Optic pathway ganglioglioma with intraventricular cyst

CASE REPORT

Optic pathway ganglioglioma with intraventricular cyst

Pietro Spennato • Mario Giordano • Claudio Ruggiero •

Ferdinando Aliberti • Maria Consiglio Buonocore • Anna Nastro •

Vittoria D’Onofrio • Delfina Bifani • Giuseppe Cinalli

Received: 3 February 2010 / Accepted: 4 August 2010

� Springer Science+Business Media, LLC. 2010

Abstract Gangliogliomas originating in the optic pathway

are rare, with less than 20 cases reported in the literature.

Diffuse, bilateral involvement of the entire optico-chiasmatic

pathway is exceptional. We report a case of suprasellar gan-

glioglioma that involved bilaterally the entire pregeniculate

optic pathway. The patient presented with visual deficit, nys-

tagmus, papilledema and acute biventricular hydrocephalus

secondary to intraventricular cyst that required urgent surgery.

Endoscopic fenestration of the tumoral cyst allowed control of

hydrocephalus and decompression of the visual pathway.

Through microsurgical procedure by pterional approach, par-

tial removal of the tumor and histological diagnosis were

accomplished 1 week later. The patient was managed with

chemotherapy and radiation therapy. He presents stable resid-

ual disease at 4-year follow-up. Embryological origins, histo-

logical features, neuroradiological appearance, management

and prognosis of optic pathway gangliogliomas are reviewed.

Keywords Ganglioglioma � Optic pathway � Suprasellar

tumor � Endoscopy � Hydrocephalus

Introduction

Gangliogliomas, first described by Perkins [1], are rare

tumors of the central nervous system, composed of a mixture

of neoplastic neurons and neoplastic glial cells. They

account for 0.4–1.3% of all brain tumors and are more

common in infancy with an incidence of 7.6% [2, 3]. Gan-

gliogliomas can occur in any part of the central nervous

system: the temporal lobe is the most common location

followed by the frontal lobe, the spinal cord, the brainstem,

the cerebellum and the pineal gland [3–5]. Involvement of

the optic pathway is usually secondary to diffusion of tumors

arising from adjacent structures, such as temporal lobe,

hypothalamus or basal ganglia [2, 6, 7]. Primary optic

pathway gangliogliomas (OPGG) are very rare, with 15

cases reported in the literature [2, 8–19]. Association with

neurofibromatosis has been reported in two cases of gan-

gliogliomas of the optic nerve [15, 17]. We report the case of

a 6-year-old boy with a large, partially cystic, suprasellar

tumor originating in the chiasm and bilaterally involv-

ing the entire pregeniculate optic pathway, that was identi-

fied as a ganglioglioma by histopathological evaluation.

Embryological origins, histological features, neuroradio-

logical appearance, management and prognosis of OPGG

are hereby reviewed.

Case report

History and examination

The patient was a 6-year-old male with no signs or family

history of neurofibromatosis. At the age of 6 months he

presented nystagmus. Repeated ophthalmological evalua-

tions showed no other visual abnormalities. No imaging of

P. Spennato (&) � C. Ruggiero � F. Aliberti � G. Cinalli

Department of Pediatric Neurosurgery, Santobono-Pausilipon

Children’s Hospital, Via Mario Fiore n.6, 80129 Naples, Italy

e-mail: [email protected]

M. C. Buonocore � A. Nastro

Department of Pediatric Neuroradiology, Santobono-Pausilipon

Children’s Hospital, Naples, Italy

V. D’Onofrio � D. Bifani

Department of Pathological Anatomy, Santobono-Pausilipon

Children’s Hospital, Naples, Italy

M. Giordano

Department of Neurosurgery, International Neuroscience

Institute, Hannover, Germany

123

J Neurooncol

DOI 10.1007/s11060-010-0341-3

the brain was obtained until the age of 6 years, when visual

loss, more marked in the right eye, and bilateral papille-

dema were finally diagnosed by a new ophthalmologist.

Magnetic resonance imaging (MRI) of the brain revealed a

large sellar and suprasellar mass involving the optic chiasm

and both optic tracts, especially on the right side (Fig. 1).

The lesion was hypointense on T1-weighted images (WI)

and hyperintense on T2-WI and FLAIR images. Cranially,

the lesion had a cystic component bulging into the third

ventricle and the frontal horn of the lateral ventricle,

especially on the right side, obstructing both foramina of

Monro and causing biventricular hydrocephalus. Then the

child was referred to our department. Upon admission,

he complained of headache and vomiting. Neurological

examination showed no abnormalities except for nystag-

mus and low visual acuity (evaluated at 1/120 in the right

Fig. 1 Midsagittal T1 (a),

coronal T2 (b) and axial T2

(c–e) MRI of the brain at

presentation, showing a large

sellar and suprasellar mass

involving optic chiasm and both

optic tracts, with cystic

component bulging into the

third ventricle causing

biventricular hydrocephalus

J Neurooncol

123

eye and 40/100 in the left eye). Fundoscopic examination

revealed bilateral papilledema and dilated and tortuous

blood vessels, more pronounced on the right side. No

endocrine dysfunction was observed.

First operation and post-operative course

The same day, an endoscopic ventriculo-cystostomy of the

cystic portion of the tumor was performed, in order to

decompress the optic pathway, resolve the hydrocephalus,

and obtain tissue sampling for diagnosis. Under general

anaesthesia, a rigid fiberscope (Channel Neuroendoscope;

Medtronic, Minneapolis, USA) was inserted into the frontal

horn of the right lateral ventricle via a precoronal burr-hole

drilled 3 cm away from the midline. The cyst projected into

the lateral ventricle, obstructing the right Monro foramen.

The cyst wall was opened with monopolar coagulation

(ME2, Codman & Shurtleff; Johnson & Johnson, Raynham,

MA, USA) and the cystic content, about 6 ml of yellowish

fluid, was aspirated with a silastic catheter. Large fragments

of the cyst walls were removed with grasping forceps and

microscissors. The cyst was multiloculated, thereafter the

intracavitary septations were also fenestrated. The post-

operative course was uneventful; headache relieved and

papilledema improved; visual acuity remained unchanged.

A computer tomography (CT) scan of the head confirmed

the collapse of the cystic component of the lesion and res-

olution of hydrocephalus (Fig. 2). Bilateral calcifications

along the optic tracts were also evident. The endoscopic

biopsy was inconclusive for diagnosis, showing only

ependymal cells: no tumor was identified in the cyst wall,

and no malignant cells in the cyst fluid.

Second operation and histological examination

One week later, the boy underwent microsurgical resection

of the tumor via right pterional approach with deposition of

the right orbital bar. At surgery, the optic nerves, the chi-

asm and the right optic tract showed to be grossly involved

by tumoral tissue. The suprasellar and retrosellar exophytic

components of the tumor were removed. The histological

examination showed the presence of two cellular compo-

nents (Fig. 3): glial cells and atypical neurons. The neurons

were enlarged, often binucleate with nuclear anomalies.

The glial component consisted of neoplastic astrocytes

arranged in pilocytic and fibrillary patterns with microcysts

and eosinophilic granular bodies. Lymphocytic perivascu-

lar infiltrates were also present. Immunohistochemical

examination showed positivity to synaptophysin and neu-

rofilament protein in the neuronal subpopulation, and to

glial fibrillary acidic protein and vimentin in the glial

component. The histopathologic diagnosis was gangli-

oglioma.

Post-operative course and adjuvant therapies

Post-operative course was uneventful, except for the

appearance of a subcutaneous, tense CSF collection, under

the skin flap that was managed with lumbar punctures and

finally insertion of a lumbo-peritoneal shunt.

Following surgery, visual acuity improved only slightly

(10/100 in the right eye and 40/100 in the left eye) and

papilledema resolved. Post-operative MRI confirmed the

partial removal of the suprasellar and retrosellar part of the

tumor with resolution of hydrocephalus. For the first post-

operative year, no further treatments were performed, and a

Fig. 2 Post-endoscopy CT scan

showing reduction of the cystic

component and resolution of

hydrocephalus. Bilateral

calcifications along the optic

tracts are evident

J Neurooncol

123

program of close neurological, ophthalmological, endocri-

nological and neuroradiological monitoring was followed.

Afterwards, the patient was referred to a foreign center

where chemotherapy with Temozolomide and Imatinib was

started. One year later, the patient’s family contacted our

center again. The case was re-discussed by a multidisci-

plinary team. Because of ecocardiographic alteration

(hypokinesis of the lateral medio-apical segment of the left

ventricle, with normal ejection fraction), chemotherapy

was stopped. At MRI, tumor dimensions were found to be

stable. Ophthalmological evaluation confirmed severe

impairment of visual function (light perception in right eye

and visual acuity of 40/100 in the left eye), with sub-

atrophic right optic disk and pale sharp left optic disk.

Endocrinological evaluation revealed the beginning of

precocious puberty: thus the tumor was considered bio-

logically active; the patient was referred to radiotherapists

and treated with high precision stereotactic conformal

radiation therapy to a dose of 54 Gy in 30 fractions.

Except for visual function, that remained stable, the boy

was clinically well at the last follow-up (4 years following

initial diagnosis; 2 years following radiotherapy), with

complete remission of his cardiological and endocrino-

logical problems and stable residual tumor at MRI. Calci-

fications remained unchanged (Fig. 4). The psychomotor

evaluation performed with Wechsler intelligence scale for

children (WISC-R) was also normal, showing an intelli-

gence quotient total (IQT) of 87, intelligence quotient

verbal (IQV) of 95, and intelligence quotient performance

(IQP) of 80.

Discussion

The biphasic cellular pattern exhibited by gangliogliomas

is not always uniform: it can range from variants with

predominant glial population to variants with prominent

neuronal population [5]. Ganglion cells must be distin-

guished from non-neoplastic neurons which might be

encapsulated into an astrocytoma: neoplastic ganglion cells

usually appear as clusters of cells of different size, often

enlarged and binucleated, with large nuclei, prominent

nucleoli, abundant cytoplasm and Nissl’s substance [4].

The positivity at immunohistochemistry for neurofilament

protein and synaptophysin aids the differentiation of gan-

glion cells with hyperplastic or neoplastic astrocytes. Glial

cells are usually proliferating fibrillary astrocytes with rare

mitotic figures [6], but also a pilocytic pattern has been

described [9]; occasionally, the glial element is composed

by oligodendroglial-like cells [4]. Gangliogliomas are

considered benign tumors, usually classified as WHO grade

1, even if some cases of malignant transformation have

been reported [5, 20, 21]. The cases of primary atypical

(WHO grade 2) and anaplastic (WHO grade 3) ganglio-

gliomas are even rarer [5]. Their classification as atypical is

dictated by the appearance of the glial cell elements

Fig. 3 Histopathological

findings: a ganglioglioma:

ganglion cells and astrocytes

intimately intermixed (EE

9100); b detail of ganglion cell

and binucleate ganglion cells

(arrows) (EE 9400);

c immunoreactivity to

synaptophysin of ganglion cells

and their processes; d GFAP

expression by neoplastic

astrocytes

J Neurooncol

123

(increased cellularity or conspicuous nuclear pleomor-

phism), the presence of microvascular proliferation and

increased proliferation index of tumoral cells ([5%).

Additional features of necrosis characterize the anaplastic

variant. In the largest published series of supratentorial

gangliogliomas [5], the 7.5-year survival rate was 98% and

the 7.5-year freedom from recurrence 97%. In earlier

studies, however, higher recurrence rates (17–24%) and

progression-related deaths were reported [4, 21]. The

prognosis of gangliogliomas appears to be correlated with

the grade of the astrocytic component [4].

The origin of the neuronal component in case of gan-

gliogliomas of the optic pathway is controversial. In fact,

normally pregeniculate optic pathway does not contain

Fig. 4 Midsagittal contrast

enhanced T1 (a), coronal T2

(b) and axial contrast enhanced

T1 (c–e) MRI of the brain

4 years following initial

diagnosis

J Neurooncol

123

Table 1 Review of primary optic pathway gangliogliomas

Age Sex History Site Surgery Adjuvant therapies Follow-up

Cogan et al.

[10]

10 F Progressive loss of

vision

Right optic nerve,

chiasm

Partial resection Immediate post-

operative period: 500 r

over a period of

31 days

4 years: alive, stable

tumor

Lowes et al.

[13]

16 M Bilateral visual loss,

headache

Right optic nerve,

chiasm

Partial resection Immediate post-

operative period:

4,000 r/150 cm2 9 2

3 years: stable

Lowes et al.

[13]

24 M Bilateral visual loss,

glaucoma

Right optic nerve,

chiasm

Partial resection Immediate post-

operative period:

4,000 r/25 cm2 9 2

Re-operation 6 months

after termination of

RT for a large residual

tumor (partial

resection)

2 years 11 months:

Alive, stable tumor

Chilton et al.

[9]

33 M 1-year history of

progressive left

visual field loss

Right optic tract,

chiasm

Biopsy Administered in the

immediate post-

operative period:

5,400 r in 28 fractions

Not available

Lu et al. [14] 38 M Decreased vision in

the right eye, retro-

orbital pain,

headache

Right optic nerve En bloc excision of the

right optic nerve

from the globe to

chiasm

No Not available

Liu et al. [2] 6 M Headache, vomiting Chiasm,

hypothalamus

Biopsy In the immediate post-

operative period:

55 Gy

5 years. Alive,

worsening of

bitemporal

hemianopsia,

Liu et al. [2] 23 M Behavioural

changes, weight

gain, increasing

appetite, visual

disturbances

Chiasm, optic

tracts

Partial resection.

Insertion of

ventriculo-peritoneal

shunt for persistent

hydrocephalus

Yes, details not

available

17 years. Alive,

worsening of the

visual function,

increase of the

cystic portion of

the tumor

Sadun et al.

[17]

16 M Neurofibromatosis

type 1. Unilateral

visual loss

Optic nerve Resection No 2 years. Alive. No

recurrences

Shuangashoti

et al. [18]

21 F Galactorrhea. Mild

liability,

progressive visual

deterioration with

bitemporal field

defects

Hypothalamus,

chiasm

Partial resection Not available Not available

Meyer et al.

[15]

71 M Neurofibromatosis

type 1

Incidental finding at

post-mortem

examination

Right optic nerve Died

Pant et al.

[16]

8 F Progressive,

complete loss of

vision

Right optic nerve,

chiasm, right optic

tract

Sub-total resection Not available 6 months. Alive

Vajramani

et al. [19]

18 M Decreased vision in

left eye, headache

Multiple nodules in

the optic chiasm,

left optic tract,

right lateral

geniculate body,

and right optic

radiation in the

temporal lobe

Steretactic biopsy Chemotherapy with

temozolomide

8 months. Alive.

Stable.

J Neurooncol

123

ganglion cells, but only the axons originating from the

ganglion cells of the retina. Two theories have been

developed. During embryological development, the optic

stalk is lined by a layer of undifferentiated cells and is

filled by nerve fibers extending from retinal ganglion cells

[6, 14]. In subsequent stages, the primitive epithelium

disappears, leaving only precursors of the supporting glial

cells [14]. Ganglion cells of ganglioglioma may originate

from these elements. An alternative hypothesis maintains

that neoplastic neurons originate from perivascular sym-

pathetic neurons [6].

Primary OPGG has been very rarely reported in the lit-

erature, as summarized in Table 1. Most often, the reported

cases involved at least one optic nerve and the chiasm

(Tables 1, 2). Bilateral involvement of the entire optic

pathway was reported in three cases [6, 12, 19]. In one of

them [19], the tumor presented as multiple, independent

nodules along the optic pathway.

Pre-operative diagnosis of OPGG, based on neurora-

diological findings, is virtually impossible, because the

neuroradiological features are not homogeneous and spe-

cific. In children, the most common suprasellar lesions are

craniopharyngiomas and optic gliomas [18]. At CT scan,

gangliogliomas appear as focal lesions with variable den-

sity and usually minimal enhancement on contrast admin-

istration. Like craniopharyngiomas, gangliogliomas are

often calcified and cystic. The appearance of calcifications

along the optic tracts may help in distinguishing optic

pathway tumors from craniopharyngiomas (Fig. 2). No

specific MR imaging alterations may distinguish between

gangliomatous neoplasms and optic pathway gliomas [14].

Both are hypointense on T1-weighted images and iso- to

hyperintense on T2-weighted images; contrast enhance-

ment is not constant [3, 22, 23] (Table 2). Pathological and

immunohistochemical evaluation are necessary for differ-

ential diagnosis (Table 2).

In our case, the entire pregeniculate optic pathway (optic

nerves, chiasm, optic tracts) was bilaterally involved and a

cystic upward extension of the tumor penetrated the third

ventricle and obstructed both Monro foramina, causing

biventricular hydrocephalus. This required an urgent sur-

gical treatment. Initially, an endoscopic minimally invasive

approach was chosen, in order to relieve the mass effect of

the cystic portion on surrounding structures (hypothalamus

and optic pathways), re-establish the CSF pathways, curing

the hydrocephalus and obtaining tissue sampling for his-

tological diagnosis. Unfortunately, the biopsy was incon-

clusive for diagnosis, showing only ependymal cells,

thereafter another surgical approach was scheduled.

Optic pathways tumors that involve chiasm and hypo-

thalamus cannot be completely resected. Because most

lesions exhibit indolent nature and respond to adjuvant

therapy, the most common modality of treatment is con-

servative surgery (biopsy or partial removal), reserving

more aggressive resection for lesions that fail to respond and

exhibit mass effect [24, 25]. In our case, because the mass

effect was already relieved by the endoscopic cyst fenes-

tration, an extensive resection was not planned. Aggressive

Table 1 continued

Age Sex History Site Surgery Adjuvant therapies Follow-up

Allen et al.

[8]

11 M Nystagmus Right optic nerve,

optic chiasm, both

optic tracts, optic

radioations

Stereotactic biopsy Multiple chemotherapy

regimens in 8 years

Radiation therapy

(54 Gy)

Surgical debulking

because progression

9 years. Malignant

transformation in

atypical teratoid/

rabdoid tumor.

Death

Jalali et al.

[12]

7 F Bilateral visual loss Diffuse involvement

of the entire

optico-chiasmatic

pathway

Biopsy SCRT (54 Gy) in

immediate post-

operative period

Not available

Gupta et al.

[11]

7 M Visual loss, diabetes

insipidus and

hydrocephalus

Both optic nerves

and chiasm

Ventriculo-peritoneal

shunt, biopsy

Not available Not available

Present report 6 M Nystagmus, visual

loss, acute

hydrocephalus

Bilateral

pregeniculate

pathway

Endoscopic

fenestration of

intraventricular cyst.

Partial resection

Chemotherapy with

temozolomide and

imatinib

SCRT (54 Gy in 30

fractions),

administered 2 years

following diagnosis

4 years: alive, stable

VA Visual acuity, RE right eye, LE left eye, SCRT stereotactic conformal radiation therapy

J Neurooncol

123

surgical resection at the time of diagnosis should be con-

sidered only in patients with tumors growing exophytically

from the optic chiasm and hypothalamus [25]. However,

also in these cases, it remains uncertain whether the long-

term follow-up outcomes in terms of disease stability and

function represent an improvement over those obtained with

more conservative surgical approaches [26].

In the reported cases of OPGG, total resection was

performed only in one case of ganglioglioma limited to one

optic nerve, without involvement of the chiasm [14]: as

expected, the patient became blind on the right eye

(preoperative visual acuity was 50/100), with ptosis and

ophthalmoplegia, but also suffered temporal hemianopsia

on the left eye, possibly due to injury of infero-lateral

retinal fibers in von Willebrandt’s genu.

In the remaining cases, partial resection or biopsy were

performed. All patients underwent adjuvant therapies: in 1

case only chemotherapy [19], in 1 case both chemotherapy

and radiotherapy [8], and in the remaining 13 cases radi-

ation therapy alone.

Radiation therapy in optic pathway tumors is associated

with excellent results in terms of disease stabilization and,

Table 2 Differences between suprasellar gangliogliomas, gliomas and craniopharyngiomas

Optic pathways gliomas Optic pathways gangliogliomas Craniopharyngiomas

Pathology Pilocytic/fibrillary astrocytes

Rarely: malignant astrocytes

Usually low grade astrocytomas

(WHO grade 1)

Pilocytic/fibrillary astrocytes

Displastic neurons

Rarely: malignant astrocytes

Usually low grade tumors

(WHO grade 1)

Microcystic epithelial tumor, with two

main aspects: broad strands, cords

and bridges of multistratified

squamous epithelium, with

peripheral palisading of nuclei,

keratin and dystrophic calcification

(adamantinous aspect); sheets of

squamous epithelium forming

pseudopapillae (papillary aspect).

(WHO grade 1)

Immunohistochemistry Presence of MAP2 and lack of

CD34 immunoreactivity in

tumoral glial cells

Synaptophysin and neurofilament

protein expressed by neuronal

subpopulation

Presence of CD34 and lack of MAP2

immunoreactivity in tumoral glial

cells

Epithelial cells immunoreactive for

keratin and cytokeratin

Clinical presentation Visual deficit, proptosis,

nystagmus, optic atrophy,

hormonal disturbances

Visual deficit, proptosis, nystagmus,

optic atrophy, hormonal

disturbances

Visual deficit, increased intracranial

pressure, hormonal disturbances

Location 10–30% unilateral optic nerve.

70% chiasm involvement/

bilateral optic nerve

3/16: unilateral optic nerve

9/16: chiasm involvement

4/16: diffuse bilateral involvement of

the entire optic pathway

20% prechiasmatic

30% infrachiasmatic

30% retrochiasmatic

10% intrasellar

10% intraventricular

Association with

neurofibromatosis (NF1)

20–50% of patients have

neurofibromatosis

2/16 were also affected by NF1 No association

Radiological findings

(MRI)

Hypointense on T1

Iso- to hyperintense on T2

Contrast enhancement not

constant

Hypointense on T1

Iso- to hyperintense on T2

Contrast enhancement not constant

± Calcifications along the optic

pathway (detectable on CT scan)

Solid part: hypointense in T1,

hyperintense in T2, variable

gadolinium enhancement. Cystic

part: hyperintense on T2.

Calcifications in the cyst wall and

solid part easily detectable on CT

scan

Treatment Surgery ± radiation therapy

± chemotherapy

Surgery ± radiation therapy

± chemotherapy

Two modalities:

(1) Radical surgery

(2) Conservative

surgery ? radiotherapy

Malignant transformation Reported very rarely only in

irradiated tumors [20]

1/16: malignant transformation in

atypical teratoid/rabdoid tumor

No malignant transformation

Prognosis 70–85% of cases 10-years

progression-free survival after

treatment

Appears similar to low grade

gliomas

Recurrence rate of 15% at 10 years

after total removal and 75% after

partial removal

J Neurooncol

123

occasionally, regression, often leading to significant

improvement in visual function [25]. However, this approach

may be detrimental for the developing brain, resulting in severe

cognitive and endocrine deficits, and it entails the risk of

radiation-induced malignancies and vasculopathy, such as

Moya Moya syndrome [25]. Thereafter, its use should be

reserved to patients older than 8 years of age with a biologi-

cally active tumor.

In our case, a policy of close clinical and neuroradio-

logical monitoring was initially adopted; radiation therapy

was administered when the boy reached 8 years of age and

when biological activity of the tumor was demonstrated by

the appearance of endocrinological disturbances (preco-

cious puberty).

The role of chemotherapic agents in optic pathway

tumors is controversial. In recent years, chemotherapy is

assuming an increasing role in the management of these

tumors, particularly for younger patients, with the aim of

avoiding or deferring radiotherapy and its complications. A

variety of regimens, most of them including carboplatin

and vincristine, have been employed, with response or

stabilization rate of 20–80% [25].

Our patient received temozolomide and imatinib, started

at another center: they were stopped because of cardiac

toxicity.

Temozolomide was also administered in a case of dif-

fuse OPGG reported by Vajramani et al. [19], but the

follow-up was too short to draw conclusions. The experi-

ence with temozolomide in low grade gliomas in children

is limited. In a recent series, the overall disease stabiliza-

tion rate in 26 patients with progressive optic pathway

pilocytic astrocytoma was 54% during a follow-up of

34 months [27]. In our opinion, temozolomide can be

considered a viable option to attempt to delay radiotherapy

in younger children with progressive tumors or in case of

failure of first-line therapy.

Most of the previously reported OPGG cases remained

stable during the follow-up (Table 1). Two patients were

reoperated because of progression of residual tumors

[8, 13]; one of these died as a consequence of tumor pro-

gression and malignant transformation in atypical teratoid/

rhabdoid tumor (AT/RT) [8]. This patient, following ste-

reotactic biopsy, received multiple chemotherapic regi-

mens over an 8-year period (the tumor showed clinical and

radiographic progression following each attempt to stop

chemotherapy). Finally, he underwent radiotherapy and

surgical debulking. At that time, the tumor encompassed

two distinct components, including a low-grade ganglio-

glioma and a highly malignant AT/RT. The authors

hypothesized that the change in clinical course may have

been due to acquisition of the INI1 mutation, with corre-

sponding histologic evolution to a rhabdoid phenotype.

Molecular and immunohistochemical studies demonstrated

inactivation and subsequent loss of protein expression

of INI1 in the rhabdoid component, while the regions of

ganglioglioma demonstrated retained nuclear expression of

this protein. Another hypothesis is that OPGG and AT/RT

were both derived from a common stem cell. The acqui-

sition of genetic alterations, possibly due to the therapy,

may have resulted in a change in the histologic appearance

and biologic aggressiveness.

In conclusion, OPGG appear similar in their indolent

course to gliomas arising in the same site, with long post-

operative survival. Thereafter, treatment strategy, including

indication to surgical debulking, chemotherapy and radio-

therapy, should be considered identical for gliomas and

gangliogliomas arising in this region. Unfortunately, when

the optic chiasm is infiltrated, the prognosis of the visual

function is unsatisfactory. A multidisciplinary team, com-

posed by neurosurgeons, oncologists, endocrinologists,

ophthalmologists and radiotherapists, is indispensable for

the adequate management of these patients.

Acknowledgment The authors thank Dr Alessandro Della Corte,

MD, PhD, for his contribution in the revision of drafts for this

manuscript.

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