Malignant peripheral nerve sheath tumors are sarcomas that are difficult to treat because of their aggressive nature.1 Only 10% to 20% of these tumors develop in the first two decades of life and up to 50% of all cases arise from plexiform neurofibroma in patients with neurofibromatosis type 1 (NF1).2,3 The approximate incidence of these tumors in the general population is 0.001% but rises to 5% to 10% in patients with NF1.2,3 Patients with prior radiation exposure have a higher incidence. The proximal parts of extremities and the sciatic nerve in particular are the most common sites of origin.1,2 This tumor is exceedingly rare in the orbit. Heterologous components such as osteoid or chondroid elements, which are commonly encountered in distant extraorbital tumors, were only reported once in a patient in a series of intraorbital malignant peripheral nerve sheath tumors.4
We present a case of intraorbital malignant peripheral nerve sheath tumor with extensive presence of bony and cartilaginous tissues developing in a 15-year-old girl without NF1. We presume that the tumor arose from a nerve in the inferior orbit, which is highly unusual considering that the supraorbital branch of the trigeminal nerve has been consistently reported as the most common orbital location.
A 15-year-old girl presented with proptosis in the right eye gradually developing within a year. Pain was not present initially but later became debilitating. Her visual acuity was 20/40 in the right eye and 20/20 in the left eye. The right globe was displaced superolaterally with restricted ocular motility. The rest of the ocular examination was unremarkable. Orbital magnetic resonance imaging studies disclosed a mildly enhancing, heterogenous retrobulbar intraconal mass measuring 11 × 27 mm with cystic cavities located in the inferomedial orbit of the right eye (Figure 1). Intracranial extension was not present. An incisional biopsy suggested malignant peripheral nerve sheath tumor. The right orbit was then exenterated. The orbital content was solid and firmly attached the apical part of the optic nerve. Cutting this part of the specimen with scissors was difficult.
Magnetic resonance imaging studies at initial presentation. (A) T1-weighted coronal image demonstrates that the main bulk of the tumor is located in the inferior orbit with an unaffected supraorbital nerve. (B) T2-weighted axial frame reveals heterogenous signal intensity probably corresponding to heterologous tissue elements within the tumor.
Histopathological examination showed that the tumor was composed of irregular intersecting fascicles of spindle cells with spindle-shaped prominent nuclei. Frequent mitotic figures and cellular and nuclear pleomorphism were observed (Figure 2A). Areas of osseous and cartilage tissue were present. There was widespread tumor infiltration of extraocular muscles and orbital fat. Immunohistochemical studies revealed diffuse vimentin and S-100 (Figure 2B) staining and partial protein gene product 9.5 positivity. Stainings for CD163, CD34, CD57, and desmin were negative. Further diagnostic work-up excluded any signs suggestive of NF1.
Histopathological sections show (A) fascicles of spindle cells with pleomorphic nuclei (hermatoxilyn–eosin, original magnifica-tion ×40) and (B) diffuse positive staining for S-100 (S-100, original magnification ×100).
The patient then received two courses of adriamycin, cyclophosphamide, and vincristine, complemented with 5400 cGy external beam radiotherapy and was free of local recurrence for 12 months. Fourteen months after the last procedure, a new tumor developed on the orbital floor that was treated with excision and radiotherapy. No systemic metastases were detected.
Malignant peripheral nerve sheath tumors are rare, spindle cell, soft tissue sarcomas mostly seen in the fourth and fifth decades with equal sex distribution except in patients with NF1 when it occurs in the teens.2 The youngest patient with orbital malignant peripheral nerve sheath tumor was a 15-month-old boy.5 The recurrence rate may be as high as 40% and hematogenous metastases to lungs and bones are frequent.2 The tumor may also spread along the nerve sheath into the subarachnoid space.6 The 10-year survival rate nears 45% but the prognosis is significantly worse if associated with NF1.2 The possible cell of origin has been suggested as Schwann cell, epineural fibroblast, perineural cell, or endoneural cell.4,6 Intraorbital cases make up 0.1% to 0.2% of all orbital tumors.4 They can develop de novo or as a result of malignant transformation from a neurofibroma or rarely from a schwannoma.2,7 In the head and neck region, tumors that involve the trigeminal nerve arise from the mandibular branch in 72% of cases, followed by the maxillary (60%) and ophthalmic (32%) branches.8 In the orbit, the supraorbital nerve of the ophthalmic branch is reported to be the most frequent site of origin.4 In our case, the origin of the tumor was presumably the infraorbital nerve, which is an unusual location. The infraorbital nerve was clearly shown as the nerve of origin in only 1 patient.6
The classic histopathological features include hypercellularity of spindle-shaped cells, high mitotic activity, cellular and nuclear pleomorphism, and occasional areas of rhabdomyoblastic, epithelioid, and glandular differentiation.4 Heterologous elements can be found in 14.7% to 16% of the tumors.9 Jakobiec et al.4 observed malignant cartilage in 1 patient and suggested that the presence of heterologous mesenchymal tissue together with neural differentiation could help distinguish malignant peripheral nerve sheath tumors from other soft tissue sarcomas. In our case, the heterogenous appearance of the tumor on T2-weighted series, particularly the hypointense areas, probably corresponded to the osseous component (Figure 1).
There are no immunohistochemical markers for malignant peripheral nerve sheath tumors, although protein gene product 9.5 positivity was described to be more sensitive than for S-100.10 Diffuse S-100 staining is unexpected in malignant peripheral nerve sheath tumor and the expression of S-100 protein is usually focal and staining can be observed in only 50% to 60% of nuclei.2 Recently, nestin, which is expressed in mammalian nervous tissue during embryonic development, has been shown to be more sensitive than any other neural markers.2
This case was remarkable for the presence of heterologous elements that were demonstrable on the magnetic resonance imaging scans as heterogenous signal intensities and the possible origin from the infraorbital nerve, which is a seldom reported affected nerve.
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- Eviatar JA, Hornblass A, Herschorn B, Jakobiec FA. Malignant peripheral nerve sheath tumor of the orbit in a 15-month-old child: nine-year survival after local excision. Ophthalmology. 1992;99:1595–1599. doi:10.1016/S0161-6420(92)31761-0 [CrossRef]
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