Clinicopathologic Reports, Case Reports, and Small Case Series
October 01, 2005

Bilateral, Localized Orbital Neurofibromas and Charcot-Marie-Tooth Disease

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Copyright 2005 American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use.2005

Arch Ophthalmol. 2005;123(10):1443-1445. doi:10.1001/archopht.123.10.1443

Localized neurofibromas are rare in the orbit and, unlike plexiform neurofibromas, are not typically associated with von Recklinghausen neurofibromatosis. To our knowledge, bilaterality of such localized neurofibromas has been reported only once.1 We report a patient known to have Charcot-Marie-Tooth disease (CMTD) who developed multiple localized neurofibromas in both orbits.

Report of a Case

A 35-year-old man, known to have CMTD polyneuropathy since the age of 12 years, was referred to us because of the accidental finding of bilateral orbital tumors on magnetic resonance imaging of the brain. The brain imaging had been requested by a neurologist after the patient developed a right-sided trigeminal neuralgia.

On evaluation, bilateral exophthalmos was noted, and this was reported by the patient to be of long-standing duration (at least 5 years). Best-corrected visual acuity was 20/30 in either eye. Hertel exophthalmometry measurements were 23 mm in both eyes. There was mild limitation of supraduction in both eyes. Tonic pupils were noted. There were no enlarged corneal nerves and no iris Lisch nodules. Fundus examination showed mild pallor of both optic nerve heads. No café au lait spots were noted on physical examination. Extensive distal muscle atrophy was seen (Figure 1A). Family history was negative for neurofibromatosis.

Figure 1.
Image not available

A, Right hand of patient showing extensive atrophy of the dorsal interossei muscles with flexion contracture of the fingers, which is characteristic of Charcot-Marie-Tooth disease. B, Computed tomographic scan of coronal cuts showing bilateral superior orbital tumors with thinning of the adjacent bone (top) and axial cuts showing 2 adjacent, interconnected tumors in each orbit (bottom).

Orbital computed tomography was performed and showed large masses filling the superior aspect of both orbits, displacing the globes inferiorly (Figure 1B). The bony orbital roof was expanded and thinned in some areas.

The patient underwent bilateral anterior orbitotomies for excisional biopsy of the tumors. Two adjacent, interconnected tumors were found in each orbit, arising from the supraorbital branch of the frontal nerve, which was noted to be thickened and in turn was resected. Postoperatively, the patient did well.

Pathologic Findings

The specimens were of comparable size, about 2.5 × 1.0 × 0.5 cm each. They consisted of well-circumscribed, nonencapsulated masses with homogeneous, soft, tan-white cut surfaces. Microscopic examination disclosed wavy bundles of proliferating, benign, spindle-shaped Schwann cells separated by collagen-producing fibroblasts that expanded the peripheral nerve tissue and formed a fusiform mass (Figure 2A). There was no nuclear atypia, mitotic figures, or necrosis. Immunohistochemistry results revealed a mixture of S100-positive and S100-negative cells (Figure 2B). These findings are consistent with neurofibroma.

Figure 2.
Image not available

A, Neurofibroma arising from a peripheral nerve shown at low magnification (trichrome, original magnification ×20) (right). Schwann cells within the neurofibroma are separated by blue-staining collagenous tissue (trichrome, original magnification ×100) (top left). The neural element in the uninvolved portion of the peripheral nerve is compact with minimal intervening collagen (trichrome, original magnification ×100) (bottom left). B, S100 protein immunoreactivity, in brown, localizes to wavy Schwann cells within the neurofibroma. They are arranged in disorderly bundles that are separated by gray-blue collagen-producing fibroblasts (original magnification ×400).


Charcot-Marie-Tooth disease is one of the most frequently encountered inherited neurologic syndromes.2 It affects both motor and sensory peripheral nerves. Typical features consist of distal muscle weakness and atrophy, impaired sensation, and hypoactive or absent deep tendon reflexes, initially involving the feet and legs and then slowly progressing to the hands and forearms. Onset is most often during the first or second decade of life. The variation in clinical manifestation is exceptionally wide.2 Several ocular abnormalities have been associated with CMTD: retinitis pigmentosa, external ophthalmoplegia and ptosis, optic atrophy, and nystagmus.3 Pupillary abnormalities have been reported in patients with CMTD, secondary to either sympathetic denervation or parasympathetic abnormalities. To our knowledge, this report presents the first case of bilateral, localized orbital neurofibromas in a patient with CMTD.

Localized neurofibromas are typically located in the superior orbit in the distribution of the ophthalmic division of the trigeminal nerve (V1). These tumors are amenable to surgical treatment because they are well circumscribed and relatively avascular. The possibility of malignant transformation of these tumors, though more common when associated with von Recklinghausen disease (10%-15%), necessitates total excision when possible.

Lately, the few reports on the simultaneous occurrence of neurofibromatosis and CMTD point to a possible genetic relationship between these 2 disorders.4 Both diseases involve the same gene locus of PMP22 on chromosome 17.

To our knowledge, bilateral, localized orbital neurofibromas were only reported once previously in a patient who had associated multiple endocrine neoplasia.1 In addition, localized orbital neurofibromas in association with CMTDhave not been previously reported, and a thorough literature search revealed only a single case of neurofibroma of the facial nerve associated with CMTD.5

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Article Information

Correspondence: Dr Ma’luf, Department of Ophthalmology, American University of Beirut–Medical Center, PO Box 113-6044, Beirut, Lebanon (

Financial Disclosure: None.

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