| OCR Text |
Show Journal of Clinical Neuro-ophthalmology 13(1): 1-7, 1993. Orbital Malignant Peripheral Nerve Sheath Tumors Treatment with Surgical Resection and Radiation Therapy Sergul A. Erzurum, M.D., Onur Melen, M.D., Gary Lissner, M.D., Deborah 1: Friedman, M.D., Alfredo Sadun, M.D., Steven E, p~ltit:1ft; M,I)" and Narsing A. Rao, M.D. © 1993 Raven Press, Ltd., New York A§ei1@§ at Hif@@ patients with primary orbital malignant peripheral rl@ftI@ §~ath illmgr8 (MPNST) is presented. Two of our patieflt§ w1w W@fEl tf~at~d with surgery and postop.erative. racliatl1€faJ'Y_af~ ff~~ g!tumor recur~en.ce. The third patient sho'Yed a gOtitl fl:1SPOI\Ill? to radiation therapy. While surgical excision rerii.aii1s th€ m<tinstay of therapy, our patients demonstrate the usefulness of ad· juvant ra:di<ition therapy in this condition. Key Words: Surgical f€§eEtWn--Postoperative irradiation- Malignant nerve sheath hiffltlf!L From the Departments of Ophthalmology (S.A.E., O.M.) and Neurology (O,M,), Northwestern University, Chicago, IllinOis; Department of N@uro)ogy and Ophthalmology (D.I.F.), SUNY Health Sdence Center, Syracuse, New York; and the Doheny Eye Institute (A.S., S.E.F., N.A.R.), University of Southern Cal-ifornia, Los Angeles, California. .' This study was initiated by Northwestern UnIVersIty, Depart-ment of Ophthalmology, Chicago, Illinois. Address correspondence and reprint requests to Dr. Onur Melen, 233 E. Erie Suite #500, Chicago, IL 60611, U.S.A, 1 Benign tumors originating from the sheaths of cranial nerves constitute 4% of all orbital tumors (1-3). These tumors are comprised of either solitary schwannomas and neurofibromas or plexiform neurofibromas associated with von Recklinghausen's disease. Most of these tumors originate from the first division of the trigeminal nerve. They are generally slow-growing tumors with low morbidity. In contrast, malignant peripheral nerve sheath tumors (MPNST) are rare in occurrence. They run an aggressive course with a tendency to recur after surgical resection. These tumors may invade intracranial structures, metastasize to distant sites, and lead to death (4-6). In this report, we describe three such cases of MPNSTs, which demonstrated a response to surgical excision and postoperative irradiation. CASE REPORTS Case 1 A 29-year-old man presented in March 1984 with a 7-month history of progressive proptosis and fullness of the right eye. His past medical history and review of systems were negative for neurofibromatosis. Visual acuity was 20/20 in both eyes. Hertel exophthalmometry readings revealed 5 mm of proptosis on the right. The extraocular movements were full, and there was decreased retropulsion of the right globe. The fundus examination was normal. Computed tomography (CT) scan of the orbits in March 1984 showed a well-circumscribed mass occupying the medial portion of the right orbit. The 2 S. A. ERZURUM ET AL. FIG. 1. Contrast-enhanced CT demonstrates a wellcircumscribed enhancing mass along the medial right orbit. The optic nerve is displaced laterally. mass appeared to be extraconal with bowing of the adjacent orbital wall without any bony destruction. Orbital echography was suggestive of a cavernous hemangioma, and a benign process was suspected. CT scan in September 1984 showed lateral displacement of the right medial rectus and optic nerve (Fig. 1). The patient requested that the mass be observed with interval CT scans until October 1985 when he developed diplopia on u The patient consented to a right frontal cre .Lyap-proach to the superior orbit for rest'Jn ~f the tumor. The tumor was located superonasally m the orbit displacing the superior oblique muscle upward, and appeared to originate from the supraorbital nerve. Although most surfaces of the tumor appeared encapsulated, tumor-free margins could not be guaranteed. Histopathological examination demonstrated a cellular spindle cell tumor with variations in cellular density from field to field. Occasional mitoses were seen (Fig. 2). Electron microscopy demonstrated neoplastic cells with long nontapered cytoplasmic ends; however, no welldefined pericellular basement membrane was seen. Immunohistochemistry demonstrated S-100 positivity. In order to exclude malignant melanoma, additional stains for melanin were performed and found to be negative. The Armed Forces Institute of Pathology reviewed the slides and confirmed our diagnosis. Postoperatively, the patient received a total of 6,000 cGy (centigray) to the entire orbit. Following therapy, the visual acuity remained 20/20 in both eyes, and Hertel exophthalmometry readings revealed 1.5 mm of proptosis on the right. There was mild resistance to retropulsion and minimal restriction of motility. The patient maintained useful vision for 4 years before developing radiation- FIG. 2. High-power view illustrating cells with pleomorphic, spindle-shaped nuclei comprising the tumor. (Hemotoxylin and eosin; x400.) I Clin Neuro-ol'hlhalmol. Vol. 13, No. 1. 1993 MALIGNANT PERIPHERAL NERVE SHEATH TUMORS 3 induced proliferative retinopathy. The patient has remained free of tumor for 6 years by clinical examination and MRI studies. Case 2 A 77-year-old man was evaluated in September 1987 for diplopia, right upper eyelid ptosis, and right lower eyelid numbness. In 1985, a right orbital tumor had been discovered at another insti-tution. At that time, the patient had presented with persistent pain in the region of the medial canthus of the right eye. The tumor was surgically removed from the right supranasal area of the orbit, but required a second resection 2 years later because of recurrence. The orbit was subsequently irradiated with a total dose of 6,000 cGy. The histopathologic diagnosis was a highly malignant mesenchymal neoplasm originating from the peripheral nerve bundles, consistent with MPNST A B FIG. 3. (A) Photomicrograph demonstrating markedly cellular tumor with fascicular pattern. Atypical cells with spindle shaped hyperchromatic nuclei are seen. (Hematoxylin and eosin; x 100.) (B) High power view illustrating tumor cells arranged i~ thin bundles resembling nerve trunks. The nuclei range In size from small to large. MitotiC figures are seen. (Hematoxylin and eosin; x400.) J Clill Neuro·ophthalmol, Vot. 13, No.1, 1993 4 S. A. ERZURUM ET AL. FIG. 4. MR imaging demonstrates posterior extension of the tumor along the course of the trigeminal nerve (arrows). (Fig. 3). The Memorial Sloane-Kettering Cancer Center reviewed the slides and confirmed the diagnosis. In September 1987, the patient was admitted to the hospital for evaluation of dysphagia due to esophageal carcinoma and underwent an esophagogastrectomy. In October 1987, neuro-ophthalmologic consultation was obtained when the patient developed diplopia. His past medical history and review of systems disclosed no evidence of neurofibromatosis. Examination revealed best corrected visual acuity of 20/50 in the right eye and 20/40 in the left eye. Pupillary functions were normal. Complete ptosis and external ophthalmoplegia were present on the right side. The right corneal reflex was lost, and cutaneous sensation over the right forehead and lower lid were diminished. Visual fields and ophthalmoscopy were unremarkable. CT scan demonstrated a mass within the cavernous sinus extending within the orbital apex and supraorbital fissure. Magnetic resonance imaging (rvv:i) revealed posterior extension of the tumor along the course of the fifth cranial nerve to Meckel's cave (Fig. 4). In addition, T2-weighted images revealed bright signal intensity within the right lateral pons extending toward the fourth ventricular surface. This corresponded to the course of the fifth nerve through the brainstem toward its motor nucleus. It was decided to treat the tumor extension with irradiation in the hope of slowing the progression. The patient received 1,980 cGy to the cavernous sinus area and an additional 3,600 cGy to the orbit. One week after completion of radiotherapy, the patient was left with a lateral rectus paralysis and 30 prism diopters of esotropia. However, the patient succumbed to the carcinoma of the esophagus and died about a month later. A postmortem examination was not granted. Case 3 A 58-year-old woman experienced numbness and pain in her right nostril, which extended to her right upper lip in early 1986. Her past medical history and review of systems disclosed no evidence of neurofibromatosis. In March 1987, examination disclosed hypesthesia along the right side of the nose, lip, and malar region. CT scan of the head, orbits, and sinuses showed a subtle thickening in the inferior mid- to anterior portion of the right orbit. There was a slight inferior convexity of the curvature of the floor of the orbit with mild bone thickening. MRI of the brain was normal. The pain in the right malar region resolved with prednisone therapy (60 mg daily), only to return in January 1988. In September 1988, clinical evaluation was unchanged and the MRI demonstrated a welldelineated mass in the inferior orbit. Repeat CT scan showed interval enlargement of the mass, expanding the bony margins of the infraorbital canal, and extending posteriorly through the inferior or- / Gin Neuro-ophthalmol, Vol. 13. No.1, 1993 FIG. 5. CT scan demonstrating interval enlargement of the orbital mass, with bony remodeling inferiorly (arrow). MALIGNANT PERIPHERAL NERVE SHEATH TUMORS 5 bital fissure (Fig. 5). A tumor originating from the maxillary division of the trigeminal nerve was suspected. An inferior orbitotomy in November 1988 disclosed a fusiform, rubbery mass, encased in the orbital floor. The diameter of the mass decreased to conform with the infraorbital canal. The mass was dissected and severed, but the proximal ends contained malignant cells on frozen section. The tumor was removed up to its entry into the sphenoid bone. The remaining posterior tumor mass was removed at craniotomy in December. Minimal anterior extension was removed during concurrent exploration by an otolaryngologist. Pathological examination showed MPNST arising from the maxillary division of the trigeminal nerve (Fig. 6). Immunohistochemistry demonstrated vimentin and 5-100 positivity, but no keratin staining. Postoperatively, the patient received a total of 5,950 cGy to the entire orbit. The irradiation resulted in marked limitation of jaw mobility, dry A B FIG. 6. (A) Low power photomicrograph demonstrating the cellular spindle-cell character of the neoplasm. Fascicular pattern is apparent. (Hemotoxylin and eosin; x40.) (8) High-power view illustrating cells with plump, pleomorphic nuclei comprising the tumor. (Hemotoxylin and eosin; x400.) JClIIJ N~uro-ophthalmol, Vol. 13, No.1, 1993 6 S. A. ERZURUM ET AL. TABLE 1. Review of orbital MPNSTs in the literature Nerve of origin" Surgical treatmentb Metastases or tumor extension Outcome" Supraorbital (13) Local excision (12) Extension to CNS/sinuses (9) Death related to MPNST (10) Infraorbital (3) Craniotomy (7) Lungs (4) Alive >3 yrs (4) Intraconal (1) Orbitotomy (5) Mediastinum (1) Inadequate follow-up (4) Ophthalmic division (1) Exenteration (5) Liver (1) Unrelated deaths (2) Number of cases in parentheses. Total number of cases reviewed was 20. The patients develop~d an average of 1.4 recurrences (range of 0 to 5). Thirteen patients received radiation therapy and two patients received chemotherapy. "When information was inadequate, those patients were not included in the tabulations. b More than one procedure was performed on some patients. eye, and mild infraduction weakness. The patient maintained useful vision until April 1990, when she developed ischemic optic neuropathy. There has been no evidence of tumor recurrence for 31/2 years. DISCUSSION Only 17 well-documented orbital malignant peripheral nerve sheath tumors (MPNST) have been reported so far in the ophthalmic literature (2,4,5,7-9). Jakobiec and Font (4) published the largest series and provided a comprehensive review of the pathologic and clinical features of these neoplasms. Objective means for identification of MPNST have been attempted by immunohistochemical studies. Series of spindle cell sarcomas have been studied to see if they could be distinguished by immunoreactivity alone. Results have shown that myelin basic protein (MBP), Leu-7, and anti-neuron specific enolase (NSE) are not representative markers of schwannian differentiation. Anti-glial fibrillary acidic protein (GFAP) is rarely expressed but may indicate schwannian differentiation. MPNSTs and leiomyosarcomas seem to share immunoreactivity for 5-100, Leu-7, NSE, and actin. Thus, these two tumors cannot be differentiated on this basis alone (10). The majority of tumors in Jakobiec and Font's (4) series were located superonasally in the orbit, indicative of its origin from the supraorbital nerve. Presenting features included subcutaneous nodule near the medial canthus, pain, proptosis, and diplopia. Despite their initial benign appearance, the tumors showed a tendency to grow posteriorly along the supraorbital nerve, extended into the region of the cavernous sinus, and progressed as far as the nucleus of the trigeminal nerve in the pons. Local recurrences were frequent despite surgical resection, and some patients suffered from metastases to regional lymph nodes, mediastinum, JClin Neuro-ophtlullmol. Vol. 13. No. 1. 1993 and lung. Two of their patients responded favorably to adjuvant radiotherapy and/or chemotherapy once recurrence was detected. Recently Lyons et al. (5) reported three additional cases of orbital MPNST. These patients presented with eye pain, redness, proptosis, and/or subcutaneous nodule near the medial canthus. All of them suffered from either extensive intracranial extension of the tumor or multiple local recurrences despite surgical excision. None of their patients received radiotherapy. One patient died of his disease, and the other two only had short-term follow-up. The authors recommended extensive surgical resection and exenteration as treatment of choice. Clinical presentation of our patients were similar to those reported in the literature (Table 1). None of them had systemic neurofibromatosis. Cases 1 and 3 were treated with surgical resection and postoperative irradiation. These patients have remained free of tumor recurrence for 6 and 3 years, respectively; however, they developed proliferative retinopathy and ischemic optic neuropathy, presumably a result of radiotherapy. Our case 2 experienced a local recurrence 2 years after the initial surgical removal. The recurrent tumor was then excised, and the orbit was irradiated. Unfortunately, he presented with cavernous sinus syndrome several months later. Additional irradiation to the posterior orbit and skull base resulted in partial resolution of ophthalmoplegia. Since these tumors have an aggressive growth pattern and potential for distant metastasis, an attempt should be made to remove these tumors totally within the orbit. If there is intracranial extension, consideration should be given to resect the tumor up to the cavernous sinus. Our limited experience with postoperative radiotherapy suggests its usefulness in prevention of local recurrence up to 6 years. This mode of treatment should be considered as an alternative to exenteration. MALIGNANT PERIPHERAL NERVE SHEATH TUMORS 7 REFERENCES 1. Harkin Je, Reed RJ. Tumors of the peripheral nervous system. In: Atlas of tumor pathology. 2nd ed. Washington, DC: Armed Force Institute of Pathology, 1969:107-26. 2. Henderson JW. Orbital tumors. 2nd ed. New York: Brian C. Decker, 1980:276. 3. Jakobiec FA, Jones IS. Neurogenic tumors. In: Diseases of the Orbit. Hagerstown, MD: Harper & Row, 1979:371-416. 4. Jakobiec FA, Font RL. Malignant peripheral nerve sheath tumors of the orbit: a clinicopathologic study of eight cases. Trans Am Ophthalmol Soc 1985;83:332-(,6. 5. Lyons q, McNab AA, Garner A, Wright JE. Orbital malig-nant peripheral nerve sheath tumours. Br J Ophthalmol 1989;73:731-8. 6. Das Gupta TK, Brasfield RD. Solitary malignant schwannoma. Ann Slirg 1970;171:419-28. 7. Schatz H. Benign orbital neurilemmoma. Arch Ophthalmol 1971;86:268-73. 8. Mortada A. Solitary orbital malignant neurilemmoma. Br J Ophthalmol 1968;52: 188-90. 9. Grinberg MA, Levy NS. Malignant neuilemmoma of the supraorbital nerve. Am J Ophthalmol 1974;78:489-92. 10. Giangaspero F, Fratamico FCM, Ceccarelli e, Brisigotti M. Malignant peripheral nerve sheath tumors and spindle cell sarcomas: an immunohistochemical analysis of multiple markers. Appl PathoI1989;7:134-44. I (!i" NClIro-0l'hthalmol, Vol. 13, No.1, 1993 |
