Saudi Journal of Ophthalmology (2010) 24, 101–104

King Saud University

Saudi Journal of Ophthalmology

www.ksu.edu.sawww.sciencedirect.com

CASE REPORT

Primary orbital ganglioneuroma in a 2-year-old healthy boy

Hattan Al-Khiary, MD a,*, Ayman Ayoubi, MD a, Sahar M. Elkhamary, MD b

a Oculoplastic and Orbit Division, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabiab Diagnostic Radiology Department, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia

Received 7 March 2010; revised 16 March 2010; accepted 16 March 2010Available online 10 April 2010

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KEYWORDS

Ganglioneuroma;

Neuroblastoma;

Unilateral proptosis;

Pediatric

Corresponding author. Add

ing Khaled Eye Specialist H

udi Arabia. Tel.: +966 1 48mail address: drkhiary@yah

19-4534 ª 2010 King Saud

view under responsibility of

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Abstract A 2-year-old healthy child presented with progressive unilateral proptosis.

Complete work up including: general examination, detailed ophthalmic evaluation and radiolog-

ical imaging were done. He underwent orbital exploration via anterior orbitotomy incision and deb-

ulking of the tumor was done.

The histopathological examination confirmed the diagnosis of orbital ganglioneuroma.

Ganglioneuroma is an unusual benign tumor of neuroplastic origin with extremely rare orbital

involvement with only one prior reported case in a youth. The tumor is slow growing and non-

metastasizing. Biopsy is necessary to differentiate it from the malignant neuroblastoma and excision

is usually curative.ª 2010 King Saud University. All rights reserved.

1. Introduction

Ganglioneuroma is a rare benign tumor of neuroblastic origin

which can grow wherever sympathetic nervous tissue is found.In addition to its association with metastatic neuroblastoma,ganglioneuroma has been associated with neurofibromatosis

type 1 and multiple endocrine neoplasia. Orbital involvementis extremely rare with only one prior reported case in a youth.

loplastic and Orbit Division,

.O. Box 7191, Riyadh 11462,

H. Al-Khiary).

ity. All rights reserved. Peer-

d University.

lsevier

We report here a case of primary orbital ganglioneuroma in apediatric young healthy male patient along with imaging andhistopathological findings along with relevant literature

review.

2. Case report

A 2-year-old Saudi boy presented to emergency room of KingKhaled Eye Specialist Hospital (KKESH) with history of

slowly progressive proptosis of the left eye of 2 months dura-tion. He was a product of normal pregnancy and delivery withnormal growth and development, and has no prior history ofocular trauma or surgery. His family history was non-

contributory.On physical examination the child was healthy with no

obvious dysmorphic features. He was able to fix and follow

in both eyes. He had 3–4 mm of left eye proptosis with someinferior globe displacement (Fig. 1) but full extra ocular move-ment. On biomicroscopy, the eye was quite with normal ante-

rior segment exam with regular and reactive pupil. His fundus

Figure 1 Clinical photograph prior to surgery showing proptosis

of the left eye.

Figure 3 Axial unenhanced CT scans demonstrate low attenu-

ation and homogeneous mass with slight to moderate patchy

homogeneous enhancement.

102 H. Al-Khiary et al.

and optic nerve exam were unremarkable. Systemic examina-tion showed the presence of two small cutaneous neurofibro-

mas in scalp area but no cafe au laut spots.CT scan and MRI of brain and orbit showed well defined,

well circumscribed, homogenous extraconal soft tissue massoccupying most of the superior orbital area, measuring

3.2 · 1.5 cm (Figs. 2 and 3). The mass was causing inferotem-poral left globe displacement. This lesion showed minimalenhancement with contrast without evidence of calcification

or bony destruction. MRI revealed a lobulated neoplasm ofthe right superior orbit that molded around the globe. Theneoplasm was enhanced with contrast (Fig. 4). Abdominal

ultrasound, CT scan of chest, abdomen and pelvis werenormal.

Orbital exploration performed through an anterior orbitot-omy via lid crease incision revealed a circumscribed lesion with

white–yellow surface without necrosis (Fig. 5). Incisionalbiopsy and debulking was performed. On gross examination,the excised mass measured 20 · 12 · 10 mm. Histopathological

Figure 2 Coronal unenhanced CT scans demonstrate low

attenuation and homogeneous mass.

Figure 4 Sagital view of an orbital T1-weighted magnetic

resonance image showing a well-defined, lobulated mass with

fibrous septations without invasion of the bone.

examination revealed scattered nests of mature ganglion cellswithin a matrix of proliferating spindle cells (representing

Schwann cells) which led to the diagnosis of Ganglioneuroma(Fig. 6). There were no features of malignancy such as hyper-cellularity, necrosis or atypia. Immunohistochemical staining

was positive for S-100 protein stain (Fig. 7).Postoperatively, the patient had a smooth course. Six

months after his surgery, the patient had no proptosis. His

MRI study showed residual mass which measured1.6 · 1.2 cm with no signs of progression.

3. Discussion

Ganglioneuroma is a rare benign tumor of neuroblastic originwhich usually originates from neural crest sympathogonia

Figure 5 Gross photograph of the neoplasm showing a circum-

scribed lesion with a variegated tan-white surface lacking necrosis.

Figure 6 Hematoxylin–eosin staining showing mature ganglion

cells within a neurofibrillary matrix and no neuroblastoma

(original magnification 200·).

Figure 7 Immunohistochemical stains showed ganglion cells

exhibiting strong cytoplasmic positivity S-100 protein.

Primary orbital ganglioneuroma in a 2-year-old healthy boy 103

along the sympathetic chain (Albonico et al., 2001). Alongwith neuroblastoma, ganglioneuromas and ganglioneuroblas-tomas are collectively known as neuroblastic or neurogenictumors.

These tumors can grow wherever sympathetic nervous tissue

is found. The most common sites involved are posterior medi-astinum (41%), retroperitoneum (37%), adrenal gland (21%)and neck (8%) (Geoerger et al., 2001). Ganglioneuromas usu-ally occur in adolescents and young adults (40–60%), but indi-

viduals of all ages can be affected. Ganglioneuromas are morefrequent in older children with median age of diagnosis between7 and 10 years (Lonergan et al., 2002). In addition to its associ-

ation with metastatic neuroblastoma, ganglioneuroma has beenassociated with neurofibromatosis type 1 and multiple endo-crine neoplasia (MEN) (Geraci et al., 1998; Lora et al., 2004).

Orbital involvement is extremely rare. A single reportedcase of orbital ganglioneuroma has been described in a 15-year-old healthy boy who had history of chronic proptosis

for 4 years (Choi et al., 2009). To the best of our knowledge,this may represent the second case of primary orbital ganglio-neuroma in a young healthy patient.

Ganglioneuromas may arise de novo or in patients who

have had chemotherapy for metastatic neuroblastoma. A singlecase was reported for a 12-year-old boy who had history ofstage IV neuroblastoma which was treated with chemotherapy

10 years prior to developing ganglioneuroma in the orbit (Can-non et al., 2004). Other cases of ganglioneuroma with orbitalextension from adjacent sinuses or optic chiasm or cranial por-

tion of optic nerve have also been reported (Choi et al., 2009;Cannon et al., 2004; Piquet et al., 1976; Cogan et al., 1961).

Neuroblastic tumors can be broadly subcategorized as neu-roblastoma, ganglioneuroblastoma, or ganglioneuroma (Can-

non et al., 2004). The three tumors differ in their degree ofcellular and extracellular maturation; immature tumors tendto be aggressive. The most benign tumor is the ganglioneu-

roma, which is composed entirely of neural elements, includingmature ganglion cells and Schwannian stroma and does notcontain neuroblasts, intermediate cells, or mitotic figures. Gan-

glioneuroblastoma is composed of both mature gangliocytesand immature neuroblasts and has intermediate malignant po-tential. Neuroblastoma is the most immature, undifferentiated

and malignant tumor of the three (Lonergan et al., 2002). Gan-glioneuromas usually enlarge slowly; rapid growth should raisesuspicion for a poorly differentiated neoplasm such as neuro-blastoma (Cannon et al., 2004).

Ganglioneuroma most often manifests as an asymptomaticmass discovered on a routine radiographic study, such as achest or abdomen radiograph (Lonergan et al., 2002). Some-

times ganglioneuroma may cause local mass effect and patientmay present with cough, abdominal pain, or dyspnea. There areno specific diagnostic signs or symptoms discriminating gan-

glioneuroma and neuroblastoma tumors (Geoerger et al.,2001). In rare cases, ganglioneuroma secretes sufficient quanti-ties of vanillylmandelic acid (VMA) or homovanillic acid

(HVA) to manifest with flushing and other symptoms ofcatecholamine excess (Lucas et al., 1994). Although elevatedcatecholamine production by neuroblastoma and ganglioneu-roblastoma occurs in 90–95% of patients, elevated levels may

also be seen in ganglioneuroma and therefore do not aid in dis-criminating between the three (Geoerger et al., 2001). In thelargest series of ganglioneuroma to date (49 cases), 37% of

the patients had elevated VMA or HVA levels (Geoergeret al., 2001). Moreover, ganglioneuroma, like neuroblastomaand ganglioneuroblastoma, may accumulate metaiodobenzyl-

guanidine (MIBG) which has been reported in up to 57% ofganglioneuromas in one study (Geoerger et al., 2001).

104 H. Al-Khiary et al.

Magnetic resonance imaging (MRI) and computed tomog-

raphy (CT) scanning are the preferred methods for imagingganglioneuromas and ganglioneuroblastomas (Lonerganet al., 2002). Nonenhanced CT scanning reveals a homoge-neous mass with less attenuation than muscle. CT may show

calcifications in two-thirds of cases. Calcification is typicallyfine and speckled but may be coarse (Ichikawa et al., 1996;Johnson et al., 1997). MRI is the modality of choice for eval-

uating the extension of the lesion. Ganglioneuromas appearhomogeneous on MRIs and have relatively intermediate signalintensity on all pulse sequences.

Ganglioneuromas, as fully differentiated neoplasms, do nothave the capability to metastasize, so extensive surgical resec-tions or chemotherapy is not normally necessary (Cannon

et al., 2004). It is important that adequate surgical samplingis obtained to allow sufficient histologic analysis and to assureno neuroblastic cellular elements are present as done in ourcase. Excision may be considered when the pathologic diagno-

sis is uncertain or visual function is compromised by the neo-plasm (Cannon et al., 2004).

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