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

Abstract

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

Complete work up including: general examination, detailed ophthalmic evaluation and radiological imaging were done. He underwent orbital exploration via anterior orbitotomy incision and debulking 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.

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 involvement is extremely rare with only one prior reported case in a youth. We report here a case of primary orbital ganglioneuroma in a pediatric young healthy male patient along with imaging and histopathological findings along with relevant literature review.

2. Case report

A 2-year-old Saudi boy presented to emergency room of King Khaled Eye Specialist Hospital (KKESH) with history of slowly progressive proptosis of the left eye of 2 months duration. He was a product of normal pregnancy and delivery with normal growth and development, and has no prior history of ocular 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 some inferior globe displacement (Fig. 1) but full extra ocular movement. On biomicroscopy, the eye was quite with normal anterior segment exam with regular and reactive pupil. His fundus and optic nerve exam were unremarkable. Systemic examination showed the presence of two small cutaneous neurofibromas in scalp area but no café au laut spots.

Figure 1.

Clinical photograph prior to surgery showing proptosis of the left eye.

CT scan and MRI of brain and orbit showed well defined, well circumscribed, homogenous extraconal soft tissue mass occupying most of the superior orbital area, measuring 3.2 × 1.5 cm (Figs. 2 and 3). The mass was causing inferotemporal left globe displacement. This lesion showed minimal enhancement with contrast without evidence of calcification or bony destruction. MRI revealed a lobulated neoplasm of the right superior orbit that molded around the globe. The neoplasm was enhanced with contrast (Fig. 4). Abdominal ultrasound, CT scan of chest, abdomen and pelvis were normal.

Figure 2.

Coronal unenhanced CT scans demonstrate low attenuation and homogeneous mass.

Figure 3.

Axial unenhanced CT scans demonstrate low attenuation and homogeneous mass with slight to moderate patchy homogeneous enhancement.

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.

Orbital exploration performed through an anterior orbitotomy via lid crease incision revealed a circumscribed lesion with white–yellow surface without necrosis (Fig. 5). Incisional biopsy and debulking was performed. On gross examination, the excised mass measured 20 × 12 × 10 mm. Histopathological examination revealed scattered nests of mature ganglion cells within 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 hypercellularity, necrosis or atypia. Immunohistochemical staining was positive for S-100 protein stain (Fig. 7).

Figure 5.

Gross photograph of the neoplasm showing a circumscribed 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.

Postoperatively, the patient had a smooth course. Six months after his surgery, the patient had no proptosis. His MRI study showed residual mass which measured 1.6 × 1.2 cm with no signs of progression.

3. Discussion

Ganglioneuroma is a rare benign tumor of neuroblastic origin which usually originates from neural crest sympathogonia along the sympathetic chain (Albonico et al., 2001). Along with neuroblastoma, ganglioneuromas and ganglioneuroblastomas are collectively known as neuroblastic or neurogenic tumors.

These tumors can grow wherever sympathetic nervous tissue is found. The most common sites involved are posterior mediastinum (41%), retroperitoneum (37%), adrenal gland (21%) and neck (8%) (Geoerger et al., 2001). Ganglioneuromas usually occur in adolescents and young adults (40–60%), but individuals of all ages can be affected. Ganglioneuromas are more frequent in older children with median age of diagnosis between 7 and 10 years (Lonergan et al., 2002). In addition to its association with metastatic neuroblastoma, ganglioneuroma has been associated with neurofibromatosis type 1 and multiple endocrine neoplasia (MEN) (Geraci et al., 1998; Lora et al., 2004).

Orbital involvement is extremely rare. A single reported case 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 ganglioneuroma in a young healthy patient.

Ganglioneuromas may arise de novo or in patients who have had chemotherapy for metastatic neuroblastoma. A single case was reported for a 12-year-old boy who had history of stage IV neuroblastoma which was treated with chemotherapy 10 years prior to developing ganglioneuroma in the orbit (Cannon et al., 2004). Other cases of ganglioneuroma with orbital extension from adjacent sinuses or optic chiasm or cranial portion 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 neuroblastoma, ganglioneuroblastoma, or ganglioneuroma (Cannon et al., 2004). The three tumors differ in their degree of cellular and extracellular maturation; immature tumors tend to be aggressive. The most benign tumor is the ganglioneuroma, which is composed entirely of neural elements, including mature ganglion cells and Schwannian stroma and does not contain neuroblasts, intermediate cells, or mitotic figures. Ganglioneuroblastoma is composed of both mature gangliocytes and immature neuroblasts and has intermediate malignant potential. Neuroblastoma is the most immature, undifferentiated and malignant tumor of the three (Lonergan et al., 2002). Ganglioneuromas usually enlarge slowly; rapid growth should raise suspicion for a poorly differentiated neoplasm such as neuroblastoma (Cannon et al., 2004).

Ganglioneuroma most often manifests as an asymptomatic mass discovered on a routine radiographic study, such as a chest or abdomen radiograph (Lonergan et al., 2002). Sometimes ganglioneuroma may cause local mass effect and patient may present with cough, abdominal pain, or dyspnea. There are no specific diagnostic signs or symptoms discriminating ganglioneuroma and neuroblastoma tumors (Geoerger et al., 2001). In rare cases, ganglioneuroma secretes sufficient quantities of vanillylmandelic acid (VMA) or homovanillic acid (HVA) to manifest with flushing and other symptoms of catecholamine excess (Lucas et al., 1994). Although elevated catecholamine production by neuroblastoma and ganglioneuroblastoma occurs in 90–95% of patients, elevated levels may also be seen in ganglioneuroma and therefore do not aid in discriminating between the three (Geoerger et al., 2001). In the largest series of ganglioneuroma to date (49 cases), 37% of the patients had elevated VMA or HVA levels (Geoerger et al., 2001). Moreover, ganglioneuroma, like neuroblastoma and ganglioneuroblastoma, may accumulate metaiodobenzylguanidine (MIBG) which has been reported in up to 57% of ganglioneuromas in one study (Geoerger et al., 2001).

Magnetic resonance imaging (MRI) and computed tomography (CT) scanning are the preferred methods for imaging ganglioneuromas and ganglioneuroblastomas (Lonergan et al., 2002). Nonenhanced CT scanning reveals a homogeneous mass with less attenuation than muscle. CT may show calcifications in two-thirds of cases. Calcification is typically fine and speckled but may be coarse (Ichikawa et al., 1996; Johnson et al., 1997). MRI is the modality of choice for evaluating the extension of the lesion. Ganglioneuromas appear homogeneous on MRIs and have relatively intermediate signal intensity on all pulse sequences.

Ganglioneuromas, as fully differentiated neoplasms, do not have the capability to metastasize, so extensive surgical resections or chemotherapy is not normally necessary (Cannon et al., 2004). It is important that adequate surgical sampling is obtained to allow sufficient histologic analysis and to assure no neuroblastic cellular elements are present as done in our case. Excision may be considered when the pathologic diagnosis is uncertain or visual function is compromised by the neoplasm (Cannon et al., 2004).