopic biopsy.33,35
17.14.4 Seizure
● Mayo clinic study showed that risk of seizure
was higher in a transcallosal approach to lateral
and third ventricle than with transcortical
approach.36
17.14.5 Hemorrhage
● Cornell study of 86 patients showed 3.5% rate of
hemorrhagic sequelae during endoscopic
procedures for intraventricular tumors, with
only 1 patient having relevant morbidity related
to hemorrhage.37
● International study of endoscopic biopsy showed
that there was always some bleeding, with 6%
having severe hemorrhage.32
17.14.6 Death
● Rare, usually related to untreated hydrocephalus
or severe bleeding.
● Only 1/59 patients with GCTs died within 30
days of surgery, according to the UK Pediatric
CNS Tumor Registry.38
● Only 1/239 patients who underwent endoscopic
biopsy died shortly after surgery.32
17.15 Radiation Therapy and
Chemotherapy
The treatment for pediatric GCTs is dictated by the
specific subtype of tumor and the extent of dis-
ease. The goal of treatment is to provide the best
Tumor
130

tumor control and cure rate while minimizing
toxic long-term side e ects. Treatment is therefore
designed specifically to address the prognosis.
Germinomas and mature teratomas have the best
prognosis—the former managed by radiation with
or without chemo and the latter managed by resec-
tion. The NGGCTs as a whole have a much worse
prognosis. Historically, the standard treatment for
all GCTs was craniospinal radiation, which was
e ective for pure germinomas, but produced unac-
ceptable outcomes for patients with NGGCTs. In
addition, the patients had significant morbidity
from their treatment of the entire neuroaxis. Multi-
ple studies have been conducted to reduce the dose
of radiation, apply chemotherapy techniques, and
reduce long-term side e ect, while maintaining or
improving long-term survival.
17.15.1 Germinomas
Germinomas are extremely sensitive to radiation.
Empiric treatment, without biopsy, has been advo-
cated by some investigators. However, biopsy is
often performed when tumor markers are normal.
Radiation therapy at doses of 50 Gy gives 85 to
greater than 90% progression-free survival (PFS)
rates, but has high long-term morbidity.39 Chemo-
therapy alone has been attempted, and although
many patients achieve a near-complete or com-
plete response, most patients eventually relapse,
and this method therefore has unacceptable PFS
rates demonstrated at 84% 2-year survival.12,40
Multiple studies have focused on reducing the
dose and field of radiation combined with chemo-
therapy, and the results of these studies have led
to the current treatment of choice—two to four
cycles of chemotherapy (typically consisting of car-
boplatin and etoposide) and relatively low-dose
radiation therapy of 24 to 36 Gy to the tumor site
(s).41,42 In addition, as the ventricular system is the
primary area of relapse, typically 18 to 24 Gy is
delivered to the whole ventricular field.12
17.15.2 NGGCTs
This group includes choriocarcinoma, endodermal
sinus (yolk sac) tumors, embryonal carcinomas,
and mixed GCTs (including mixed NGGCT elements
with pure germinoma elements). Surgery is rarely
needed for a tissue diagnosis in this group as
tumor markers usually assist in making the diag-
nosis, although surgery may be indicated for
hydrocephalus. Compared to germinomas, the
NGGCTs are relatively resistant to radiation and
have a worse prognosis. In the past, these tumors
have been treated with craniospinal radiation and
have had a 3-year survival rate of 20 to 45%.12,39
Chemotherapy used prior to radiation has shown
objective responses, including complete responses
after two to four cycles of chemotherapy.43,44 Che-
motherapy without radiation has been attempted
but 50% of patients treated by this method
recurred, and at 65% 2-year survival, chemother-
apy alone would not be considered acceptable for
this group of patients.40 Chemotherapy combined
with radiation has been the focus of most research
protocols to help improve the survival. Currently,
the standard is chemotherapy (typically consisting
of carboplatin, etoposide, and ifosfamide) followed
by radiation therapy (45–54 Gy) to the tumor site
(s). Whole ventricular field radiation of 30 Gy with
or without craniospinal radiation is usually recom-
mended. Institution of adjuvant therapy often
reduces the size and vascularity of the tumor,
thereby facilitating complete removal at the time
of a second-look surgery, which may be indicated
in the presence of residual or progressive disease
after the completion of therapy.41,42
17.15.3 Teratomas
Surgical removal is the treatment of choice for
mature teratoma. Chemotherapy and radiation are
not typically recommended. Chemotherapy is
employed in patients with immature teratomas;
however, radiation therapy is controversial and
likely has no role.45 The best treatment for terato-
mas with malignant transformation is unclear.12
17.15.4 Relapse
Tumor recurrence occurs in 2 to 10% of patients
with standard germinoma, and higher rates of
relapse occur in NGGCT. Some recurrences are
related to an incorrect initial diagnosis, to malig-
nant transformation after therapy, or to simple
local recurrence. Surgical biopsy and possible
resection could be considered. If the patient has
not yet received radiation, then salvage with focal
or craniospinal radiation is recommended. Alter-
native chemotherapy agents have been reported
with some success, such as cyclophosphamide, cis-
platin, thiotepa, and others. High-dose chemother-
apy with stem cell rescue has also been successful
in some patients with or without additional focal
radiation.12,46,47
Germ Cell Tumors
131

17.16 Prognosis
The histologic subtype is the single most predic-
tive factor of outcome.42
17.16.1 Germinomas
● Germinomas are highly curable with 10-year
overall survival rates greater than 90% with
biopsy followed by adjuvant therapy.12
● Studies have shown an excellent oncologic
outcom e with 40 to 50 Gy of radiation
therapy to the whole ventricle or a larger
field, but there is a high rate of
complications including neuroendocrine
deficiencies, growth retardation, and cognitive
consequences.42,48,49
● Chemotherapy followed by reduced dose
radiation therapy has produced 10-year PFS
rates in the range of 75 to 93% with less
complications than high-dose radiation
therapy.41,42
● The degree of elevation of b-HCG has been
controversial regarding a prognostic risk factor,
but overall has not been shown to a ect
outcome.50,51
17.16.2 NGGCTs
● NGGCTs are relatively resistant to radiation
therapy and chemotherapy and are associated
with a less favorable outcome.42,48,49
● The addition of chemotherapy to radiation
clearly improves the outcome of patients versus
radiation alone.52
● A “sandwich” approach of chemotherapy,
followed by radiation, followed by further
chemotherapy, showed improved rates of 4-year
survival of 74%.44
● Upfront chemotherapy can induce complete
responses, but rates of 75% 6-year overall
survival have been shown when used in
combination with radiation.53 Another study has
shown a 5-year 79% event-free survival with the
approach of chemotherapy followed by
radiation.54
● Chemotherapy regimens must be chosen
carefully, as some chemotherapy regimens have
shown inferior results to others. The toxicities of
each regimen must be considered, such as
ototoxicity in particular when used in
conjunction with radiation.54
17.17 Surgical Pearls
● Intracranial GCTs predominantly occur within
the third ventricle, primarily in the pineal and
suprasellar areas.
● While pineal and suprasellar region tumors in
infants and children are often GCTs, there are
many other tumor types that occur in these
regions.
● GCTs have a propensity to be present along the
entire neuraxis. If the clinical situation allows,
obtain a brain and total spine MRI before
performing surgery or initiating adjuvant
therapy.
● If GCT is in the di erential diagnosis, be sure to
send serum tumor markers (AFP, b-HCG, PLAP)
before making a decision to perform surgery.
Also send CSF markers if they can be safely
obtained. b-HCG can be minimally elevated even
in germinomas.
● If tumor markers are highly suggestive of an
NGGCT, such as choriocarcinoma (b-HCG) or
endodermal sinus tumor (AFP), unless otherwise
indicated, surgery may be avoided without a
diagnostic biopsy or resection. Surgery is often
performed for hydrocephalus, nondiagnostic
radiographs or tumor markers, or residual
disease after chemotherapy and/or radiation
therapy.
● Mature teratoma is the only intracranial GCT for
which complete, upfront resection is
recommended. Germinoma is often biopsied,
followed by radiation and chemotherapy. Other
NGGCTs are often treated with upfront
chemotherapy and radiation therapy, followed
by resection of residual lesions if necessary.
● Obstructive hydrocephalus is often present at
diagnosis and is the source of most of the
common presenting symptoms (headache,
vomiting, Parinaud’s syndrome).
● Dilated ventricles at presentation provide a safe
and e ective route through which tissue
diagnosis can be obtained endoscopically.
Combined ETVand tumor biopsy, through either
a single or dual burr hole approach, can
e ectively treat hydrocephalus and provide
diagnostic tissue. Tiny biopsy specimens carry
the risk of misdiagnosis due to sampling error.
● Germinomas biopsied followed by adjuvant
therapy and completely resected mature
teratomas carry an excellent prognosis. Other
NGGCTs often carry a much poorer prognosis
Tumor
132

17.18 Common Clinical
Questions
1. What is the most common germ cell tumor of
childhood?
2. For intracranial germ cell tumors, describe the
most common general locations and the
variations that occur based on gender.
3. Describe the World Health Organization’s
classification of germ cell tumors and tumor
markers associated with the various tumors.
4. How do serum and/or CSF tumor marker levels
impact surgical decision-making and expected
prognosis?
5. What is the most common surgical approach to
a child with obstructive hydrocephalus and a
pineal region mass suspected to be germinoma?
Describe the operative approach.
17.19 Answers to Common
Clinical Questions
1. Sacrococcygeal teratomas account for close to
50% of all germ cell tumors prior to age 5.
Intracranial germ cell tumors account for a
small proportion of all germ cell tumors and
occur with much less frequency than gonadal
and other extragonadal locations (mediastinum,
retroperitoneal, etc.).
2. Most intracranial germ cell tumors occur
around the third ventricle. Males more
commonly have tumors in the pineal region and
females are more likely to have tumors in the
suprasellar area.
3. The 2007 WHO classification of tumors divides
intracranial germ cell tumors into germinomas
and nongerminomatous germ cell tumors
(NGGCTs). Pure germinomas tend to be negative
for b-HCG and AFP. Syncytiotrophoblastic
germinomas can frequently be positive for b-
HCG. Endodermal sinus tumors (yolk sac
tumors) typically secrete AFP. Choriocarcinomas
typically secrete b-HCG. Mature teratomas are
negative for b-HCG and AFP.
4. Patients with markedly elevated b-HCG and/or
AFP likely have choriocarcinoma, endodermal
sinus tumor, immature teratoma, or some other
mixed GCT. These NGGCTs often carry a much
worse prognosis than germinomas or
teratomas, and they may benefit from
chemotherapy or radiation therapy prior to
attempted resection. Tumors that are negative
for tumor markers are more likely to be
germinoma, teratomas, or some other non-GCT.
Upfront surgery is often performed in these
tumors that are negative for tumor markers.
5. Children w ith obstructive hydrocephalus and
a suspected pineal region germ inom a are
often treated w ith endoscopic third
ventriculostomy and an endoscopic biopsy
during the sam e operation. Use of a rigid
endoscope usually requires two separate
frontal burr holes in order to optim ize the
surgical angle for each stage of the procedure:
ETV is perform ed through a burr hole near
the coronal suture and tum or biopsy is
perform ed through a m ore anterior frontal
burr hole. Use of a flexible endoscope for ETV
and biopsy can often be perform ed through a
single burr hole.
References
[1] Lieuw K, Haas-Kogan D, Ablin A. Intracranial germ cell
tumors. In: Gupta N, Banerjee A, Haas-Kogan D, eds. Pediatric
CNS Tumors. Berlin: Springer-Verlag; 2004:107–121
[2] Frazier A, Amatruda J. Pediatric germ cell tumors. In: Orkin S,
Fisher D, Look A, Lux S, Ginsburg D, Nathan D, eds. Oncology
of Infancy and Childhood. Philadelphia, PA: Saunders
Elsevier; 2009:911–961
[3] Altm an RP, Randolph JG, Lilly JR. Sacrococcygeal teratoma:
American Academy of Pediatrics Surgical Section Survey-
1973. J Pediatr Surg. 1974; 9(3):389–398
[4] Isaacs H, Jr. Perinatal (fetal and neonatal) germ cell tum ors. J
Pediatr Surg. 2004; 39(7):1003–1013
[5] Bernstein L, Smith M, Liu L, Deapen D, Friedman D. Germ cell,
trophoblastic and other gonadal neoplasms. In: SEER Cancer
Statistics Review. Bethesda, MD: National Cancer Institute;
2007:125–137
[6] Ries L, Smith M, Gurney J, et al. Cancer incidence and survival
among children and adolescents: United States SEER
Program 1975–1995. In: National Cancer Institute SP, ed.
Volume 99–4649. Bethesda, MD: NIH Publication, 1999:179
[7] Jennings MT, Gelman R, Hochberg F. Intracranial germ-cell
tumors: natural history and pathogenesis. J Neurosurg. 1985;
63(2):155–167
[8] Echevarría ME, Fangusaro J, Goldman S. Pediatric central
nervous system germ cell tumors: a review. Oncologist.
2008; 13(6):690–699
[9] Jellinger K. Primary intracranial germ cell tumours. Acta
Neuropathol. 1973; 25(4):291–306
[10] Hayashi N, Murai H, Ishihara S, et al. Nationwide investigation
of the current status of therapeutic neuroendoscopy for
ventricular and paraventricular tumors in Japan. J Neurosurg.
2011; 115(6):1147–1157
[11] Matsutani M, Sano K, Takakura K, et al. Primary intracranial
germ cell tumors: a clinical analysis of 153 histologically
verified cases. J Neurosurg. 1997; 86(3):446–455
[12] Jubran RF, Finlay J. Central nervous system germ cell tumors:
controversies in diagnosis and treatment. Oncology
(Williston Park). 2005; 19(6):705–711, discussion 711–712,
715–717, 721
[13] Buetow SA. Epidemiology of testicular cancer. Epidemiol Rev.
1995; 17(2):433–449
Germ Cell Tumors
133

[14] Louis D, Ohgaki H, Wiestler O, Cavenee WK. WHO
classification of tum ours of the central nervous system. In:
Louis D, Ohgaki H, Wiestler O, Cavenee WK, eds. WHO
Classification of Tumours of the Central Nervous System.
Albany, NY: WHO Publication System; 2007:203
[15] Packer RJ, Cohen BH, Cooney K. Intracranial germ cell tumors.
Oncologist. 2000; 5(4):312–320
[16] Sano K, Matsutani M, Seto T. So-called intracranial germ cell
tum ours: personal experiences and a theory of their
pathogenesis. Neurol Res. 1989; 11(2):118–126
[17] Sano K. Pathogenesis of intracranial germ cell tumors
reconsidered. J Neurosurg. 1999; 90(2):258–264
[18] Louis DN, Ohgaki H, Wiestler OD, et al. The 2007 WHO
classification of tumours of the central nervous system. Acta
Neuropathol. 2007; 114(2):97–109
[19] Parsa A, Pincus D, Feldstein N, Balmaceda C, Fetel M, Bruce J.
Pineal region tumors. In: Keating R, Goodrich J, Packer R, eds.
Tumors of the Pediatric Central Nervous System. New York,
NY: Thieme, 2001:308–325
[20] Bjornsson J, Scheithauer BW, Okazaki H, Leech RW. Intracranial
germ cell tumors: pathobiological and immunohistochemical
aspects of 70 cases. J Neuropathol Exp Neurol. 1985; 44(1):32–
46
[21] Okada Y, Nishikawa R, Matsutani M, Louis DN. Hypomethylated
X chromosome gain and rare isochromosome 12p in diverse
intracranial germ cell tumors. J Neuropathol Exp Neurol. 2002;
61(6):531–538
[22] Kamakura Y, Hasegawa M, Minamoto T, Yamashita J, Fujisawa
H. C-kit gene mutation: common and widely distributed in
intracranial germinomas. J Neurosurg. 2006; 104(3) Suppl:
173–180
[23] Iwato M, Tachibana O, Tohma Y, et al. Alterations of the
INK4a/ARF locus in human intracranial germ cell tum ors.
Cancer Res. 2000; 60(8):2113–2115
[24] Zimmerman RA, Bilaniuk LT. Age-related incidence of pineal
calcification detected by computed tomography. Radiology.
1982; 142(3):659–662
[25] Watanabe S, Aihara Y, Kikuno A, et al. A highly sensitive and
specific chemiluminescent enzyme immunoassay for
placental alkaline phosphatase in the cerebrospinal fluid of
patients with intracranial germinomas. Pediatr Neurosurg.
2012; 48(3):141–145
[26] Miyanohara O, Takeshima H, Kaji M, et al. Diagnostic
significance of soluble c-kit in the cerebrospinal fluid of
patients with germ cell tumors. J Neurosurg. 2002; 97(1):
177–183
[27] Kawaguchi T, Kumabe T, Kanamori M, et al. Logarithmic
decrease of serum alpha-fetoprotein or human chorionic
gonadotropin in response to chemotherapy can distinguish a
subgroup with better prognosis among highly malignant
intracranial non-germinomatous germ cell tum ors. J
Neurooncol. 2011; 104(3):779–787
[28] Boop FA. Germ cell tumors. J Neurosurg Pediatr. 2010; 6(2):
123–, discussion 124
[29] Souweidane MM, Krieger MD, Weiner HL, Finlay JL. Surgical
management of primary central nervous system germ cell
tum ors: proceedings from the Second International
Symposium on Central Nervous System Germ Cell Tumors. J
Neurosurg Pediatr. 2010; 6(2):125–130
[30] Ray P, Jallo GI, Kim RY, et al. Endoscopic third
ventriculostomy for tum or-related hydrocephalus in a
pediatric population. Neurosurg Focus. 2005; 19(6):E8
[31] O’Brien DF, Hayhurst C, Pizer B, Mallucci CL. Outcomes in
patients undergoing single-trajectory endoscopic third
ventriculostomy and endoscopic biopsy for midline tumors
presenting with obstructive hydrocephalus. J Neurosurg.
2006; 105(3) Suppl:219–226
[32] Constantini S, Mohanty A, Zymberg S, et al. Safety and
diagnostic accuracy of neuroendoscopic biopsies: an
international multicenter study. J Neurosurg Pediatr. 2013;
11(6):704–709
[33] Shono T, Natori Y, Morioka T, et al. Results of a long-term
follow-up after neuroendoscopic biopsy procedure and third
ventriculostomy in patients with intracranial germinomas. J
Neurosurg. 2007; 107(3) Suppl:193–198
[34] Uschold T, Abla AA, Fusco D, Bristol RE, Nakaji P.
Supracerebellar infratentorial endoscopically controlled
resection of pineal lesions: case series and operative
technique. J Neurosurg Pediatr. 2011; 8(6):554–564
[35] Luther N, Stetler WR, Jr, Dunkel IJ, Christos PJ, Wellons JC, III,
Souweidane

MM.

Subarachnoid

dissemination

of
intraventricular tumors following simultaneous endoscopic
biopsy and third ventriculostomy. J Neurosurg Pediatr. 2010; 5
(1):61–67
[36] 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(6):1483–1496, discussion 1496
[37] Luther N, Cohen A, Souweidane MM. Hemorrhagic sequelae
from
intracranial neuroendoscopic procedures for
intraventricular tumors. Neurosurg Focus. 2005; 19(1):E9
[38] O’Kane R, Mathew R, Kenny T, Stiller C, Chumas P. United
Kingdom 30-day mortality rates after surgery for pediatric
central nervous system tum ors. J Neurosurg Pediatr. 2013; 12
(3):227–234
[39] Ho man HJ, Otsubo H, Hendrick EB, et al. Intracranial
germ -cell tum ors in children. J Neurosurg. 1991; 74(4):
545–551
[40] Balm aceda C, Heller G, Rosenblum M, et al. Chemotherapy
without irradiation–a novel approach for newly diagnosed
CNS germ cell tum ors: results of an international
cooperative trial. The First International Central Nervous
System Germ Cell Tum or Study. J Clin Oncol. 1996; 14(11):
2908–2915
[41] Matsutani M, Ushio Y, Abe H, et al. Japanese Pediatric Brain
Tumor Study Group. Combined chemotherapy and radiation
therapy for central nervous system germ cell tumors:
preliminary results of a Phase II study of the Japanese Pediatric
Brain Tumor Study Group. Neurosurg Focus. 1998; 5(1):e7
[42] Kanamori M, Kumabe T, Saito R, et al. Optimal treatment
strategy for intracranial germ cell tumors: a single institution
analysis. J Neurosurg Pediatr. 2009; 4(6):506–514
[43] Kellie SJ, Boyce H, Dunkel IJ, et al. Primary chemotherapy for
intracranial nongerminomatous germ cell tum ors: results of
the second international CNS germ cell study group protocol.
J Clin Oncol. 2004; 22(5):846–853
[44] Robertson PL, DaRosso RC, Allen JC. Improved prognosis of
intracranial non-germinoma germ cell tumors with
multimodality therapy. J Neurooncol. 1997; 32(1):71–80
[45] Garrè ML, El-Hossainy MO, Fondelli P, et al. Is chemotherapy
e ective therapy for intracranial immature teratoma? A case
report. Cancer. 1996; 77(5):977–982
[46] Modak S, Gardner S, Dunkel IJ, et al. Thiotepa-based high-
dose chemotherapy with autologous stem-cell rescue in
patients with recurrent or progressive CNS germ cell tum ors.
J Clin Oncol. 2004; 22(10):1934–1943
[47] Malone K, Croke J, Malone C, Malone S. Successful salvage
using combined radiation and ABMT for patients with
recurrent CNS NGGCT following failed initial transplant. BMJ
Case Rep. 2012; 2012:bcr2012006298
Tumor
134

[48] Kersh CR, Constable WC, Eisert DR, et al. Primary central
nervous system germ cell tumors. E ect of histologic
confirmation on radiotherapy. Cancer. 1988; 61(11):2148–
2152
[49] Shirato H, Nishio M, Sawamura Y, et al. Analysis of long-term
treatment of intracranial germinoma. Int J Radiat Oncol Biol
Phys. 1997; 37(3):511–515
[50] Ogino H, Shibam oto Y, Takanaka T, et al. CNS germ inom a
w ith elevated serum hum an chorionic gonadotropin
level: clinical characteristics and treatm ent outcom e. Int
J Radiat Oncol Biol Phys. 2005; 62(3):803–808
[51] Sawamura Y, Ikeda J, Shirato H, Tada M, Abe H. Germ cell
tum ours of the central nervous system: treatment
consideration based on 111 cases and their long-term clinical
outcomes. Eur J Cancer. 1998; 34(1):104–110
[52] Itoyama Y, Kochi M, Kuratsu J, et al. Treatment of intracranial
nongerminomatous malignant germ cell tumors producing
alpha-fetoprotein. Neurosurgery. 1995; 36(3):459–464,
discussion 464–466
[53] da Silva NS, Cappellano AM, Diez B, et al. Primary
chemotherapy for intracranial germ cell tumors: results of
the third international CNS germ cell tumor study. Pediatr
Blood Cancer. 2010; 54(3):377–383
[54] Yoo KH, Lee SH, Lee J, et al. Improved outcome of central
nervous system germ cell tumors: implications for the role of
risk-adapted intensive chemotherapy. J Korean Med Sci.
2010; 25(3):458–465
Germ Cell Tumors
135

18 Pineal Region Tumors
Scellig S.D. Stone, Alan R. Cohen
18.1 Introduction
Pineal region tumors account for less than 1% of
central nervous system tumors in adults; however,
this number is upward of 3% for pediatric brain
tumors.1 The prevalence is higher in Asian coun-
tries and males (~3:1 overall male:female ratio,
~12:1 for germ cell tumors [GCTs] specifically).
18.2 Anatomy and Physiology
The pineal gland sits within the pineal region,
corresponding to the posterior incisural space
(Fig. 18.1).2 The pineal region contains many
critical neural and vascular structures, and a work-
ing knowledge of this anatomy is of critical impor-
tance in order to successful navigate its confines
surgically. The borders of the pineal region
include:
● Superior: The splenium of the corpus callosum,
hippocampal commissure, and posterior aspect
of the tela choroidea.
● Anterior: The posterior aspect of the third
ventricle including the habenular and posterior
commissures, between which the pineal gland
attaches, and the quadrigeminal plate.
● Inferior: The cerebellum, mainly vermis.
● Lateral: The pulvinar nucleus of the thalamus
and the medial cerebral hemispheres.
● Posterior: The tentorial apex.
Fig. 18.1 Sagittal view of the pineal region. Arrows indicate approximate trajectories used for infratentorial
supracerebellar (a) occipital transtentorial (b) and range of interhemispheric retrocallosal or transcallosal (c) surgical
approaches.
136

Along with the gland, many critical vascular struc-
tures course through the pineal region, including:
● Arteries:
– The posterior cerebral and superior cerebellar
arteries.
– The lateral and medial posterior choroidal
arteries, the latter of which primarily supplies
the pineal gland.
● Veins:
– The vein of Galen.
– The basal veins of Rosenthal.
– The internal cerebral veins.
– The internal occipital veins.
– The vein of the cerebellomesencephalic fissure
(also known as precentral cerebellar vein).
The pineal gland itself arises as a diencephalic
diverticulum during embryogenesis.3 It is mainly
composed of pineocytes, melatonin-producing
neurosecretory cells that are believed to regulate
circadian rhythms, arranged in lobules among a
fibrovascular and glial stroma. The gland typically
develops radiographically visible calcifications by
the second decade of life.4
18.3 Classification of Tumors
Pineal region tumors can be classified by identity
and proportion using the following schema1,5,6
(special note—published series generally include
adults and the limited pediatric literature suggests
some greater variability7,8,9):
● 60%—GCTs:
– Ger minoma s: dysgerminoma, seminoma,
atypical teratoma.
– Nonger minomatous GCTs (NGGCTs):
○ Embryonal carcinoma.
○ Endodermal sinus tumor.
○ Choriocarcinoma.
○ Teratoma: only NGGCT either malignant or
benign, more likely ○ Mixed GCTs.
● 35%—neuroepithelial tumors:
– 25%—pineal parenchymal tumors:
○ Pineocytoma (WHO I) →astrocytic, neuronal
or comb.
○ Di erentiation more likely if >age 20.
○ Pineoblastoma (WHO IV) →pineocytic or
retinoblastomatous di erentiation more
likely if ○ Pineal parenchymal tumor of intermediate
di erentiation (WHO II, III).
– 10%—other neuroepithelial tumors:
○ Astrocytoma/glioblastoma.
○ Ependymoma.
○ Oligodendroglioma.
○ Choroid plexus papilloma/carcinoma.
○ Atypical teratoid rhabdoid tumor.
○ Papillary tumor of the pineal region (derived
from subcommissural organ).
– 5%—other tumors:
○ Meningioma.
○ Hemangiopericytoma.
○ Lipoma.
○ Primary melanocytic tumors.
○ Metastases.
● Nonneoplastic lesions:
– Pineal cysts (common incidental finding on
autopsy or magnetic resonance imaging
[MRI]).
– Arachnoid cyst.
– Va scular malfor mations:
○ Cavernous malformation.
○ Arteriovenous malformation.
○ Vein of Galen aneurysm.
– Der moid/epider moid cysts.
– Infectious/inflammator y lesions (abscess,
tuberculoma, etc.).
18.4 Clinical Presentation
Pineal region tum ors may present in several
ways based on local mass-related and remote
e ects.
18.4.1 Local Mass-related E ects
● Noncommunicating hydrocephalus is the most
common presentation:
– Headache, vomiting, lethargy, memory
disturbance, increasing head circumference,
full/bulging fontanel, papilledema.
● Par inaud’s syndrome due to quadrigeminal
plate compression:
– Supranuclear paralysis of conjugate upward
gaze.
– Light-near dissociation of accommodation
(sluggish to light).
– Paralysis of convergence.
● Cerebellar dysfunction due to cerebellar
compression:
– Ataxia, tremor.
● Pineal apoplexy manifesting as acute neurologic
deterioration following hemorrhage:
Pineal Region Tumors
137

– Headache, nausea, emesis, meningismus,
visual disturbance, decreased level of
consciousness.
18.4.2 Remote E ects
● Endocrinological disturbances:
– Precocious puberty (luteinizing hormone–like
e ect of beta-human chorionic gonadotropin
[beta-HCG] secretion).
– Diabetes insipidus (DI; strong association with
GCTs).
● Radiculopathy/myelopathy due to cerebrospinal
fluid (CSF) seeding and drop metastases.
● Symptoms of concomitant tumors:
– Retinoblastomas may occur in combination
with pineoblastomas, referred to as “trilateral
tumor.”
– Pineal region germinomas may present with a
symptomatic suprasellar tandem lesion (DI,
visual disturbance, hypopituitarism).
18.5 Investigations
18.5.1 Imaging
Contrast-enhanced craniospinal MRI is generally
indicated to evaluate the lesion and look for evidence
of tandem or disseminated disease (Fig. 18.2).
Computed tomography (CT) may demonstrate char-
acteristic patterns of calcification:
● Pineal parenchymal tumors may push or
“explode” existing calcifications peripherally.
● Other tumors, such as germinomas, may
“engulf” the calcified gland.
Calcification of the pineal gland prior to age 10
may suggest pathology; however, physiologic
calcification has been reported at younger ages
and thus should be interpreted w ith caution.4
Choriocarcinom a has a tendency for hem orrhagic
presentation.
18.5.2 Laboratory
GCT markers can narrow the diagnosis of pineal
region tumors, although mixed GCTs may compli-
cate interpretation.10 Serum markers should be
sent on all patients as they are nearly as sensitive
as direct CSF sampling. In cases without obstruc-
tive hydrocephalus, CSF may be sampled by lum-
bar puncture for markers and cytology. Potentially
useful markers include:
● Alpha-fetoprotein (AFP) →predominance
suggests endodermal sinus (also known as “yolk
sac”) tumor
Fig. 18.2 MRI of (a, b) pineal region
germinoma and (c, d) pineoblastoma.
(a) Sagittal contrast-enhanced T1-
weighted MRI demonstrating tandem
pineal and suprasellar enhancing le-
sions. (b) Coronal T2-weighted image
demonstrating lateral ventricular en-
largement with transependymal flow,
and displacement of the internal cer-
ebral veins above and basal veins of
Rosenthal laterally to the lesion.
(c) Axial T2-weighted MRI demon-
strating a mass in the posterior third
ventricle/pineal region with associated
hydrocephalus. The internal cerebral
veins can be seen as flow voids draped
over the posterior aspect of the lesion
bilaterally. (d) Heterogeneously
enhancing mass in the posterior
third ventricle/pineal region.
Tumor
138

● Beta-HCG →predominance suggests
choriocarcinoma.
● Placental alkaline phosphatase →predominance
suggests germinoma.
Positive markers are diagnostic for malignant GCTs
and obviate the need for a tissue diagnosis. Serial
testing of markers can also provide a useful means
of monitoring response to therapy and detecting
occult metastases. In certain cases, it may also be
useful to complete a full endocrine workup,
including tests of pituitary function.
18.6 Management
A sellar/suprasellar lesion, midbrain compression, or
obstructive hydrocephalus should prompt a formal
ophthalmological evaluation. Emergent hydroce-
phalus may necessitate ventriculostomy placement
for stabilization.
The presence of classic-appearing tandem or bifo-
cal tumors in the pineal and suprasellar regions,
without elevation of markers, is considered diagnos-
tic for germinoma and generally negates the need
for a tissue diagnosis. With classic appearance on
imaging, upfront open resection should be consid-
ered for certain cases, such as meningioma, tera-
toma, and epidermoid. In all other scenarios, a
tissue diagnosis is needed.
In the setting of hydrocephalus, endoscopic
transventricular biopsy and CSF sampling for
markers are preferred. Symptomatic obstructive
hydrocephalus may be simultaneously treated by
endoscopic third ventriculostomy (ETV), thus
avoiding a shunt with subsequent potential for
abdominal seeding of malignancy.
In the absence of hydrocephalus, stereotactic
biopsy and/or cyst drainage is an option in experi-
enced hands, with one large series of 370 patients
indicating a diagnostic yield of 94%, morbidity of
8.1%, and mortality of 1.3%.11 However, proximity
with critical venous structures limits its use by
many centers. Sampling error can also theoreti-
cally complicate any procedure involving minimal
tissue sampling.
When less invasive tissue sampling is not appli-
cable and a pathognomonic imaging/marker diag-
nosis is not made, open biopsy with CSF sampling
should be considered.
18.7 Treatment and Outcomes
Overall treatment options include serial observa-
tion, surgical resection, focal and/or craniospinal
radiation, and chemotherapy. These modalities are
used in isolation or combination depending on the
specific histopathologic diagnosis, and vary by
institution. Typical treatments and outcomes for
key tumors are summarized in Table 18.1.5,6,12,13
18.8 Endoscopic and
Microsurgical Approaches
Although stereotactic biopsy is an option (see Ma-
nagement section), surgical treatment more com-
monly involves endoscopy or open microsurgery
to achieve CSF diversion as needed, obtain a diag-
nosis, and resect the lesion when appropriate.
18.8.1 Anterior Neuroendoscopic
Endoscopic transventricular surgery, pioneered in
the 1970s by Fukushima for the purpose of tumor
biopsy, can permit sampling of CSF, treatment of
hydrocephalus, and biopsy of pineal tumors.14,15
Complete resection is precluded by the limited
ability to achieve hemostasis, confined approach
angles, and the small number and size of available
instruments.
The patient is placed supine with a flexed neck.
Generally, the nondominant hemisphere is trans-
gressed. Planned entry points for tumor biopsy in
the posterior third ventricle/pineal region are gen-
erally at or just medial to the midpupillary line,
several centimeters anterior to the coronal suture,
and can be refined using neuronavigation to visu-
alize access to the lesion via straight passage
through the foramen of Monro. In contrast, the
optimal entry point for an ETV is more posterior,
near the coronal suture. Rigid endoscopes gener-
ally provide the best optics and potentially most
working ports for instrument flexibility; however,
separate entry points may be required if both an
ETV and tumor biopsy are performed. The use of a
single burr hole somewhere between these opti-
mal sites and angled scopes may resolve this issue
(Fig. 18.3).16 Alternatively, a flexible endoscope
can be used. Care must be taken to avoid retrac-
tion injury to the fornices. If needed, an ETV is
Pineal Region Tumors
139

Table 18.1 Treatment strategies and outcomes for selected pineal region tumors
Tumor

Typical treatment strategy (other options)

Outcomes
GCTs
Germinoma

Local radiation, craniospinal radiation + local
boost, ± chemotherapy (with lowered radiation
dose)
80–95% 5-y OS
Mature teratoma (congenital form) Surgical resection

80–95% 5-y OS
>90% mortality
Immature teratoma + malignant
component
Surgical resection + local radiation, surgical
resection alone ( +craniospinal radiation +
chemotherapy)
Surgical resection + craniospinal radiation
( +local boost +chemotherapy)
60–70% 5-y OS
Other malignant NGGCT

Craniospinal radiation + local boost ± surgical
resection ± chemotherapy
25% 5-y OS
Pineal parenchymal tumors
Pineocytoma

Initial observation, surgical resection ( +local
radiation or local radiation alone if<3 cm)
80–90% 5-y OS
Intermediate differentiation

Low grade: surgical resection ( +chemotherapy ±
radiation)
High grade: surgical resection + chemotherapy+
radiation
75% 5-y OS
40% 5-y OS
Pineoblastoma

Craniospinal radiation +local boost +chemotherapy
(± surgical resection)
10–20% 5-y OS, less if+ CSF
Other notable tumors
Low-grade glioma

Observation or individualized multimodality

75% 5-y OS
High-grade glioma

Radiation + chemotherapy (± surgical resection)

10% 5-y OS
Abbreviations: CSF, cerebrospinal fluid; GCTs, germ cell tumors; NGGCT, nongerminomatous germ cell tumor; OS, overall
survival.
Fig. 18.3 Anterior neuroendoscopic
trajectories as projected onto the
midsagittal plane. The lateral position,
typically at or just medial to the
midpupillary line, is not depicted.
(a) Optimal burr hole location for
straight trajectory to biopsy posterior
third ventricular lesion, (b) intervening
entry point to permit both biopsy and
third ventriculostomy, and (c) optimal
burr hole location for third ventricu-
lostomy.
Tumor
140

generally performed prior to tumor biopsy
because bleeding post biopsy can obscure visual-
ization of anatomical landmarks. The success of
endoscopic biopsy may be negatively a ected by
limited tissue sampling, although direct visualiza-
tion of the lesion allows selective sampling from
multiple regions. An external ventricular drain
may be left in place when ETV function is uncer-
tain or following excessive intraventricular hemor-
rhage.
18.8.2 Microsurgery
Although multiple options and variances exist,
two main open approaches to the pineal region
are most commonly used: the infratentorial supra-
cerebellar and occipital transtentorial approaches
(Fig. 18.1).15,17 A parietal posterior interhemi-
spheric and other routes are also discussed briefly.
The choice of approach is partially dictated by the
extent of the lesion, its relationship to critical
neurovascular structures in the pineal region,
the goal(s) of surgery, and surgeon familiarity/
comfort.
Infratentorial Supracerebellar
Pioneered by Krause and further refined/popular-
ized by Stein in the early 1900s, this approach
lends itself to small- to medium-sized lesions that
are largely confined to the pineal region and below
the vein of Galen.18,19 Following the natural plane
between the cerebellum and tentorium minimizes
brain retraction (Fig. 18.1).
Positioning
If performed using the sitting position, cerebellar
retraction and venous pressure can be minimized,
although downsides include the risk of venous
embolism and surgeon discomfort. The prone posi-
tion with neck flexion (or “Concorde” position) less-
ens the risk of venous embolism but necessitates
cerebellar retraction in most cases. A modified lat-
eral position can be employed to balance the pros
and cons of these alternatives, although anatomic
orientation may be less familiar.
Dissection
Through a midline skin incision, a bone flap is ele-
vated extending just above the transverse sinus to
the foramen magnum, with care taken to protect
the torcular and transverse sinuses. The dura
mater is opened with an inverse semicircular inci-
sion, based at the transverse sinuses, extending
the full width of the craniotomy. Bridging veins
from the midline superior cerebellar surface to the
tentorium are sacrificed as needed; however, post-
operative cerebellar venous congestion and swel-
ling may occur if lateral veins are taken in excess.
The precentral cerebellar vein and associated thick
arachnoid membrane are typically taken and
opened respectively, gaining exposure to the lesion
(Fig. 18.4).
Fig. 18.4 View of a pineal region tumor after arachnoid opening from an infratentorial supracerebellar approach. Note
the cerebellum retracted inferiorly.
Pineal Region Tumors
141

Occipital Transtentorial
Initially described by Heppner in 1959 and later
modified by Jamieson, this approach allows access
to relatively large lesions extending beyond the
pineal region and into the third ventricle and
lesions in the region of the cerebellomesence-
phalic cistern (Fig. 18.1).20,21
Positioning
The prone position with relatively neutral neck
flexion allows a surgical trajectory perpendicular
to the floor and generally provides the easiest ori-
entation. Alternatively, a semi-lateral position may
be used to allow gravity to retract the cerebral
hemisphere.
Dissection
The skin incision can take the form of a three-sided
flap designed to preserve scalp blood supply, or a
paramedian incision with a superolaterally curved
extension allowing lateral/inferior reflection of the
scalp. A large bone flap is elevated extending just
below and across the transverse and superior sag-
ittal sinuses, respectively, allowing dural reflection
across each. Bridging veins draining the occipital
lobe into the superior sagittal sinus are generally
safely anterior, but some entering the transverse
sinus may partially obstruct access and warrant
consideration of either limited sacrifice or a con-
tralateral approach. An occipital ventriculostomy
allows greater decompression of the ipsilateral
occipital lobe and thus less chance of retraction
injury. The tentorium is divided as needed from
anterior to posterior, staying lateral to the straight
and stopping short of the transverse sinuses
(Fig. 18.5). Further contralateral exposure can be
gained by dividing the inferior sagittal sinus and
incising the falx.
Posterior Interhemispheric
Transcallosal and/or Retrocallosal
Originated by Dandy in the 1920s and later modi-
fied by others including McComb, this is primarily
an option for lesions truly in the posterior third
ventricle that push the internal cerebral veins pos-
teriorly and inferiorly such that the lower angle
associated with the above approaches would
require excessive mobilization of the veins
(Fig. 18.1).22,23
Positioning
The patient may be placed prone with slight neck
extension. Semi-prone positioning can be used to
promote gravity retraction of the cerebral hemi-
sphere, although orientation is more challenging.
Preoperative assessment of bridging vein anatomy
can help determine the optimal side of approach,
with preference to the nondominant side if veins
are not an issue.
Dissection
A coronally oriented straight skin incision across
midline, or inverted U across midline and reflected
inferolaterally, can be used to both maximize
exposure and preserve scalp blood supply. A large
bone flap over the vertex and extending across
Fig. 18.5 View of pineal region tumor after dividing tentorium and opening arachnoid from a right occipital
transtentorial approach.
Tumor
142

midline allows greater flexibility to avoid bridging
veins and alter trajectory. The dura is reflected
over the superior sagittal sinus. After confirming
trajectory and identifying/protecting the perical-
losal arteries, a limited callosotomy or subsplenial
approach is used to access the lesion.
Posterior Transcortical, Posterior
Subtemporal, Paramedian
Supracerebellar, Combined
These are rarely used due to the extent of brain
transgressed, need for temporal lobe retraction,
invasiveness, and/or limited exposure.15,17 A trans-
cortical approach is reserved for select cases with
a very dilated lateral ventricle and is generally per-
formed through a high parietal transcortical route
in order to minimize injury to the visual pathways.
For large lesions with significant anterior exten-
sion, a combined or staged approach using both a
posterior pineal and an anterior route to the third
ventricle may be needed.
18.9 Complications
The nature and expected frequency of complica-
tions related to surgical management of pineal
tumors vary widely depending on the nature of
individual lesions and the approach selected. Most
modern series report permanent morbidity and
mortality rates below 10%.24
Venous sinus injury during exposure can lead
to air em bolism , thus experienced anesthesia,
blood product availability, a plan for m anage-
m ent, and the use of end-tidal carbon dioxide
and cardiac doppler m onitors are recom mended.
Venous insu ciency and infarction can result
from excessive interruption of cerebellar venous
drainage, anterior occipital/posterior parietal/lat-
eral occipital bridging veins. In the case of the
cerebellum , this can lead to postoperative swel-
ling with obstructive hydrocephalus or tonsillar
herniation. Deep venous injury m ust be avoided
and can lead to severe m orbidity or m ortality.
Direct or indirect injury to brain regions from
venous or arterial insu ciency, or retraction
injury, can cause focal neurologic deficits such as
cerebellar dysfunction, contralateral hem ianopia
due to visual cortex or optic radiation injury,
contralateral hem iparesis, and contralateral sen-
sory deficits including stereognosis. Retraction
injury can be m inim ized through the use of
temporary CSF drainage via lum bar drain or
ventriculostomy and/or hyperosm olar therapy. A
corpus callosotomy of less than 2 cm in length is
generally well tolerated; however, injury can
rarely lead to disconnection syndrom es. Excision
of lesions closely abutting or involving the m id-
brain frequently results in at least transient
extraocular m ovem ent abnorm alities including
im paired upgaze and convergence.
In the immediate postoperative period, intensive
care unit monitoring is required with particular
attention paid to signs of hemorrhage (particularly
when an incomplete resection has been per-
formed) and hydrocephalus. Should concern exist
over the potential for seizures secondary to corti-
cal injury, one may consider a prophylactic antie-
pileptic in the immediate postoperative period. A
short course of peri- and postoperative steroids
may be considered if considerable cerebral swel-
ling is anticipated.
18.10 Common Clinical
Questions
1. How do pineal region lesions typically present
clinically?
2. Which pineal region lesions classically present
with marked and relatively specific elevated
serum and/or CSF AFP, and beta-HCG?
3. What features of a pineal region lesion may
help a surgeon decide between using a
supracerebellar infratentorial versus occipital
transtentorial approach?
4. Name five pineal region tumors for which
complete surgical resection is often the sole
treatment.
18.11 Answers to Common
Clinical Questions
1. Clinical features include: local mass-related
e ects (including symptoms of raised
intracranial pressure due to hydrocephalus,
Parinaud’s syndrome due to quadrigeminal
plate compression, cerebellar dysfunction due
to compression, and less commonly pineal
apoplexy following hemorrhage), remote e ects
(including endocrinological disturbances such
as precocious puberty and DI, and
radiculopathy/myelopathy due to CSF seeding),
and symptoms of concomitant tumors
(including ocular symptoms due to
retinoblastoma or suprasellar lesions).
Pineal Region Tumors
143

2. A marked and relatively specific elevation of
AFP is classically seen with endodermal sinus
tumors, and beta-HCG with choriocarcinoma.
3. The supracerebellar infratentorial approach
lends itself to small- to medium-sized lesions
that are largely confined to the pineal region
and below the vein of Galen. The occipital
transtentorial may be more appropriate for
large lesions extending beyond the pineal
region and into the third ventricle, or into
cerebellomesencephalic cistern.
4. Complete surgical resection can be curative for
many pineal region tumors. Examples include:
meningioma, epidermoid, mature teratoma,
pineocytoma, intermediately di erentiated
pineal parenchymal tumor with low-grade
features, and low-grade glioma.
References
[1] Al-Hussaini M, Sultan I, Abuirmileh N, Jaradat I, Qaddoumi I.
Pineal gland tumors: experience from the SEER database. J
Neurooncol. 2009; 94(3):351–358
[2] Rhoton AL, Jr. Tentorial incisura. Neurosurgery. 2000; 47(3)
Suppl:S131–S153
[3] Sadler TW. Langman’s Medical Embryology. 9th ed.
Philadelphia, PA: Lippincott Williams & Wilkins; 2004:534
[4] Barkovich AJ. Diagnostic Imaging Pediatric Neuroradiology.
Salt Lake City, UT: Amirsys; 2007
[5] Louis DN. WHO Classification of Tumours of the Central
Nervous System. 4th ed. Lyon: International Agency for
Research on Cancer; 2007
[6] Perry A, Brat DJ. Practical Surgical Neuropathology: A
Diagnostic Approach. Philadelphia, PA: Churchill Livingstone/
Elsevier; 2010
[7] Bailey S, Skinner R, Lucraft HH, Perry RH, Todd N, Pearson
AD. Pineal tum ours in the north of England 1968–93. Arch
Dis Child. 1996; 75(3):181–185
[8] Edwards MS, Hudgins RJ, Wilson CB, Levin VA, Wara WM.
Pineal region tumors in children. J Neurosurg. 1988; 68(5):
689–697
[9] Kang JK, Jeun SS, Hong YK, et al. Experience with pineal
region tumors. Childs Nerv Syst. 1998; 14(1—2):63–68
[10] Bernstein M, Berger MS. Neuro-oncology: The Essentials. 2nd
ed. New York, NY: Thieme; 2008
[11] Regis J, Bouillot P, Rouby-Volot F, Figarella-Branger D, Dufour
H, Peragut JC. Pineal region tumors and the role of
stereotactic biopsy: review of the mortality, morbidity, and
diagnostic rates in 370 cases. Neurosurgery. 1996; 39(5):
907–912, discussion 912–914
[12] Villano JL, Propp JM, Porter KR, et al. Malignant pineal germ-
cell tumors: an analysis of cases from three tumor registries.
Neuro-oncol. 2008; 10(2):121–130
[13] Schild SE, Scheithauer BW, Haddock MG, et al. Histologically
confirmed pineal tumors and other germ cell tumors of the
brain. Cancer. 1996; 78(12):2564–2571
[14] Fukushima T, Ishijima B, Hirakawa K, Nakamura N, Sano K.
Ventriculofiberscope: a new technique for endoscopic
diagnosis and operation. Technical note. J Neurosurg. 1973;
38(2):251–256
[15] Little KM, Friedman AH, Fukushima T. Surgical approaches to
pineal region tum ors. J Neurooncol. 2001; 54(3):287–299
[16] Robinson S, Cohen AR. The role of neuroendoscopy in the
treatment of pineal region tumors. Surg Neurol. 1997; 48(4):
360–365, discussion 365–367
[17] Yamamoto I. Pineal region tumor: surgical anatomy and
approach. J Neurooncol. 2001; 54(3):263–275
[18] Bruce JN, Stein BM. The infratentorial supracerebellar
approach. In: Apuzzo MLJ, ed. Surgery of the Third Ventricle.
2nd ed. Baltimore, MD: Williams & Wilkins; 1998:697–719
[19] Krause F. Chirurgie des Gehirns und Rückenmarks nach
eigenen Erfahrungen. Berlin: Urban & Schwarzenberg; 1911
[20] Jamieson KG. Excision of pineal tumors. J Neurosurg. 1971;
35(5):550–553
[21] Heppner F. On operation technic in pinealoma [in German].
Zentralbl Neurochir. 1959; 19:219–224
[22] McComb JG, Levy ML, Apuzzo MLJ. The posterior
interhemispheric retrocallosal and transcallosal approaches
to the third ventricle region. In: Apuzzo MLJ, ed. Surgery of
the Third Ventricle. 2nd ed. Baltimore, MD: Williams &
Wilkins; 1998:743–777
[23] Dandy WE. An operation for the removal of pineal tumors.
Surg Gynecol Obstet. 1921; 33:113–119
[24] Bruce JN. Pineal tumors. In: Winn HR, ed. Youmans
Neurological Surgery. Vol 2. 6th ed. Philadelphia, PA: Elsevier
Saunders; 2011:1359–1372
Tumor
144

19 Intraventricular Tumors in Children
Bryan S. Lee, Vikram B. Chakravarthy, Nir Shimony, Violette M.R. Recinos
19.1 Introduction
Intraventricular tumors are rare primary central
nervous system (CNS) neoplasms located within
the ventricular system; these tumors occur more
commonly in the pediatric population and make
up 16% of all pediatric intracranial tumors.1 Intra-
ventricular tumors can be categorized into pri-
mary and secondary intraventricular tumors,
depending on their origin. Primary tumors develop
from within the ventricle, arising from the epen-
dyma, subependymal glia of the ventricle, and cho-
roid plexus, which include ependymoma, choroid
plexus papilloma (CPP) and choroid plexus carci-
noma (CPC), subependymal giant cell astrocytoma
(SEGA), subependymoma, central neurocytoma,
and intraventricular astrocytoma and meningi-
oma.2,3 Secondary tumors are also called paraven-
tricular tumors that develop from the brain paren-
chyma, and bulge into the ventricle (greater than
two-thirds of the tumor volume by definition).2
They include medulloblastoma, meningioma,
astrocytoma, lymphoma, craniopharyngioma, and
germ cell tumors. The most common intraventric-
ular tumors in the pediatric population are epen-
dymoma, CPP, and astrocytomas located in the
lateral and frontal horns.4 Other less common
tumors include SEGA, oligodendroglioma, sube-
pendymoma, pilocytic astrocytoma in the cerebel-
lum, neurocytoma, and CPC.4 Pilocytic astrocytoma
is considered the most common pediatric brain
tumor, comprising 15% of pediatric brain tumors.5
Pilocytic astrocytoma, however, is paraventricular
in location and, therefore, comprises only a small
fraction of all pediatric intraventricular tumors.6
● The incidence of pediatric cancer, including brain
tumors, has increased over the last three
decades.7
● Intraventricular tumors compose 0.8 to 1.6% of
all pediatric CNS tumors. The majority of
intraventricular tumors are benign.4
● Within the lateral ventricle, approximately 43%
occur in the frontal horn and foramen of Monro,
whereas 22% occur in the body and septum
pellucidum, 20% in the atrium, 9% in the
temporal horn, and 6% in the occipital horn.3,8
● Lateral ventricular tumors in younger children
are most commonly CPPs and CPCs, where in the
older pediatric group low-grade gliomas,
including ependymomas, pilocytic astrocytomas,
and SEGAs, are more frequently found.9
● Genetic predisposition has been shown to be
associated with intracranial tumors, and most of
these congenital syndromes are transmitted as
autosomal dominant traits within tumor
suppressor genes.4 Neurofibromatosis type I is
associated with pilocytic astrocytoma,
neurofibromatosis type II with ependymoma,
tuberous sclerosis with SEGA, Turcot’s syndrome
with astrocytoma, Li–Fraumeni syndrome with
malignant astrocytoma, and rhabdoid
predisposition syndrome with CPC.10
19.2 Ependymoma
● Incidence and epidemiology: Ependymomas are
circumscribed tumors that usually arise from the
floor of the fourth ventricle, whereas in adults
these tumors more commonly involve the spinal
cord, and are commonly associated with
calcification, hemorrhage, and cysts.4
Ependymomas that occasionally grow out of the
fourth ventricle through foramina of Luschka
and Magendie to involve the cisterns are
categorized as plastic ependymomas.11
Ependymoma is a rare tumor with the incidence
of 2.1 to 2.5 per 1 million children younger than
15 years of age; however, it is one of the most
common intraventricular tumor in the pediatric
population.4,12
● Prognosis: The time of diagnosis is known to
determine the outcome in patients with
ependymoma, likely secondary to lower rate of
complete resection, no radiation therapy, and
aggressive nature of the tumor itself.13 The
extent of resection is considered to be the most
significant prognostic factor: 5-year overall
survival (OS) for patients undergoing gross total
resection is 66%, whereas it is 25% for subtotal
resection.14 Three-year progression-free survival
rate for patients surgically treated overall was
26%.15
● Histopathology and neuroradiology: Most
ependymomas are World Health Organization
(WHO) grade II lesions and are well-delineated
uniform cells with moderate cellularity and
monomorphic round nuclei.16 These cells exhibit
perivascular pseudorosettes, also known as
145

Homer Wright rosettes, more commonly than
true ependymal rosettes, also known as Flexner–
Wintersteiner rosettes, and are typically GFAP
positive (Fig. 19.1). Ependymomas are well-
demarcated lesions that are hypointense on T1-
weighted magnetic resonance imaging (MRI)
and hyperintense on T2-weighted MRI, with
heterogeneous enhancement with gadolinium
administration (Fig. 19.2).17
19.3 Choroid Plexus Papilloma
and Carcinoma
● Incidence and epidemiology: CPPs occur
predominantly in the lateral ventricle in
children, more specifically in the left atrium,
contrary to the fourth ventricular location in
adults.14,18 CPP tumors occur most frequently in
pediatric patients younger than 3 years of age,
and comprise approximately 0.5% of all
intracranial tumors but almost 12% of all
pediatric brain tumors for children younger than
2 years of age.14
● Prognosis: CPP treated surgically w ith
complete resection is know n to have 5-year
survival rate of approxim ately 100%.14 CPCs are
frequently invasive w ith a relatively poor
prognosis, with a 5-year OS rate of 40 to
50%.18,19
● Histopathology and neuroradiology: Histological
hallmarks of CPP include single layer of cuboidal
epithelial cells around a fibrovascular core, and
positive staining for cytokeratin, GFAP, vimentin,
and S100 (Fig. 19.3). Whereas ependymomas
Fig. 19.1 Histopathology of ependymoma exhibiting
perivascular pseudorosettes, also known as Homer
Wright rosettes.
Fig. 19.2 MRI of ependymoma, demonstrating (a) a well-demarcated lesion hypo-/isointense on T1-weighted sagittal
sequence and (b) hyperintense on T2-weighted axial sequence, (c) with heterogeneous enhancement with gadolinium
on T1-weighted axial sequence.
Fig. 19.3 Histopathology of CPP showing single layers
of cuboidal epithelial cells around a fibrovascular core.
Tumor
146

are uniformly GFAP positive, CPPs are di usely
but not uniformly GFAP positive.20 CPC is an
aggressive neoplasm that is typically
characterized by cellular anaplasia, nuclear
pleomorphism, prominent mitoses, necrosis, and
overall loss of di erentiated papillary choroid
structure.20 CPCs retain cytokeratin positivity
but less typically stain with S100.21 CPP and CPC
are both hypointense on T1-weighted sequence
and hyperintense on T2-weighted sequence,
with homogeneous enhancement with
gadolinium administration (Fig. 19.4 and
Fig. 19.5).
19.4 Subependymoma
● Incidence and epidemiology: 82% of patients are
older than 15 years of age, with majority being
middle-aged and older males. Often found at
autopsy in asymptomatic patients. Most are
found to be smaller than 2 cm in size with
symptomatic lesions measuring 3 to 5 cm in
diameter. Patients commonly present with
symptoms secondary to hydrocephalus, due to
ventricular obstruction.22
● Prognosis: Benign lesions (WHO grade I) with
low recurrence rate after gross total resection.
Extraventricular extension is very rare.23 Even
with partial resection, postoperative adjuvant
radiation or chemotherapy is not indicated due
to a low risk for recurrence.
● Histopathology and neuroradiology:
Subependymomas are typically found in the fourth
ventricle and exhibit clusters of small nuclei in a
dense fibrillary background of neuroglial fibers,
often described as “islands of blue in a sea of pink”
Fig. 19.4 MRI of CPP showing hypo-/isointense on (a) T1-weighted sagittal sequence and (b) hyperintense on
T2-weighted axial sequence, (c) with homogeneous enhancement with gadolinium on T1-weighted axial sequence.
Fig. 19.5 MRI of CPC demonstrating (a) hypointensity on T1-weighted sagittal sequence and (b) hyperintensity on
T2-weighted axial sequence, (c) with enhancement with gadolinium on T1-weighted axial sequence.
Intraventricular Tumors in Children
147

(Fig. 19.6).24,25 On MRI, they appear hypointense
on T1-weighted sequence and hyperintense on T2-
weighted sequence. Subependymoma in the lateral
ventricles is the only intraventricular tumor that
does not enhance with gadolinium administration
on T1-weighted sequence.24 Subependymoma in
the fourth ventricle, however, can have
heterogeneous contrast enhancement
(Fig. 19.7).26 Calcification is present in 31%
and cystic lesions are present in 18%.
19.5 Subependymal Giant Cell
Astrocytoma
● Incidence and epidemiology: Most common
neoplasm associated with tuberous sclerosis
(20%), arising in the first two decades of life,
typically presenting with seizures. SEGAs are
slow-growing glioneuronal tumors, usually 2 to
3 cm at time of diagnosis, which eventually lead
to ventricular obstructions.
● Prognosis: Benign (WHO grade I) tumors. Earlier
diagnosis is associated with increased survival.
Open-label, prospective clinical trial over 5 years
demonstrated e ectiveness of everolimus in
preventing the growth of SEGA lesions with no
significant toxicities or side e ects. In this study,
no patients progressed to requiring surgical
intervention.27
● Histopathology and neuroradiology: SEGAs are
located near the foramen of Monro. They are
composed of relatively large cells that resemble
gemistocytic astrocytes, but often have
“ganglioid” nuclei with prominent nucleoli and
elongated fibrillar processes.28 Nuclear
pleomorphism and mitoses may be present;
however, they do not indicate anaplastic change.
Immunohistochemistry demonstrates both glial-
and neuronal-associated antigens.28 On
computed tomography (CT), SEGA appears iso-
to hypodense with presence of calcifications. At
times, they can be hyperdense, indicating
presence of hemorrhage. On MRI, it
demonstrates avidly contrast-enhancing mass in
T1-weighted image, located at or near the
foramen of Monro.22
19.6 Central Neurocytoma
● Incidence and epidemiology: Most commonly
occur in older children and young adults,
extremely rare in the pediatric age group,
Fig. 19.6 Histopathology of subependymoma exhibit-
ing clusters of small nuclei in a dense fibrillary
background of neuroglial fibers.
Fig. 19.7 MRI of subependymoma demonstrating (a) iso-/hypointensity on T1-weighted sagittal sequence and (b) iso-/
hyperintensity on T2-weighted axial sequence, (c) with mild enhancement with gadolinium on T1-weighted axial
sequence.
Tumor
148

presenting with symptoms of elevated
intracranial pressure. The median age in a ected
children is 16 years.29 Constitute 0.25 to 0.5% of
all intracranial tumors. Clinical presentation
includes symptoms arising from elevated
intracranial pressure, such as headaches, nausea/
emesis, and visual deficits.
● Prognosis: Low-grade tumor (WHO II), good
prognosis with surgical excision being the
mainstay of treatment. Complete tumor removal
leads to better tumor control and survival. There
is little evidence of the use of adjuvant
radiotherapy in children. However, after subtotal
resections adjuvant radiotherapy can aid in local
tumor control. Extraventricular extension is
associated with poor prognosis. The atypical
variant demonstrates increased Ki-67 activity
leading to aggressive biologic behavior.23
● Histopathology and neuroradiology: Arising
from the third or lateral ventricle in the region of
the foramen of Monro with attachment to the
septum pellucidum commonly. Composed of
small, well-di erentiated neurons with uniform
round nuclei, fine chromatin, and occasional
nucleoli in a loose neuropil-like background.
Fixation artifact may demonstrate perinuclear
clearing. Hematoxylin–eosin staining
demonstrates immunoreactivity for
synaptophysin and neuron-specific enolase.
Atypical variant can present with microvascular
proliferation, focal necrosis, and elevated mitotic
activity.28 On CT, calcifications are routinely
found. On MRI, these tumors are T1 iso- to
hypointense and T2 iso- to hyperintense, with
mild to moderate heterogeneous contrast
enhancement (Fig. 19.8).30
19.7 Clinical Presentation
Clinical symptoms of intraventricular tumors are
secondary to obstructive hydrocephalus from
obstruction of cerebrospinal fluid (CSF) flow, or
secondary to nonobstructive, communicating
hydrocephalus from overproduction of CSF. Typical
manifestations of hydrocephalus include head-
ache, nausea, emesis, vision changes, papilledem a,
and altered mental status. In the younger age
group, common signs and symptoms also include
increased head circumference, irritability, and fail-
ure to thrive. More than half the pediatric patients
younger than 2 years of age present with tense
fontanelles, macrocrania, and diastasis of the cra-
nial sutures.14
Relatively uncommon features
include seizures, memory loss due to mass e ect
on the fornix, and spontaneous hemorrhage.8
● The majority of tumors of the lateral and third
ventricles are benign. Typically, clinical
symptoms do not appear until the lesions
enlarge to the size of a few centimeters causing
mass e ect on adjacent parenchyma.31
19.8 Surgical Approach and
Techniques
Both primary and secondary intraventricular
tumors can be removed via either standard open
craniotomy or endoscopic approach. Traditionally,
transcortical approach has been used, but more
recently, transcallosal-interhemispheric approach
is favored as it can provide direct access to the ven-
tricles without passing through significant
amounts of parenchyma.32 Surgical approaches to
Fig. 19.8 MRI of central neurocytoma appearing (a) iso-/hypointense on T1-weighted sagittal sequence, (b) iso- to
hyperintense on T2-weighted axial sequence, and (c) with mild heterogeneous gadolinium enhancement on
T1-weighted axial sequence.
Intraventricular Tumors in Children
149

intraventricular tumors are summarized in the fol-
lowing (Table 19.1).
● Lateral ventricular tum ors: Anterior
transsulcal approach, posterior transsulcal
approach, posterior transcallosal approach,
posterior temporal approach, and inferior
temporal approach can be employed.
– Anterior transsulcal (transsuperior frontal
sulcus) approach is frequently used for tumors
located in the anterior lateral ventricles and
preferable for lesions with large, midline-
draining cortical veins.31
– Posterior transsulcal approach, in which
craniotomy extends over the superior parietal
lobule, is the preferred method to gain access
to the atrium of the lateral ventricle. One
should be careful not to injure the optic
radiations in the lateral wall of the atrium.
– Posterior transcallosal approach can provide
easy access to the roof and medial portion of
the atrium by splitting the splenium of the
corpus callosum, but due to high risk of alexia,
this approach should not be used in patients
with homonymous hemianopsia contralateral
to the dominant hemisphere.31
– Posterior temporal approach provides access
to the lateral part of the atrium, and as it
exposes above the plane of the transverse
sinus, care should be taken not to injure the
vein of Labbé.
– Inferior temporal approach is commonly used
to gain access to tumors located in the
temporal horns.
● Anterior third ventricular tum ors:
Transforaminal and interforniceal approach,
lateral subfrontal approach, pterional approach,
and endoscopic approach can be used.
– Anterior transcallosal approach is the most
frequently used as it provides several paths of
dissection to open into the third ventricle
without injuring the cortical tissue.31 Lesions
that are located anterior to the foramen of
Monro and inferior to the third ventricle may
not be easily accessible with this approach.8
– Lateral subfrontal approach is useful for
midline suprasellar and anterior third
ventricular tumors.8
– Pterional approach is used to gain access to
suprasellar tumors that extend into the
anterior third ventricle.8
– Endoscopic approach is a suitable option for
intraventricular tumors due to fluid-filled
nature of the ventricles and the possibility of
biopsy under direct visualization, and the
ability to open obstruction via fenestration to
restore normal CSF flow.33 The risks and
limitations of endoscopic approach include
high bleeding risk due to no surrounding brain
parenchyma to tamponade, the inability to
remove tumors with high vascularity and
fibrous consistency, and the possibility of the
tumor being engulfed by adjacent
neurovascular structures that cannot be
mobilized.2,31
● Posterior third ventricular tum ors:
Transcallosal transvelum interpositum approach,
infratentorial supracerebellar approach, and
occipital transtentorial approach may be used.31
– Transcallosal transvelum interpositum
approach allows the choroidal dissection,
removal, and reflection to gain visibility and to
minimize contact with vessels.
– Infratentorial supracerebellar approach is
suitable for midline tumors in the pineal
region as it avoids the need for retraction of
the cerebral hemispheres.
– Occipital transtentorial approach is useful for
lesions with supra- or infratentorial
components.31
● All surgical approaches are designed to minimize
the disturbance of normal anatomy.
● The ideal surgical exposure involves creation of
su cient space for total resection if possible,
visualization and identification of associated
vessels, direct trajectory, and minimal brain
retraction.3,4,8,19
● When approaching third ventricular tumors, the
structures at most risk of injury include fornices
and vessels within the velum interpositum,
which include internal cerebral veins and the
medial posterior choroidal arteries.2
● If tumor has cystic components, care should be
taken during decompression not to allow the
cystic components to escape into the ventricle or
subarachnoid space and then cause aseptic
meningitis. Tumors without cystic components
should be internally decompressed to reduce
tension in the surrounding structures.31
19.9 Postoperative
Management and
Complications
Postoperative care after surgical treatments of
intraventricular tumors usually requires intensive
care unit monitoring due to rather high rate of
complications (up to 20%).6 Patients are placed on
Tumor
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Intraventricular Tumors in Children

perioperative antibiotics for 24 hours and on high-
dose steroids to be tapered o over 10 to 14 days.
For patients with tumors resected via transcortical
approach, antiepileptic medication is also used for
seizure prophylaxis.4 Complications include cere-
bral edema, intraventricular hemorrhage, subdural
and epidural hematoma, and memory di culties
arising from forniceal injury.34
19.10 Common Clinical
Questions
1. Where is the most common location of CPP in
children and in adults?
2. What are histological hallmarks of
ependymoma?
3. What is the only intraventricular tumor that
does not enhance with contrast on MRI?
4. What are some commonly performed endoscopic
procedures for intraventricular tumors?
5. What can result in significant blood loss when
removing the intraventricular tumors?
6. What can prevent postoperative CSF
obstruction and resultant symptoms of
increased intracranial pressure, such as
headaches and altered mental status?
19.11 Answers to Common
Clinical Questions
1. CPP is most commonly located in lateral
ventricle, more specifically left atrium, whereas
it is fourth ventricle in adults.
2. Ependymoma is associated with perivascular
pseudorosettes, also known as Homer
Wright rosettes, more commonly than true
ependymal rosettes, also known as Flexner–
Wintersteiner rosettes.
3. Subependymoma in the lateral ventricles is the
only intraventricular tumor that does not
enhance with gadolinium administration on MRI.
4. Some commonly performed endoscopic
procedures for intraventricular tumors include
endoscopic septal fenestration, tumor biopsy
with or without endoscopic third
ventriculostomy (ETV), and endoscopic removal
of tumors. Endoscopic management o ers
advantages, such as the ability to divert CSF via
ETVor septal fenestration. Although endoscopic
excision of solid intraventricular tumors
remains challenging, tumor biopsy and cyst
resection are commonly performed with high
success rate.35
5. As most operative techniques result in creating
exposure much smaller than the tumor itself,
and as tumor gets removed in a piecemeal
fashion, vascular supply to the tumor is not
exposed early, resulting in possible large
volume of blood loss.35
6. It is generally recommended to remove blood
and air from within the ventricles. Moreover,
placing cotton over the foramen of Monro
during the early course of the surgery can also
prevent pooling of blood into the third
ventricle.
References
[1] Dolecek TA, Propp JM, Stroup NE, Kruchko C. CBTRUS
statistical report: primary brain and central nervous system
tum ors diagnosed in the United States in 2005–2009. Neuro-
oncol. 2013; 15(5):646–647
[2] Anderson RC, Walker ML. Neuroendoscopy. In: Albright AL,
Pollack IF, Adelson PD, eds. Principles and Practice of
Pediatric Neurosurgery. New York, NY: Thieme; 2008:131–
144
[3] Santoro A, Salvati M, Frati A, Polli FM, Delfini R, Cantore G.
Surgical approaches to tum ours of the lateral ventricles in
the dominant hemisphere. J Neurosurg Sci. 2002; 46(2):60–
65, discussion 65
[4] Bettegowda C, Chen LC, Mehta VA, Jallo GI, Rutka JT.
Supratentorial tumors in the pediatric population:
multidisciplinary management. In: Quiñones-Hinojosa A, ed.
Schmidek & Sweet Operative Neurosurgical Techniques.
Philadelphia, PA: Elsevier; 2012:669–683
[5] Taylor MD, Sanford RA, Boop FA. Cerebellar pilocytic
astrocytomas. In: Albright AL, Pollack IF, Adelson PD, eds.
Principles and Practice of Pediatric Neurosurgery. New York,
NY: Thieme; 2008:655–667
[6] Gökalp HZ, Yüceer N, Arasil E, et al. Tumours of the lateral
ventricle. A retrospective review of 112 cases operated upon
1970–1997. Neurosurg Rev. 1998; 21(2–3):126–137
[7] Desmeules M, Mikkelsen T, Mao Y. Increasing incidence of
primary malignant brain tumors: influence of diagnostic
methods. J Natl Cancer Inst. 1992; 84(6):442–445
[8] Anderson RC, Ghatan S, Feldstein NA. Surgical approaches to
tum ors of the lateral ventricle. Neurosurg Clin N Am. 2003;
14(4):509–525
[9] Jelinek J, Smirniotopoulos JG, Parisi JE, Kanzer M. Lateral
ventricular neoplasms of the brain: di erential diagnosis
based on clinical, CT, and MR findings. AJNR Am J
Neuroradiol. 1990; 11(3):567–574
[10] Sévenet N, Sheridan E, Amram D, Schneider P, Handgretinger
R, Delattre O. Constitutional mutations of the hSNF5/INI1
gene predispose to a variety of cancers. Am J Hum Genet.
1999; 65(5):1342–1348
[11] Courville CB, Broussalian SL. Plastic ependymomas of the
lateral recess. Report of eight verified cases. J Neurosurg.
1961; 18:792–799
[12] Robinson LL. General principles of the epidemiology of
childhood cancer. In: Pizzo PA, Poplack DG, eds. Principles
and Practice of Pediatric Oncology. Philadelphia, PA:
Lippincott; 1997:1–9
[13] Horn B, Heideman R, Geyer R, et al. A multi-institutional
retrospective study of intracranial ependymoma in children:
Tumor
152

identification of risk factors. J Pediatr Hematol Oncol. 1999;
21(3):203–211
[14] Souweidane MM. Brain tum ors in the first two years of life.
In: Albright AL, Pollack IF, Adelson PD, eds. Principles and
Practice of Pediatric Neurosurgery. New York, NY: Thieme;
2008:489–510
[15] Geyer JR, Zeltzer PM, Boyett JM, et al. Survival of infants with
primitive
neuroectodermal tumors or
malignant
ependymomas of the CNS treated with eight drugs in 1 day:
a report from the Childrens Cancer Group. J Clin Oncol. 1994;
12(8):1607–1615
[16] Weitman DM, Cogen PH. Infratentorial ependymoma. In:
Keating RF, Goodrich JT, Packer RJ, eds. Tumors of the
Pediatric Central Nervous System. New York, NY: Thieme;
2001:232–238
[17] Yuh EL, Barkovich AJ, Gupta N. Imaging of ependymomas:
MRI and CT. Childs Nerv Syst. 2009; 25(10):1203–1213
[18] Ellenbogen RG, Winston KR, Kupsky WJ. Tumors of the choroid
plexus in children. Neurosurgery. 1989; 25(3):327–335
[19] Berger C, Thiesse P, Lellouch-Tubiana A, Kalifa C, Pierre-Kahn
A, Bou et E. Choroid plexus carcinomas in childhood: clinical
features and prognostic factors. Neurosurgery. 1998; 42(3):
470–475
[20] Ellenbogen RG, Donovan DJ. Choroid plexus tumors. In: Keating
RF, Goodrich JT, Packer RJ, eds. Tumors of the Pediatric Central
Nervous System. New York, NY: Thieme; 2001:339–350
[21] Paulus W, Jänisch W. Clinicopathologic correlations in
epithelial choroid plexus neoplasms: a study of 52 cases. Acta
Neuropathol. 1990; 80(6):635–641
[22] Koeller KK, Sandberg GD, Armed Forces Institute of Pathology.
From the archives of the AFIP. Cerebral intraventricular
neoplasms: radiologic-pathologic correlation. Radiographics.
2002; 22(6):1473–1505
[23] Phi JH, Kim DG. Rare pediatric central neurocytomas.
Neurosurg Clin N Am. 2015; 26(1):105–108
[24] Fishback JL. Neuropathology. In: Moore SP, Psarros TG, eds.
The Definitive Neurological Surgery Board Review.
Philadelphia, PA: Lippincott; 2005:108–133
[25] Gandolfi A, Brizzi RE, Tedeschi F, Paini P, Bassi P. Symptomatic
subependymoma of the fourth ventricle. Case report. J
Neurosurg. 1981; 55(5):841–844
[26] Chiechi MV, Smirniotopoulos JG, Jones RV. Intracranial
subependymomas: CT and MR imaging features in 24 cases.
AJR Am J Roentgenol. 1995; 165(5):1245–1250
[27] Franz DN, Agricola K, Mays M, et al. Everolimus for
subependymal giant cell astrocytoma: 5-year final analysis.
Ann Neurol. 2015; 78(6):929–938
[28] Gray F, Duyckaerts C, Girolami UD. Escourolle and Poirier’s
Manual of Basic Neuropathology. New York, NY: Oxford; 2014
[29] Rades D, Fehlauer F, Schild SE. Treatment of atypical
neurocytomas. Cancer. 2004; 100(4):814–817
[30] Karthigeyan M, Gupta K, Salunke P. Pediatric central
neurocytoma. J Child Neurol. 2017; 32(1):53–59
[31] Patel TR, Gould GC, Baehring JM, Piepmeier JM. Surgical
approaches to lateral and third ventricular tumors. In: Quiñones-
Hinojosa A, ed. Schmidek & Sweet Operative Neurosurgical
Techniques. Philadelphia, PA: Elsevier; 2012:330–338
[32] Shucart WA, Stein BM. Transcallosal approach to the anterior
ventricular system. Neurosurgery. 1978; 3(3):339–343
[33] Souweidane MM, Sandberg DI, Bilsky MH, Gutin PH.
Endoscopic biopsy for tumors of the third ventricle. Pediatr
Neurosurg. 2000; 33(3):132–137
[34] Apuzzo ML, Chikovani OK, Gott PS, et al. Transcallosal,
interfornicial approaches for lesions a ecting the third
ventricle: surgical considerations and consequences.
Neurosurgery. 1982; 10(5):547–554
[35] Greenfield JP, Souweidane MM, Schwartz TH. Endoscopic
approach to intraventricular brain tumors. In: Quiñones-
Hinojosa A, ed. Schmidek & Sweet Operative Neurosurgical
Techniques. Philadelphia, PA: Elsevier; 2012:351–356
Intraventricular Tumors in Children
153

20 Posterior Fossa Tumors
Christian A. Schneider, Nir Shimony, Karl F. Kothbauer
20.1 Introduction
Following accidents, the leading cause of death in
children is cancer.1 Tum ors of the central nervous
system (CNS) are the m ost com m on solid pedia-
tric neoplasm s.2 Sixty percent of these tum ors
arise in the posterior fossa.3 The symptom s of a
posterior fossa tum or are more specific to its
infratentorial localization than to its histological
type. The m ost frequent complaints are symp-
tom s related to hydrocephalus, followed by
symptom s of brainstem , cerebellar, and cranial
nerve (CN) dysfunction. Alm ost every patient
w ith a newly diagnosed posterior fossa m ass
lesion m ust be rapidly evaluated and treated.4
Because symptom s of irritability, vom iting,
and headaches are such everyday complaints in a
pediatricians’ practice, the average symptom atic
period to the diagnosis of a brain tum or is around
6 m onths, and 25% of all children have previou-
sly undergone gastrointestinal workup.1
This
explains w hy children w ith brain tum ors are
often seen in an em ergency setting, w hen clinical
decompensation is im m inent. Especially acute
obstructive hydrocephalus is feared and can lead
to rapid clinical deterioration necessitating
urgent cerebrospinal fluid (CSF) diversion
surgery.4
Medulloblastoma (MB), pilocytic astrocytoma
(PA), and ependymoma (EP) are the three most
common tumors in the pediatric posterior fossa.3
In all three, the extent of resection is the most
important predictor of oncologic outcome
(although for MB this statement is currently chal-
lenged5), meaning that the mere presence of a
posterior fossa mass lesion usually implicates indi-
cation for surgery.1 As a rule of thumb, tumor sur-
gery should be performed as soon as possible but
preferably in an elective setting, when the sta
specialized in the management of these tumors is
readily available. This includes neurosurgeon, neu-
roanesthetist, neuropathologist, neuromonitoring
specialist, and neurosurgical scrub nurse.4
20.2 Neurosurgical
Management of Pediatric
Posterior Fossa Tumors
20.2.1 Diagnostic Evaluation
● Symptoms of increased intracranial pressure
(ICP) or CN deficits usually lead to brain imaging
before a neurosurgeon is involved. Obtaining a
detailed history and a diligent neurological exam
is self-evident.
● With the presence of a posterior fossa mass
lesion, contrast-enhanced magnetic resonance
imaging (MRI) of the head and the whole spine
(to assess for drop metastases before
postsurgical changes render the evaluation
di cult) is mandatory.4
● There is no imaging modality that can determine
the histology of a posterior fossa tumor with
certainty, but experienced pediatric
neuroradiologists are able to predict the
histology in 90% of the cases.1
● A lumbar puncture is rarely needed
preoperatively and can be even dangerous in the
presence of a posterior fossa mass lesion.
Diagnostic lumbar CSF is usually obtained in the
postoperative period in tumors prone to spinal
dissemination. A postoperative waiting period of
10 to 14 days is recommended to minimize the
risk of false-positive lumbar CSF samples.4,6
● A formal ophthalmologic evaluation is useful
when visual symptoms or oculomotor
disturbances are present, to obtain a
preoperative baseline examination. In case of
dysfunction of the lower CNs with swallowing
di culty, facial weakness, hearing loss, or
vestibular symptoms, ENTservice should be
consulted early.
20.2.2 Preoperative Management
● Admission and close observation of neurological
status and vital signs in an intensive care setting
154

are usually mandatory. Never discharge a patient
with a newly diagnosed posterior fossa tumor!
Especially in infants, circulatory response
(bradycardia and hypertension) can be the only
symptom of an acute deterioration. Close
monitoring of head circumference and status of
the fontanel in infants is part of that observation.
● Steroids are useful in the symptomatic patient
and are generally administered on admission.
● Mannitol should be given in a surgical setting
only or to buy time to an emergency surgical CSF
diversion procedure, when acute hydrocephalic
deterioration and herniation signs are present.
● Seizures rarely occur in posterior fossa tumors
without leptomeningeal dissemination. The
empiric administration of antiepileptic drugs in
a seizure-free patient is not indicated.4
● Opiates and benzodiazepines are not
contraindicated but can lead to severe
respiratory depression in the presence of a
significant posterior fossa mass lesion.
● Hydration and adequate administration of
antiemetic drugs are important—especially in
infants with frequent vomiting.
● Preoperative blood work must include a
coagulation status and a type-and-screen
evaluation.
20.3 Surgical Considerations
20.3.1 General
● The psychological impact on patients newly
diagnosed with a brain tumor and their parents
must be taken into account. Preoperative
communication with the family is obviously of
the utmost importance. In addition, updates
from the operation theatre during surgery are
always highly appreciated, especially during a
long case. As a treating neurosurgeon, you will
be following these patients for many years,
meaning that establishing a relationship based
on trust and communication at the beginning of
treatment will make future management easier
for all parties involved.
● Brain tumor resection can cause significant
blood loss. This is especially concerning in
infants with a small total blood volume.
Anesthetist (availability of blood products),
scrub nurse (preparation of patties, hemostatic
materials, working bipolar coagulation forceps,
and suction), and surgeon (meticulous
hemostasis) should anticipate this and pay close
attention to blood loss during the case (and
should also appreciate “hidden blood” in
drainage bags, drapes, and pads).1
● Upon induction, the usual perioperative surgical
antibiotic prophylaxis is administered (i.e.,
cefazolin 30 mg/kg). The authors recommend a
single additional dose of steroids on induction
(i.e., dexamethasone 8 mg). Occasionally,
mannitol (0.5 g/kg) can be useful before opening
the dura to help achieve a relaxed situation in
the posterior fossa.4
Positioning
To access the posterior fossa, three options of pa-
tient positioning cover most of the surgeon’s needs:
Prone and “Concorde” Position
After induction (supine), the head is fixed in a skull
clamp (i.e., pediatric Mayfield, Sugita) and the pa-
tient flipped over onto the operating table, the latter
padded with pressure distributing gel cushions and
other positioning material. After adjusting the head
and inclining it in the neck (for the “Concorde” posi-
tion), the skull clamp is secured to the end of the
table. Always leave a distance of two fingers width
between chin and chest. The table is then adjusted
in a reversed Trendelenburg fashion, until the oper-
ating field is horizontal. In children younger than 2
years, a horseshoe headrest is preferred to obviate
the risk of complications related to pin fixation.1
Advantage: Standard midline approaches and
paramedian approaches are covered. The risk of air
embolism is low. The position for surgeon and
assistant is comfortable and intuitive (face-to-face
configuration of the microscope).
Disadvantage: The venous pressure is higher and
the posterior fossa tighter compared to the sitting
position.
Lateral Decubitus and “Park Bench”
Position
The patient is positioned on his side with the head
turned toward the floor. This position covers lat-
eral approaches to the cerebellopontine angle and
far lateral approaches to the ventral region of the
brainstem.
Advantage: The cerebellar hemisphere follows
gravity and “falls away” from the operating field.
The risk of air embolism is low.
Disadvantage: The venous pressure is higher and
the posterior fossa tighter compared to the sitting
position.
Posterior Fossa Tumors
155

Sitting Position
Some surgeons still prefer the sitting position
under the aspect of a relaxed situation in the
posterior fossa and a negative venous pressure,
allowing for a fairly bloodless surgery. In pediatric
neurosurgery, the sitting position is possible but
mostly avoided.1,7 Large osseous sinuses and an
occipital sinus are often present, enhancing the
risk of air embolism. In addition, rapid drainage of
CSF can empty the ventricular system and lead to
significant pneumocephalus and subdural hema-
tomas.1 If the sitting position is considered, pre-
operative echocardiography must exclude a patent
foramen ovale being an absolute contraindication.
Precordial Doppler sonography during the case is
also mandatory, allowing for a fast reaction of the
surgeon to air embolism (i.e., packing the opera-
tion field with wet compresses, waxing bony
sinuses, performing hemostasis, and—ultimately—
lowering the head of the patient).
Management of Hydrocephalus
● Obstructive triventricular hydrocephalus is
reported in 80% of children with posterior fossa
tumors and often is the factor responsible for
symptoms and deterioration.8,9
● Thirty percent of these children will ultimately
need a permanent CSF diversion after tumor
resection.10
● Risk factors for a postresectional hydrocephalus
requiring surgical treatment are10,11:
– Age <2 years.
– Presence of transependymal edema.
– Preresectional moderate or severe
hydrocephalus.
– Presence of cerebral metastases.
– Diagnosis of MB, EP, or dorsal exophytic
brainstem glioma.
● Some controversy exists about the best way to
treat hydrocephalus secondary to posterior fossa
tumors. The options are pre- or postoperative
external ventricular drain (EVD), shunt, or
endoscopic third ventriculostomy (ETV).
● ETVobviates the need for a shunt by creating an
opening in the floor of the third ventricle, taking
advantage of the much larger CSF resorption
capacity of the external CSF spaces, bypassing a
usually compressed aqueduct.
● Some evidence suggests that a preresectional
ETV lowers the need for a postoperative
shunt.8,12 Opponents to this technique argue that
in 70% of the cases hydrocephalus is su ciently
treated by tumor removal, requiring neither ETV
nor shunt, and that a prophylactic ETV puts the
patients at risk of an additional intervention.
● Although only 30% of the patients will need CSF
diversion after tumor removal, an EVD is often
left behind during resection for safety reasons.
The EVD is weaned during the following
postoperative week. If EVD weaning is not
successful, both options of ETVand shunt can be
discussed again.
● The advantage of not having a permanent shunt
in place, with all its downside of hardware
failure, infection, and blockage, justifies in the
authors’ opinion the trial of a postresectional
ETV, even if this could mean a prolongation of
hospital stay in case shunting is ultimately
needed.
● In the prone position, EVD positioning can be
more di cult when choosing an occipital entry
point. The use of a burr hole ultrasound probe is
highly recommended to prevent catheter
malpositioning and the need for several
“attempts.”
● Care must be taken to slowly release CSF from an
EVD. Rapid changes in ICP can lead to circulatory
reactions and, in the worst case, to perfusion
issues of the retinas already at risk by the prone
position. This problem can be addressed by
immediately closing the EVD after placement to
only drain CSF in the presence of a “tight
posterior fossa.”
Surgical Approaches to the
Posterior Fossa
Midline Tumors
Many of the pediatric tumors in the posterior fossa
are midline lesions arising from the brainstem or
the roof of the fourth ventricle. Both intracranial
approaches described in the following are covered
with a midline suboccipital craniotomy. The inion
is often palpable and the position of the transverse
sinus is approximated by a line drawn from the
inion to both auditory meatuses.13 A straight mid-
line incision is carried down to the bone along the
midline avascular plane. The posterior arch of C1
and the spinous process of C2 are exposed to
establish bony landmarks of the craniocervical
junction. Care is taken not to injure the dura at this
point because some patients present with a non-
fused C1 arch, leaving a midline gap. Many sur-
geons routinely remove the C1 lamina, feeling that
this helps normalizing CSF flow across the foramen
Tumor
156