Neurenteric cysts are rare, congenital lesions that can occur anywhere along the neuraxis.[1] They typically present in children and young adults. When they are recognized, neurenteric
cysts are more commonly found in the spinal canal and much less frequently intracranially.[2] The posterior fossa is the most common intracranial location.[3] Neurenteric cysts are thought to slowly expand by accumulation of the cyst contents.
Here we present an unusual case of a 53-year-old woman who complained of headache
and weakness in all four extremities. She was found to have a large posterior fossa
neurenteric cyst. A computed tomography (CT) done approximately a year and a half
earlier failed to reveal any obvious abnormality. We describe this case, the surgical
management, and the histopathology, and discuss this case in view of current theories
of neurenteric cysts.
CASE REPORT
History and Examination
A 53-year-old woman with a medical history significant for hypertension presented
with a 3-day history of headaches and a subjective feeling of weakness in all four
extremities, worse in the upper extremities than in the lower extremities. On detailed
neurological examination, there were no abnormal findings except for slightly decreased
strength in bilateral triceps, hand intrinsic muscles, and hip flexors. Routine laboratory
tests, chest X-ray, and electrocardiogram were all normal.
Neuroimaging
A noncontrast head CT was obtained on admission that demonstrated a large, extra-axial
hyperdense mass (3.9 × 2.2 × 3.0 cm) in the posterior fossa with significant mass
effect on the pons and medulla (Fig. [1]). The patient had undergone a noncontrast head CT scan 17 months earlier when she
had complained of frequent headaches. This study was read as normal by the neuroradiologist,
although there appears to be a small extra-axial lesion on the right near the medulla
upon closer review (Fig. [2], arrow). The dimension of this lesion is ~1.2 × 0.75 × 1.0 cm.
Figure 1 Serial CT scan images done at the time of admission (clockwise from top left) show
a hyperdense lesion anterior to the brain stem extending from the foramen magnum up
to the tentorium.
Figure 2 Serial CT scan images (clockwise from top left) obtained 17 months before admission
failed to demonstrate significant pathology and were read as normal. A small hyperdensity
to the right of the medulla can be seen (arrow).
Magnetic resonance imaging (MRI) of the brain with and without gadolinium administration
was then obtained on this admission (Fig. [3]). This study demonstrated that the mass was nonenhancing. The mass itself was hyperintense
compared with brain parenchyma on T1-weighted imaging and iso- to hypointense on T2-weighted
imaging suggesting a cyst with highly proteinaceous contents. In addition, the flow
voids of the basilar artery and its branches appeared to be stretched over the surface
of the cyst with perforators to the brain stem passing through it. The preliminary
diagnosis based on these findings was a neurenteric cyst, although other types of
cystic lesions such as dermoid cyst or cystic schwannoma were also considered.
Figure 3 MRI images obtained on admission. (A) Sagittal T1-weighted images show a large mass
anterior to the brain stem that is hyperintense to CSF and brain parenchyma. (B) Axial
T2-weighted image through the pons shows that the lesion is hypointense to CSF and
brain suggesting high protein content. A granuloma on the surface of the brain stem
is visible (arrowhead). (C) Precontrast axial T1-weighted image shows the significant
compression of the pons and distortion of the fourth ventricle. The basilar artery
is pushed far anterior to the brain stem (white arrow). (D) Postcontrast axial T1-weighted
images show that there is no significant enhancement of the lesion.
Operation
The patient was taken to the operating room, and a left retrosigmoid approach was
performed. The patient was positioned supine with the head turned ~80 degrees to the
right. Somatosensory-evoked potentials, motor-evoked potentials, facial nerve-monitoring,
and brain stem auditory-evoked responses were obtained. A curvilinear incision was
made behind the left ear, extending ~6 cm behind the postauricular crease. The scalp
and suboccipital muscles were elevated and retracted in layers. A 4 × 4 cm retrosigmoid
craniotomy was performed, and then the sigmoid sinus was skeletonized from the transverse-sigmoid
junction down to the jugular bulb to widen the exposure.[4] The dura was opened such that sigmoid sinus and the transverse sinus were reflected
anteriorly and superiorly, respectively, to maximize the exposure along the petrous
ridge.
Following release of cerebrospinal fluid (CSF) from the cisterna magna, gentle retraction
on the left cerebellar hemisphere brought the lesion into view. The cyst filled the
entire cerebellopontine angle from the trigeminal nerve above, down to foramen magnum
below. The CN VII/VIII nerve complex was stretched across the top of the cyst (Fig.
[4]). The translucent cyst walls were filled with tan, viscous contents. Using standard
microsurgical techniques, the cyst was opened and evacuated by working through three
“corridors”: the interval between the trigeminal nerve and the CN VII/VIII nerve complex,
the interval between the CN VII/VIII nerve complex and the lower cranial nerves, and
between the lower cranial nerves and the foramen magnum (Fig. [5]). Following removal of the cyst contents, resection of the cyst wall was done sharply
where possible. The cyst wall was tightly adherent to the cranial nerves, the surface
of the brain stem, and the basilar artery and its branches. A gross total resection
of the cyst wall was limited by these structures. Firm deposits on the surface of
the pons were sharply resected. There was no evidence of a bony anomaly of the clivus
or skull base associated with the cyst. The dura was closed in a watertight fashion.
The bone was replaced with cranial fixation plates, and bony defects were filled with
hydroxyapatite-based bone substitute. The suboccipital muscles and scalp were closed
in a standard fashion. Intravenous steroids, which were started prior surgery, were
gradually tapered off.
Figure 4 Operative view of the neurenteric cyst. The trigeminal nerve (arrowhead) and the
CN VII/VIII nerve (arrow) complex are seen crossing the field. The cyst is filled
with viscous, tan fluid.
Figure 5 Microsurgical resection of the neurenteric cyst. (Top left) Opening of the cyst wall
between the trigeminal nerve and the VII/VIII nerve complex. (Top right) Sharply dissecting
the cyst wall from the VII/VIII nerves. (Middle left) Dissection of the cyst wall
from the lower cranial nerves. (Middle right) Partial removal of the cyst contents
and the cyst wall reveal the basilar artery (arrowhead). (Lower left) Granuloma on
the surface of the pons (arrow). (Lower right) Basilar artery (arrowhead) surrounded
by remnants of the cyst wall.
Histopathological Findings and Postoperative Course
Multiple microscopic sections of the cyst wall revealed pseudostratified, ciliated
epithelium confirming the diagnosis of neurenteric cyst (Fig. [6]). In some areas, the cyst wall demonstrated marked squamous metaplasia. The cyst
wall showed evidence of recent and old hemorrhage (fresh blood and hemosiderin-laden
macrophages). The firm deposits on the brain stem represented xanthogranulomatous
reaction. Special stains also showed the presence of amyloid deposits within the cyst
wall. Examination of the cyst contents revealed histiocytes, cholesterol crystals,
and keratin debris.
Figure 6 Histopathological examination of neurenteric cyst. (Top left) Low power view of the
cyst wall (HE stain). (Top right) High power view of the cyst wall showing pseudostratified
ciliated (arrow) epithelium (HE stain). (Bottom left) Part of the cyst wall showing
squamous metaplasia with amyloid deposits in the stroma (HE stain). (Bottom right)
High power view of the xanthogranulomatous reaction showing multinucleated giant cells,
cholesterol clefts, and macrophages (HE stain).
Postoperatively, the patient had a House-Brackmann Grade III left facial palsy and
no other deficits. The facial weakness resolved completely by 12 weeks postoperatively.
The patient did not develop any signs or symptoms of aseptic meningitis. Immediate
and 3-month delayed postoperative imaging revealed no evidence of residual cyst and
re-expansion of the pons with resolution of the distortion of the fourth ventricle
and posterior fossa structures (Fig. [7]). Imaging of the entire spinal axis at 3 months postoperatively did not reveal any
evidence of dissemination.
Figure 7 Postoperative MRI after 3 months. (Top left) Sagittal T1 image shows no residual
cyst. (Top right) Axial T2 image shows resection of cyst and resolution of the distortion
of the brainstem. (Bottom left) Axial T1 image shows normal medulla. (Bottom right)
Postcontrast T1-axial image through pons shows no evidence of residual cyst.
DISCUSSION
Pathology
Neurenteric cysts are lesions filled with fluid, sometimes clear and occasionally
cloudy, and lined by a thin wall of pseudostratified or stratified cuboidal epithelium
resting on a basement membrane.[2]
[5]
[6] The cells lining the cyst walls can be ciliated, nonciliated, or mixed.[7] On gross examination, yellow, white, gray, and red cyst walls have all been noted.
The fluid of the cyst, however, is often a clear, yellowish, or brown oily substance.
Similar to our case, Ko et al reported finding a yellowish nodule composed of foamy
histiocytes and chronic inflammatory cells within a prepontine neurenteric cyst that
had undergone xanthomatous changes.[8] Schwartz et al found xanthogranulomatous change as a marked feature of a cerebellopontine
angle neurenteric cyst.[9]
While these cysts are believed to be congenital, confusion surrounds the precise pathogenesis
of neurenteric cysts and has led to an assortment of other names (e.g., archenteric
cyst, bronchogenic cyst, endodermal cyst).[1]
[3]
[10]
[11]
[12]
[13]
[14] The name, neurenteric cyst, however, is the most accepted.[6]
Precisely how the endodermal tissue of a neurenteric cyst comes to be found intracranially
is still a matter of controversy. The current theories of neurenteric cyst development
have been well summarized recently by several authors.[1]
[2]
[3]
[15]
[16]
[17] The most commonly held theory is that neurenteric cysts result from an error in
the separation of the notochord (the embryonic vertebral column) and the foregut as
the neurenteric canal closes during the process of excalation near the third week
of gestation.[2]
The epithelium of neurenteric cysts often stains positive for epithelial membrane
antigen, cytokeratin, and carcinoembryonic antigen.[1] Neurenteric cysts test negative for characteristic neuroectodermal markers such
as glial fibrillary acidic protein, S100, neuron-specific enolase, and vimentin.[18] These staining properties and the histopathological findings of respiratory/gastrointestinal
epithelia strongly suggest neurenteric cysts are endodermal in origin.
Epidemiology and Clinical Presentation
While these lesions are being found at higher frequencies in the central nervous system
(CNS) due to advances in neuroradiology, neurenteric cysts are most commonly found
outside of the CNS, in the posterior mediastinum.[18]
[19] They may also be found as a communication between the CNS and mediastinum or the
CNS and the abdominal viscera.[1]
[19]
[20]
[21] After the posterior mediastinum, the spinal canal is the second most common location
for a neurenteric cyst, particularly along the spinal cord's ventral aspect.[13] Spinal neurenteric cysts may be associated with other anomalies such as dysraphism,
hemivertebrae, and VACTERL anomalies.[13] Neurenteric cysts account for ~0.3 to 0.5% of all spinal tumors, half of these are
associated with the above-listed deformities.[18]
[22] The least common location for a neurenteric cyst is the intracranial compartment.[23]
Intracranial neurenteric cysts are rare, although more than 80 cases of intracranial
neurenteric cysts have been reported in the literature.[18] The most common site is the midline posterior fossa. Unlike spinal neurenteric cysts,
these cysts are almost never associated with a bony anomaly of the clivus or skull
base. In a review of the literature, Bejjani et al found 46 cases of neurenteric cysts
in the posterior fossa, over half of which were located anterior to the brain stem
and roughly a fifth of the cases were located within the fourth ventricle.[3] Others have reported intracranial neurenteric cysts near the lower clivus,[18] the medulla oblongotta,[24] the parietal convexity,[25] within the optic nerve,[26] and extradurally.[7]
[27]
There is a bimodal age distribution at presentation for intracranial neurenteric cysts,
with a small peak in the first decade and a larger peak in the third and fourth decades.
However, cases have been reported in neonates as well as patients in the eighth decade.[3]
[24]
[28] Both female and male predominance have been reported.[3]
[29]
The most common presenting complaint for intracranial neurenteric cysts is headache.[3] Gait disturbance, extremity weakness, and sensory complaints are reported to be
common but less frequent.[3] Other symptoms have also been reported such as ataxia and memory problems.[30]
[31] The symptoms may result from mass effect, irritation of surrounding neural structures,
or inflammation.[3]
[18]
[32] Malignant transformation of a neurenteric cyst is believed to be extremely rare.
There are six reported cases in the literature.[33]
[34]
[35]
Imaging
The radiographic appearance of neurenteric cysts can be quite variable. The typical
radiological findings have been well summarized by Preece et al.[29] On CT, neurenteric cysts may appear hypodense (such as CSF) or hyperdense as in
our case. The lesion on T1- and T2-weighted MRI may have low, high, or mixed signal
intensities. Signal intensity appears to be a function of the cyst–fluid protein content.
Highly proteinaceous cysts tend to have T1 signals isointense to hyperintense compared
with CSF as in the case presented here. On T2-weighted imaging, neurenteric cysts
tend to be hyperintense. Neurenteric cysts do not enhance. Given the variability in
their radiological appearance, however, one must also consider other intracranial
cystic lesions such as arachnoid cysts, epidermoids, dermoids, Rathke cleft cysts,
ependymal cysts, and cystic tumors such as schwannomas. CT can help to exclude arachnoid
cysts, for example, if the neurenteric cyst is hyperdense to CSF. Fat suppression
MRI can help rule out dermoids. Diffusion imaging can also help rule out dermoid and
epidermoid cysts as these cysts often exhibit greater restriction than neurenteric
cysts.
Expansion
Neurenteric cysts are typically thought to be benign and slow growing.[6] We could find no other case of a rapidly expanding neurenteric cyst documented in
the literature. Typically, these cysts have been operated on when they become symptomatic,
and no serial imaging has been obtained before surgery. Rarely, a neurenteric cyst
has been documented as a slowly expanding lesion. Ito et al found a small increase
in the size of a cerebellopontine angle cyst by CT, 6 years after the initial examination.[36] Shakudo et al noted a change in the size of a neurenteric cyst anterior to the brain
stem over 33 months.[37] Although the size change was not as dramatic as in our case, the signal intensity
on MRI of the cyst contents changed as well. This change led the authors to conjecture
that the balance of secretion and resorption by the cyst led to the increase in size.
Finally, Fuse et al found a case of a neurenteric cyst at the craniocervical junction
that also enlarged slightly over 4 years.[38]
The most interesting aspect of our case is the rapid increase in size over approximately
a year and a half. The cyst that we removed is one of the largest posterior fossa
cysts documented to date. Along with the marked increase in dimension, the volume
of the cyst increased by ~25-fold. The mechanism of this marked expansion is unclear.
We considered increased secretion, hemorrhage, and inflammation as possible explanations.
Accelerated secretion seems an unlikely cause for growth. The epithelium of the cyst
in our case contained very few mucin-secreting cells. At least half of intracranial
neurenteric cysts lack a preponderance of goblet cells.[29] Considering hemorrhage, we saw no evidence of vascularity within this lesion (grossly
or microscopically). Indeed, neurenteric cysts are prototypically avascular. However,
there was histological evidence of hemorrhage. The acute blood products in the cyst
contents were presumably related to surgery, but hemosiderin-laden macrophages were
also present in the cyst wall. Inflammation could also be partly responsible for the
size increase. We did find many histiocytes and abundant keratinaceous debris in the
cyst along with xanthogranulomatous deposits on the brain stem. A cycle of inflammation
and hemorrhage followed by more inflammation could be responsible for the increase
in cyst size.
Treatment
Complete removal of a neurenteric cyst is thought to be the ideal treatment as this
relieves mass effect, eliminates the risk of recurrence, and reduces the chance of
dissemination. Removal of the cyst contents is typically achieved by marsupialization,
but complete removal of the cyst wall may be hindered by tight adherence to the surrounding
structures. A radical resection of the cyst wall was performed in our case, but adherence
to the surface of the brain stem, cranial nerves, and basilar artery branches meant
that small remnants of the wall probably remain. Recurrence and craniospinal dissemination
can occur.[35]
[39]
[40] Because of the possibility of recurrence, dissemination, and malignant transformation,
long-term serial imaging is recommended on follow-up. We plan to follow this patient
long term with serial MRI.
CONCLUSION
We demonstrate in this report that neurenteric cysts can expand rapidly even in adult
patients. Microsurgical techniques are essential in managing posterior fossa neurenteric
cysts as they tend to engulf and adhere to critical neurovascular structures. In addition,
close monitoring of even small, asymptomatic neurenteric cysts may be indicated given
that they can expand rapidly. Given the low but significant rate of recurrence after
surgery, close follow-up is advised.
