Nerve Sheath Tumors Involving the Spine

Introduction

In 1887, Sir Victor Horsley performed the first successful surgical excision of a spinal intradural extramedullary (IDEM) tumor, which was diagnosed by William Gower. Since then, advances in imaging, anesthesia, surgical techniques, and monitoring have made surgical resection of these tumors one of the more gratifying experiences for both neurosurgeons and patients.

The true incidence of intradural spinal tumors is unknown, as most hospital-based studies have a selection bias. In a 10-year population-based study in Iceland from 1954 to 1963, the incidence of intradural spinal tumors was 1.1 per 100,000 people per year. Seppala et al. estimated the incidence of new spinal schwannomas to be 0.3 to 0.4 per 100,000 people each year. In adults, around half of spinal tumors are IDEM, and roughly half of these are nerve sheath tumors (NSTs). In children, a larger proportion of tumors are intramedullary, and a smaller percentage is IDEM.

The term spinal nerve sheath tumor (SNST) refers to spinal schwannomas, neurofibromas, and malignant NSTs. These can be completely intradural, extradural, or mixed (dumb-bell tumors). They usually arise from the dorsal sensory nerve root and are frequently amenable to complete resection using standard microsurgical techniques. However, their management can sometimes be challenging, especially with large extradural tumors, large multicompartmental tumors, in patients with neurofibromatosis (NF) and multiple tumors, malignant tumors, and when spinal stability after resection is in question. There are also concerns about the resection of the involved but potentially functional nerve root in an effort to get gross total resection.

The purpose of this chapter is to address the previously mentioned concerns, along with a discussion of the pathology, clinical features, and surgical management of SNSTs.

Classification and Pathology

The current classification divides benign NSTs into schwannomas and neurofibromas, and groups all malignant variants of this entity into a single group called malignant nerve sheath tumors (MNSTs) .

Schwannomas are well-encapsulated tumors that arise from a single-nerve fascicle and displace other uninvolved fascicles by progressive tumor growth. Although they can occur anywhere along the peripheral nerves, the vestibular part of the eighth cranial nerve and dorsal spinal rootlets are generally favored locations. Histologically, schwannomas are characterized by compact and cellular Antoni A areas with palisading arrangements called Verocay bodies and less cellular Antoni B areas that have microcystic changes without palisading. The neoplastic cells in schwannomas are Schwann cells that stain for S-100, vimentin, and Leu-7. ^, The tumor rarely contains any functional neural tissue. Secondary changes such as hyalinization, cysts, micro-hemorrhages, and even mineralization are observed. Variants include ancient schwannomas, cellular schwannomas, and melanotic schwannomas. Schwannomas can occur in a sporadic manner, or in certain conditions such as NF-2, schwannomatosis, and Carney complex. NF-1 and NF-2 are discussed in more detail as follows. Schwannomatosis refers to the occurrence of multiple schwannomas without other defining features of NF-1 or NF-2. ^, Patients with a Carney complex have facial pigmentation, cardiac myxomas, endocrine abnormalities, and melanotic schwannomas—10% of which may be malignant. ^,

Neurofibromas occur primarily in patients with NF-1 but can also occur sporadically in cutaneous and deep peripheral nerves. They are less well-encapsulated than schwannomas and typically present with more diffuse expansions of the nerve rather than a discrete, dissectable mass. They may have single or multiple fascicles that enter and leave the nerve, making surgical removal almost impossible without sacrificing the peripheral nerve. The nerve of origin is often nonfunctional upon presentation. Plexiform neurofibromas have a predominant intrafascicular histologic growth pattern with redundant loops of expanded nerve fascicles. The presence of axons within the tumor helps distinguish a neurofibroma from a schwannoma. The spindle cells may also stain with S-100 and Leu-7, but these stains are positive less frequently than in schwannomas. They also lack densely packed structures like Antoni-A areas. The presence of mucopolysaccharides in the loose connective tissue also distinguishes neurofibromas from schwannomas.

Malignant peripheral nerve sheath tumors (MPNSTs) represent 5% to 10% of soft tissue sarcomas. They are malignant neoplasms that usually arise in the presence of a neurofibroma or, very rarely, a schwannoma. The term currently includes tumors from multiple different classification schemes used in the past, such as neurosarcoma, neurofibrosarcoma, and malignant neuroma. A histologic diagnosis is often difficult, given their heterogeneity and de-differentiation. As many as 67% of MNSTs stain for S-100 and are thought to be composed, at least partially, of cells that differentiate toward Schwann cells. However, the staining patterns of these tumors are somewhat erratic. Around half of these tumors occur in patients with NF-1. Conversely, only approximately 5% of all patients with NF-1 will develop MNSTs. ^, The principal differential diagnosis includes cellular schwannoma, fibrosarcoma, malignant fibrous histiocytoma, synovial sarcoma, and leiomyosarcoma.

Neurofibromatosis

The NF are two distinct and well-described autosomal dominant genetic syndromes caused by mutations in genes coding for neurofibromin on chromosome 17 (NF-1) and merlin on chromosome 22 (NF-2). Both are transmitted in an autosomal dominant pattern but can also occur as a result of spontaneous mutation. These deficits predispose patients to the development of both benign and malignant NSTs. NF-1 (Von Recklinghausen disease) is the more common condition (1 in 2500) and has a strong association with MNSTs.

The diagnosis of NF-1 is based on the presence of two or more of the following seven criteria ^, :

• 1.

  Six or more café au lait macules over 5 mm in greatest diameter in prepubertal individuals or over 15 mm in greatest diameter in postpubertal individuals

• 2.

  Two or more neurofibromas of any type or one plexiform neurofibroma

• 3.

  Freckling in the axillary or inguinal regions (Crowe sign)

• 4.

  Optic glioma

• 5.

  Two or more Lisch nodules (iris hamartomas)

• 6.

  A distinctive osseous lesion such as sphenoid dysplasia, or thinning of long bone cortex with or without pseudoarthrosis

• 7.

  A first-degree relative (parent, sibling, or offspring) with NF-1 by the above criteria

NF-2 is much less common than NF-1 (1 in 50,000 people). It was first recognized as a distinct entity in 1970. Cutaneous manifestations are less common than that in NF-1. In fact, in older literature, NF-2 was referred to as the “central form” of NF, compared to the peripheral form, now called NF-1. The criteria for the diagnosis of NF-2 are met by an individual who satisfies one of the following conditions ^, :

• 1.

  Bilateral acoustic neuromas

• 2.

  A first-degree with NF-2 and either

  • a.

    Unilateral acoustic neuroma, or

  • b.

    Two of the following:

    • Neurofibroma

    • Meningioma

    • Glioma

    • Schwannoma

    • Juvenile posterior subcapsular cataract

Spinal NSTs occur much more frequently in patients with NF. Multiple spinal neurofibromas are seen almost exclusively in patients with NF-1. However, multiple spinal schwannomas can occur without NF, albeit uncommonly. NF-1 patients commonly have multiple SNSTs, usually neurofibromas. The occurrence of multiple SNSTs in NF-2 patients is uncommon, but when they do occur, they are usually schwannomas. ^,

Tumor Location

SNST occurrence is almost equally distributed at all levels of the spinal column, but cervical or lumbar predilections have also been described. ^, In a recent series from Japan, 28 out of 149 SNSTs treated between 1980 and 2001 arose from the first two cervical roots, 54 from C3 to C8 roots, 38 from the thoracic spine, 13 from the conus region, and 43 from the remaining lumbosacral spinal roots. In Seppala’s series, 26% of all schwannomas were cervical, 30% were thoracic, 18% were in the region of conus medullaris, and 21% were lumbosacral. In contrast, out of 179 SNSTs analyzed by Conti et al., almost half were in the lumbosacral region, one-third in the thoracic region, and the rest in the cervical spine.

Two-thirds or more of all SNSTs are purely intradural. The rest all variably divide between pure extradural and dumb-bell tumors. In extremely rare cases, purely intramedullary schwannomas have been described. They presumably arise from aberrant Schwann cells or small nerves entering the spinal cord around penetrating spinal arteries.

In the series by Seppala et al. of 187 spinal schwannomas, 66% were intradural, 13% were extradural, and 19% were both intra- and extradural. Analyzing the series further, they found that cervical tumors had a higher likelihood of being purely extradural. They attributed this to the relatively short intradural cervical nerve roots, as compared to thoracic and lumbar roots. This has also been our experience at the University of Miami. In their series, 76% of cervical tumors had an extradural component, while this was the case only in 28% of thoracic tumors and 11% of lumbar tumors. Neurofibromas, on the other hand, are more commonly extradural or dumbbell-shaped. Jinnai and Koyama analyzed 149 cases of SNSTs and found that strictly intradural tumors compose only 8% of tumors of the first two cervical roots. The percentage of these tumors increased gradually from the high cervical region to the thoracolumbar region, where it was more than 80%. In contrast, the percentage of strictly extradural tumors gradually decreased from the cervical to the lumbar region. They also attributed these changes in the growth pattern to the anatomic features of the spinal nerve roots, which have a longer intradural component at the more caudal portion of the spinal axis.

Clinical Presentation

SNSTs occur equally in males and females. They usually peak in the fourth to fifth decades, and are uncommon in children and the elderly. About half of all IDEMs in adults are NSTs, compared with less than 5% in children. Most spinal tumors in children tend to be intramedullary.

On presentation, signs and symptoms are not specific to the tumors themselves but are related to the radiculopathy and myelopathy caused by these tumors at various spinal levels. Radicular pain is a common initial complaint and can be attributed erroneously to a prolapsed disc in the cervical or lumbar region. Local pain related to dural stretching is also not uncommon. Subjective sensory complaints are very common but can sometimes be difficult to define objectively. A sensory level may exist in advanced cases. Sensory deficit could be related either to the radiculopathy at the level of the tumor or to spinal cord compression of the dorsal columns and/or spino-thalamic tracts. This is in contrast with the early loss of pain and temperature and relative sparing of touch and proprioception in cases of intramedullary tumors. Focal lower motor neuron weakness could be seen in the upper or lower extremities in cases of cervical or lumbar SNSTs, again due to nerve root involvement, but this is uncommon compared with sensory findings. Spastic weakness due to compression of the corticospinal tracts can occur with cervical or thoracic tumors due to cord compression. Bladder and bowel involvement is usually late, and is more common in lesions affecting the conus.

Brown-Sequard syndrome is not uncommonly seen in these patients due to the frequent lateral/dorsolateral location of these tumors with respect to the spinal cord. Indeed, SNSTs are one of the most common causes of partial or complete Brown Sequard syndrome in clinical practice. The classic progression from radicular symptoms and segmental motor-sensory symptoms, to Brown-Sequard syndrome, then to complete cord impairment is rarely seen in modern times due to early diagnosis and intervention.

The presence of multiple tumors or tumors at a young age should raise the suspicion of NF, and an appropriate workup should be commenced, including imaging of the entire neuraxis.

Imaging Features

Magnetic resonance (MR) imaging is the modality of choice. Schwannomas are usually isointense (75%) or hypointense (25%) on T1, and hyperintense on T2-weighted images with intense contrast enhancement. Cystic changes may sometimes be seen in 20% to 40% of cases. MRI defines the anatomy in all three planes and reveals the tumor’s relationship to the spinal cord, nerve roots, and surrounding structures. These tumors usually remodel the surrounding structures, expanding in whatever space is available to them. Dumb-bell lesions are more common in the lower spine than in the cervical spine. Due to space constraints, dumb-bell tumors are smaller within the canal, but can expand to large sizes in the relatively open spaces of the retroperitoneum or the chest. Infiltration and invasion of surrounding structures is not seen unless there is a malignant change.

MR angiography (MRA) is obtained to identify the relationship of the tumor to the vertebral artery, especially in dumb-bell and extradural tumors. This is particularly important for surgical planning. If both MRI and MRA are inconclusive, regular angiography may be considered to define adjacent vascular anatomy. On rare occasions, preoperative embolization may be helpful if the tumor is large, has many flow voids on MRI, and embolization of the feeding vessels is feasible. A preoperative vertebral balloon occlusion test and planned vertebral artery sacrifice are other reasons for regular angiography to be obtained during the preoperative workup.

Computed tomography (CT) scanning may demonstrate tumor calcification and help in defining bony anatomy. The tumor itself is usually isodense to the cord on CT scans and enhances on contrast. CT scan is usually not indicated unless spinal stability is in question before or after surgery and the patient is being considered for bony fusion. This scenario is relatively uncommon.

Regular myelogram is mostly of historical interest and has largely been replaced by CT-myelogram. It is a useful modality in patients in whom MRI cannot be obtained, and defines both the bony anatomy and the level of the block in the spinal CSF.

Plain X-rays are no longer universally obtained in patients suspected of having SNSTs. They may demonstrate an enlarged neural foramen, increased interpedicular distance, scalloping of posterior vertebral bodies, and thinning of pedicles. These changes are nonspecific and are due to the slow growth of tumors over time causing bony remodeling. Some of these changes can be seen in NF-1, even without neurofibromas.