1. Journal of Radiosurgery and SBRT Vol. 0 2011 1
Case Report
CyberKnife radiosurgery can control recurrent epidermoid cysts of
the central nervous system
Robert E. Lieberson, MD,1
Amanda Mener,1
Clara Choi, MD PhD,1
Maziyar A. Kalani, MD,1
Scott G. Soltys,
MD,2
Iris C. Gibbs, MD,2
Gary Heit MD PhD,3
John R. Adler, MD,1
and Steven D. Chang, MD,1
1
Department of Neurosurgery, Stanford University Medical Center, Stanford, CA, USA
2
Department of Radiation Oncology, Stanford University Medical Center, Stanford, CA, USA
3
Department of Neurosurgery, Kaiser Permanente Group, Redwood City, CA, USA
Corresponding Author: Robert E. Lieberson, MD, Department of Neurosurgery, Stanford University, 300 Pasteur Drive, Room
R-205, Stanford, CA 94305, USA, robert.lieberson@stanford.edu, +1-650-723-5573 (office), +1-650-725-1784 (fax)
(Received August 3, 2011; accepted August 26, 2011)
Epidermoid cysts of the central nervous system may be
difficult to resect and recurrent lesions may be impossible
to control with open surgery. We identified three patients
with recurrent epidermoids treated with radiosurgery at
Stanford. One patient with a middle fossa lesion that had
been resected twice in six years, presented with a 4.5 cubic
centimeter recurrence and was treated with radiosurgery.
Follow-up scans over three years showed no additional
growth. Two patients had spinal lesions. One had undergone
numerous, unsuccessful procedures in the three years before
the radiosurgical treatment and subsequent open resection
of a 3.8 cubic centimeter recurrence. His scans remain
unremarkable eight years after treatment. The other, with
acaudaequina mass, had required five open resections in 11
years. Following the last resection, the residual was treated
radiosurgically. The lesion eventually increased in size,but
becamesymptomaticonlyaftersevenyears.Asecondcourse
of radiosurgery was delivered. We believe that stereotactic
radiosurgery can be safe for some epidermoid cysts of the
central nervous system, decreases their growth rate, and may
facilitate subsequent open surgery. It should be considered
for select individuals with recurrent or unresectable lesions.
Key words: Epidermoid Cyst, Central Nervous System,
Brain, Spine, Stereotactic Radiosurgery, CyberKnife,
Gamma Knife, Linear Accelerator
INTRODUCTION
Epidermoid cysts of the central nervous system
(CNS) are rare, accounting for only 0.3% to 1.8% of
intracranial mass lesions [1] and 0.7% those in the
spine.[2] They originate from embryonal cell rests left
behind during embryogenesis or following trauma. [3,
4] Epidermoids may be difficult to resect completely
and are prone to recurrence. [5, 6]
Conventional radiotherapy treatment has been
reported for intracranial [7] and spinal epidermoids. [8]
Kida et al [9] first described the use of stereotacticra-
diosurgery (SRS) for intracranial epidermoids. We are
unaware of any other reports discussing the use of SRS
for spinal epidermoids.
We present one recurrent intracranial epidermoid
and two recurrent spinal epidermoids treated with
CyberKnife SRS.
METHODS
With the approval of the Institutional Review Board,
we identified and reviewed the records of three patients
with recurrent epidermoids treated at the Stanford
CyberKnife Center. Members of the Neurosurgery
Department reviewed their diagnostic imaging studies
and re-examined each of the patients.
CASE REPORTS
Patient 1
In September 1999, patient 1, a 53 year-old woman,
presented to our spine clinic with a two-month history of
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2. R. E. Lieberson et al.
2 Journal of Radiosurgery and SBRT Vol. 0 2011
progressivelysevere,intermittent,bilaterallowerextremity
numbness,weaknessandcrampingwithoutbowelorblad-
der complaints. The examination showed only 4/5 weak-
nessinthelefttibialisanteriorandextensorhallucislongus.
A magnetic resonance image (MRI) scan demonstrated an
intramedullary lesion of the conus, 3.9 centimeters (cm)
in greatest extent. In October 1999, patient 1 underwent
a T12
to L2
laminectomy, gross total resection of the epi-
dermoid. Within a year, her symptoms returned. In Octo-
ber 2000, we performed a second open resection a for a
3.8 cm recurrence seen on MRI. The surgeon reported
that it was impossible to develop a plane between the cyst
wall and the cord and a gross total resection could not
be completed. Painful recurrences in July and August of
2001, which were both associated with increased numb-
ness, worsened weakness, and incontinence of bowel and
bladder. Two MRI-guided-aspirations of prominent cystic
components were completed, removing 4 cubic centim-
eters (cc) and then 2 cc of keratinized material from
the lesion, reducing its volume by approximately 30%
by MRI. An MRI in May 2002 (Figure 1A) showed a
3.8 cm recurrence and, consequently, the patient received
SRS. In a single session, we delivered a marginal dose
of 18 Gray (Gy) to the 81% isodose line. The patient’s
pain, numbness, weakness, and incontinence improved
within weeks. Three months following SRS, an additional
aspiration procedure was required. Because of recurrent
symptoms, in January 2003, the lesion was re-explored
and the 2.3 × 1.4 × 1.2 cm recurrence was removed with
intraoperative monitoring. During surgery, there was a
well-developed cleft around the lesion and it was possible
to easily separate and remove at least 80% of the cyst wall
from the cord. Only the most cranial and caudal compo-
nents could not be resected due to changes in monitor-
ing potentials with manipulation of those portions. At her
most recent neurosurgical follow-up visit in June 2009,
she was clinically stable, complaining only of residual
bladder incontinence and hypalgesia of the right foot.
Although two small areas of cyst wall were not removed,
the most recent, post-operative MRI showed no evidence
of any residual (Figure 1B).
Patient 2
Patient 2, a 62-year-old man at the time, was first
seen at Stanford in February 2004. He had undergone-
four separate L3
to S1
laminectomies for pain, numb-
ness, and weakness (1991, 1995, 1999, and 2002). MRI
scans in 2003 showed a residual lesion extending from
L3
to S1
. In February 2004, the fifth was completed. At
surgery, it was felt that the entire contents of the cyst
and most of the cyst wall had been removed. Because of
his history of multiple prior recurrences, elective SRS
to the resection cavity followed the open procedure. A
total of 22Gy prescribed to the 81% isodose line was
delivered in two sessions to the 39.6 cc resection bed.
Symptoms of pain, a unilateral foot drop, and numbness
remained stable. In January 2011, increasing urinary
symptoms led to an MRI, which showed a cystic recur-
rence, with a cavity measuring 7.1 cm in greatest extent.
We felt that an open surgery would unlikely be effec-
tive and recommended an additional course of SRS. In
March 2011 we delivered 22Gy prescribed to the 75%
isodose line in two sessions (Figure 2). In the brief time
Figure 1. Patient 1.The image on the left (A), shows
a T2 weighted MRI obtained prior to radiosurgery in
2002. A 3.8 cm cystic recurrence is seen within the
conusmedullaris at the L1-2 level.The image on the right
(B), shows a similar T2 weighted MRI taken following
both radiosurgery and the open resection. There is no
evidence of residual tumor within the conus.
Figure 2. Patient 2. This image shows the most recent
radiosurgical plan as delivered in 2011. The black
outline surrounds the cystic, epidermoid lesion. The
white outline surrounds the nerve roots, anterior and to
the right of the mass.
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3. Radiosurgery for recurrent epidermoids (revised)
Journal of Radiosurgery and SBRT Vol. 0 2011 3
that has elapsed following treatment, there have been
no changes in complaints or findings.
Patient 3
Patient 3, a 48-year-old man, was referred to Stan-
ford in November 2007. The patient related a his-
tory of headaches and seizures which began in the
early 1990s. Computerized tomography (CT) scans
at that time were reportedly unremarkable. By 2000,
increasingly symptoms prompted a re-evaluation, and
an MRI showed a 3.7 cm diameter lesion occupying
right anterior middle fossa. Aftera first craniotomy
and reported gross total resection in October 2000, an
MRI showed no residual. Serial MRI scans showed
a recurrence that by July 2006, was 3 cm in greatest
diameter. A second right temporal craniotomy was
completed and it was felt that a gross total resection
had been achieved. Although the immediate post-op-
erative scans reportedly showed no residual, only one
year later, a follow-up MRI showed a 2.3 cm diam-
eter recurrence in the sylvian fissure and suprasellar
cistern. He was referred to Stanford for SRS. At the
time, the patient reported increased headache and
five to six seizures per day, but the physical examination
was unremarkable. In November 2007, we delivered
a marginal dose of 24Gy prescribed to the 75%
isodose line, in three sessions, for a lesion measuring
2.3 cm in maximum diameter and 4.5 cc in volume
(Figure 3A). The most recent scan of August 2010
showed that the lesion remained unchanged by MRI
(Figure 3B). When last examined, in November 2010,
the patient was seizure free and denied significant
headaches.
DISCUSSION
Epidermoid cysts are also known as cholesteoto-
mas or “pearly tumors.” Verattus is credited with the
first description of an epidermoid in 1745 and in 1807,
Pinson, an artist working with Dupuytren at the Hotel
Dieu, constructed a wax model of one of these lesions.
[10] Cruveilhier, a French pathologist, characterized
them more completely in 1829 and described them as
having a “mother-of-pearl” appearance. [11] In 1839,
Mueller coined the term “cholesteotoma” because of the
abundant choldesterol crystals seen in some specimens
and, since then, any masses containing cholesterin have
been referred with this moniker. Von Remakfirst identi-
fied their epithelial cell origin in 1854. [12] It was not
until 1920 that the first successful surgical treatment of
an epidural was described by Bailey. [13]
Epidermoids of the CNS originate from embryo-
nal cell rests or from fragments of epithelial tissue left
behind following surgery, lumbar puncture, or other
trauma. [3, 4] They are composed of squamous epithe-
lial cells and connective tissues components surround-
ing degenerated, desquamated skin. Epidermoids do
not contain skin appendages, such as hair. [14] They
grow slowly along natural cleavage planes, and may
be clinically apparent only after years of growth. [5]
Malignant transformation is uncommon. [15] They are
more common in women (54%) and, although most
are congenital, they often do not present until the fifth
decade. [14] Headache, seizures, intracranial hyperten-
sion, and focal deficits related to lesion location are the
most common presenting symptoms and signs. Epider-
moids are usually homogeneously hypodense on CT,
and may have an enhancing rim or irregular calcified
inclusions. On magnetic resonance imaging (MRI),
they are hypointense on T1-weighted sequences and
hyperintense on T2-weighted images. [5] The differ-
ential diagnosis may include arachnoid cysts and less
commonly glioma, metastasis, lymphoma, or infection,
and MRI diffusion studies may be helpful in differenti-
ating epidermoids from other cystic lesions of the CNS.
[3, 16, 17] Epidermoids occur in the cerebellopontine
angle (37.3%), theparasellar cisterns (30%), the middle
cranial fossa (18%), within the diploë (16%), or in the
spinal canal (5%). [18-20] Although most epidermoids
are in the intradural-extramedullary space, they can
be extradural, or transdural, and they will rarely occur
within the substance of the spinal cord and intramedul-
lary epidermoids of the brain have been reported. [3, 6,
21] Epidermoids exhibit linear, rather than logarithmic
growth, explaining their slower expansion compared to
some CNS tumors. [22] Surgical gross total resection
remains the goal for most treatment, but there remains
controversy regarding the appropriateness of subtotal
Figure 3. Patient 3. The image on the left (A), shows
the most recent radiosurgical plan, completed in 2007.
The image on the right (B), is the most recent MRI,
obtained following the radiosurgicaltreatmentof 2010.
There has been no interval change or increase in the
size of the lesion.
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4. R. E. Lieberson et al.
4 Journal of Radiosurgery and SBRT Vol. 0 2011
resection when the risk of post-operative deficits might
be increased. [5]
Although radiotherapy has been described as inef-
fective for epidermoid cysts, [3, 5, 11] its successful use
has been described. [7, 8] Parikh et al reported that 50Gy
delivered in 25 daily sessions yielded radiographic and
symptomatic control of a previously resected, recurrent
cerebello-pontine angle epidermoid after a two-year
period of follow-up. [7] Bretz et al treated a recurrent
intraspinal C6-T2 epidermoid, causing sensory and
motor deficits, with 46 Gray in 23 daily fractions. [8]
The patient, followed radiographically for two years
and clinically for six years, remained stable without
increased symptoms or evidence of re-growth.
Kida et al [9] first reported the use of stereotactic
radiosurgery (SRS) for intracranial epidermoids. They
treated seven patients with trigeminal neuralgia or hemi-
facial spasm secondary to posterior fossa cysts. The
pain or spasms resolved in five of their seven patients
after Gamma Knife therapy. They achieved local control
in all of their patients, and in two patients, the lesions
reportedly decreased in size after a mean follow-up of
52.7 months. We were unable to find any other reports
describing the use of radiosurgery for intracranial epi-
dermoid cysts. We are aware of no prior reports describ-
ing the use of SRS for spinal epidermoids.
In our three patients, SRS was safe, we saw no
radiation related complications, and SRS appeared to
prevent or delay recurrence. Patient 3, who had a mid-
dle fossa lesion, had radiographic recurrences within a
year following each of two craniotomies. MRI scans
show him to be disease free three years after radio-
surgery. Patient 2 had required five open resections in
a period of 13 years; an average of one operation every
2 ½ years. Following the last open surgery, we delivered
SRS to the resection cavity and patient 2 did not require
any additional intervention for seven years. Patient 1
had undergone two open and two percutaneous proce-
dures in the 2 ½ years before SRS. Although ongoing
symptoms forced us to re-resect the epidermoid shortly
after the SRS treatment, patient 1 now remains without
radiographic or clinical evidence of a recurrence after
eight years. We believe that, without SRS, the time to
the next recurrence for each of our patients would have
been similar to that observed before SRS. Although
we are confident that we delayed the recurrence of the
lesion, we cannot assume that we have achieved any
cures. Epidermoids are slow growing and the time to
recurrence can be a decade or more. [22]
We have used SRS in a variety of situations. For
patient 3, SRS was used to treat a recurrence following
surgery. Repeat courses of radiosurgery for recurrences
have previously been reported as safe for a variety of
other conditions, including arteriovenous malforma-
tions, [23] acoustic neuromas, [24] ependymomas,
[25] chordomas, [26] and nasopharyngeal carcinomas.
[27] Radiosurgery to the resection bed of a metastasis
improves local control. [28] Patient 2 received SRS
both to treat a post-operative resection cavity and also
as a salvage procedure for a recurrence after SRS. SRS
has been employed to decrease vascularity prior to
planned resections for hemangioblastomas, [29] renal
cell metastases, [30] and arteriovenous malformations.
[31] SRS may create an improved capsule or a more
defined plane around some lesions. Kamitani et al,
reported that a capsule around the radiated hemangiob-
lastoma, “made resection easy.” [29] Sanchez-Mejia
et al reported that following SRS, the tissue planes of
separation around the AVMs were more “distinct.” [31]
Patient 1 was treated with SRS prior to an unplanned
open resection. At surgery, we found a clear plane that
separated most of the lesion from surrounding cord,
facilitating a near total resection.
Patient 1’s care was particularly interesting for two
reasons. First, we believe that the lesion was more eas-
ily resected as a result of the SRS treatment. Patient 1
had undergone four procedures before the SRS treat-
ment. During each operation, the intramedullary conus
lesion could not be separated from the surrounding
cord. Shortly following SRS, and because of increasing
symptoms, we were forced to operate. Whereas before
SRS we were unable to develop a plane around the lesion
before SRS, after SRS it was possible to remove the
lesion almost entirely because of a well developed cleft
that had not been present at the time of the earlier oper-
ations. Second, patient 1’s unplanned surgery following
SRS might have been predicted. Since the expansion of
the cavity in other cystic lesions, such as hemangiob-
lastomas, does not stop for some time after SRS, we
believe that this may also be true for epidermoids.
Patients with multiply recurrent epidermoids have
a high-risk of complication. Given the location of the
lesions in our patients, had additional open surger-
ies been required, there would probably have been
injury to the involved structures of the cavernous sinus
(patient 3) or to the conus and caudaequina (patient 2 and
patient 1). Others have argued that a gross total resection is
not always the best approach and, alternatively, a debulk-
ing with planned subsequent surgeries over the course of
a patient’s lifetime may be safer. [3, 5, 32, 33] Instead,
consideration of planned post-operative radiosurgery for
those patients where a gross total resection is not possible,
or is excessively risky, might be appropriate.
Although we have not seen evidence of any radia-
tion related complications in our patient population,
potential risks could include radiation necrosis or mye-
lopathy. Epidermoids can also spontaneously undergo
malignant degeneration. [15] Although the mechanism
is not well understood and is thought to involve chronic
inflammation, cyst rupture, and subtotal resection of the
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5. Radiosurgery for recurrent epidermoids (revised)
Journal of Radiosurgery and SBRT Vol. 0 2011 5
cyst wall, [34] SRS could theoretically increase the risk
of a malignant conversion.
CONCLUSION
Others have discussed radiation therapy and SRS
as possible treatments for epidermoids of the central
nervous system, however, we describe the first use of
SRS for spinal epidermoid cysts. Our patients all had
multiply recurrent lesions and we believe that the use
of SRSprevented or significantly delayed subsequent
recurrences. We believe that SRS should be considered
for some epidermoids that are difficult or impossible
to resect, or for epidermoids in patients who would
not tolerate or might not accept an open procedure.
For those patients who must have surgery because
of mass effect, but for whom a gross total resection
might be excessively risky, a planned subtotal resec-
tion followed by radiosurgery might be an appropriate
consideration. Our recommendations are preliminary.
The study of a larger cohort, followed for a much
longer period, would be required to perfect treatment
recommendations.
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