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Acta Neurochir (Wien) (2007) 149: 399–406
DOI 10.1007/s00701-006-1091-z
Printed in The Netherlands
Neurosurgical Technique
Novel application of computer-assisted cisternal endoscopy
for the biopsy of pineal region tumors: cadaveric study
A. S. Youssef1 , J. T. Keller2, and H. R. van Loveren1
1
2
Department of Neurosurgery, University of South Florida, Tampa, Florida, USA
Department of Neurosurgery, The Neuroscience Institute, University of Cincinnati College of Medicine
and the Mayfield Clinic, Cincinnati, Ohio, USA
Received June 28, 2006; accepted December 8, 2006; published online February 26, 2007
# Springer-Verlag 2007
Summary
Background. Long-standing debate continues about
the management and biopsy of pineal tumors because
of their complex microsurgical anatomy and deep location. Inspired by the concept of biopsy under direct visualization in the absence of hydrocephalus, we explored
the effectiveness of neuroendoscope outside of its traditional territory using a new minimally invasive technique,
computer-assisted cisternal endoscopy (CACE), for the
biopsy of pineal tumors.
Method. Five cadaver heads were dissected to expose the pineal region through the posterior fossa. In
the other 5 heads, a rigid endoscope-wand combination
was introduced in the supracerebellar space lateral to the
arachnoid of the superior cerebellar cistern in midline.
Endoscopic exposure of the pineal gland was correlated
with the real-time image of the localizing wand. After
the wand was removed, arachnoid was further dissected
from the deep veins and the pineal gland, and a fourquadrant biopsy was obtained.
Findings. The combination of technologies of frameless guided stereotaxy and neuroendoscopy enhanced our
ability to navigate the ventriculoscope in narrow spaces
(e.g., posterior fossa cisterns). Compared with transventricular and conventional stereotactic trajectories, application of CACE in supracerebellar infratentorial trajectory
offered the shortest route to the pineal region, anatomical
orientation, no violation of eloquent neurovascular structures, and adequate visibility to deep veins and arteries.
Conclusions. CACE may be used to approach pineal
lesions outside the cerebral ventricular system for biopsy
or debulking. Continuous computer updates on the endoscope position allows its safe navigation in narrow
spaces (e.g., cerebrospinal fluid cistern). Its success will
await future surgical trials.
Keywords: Biopsy; cisternal endoscopy; endoscopy;
pineal gland; pineal tumors.
Introduction
Tumors of the pineal gland are rare, accounting for
0.4–1% of intracranial tumors in European and American literature and 4% in the Japanese literature [1, 18].
Pineal tumors typically affect males (4:1) under 20 years
of age [12]. More than 17 different tumor types arise
from the pineal region, reflecting the complex and heterogeneous nature of this glandular tissue [6, 9, 11]
(Table 1). Germinoma, which is the most common type,
accounts for 43–70% and 21–44% of pineal region
tumors in Japanese and American=European populations, respectively. Germinoma is followed by astrocytoma, teratoma, pineoblastoma, and others [12, 15, 16].
Pineal tumors lie deep within the cranium closely
related to the deep venous system, which represents
the cornerstone in selection of surgical approach to the
pineal region. The complex microsurgical anatomy and
deep location of this region continues to foster a longstanding debate about management of pineal tumors,
400
A. S. Youssef et al.
Table 1. Pathological classification of pineal tumors (with permission from the University of South Florida)
Tumor category
Specific types
Germ-cell tumors
germinoma (atypical teratoma), teratoma and teratoid tumors (dermoid and epidermoid), chorioepithelioma,
embryonal carcinoma (EST or yolk sac carcinoma), rhabdomyosarcoma, combination of the above
Pineal parenchymal cell tumors
pinealblastoma (or pineoblastoma), pinealcytoma (or pineocytoma), pinealcytoma=blastoma
Tumors of supporting (glial
stroma) or adjacent tissues
gliomas (astrocytoma, spongioblastoma, ependymomas, choroid plexus papilloma), ganglioneuroma
and ganglioglioma, meningioma, hemangiopericytoma, chemodectoma, melanoma (malignant)
Non-neoplastic cysts and
vascular lesions
degenerative cysts, arachnoid cysts, vascular lesions (aneurysm of vein of Galen, arteriovenous
malformation, cysticercosis)
specifically the use of direct surgical treatment versus
conservative irradiation with drainage procedures.
The two worldwide surveys about pineal tumor
management conducted in 1992 [12] and 1998 [13]
identified the growing trend of obtaining histological
diagnosis before radiotherapy and=or chemotherapy for
several reasons. First, 36–50% of pineal tumors are
either benign or radio-resistant. Second, radiation therapy
exerts harmful effects on children with pineal tumors.
Third, minimally invasive procedures (i.e., neuroendoscopy, stereotactic surgery, radiosurgery=radiation
therapy) are widely accepted as safe neurosurgical treatments. Finally, identification of the exact histological
type allows a more specific use of therapeutic tools,
specifically radiation and new chemotherapeutic agents.
Histological diagnosis for pineal region tumors is
achieved through direct surgery or biopsy techniques.
Direct surgery not only is curative for benign lesions
but provides a generous amount for tissue biopsy. Closed
biopsy techniques include stereotactic and neuroendoscopic biopsy. Stereotactic biopsy can be limited by
inadequate amounts of specimen, especially for mixed
tissue and rare cell types, which are difficult to interpret,
increase the diagnostic error, and the risk of hemorrhage.
Neuroendoscopic biopsy is more favorable in lesions
associated with hydrocephalus; it often requires use of
a flexible endoscope, which is sometimes technically
difficult.
In this cadaveric study, we evaluate the effectiveness
of computer-assisted cisternal endoscopy (CACE) to
overcome the above-mentioned limitations in the biopsy
of pineal region tumors. A computer-assisted endoscopic
technique previously applied for transventricular biopsy
offered advantages including planning the entry point,
localizing the ideal target trajectory, and obtaining an
intraoperative computer update on the endoscope location [14]. In our microsurgical laboratory, we studied
the anatomy of the pineal region in cadavers, incorporating stereotactic and neuroendoscopic advances into
one biopsy technique that adds real-time neuroimag-
ing orientation to the navigating endoscope. Finally,
we evaluated different surgical trajectories to the pineal
region on the basis of the distance to the target, natural
anatomical passages, and obstacles created by important
neurovascular structures and eloquent brain tissue. We
studied the use of the supracerebellar cistern as a new
trajectory to navigate the neuroendoscope and biopsy the
pineal gland with this minimally invasive technique.
Methods and materials
Cadaveric preparation
In 10 cadaver heads, both the internal carotid arteries,
vertebrobasilar system, and jugular veins were cannulated and irrigated with warm tap water. Heads were
soaked in 70% ethyl alcohol solution for 24 hours.
Arterial and venous systems were injected with pigmented-silicone latex compound (Dow-Corning, Midland,
MI) that then hardened overnight. All heads were preserved in a 70% ethyl alcohol solution. Five of 10 heads
were dissected to expose the pineal region through the
posterior fossa. Sagittal sections were made through this
region to study its microsurgical anatomy. The other five
heads underwent scanning in the GE High-Speed scanner (General Electric Systems, Milwaukee, WI). Fiducial markers were placed around the occipital=parietal
region using a 0-degree angulation and 3-mm thick axial
slices for frameless guided (Radionics OTS Frameless
Stereotaxy, Radionics Inc., Burlington, MA) localization of the pineal region. Taking advantage of the radiographic characteristics of silicone, we identified the
pineal gland by the overlying confluence of siliconeinjected veins that appear as hyperdense structures on
computed tomographic (CT) scans (Fig. 1).
Computer-assisted cisternal endoscopy (CACE)
A straight, rigid, 0-degree, 5-mm Gaab endoscope
with a working channel (Codman and Shurtleff Inc.,
401
Endoscopic biopsy of pineal tumors
lected as a target (Fig. 2). A localizing wand was used
to map the transverse sinus and torcular to plan the keyhole access to the supracerebellar space. The keyhole
was placed paramedian within 1 inch of midline with
Fig. 1. Computed tomography scan of a cadaveric head showing
hyperdense silicone-injected vessels. Note the confluence of deep veins
adjacent to the pineal gland (with permission Mayfield Clinic)
Randolph, MA) and a set of endoscopic surgical instruments were prepared for use.
Keyhole access
The pre-scanned cadaveric head was placed in a Mayfield head holder (Integra Lifesciences Co., Falmouth,
Cornwall, England) and positioned to mimic the semisitting position. Stereotactic fiducials were registered to
frameless stereotactic system (Radionics Inc., Burlington,
MA). The pineal gland was identified on CT scan in
three different planes by the confluence of radio-opaque
silicone-injected deep veins into the great vein and se2
Fig. 2. Neural and vascular structures of the pineal region. (A) View
through the supracerebellar trajectory. (B) Lateral view of the pineal
region after removal of the parieto-occipital lobes and part of the
mesencephalon. (C) Sagittal cut through the pineal region after partial
removal of the cerebellum. AqS Aqueduct of Sylvius, BVR basal vein
of Rosenthal, CA calcarine artery, ICV internal cerebral vein, IOV
internal occipital vein, PC posterior commissure, PCA posterior cerebral artery, PChA posterior choroidal artery, PG pineal gland, POA
parieto-occipital artery, QP quadrigeminal plate, S splenium, SCA
superior cerebellar artery, SS straight sinus, SVV superior vermian vein,
Tent tentorium cerebelli, VCMF vein(s) of the cerebellomesencephalic
fissure, VG vein of Galen (with permission Mayfield Clinic)
402
A. S. Youssef et al.
its upper third overlying the right transverse sinus and
the lower two thirds exposing the cerebellum and supracerebellar space.
channel with intermittent irrigation. With direct visualization of the pineal gland, a four-quadrant biopsy was
obtained while the deep veins were completely secured.
Endoscopic exposure
Results
After placement of the keyhole, the dura below the
transverse sinus was incised and the cerebellum was
retracted downward using a ¼ inch Budde-Halo selfretaining retractor blade (Integra Lifesciences Co.) to
open the supracerebellar infratentorial space. The rigid
endoscope-wand combination was introduced in the
supracerebellar space lateral to the arachnoid of the superior cerebellar cistern in midline. Bridging veins from
the cerebellum were divided and the cerebellum was
further retracted. Continuous real-time update on the position of the endoscope tip and distance from the pineal
gland was obtained (Fig. 3). The arachnoid of the superior
cerebellar cistern was opened at its junction with the
quadrigeminal cistern where the target pineal gland is
located. Endoscopic exposure of the pineal gland was correlated with the real-time image of the localizng wand.
In this cadaveric study, the combination of technologies of frameless guided stereotaxy and neuroendoscopy
enhanced our ability to navigate the ventriculoscope in
narrow spaces such as the posterior fossa cisterns. Compared with transventricular and conventional stereotactic
trajectories, the application of CACE in supracerebellar
infratentorial trajectory offered the shortest route to the
pineal region, allowed easy anatomical orientation, did
not necessitate the violation of eloquent neurovascular
structures, and provided adequate visibility to the deep
veins and arteries. We describe the microsurgical anatomy pertinent to this technique.
Biopsy
After the localizing wand was removed, the arachnoid
was further dissected from the deep veins and the pineal gland using endoscopic instruments via the working
Microsurgical anatomy
The pineal region is located at the junction between
the supratentorial and infratentorial compartments posterior to the midbrain in the posterior incisural space.
When viewed through the supracerebellar infratentorial
approach, the pineal region resembles a cave with walls,
roof, floor, and contents. The pineal region comprises
cerebrospinal fluid (CSF) cisterns, vascular structures,
neural structures, and ventricles – each with relevant
anatomy and anatomical relationships.
Cerebrospinal fluid cisterns
The route to the pineal gland and its ‘‘cave’’ is lined
by arachnoid-mater forming cisterns: superior cerebellar
and quadrigeminal cisterns. The superior cerebellar cistern is the first cistern encountered in exposure, situated
midline between the superior part of the vermis and the
arachnoid underlying the straight sinus. This cistern
forms a corridor that leads anteriorly to the quadrigeminal cistern and communicates laterally with the subarachnoid space overlying the cerebellar hemispheres.
It contains branches of the superior cerebellar artery
and superior vermian vein. The quadrigeminal cistern
is formed by the arachnoid lining of the pineal cave.
Its boundaries and anatomical structures correspond to
those of the pineal region.
Fig. 3. Endoscopic view of the pineal region through the supracerebellar-infratentorial trajectory. BVR Basal vein of Rosenthal, ICV
internal cerebral vein, VCMF vein(s) of the cerebellomesencephalic
fissure, VG vein of Galen, QP quadrigeminal plate, PG pineal gland
(with permission Mayfield Clinic)
Vascular structures
The venous anatomy of the pineal region is complex –
multiple veins converge to drain into the straight sinus
403
Endoscopic biopsy of pineal tumors
through the great vein of Galen on top of the pineal
gland (Fig. 2A–C). Bridging veins from the cerebellum
to tentorial sinuses may be found early in the exposure
of the supracerebellar space. Vein(s) of the cerebellomesencephalic fissure is identified posterior to the pineal
gland after dissection of the quadrigeminal cistern arachnoid in midline. It drains the superior cerebellar peduncles into the superior vermian vein or directly into vein
of Galen. The superior vermian vein receives the cerebellomesencephalic vein and cerebellar veins, and then
passes forward above the pineal gland to reach the
vein of Galen (Fig. 2C). Internal cerebral veins are
paramedian where they exit the velum interpositum of
the third ventricle joining to form the vein of Galen
in midline. Basal veins of Rosenthal pass laterally
from the ambient cistern around the midbrain, enter
the quadrigeminal cistern, and drain medially into internal cerebral veins or vein of Galen (Fig. 2B). The internal occipital veins located far lateral and superior in
the supracerebellar infratentorial exposure arise in the
area of the calcarine and parieto-occipital sulci and
pass anteromedially to terminate into vein of Galen
(Fig. 2A).
Arteries in the pineal region are the posterior cerebral
artery and superior cerebellar arteries. These arteries
enter the lower anterior part of the quadrigeminal cistern
and course below and lateral to the pineal gland. The
posterior cerebral artery divides into calcarine and parietooccipital branches (Fig. 2B). The medial posterior
choroidal artery on each side enter the quadrigeminal
cistern and turn forward passing by the pineal gland to
enter the velum interpositum. The superior cerebellar
artery passes through the cerebellomesencephalic fissure
and branches below the free tentorial edge to supply the
tentorial surface of the cerebellum.
Neural structures
The pineal cave is found after crossing the supracerebellar corridor. This cave has a floor, roof, and anterior
and lateral walls formed by different neural structures.
The anterior wall consists of the posterior third ventricle
and the pineal gland attached to the third ventricular roof
at the habenular commissure and posterior commissure
(rostral to caudal). The medial pulvinar forms the lateral
part of the anterior wall. The quadrigeminal plate forms
the lower part of the anterior wall (Fig. 2C). The trochlear nerves exit the brain stem below the inferior colliculi, turning forward around the midbrain and below
the pulvinars to enter the ambient cistern. The roof is
formed by the splenium of corpus callosum. The lateral
wall is formed by the crus of fornix and the occipital
cortex. The floor is formed by the anterior superior part
of the cerebellum.
Summary
The deep veins are located superomedial and the
arteries are located inferolateral in the supracerebellar
infratentorial trajectory to the pineal gland (Fig. 2A).
Study of microsurgical anatomy showed that the supracerebellar infratentorial corridor is a classic trajectory to
the pineal region that can be cautiously reapplied to
biopsy the pineal region through a new closed biopsy
technique.
Discussion
In our application of CACE in five cadaveric heads,
frameless stereotaxy was useful to plan key-hole placement in relation to the midline and transverse sinus, and
to provide continuous real-time computer updates on
the endoscope’s position in the supracerebellar space.
The endoscope provides direct visualization of anatomy,
dealing with bridging veins early in exposure and arachnoid dissection of the superior cerebellar cistern and
quadrigeminal cistern to expose the deep veins and pineal gland.
Management of pineal tumors
Tumors in the pineal region have captured the interest of neurosurgeons because of their deep location in
the cranium, close relation to the deep venous system,
and their great variability in pathology and prognosis. Identification of the exact histological nature makes
it possible to tailor therapy according to tumor type
and potentially improve the patient’s outcome. Whereas
maximum surgical resection may be required in nongerminomatous germ cell tumors (NGGCTs) and benign tumors, adjuvant therapy is more often the more
reliable therapeutic method in germ cell tumors. Platinum-based multiagent chemotherapy has improved
the outcome in patients with NGGCTs [7]. Radiotherapy is required in all pineal region tumors (except for
mature and immature teratomas) with careful consideration given to the dose administered. The extent and
dose of radiation is tailored to the specific pathology.
Pineoblastomas have a high risk of spinal failure; radiation should be delivered to the craniospinal axis. Germinomas pose a moderately high risk of spinal failure
that can only be treated with whole brain irradiation in
404
the absence of spinal seeding. In one large series reporting 5-year survival rates of patients with pineal
tumors treated by histological diagnosis and adjuvant
tumor specific therapy, Schild et al. noted the outcome
largely depended on tumor type and radiation dose
[23]. While the fore-mentioned examples highlight
the necessity for tissue diagnosis to deliver the ultimate
management to pineal tumors, they obviously do not
settle the long standing debate about the indications for
biopsy.
A. S. Youssef et al.
culoscope has permitted safer access to pineal tumors,
biopsy under direct visual observation, possible coagulation of tumor capsule, and the ability to perform
therapeutic third ventriculostomy through the same procedure. However, endoscopic biopsy may often be difficult to perform in the absence of large ventricles; it may
be more effective in intraventricular tumors and poses
difficulty in the manipulation of a flexible ventriculofiberscope.
Computer-assisted cisternal endoscopy (CACE)
Biopsy techniques
Tumor specimens for diagnosis can be obtained through
direct operative approaches, stereotactic biopsy, and endoscopic transventricular approach. Direct surgery is advantageous for obtaining a generous tissue biopsy, being
curative for benign tumors, in addition to offering flexibility of a 3-dimensional view of the operative microscope. However, surgery can be associated with possible
complications and is not curative in more than 75% of
pineal tumors that are locally or metastatically invasive.
Frame-based or frameless-guided stereotactic biopsy of
the pineal region tumors has emerged as a reliable, less
invasive technique.
The two primary surgical trajectories to the pineal
region for stereotactic biopsy are the posterolateral transparieto-occipital approach and anterolateral transfrontal
approach via the anterior limb of the internal capsule.
The former trajectory is used for lesions with significant
superolateral extension; the latter is more often used for
most pineal lesions. The relatively small volume of
tumor obtained by stereotactic biopsy challenges the
pathologist because of the increased risk of diagnostic
error [2, 5]. Furthermore, pineal lesions of mixed cell
types are found in 15% of patients and can be misdiagnosed with small biopsies even by experienced neuropathologists [3]. Closed biopsies may also carry risks of
intraoperative bleeding from injury to the deep veins or
hypervascular tumors or metastatic seeding and tumor
implantation along the biopsy tract.
Limitations of closed needle biopsy in the pineal
region prompted the need for more direct biopsy techniques. Fukushima introduced the concept of endoscopic biopsy of intraventricular tumors under visual
control with a flexible ventriculofiberscope [8]. Since
then and as a result of the tremendous advances in
endoscopic technology, endoscopic biopsy has become
more widely used in intraventricular lesions (including
pineal tumors) with higher success. The flexible ventri-
The supracerebellar infratentorial approach has been
used by most neurosurgeons with a remarkable degree
of success in the approach to pineal tumors but had
not yet been used as a trajectory during closed biopsy.
Use of the supracerebellar infratentorial route for biopsy of the pineal region under direct neuroendoscopic
visualization with frameless guided stereotactic guidance enhanced our ability to navigate the ventriculoscope in narrow spaces (e.g., posterior fossa cisterns).
Of several recent reports that described the combination of stereotaxy and endoscopy to enhance target
localization [4, 10, 19], Rhoten et al. used frameless
stereotactic techniques [19] but no one applied this
technology outside the ventricular system to biopsy the
pineal region.
At the beginning of our study, midline placement of
the key burr hole required additional drilling of thicker
bone and led to the torcular herophilli (which is unnecessary for exposure), mandated arachnoid dissection
early in exposure, and necessitated more manipulations
of the endoscope. By relocation of the entry point to the
paramedian position, we switched to the paramedian
supracerebellar trajectory, which allows a more comfortable manipulation of the endoscope and advanced dissection of the superior cerebellar arachnoid closer to the
target (at its junction with the quadrigeminal cistern)
with real-time computer localization of the target. The
paramedian working angle is less steep than the midline
angle and offers further access anterolateral to the pineal
gland.
Use of a localizing wand permits real-time computer
updates on the tip position of the endoscope. The wand
can be replaced by the instrument registry technology
currently available in frameless stereotaxy that allows
registration of the rigid endoscope to serve as a localizing wand at the same time.
Our initial application of the CACE technique for
exposure and biopsy of the pineal region was performed
405
Endoscopic biopsy of pineal tumors
in cadaveric brains without pathological conditions. A
limitation of our study is that the role of this biopsy
technique has yet to be proven in the operating room
in patients with pineal tumors, especially without coexisting hydrocephalus. This technique may become a
valuable addition to current biopsy techniques. It combines the advantages of being minimally invasive with
the potential to yield a direct generous biopsy as in
surgery but may decrease the risk of closed intraoperative bleeding. Additionally the technique may help to
achieve tumor debulking or even resection.
Technical challenges
The view of a novel minimally invasive approach in
the cadaver laboratory should not be shortsighted. The
CACE approach still awaits the test of real surgery in
order to evaluate and overcome the expected difficulties
such as the following obstacles: first, the cerebellar
retraction in presence of bridging veins in the supracerebellar space; second, arachnoid dissection around
major veins in the pineal region, and third, vascular
tumors with the risk of bleeding. In its initial application in real surgery, we envision use of a larger craniotomy exposure for CACE in which to introduce the
endoscope early on and allow adequate vision and coagulation of bridging veins. Arachnoid dissection deep
in exposure can be performed using a rigid endoscope,
which can reach deep and anterolateral to the major
veins of the pineal region with more detailed anatomical view. The larger craniotomy will eventually be
tailored to a ‘key-hole’ exposure once experience and
comfort accumulate with CACE.
The modern technology in neuroendoscopy has offered technical flexibility in manipulation, dissection
and thermocoagulation hemostasis through a multicompartment working channel. Yet, the surgical microscope
can intervene when bleeding becomes a challenging task
in minimally invasive surgery.
Conclusions
Computer-assisted cisternal endoscopy may be used
to approach lesions outside the cereberal ventricular system to obtain a biopsy or perform debulking. Continuous
computer update on the endoscope position allows its
safe navigation in narrow spaces like the cerebrospinal
fluid cistern. This technique can be applied to biopsy
pineal tumors in the absence of hydrocephalus and its
success will await future surgical trials.
Acknowledgements
The authors thank Norberto Andaluz, M.D., Khaled M. Abdel Aziz,
M.D., Ph.D., and Salah K. Hemida, M.D., Ph.D. for cadaveric preparation and technical assistance.
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