Review Article
Intrinsic Brainstem Neurenteric Cyst with Extensive Squamous Metaplasia in a Child
Sui-To Wong, Gregory S. Moes, Kwong-Yui Yam, Dawson Fong and Dachling Pang*
Corresponding Author: Dachling Pang, Kaiser Permanente Medical Center, Department of Paediatric Neurosurgery, 280 W. MacArthur Blvd., Oakland, CA 94611. Tel: (510)752-1759, Fax: (510) 752-1758. E-mail:
Received: February 26, 2016; Revised: April 25, 2016 ; Accepted: March 22, 2016
Citation: Wong S T, Moes G S, Yam K Y, Fong D & Pang D (2016) Intrinsic Brainstem Neurenteric Cyst with Extensive Squamous Metaplasia in a Child. J Neurosurg Imaging Techniques, 1(1): 26-37.
Copyrights: ©2016 Wong S T, Moes G S, Yam K Y, Fong D & Pang D. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Share :
  • 1613

    Views & Citations
  • 613

    Likes & Shares

Intrinsic brainstem neurenteric cysts (IBNCs) are rare. We report the first paediatric case of a16-month-old girl with an enlarging intra-axial cyst in the pontomedullary segment of the brainstem, which had magnetic resonance imaging (MRI) signal characteristics consistent with those of neurenteric or epidermoid/dermoid cysts. At craniotomy, the cyst contained viscous mucin fluid which was drained and the cyst wall showed ciliated columnar epithelium embedded with mucin-secreting goblet cells consistent with an IBNC, on a background of extensive squamous metaplasia. She needed a second craniotomy because of cyst recurrence. The specimen from the second operation contained only squamous epithelium, highlighting the difficulty in differentiating between IBNC and epidermoid cyst purely on histopathology. Because of its brainstem location and adherent nature of its lining, complete resection of the neurenteric cyst was abandoned for instillation of hydrogen peroxide solution. The embryogenesis of brainstem neurenteric cyst is likely similar to that of split cord malformation, with the endomesenchymal tract occurring at a rostral segment of the gastrulating embryo.


Keywords: Intrinsic brainstem neurenteric cyst, Epidermoid, Embryogenesis, Hydrogen peroxide.


About 160 cases of intracranial neurenteric cyst have been reported in the literature [1-5], over 75 % of  which are in the posterior fossa, including inside the fourth ventricle and at the craniocervical junction [3,6]. These cysts are mostly extra-axial though they may compress and distort the brainstem. Only 2 cases of true intrinsic brainstem neurenteric cyst (IBNC) have been reported, both in adults [7,8]. Conversely, intrinsic brainstem epidermoid cysts (IBEpiCs), which share many clinical and imaging characteristics with IBNC, have been observed in 6 children and 3 adults [9-14].

We report a 16-month-old baby girl with an IBNC at the pontomedullary region. The embryogenesis of IBNC is discussed, as are their salient clinical and neuroimaging characteristics, the technique of resection, and their histopathology. Comparisons are made with paediatric IBEpiC, with an aim to distinguish between these two entities prior to making therapeutic decisions.


Case Report

A 16-month-old baby girl was incidentally found to have an intra-axial hypodense lesion at the pontomedullary region on computerized tomography (CT) done for a minor head injury (Figure 1A).

She had no neurological deficits.  Magnetic resonance imaging (MRI) showed a 1.6 cm intra-axial cystic lesion involving the lower pons and upper medulla. The cyst was hypointense to brain but slightly brighter than cerebrospinal fluid (CSF) on T1-weighted sequence, with a central area of iso-intensity (Figure 1B and D). It was hyperintense on T2-weighted sequence (Figure 1C), and had no enhancement with gadolinium (Figure 1E).  Moderate restriction was seen on diffusion-weighted imaging (DWI) (Figure 1F). She remained asymptomatic for 8 months, but at age 2, started to have mimetic facial asymmetry progressing rapidly to a frank right facial nerve palsy (upper motor neuron type, House and Brackmann grade 3/6), markedly impaired conjugated gaze to the right, and left hemiparesis.

Repeat MRI showed that the cyst had enlarged and part of its wall now enhanced with gadolinium (Figure 2). She underwent a midline suboccipital craniotomy. Intraoperatively, the 4th ventricular floor was diffusely expanded by the cyst, which was entered by cutting through the extremely thin floor under electrophysiological monitoring and ultrasound guidance. The content was mucinous. The wall of the cyst was translucent and tightly adherent to the brainstem. A small nodule was found on the superior aspect of the cavity, which was removed and sent for histopathology. The anterior wall of the cyst appeared diaphanous, and on opening it the basilar artery was visualized (Figure 3).


Histopathology: The mural nodule was composed of gliotic brain and inflammatory granulation tissue mostly covered by non-keratinizing stratified squamous epithelium (Figure 4A).  Ciliated pseudostratified epithelium bounded by a basement membrane was focally identified (Figure 4B). Special staining with mucicarmine and Alcian blue revealed rare mucin-containing goblet cells within the ciliated epithelium (Figure 4C).  No other tissue components were identified.  The overall features were consistent with an intrinsic neurenteric or endodermal cyst with extensive squamous metaplasia [15-17].


Post-operative MRI at 3 and 10 months showed a small residual cyst, which remained unchanged during this period (Figure 5A-D). Neurologically, her facial palsy resolved, but the impaired right conjugated gaze only improved slightly. Fifteen months after the first operation, the right facial palsy and left hemiparesis recurred, with a clumsy left hand and hemiparetic gait. Repeat MRI showed that the residual cyst had enlarged and was now situated more on the right side of the pontomedullary segment of the brainstem(Figure 6 A,B). She underwent a right retrosigmoid craniotomy. Intraoperatively, the lateral medulla oblongata was grossly expanded by the cyst, and the surface of the brain at maximum distension was smooth and supple. Direct electrical stimulation of the distended medulla with a bipolar coaxial probe using a current of 3 miliampere elicited no motor response. A longitudinal incision was made on the medulla over the thinnest part of the cyst wall, and viscous mucin extruded through the slit-opening. No “cheesy” material or other solid component was found within the cyst after widening of the opening by excising a 5-mm diameter piece of the thinned-out medulla, with the cyst wall tightly adherent to its inner surface (Figure 7). A distinct layer could not be peeled off from the wall of the cavity because the cyst wall itself was exceedingly thin and fragile, and so translucent that the interior of the cavity resembled smooth, compressed brainstem. Three percent hydrogen peroxide (H2O2)solution was applied to the cyst cavity for 3 minutes. Spillage of the H2O2 and bubbles exuberation were controlled by continuous suction.


Histopathologically, the medulla cum cyst wall specimen was composed of a thin layer of gliotic brain with rare axons and neurons, lined by a 0.1 mm thick membrane of non-keratinizing stratified squamous epithelium.  Ciliated epithelium and mucin-positive goblet cells were not identified (Figure 8A-C).


Post-operatively, her neurological deficits gradually recovered. At 2 months, she had residual impaired

conjugated gaze to the right, but at 1 year, her right conjugated gaze was restored nearly to full range.


MRI on post-operative day 7 showed a 6 mm x 8mm residual cavity (Figure 9A), but MRI at post-operative 9months showed complete collapse of the cavity to a slit with no cyst recurrence (Figure 9B).




Most intracranial neurenteric cysts are extraaxial lesions located caudal to the spheno-occipital synchondrosis, i.e. caudal to the dorsum sellae (see below).Neurenteric cysts intrinsic to the brainstem are rare; only 2 adult cases have been reported (Table 1) [7,8]. Our patient, who became symptomatic at age 2, is the first paediatric case, whilst the 2 adult patients presented with symptoms at ages 23 and 66. The cyst in our patient was more rostrally located, in the pontomedullary region; while the other 2 cysts were in the medulla and cervicomedullary junction (Table 1) [7, 8].


The imaging features of intracranial neurenteric cysts are highly variable [18-20]. On CT, the cyst content varies widely in attenuation, from being hypodense to hyperdense. MRI is the diagnostic test of choice, which typically shows a round and/or lobulated, non enhancing mass with signal intensities varying with its protein content. Most cysts are densely proteinaceous and are therefore hyperintense on T1-weighted images, strongly hyperintense on T2- weighted images, and more hyperintense than CSF on FLAIR. They may show mild restriction on DWI [19,20]. For the 3 intrinsic lesions, only ours and Cho et al’s patient had pre-operative multi-sequences MRI and the findings in both patients are consistent with those of the intracranial extraaxial neurenteric cysts mentioned-above. In our patient, the nodular gadolinium enhancement in the cyst wall was only detectable in the second MRI when the patient became symptomatic, which may signify reactive changes in the cyst lining (Figure 1 and 2).


Given the above imaging features of intrinsic neurenteric cysts, there are 4 main differential diagnoses: epidermoid/dermoid cysts, cystic tumours, parasitic cysts, and abscesses [19 -21], of which IBEpiC is the most difficult to be differentiated from IBNCs. In all 6 reported cases of paediatric IBEpiC [9-14,20,21], the cysts are at the pontomedullary region as in our patient; and in the 5 cases who had MRI, the signal characteristics are similar to those of intracranial neurenteric cysts (Table 2). For example, 4 of the epidermoids are hypointense on T1-weighted images, hyperintense on T2-weighted images; and all have minimal or no cyst wall enhancement [9-13,18]. Four cases of IBEpiC studied with DWI showed restricted diffusion [9,10,12,13]. Intra-axial dermoids have the same imaging characteristics as epidermoids [22]. Regarding the others on the diagnostic list, cystic brainstem tumours such as gliomas or haemangioblastomas usually have brightly enhancing solid components, and their cyst content shows no restriction on DWI [23].  Parasitic cysts near the brainstem such as neurocysticercosis have MRI signal intensities similar to CSF, and are commonly multiple and located extra-axially [19]. Abscesses typically have ring-enhancement, restriction on DWI and exuberant perilesional oedema.


Ultimately, the diagnosis of IBNC can only be definitively made by histology; even its intra-operative appearance can be confused with that of an IBEpiC (Tables1 & 2) [7-14]. Histologically, epidermoid cysts are lined by keratinizing stratified squamous epithelium without skin adnexae such as hair or sweat and sebaceous glands.  The epithelial lining of neurenteric cysts is more diversified but the epithelium should always contain ciliated cuboidal or columnar cells within a simple or pseudostratified background. Mucin from scattered goblet cells is a constant feature, suggesting a similar embryologic origin as the lining of the gastrointestinal and respiratory tracts, both originated from endoderm of the yolk sac.  Moreover, the epithelial lining of neurenteric cysts may undergo squamous metaplasia in response to surgical trauma or chronic irritation, as in our case. When the squamous metaplasia becomes prominent and the tissue sampling is limited as during our second operation, the distinction between epidermoids and neurenteric cyst by histology alone is almost impossible. Fortunately, we were able to confirm the diagnosis of IBNC from the ciliated columnar epithelium and mucin-producing goblet cells recovered from the first operation, presumably before extensive iatrogenic squamous metaplasia set in.


Several embryogenetic mechanisms have been proposed to explain the presence of endodermal derivatives within the brainstem, itself of ectodermal origin [3,7]. We think the most plausible embryogenetic scenario is the occurrence of an aberrant adhesion between the ectoderm and endoderm, as in the genesis of split cord malformation, which permits continuous contact between the two germ layers [24].  Normally, the elongating notochord cleaves the ectoderm from the endoderm in the midline where actively migrating pro-chordal cells from each side of Hensen’s node merge into a single solid tube. The ecto-endodermal adhesion, in turn, exists as a result of a more basic embryological error, the focal failure of midline integration of the pro-chordal cells [25,26]. With the incorporation of mesodermal cells from the surrounding mesenchyme, this ecto-endodermal adhesion then becomes an endomesenchymal tract that stretches from the york sac to the amniotic sac, traverses the embryonal midline, and bisects the notochord and the neural plate at a focal spot, allowing the temporary translocation of endodermal cells on to the evolving neuro-ectoderm [24]. The notochord normally extends as far rostrally as the level of the neuromere D2 [27]. This corresponds to the rostral end of the first occipital somite, just caudal to the future synchondrosis separating the occipital clivus from the sphenoid bone, which is derived from the (non-somitic) chondrocranium. This theory thus accounts for neurenteric cysts formed as rostrally as the midbrain/diencephalon junction, but always behind the dorsum sellae.


The final appearance of this basic developmental error depends on the rather random secondary evolvement of the endomesenchymal tract, which tends to be more dramatic in the spine, where a complete cutaneo-endomesenchymal tract with colliding dermoid and neurenteric cysts within the median cleft of a split spinal cord has been reported [28]. In the brainstem, only 4 convincing examples of split brain stem have been reported, only 1 had a persistent stalk within the median cleft [29-32]. One assumes that the majority of endomesenchymal tracts in the brainstem involute, but not before leaving behind an island of endodermal cells within the anterior neural plate, forming a neurenteric cyst either in front of the brainstem or completely within its substance.


Intra-operatively, all 3 known cases of IBNC contained viscous fluid that was easily aspirated [7,8]. However, total excision of the cyst walls was never possible because the epithelial linings of the cysts were invariably too thin (Table 1, Figures 3 and 7). The specimen obtained from the second operation of our patient reveals that the epithelial lining is only 0.1mm to 0.2mm thick, being densely adherent to the functional albeit distorted brainstem (Figure 3e). Its radical excision would not only be technically difficult but very risky even with sophisticated intraoperative neurophysiological monitoring [7-14,22,33,34]. To avoid damaging the delicate brainstem, we chose to leave behind the diaphanous cyst lining during both operations, but while dealing with the recurrent lesion, we instilled H2O2solution into the cyst cavity with the intention of destroying the cellular component of the epithelium in situ. Neurosurgical use of H2O2as a cytotoxic agent has been well documented.  Mesiwala et al. found that 3%H2O2 solution applied for 5 minutes to the surface of rat brains caused significant injury to the arachnoid as well as neurons and glial cells to a depth of 1mm in rats, and similar degrees of injury to human brains have been observed in tumor surgery [35]. The depth of cytocidal effect can be gauged by the time of exposure of brain tissue to H2O2. Likewise, in vitro human corneal epithelial cells have been found to be damaged byH2O2 at a concentration as low as 0.003%[36], and in vivo animal studies produced similar results with more concentrated H2O2solutions [37].




We describe the first case of paediatric IBNC, which shares similarities with reported examples of paediatric IBEpiC in clinical, imaging and intraoperative findings. Squamous metaplasia in IBNC may make its differentiation from an IBEpiC difficult even with histopathology.  IBNC is a surgical disease, and due to its specific location, the adherent nature of its lining, and its propensity to recur when present elsewhere in the neuraxis, techniques other than complete resection of its epithelial lining should be explored.


Breshears JD, Rutkowski MJ, McDermott MW, Cha S, Tihan T, et al. (2015)

Surgical Management of Intracranial Neuroenteric Cysts: The UCSF Experience. J

Neurol Surg B Skull Base 6: 475-479.


2. Chakraborty S, Priamo F, Loven T, Li J, Insinga S, et al. (2016) Supratentorial Neurenteric Cysts: Case Series and Review of Pathology, Imaging, and Clinical Management. World Neurosurg 85: 143-152.


3. Gauden AJ, Khurana VG, Tsui AE, Kaye AH (2012) Intracranial neuroenteric cysts: a

concise review including an illustrative patient. J Clin Neurosci 19: 352-359.


4. Little MW, Guilfoyle MR, Bulters DO, Scoffings DJ, O'Donovan DG, et al. (2011) Neurenteric cyst of the anterior cranial fossa: case report and literature

review. Acta Neurochir (Wien) 153: 1519-1525.


5. Prasad GL, Sharma BS, Mahapatra AK (2015) Ventral foramen magnum neurenteric cysts: a case series and review of literature. Neurosurg Rev.


6. Miller CM, Wang BH, Moon SJ, Chen E, Wang H (2014) Neurenteric cyst of the area

postrema. Case Rep Neurol Med 718415.


7. Cho JM, Ahn JY, Kim SH, Lee KS, Chang JH (2010) An endodermal cyst mimicking anintra-axial tumor in the medulla oblongata. Childs Nerv Syst 26: 853-856.


8. Lach B, Russell N, Atack D, Benoit B (1989) Intraparenchymal epithelial

(enterogenous) cyst of the medulla oblongata. Can J Neurol Sci 16: 206-210.


9. Mishra SS, Panigrahi S, Dhir MK, Pattajoshi AS (2014) Intrinsic brainstem white

epidermoid cyst: An unusual case report. J Pediatr Neurosci 9: 52-54.


10. Caldarelli M, Colosimo C, Di Rocco C (2001) Intra-axial dermoid/epidermoid tumors ofthe brainstem in children. Surg Neurol 56: 97-105.


11. Fournier D, Mercier P, Menei P, Pouplard F, Rizk T, et al. (1992) Recurrent intrinsic

brain stem epidermoid cyst. Childs Nerv Syst 8: 471-474.


12. Gopalakrishnan CV, Dhakoji A, Nair S (2012) Epidermoid cyst of the brainstem in

children: case-based update. J Child Neurol 27: 105-112.


13. Recinos PF, Roonprapunt C, Jallo GI (2006) Intrinsic brainstem epidermoid cyst. Casereport and review of the literature. J Neurosurg 104: 285-289.


14. Weaver EN Jr, Coulon RA Jr (1979) Excision of a brain-stem epidermoid cyst. Case

report. J Neurosurg 51: 254-257.


15. Friede RL (1975) Developmental Neuropathology. Springer-Verlag, USA.


16. Love S (2015) Greenfield's Neuropathology. (9th edn), CRC Press, USA.


17. Perry A, Scheithauer BW, Zaias BW, Minassian HV (1999) Aggressive enterogenous cyst with extensive craniospinal spread: case report. Neurosurgery 44: 401-404.


18. Medhi G, Saini J, Pandey P, Mahadevan A, Prasad C (2015) T1 hyperintense prepontine mass with restricted diffusion--a white epidermoid or a neuroenteric cyst? J

Neuroimaging 25: 841-843.


19. Osborn AG, Preece MT (2006) Intracranial cysts: radiologic-pathologic correlation

and imaging approach. Radiology 239: 650-664.


20. Preece MT, Osborn AG, Chin SS, Smirniotopoulos JG (2006) Intracranial neurentericcysts: imaging and pathology spectrum. AJNR Am J Neuroradiol 27: 1211-1216.


21. Nguyen JB1, Ahktar N, Delgado PN, Lowe LH (2004) Magnetic resonance imaging and proton magnetic resonance spectroscopy of intracranial epidermoid tumors. Crit Rev Comput Tomogr 45: 389-427.


22. Park JG, Babu R, Kranz PG, McLendon RE, Adamson C (2013) Intraaxial dermoid cyst of the medulla. J Neurosurg. 119: 442-445.


23. Taillibert S, Le Rhun E, Chamberlain MC (2014) Intracranial cystic lesions: a

review. Curr Neurol Neurosci Rep 14: 481.


24. Pang D, Dias MS, Ahab-Barmada M (1992) Split cord malformation: Part I: A unifiedtheory of embryogenesis for double spinal cord malformations. Neurosurgery 31: 451-480.


25. Dias MS, Pang D (1995) Split cord malformations. Neurosurg Clin N Am 6: 339-358.


26. Pang D (2015) Split Cord Malformation: From Gastrulation to Operation. Pediatric Neurosurgery: Tricks of the Trade. Thieme, USA.


27. Müller F, O'Rahilly R (2003) The prechordal plate, the rostral end of the notochord

and nearby median features in staged human embryos. Cells Tissues Organs 173: 1-20.


28. Pang D (2012) Surgical Management of Spinal Dysraphism: Schmidek and Sweet Operative Neurosurgical Techniques. (6th edn), Saunders, Philadelphia PA, USA.


29. Jain NR, Jethani J, Narendran K, Kanth L (2011) Synergistic convergence and split

pons in horizontal gaze palsy and progressive scoliosis in two sisters. Indian J

Ophthalmol 59: 162-165.


30. Jayasekera BA, Pereira EA, Magdum S (2014) Split mesencephalon: diplomyelia of thebasicranium. Br J Neurosurg 28: 403-405.


31.Ramdurg SR, Gubbi S, Odugoudar A, Kadeli V (2014) A rare case of split pons with

double encephalocoele, dermal sinus tract, and lipomeningomyelocele: a case

report and review of literature. Childs Nerv Syst 30: 173-176.


32. Rustamzadeh E1, Graupman PC, Lam CH (2006) Basicranial diplomyelia: an extension of the split cord malformation theory. Case report. J Neurosurg 104: 362-365.


33. Al-Ahmed IH, Boughamoura M, Dirks P, Kulkarni AV, Rutka JT, et al. (2013)

Neurosurgical management of neurenteric cysts in children. J Neurosurg Pediatr

11: 511-517.


34. Hashimoto M, Yamamoto J, Takahashi M, Saito T, Kitagawa T, et al. (2011) Surgical strategy forintracranial endodermal cyst--case report. Neurol Med Chir 51: 531-534.


35. Mesiwala AH, Farrell L, Santiago P, Ghatan S, Silbergeld DL (2003) The effects of

hydrogen peroxide on brain and brain tumors. Surg Neurol 59: 398-407.


36. Tripathi BJ, Tripathi RC (1989) Hydrogen peroxide damage to human corneal epithelialcells in vitro. Implications for contact lens disinfection systems. Arch

Ophthalmol 107: 1516-1519.


37. Maurer JK, Molai A, Parker RD, Li L, Carr GJ, et al. (2001) Pathology of ocular irritation with bleaching agents in the rabbit low-volumeeye test. Toxicol Pathol 29: 308-319.