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Clinicopathologic Reports, Case Reports, and Small Case Series
May 2002

Malignant Peripheral Nerve Sheath Tumor in the Orbit of a Child With Acute Proptosis

Arch Ophthalmol. 2002;120(5):653-655. doi:

Malignant peripheral nerve sheath tumor (MPNST) is an extremely rare orbital tumor and only 34 cases have previously been reported110 Of these, only 5 were childhood cases of MPNST occurring in the orbit.3,4,79 We report a sixth case of this disease in the orbit of an 11-year-old girl who had rapidly progressive proptosis and optic nerve compression.

Report of a Case

An 11-year-old girl was referred with a 5-day history of rapidly progressive painless proptosis of the left eye and a corrected visual acuity that had decreased from 6/5 to 6/12 over the previous 24 hours. On examination, the left eye was noted to have a 5-mm axial proptosis with a relative afferent pupillary defect and a swollen optic disc. Ocular motility was unrestricted and she did not complain of diplopia. There was no palpable periorbital mass and no periorbital neurosensory deficit. She was otherwise healthy with no significant medical history. A magnetic resonance imaging (MRI) scan showed a large, ovoid, intraconal mass in the left orbit that extended from the orbital apex to the posterior aspect of the globe. There was no evidence of extra-orbital extension. The mass was clearly separate from the optic nerve (Figure 1) and had produced pressure erosion of the lateral orbital wall. It showed a homogeneous signal on T1 images with small cystic areas on T2 scans. There was diffuse enhancement following contrast, with focal areas of more prominent enhancement (Figure 2).

Figure 1.
T1-weighted precontrast axial
magnetic resonance image demonstrating a well-defined, homogeneous, intraconal
mass in the left orbit. The mass is clearly separate from the optic nerve
and displaces it superomedially.

T1-weighted precontrast axial magnetic resonance image demonstrating a well-defined, homogeneous, intraconal mass in the left orbit. The mass is clearly separate from the optic nerve and displaces it superomedially.

Figure 2.
T1-weighted postcontrast coronal
magnetic resonance image demonstrating diffuse enhancement of the mass with
focal peripheral enhancement.

T1-weighted postcontrast coronal magnetic resonance image demonstrating diffuse enhancement of the mass with focal peripheral enhancement.

A medial transconjunctival incisional biopsy of the tumor was performed and 4 pieces of tissue were sent for histologic evaluation. Histologic findings showed a biphasic tumor with a cellular small round blue cell component (Figure 3) merging with a cellular spindle cell component (Figure 4). There was no necrosis, but apoptotic cells often were noted in the specimen. Although mitoses were infrequent (1/20 high-power field), some morphologically abnormal mitotic figures were present. The spindle-shaped cells showed ill-defined cytoplasm and contained hyperchromatic, pleomorphic, serpiginous nuclei. The round cells showed little cytoplasm and contained moderately pleomorphic nuclei with coarse hyperchromatic chromatin and irregular nuclear contours. Nucleoli were inconspicuous. The round cell component contained rosettelike structures with hypereosinophilic fibrillary cores (Figure 5). The overall appearances raised the differential diagnosis of spindle cell neuroblastoma, primitive neuroectodermal tumor (PNET), neuroepithelioma, and MPNST with a PNET-like component. Both the round cell and spindle cell components were positive for S100 protein and glial fibrillary acidic protein (GFAP) (Figure 6). Test results for neuron-specific enolase (NSE) were positive, predominantly in the small round cell component. Test findings for neurofilament, synaptophysin, chromogranin, cytokeratin, CAM 5.2, epithelial membrane antigen, desmin, and actin were all negative. (All antibodies were provided by Dako, Ely, Cambridgeshire, United Kingdom.) Test results for the MIC-2 gene product (Dako) and β2-microglobulin (Dako) were also negative.

Figure 3.
Section of tumor showing a primitive
neuroectodermal tumor–like area with a mitotic figure (hematoxylin-eosin,
original magnification ×400).

Section of tumor showing a primitive neuroectodermal tumor–like area with a mitotic figure (hematoxylin-eosin, original magnification ×400).

Figure 4.
Section of tumor showing a spindle
cell region with nuclear palisading (hematoxylin-eosin, original magnification
×160).

Section of tumor showing a spindle cell region with nuclear palisading (hematoxylin-eosin, original magnification ×160).

Figure 5.
Section of tumor showing spindle
cells merging with the primitive neuroectodermal tumor–like component.
Some of the primitive neuroectodermal tumor–like structures showed eosinophilic
fibrillary cores (hematoxylin-eosin, original magnification ×160).

Section of tumor showing spindle cells merging with the primitive neuroectodermal tumor–like component. Some of the primitive neuroectodermal tumor–like structures showed eosinophilic fibrillary cores (hematoxylin-eosin, original magnification ×160).

Figure 6.
Glial fibrillary acidic protein
immunohistochemistry (original magnification ×160).

Glial fibrillary acidic protein immunohistochemistry (original magnification ×160).

Electron microscopy showed that the cells in both the round cell and the spindle cell areas were similar. They contained a few cisternae of rough endoplasmic reticulum and mitochondria. The cytoplasmic matrix contained monoribosomes, polyribosomes, and focally abundant intermediate filaments; in the round cell areas, cells in clusters were closely juxtaposed with no intervening matrix. Where the clusters contacted stroma, cell surfaces exhibited stretches of lamina, as well as bundles of slender collagen fibrils (Figure 7). Better developed lamina was also present over spindle cells (Figure 8). These cells also had long coarse cytoplasmic processes containing relatively large numbers of intermediate filaments and fewer membranous organelles. No glycogen, neuroendocrine granules, processes containing microtubules, or bundles of striated muscle myofilaments were seen.

Figure 7.
Electron micrograph showing primitive
neuroectodermal tumor–like and spindle cell components (original magnification
×16 000).

Electron micrograph showing primitive neuroectodermal tumor–like and spindle cell components (original magnification ×16 000).

Figure 8.
Electron micrograph showing reduplicated
basal lamina (original magnification ×33 000).

Electron micrograph showing reduplicated basal lamina (original magnification ×33 000).

The patient underwent left orbital exenteration with a complete apical clearance, and 6 weeks later she received postoperative radiotherapy. She has since made a complete recovery with no recurrence or metastatic disease after 4 years' follow-up.

Comment

Thirty-four cases of MPNST of the orbit have been reported.110 Seventeen arose from the trigeminal nerve, mainly from its supraorbital branch. 3 Five previously reported tumors occurred in children. The youngest reported patient, born with Kartagener syndrome, was 4 days old when the tumor was detected on an MRI scan. After confirmation from anterior orbital biopsy results at age 5 days, he underwent an exenteration at age 6 weeks and has been reported to be tumor free at age 27 months.8 One tumor in the orbit of a 50-day-old male infant showed features of a plexiform MPNST.4 Despite orbital exenteration and radiotherapy, he died within 6 months of diagnosis. The third child had previously received radiotherapy for bilateral retinoblastomas and developed an anaplastic sarcoma arising in an orbital neurofibroma.3 The fourth child, a 15-month-old boy, underwent lateral orbitotomy with cryoexcision of a retrobulbar MPNST in association with a myxoid neurofibroma. Histologically the MPNST pseudocapsule was intact and 9 years later the child was still disease free.9 The fifth case was diagnosed in a 23-year-old man who had rapid-onset orbital proptosis and pain in the left eye.7 Biopsy specimens taken at the time were compared with specimens from an incomplete excision of the tumor taken when he was 5 years old and that was previously diagnosed as fibromatosis. Both specimens were found to be MPNST. He underwent orbital exenteration and was reported to be alive without recurrence 8 months later. This was 18 years after initial tumor presentation and is the longest reported survival.

The current case clearly showed features of a rapidly evolving malignant neoplasm: rapid growth, marked cellularity, mitotic activity, and apoptotic figures, and abnormal mitoses indicated its malignant potential. The ultrastructure indicated schwannian differentiation that supported a diagnosis of MPNST. In addition, the round blue cell component of the tumor showed no immunoreactivity for synaptophysin, MIC-2 gene product, or β2-microglobulin, and electron microscopy showed it was devoid of neuroendocrine granules and processes containing microtubules. All of these features exclude the diagnoses of neuroblastoma, neuroepithelioma, and true PNET.6 Meis et al5 reported on PNET-like foci in 15 cases of nonorbital childhood MPNSTs that closely resemble those in the current case. They found that PNET-like foci do not adversely affect the prognosis. They also determined that 56% of MPNSTs were positive for S100 protein.5 The presence of GFAP in MPNSTs is uncommon, but Gray et al10 reported GFAP reactivity in 2 cases in their series.

In conclusion, MPNSTs should be considered in the differential diagnosis of malignant orbital tumors in children. This disease has a poorer prognosis than most childhood malignancies, and complete surgical excision is essential to provide a chance of cure. Our case showed an unusually rapid progression with acute presentation of proptosis and optic nerve compression. Immunohistochemistry showed the presence of GFAP although reports of GFAP positivity are exceptional in MPNSTs. A poorly differentiated PNET-like small cell component was also present.

We wish to thank Roger Lait, MRCP, FRCR, for providing the MR scans and Pat Tarpey for electron microscopy.

Corresponding author: B. Leatherbarrow, FRCS, FRCOphth, Royal Eye Hospital, Oxford Road, Manchester M13 9WH, England (e-mail: bollin@mighty-micro.co.uk).

References
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Eviatar  JAHornblass  AHerschorn  BJakobiec  FA Malignant peripheral nerve sheath tumor of the orbit in a 15-month-old child: nine-year survival after local excision. Ophthalmology. 1992;991595- 1599. Article
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