Primary spinal cord tumors comprise 3% to 4% of all primary central nervous system (CNS) tumors in adults.¹ Age-adjusted incidence rates are slightly higher for men than women, 0.68 versus 0.61 per 100,000 person-years, respectively.¹ Most of these tumors present as extramedullary tumors (70%), whereas intramedullary tumors are less common (30%). Approximately 15% to 25% of spinal tumors involve the cervical spine, including the foramen magnum; 50% to 55% involve the thoracic spinal canal; and 25% to 30% involve the lumbosacral spine.

In the pediatric population, spinal cord tumors are slightly more common, 5% to 6% of all primary CNS tumors.¹ Although ependymomas and nerve sheath tumors are the most common histologic types, gliomas make up a larger percentage of tumors in children as compared with adults¹ (Table 28-1).

TABLE 28-1 Distribution of Primary Spinal Cord Tumors by Histologic Type (CBTRUS 2010)

Histologic Type	Adult Distribution	Pediatric Distribution
Nerve sheath tumor	40.5%	15.7%
Glial origin
Ependymoma	33.6%	24.1%
Pilocytic astrocytoma	1.4%	12.6%
Other glioma	4.1%	13.3%
Meningeal tumor	6.1%	10.1%
Hemangioma	2.6%	NA

NA, not available.

The etiology of spinal cord tumors is largely unknown. Depending on the histologic type, they may be associated with genetic syndromes such as neurofibromatosis 1 and 2 as well as von Hippel-Lindau disease.

Prevention and Early Detection

There is no known method for prevention of spinal cord tumors. Early detection relies on careful neurologic examination and consideration of the possibility of a spinal cord tumor in the differential diagnosis. Because of the rarity of these tumors, there are no recommendations for routine screening, even in higher-risk populations.

Biologic Characteristics and Molecular Biology

The diversity of primary spinal axis tumors partly results from the large spectrum of phenotypically distinct cells in the axis that are capable of neoplastic transformation.² The genetic and molecular bases of spinal cord tumors are not yet well understood and vary depending on histologic findings.³ Most tumors are histologically benign but can cause significant morbidity by direct compression of important neural structures.

Histologic typing is an important prognostic factor in spinal cord tumors. Patients with ependymomas have a longer median survival time than those with astrocytomas. Additionally, low-grade (vs. high-grade) and pilocytic (vs. diffuse fibrillary) astrocytomas have a more favorable prognosis.

Anatomy, Pathology, and Pathways of Spread

Anatomy

Enclosed in the bony vertebral column, the spinal cord extends from the medulla oblongata of the brainstem to approximately the level of L1or L2 at the conus medullaris. It measures approximately 43 to 45 cm. The periphery of the cord is composed of white matter, which contains sensory and motor tracts, and the central region contains the butterfly-shaped gray matter, which houses nerve cell bodies. Three layers of meninges, the innermost pia mater, arachnoid mater, and outer dura mater, cover the elliptically shaped spinal cord and are continuous with the brainstem and brain. The delicate pia mater envelops the spinal cord and blood vessels. From this layer extend the denticulate ligaments, which connect with the dense, protective dura mater to stabilize the cord within the spinal canal. The dura mater terminates beyond the conus medullaris at the filum terminale, a strand of fibrous tissue that attaches to the coccyx, providing longitudinal support to the cord. Between these two layers lies the arachnoid, which is filled with cerebrospinal fluid (CSF).

The spinal cord is responsible for transmitting motor and sensory neural signals between the peripheral nervous system and the brain and contains its own independent pathways for coordinating certain reflexes (Fig. 28-1). Functionally, the cord is divided into 31 segments. At each level, a pair of spinal nerves exits: 8 cervical, 12 thoracic, 5 lumbar, and 5 sacral pairs and 1 coccygeal pair. In the cervical region, the spinal nerves exit above the corresponding vertebrae, whereas from the thoracic region and downward, the spinal nerves exit below the equivalent named vertebrae. Although the vertebral column continues to lengthen until adulthood, the canal and the cord are actually much shorter than the column because both stop lengthening at approximately 4 years of age. This growth differential is responsible for the formation of the cauda equina, a collection of the lower lumbar, sacral, and coccygeal nerves that fills the lower spinal column beyond the conus medullaris.

Figure 28-1 Spinal cord anatomy (1) Posterior column. (2) Lateral spinothalamic tract. (3) Lateral corticospinal tract. (4) Anterior horn cells. (5) Dorsal root. (6) Ventral root. (7) Dura. (8) Epidural space. (9) Vertebral body.

Adapted from Netter FH, Freidberg SR, Baker RA: Disorders of spinal cord, nerve root and plexus. In Netter FH, Jones HR Jr, Dingle RV [eds]: The Ciba Collection of Medical Illustrations, Vol 1. Nervous System, Part II. West Caldwell, New Jersey, Ciba-Geigy, 1986, pp 181-189. Copyright 1983. Novartis. Reprinted with permission from The Netter Collection of Medical Illustrations, Vol. 1, Part II. Illustrated by Frank H. Netter, M.D. All rights reserved.

The blood supply comes from a single anterior spinal artery (75%) and two smaller posterior arteries (25%). The cervical region relies on the vertebral and inferior cerebellar arteries, while the thoracic and lumbar regions depend on the radicular arteries. Venous drainage occurs through a vast complex network of plexuses.

Tumors are classified based on their location (Fig. 28-2). Intradural tumors include both intramedullary and extramedullary tumors. Intramedullary tumors develop from the cells that make up the spinal cord and cauda equina, and extramedullary tumors arise from the supportive tissues that lie outside the spinal cord and cauda equina, such as the meninges, vascular supply, and connective tissue. Extradural tumors arise from the vertebral canal itself or supportive tissues surrounding the dura.

Figure 28-2 Location within the spinal column. ed, extradural; ie, intradural extramedullary; ii, intradural intramedullary.

From Shiff D: Principles of Neuro-oncology. New York, 2005, McGraw-Hill.

Pathology and Pathways of Spread

The overall and anatomic distributions of histologic types are listed in Tables 28-1 and 28-2. Intradural extramedullary schwannoma (neurilemmoma) and meningioma are the most common intradural tumors, although occasionally they may present as extradural tumors. Other intradural extramedullary tumors include epidermoid and drop metastases of intracranial primary tumors such as medulloblastoma. The most common intramedullary tumors are those derived from glial precursors, most frequently, ependymomas and astrocytomas of low to intermediate grade. Nonneoplastic conditions may mimic spinal cord tumors (Fig. 28-3), including acute transverse myelitis, Angiostrongylus cantonensis infection, infectious meningitis, intradural disc hernia, pseudotumor, sarcoidosis, and tuberculosis.⁴^–⁸

TABLE 28-2 Anatomic Distribution of Spinal Tumors by Histologic Type

Extradural Tumors	Intradural Extramedullary Tumors	Intradural Intramedullary Tumors
Chondroblastoma Chordoma Chondrosarcoma Hemangioma Lipoma Lymphoma Meningioma Metastasis Neuroblastoma Neurofibroma Osteoblastoma Osteochondroma Osteosarcoma Sarcoma Vertebral hemangioma

Ependymoma, myxopapillary type

Figure 28-3 A pseudotumor, mimicking a neoplastic lesion, is shown in a sagittal-view, T1-weighted MR image with contrast (left) and in a T2-weighted image (right).

The predominant mode of spread of primary tumors is by direct extension. Spread along the subarachnoid space with spinal or cranial involvement of the meninges may also occur. One should not always assume that the spinal cord tumor found on imaging is the primary lesion. Although CSF seeding is uncommon, supratentorial tumors that show a tendency toward leptomeningeal metastases include 1.2% of glioblastomas and 1.5% of anaplastic gliomas.⁹ There are no lymphatics in the spinal cord, and hematogenous spread is rare.

Clinical Manifestations, Patient Evaluation, and Staging

The clinical presentation of tumors of the spinal axis is a function of the local anatomy (see Fig. 28-1). Within the spinal canal, there exists a well-defined extradural space containing epidural fat and blood vessels. The extradural space communicates with adjacent extraspinal compartments via the intervertebral foramina.

A spinal cord tumor produces local and distal symptoms and signs; the latter reflect involvement of motor and sensory long tracts within the spinal cord. These allow localization of the level of the lesion based on clinical findings.

Clinical Workup

The diagnostic approach to primary spinal cord tumors is shown in Figure 28-4. In addition to focusing on neurologic symptoms, the history should include an evaluation of the patient’s functional status and symptoms, which may suggest metastatic disease or nonmalignant causes of spinal cord tumors.

Figure 28-4 Diagnostic algorithm for primary spinal cord tumors. CSF, cerebrospinal fluid.

Physical examination should involve an extensive neurologic assessment. Flaccid weakness, atrophy, fasciculations, and reduced deep tendon reflexes are seen in corresponding myotomes with involvement of the anterior horn cells and the ventral roots (lower motor neuron lesions). A tumor involving the lateral corticospinal tracts can cause weakness, spasticity, extensor plantar response (Babinski’s sign), and hyperreflexia (upper motor neuron lesion). Motor weakness and spasticity are seen with tumors above the conus medullaris. Weakness and flaccidity are seen with tumors below the conus because the tumors compress the peripheral nerve roots of the cauda equina. A tumor restricted to the conus should not cause weakness, although one also involving the cauda equina or the lumbar enlargement of the spinal cord will do so.

Sensory impairment often helps to localize the level of the tumor based on loss of dermatome function, although the upper level of impaired long-tract function may be several segments below the actual tumor (Fig. 28-5). A lesion involving the lateral spinothalamic tract causes numbness, paresthesias, and decreased temperature sensation over the contralateral limb or trunk below the lesion. This produces the classic finding of a sensory level, which is best demonstrated with a pin or a large metal or cold object to test temperature sensation and with observation for absence of perspiration. A lesion in the posterior column causes an ataxic or tabetic gait. Standing posture is affected with the eyes closed (Romberg’s sign). Paresthesias can occur below the level of the lesion.

Figure 28-5 Anterior (A) and posterior (B) views of the dermatomes. C, cervical; T, thoracic; L, lumbar; S, sacral.

CREDIT LINE: Adapted from Netter FH, Freidberg SR, Baker RA: Disorders of spinal cord, nerve root, and plexus. In Netter FH, Jones HR Jr, Dingle RV (eds): The Ciba Collection of Medical Illustrations, Vol 1. Nervous System, Part II. West Caldwell, New Jersey, Ciba-Geigy, 1986, pp 181-189; Keegan JJ, Garrett FD: The segmental distribution of cutaneous nerves in the limbs of man. Anat Rec 102:409, 1948.

Because pain and temperature pathways cross over in the spinal cord and proprioceptive and motor pathways do not, a unilateral spinal cord lesion can result in ipsilateral paralysis and proprioceptive loss as well as contralateral pain and temperature loss below the level of the lesion. Because light touch travels in two pathways, one that crosses in the spinal cord (spinothalamic tract) and one that does not (posterior columns), it is usually spared in unilateral lesions. This combination of findings is known as the Brown-Séquard syndrome.

Both genitourinary and bowel symptoms can result from a spinal cord tumor. Bladder symptoms include hesitancy, dribbling, incontinence, urgency, or acute retention. Loss of bladder control is seen early in the presentation of tumors in or below the conus and later in tumors above the conus. Cone lesions above L1 can lead to impotence or reflex priapism. Lesions involving S2 to S4 may produce loss of erection and ejaculation ability. Decreased genital sensation can occur from lesions affecting the S2 nerve roots. If bowel control is affected, constipation occurs more frequently than incontinence.

The most common presenting symptom from spinal canal tumors is pain, caused by nerve root compression, bony destruction, or, more subtly, pressure on the dura or deafferentation. The pain may be radicular, midline, or centrally located. Radicular pain is secondary to involvement of the posterior roots and is typically described as shooting pain in the dermatomal distribution. The nerve can be compressed inside of or outside of the dura. Midline spinal pain presents as discomfort localized to the area of the tumor and is thought to arise from pain-sensitive structures in the dura and extradural tissues. Characteristically, pain is more severe with extradural lesions. With spinal cord compression, a dull or burning pain, more widespread than segmental spinal or radicular pain, sometimes occurs. This type of pain, although relatively rare, has numerous designations, including central pain, causalgia, and deafferentation pain. It involves a limb or trunk below the lesion. Pain is the most common presenting symptom in patients with sacrococcygeal tumors. Headache may be caused by elevated intracranial pressure, which is unusual in patients with primary spinal cord tumors, with the exception of large tumors involving the foramen magnum. It can be caused by upward seeding of the tumor or by the development of carcinomatous meningitis from malignant tumors.

The clinical presentation of a spinal tumor rarely indicates whether it is extradural or intradural. However, intramedullary tumors can cause a characteristic neurologic syndrome. Early on, decreased temperature and pain sensation occurs in the dermatomes of the spinal segments occupied by the tumor and two or three segments caudal to the lesion. Other sensory modalities are not diminished while the tumor is confined to the central cord. This “dissociated” sensory loss is rarely seen with extramedullary tumors. Additionally, weakness and atrophy are early findings in the myotomes of the corresponding cord segments involved by tumor. As the tumor grows transversely, reflexes produced at the level of the tumor disappear and spastic paralysis with hyperreflexia develops below the lesion. Eventually, all sensory modalities are affected. Cervical tumors can produce Horner’s syndrome by interrupting unilateral autonomic pathways.

Lesions in the conus medullaris can produce several symptoms, including saddle anesthesia, acute urinary retention, incontinence of bowel and bladder, and impotence. If the lesion remains confined to the conus, it will not cause paralysis of the lower limbs and the ankle reflexes are preserved. More commonly, tumors originating in the conus are diagnosed when they have enlarged enough to cause signs characteristic of intramedullary tumors. These findings can also be mixed with those caused by growth of the tumor in the direction of the cauda equina, such as radicular pain.

Lesions of the cauda equina can cause radicular pain in the thigh, weakness, and atrophy of muscles, including the gluteus, hamstring, gastrocnemius, and anterior tibialis muscles. Saddle anesthesia, absent ankle reflexes, impotence, urinary urgency or acute retention, and constipation are also commonly seen. Depending on the location of the lesion, other reflexes may be affected.

Neuroimaging

Certain tumors may display characteristics on plain films such as the calcifications seen in meningiomas. Increased intracranial pressure can cause enlargement of the bony spinal canal, erosion of the pedicles, and scalloping of the posterior wall of the spinal canal. Computed tomography (CT) can be useful for evaluating the vertebral column in extradural tumors. Myelography has been replaced by more advanced, less invasive imaging but can be useful in patients who cannot tolerate MRI,

MRI is the diagnostic study of choice in the evaluation of intramedullary and extramedullary spinal cord lesions. A complete description of the fundamentals of MRI is beyond the scope of this chapter. Most spinal cord tumors enhance with contrast medium, the most common exception being World Health Organization (WHO) grade II gliomas. Edema appears as an area of low-signal intensity on T1-weighted MRI images and high-signal intensity on T2-weighted MRI images. Tumor infiltration may be differentiated from edema by suppression of cerebrospinal fluid (CSF) signal using fluid-attenuated inversion recovery (FLAIR) sequences. MR spectroscopy may help to differentiate tumor from spinal cord necrosis by evaluating the regional distribution of chemicals associated with energy metabolism in the tumor. Imaging of the entire neuraxis is strongly recommended in the initial workup, and brain imaging should be performed in patients with ependymomas.

Cerebrospinal Fluid Examination

Examination of CSF may occasionally be useful for differential diagnosis and for monitoring of therapeutic response. Because of the risk of herniation caused by increased intracranial pressure, neuroimaging studies should precede lumbar puncture. When obstruction of CSF flow occurs because of tumor expansion, patients can develop hydrocephalus; be wary of performing a lumbar puncture in a patient with a spinal cord tumor who presents with a headache.

CSF examination is especially useful in the management of tumors that may seed the subarachnoid space and spread via the CSF, such as medulloblastoma and ependymoma. The appearance of xanthochromic CSF, because of high protein content with an absence of erythrocytes, is characteristic of spinal cord tumors obstructing the subarachnoid space and is examined for malignant cells (cytologic testing), protein, and glucose. A high protein concentration with normal glucose levels and normal cytologic findings is seen in spinal cord tumors, although if the tumor has seeded the meninges, the glucose level may be low and cytologic testing may reveal a malignant tumor.

Histologic Confirmation of Disease

The approach for histologic confirmation depends on the clinical presentation and suspected histologic type. The morbidity of potential biopsy should be weighed against the benefits of confirming the histologic type and whether it would change management. Image guidance can be used to improve safety and efficacy of biopsy. In patients presenting with acute spinal cord compression, surgical decompression should be considered to relieve progression of neurologic symptoms and establish a diagnosis.

Staging

There are no routine staging systems for the classification of spinal tumors.

Primary Therapy

General Principles of Surgery

Surgery has traditionally been the mainstay of therapy for spinal cord tumors.¹⁰ As modern diagnostic and therapeutic techniques such as MRI, the operating microscope, microsurgical tools, and intraoperative neurophysiologic assessment have become available, more aggressive surgical intervention has become a more prevalent treatment strategy.¹¹ This section will discuss general principles of surgery for CNS lesions, depending on anatomic location within the spinal cord. The outcome of surgery and its role in multidisciplinary management are described in the sections for each individual type of tumor. Table 28-3 shows an overview of the outcomes of the most common spinal cord tumors by treatment modality.

TABLE 28-3 Outcomes of the Most Common Spinal Cord Tumors by Treatment Modality

Surgery of Intramedullary Tumors

The most common intramedullary tumors are ependymomas and astrocytomas. Modern series advocate maximum safe resection of intramedullary spinal tumors. The ability to resect these tumors completely varies widely, from less than 10% to as much as 86%, depending on the histologic type.^12,¹³^–¹⁹ Most completely resectable lesions are WHO grade I tumors because higher-grade tumors are defined by their infiltrative potential.^16,²⁰^–²⁴ The gross total resection (GTR) rates for ependymomas range from 19% to 100%, whereas 0% to 43 % of astrocytomas are resectable.²⁵^–²⁸ For infiltrative astrocytomas, the role of surgery is most frequently limited to biopsy for diagnosis. Laminectomy offers limited functional benefit by decompressing the spinal cord in the case of bulky infiltrative tumors. Functional postoperative outcomes may be excellent in selected cases, with the majority of patients (72% to 79%) experiencing either improvement or stabilization of their preoperative presenting symptoms, often after transient postsurgical worsening.^12,^19,^29,³⁰ The incidence of total, permanent postoperative paralysis is reported at 1%.¹¹ Paralysis is often the result of unpredictable, sporadic vascular events.

Intramedullary tumors are almost always approached through a laminectomy exposure with the patient in the prone position.¹¹ After the dura is opened, a longitudinal myelotomy is made over the widened region of the spinal cord, where imaging demonstrates the closest approximation of the tumor to the surface and the incision is deepened several millimeters until the tumor surface is reached. Infiltrative tumors with poorly defined dissection planes cannot be removed completely and, therefore, biopsy for diagnosis is often the safest course of action. When there is an exophytic component to the tumor, maximum safe debulking is typically performed.

Both intramedullary and extramedullary tumors can be associated with a CSF-filled syrinx dilating the central canal. The preferred treatment is tumor removal. If this is not possible, even modest shrinkage of the tumor by means of irradiation can stabilize or even reduce the size of a syrinx. Postoperatively, a syrinx can form from scarring in the central canal. A syrinx drainage procedure may not result in a significant improvement in neurologic function, and the apparent benefit is stabilization or slowing of the decline in function.

Postoperative Management

Corticosteroids are routinely administered before, during, and after surgery to minimize edema of the spinal cord. Intravenous or oral dexamethasone or high-dose intravenous methylprednisolone is most often the agent of choice. Once maximum symptom resolution has occurred, usually approximately 7 days after high-dose glucocorticoids are begun, tapering of steroids as rapidly as possible without resultant symptomatic worsening minimizes the chance for and extent of the numerous serious side effects of these agents.

Complications of Surgery

In patients who are neurologically intact before surgery, the incidence of significant acute morbidity is generally below 5% for extramedullary tumors and as low as 5% for carefully selected patients with intramedullary tumors.¹¹ Spinal deformities, including scoliosis and kyphosis, as well as infection and CSF leakage, can occur.^31,³² The development of postlaminectomy spinal deformities is a serious postoperative complication, occurring in up to 40% of pediatric and adolescent patients, and may be observed as soon as 8 months postoperatively.³³

General Principles of Radiation Therapy

The intent of radiation therapy in the treatment of spinal cord tumors is to improve local control and neurologic function while potentially increasing survival times. Outcomes of radiation therapy and its role in multidisciplinary management are described in the subsequent section for each individual type of tumor.

Because of the potential for growth and developmental side effects, the use of irradiation in children and infants with spinal cord tumors is controversial. Some authors do not recommend postoperative radiation therapy, and suggest that observation with close imaging follow-up and re-resection at the time of second occurrence is a better approach.¹² With this strategy, radiation therapy may be avoided or used only for children with multiply recurrent tumors.

General Principles of Chemotherapy

The efficacy of chemotherapy may be limited by the intact blood–nervous system barrier. Regional drug delivery may be in the form of intracerebrospinal fluid therapy, intra-arterial infusion, and intratumoral therapy. Extramedullary spinal tumors gain their blood supply from meningeal blood vessels that are significantly more permeable than those of the brain, and chemotherapy may be of more use for these tumors. Drugs that have some efficacy in treating primary CNS malignant tumors and that are thought to cross the blood-brain barrier have been used in the treatment of malignant glial tumors of the spinal cord; however, no clear benefit from the use of chemotherapy has been demonstrated thus far.*

Locally Advanced Disease and Palliation

The principles of treatment are the same for patients with more locally advanced disease and palliation as for definitive treatment. Because of the severity of symptoms related to lack of control of spinal cord tumors, in most cases the dose should not be substantially decreased, although this may be a consideration with very large fields. End-stage patients requiring palliation of pain and mass effect are typically treated based on the general principles of palliative management, and the reader is referred to the chapter on the corresponding topic. For radiotherapeutic palliation, fractionation regimens are similar to those used for spinal column metastases.

Irradiation Techniques and Tolerance

Definitions of Treatment Volumes

Three-dimensional treatment planning based on International Commission on Radiation Units (ICRU) volume definitions is the norm.^39,⁴⁰ The gross target volume (GTV) represents the grossly visible disease burden. Typically, this is the T1-enhancing abnormality on MRI or the nonenhancing tumor seen on T2 or FLAIR images. If there is no residual abnormality after a surgical resection, the tumor resection cavity is defined to be the GTV. Surrounding edema is not considered part of the GTV. The clinical target volume (CTV) is the T2 or FLAIR abnormality (which does include edema) on MRI as well as any areas potentially containing microscopic disease. Suggested definitions and doses to be delivered to the GTV and CTV are listed by histologic diagnosis in Table 28-4. The planning target volume (PTV) adds a dosimetric margin that takes into account uncertainties in daily treatment setup and physiologic variations that are difficult or impossible to control, such as (potential) fluctuations in the mass effect from cord edema that may occur over the course of treatment. Organs at risk typically include the thyroid and salivary glands, esophagus, lungs, heart, stomach, small bowel, liver, kidneys, bladders, ovaries, testicles, and uninvolved portions of the spinal cord itself.

Treatment Techniques

The most common approaches include a single posterior field (PA), opposed lateral fields, a PA field with opposed laterals, and oblique wedge-pair fields.⁴¹ They are typically designed to treat the CTV and GTV. For tumors in the cervicothoracic region, a split-beam approach is sometimes used. The central axis is placed just above the shoulders. Opposed lateral fields are used to treat the upper spine, whereas a PA field is used for the area of the spine below. Tumors in the thoracic region are often treated with a three-field approach using a PA field and opposed lateral beams. In the lumbar region, care must be taken to minimize the dose to the kidneys; a four-field approach using AP/PA and opposed lateral beams with the AP/PA beams preferentially weighted may be useful.

The advent of intensity-modulated radiation therapy (IMRT) techniques now allows for the development of sophisticated treatment plans, using several beam directions and treatment fields. It is therefore crucial to compare different treatment and field setups using dose-volume histograms in order to select the most appropriate option.

Certain neoplasms require treatment of the entire craniospinal axis. Several modifications of this approach are used in clinical practice (Fig. 28-6). Patients may be treated either in the supine or prone position, often in an immobilization cast to ensure daily positional reproducibility.^42,⁴³ The intracranial contents, including the upper one or two segments of the cervical cord, are treated through opposed lateral fields. Customized blocks protect the normal head and neck tissues from the primary radiation beam. The spine is treated through one or two posterior fields, depending on the size of the patient. In one method, the collimator for the lateral cranial fields is angled to match the divergence of the upper border of the adjacent spinal field, and the treatment couch is angled so that the inferior border of the cranial field is perpendicular to the superior edge of the spinal field. Alternatively, one may dispense with collimator and couch angles by calculating appropriate gaps. The gap is calculated so that the 50% isodose lines meet at the level of the anterior spinal cord. All junction lines are moved 0.5 to 1 cm every 8 to 10 Gy to avoid overdosing or underdosing segments of the cord. This is accomplished by shortening the inferior margin of the lateral cranial fields, symmetrically lengthening the superior and inferior margins of the posterior spinal field, and shortening the cranial margin of the caudal spinal field; a fixed block is placed at the inferior margin of the caudal spinal field to keep the lower margin of the irradiated volume at the same location.

Figure 28-6 Two- and three-dimensional treatment planning images of craniospinal axis radiation therapy. Patients are treated in the supine or prone position, and an immobilization cast often is used to ensure positional reproducibility. Intracranial contents and the upper one or two segments of the cervical cord are treated through opposed lateral fields. Customized blocks protect the normal head and neck tissues from the primary radiation beam. The spine is treated through one or two posterior fields.

IMRT is a treatment delivery method that may be used to further optimize the dose distribution. Because multiple critical sensitive organs are located near the spinal cord, improved dose distribution should allow the dose to these structures to be minimized. Because most spinal cord tumors typically recur locally, IMRT should allow the exploration of anatomic/biologic treatment planning and delivery in order to optimize different doses to different cell populations within heterogeneous volumes. The use of image guidance may also allow for reduced margins for sparing of critical structures. The use of IMRT is currently under investigation at multiple institutions.^44,⁴⁵

Stereotactic radiosurgery (SRS) and body radiotherapy (SBRT) deliver a highly conformal high dose of radiotherapy with stereotactic guidance. Doses may be delivered as a single dose (SRS) or as a short fractionated course (SBRT). Potential advantages include patient convenience with a shorter treatment course and the steep dose gradient at the edge of the field, which may allow for greater tissue sparing. SRS for primary spinal cord tumors remains experimental at this time but is an active area of research.⁴⁶^–⁴⁸

Tolerance of the Spinal Cord and Lumbosacral Nerve Roots

A dose of 45 to 50.4 Gy in 25 to 28 fractions over 5 or weeks is usually considered to be safe. The risk of myelopathy is less than 1%, well below the steep portion of the dose-response curve.^46,^49,⁵⁰ It is estimated that with conventionally fractionated irradiation (1.8 to 2 Gy per fraction in five fractions per week), at 5 years the incidence of myelopathy is 5% for doses in the range of 57 to 61 Gy (tolerance dose TD_5/5) and 50% for doses of 68 to 73 Gy (TD_50/5).⁴⁹ There is no convincing evidence that the cervical and thoracic cord differ in their radiosensitivity and there appears to be little change in tolerance with variations in the length of cord irradiated.⁴⁹ Table 28-5 shows a range of isomorbid fractionation schemes, all of which carry a 5% risk of radiation myelopathy.

TABLE 28-5 Fractionation Schemes with a 5% Risk of Radiation-Induced Spinal Cord Myelopathy

Dose per Fraction (Gy)	No. Fractions	Total Dose (Gy)
2	29	58
3	13	39
3.3	11	33
4	7	28
5	5	25
10	1	10

Data from references 50, 98, 116, 206–209, 210, 211–214.

The tolerance of the lumbosacral nerve roots appears to be somewhat higher than that of the spinal cord. Most series report a 0% complication rate if patients are treated to doses of 70 Gy (or equivalent) as long as fraction sizes are kept at or below 2 Gy.⁵¹^–⁵³

The Quantitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) reviewed data from preclinical, conventional, reirradiation, and SBRT studies in order to refine normal tissue dose/volume tolerance guidelines.⁵⁴ Based on this, a total dose of 54, 60, or 69 Gy with conventional 2-Gy once-daily fractionation was associated with a myelopathy rate of less than 1%, 6%, and 50%, with a calculated strong dependence on dose/fraction (α/β = 0.87 Gy). With reirradiation of the full cord cross section at conventional fractionation, cord tolerance appears to increase at least 2% at 6 months after an initial course of radiation therapy. For partial cord irradiation as part of spinal SRS, a maximum cord dose of 13 Gy in a single fraction or 20 Gy in three fractions appeared to have a minimal (<1%) risk of injury.⁵⁵

Primary Therapy By Tumor Type

Astrocytoma

Astrocytomas represent 7% to 11% of all primary spinal tumors. They are the most common intramedullary spinal cord tumors and comprise 35% to 45% of all reported cases of intramedullary tumors. The median age at presentation is approximately 35 years.^16,⁵⁶^–⁵⁸ There does not appear to be a difference in the age of presentation between low- and high-grade tumors.¹⁶ In children, 75% to 90% of intramedullary spinal cord tumors are astrocytomas and 85% to 95% of these are low-grade, fibrillary, or juvenile pilocytic astrocytomas (Fig. 28-7). Fewer than 10% of pediatric and 25% of adult spinal cord astrocytomas are malignant.*

Figure 28-7 MRI of an upper cervical spine pilocytic (WHO grade I) astrocytoma. Shown are (left to right) sagittal-view, T1-weighted; coronal-view, fluid-attenuated inversion recovery (FLAIR); coronal-view, T1-weighted view with contrast; axial-view, T1-weighted, spoiled gradient-recalled (SPGR) with contrast; and axial-view, T2-weighted image.

Motor weakness is the most common presenting symptom in astrocytomas, occurring in up to 87% of patients. The median time from onset of symptoms to diagnosis ranges from 6 months to 2 years.^16,^41,^57,⁶⁰ In general, high-grade astrocytomas tend to have a shorter prodrome (median duration, 1.6 to 7 months) than low-grade tumors (median duration, 2 years).^16,^29,⁵⁶ Tumor dissemination by spread along the subarachnoid space is reported in up to 58% of patients with high-grade astrocytomas.^56,⁶¹ Approximately 1% of WHO grade III to IV spinal cord astrocytomas have multifocal disease at presentation.¹⁰

Prognostic Factors

The most significant prognostic factors in patients with primary spinal cord astrocytomas are tumor histology, grade, and performance status.† High histopathologic grade is typically associated with a high risk of mortality and short median survival time. The 10-year overall survival (OS) of patients with pilocytic astrocytomas is 81%, in contrast to 15% for patients with diffuse fibrillary astrocytic tumors.⁶⁹ For patients with WHO grade I to II spinal cord astrocytomas, the 5-year OS are 48% to 89%, but they are only 0% to 33% for WHO grade III to IV lesions; the latter have a median survival time of approximately 6 months.^56,^58,^60,^65,⁷⁰ Other factors thought to be prognostic include young age (patients <18 years old live the longest, whereas those >40 years of age do poorly); the pattern of failure (local vs. disseminated, with the latter pattern developing in approximately 60% of patients with high-grade tumors); and duration of symptoms prior to diagnosis (<6 months vs. >6 months, with patients with a short duration doing worse).‡ In most series, neither extent of resection nor adjuvant radiation therapy appears to be prognostic, although this remains controversial.§

Treatment and Outcomes

The treatment of choice for intramedullary astrocytomas is complete excision of the tumor, when it can be safely accomplished without neurologic compromise.⁷⁵ Otherwise, an incomplete excision is typically performed for grade I lesions and biopsy alone is the surgical strategy for the nonexophytic component of an infiltrative glioma. Gross total resection (GTR) is typically extremely difficult to achieve due to the infiltrative nature of all but the pilocytic lesions, with most authors reporting a 0% to 50% likelihood of GTR for spinal cord astrocytoma.* In patients with favorable prognostic factors (low-grade histologic findings, good performance status, and young age), observation with serial imaging studies, reserving irradiation for local recurrence, is an appropriate management option, particularly for young children.^11,^65,^70,⁷⁷ In the remainder of patients, adjuvant irradiation (RT) is usually recommended because progression of tumor in the spinal cord may lead to significant neurologic impairment.† Doses have traditionally been based on the experience with cerebral tumors, with lower-grade tumors typically receiving 45 to 54 Gy and high-grade tumors receiving higher doses.^41,^77,⁷⁹

The overall outcomes are similar for patients with low-grade gliomas of the spinal cord treated either by GTR or subtotal resection (STR) or biopsy followed by external beam irradiation (EBRT), with most series reporting OS at 5 and 10 years in the ranges of 55% to 100% and 39% to 83%, respectively, and disease-free survival (DFS) of 38% to 93% and 26% to 80% at 5 and 10 years, respectively. Postoperative EBRT has shown a survival benefit for patients with infiltrative gliomas (24 months vs. 3 months) but not with pilocytic tumors.^41,⁶⁶ However, postoperative EBRT may improve progression-free survival (PFS) in low-grade and intermediate-grade astrocytomas.⁶⁶ Overall long-term local control rates for gliomas range from 31% to 100%, with grade being the strongest predictor.‡ A comparison of survival and local control rates is shown in Table 28-3.

With high-grade tumors in adults and children, the median survival time is quite poor (4 to 10 months) despite surgery and EBRT; approximately two thirds of patients die of both local and disseminated disease.§ One small series suggested a survival benefit for patients with high-grade tumors treated with craniospinal axis irradiation.⁸²

Data specific to adjuvant chemotherapy (after surgery and/or radiation therapy) for spinal cord astrocytomas are scant and composed mostly of small retrospective series.^23,^35,^37,⁷² In two small trials, children with high-grade spinal astrocytoma had a 5-year PFS of 46% to 50% and a 5-year OS of 54% to 88% when chemotherapy was given either in the adjuvant setting or at the time of relapse.^37,⁷² Overall, although there is no clear evidence of a difference in outcomes with or without chemotherapy for spinal cord tumors, chemotherapy is usually given for patients with malignant astrocytoma.^34,⁸³ Temozolomide has shown modest activity in patients with recurrent disease.⁸⁴

Ependymoma

Ependymomas, which are glial tumors, are approximately equal in incidence to astrocytomas. The mean age at presentation is 30 to 39 years. These tumors are more common in adults than in children, and in males than in females.^85,⁸⁶ The median duration of symptoms prior to presentation is 2 to 4 years.^16,^28,^57,⁸⁶ Two-thirds occur in the lumbosacral region, 40% from the filum terminale^28,⁸⁷ (Fig. 28-8). Because of the propensity of these tumors for seeding the craniospinal axis, CSF evaluation and craniospinal MRI are strongly recommended for patients diagnosed with ependymoma. It is also important to note that 11% of patients with intracranial ependymomas have documented spinal metastases, so imaging of the brain may be indicated to rule out a primary brain tumor⁸⁸ (Fig. 28-9).

Figure 28-8 MRI of a sacral ependymoma. Shown are T1-weighted image with contrast medium (left) and T2-weighted sagittal image (right).

Figure 28-9 MRI of a myxopapillary ependymoma with drop metastases. Shown are T1-weighted, coronal-view image (left) and sagittal-view image (right), both with contrast enhancement.

Pathology

Ependymomas arise from ependymal cells and typically occur in the central canal of the spinal cord, the filum terminale, and the white matter adjacent to a ventricular surface. They are either low-grade tumors or anaplastic tumors, the latter being more likely to disseminate via the CSF. The majority of tumors are of a low grade.^14,^27,^57,⁸⁹ Myxopapillary ependymomas are low-grade tumors that typically occur in the lumbosacral region (filum terminale), are well-differentiated, and are often encapsulated but can seed the CSF, typically going to the thecal sac.^90,⁹¹ Myxopapillary ependymomas often progress slowly and cause milder-than-expected neurologic deficits for their size. Some published series have included ependymoblastomas; however, these are primitive neuroectodermal tumors (PNETs), which have a high propensity to disseminate throughout the CNS and therefore should be considered in the medulloblastoma-PNET family of tumors.

Prognostic Factors

Multiple factors have been reviewed in the literature as being prognostic for local recurrence and survival. Factors prognostic for a favorable outcome include patient age less than 40 years; tumors with a lumbosacral location, myxopapillary histologic findings, and/or a grade of World Health Organization (WHO) grade I; tumors amenable to GTR or STR; and good preoperative function of the patient.* Some authors believe that the volume of residual disease appears to correlate with a worse outcome after EBRT, whereas other authors have found no differences in outcomes when comparing complete excision with STR followed by EBRT.^27,^87,⁹⁴^–⁹⁶ Myxopapillary subtypes appear to be associated with a favorable prognosis, potentially because of ease of resection due to their anatomic location.⁹² Five-year OS for the myxopapillary subtype and for WHO grade I tumors are 97% to 100%, and the 5-year disease-specific survival (DSS) is 97%.^93,⁹⁴ Recently, the expression of erb-B2 and erb-B4 has been identified as a negative prognostic marker, especially in intracranial ependymomas, but the prognostic significance of these substances in spinal ependymomas is not clear.

Treatment and Outcomes

Most intradural extramedullary ependymomas are myxopapillary and are often amenable to complete surgical resection if they are not multifocal.^86,^90,^97,⁹⁸ The goal of surgery is GTR. Every attempt should be made to remove myxopapillary tumors as a whole as opposed to piecemeal removal, because of the risk of seeding, including upward seeding to the cranial nerves. The potential for cure may increase the severity of a hopefully transient deficit that surgeon and patient may be willing to incur and illustrates the importance of prospective multidisciplinary management of these tumors. Typically, complete resection is achievable in 79% to 100% of modern series.* Some authors report complete resection rates as low as 19% to 50%, but these data tend to be from older series or those with a significant number of high-grade tumors.^16,^57,^76,^87,⁹² Five- and 10-year OS for all spinal cord ependymomas is 67% to 100% and 68% to 100%, respectively.† DSS at 5 and 10 years is 69% to 96% and 62% to 93%, respectively.^16,^89,⁹² Local control rates after GTR are 95% to 100%.^14,^26,⁹⁹ Late failures may occur more than 4 years after curative surgery, particularly with the myxopapillary subtype, so long-term follow-up is warranted.^101,¹⁰²

Postoperative EBRT appears to improve local control in patients with subtotally resected ependymomas, with all high-grade lesions, and with craniospinal axis dissemination (positive CSF or MRI scan); not all authors agree on this, with many series showing increasing age to be the most significant predictor.‡ In most series, the outcome for STR followed by EBRT appears to be similar to that of complete excision. Typically, the dose given to the tumor bed is 49 to 56 Gy, whereas the craniospinal axis (if indicated) receives 30 to 36 Gy.^27,^93,⁹⁹ Low-grade lesions with a low risk of seeding are typically treated with limited fields to 50.4 to 55.8 Gy in 1.8-Gy daily fractions. In patients with tumors at high risk of seeding, when pretreatment CSF cytologic studies reveal malignant cells, or if the spinal MRI scan shows evidence of leptomeningeal disease, the craniospinal axis should be treated to 36 Gy in 1.5- to 1.8-Gy daily fractions. Subsequently, the primary tumor site is boosted to a total dose of 50.4 to 55.8 Gy. If gross leptomeningeal spread is evident, the craniospinal axis dose should be 39.6 Gy (1.8 Gy/fraction) or 40.5 Gy (1.5 Gy/fraction), with the same boost dose to the primary tumor as previously discussed.

In patients undergoing incomplete resection followed by EBRT, OS at 5, 10, and 15 years is 67% to 100%, 67% to 100%, and 75%, respectively.^26,^27,^66,^93,⁹⁴ Cause-specific survival (CSS) at 5, 10, and 15 years for all tumors is 74% to 93%, 50% to 93%, and 35% to 46%, respectively.^66,^89,^92,¹⁰⁸ CSS at 5 years is 87% to 97% for myxopapillary and low-grade lesions and 27% to 71% for high-grade tumors.^93,⁹⁴ DFS at 5 and 10 years is 59% and 59%, respectively.⁹² Local control rates are 88% to 100%.^27,^94,^99,¹⁰⁹

There is no strong body of evidence thus far demonstrating that the addition of chemotherapy to EBRT improves the outcome.^36,^38,¹¹⁰^–¹¹² A single trial of etoposide for recurrent spinal ependymoma has shown a median response duration of 15 months, with a median survival time of 16 months.³⁸ Patients who were responders had a median survival time of 20 months, whereas those who did not respond lived only 4 months; the results approached statistical significance. Pediatric patients with anaplastic ependymoma or ependymoblastoma are routinely given chemotherapy.^113,¹¹⁴ A recent trial has started evaluating cytotoxic agents in combination with erb-B inhibitors, but further clinical research in this area is necessary.

Meningioma

Spinal meningiomas make up only 8% of all meningiomas but 25% to 46% of all spinal neoplasms.^115,^116,¹¹⁷ They tend to occur in females three to seven times more commonly than in males.§ Most patients are over the age of 40 years, with a mean age at diagnosis of 49 to 63 years.^118,¹¹⁹ The incidence appears to be bimodal, the first peak being in the third decade of life, with a second larger peak seen after age 50 years, especially in the sixth and seventh decades of life.^118,¹¹⁹ In younger patients, 13% have neurofibromatosis type 2.¹¹⁹ Younger patients (<50 years of age) have a recurrence rate of 23% versus 5% in older patients, though not all authors agree that young age in and of itself carries a worse prognosis.^115,¹¹⁹

The most common site is the thoracic region, where 55% to 80% of tumors occur, whereas cervical lesions make up approximately one-third of all lesions.^115,^116,^118,^119,¹²⁰ The incidence by location varies with age: before age 50 years, 39%, 56%, and 5% of lesions occur in the cervical, thoracic, or lumbar spine, respectively; in patients over age 50 years, 16%, 80%, and 5% occur in the cervical, thoracic, or lumbar spine, respectively.¹¹⁹

Treatment and Outcomes

The mainstay of treatment of spinal meningiomas is surgical resection. Meningiomas in most patients can be removed through a posterior (laminectomy) approach because they are commonly in a lateral or anterolateral location, and even the more anteriorly placed tumors cause enough lateral displacement of the spinal cord to allow access for resection without traction on the spinal cord. If the tumor is located anterior to the spinal cord, it may require an anterior approach, including corpectomy with arthrodesis. Anteriorly situated meningiomas are sometimes unresectable because of their encasement of the anterior spinal cord or because they lie at the foramen magnum of a vertebral artery.

Functional improvement of neurologic deficits is seen in 66% to 100% of patients.^31,^118,^120,¹²¹ Complete resection is achievable in 82% to 100% of cases, with a 1% to 6% late local failure rate.^116,^120,¹²¹ With STR, late local recurrence rates range from 17% to 100%.^31,^116,¹²¹ Because local failures can take place even decades after surgery, the actual late failure rate may be even higher, similar to that seen in patients with intracranial meningiomas. In one large series, after complete resection, recurrence-free rates at 5, 10, and 15 years were 93%, 80%, and 68%, respectively, and after STR, recurrence-free rates at 5, 10, and 15 years were 63%, 45%, and 9%, respectively.¹¹⁵ Therefore, the necessity for life-long follow-up cannot be overemphasized. Because local failure rates in the spine are higher with STR, some authors recommend radiation therapy.

The role of irradiation is not well understood due to the small number of cases reported in the literature, and most clinicians extrapolate from the data on irradiation of intracranial meningiomas.^118,^120,¹²² The expected outcome of radiation therapy is long-term stabilization of disease.¹²³ Patients who undergo complete resection should be observed. Even those with STR who either have improvement of their neurologic status or are asymptomatic postoperatively can be closely followed. When patients are irradiated, the dose delivered is typically 52.2 to 54 Gy, based on the data from the treatment of intracranial meninigoma.¹²³ Single-fraction SRS must be considered investigational at this time.^124,¹²⁵

Hydroxyurea chemotherapy has been used but has minimal activity.¹²⁶

Chordoma

Chordomas are slow-growing neoplasms thought to be remnants of the embryonic notochord. They make up approximately 4% of spinal tumors. Approximately 24% to 35% arise in the region of the base of the skull; as many as 17% are thought to have originated in the cervical spine; 11% to 15% are known as chordomas of the mobile spine and arise in the true vertebral region (usually, the lumbar region); and 50% to 58% arise in the sacrococcygeal region.^127,^128,¹²⁹ Most chordomas occur during the fourth decade of life, with a male to female ratio of 2 to 1, though sacrococcygeal chordomas tend to arise in the fifth and sixth decades.^53,^130,¹³¹^–¹³⁴

Prognostic Factors

Several prognostic factors have been identified. Location is prognostic for survival, with a 5-year OS of 66% for sacrococcygeal tumors and 50% for vertebral lesions.¹³⁵ Overall, 14% to 39% of patients develop metastases at a median of 5 years, most commonly to the lungs.* The incidence of metastases varies by location of the primary tumor: 26% to 44% of patients with sacrococcygeal lesions develop metastatic disease (usually to the thecal sac), whereas 61% of those with vertebral primaries can metastasize, typically in a caudal direction. In some series, skull base lesions have rarely been reported to metastasize.^53,¹³² Gender may also be prognostic: 5-year and 8-year local control rates are 81% and 75% for men and 65% and 17% for women, respectively.^139,¹⁴⁰ The prognostic importance of age is controversial; in some series, children have a higher incidence of metastases, but in other series, patients over the age of 52 years have a worse local control rate.^127,^141,¹⁴² Finally, residual microscopic disease after resection (either tumor spillage or positive margins) increases the risk of local relapse to 60% to 64% from 25% to 28% after GTR.^134,¹⁴³ Primary tumor size less than 8 cm has also been suggested as a good prognostic factor.¹⁴²

Treatment and Outcomes

Although en bloc GTR has traditionally been advocated for these lesions, it is rarely possible. As such, most patients undergo STR or biopsy followed by EBRT. However, surgery is an important component of treatment despite potential morbidity; a recent large database review showed that patients who had undergone resection had significantly prolonged survival times.¹⁴² In most series, patients have been treated with conventional photon radiotherapy, typically to doses of 55 to 70 Gy in 2-Gy fractions, with 5-year OS of 38% to 58%.† Although EBRT prolongs the disease-free interval, most tumors recur unless they have also been completely resected; local progression is the most common cause of death.¹³⁰ In one older series, the local control rate of sacrococcygeal tumors was 0% with either surgery or EBRT as monotherapy but 40% when the two were combined.¹²⁹

Some treatment series using conventional photon radiation therapy suggest that local control rates improve with increasing radiation doses. With doses of less than 40 Gy, more than 48 Gy, more than 50 Gy, and more than 55 Gy, 5-year DFS is approximately 0%, 13%, 31%, and 41%, respectively.^53,¹⁴⁵ However, not all authors have found that increased dose improves outcome.^147,¹⁴⁸

In order to improve the therapeutic ratio when treating residual or recurrent disease, most authors now advocate a combination of photon and charged particle therapy (typically, with protons).^127,^135,¹⁴⁹^–¹⁵⁶ When patients are treated either immediately after maximum resection or at the time of recurrence, with median doses of 65 to 76 Gy equivalents using charged particle radiation therapy (with or without photons), local control rates at 3, 5, and 10 years are 67% to 71%, 40% to 75%, and 54%, respectively, with OS at 3, 5, and 10 years at 88% to 97%, 75% to 80%, and 54%, respectively.^52,^127,^152,^153,¹⁵⁷

SRS has also been used in the treatment of residual and recurrent cervical spine chordoma. A mean dose of 19 Gy in a single fraction prescribed at the tumor margin resulted in a 4-year local control rate of 80% without neurologic sequelae in one series.¹⁵⁸

The experience with interstitial irradiation is minimal. This modality has fallen out of favor with the advent of charged particle therapy and radiosurgery.¹⁵⁹^–¹⁶¹

Chondrosarcoma

Primary chondrosarcoma of the spine is a rare, slowly growing tumor thought to originate from primitive mesenchymal cells or from the embryonal rests of the cranial cartilaginous matrix. Spinal chondrosarcomas are slightly more common in men than in women.¹⁶² The mean and median ages of presentation are 45 years and 51 years, respectively.^163,¹⁶⁴ Of the axial skeleton chondrosarcomas, 33% occur in the mobile spine, most often in the thoracic region.^163,¹⁶⁴ Another 33% arise in the sacrum.¹⁶⁵

Patients with spinal chondrosarcomas typically have a long-term OS of 25% to 54%.¹⁶²^–¹⁶⁴ ¹⁶⁶ Adverse prognostic factors include positive surgical margins, high tumor grade, and older patient age.^165,¹⁶⁶ Twelve percent to 19% of lesions are grade 4 tumors, which carry a poor prognosis (3-year OS of only 14%; median survival time of 2.7 years; 75% to 86% incidence of metastases).^165,¹⁶⁶

Treatment and Outcomes

Surgical resection is the mainstay of treatment of these lesions. OS after any degree of resection is 55% to 72%, 67%, and 63% at 5, 10, and 15 years, respectively.^164,¹⁶⁵ The median survival time is typically 6 years, with local control rates ranging from 36% to 72%.¹⁶³^–¹⁶⁶ Patients with GTR have a better outcome than those with STR. After complete resection, the local control rate is 97%, with a 90% 10-year OS and an 84% DFS.¹⁶⁵ Many chondrosarcomas have indolent courses, but others behave more aggressively. Radiation therapy after incomplete resection has been shown to lengthen the disease-free interval from 16 to 44 months in one series.¹⁶³ Chemotherapy has not been shown to improve outcomes.¹⁶³

Miscellaneous Primary Spinal Tumors

Chloroma

Spinal canal chloroma (also known as granulocytic sarcoma) is defined as an extramedullary localized tumor mass of blasts of granulocytic lineage. This tumor can arise during the course of acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS), either at the same time as the initial tumor or at relapse, but also as an isolated tumor without any signs of medullar involvement. Spinal chloromas occasionally precede the development of systemic disease by weeks to years. Spinal complications of chloromas, such as cord compression secondary to epidural tumor or cauda equina syndrome, have been described but are uncommon. The median age at presentation is 22 years, with a 7.8:1 male-to-female ratio. The thoracic spine is most commonly involved (73%), followed by the lumbar region (34%), sacral region (23%), and cervical region (5%). Multiple noncontiguous areas of involvement are found in 18% of patients.

The most effective treatment appears to be multimodality therapy coupled with early diagnosis. Options include surgical decompression, intravenous and/or intrathecal chemotherapy, radiation therapy at doses of 20 to 30 Gy or any combination of these treatments. Patient survival times range from 18 days to 9.5 years after diagnosis. In a review of the literature, no clear relationship could be found between the specific treatment modality used and the length of survival. Those receiving systemic therapy soon after diagnosis experienced the longest disease-free episodes, however.¹⁶⁷

Epidermoid Tumor

Epidermoid tumors are rare tumors of male preponderance, most commonly found in the lumbosacral region. Complete surgical excision is usually curative. Incompletely excised tumors may recur, but due to their slow growth, this may take several years.

Hemangioblastoma

Intramedullary hemangioblastomas are slowly growing vascular tumors composed of endothelial and stromal components and account for 3% to 13% of intramedullary spinal tumors.^61,⁶⁴ The male to female ratio is 1.8 to 1.¹⁶⁸ The median age at presentation is 36 years for sporadic lesions, whereas patients with von Hippel-Lindau syndrome typically present a decade earlier and have multiple tumors. Multiple CNS hemangioblastomas are diagnostic of von Hippel-Lindau syndrome. Multiply recurrent hemangioblastoma may also raise the suspicion of von Hippel-Lindau syndrome. Patients with isolated spinal hemangioblastoma should be screened for other manifestations of von Hippel-Lindau syndrome by ophthalmologic evaluation, brain MRI, and abdominal CT scanning to rule out retinal and cranial hemangioblastoma and renal tumors, respectively. In patients with von Hippel-Lindau syndrome, 51% of neuraxis lesions are located in the spinal cord and only 29% are completely intramedullary, with the remainder having an extramedullary component¹⁶⁹ (Fig. 28-10).

Figure 28-10 MRI of a spinal hemangioblastoma with an associated syrinx in the setting of von Hippel-Lindau syndrome. Shown are a T1-weighted image with contrast enhancement (left) and a T2-weighted sagittal-view image (right).

Factors prognostic for favorable outcome (defined as improvement or stabilization of neurologic function) are minimal or no preoperative neurologic deficits, lesions smaller than 0.5 cm², dorsally located lesions, and total surgical removal of the lesion.^169,¹⁷⁰ Progressive syringomyelia is a negative prognostic factor with respect to preservation of neurologic function and is often recalcitrant to treatment attempts.

Surgical resection is the mainstay of treatment for symptomatic lesions. Hemangioblastomas are extremely vascular tumors occurring in the spinal intramedullary compartment. The dorsal location of most of these lesions and the commonly associated cyst help to simplify the removal somewhat because the cyst provides a safe route for approaching the tumor. Removal of the enhancing tumor is satisfactory to prevent reaccumulation of the cyst, and the remainder of the cyst wall may, therefore, be left intact. Tumor margins are addressed first and feeding arteries are coagulated. Then the tumor is dissected and removed en bloc. After surgical resection, 41% to 68% of patients experience improvement of neurologic function and another 32% to 84% have stabilization of their preoperative function.^168,^169,¹⁷¹

Although SRS is an option for cerebellar hemangioblastoma, it has not been properly evaluated for spinal hemangioblastoma because of concerns regarding the radiation tolerance of the spinal cord. A small series suggests safety and efficacy.^172,¹⁷³

Lipoma

Primary spinal lipomas are benign, congenital, intradural-extramedullary lesions located in the cervicothoracic region. These tumors account for approximately 1% of spinal cord tumors. The classic presentation is that of a slow ascending spastic monoparesis or paraparesis with rapid late deterioration.

Early surgical decompression is mandatory for preservation of existing neurologic function, but complete surgical debulking is almost impossible due to the infiltrative nature of the tumors.¹⁷⁴^–¹⁷⁶ There is no known role for radiation therapy or chemotherapy.

Lymphoma

Primary spinal cord lymphomas are uncommon lesions. Only 4% of lymphomas are primary epidural tumors of which 90% are of B-cell origin ^177,¹⁷⁸ (Fig. 28-11). Typically, lymphomas involving the spinal cord are seen in the context of primary CNS non-Hodgkin’s lymphoma, with 27% having positive CSF findings and 16% eventually developing leptomeningeal disease involving the spine.¹⁷⁸

Figure 28-11 MRI of a lymphoma involving the bone and spinal cord. Shown is a sagittal-view, T1-weighted image with contrast enhancement.

If the initial presentation is one of spinal cord compression, management is similar to that of other metastatic tumors described below, although rapid responses may be seen with steroids, chemotherapy, and irradiation to a median dose of 38 Gy.¹⁷⁷ Lengthy administration of preoperative steroids may result in disappearance of the tumor by the time of surgery (ghost-tumor effect). Otherwise, management is similar to that of cerebral non-Hodgkin’s lymphoma. After decompressive laminectomy, subtotal tumor resection, and spinal irradiation, the local control rate is 60%, with a median duration of survival of 42 months.¹⁷⁷

Neurocytoma

Central neurocytoma has been reported to arise in the spine.^179,¹⁸⁰ Staining for synaptophysin and neurospecific enolase allows these tumors to be reliably distinguished. As in the brain, their behavior is variable. Because this tumor arises centrally in the spinal cord, observation or irradiation may be the primary management strategy, with resection reserved for tumors with progressive neurologic deficits.

Sarcoma

Primary sarcomas of the spinal cord are exceedingly rare, accounting for 0.7% of CNS malignant tumors; 5.6% of these are found in the spinal canal.¹⁸¹ Malignant fibrous histiocytoma represents the most common histologic diagnosis; tumors arise from the nerve roots of the cauda equina, the spinal cord, or the spinal blood vessels.^181,¹⁸² Surgical debulking and postoperative EBRT to approximately 60 Gy in 1.8- to 2-Gy fractions represents the typical treatment approach described in the literature.^181,¹⁸² The 5-year OS of patients with high-grade lesions is significantly worse at 28% than the 83% reported with low-grade lesions. The role of chemotherapy is not known.

Schwannoma

Spinal schwannoma may present simultaneously in both the spinal canal and the thoracic cavity. These dumbbell-shaped tumors are typically benign and may involve the spinal cord and spinal nerves via the neural foramina. Surgical resection is the treatment of choice.^32,^183,¹⁸⁴ Schwannomas arise from spinal rootlets (most often, the dorsal rootlets) and may grow along the nerve root in a dumbbell fashion through a neural foramen. Therefore, resection requires removal of sections of the involved rootlets. Only 3% of these tumors are malignant; adjuvant EBRT has been used in such cases.¹⁸⁵ Outcomes are mixed.^183,¹⁸⁵

Teratoma

True intramedullary teratoma is an extremely rare tumor, with only nine cases reported in the literature. Early surgical resection is recommended to preserve neurologic status. Because teratomas may adhere to the functional neural tissue of the spinal cord in such a way that no dissection plane is available, complete resection is often not possible. A low-grade histopathologic status predominates, so the symptomatic recurrence of incompletely resected mature teratomas is often slow and may eventually require a second surgical procedure.¹⁸⁶ Radiation therapy is generally reserved for multiply recurrent, subtotally resected disease.

Vertebral Hemangioma

Vertebral hemangiomas are benign growths of endothelial origin typically located in the thoracic and upper lumbar spine. They are the most common benign spinal column tumors, with an incidence of approximately 11%. Because vertebral body hemangiomas are most frequently stable over long periods of time, some authors consider them to be nonneoplastic. Growth causing progressive symptoms has been documented. Only 1% to 2% of patients develop clinically significant pain. New onset of back pain followed by subacute progression of a thoracic myelopathy, typically over a period of 4 to 5 months, is the most common presentation for patients with neurologic deficit.¹⁸⁷ These tumors also occasionally cause root and cord compression syndromes. A preoperative diagnosis of compressive vertebral hemangioma can be made from 65% of radiographs and 80% of CT examinations, whereas asymptomatic vertebral hemangioma is much more easily recognized with this imaging combination.¹⁸⁸

Treatment is initiated only when progressive symptoms, including focal pain or progressive neurologic deficit, develop. Historically, standard treatment consisted of surgical removal of the lesion. Endovascular embolization of these very vascular growths may also provide pain control. Vertebroplasty has high reported rates of success. The local control rate at 3 years is 70%. Of lesions that regrow, 90% recur within the first 2 years.¹⁸⁹

Irradiation is an effective treatment alternative. A meta-analysis demonstrated that a total dose of 30 Gy given in 2-Gy fractions resulted in a 57% complete amelioration of pain and 32% partial improvement of pain.¹⁹⁰ A second, smaller analysis showed an apparent dose-response effect. Patients treated with the biologic equivalent 36 to 44 Gy in 2-Gy fractions had significantly better complete pain relief than those treated with 20 to 34 Gy (82% vs. 39%, respectively).¹⁹¹

Treatment Complications

Radiation myelopathy may present as a transient early delayed or late delayed reaction. Transient radiation myelopathy is clinically manifested by momentary, electrical shock-like paresthesias or numbness radiating from the neck to the extremities, precipitated by neck flexion (Lhermitte’s sign).¹⁹² The syndrome typically develops 3 to 4 months after treatment and spontaneously resolves over the following 3 to 6 months without therapy. It is attributed to transient demyelination caused by radiation-induced inhibition of myelin-producing oligodendroglial cells in the irradiated spinal cord segment.¹⁹²^–¹⁹⁴

Irreversible radiation myelopathy usually is not seen earlier than 6 to 12 months after completion of treatment. Typically, half of the patients who develop radiation-induced myelopathy in the cervical or thoracic cord region will do so within 20 months of treatment and 75% of cases will occur within 30 months.¹⁹⁵ The signs and symptoms are typically progressive over several months, but acute onset of plegia over several hours or a few days is possible. It is thought to be multifactorial in origin, involving demyelination and white matter necrosis ultimately due to oligodendroglial cell depletion and microvascular injury. The diagnosis of radiation myelopathy is one of exclusion; a history of radiation therapy in doses sufficient to result in injury must be present. The region of the irradiated cord must lie slightly above the dermatome level of expression of the lesion; the latent period from the completion of treatment to the onset of injury must be consistent with that observed in radiation myelopathy; and local tumor progression must be ruled out.

There are no pathognomonic laboratory tests or imaging studies that conclusively diagnose radiation myelopathy. MRI findings include swelling of the spinal cord with hyperintensity on the T2-weighted images with or without areas of contrast enhancement.^193,¹⁹⁶ There is no known consistently effective treatment for radiation myelitis.^197,¹⁹⁸ The probability of dying from radiation myelopathy is approximately 70% with cervical lesions and 30% with thoracic spinal cord injury.¹⁹⁹

Radiation side effects in children include growth abnormalities such as decreased vertebral height, kyphosis, and scoliosis.²⁰⁰ Secondary malignant disease, including bone or soft tissue sarcomas and glioblastoma multiforme lesions, has been reported after irradiation of spinal cord tumors.²⁰¹^–²⁰³

Treatment Algorithm, Challenges, and Future Possibilities

Treatment Algorithm

Primary tumors of the spinal cord are uncommon lesions. Much of the literature groups these tumors together by location (intramedullary vs. extramedullary) when reporting outcomes. However, spinal cord tumors clearly behave differently depending upon the histologic type, and this needs to be taken into account when making management decisions. Nonetheless, the primary treatment for most spinal cord tumors continues to be surgical resection, with irradiation recommended for patients in whom a complete resection cannot be achieved and for those at high risk of recurrence. The role of chemotherapy in the management of spinal cord tumors remains unclear. A general simplified treatment algorithm is shown in Figure 28-12.

Figure 28-12 Treatment algorithm for the general management of primary spinal tumors. Details about the histologic diagnosis and radiation therapy are provided in the text and Table 28-4.

Challenges and Future Possibilities

The most significant future advances one may anticipate are the possibilities of noninvasively obtaining an accurate tissue diagnosis of a suspicious spinal cord lesion and accurately measuring treatment response. To this extent, novel MRI contrast agents could serve as biochemical reporters of various cellular functions.²⁰⁴ These newer contrast agents could be tailored to report on the physiologic status or metabolic activity of biologic systems: enzyme-activated agents correlate developmental biologic events with gene expression; calcium-activated agents can measure intracellular signal transduction; pH-activated agents provide a blood oxygen level-dependent (BOLD) signal that might be used for noninvasive mapping of human nervous system function; and T2-activated agents can detect specific oligonucleotide sequences. The agents of interest are currently under investigation in the setting of primary brain tumor treatment, and it remains to be seen how the results will be applied to spinal cord therapy. Regarding toxicity, better refinements in dose and volume tolerance are necessary, with improvements presented in the recent QUANTEC study.⁵⁵ Long-term data on patients treated with hypofractionated regimens and SBRT are awaited.

Critical References

1 CBTRUS. Statistical report. Primary brain and central nervous system tumors diagnosed in the United States in 2004-2006. Hinsdale, Illinois: Central Brain Tumor Registry of the United States; 2010.

2 Cancer International Agency of Research on Cancer (IARC): World Health Organization Classifiction of Tumours: Pathology and Genetics: Tumours of the Nervous System, ed 2. Oxford University Press, Lyon, France, 2000..

12 Constantini S, Miller DC, Allen JC, et al. Radical excision of intramedullary spinal cord tumors. Surgical morbidity and long-term follow-up evaluation in 164 children and young adults. J Neurosurg. 2000;93:183-193.

32 Seppala MT, Haltia MJ, Sankila RJ, et al. Long-term outcome after removal of spinal schwannoma. A clinicopathological study of 187 cases. J Neurosurg. 1995;83:621-626.

34 Stewart LA. Chemotherapy in adult high-grade glioma. A systematic review and meta-analysis of individual patient data from 12 randomised trials. Lancet. 2002;359:1011-1018.

36 Robertson PL, Zeltzer PM, Boyett JM, et al. Survival and prognostic factors following radiation therapy and chemotherapy for ependymomas in children. A report of the Children’s Cancer Group. J Neurosurg. 1998;88:695-703.

37 Doireau V, Grill J, Zerah M, et al. Chemotherapy for unresectable and recurrent intramedullary glial tumours in children. Brain tumours subcommittee of the french society of paediatric oncology (SFOP). Br J Cancer. 1999;81:835-840.

40 ICRU Report 62. Prescribing, recording and reporting photon beam therapy (supplement to ICRU Report 50). Besthesda, Maryland, Nuclear Technology, 1999.

41 Minehan KJ, Brown PD, Scheithauer BW, et al. Prognosis and treatment of spinal cord astrocytoma. Int J Radiat Oncol Biol Phys. 2009;73:727-733.

50 Marcus RBJr, Million RR. The incidence of myelitis after irradiation of the cervical spinal cord. Int J Radiat Oncol Biol Phys. 1990;19:3-8.

66 Abdel-Wahab M, Etuk B, Palermo J, et al. Spinal cord gliomas. A multi-institutional retrospective analysis. Int J Radiat Oncol Biol Phys. 2006;64:1060-1071.