Orbital Schwannoma

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Article initiated by:
Adam R. Sweeney, MD, Nicolaas Piet DeRuyter
All contributors:
Adam R. Sweeney, MD, Krista Stewart, MD, Jill Wells, MD, Michael T Yen, MD, Cat Nguyen Burkat, MD FACS, Adam de la Garza, MD, Manpreet Tiwana, MD, Jan P. Ulloa-Padilla, M.D.
Assigned editor:
Jan P. Ulloa-Padilla, M.D.
Review:
Assigned status Up to Date
 by Jan P. Ulloa-Padilla, M.D. on September 15, 2024.


Orbital Schwannoma
DiseasesDB
33713


Orbital schwannoma

Disease

Orbital schwannoma is a rare type of peripheral nerve sheath tumor (PNST) that varies in clinical presentation. Orbital schwannomas typically involve the head and neck, and rarely occur within the orbit. Other tumor types within this family include neurofibromas and malignant PNSTs, which are more commonly seen in patients with neurofibromatosis (NF). Orbital involvement is seen in 11-28% patients with NF-1 or family history of NF, however the risk of specifically developing orbital schwannoma within those populations is 1.5%.[1] [2] [3] [4] Benign schwannomas present usually between the 2nd and 6th decade of life, and there has been no racial association identified.[5] [6] These tumors rarely undergo malignant transformation.[7] [8] The variation in size and tumor location often creates unique therapeutic challenges.

Etiology

Schwannomas arise from hyperplasia of the myelin-producing schwann cells. The molecular etiology of this hyperplasia is not completely understood, but with knowledge of neurofibromatoses pathology it has become more clear. In NF-1, biallelic loss of tumor suppressor gene neurofibromin on 17q11.2 leads to unbridled Ras gene signal transduction, promoting schwann cell hyperplasia. In NF-2, loss of the merlin gene (22q11.2) also promotes schwann hyperplasia. These tumors typically affect cranial sensory nerves, primarily V1 and less commonly V2[9] [10], cranial nerves in the orbit[10][11], and those that supply the extraocular muscles.[12] [13] Furthermore, schwannomas have been observed within the globe, with infiltration of the ciliary body[14] [15], choroid [16] [17] [18], iris [19], sclera [20] [21], posterior ciliary nerve [22] [23]. Rarely, the optic nerve appears to be involved[24] [25] [26] [27] [28], which has been attributed to autonomic perivascular nerves surrounding the nerve sheath.[27]

Presentation

Orbital schwannomas present insidiously with gradual non-pulsating proptosis and occasionally lid swelling. A majority of these tumors infiltrate the superior quadrant causing inferiorly displaced proptosis or frank hypoglobus.[5][29] [30] In late presentations, patients can experience diplopia, eye movement limitation, diminished visual acuity, and symptoms of optic nerve compression including scotomas, dyschromatopsia, and impaired contrast sensitivity. Depending on which nerve is affected, patients may have pain or paresthesias in distribution of the nerve. In severe cases, there may be a palpable orbital mass. Schwannomas rarely have bilateral orbital involvement, with only one case reported. [31]


Differential diagnosis

The differential diagnosis includes other types of PNSTs including neurofibromas or malignant PNSTs, meningioma, cavernous hemangioma, lymphangioma, fibrous histiocytoma, lymphoma, dermoid cyst, hemangiopericytoma, pleomorphic adenoma of the lacrimal gland. It is nearly impossible to differentiate between these tumors based on clinical exam alone.

Imaging is extremely useful to identify and assess, but some tumors will be difficult to distinguish and will need pathology. Imaging should focus on size, location, spread, and rate of growth, particularly if serial imaging is used.

Differential for imaging is broken down as written below

Intraconal - Cavernous malformation, venous varix, metastasis, schwannoma, lymphatic malformation

Extraconal

  • Lacrimal Gland - Dacryoadenitis, sarcoidosis, sjogrens syndrome, GPA
  • Bony Lesion - Dermoid cyst, granuloma, osteoblastoma, fibrous dysplasia
  • Periorbital - Mucocele, fungal infection, encephalocele, capillary hemangioma

Other - Solitary fibrous tumor, cavernous venous malformation, malignant PNST

Miscellaneous - Malignancy, idiopathic orbital inflammation, rhabdomyosarcoma, neuroblastoma, orbital cellulitis

Diagnostic procedures

There are multiple imaging modalities for orbital schwannoma evaluation and surveillance. Computed tomography (CT) is optimal for assessing bony erosions and planning surgery, whereas magnetic resonance imaging (MRI) characterizes tumor and involvement with adjacent soft tissue structures.[32]


CT

On CT imaging, orbital schwannomas appear as smooth, round, elongated, and homogenous lesions with a density similar to extraocular muscle.[33] Additionally, CT can reveal calcification in primary tumors. [10][34] They have strong enhancement with CT contrast.[10] They are smooth, well-circumscribed tumors that will mold to the shape of the cavity and grow along the axis of the orbit.[33] Orbital schwannomas are more oval or spindle shaped compared to other PNSTs. They are typically extraconal, whereas other masses on the differential such as hemangiomas, are often intraconal.[35] Schwannomas have a propensity to invade through the superior orbital fissure compared to meningiomas. [30][36] In addition, CT will reveal their characteristic expansion into bone without eroding fissures,[37] which occurs less with neurofibromas.[5][33][38]

MRI

Schwannomas typically have hypointense signaling on T1 and hyperintense signals on T2. MRI can reveal both homogenous or heterogenous enhancement and correlate with histology and morphology of tumors.[39] [40] [41] Antoni A regions have intermediate intensities with T1 and T2, but Antoni B are hypointense on T1 and hyperintense on T2. There is no contrast enhancement, but there may be cystic degeneration in about 41% of schwannomas-- these regions may correlate to Antoni B regions.[42] MRI may distinguish schwannoma from lymphoma because lymphoma has intermediate T2 and molds around neighboring structures, whereas schwannomas encroach and deform the vicinity.[36] Dermoid cysts are similar in shape, but are hyperintense on T1 and lack gadolinium enhancement. (160) Solitary fibrous tumors are similar in T1 and T2 intensities and locations, but one can use dynamic contrast enhanced MRI to distinguish between the two. In dynamic contrast MRI, solitary fibrous tumors will have a smoother washout curve owing to their high cellular stroma, whereas schwannomas show a plateau washout due to a nonuniform and loose cellular arrangement.[43] Dynamic MRI enhancement will differentiate cavernous hemangiomas because cavernous hemangiomas will show progressive enhancement in later images.[44]


Ultrasound

B-scan ultrasonography can be used for rapid evaluation, follow up, or progression of schwannomas. On ultrasound, they appear as round, well-defined, solid lesions with a reflective surface. They can also appear as heterogenous or cystic masses with different tissue interfaces that affect the signal intensity.[10][29][45] Acoustic hollows on ultrasound are suggestive of intratumor hemorrhage.[46]


Pathology

Most schwannomas are described as “conventional” but there are four additional histological variants: cellular, melanotic, plexiform, and neuroblastoma.[47] [48] [49] All of the subtypes stain strongly for S-100, a protein found in cells derived from the neural crest.[50] Staining for Type 4 collagen identifies pericellular collagen deposition. [51] [52] Additionally, schwannomas stain positively for SOX10, p16, and neurofibromin, but they are negative for the epidermal growth factor receptor. In the orbit, most schwannomas are of conventional variety, followed by cellular; other variants are very rare in the orbit. Conventional and cellular subtypes are identified by their fibrous, smooth capsule from the perineurium of nerve origin. The melanotic subtype has a thin fibrous membrane, but the capsule is not seen well and may be lobulated in the plexiform variant. [53] [54] Smaller schwannomas grow eccentrically from the parent nerve[55] Larger schwannoma can outgrow the parent nerve, but unlike a neurofibroma, will not diffusely infiltrate. On light microscopy, schwannomas have a biphasic histologic morphology of variable patches of Antoni A and Antoni B patterns. Antoni A patterns are hypercellular with bundles and fascicles of compact spindle cells containing indistinguishable cytoplasmic borders arranged in parallel along their long axis. Additionally, Antoni A patterns have Verocay bodies, which are nuclear areas surrounded by clusters of elongated spindle cell nuclei arranged in palisades. Periodic Acid Schiff staining and immunoperoxidase assay for laminin are strongly positive, proving each cell makes a basement membrane. There may be mitoses but will not be aggressive. Antoni B phases are hypocellular and less organized. Antoni B patterns have vacuolated cells arranged in sheets within a myxoid or microcystic matrix. Within this pattern there are small, irregular, hyalinized vessels surrounded by inflammatory foamy histiocytes and collagen fibers.

  • In contrast to the conventional subtype, the cellular schwannoma has minimal to absent Antoni B tissue pattern with cells that are packed tightly in fascicles. These may look like Antoni A, but they have poorly formed Verocay bodies. Cells may also show atypia and increased mitoses, raising suspicion for malignancy. One should also consider smooth muscle neoplasms and distinguish from cellular schwannomas by immunostaining for smooth muscle actin.[56]
  • The plexiform subtype is similar to conventional because it contains a true capsule and cell type population.[50] However, it originates from a nerve plexus or ganglion bundles of palisading spindle cells surrounding the parent nerve.[53] Plexiform schwannomas are characterized by more Antoni type A patterns versus type B. It may be confused with sarcoma because of its high cellularity, but without mitotic activity, atypia, and necrosis with strong S-100 immunostaining, it is unlikely to be so.
  • Melanotic subtypes are extremely rare tumors with only one case invading the orbit.[57] Melanotic contains variable pigment and stains for HMB-45 and Melan-A. Pigmentation is strongest in melanophages. They can be difficult to distinguish between malignant melanoma but must rely on histomorphology, cytoarchitecture, and malignancy features.
  • Neuroblastoma is also exceedingly rare, with only one orbital case documented.[49] The hallmark feature is the “giant rosette,” a central eosinophilic collagenous core surrounded by small round or oval cells with hyperchromatic nuclei. Malignant features are low to absent. Immunohistochemical staining is similar to conventional, but negative for synaptophysin CD99 and neuron-specific enolase.[20]
  • Cystic schwannoma is a type of conventional schwannoma but has degenerative microcystic and myxoid areas that have coalesced to form a macrocyst seen on low power microscopy. [58] [59]
  • Ancient schwannoma are seen in conventional and cellular subtypes which have degenerated over time and include microcystic changes, hemorrhages, and calcification.[31][60] [61] They have cellular atypia and pleomorphism, leading to confusion with sarcoma. But the absence of mitotic figures, A and B regions, and S-100 positive differentiates it from sarcoma.

General treatment

Surgery

The primary treatment of orbital schwannoma is excision, ideally with maintenance of the capsular integrity. Numerous surgical approaches have been described. Most schwannomas occupy the superior orbit, requiring an anterior orbitotomy through an upper eyelid crease incision or sub-brow incision.[62] A lateral orbitotomy can be performed for superolateral tumors.

Inferior or medial lesions require inferior transconjunctival incisions. Relatively anterior medial tumors can be accessed through a transcaruncular incision.[62] Posterior medial wall tumors near the orbital apex can be accessed through an endoscopic endonasal approach.[63] If a schwannoma involves the superior orbital fissure, co-surgery with a neurosurgeon is recommended, as excision of a schwannoma in this location may require pterional-extradural approach, which provides appropriate exposure to the superior posterior orbit, superior orbital fissure, and optic canal.[64] Regardless of the chosen approach, the surgeon should differentiate the nerve as sensory from motor before sacrificing it. This can be avoided through microsurgery or attentive dissection of the capsule. Tumors can be treated through debulking with serial imaging to observe tumor progression.

Radiotherapy:

Radiation treatment of schwannomas is evolving. Early studies noted complications of optic neuropathy. Fractionated radiation can treat smaller tumors to reduce radiation exposure, but unfortunately, the optic nerve sustains equal doses of radiation as the tumor.[65] Reports have observed optic nerve neuropathy with as little as 8- 12 doses gray. [66] [67] However, radiation therapy has been warranted to aid in surgical management of tumors in compact areas with important neighboring neurovascular bundles. Of recent, gamma knife stereotactic therapy has been used. One study showed tumor size reduction or stability using gamma knife therapy.[67] Single gamma knife treatment is not recommended for apex schwannomas because of the likelihood of optic nerve damage and associated visual field defects and acuity loss. [68] [69] Instead, multisession gamma knife therapy is indicated for orbital schwannomas; one study showed tumor stability or reduction in 6/7 patients and two of them had vision reduction. This technique can be used in treatment for smaller, unresectable, unreachable, or post-surgical benign schwannomas. It is an alternative to extraction but indications vary and are not well established.

Decompression

If resection is not possible, bony or fat orbital decompression may be a suitable alternative to improve patient quality of life. This is especially true in apical schwannomas where optic nerve compression can occur due to compact spacing. Two studies have demonstrated decompression was helpful in cases with slow growing apical tumors and reliable follow-up. [70] [71] This option is indicated for benign, slow growing schwannomas in older patients with intact vision, rapidly evolving clinical decline, no malignancy, and agree to serial imaging after the procedure. Adverse effects include diplopia, hypoglobus, enophtalmos, and rarely, cerebrospinal fluid.

Medical follow up

Long term follow up is required for recurrence and malignant transformation. After stable MRI images have been obtained over several years, patients may be followed annually or bi-annually.

Prognosis

Following complete surgical excision, there is generally a good prognosis with very low risk of recurrence.[42] One report showed non-worsened visual acuity in 19/22 and 22/22 patients with nearly half having restricted eye movement following surgery that improved over time. Additionally, few of those patients had chronic ptosis and fixed mydriasis.[6] In the absence of neurofibromatoses, few schwannomas will recur after complete excision.[59][72] [73] [74]

References

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  30. ↑ 30.0 30.1 Wang Y, Xiao LH. Orbital schwannomas: findings from magnetic resonance imaging in 62 cases. Eye . 2007;22(8):1034–9.
  31. ↑ 31.0 31.1 Sales-Sanz M, Sanz-Lopez A, Romero JAC. Bilateral simultaneous ancient schwannomas of the orbit. Ophthal Plast Reconstr Surg. 2007 Jan;23(1):68–9.
  32. ↑ Park WC, Abraham White W, Woog JJ, Garrity JA, Kim Y-D, Lane J, et al. The Role of High-Resolution Computed Tomography and Magnetic Resonance Imaging in the Evaluation of Isolated Orbital Neurofibromas. Am J Ophthalmol. 2006;142(3):456–63.
  33. ↑ 33.0 33.1 33.2 Dervin JE, Beaconsfield M, Wright JE, Moseley IF. CT findings in orbital tumours of nerve sheath origin. Clin Radiol. 1989 Sep;40(5):475–9.
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  38. ↑ Shields JA, Kapustiak J, Arbizo V, Augsburger JJ, Schnitzer RE. Orbital neurilemoma with extension through the superior orbital fissure. Arch Ophthalmol. 1986 Jun;104(6):871–3.
  39. ↑ Abe T, Kawamura N, Homma H, Sasaki K, Izumiyama H, Matsumoto K. MRI of orbital schwannomas. Neuroradiology. 2000 Jun;42(6):466–8.
  40. ↑ Mulkens TH, Parizel PM, De Schepper AM, van de Heyning PH, Forton GE, Martin JJ, et al. MRI of acoustic schwannoma: a retrospective study of 89 tumours. Rofo. 1993 Apr;158(4):362–7.
  41. ↑ Shen WC, Yang DY, Ho WL, Ho YJ, Lee SK. Neurilemmoma of the oculomotor nerve presenting as an orbital mass: MR findings. AJNR Am J Neuroradiol. 1993 Sep;14(5):1253–4.
  42. ↑ 42.0 42.1 Kashyap S, Pushker N, Meel R, Sen S, Bajaj MS, Khuriajam N, et al. Orbital schwannoma with cystic degeneration. Clin Experiment Ophthalmol. 2009 Apr;37(3):293–8.
  43. ↑ Zhang Z, Shi J, Guo J, Yan F, Fu L, Xian J. Value of MR imaging in differentiation between solitary fibrous tumor and schwannoma in the orbit. AJNR Am J Neuroradiol. 2013 May;34(5):1067–71.
  44. ↑ Xian J, Zhang Z, Wang Z, Li J, Yang B, Chen Q, et al. Evaluation of MR imaging findings differentiating cavernous haemangiomas from schwannomas in the orbit. Eur Radiol. 2010 Sep;20(9):2221–8.
  45. ↑ Purcell SM, Dixon SL. Schwannomatosis. An unusual variant of neurofibromatosis or a distinct clinical entity? Arch Dermatol. 1989 Mar;125(3):390–3.
  46. ↑ Byrne BM, van Heuven WA, Lawton AW. Echographic characteristics of benign orbital schwannomas (neurilemomas). Am J Ophthalmol. 1988 Aug 15;106(2):194–8.
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  48. ↑ Kleihues P, Sobin LH. World Health Organization classification of tumors. Cancer. 2000 Jun 15;88(12):2887.
  49. ↑ 49.0 49.1 Kukreja M, Gupta R, Julka A, Sharma MC. Neuroblastoma-like schwannoma as a rare cause of proptosis: a case report. Can J Ophthalmol. 2007;42(4):624–5.
  50. ↑ 50.0 50.1 Goldblum JR, Weiss SW, Folpe AL. Enzinger and Weiss’s Soft Tissue Tumors. Elsevier Health Sciences; 2013. 1176 p.
  51. ↑ Pekmezci M, Reuss DE, Hirbe AC, Dahiya S, Gutmann DH, von Deimling A, et al. Morphologic and immunohistochemical features of malignant peripheral nerve sheath tumors and cellular schwannomas. Mod Pathol. 2015 Feb;28(2):187–200.
  52. ↑ Huang H-Y, Park N, Erlandson RA, Antonescu CR. Immunohistochemical and ultrastructural comparative study of external lamina structure in 31 cases of cellular, classical, and melanotic schwannomas. Appl Immunohistochem Mol Morphol. 2004 Mar;12(1):50–8.
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  54. ↑ Morgenstern KE, Vadysirisack DD, Zhang Z, Cahill KV, Foster JA, Burns JA, et al. Expression of sodium iodide symporter in the lacrimal drainage system: implication for the mechanism underlying nasolacrimal duct obstruction in I(131)-treated patients. Ophthal Plast Reconstr Surg. 2005 Sep;21(5):337–44.
  55. ↑ Wippold FJ, Lubner M, Perrin RJ, Lammle M, Perry A. Neuropathology for the Neuroradiologist: Antoni A and Antoni B Tissue Patterns. AJNR Am J Neuroradiol. 2007;28(9):1633–8.
  56. ↑ Scheithauer BW, Erdogan S, Rodriguez FJ, Burger PC, Woodruff JM, Kros JM, et al. Malignant peripheral nerve sheath tumors of cranial nerves and intracranial contents: a clinicopathologic study of 17 cases. Am J Surg Pathol. 2009 Mar;33(3):325–38.
  57. ↑ Jensen OA, Bretlau P. Melanotic schwannoma of the orbit. Immunohistochemical and ultrastructural study of a case and survey of the literature. APMIS. 1990 Aug;98(8):713–23.
  58. ↑ Lam DSC, Ng JSK, To KF, Abdulah V, Liew CT, Bryant SA. Cystic schwannoma of the orbit. Eye . 1997;11(6):798–800.
  59. ↑ 59.0 59.1 Subramanian N, Rambhatia S, Mahesh L, Menon SV, Krishnakumar S, Biswas J, et al. Cystic schwannoma of the orbit-a case series. Orbit. 2005 Jun;24(2):125–9.
  60. ↑ Khwarg SI, Lucarelli MJ, Lemke BN, Smith ME, Albert DM. Ancient schwannoma of the orbit. Arch Ophthalmol. 1999 Feb;117(2):262–4.
  61. ↑ Moloney G, Brewer J, O’Donnell BA. “Ancient” schwannoma of the orbit. Clinical and Experimental Ophthalmology. 2004;32(6):637–8.
  62. ↑ 62.0 62.1 Goldberg RA, Rootman DB, Nassiri N, Samimi DB, Shadpour JM. Orbital Tumors Excision without Bony Marginotomy under Local and General Anesthesia. J Ophthalmol. 2014 Apr 14;2014:424852.
  63. ↑ Sun MT, Wu W, Yan W, Tu Y, Selva D. Endoscopic Endonasal-Assisted Resection of Orbital Schwannoma. Ophthal Plast Reconstr Surg [Internet]. 2015 Jul 14; Available from: http://dx.doi.org/10.1097/IOP.0000000000000528
  64. ↑ Schick U, Bleyen J, Hassler W. Treatment of orbital schwannomas and neurofibromas. Br J Neurosurg. 2003 Dec;17(6):541–5.
  65. ↑ Kim BS, Im Y-S, Woo KI, Kim Y-D, Lee J-I. Multisession Gamma Knife Radiosurgery for Orbital Apex Tumors. World Neurosurg. 2015;84(4):1005–13.
  66. ↑ Laskin WB, Weiss SW, Bratthauer GL. Epithelioid variant of malignant peripheral nerve sheath tumor (malignant epithelioid schwannoma). Am J Surg Pathol. 1991 Dec;15(12):1136–45.
  67. ↑ 67.0 67.1 Xu D, Liu D, Zhang Z, Zhang Y, Song G. Gamma knife radiosurgery for primary orbital varices: a preliminary report. Br J Ophthalmol. 2010;95(9):1264–7.
  68. ↑ Hayashi M, Tamura N, Maruyama T, Nakaya K, Ochiai T, Chernov M, et al. Current Treatment Strategy of Gamma Knife ® Surgery for Vestibular Schwannoma: Image-Guided and Robotized Microradiosurgery. In: Radiosurgery. 2010. p. 175–88.
  69. ↑ Kim M-S, Park K, Kim JH, Kim Y-D, Lee J-I. Gamma knife radiosurgery for orbital tumors. Clin Neurol Neurosurg. 2008 Dec;110(10):1003–7.
  70. ↑ Almond MC, Cheng AG, Schiedler V, Sires BS, Most SP, Jian-Amadi A. Decompression of the orbital apex: an alternate approach to surgical excision for radiographically benign orbital apex tumors. Arch Otolaryngol Head Neck Surg. 2009 Oct;135(10):1015–8.
  71. ↑ Kloek CE, Bilyk JR, Pribitkin EA, Rubin PAD. Orbital decompression as an alternative management strategy for patients with benign tumors located at the orbital apex. Ophthalmology. 2006 Jul;113(7):1214–9.
  72. ↑ Chisholm IA, Polyzoidis K. Recurrence of benign orbital neurilemmoma (schwannoma) after 22 years. Can J Ophthalmol. 1982 Dec;17(6):271–3.
  73. ↑ Kron M, Bohnsack BL, Archer SM, McHugh JB, Kahana A. Recurrent orbital schwannomas: clinical course and histopathologic correlation. BMC Ophthalmol. 2012 Aug 31;12:44.
  74. ↑ Röhrich M, Koelsche C, Schrimpf D, Capper D, Sahm F, Kratz A, et al. Methylation-based classification of benign and malignant peripheral nerve sheath tumors. Acta Neuropathol. 2016;131(6):877–87.
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