PERIPHERAL NERVE TUMORS OF THE ORBIT

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IMAGING IN OPHTHALMOLOGY I1

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PERIPHERAL NERVE TUMORS OF THE ORBIT Gregory S. Carroll, MD, Barrett G . Haik, MD, James C. Fleming, MD, Robert A. Weiss, MD, and Mahmood F. Mafee, MD, FACR

The orbit is host to many peripheral nerves including sensory nerves, which are branches of cranial nerve V; sympathetic and parasympathetic fibers; and oculomotor, trochlear, and abducent nerves to the extraocular muscles. Approximately 4% of all orbital neoplasms are peripheral nerve tumors and primarily consist of neurofibromas and neurilemmomas or schwannomas. Of these, 2% of the lesions are plexiform neurofibromas; 1% isolated neurofibromas; and 1%schwannomas (or ne~rilemmoma).~ Malignant peripheral nerve tumors (malignant schwannoma, neurofibrosarcoma) do arise in the orbit but are extremely rare.4 The sensory nerves appear to give rise to peripheral nerve tumors with greater frequency as compared with motor nerves, because many patients complain of pain but retain ocular motility. As with most space-occupying lesions of the orbit, patients present with slowly progressive proptosis or displacement of the globe and may not develop diplopia until the lesion is large enough to limit ocular excursion. The visual acuity often is not affected unless the tumor compresses the optic nerve, which can occur earlier in lesions arising in the orbital apex. NEUROFIBROMA

Neurofibromas may occur in one of four patterns: (1) plexiform, (2) diffuse, (3) localized or This work was supported in part by grants from the St. Giles Foundation, New York, New York and Research to Prevent Blindness, New York, New York

circumscribed, and (4) postamputation neuromas.5 Plexiform neurofibromas present in infancy or childhood and most commonly involve the eyelids. The early presenting sign is a visible or palpable mass in the eyelid with subsequent ptosis and eventual hypertrophy of the eyelid. The tumor tends to localize to the lateral third of the eyelid and consists of cords and nodules giving rise to a “bag of worms” on palpation. During adolescence, the tumor often extends to the forehead, temple, and superior orbit leading to downward displacement of the globe. This displacement may be difficult to evaluate in the presence of extensive hypertrophy of the eyelid (Fig. 1).Flexiform neurofibroma involvement of the eyelid is considered to be virtually pathognomonic for neurofibromatosis (von Recklinghausen’s disease). Diffuse neurofibromas have an appearance similar to plexiform neurofibromas with infiltration of orbital fat and extraocular muscles, but these lesions are less likely to be associated with von Recklinghausen‘s disease.lo Circumscribed or localized neurofibromas often present as a slow-growing tumor that exerts a mass effect with displacement of the globe in the direction opposite that of the tumor. The tumor may occur along any sensory nerve but is more common in the superior quadrants. When these lesions arise near the lacrimal gland, they have the clinical appearance of primary lacrimal gland tumors? Visual acuity is often unaffected and pain is uncommon. These lesions are most commonly seen in the third to fifth decades of life. Histologically, plexiform neurofibromas are un-

From the Department of Ophthalmology, University of Tennessee, Memphis (GSC, BGH, JCF), Memphis, Tennessee; and the Departments of Ophthalmology (RAW) and Radiology (MFM), the Eye and Ear Infirmary (MFM), and the MR Imaging Center (MFM), University of Illinois at Chicago, Chicago, Illinois ~

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than 15 cases reported in the literat~re.~ Division of these tumors into subtypes is not clearly evident in the majority of cases and they arise from Schwann cells, perineural cells, and fibroblasts of the nerve heath.^ Uniform histologic description and definition of tissue origin is difficult, but all lesions demonstrate malignant aspects, such as variable nuclear size and shape with increased mitotic activity, increased cellularity, and indistinct cell boundaries. IMAGING CHARACTERISTICS

Figure 1. Extensive involvement of the left eyelid and temporal fossa with plexiform neurofibroma.

encapsulated and have an organoid appearance with proliferating units surrounded by perineurium enclosing axons, Schwann cells, and endoneurial fibroblasts. There is a marked increase in vascularity, which leads to profuse bleeding at the time of surgery. This increased vascularity is reflected by marked contrast enhancement on CT and MR imaging scans. Solitary neurofibromas often demonstrate a pseudocapsule, but a true perineurium is not seen. They are composed of wavy bundles of peripheral nerve sheath cells with comma-shaped nuclei and hyaluronic acid and collagen in the stroma.5 SCHWANNOMAS (NEURILEMMOMA) On clinical examination, schwannomas and neurofibromas are nearly indistinguishable because they both arise from sensory nerves and demonstrate slow progressive growth with ocular displacement. These lesions may occur near the orbital apex leading to optic nerve compression and visual loss. Unlike solitary neurofibromas, schwannomas are well encapsulated. They most commonly have a smooth oval or fusiform appearance but may demonstrate a multilobulated appearance. Schwannomas and neurofibromas are primarily differentiated on histopathology. Schwannomas are encapsulated by the perineurium of the nerve of origin and the classic feature is the alternation within the lesion of solid cellular areas, referred to as an Antuni A pattern, and loose myxoid tissue with stellate or ovoid nuclei, referred to as an Antoni B pattern. Nuclear pallisading is more common than in neurofibromas and the highly organized picket fence appearance of nuclei is referred to as Vevocay bodies. In contrast to neurofibromas, schwannomas do display clear-cut evidence of Schwann cell origin.I2 MALIGNANT PERIPHERAL NERVE TUMORS Malignant nerve sheath tumors (neurofibrosarcoma, malignant schwannoma) are rare, with less

Plain films of any peripheral nerve sheath tumor discussed often show enlargement of the bony orbit, especially when the lesions develop in early infancy or childhood. CT of solitary neurofibromas and schwannomas demonstrates a well-circumscribed homogeneous tumor with density similar to brain (Figs. 2 4 ) . A heterogeneous center may be seen in tumors that have undergone central necrosis or those lesions with varying internal cellularity, such as schwannomas, that have areas of Antoni A, Antoni B, and myxoid stroma intermixed in varying proportions (Fig. 5). Both tumors enhance well with contrast. CT often does not reveal the multinodular or lobulated appearance of these tumors well, depending on section thickness and orientation (Fig. 6). Plexiform neurofibromas and diffuse neurofibromas are well-enhancing lesions with irregular borders and an infiltrative appearance, because these lesions can extend into nearly all orbital structures, such as lacrimal gland, fat, and extraocular muscles. In the case of plexiform neurofibromas, the tumor involves the eyelid and often extends to surrounding areas, such as the temporal fossa and forehead region (Fig. 7). When evaluating a CT scan of a plexiform neurofibroma, one should also look for other findings consistent with neurofi-

Figure 2. Coronal CT scan of circumscribed neurofibroma (arrow] of right supraorbital (frontal) nerve. Note the inferotemporal displacement of the globe and the downward displacement of the levator palpebrae-superior

rectus complex.

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Figure 3. A, Coronal non-contrast-enhanced CT scan shows a schwannoma (arrow) of the right inferior orbit. B, Postcontrast coronal CT scan of the schwannoma in A, showing the diffuse contrast enhancement (arrow).

Figure 4. Postcontrast serial axial CT scans of a schwannoma showing the well-defined extraconal mass (arrow) in the medial aspect of the right orbit. (Courtesy of M. F. Mafee, MD, Chicago, IL.)

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Figure 5. A, lntraoperative photograph demonstratingthe smooth fusiform nature of a solitary neurofibroma at the time of excision. 6,lntraoperative photograph showing the internal characteristics of a neurofibroma. Note the solid cellular areas intermixed with loose myxoid stromas, which is often seen on CT or MR as areas of heterogeneity.

Figure 6mA Axial postcontrast CT Scan demonstrating an anterior kedial orbital neurofibroma (N), 6,Coronal CT Scan of tumor on A showing its mu,tinodular configuration not readily Seen in a single axial view. Note the compression atrophy of the orbital roof (arrow).

Figure 7. Axial CT scan of plexiform neurofibromaswith diffuse superior orbital and temporal fossa infiltration.

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Figure 8. A, Axial postcontrast T1-weighted MR scan of a neurofibroma demonstrating heterogeneous enhancement with displacement of optic nerve. Note the extension into the anterior cavernous sinus (arrow) indicating the mass is not arising from the optic nerve. 6,Sagittal postcontrast T1-weighted MR scan of neurofibroma in A, which shows the tumor extension into the cavernous sinus (arrow). C, Axial T2-weighted MR scan of neurofibroma in A and 6,showing the large retrobulbar intraconal neurofibroma (arrows). (Courtesy of M. F. Mafee, MD, Chicago, IL.)

bromatosis, such as dysplasia of the sphenoid wing and orbital roof defects. The globe on the affected side may be enlarged and the entire uveal tract may be involved by neurofibroma. MR imaging of solitary neurofibromas and schwannomas demonstrates a well-circumscribed oval or fusiform mass that is hypointense to orbital fat and isointense to extraocular muscles and brain on T1-weighted images. On T2-weighted images the tumors are hyperintense to orbital fat. The myxoid regions of the tumor with its greater water content shows a greater signal intensity on T2weighted images as compared with the more cellular regions of the tumor (Figs. 8 and 9). Both tumors show heterogeneous contrast enhancement with the mucoid matrix and cystic component demonstrating greater enhancement than the cellular regions (Figs. 10 and 11). Orbital plexiform and diffuse neurofibromas appear as an ill-defined mass with extension into surrounding tissues and at times through the supe-

rior orbital fissure. The lesions demonstrate a heterogeneous hypointensity on T1-weighted MR images relative to orbital fat. The lesions show a high signal intensity on T2-weighted MR images relative to fat and they show a variable degree of contrast enhancement better seen with fat-suppression techniques.’,z, 8, The CT and MR imaging appearance of malignant nerve sheath tumors is similar to the nonmalignant tumors with the exception of bone destruction best demonstrated on CT imaging. DISCUSSION

Solitary neurofibromas and schwannomas have a similar clinical and radiologic appearance. Both tumors are readily amenable to surgical excision either through an anterolateral orbitotomy or a combined neurosurgical approach when the lesions are located in the posterior orbit. The surgical excision is relatively bloodless and most of the

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Figure 9. A, Postcontrast axial CT scan demonstrating a well-enhancing intraconal neurofibroma (arrow) of the posterior orbit. B, Axial T1-weighted MR scan of a posterior neurofibroma (arrow) as in A. Tumor is isointense to brain and hypointense to orbital fat. C,Axial fat-suppressed Ti-weighted MR scan of tumor seen in A and B demonstrating the marked contrast enhancement of a posterior neurofibroma (arrow). (Courtesy of M. F. Mafee, MD, Chicago, IL.)

tumors can be removed intact. The primary reason to distinguish between neurofibromas and schwannomas is that neurofibromas are generally believed to be more likely to undergo a malignant transformation, even though this transformation is quite rare.5 The treatment of plexiform neurofibromas is much less satisfying.These lesions are quite vascular and are diffusely infiltrative, often involving normal structures, such as extraocular muscles. Thus, complete removal without total exenteration is unachievable. The plexiform neurofibroma also has a high rate of recurrence and the patient may require multiple surgeries to attain an acceptable cosmetic and functional result. With the advent of combined intracranial and orbital approaches, and the use of new instrumentation, such as the carbon-dioxide laser, advances have been made in recent years that may improve results. In addition, patients with plexiform neurofibromas and von Recklinghausen’s disease require careful evaluation because they may have other manifestations

of their disease, such as dysplasia of the sphenoid wing and pulsatile proptosis, which may influence surgical planning. The current standard of treatment is initial conservative debulking of the primary tumor mass with secondary reconstruction of the eyelid and facial structures at a later date. When the vision is poor due to amblyopia or optic nerve compromise, exenteration with orbital reconstruction and a prosthesis may be considered as the primary procedure, reducing the possibility of future malignant transformation. Malignant peripheral nerve tumors are highly aggressive and often extend to the middle cranial fossa. Current treatment consists of radical excision with radiotherapy or chemotherapy. Despite aggressive therapy, the majority of patients experience recurrences in the midbrain region and the 5year survival rate is low. CONCLUSION

Neurofibromas and schwannomas are relatively rare orbital neoplasms with similar clinical and

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Figure 10. A, Axial T1-weighted MR scan of an extraconal schwannoma (arrow) demonstrating the hypointensity to orbital fat and isointensity to brain in this tumor. B,Axial T2-weighted MR scan of a schwannoma (arrow) as seen in A showing the homogeneous hyperintensity. C, Coronal fat-suppressed T1-weighted MR scan of a schwannoma (arrow) as seen in A and 6 showing marked contrast enhancement. Note the normal enhancement of the extraocular muscles and lacrimal gland in this pulse sequence.

radiologic characteristics. Solitary neurofibromas and schwannomas are readily amenable to surgical resection and the main reason to distinguish the two is that neurofibromas have a low but real malignant potential. Plexiform and diffuse neurofibromas are difficult to treat because of their diffuse infiltrative nature and high rate of recurrence.

Plexiform neurofibromas are pathognomonic for von Recklinghausen’s neurofibromatosis and other signs of the disease should be elicited.

ACKNOWLEDGMENTS m e authors gratefully acknowledge the assistance of Mark Alan Greenwald, CRA, in the preparation of the

Figure 11. Coronal, postcontrast T1-weighted MR scan showing a mass (m) compatible with a schwannoma, showing marked contrast enhancement. (Courtesy of M. F. Mafee, MD, Chicago, IL.)

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figures and Mary E. Smith, MPH, RDMS, in editing of the manuscript.

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Address reprint requests to Gregory S. Carroll, MD Department of Ophthalmology University of Tennessee, Memphis 956 Court Avenue, Suite D 228 Memphis, TN 38163 e-mail: gcarroll8mail.eye.utmem.edu