Ganglioneuromas are rare benign neoplasms of neuroblastic origin thathave been reported in multiple anatomic locations. Orbital involvement isextremely rare, with only a single reported case of direct extension to theorbit from an adjacent parasinus. This is the first reported case of a ganglioneuromaarising in the orbit.
A 12-year-old African American male had progressive proptosis of theright eye during a 1-year period (Figure 1).The child had a history of stage IV neuroblastoma 10 years earlier that hadoriginated in the adrenal gland and was treated with 7 courses of cyclophosphamideand teniposide after induction with adriamycin and cyclophosphamide. Neuroblastomawith metastases was confirmed by biopsy of the adrenal gland prior to inductionof chemotherapy. No additional surgery was performed because of the advancedstage of the disease, and the patient responded to chemotherapy and remainedin remission. His past medical history also included multiple cutaneous ganglioneuromasof the abdomen and gastrointestinal ganglioneuromas. He was profoundly mentallyhandicapped since infancy. Eye examination revealed no light perception inboth eyes. He had 4 mm of proptosis of the right eye. His pupils were slowlyreactive to light with no afferent pupillary defect. The cornea of the righteye evidenced diffuse punctate epithelial erosions and moderate conjunctivalinjection. Results of an anterior segment examination of the left eye werenormal. Ductions were full in both eyes. Dilated funduscopic examination revealedoptic nerve pallor with cup to disc ratio of 0.6 in both eyes. The macula,retina, and vitreous were normal in both eyes.
Clinical photograph prior to surgeryshowing proptosis of the right eye.
Magnetic resonance imaging revealed a lobulated neoplasm of the rightsuperior orbit that molded around the globe (Figure 2 and Figure 3). Theneoplasm was enhanced with contrast and appeared homogeneous in composition.There was no evidence of involvement of the bone. Orbital exploration viaan anterior orbitotomy incision revealed a circumscribed lesion with a gray-tansurface without necrosis (Figure 4).Histopathologic examination of an incisional biopsy revealed neural tissuecontainingmature ganglion cells, and no neuroblastic elements were pres-ent.Because of progressive proptosis and corneal exposure, debulking was performed.Extensive histologic sampling revealed the neoplasm to be composed entirelyof mature ganglioneuromatous tissue; again, no foci of neuroblastoma or sarcomawere detected (Figure 5). Immunohistochemicalstains showed ganglion cells exhibiting strong cytoplasmic positivity forneuron-specific enolase and synaptophysin; only occasional ganglion cellsdemonstrated weak positivity for neurofilament and S-100 protein. The spindlecell component of the neoplasm demonstrated strong cytoplasmic positivityfor S-100 protein, neurofilament, synaptophysin, and neuron-specific enolase.The immunohistochemical findings are consistent with ganglioneuroma.1
Axial view of an orbital T1-weightedmagnetic resonance image revealing a superior orbital neoplasm.
Coronal view of an orbital T1-weightedmagnetic resonance image showing a neoplasm without invasion of the bone.
bo Gross photograph of the neoplasmshowing a circumscribed lesion with a variegated tan-white surface lackingnecrosis.
Hematoxylin-eosin staining showingmature ganglion cells within a neurofibrillary matrix and no neuroblastoma(original magnification × 200).
Neuroblastic neoplasms can be broadly subcategorized as neuroblastoma,ganglioneuroblastoma, or ganglioneuroma.2 Ganglioneuromasare benign neoplasms composed of neural elements, including mature ganglioncells. Grossly, ganglioneuromas appear circumscribed with a gray or tan cutsurface having a whorled appearance on sectioning. In addition to its associationwith metastatic neuroblastoma, ganglioneuroma has been associated with neurofibromatosistype 13 and multiple endocrine neoplasia.4 Ganglioneuromas of the gastrointestinal tract arenot uncommon in the neurofibromatosis. They also commonly arise from the sympatheticchain and can be found in the retroperitoneum or posterior mediastinum.5 A single orbital case has been documented that describedlocal extension from the sinuses.6 Metastasesdo not occur; however, patients who have had metastatic neuroblastoma maydevelop ganglioneuromas that are thought to represent rests of neuroblastomacells that have undergone differentiation to ganglioneuromas.7 Theseneoplasms are rare compared with other neurogenic lesions, such as neurofibromaand schwannoma. To our knowledge, ours represents the first case of ganglioneuromaarising in the orbit.
Ganglioneuromas may arise de novo or in patients who have had chemotherapyfor metastatic neuroblastoma. Typically, they enlarge slowly; rapid growthshould raise suspicion for a poorly differentiated neoplasm. Neoplasms ofprimitive neuroectodermal origin, such as neuroblastoma, contain pluripotentcells that have the capacity to differentiate into mature cellular elements,such as ganglion cells.8 When ganglion celldifferentiation is present within an otherwise typical neuroblastoma, theterm ganglioneuroblastoma is appropriate. In the present case, clinical uncertaintyregarding cellular composition coupled with progressive proptosis and itsassociated corneal complication prompted debulking of the lesion. The historyof metastatic neuroblastoma and the presence of multiple ganglioneuromas lendcredence to the theory purporting the presence of rests of metastatic neuroblastomathat subsequently undergo maturation. Ganglioneuromas, as fully differentiatedneoplasms, do not have the capability to metastasize, so extensive surgicalresections or chemotherapy is not normally necessary, provided surgical samplingis sufficient to allow adequate histologic analysis and to assure no neuroblasticcellular elements are present. Excision may be considered when the pathologicdiagnosis is uncertain or visual function is compromised by the neoplasm.
Correspondence: Dr Cannon, University ofArkansas for Medical Sciences, Jones Eye Institute, 4301 W Markham, Slot 523,Little Rock, AR 72205 (firstname.lastname@example.org).
Financial Disclosure: None.
Funding/Support: This study was supported inpart by an unrestricted grant from Research to Prevent Blindness Inc, NewYork, NY.
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