Malignant peripheral nerve sheath tumor (MPNST) is an extremely rare
orbital tumor and only 34 cases have previously been reported1- 10
Of these, only 5 were childhood cases of MPNST occurring in the orbit.3,4,7- 9
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.
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
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 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.
Section of tumor showing a primitive
neuroectodermal tumor–like area with a mitotic figure (hematoxylin-eosin,
original magnification ×400).
Section of tumor showing a spindle
cell region with nuclear palisading (hematoxylin-eosin, original magnification
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).
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.
Electron micrograph showing primitive
neuroectodermal tumor–like and spindle cell components (original magnification
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.
Thirty-four cases of MPNST of the orbit have been reported.1- 10
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
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: firstname.lastname@example.org).
Briscoe D, Mahmood S, O'Donovan DG, Bonshek RE, Leatherbarrow B, Eyden BP. Malignant Peripheral Nerve Sheath Tumor in the Orbit of a Child With Acute Proptosis. Arch Ophthalmol. 2002;120(5):653-655. doi: