Clival and Craniovertebral Junction Chordomas

Chordomas are rare, aggressive, locally destructive tumors of presumed notochordal origin that arise along the vertebral axis and show a proclivity for the spheno-occipital and sacral regions.^1,9,37,47 Chordomas of the clivus and craniovertebral junction are the most common extradural neoplasms in this region. The overall incidence of chordomas is 0.2 to 0.5 per 100,000 persons per year, and they account for about 0.15% of all intracranial tumors. About 25% of chordomas occur at the base of the skull, arising from the clivus. Although usually midline, the notochord may have distal projections that extend to the clinoid processes of the petrous bones. Most patients experience symptoms referable to the tumor for more than a year before diagnosis.

Pathology

Chordomas have been divided into classic chordomas, chondroid chordomas, and atypical chordomas.⁴⁸ Classic chordomas are lobulated, pinkish gray, gelatinous tumors that infiltrate bone but may appear grossly as somewhat demarcated; they account for 80% to 85% of all chordomas. Histologically, they exhibit a variable mix of sheets and cords or clusters of small polygonal cells with eosinophilic cytoplasm and hyperchromatic nuclei. A myxoid matrix is present. Cytologic atypia is absent or minimal.

A subpopulation, the chondroid chordoma, arises in the spheno-occiput and exhibits cartilaginous differentiation. Some authors dispute the existence of chondroid chordomas, preferring to regard these cartilage-containing neoplasms as chondrosarcomas. Chondroid chordomas have a more indolent clinical course; the survival rate is 15.8 years, compared with 4.1 years for typical classic chordomas.^47,48 Chondroid chordomas account for 5% to 15% of all chordomas.

Atypical chordomas have a sarcomatoid appearance, with round cells and epithelial or spindle cells present with large areas of necrosis. These solid tumors are aggressive and account for 1.3% to 8% of all chordomas. In the series by Heffelfinger and coworkers, only one patient with an atypical chordoma survived more than 10 years, whereas almost 50% of those with chondroid chordomas survived more than 10 years.⁴⁸ The frequency of mitotic figures, nuclear pleomorphology, and hyperchromatism does not appear to affect the ultimate outcome.^49,50 In rare circumstances, chordomas may dedifferentiate into malignant chondrosarcomas, fibrosarcomas, and even osteosarcomas.⁵¹

The immunohistochemical profile of reactivity with antibodies to vimentin cytokeratin, epithelium membrane antigen, and S-100 protein tend to distinguish chordomas from other sarcomatoid round cell or myxoid neoplasms.^49,50 Chondrosarcomas are negative for cytokeratin, epithelium membrane antigen, and carcinoembryonic antigen. Vimentin and S-100 protein are present in both chondrosarcomas and chordomas. Immunostaining from keratin has no prognostic value regarding the aggressiveness of the tumor. Chondrosarcomas have been lumped with chordomas because of supposed parallel lines of occurrence, location, and aggressive behavior.

Imaging Characteristics

Cranial-based chordomas are clearly defined by the use of high-resolution CT, on which they appear as solitary or multiple areas of decreased attenuation within the clivus. T2-weighed MRI reveals a bright signal from the marrow in the skull base, signifying replacement of bone by tumor.^9,25 At times, calcification is noted in the abnormal areas in the retropharyngeal space, representing sequestered bone fragments in tumor. Chordomas enhance with intravenous contrast and are well visualized by MRI. Chordomas are isointense on T1-weighted MRI (Fig. 308-2).

FIGURE 308-2 A, Composite of parasagittal and midsagittal gadolinium-enhanced magnetic resonance imaging (MRI) of the head and upper spinal canal in a 42-year-old women with craniocervical chordoma. She presented with dysphagia, nasal regurgitation, unsteady gait, headaches, and tongue atrophy. Note the hindbrain herniation as a result of the tumor mass. B, Composite of T1-weighted gadolinium-enhanced MRI in the axial plane through the fourth ventricle (left) and foramen magnum (right). There is retropharyngeal as well as extradural and intradural tumor that engulfs the left vertebral artery. C, Reformatted computed tomography (CT) of the craniovertebral junction in the frontal projection through the plane of the odontoid process. The occipital condyles are eroded bilaterally. D, Composite of postoperative T1-weighted MRI in the parasagittal and midsagittal plane at the craniocervical junction. The hindbrain herniation has receded significantly. There is no evidence of tumor visible 11 years after transpalatopharyngeal resection of the clivus and craniovertebral junction chordoma.

Presentation

Chordomas usually occur in adults, with a peak incidence occurring in the fourth decade of life.^9,47,52 Less than 5% of these tumors arise in children, and they have a predilection for the spheno-occipital region.⁵ Headaches are often occipitocervical in location and aggravated by changes in craniovertebral positioning. In my series, 55% of patients benefited from craniovertebral stabilization in addition to tumor resection, owing to involvement of the occipital condyles.^15,25 Lateral extension of these tumors can give rise to unilateral symptoms, such as hypoglossal nerve palsy. Larger tumors have the potential to cause both upper and lower cranial nerve palsies and a variety of problems related to brainstem compression. Chordomas often cause symptoms from local growth into the nasal cavity, pharynx, and paranasal sinuses.

Surgical Series

Although the number of reported cases of untreated intracranial chordoma is small, only brief survival after diagnosis is a consistent finding. Several series of aggressive surgical extirpation followed by conventional radiation and proton-beam therapy are discussed here.

Forsyth and colleagues reviewed 51 intracranial chordomas treated surgically between 1960 and 1984 at the Mayo Clinic.⁵² The median age at presentation was 46 years, and 19 tumors were classified as chondroid chordomas. Eleven patients (22%) underwent biopsy, and 40 patients (78%) had subtotal resection. The survival rates for patients who underwent biopsy were 36% and 0% at 5 and 10 years, respectively, whereas survival rates for those with subtotal resections were 55% and 45% at 5 and 10 years, respectively. Patients who underwent postoperative radiation therapy tended to have longer disease-free survival times. Disease-free survival was the same for patients with chondroid chordomas as for those with typical chordomas.

Watkins and associates described 38 patients treated at the National Hospital of Neurology and Neurosurgery in London between 1958 and 1988.⁵³ Craniotomies were used in 28 patients, and transoral or transmaxillary routes were used in 10 others. All patients underwent postoperative external-beam radiotherapy of 50 to 60 Gy. Recurrence developed in 23 patients, and 13 died within 5 years. Twelve patients were lost to follow-up. The authors concluded that two groups existed: one with indolent disease and another with aggressive growth and poor outcome.

In a more recent publication in 2001, Crockard and associates described a multidisciplinary approach to skull base chordomas.⁵⁴ A primary first time surgery was done in 24 and redo surgery (initial surgery elsewhere) in 18. A total removal was made in 2, radical 30 and subtotal or partial in the remainder. However, morbidity was significant, with CSF leak in 15, meningitis in 3, new cranial nerve abnormalities in 6 and persistent dysphonia in 4 patients. Three patients died.

Gay and colleagues reviewed the management of 46 chordomas and 14 chondrosarcomas involving the cranial base between 1984 and 1993 at the University of Pittsburgh.⁴⁷ They recommended an aggressive approach to achieve long-term recurrence-free survival. Fifty percent of patients had undergone previous surgery before referral, and 22% had undergone previous external-beam radiation therapy. The surgical approach was a subtemporal-infratemporal fossa approach, sometimes combined with a transpetrous approach. In other instances, an extended subfrontal approach was used, and in a few cases, the lateral transcondylar approach was used. There was a high tendency to stay between the subtemporal-infratemporal fossa approach and the extended subfrontal approach. Using this technique, the rate of total or near-total resection was 67%. Eighteen patients had died by the 5-year follow-up. Postoperatively, 20% of patients underwent external-beam, proton-beam, or gamma radiation therapy. In patients who had total resection, the overall 5-year recurrence-free survival rate was 84%, compared with 64% in those with partial resection. However, the rate of morbidity was high. Thirty percent developed CSF leaks, 10% experienced meningitis, and 80% had an immediate new cranial nerve deficit. Using the Karnofsky performance score, 40% of patients had permanent functional deterioration. Based on this experience, the authors advocated aggressive initial surgical resection, with the sparing application of radiation therapy.

In 1997, Al-Mefty and Borba reported their results with an aggressive surgical approach combined with postoperative proton-beam therapy in 25 patients treated between 1990 and 1996.⁹ Radical or subtotal (>90%) removal was achieved in 84% of patients undergoing multiple procedures, when necessary, and extensive drilling of bone beyond the limits of tumor involvement. Postoperatively, 68% of the patients received a mean of 68-cGy–equivalent proton-beam radiotherapy. The postoperative mortality rate was 4%. The postoperative rate of morbidity, however, was 48%, although only 8% suffered permanent neurological deficits. Eighteen percent of the patients treated with proton-beam therapy developed radiation necrosis. The mean follow-up was only 25 months, however, making conclusions about outcome and survival difficult.

In a subsequent follow-up, Colli reviewed the series of Al-Mefty published in 2001.⁵¹ There were 55 chordomas and 10 chondrosarcomas. Follow-up of 1 to 150 months was reported, with a median of 38 months. A radical or subtotal removal was performed in 77.8% of patients. At 5-year follow-up, the mortality rate was 14.3%. The recurrence-free survival rates were 100% for chondrosarcomas and 50.7% for chordomas. Of those who received proton-beam therapy, 90.9% survived, as opposed to only 19.4% who received conventional postoperative radiation therapy. However, the complication rate was 60%, and 28.6% had a permanent worsening in neurological deficit. A transient deficit was present in 22.8%, which included new cranial nerve palsy, CSF leak, and hydrocephalus. The authors concluded that the survival was best with radical resection followed by proton-beam therapy.

Maira and coworkers³⁷ achieved total tumor removal in 7 of 10 patients undergoing repeated transsphenoidal procedures for chordoma. They reported no evidence of disease in these patients at a mean of 38 months after surgery and encountered a cranial nerve complication in only 1 patient.

Couldwell and colleagues reported on a variation of the standard transsphenoidal approach to the sella with emphasis on extended approaches and parasellar approaches.³⁶ This series of 105 patients reported in 2004 included 18 clivus chordomas. Total removal was accomplished in 66%. A hemiparesis was seen in 1 patient and new cranial nerve deficits in 2 patients, and an internal carotid occlusion was also found. Three patients had internal carotid artery hemorrhage, and 1 patient had a CSF leak, which was persistent. No deaths were reported.

During the past 15 years, cranial-based exposures of the clivus and upper cervical-craniovertebral chordomas have become accepted. Thus, it is important to compare recent series with at least a 5- to 10-year follow-up. Since 1985, 25 males and 18 females with cranial-base chordomas have been treated at the University of Iowa Hospitals and Clinics.^15,25 Fourteen (34%) had undergone previous surgery; 11 (25%) had undergone previous radiation therapy, 5 of whom had proton-beam therapy. The 43 patients underwent 49 skull base procedures, and 9 required stabilization. Fifteen patients underwent a transoral-transpalatopharyngeal approach, 8 underwent a transmaxillary approach, 6 underwent a transsphenoethmoidal approach, 4 underwent an infratemporal fossa primary approach, 4 underwent a lateral extrapharyngeal approach, 6 underwent a transcondylar approach, 5 underwent a transfacial approach, and 1 underwent a transbasal approach. Gross total resection was possible in 12 of the 43 individuals (Fig. 308-3). Subtotal resection (>90%), which was documented on postoperative MRI, was achieved in 14 individuals. Seven patients died during the 15-year follow-up period. All patients had typical chordomas and underwent detailed histologic and immunohistochemical analysis of the tumor. Of the 15 individuals who underwent a transpalatopharyngeal approach, 5 died, 3 patients within 2 years of the transoral procedure at my institution. Each of these 3 patients had previously undergone more than four operative approaches to the tumor and had also undergone proton-beam therapy. The time from proton-beam radiation to the recurrence presenting at my institution was less than 3 years. There were no cases of postoperative CSF leakage, meningitis, or new cranial nerve deficits.

FIGURE 308-3 A, Axial gadolinium-enhanced magnetic resonance imaging (MRI) through the skull base in a patient with chordoma of the clivus and the anterior midline skull base. He presented with difficulty breathing, left sixth nerve palsy, and pain in the left trigeminal distribution. The tumor extends between the two pterygoid plates and occupies the anterior midline skull base with clival erosion. The carotid arteries are encased. B, Midsagittal gadolinium-enhanced MRI of the skull base revealing extensive tumor in the anterior midline skull base from the cribriform plate including the dorsum sellae to the anterior atlantal arch. C, Postoperative axial MRI through the plane of the lower brainstem and the anterior cranial base. The patient underwent a Le Fort I drop-down, swing-door maxillotomy with tumor resection. He underwent postoperative proton-beam therapy. It is now 9 years after his operative procedure. D, Postoperative gadolinium-enhanced midsagittal MRI of the head and face. There is enhancement of the dural graft and the tectorial membrane.

Samii and associates,⁵⁵ in a recent review of 49 patients who had undergone resective surgeries at a single institution, came to the conclusion that complete tumor removal was accomplished in 49% and subtotally in 51%. The 5- and 10-year survival rates were 65% and 39%, respectively.

Chordomas in children are rare.^3,5,56–59 Classic chordoma is seen in 28% and atypical chordoma in 72%. Thus, the prognosis reflects atypical lesions. All children with atypical lesions died within a mean of 6 months. Patients with classic chordomas treated within the past 10 years have survived a mean of 17 months. Metastasis occurs in about 60% of children younger than 5 years.

In a clinical pathologic study of 73 cases of children and adolescents referred to the Massachusetts General Hospital for proton-beam therapy for skull base chordoma between 1981 and 2003, good control with proton-beam therapy was achieved in children.⁵⁶ Metastasis occurred in 58% of children younger than 5 years, whereas only 8.5% of those older than 5 years had subsequent metastasis. In an earlier combined study from Loma Linda, California, chondrosarcomas fared better over the long term than chordomas, and tumor recurrences were thought to be higher in patients who had tumor volume of more than 25 mL.⁶⁰

Radiation Therapy

The role of radiation therapy in the management of skull base chordomas is now fairly well established. Amendola and colleagues concluded that conventional radiation therapy provided better local control when administered postoperatively than when delivered for a recurrence after surgical resection.⁶¹ Patients receiving more than 80 Gy had an 80% local control rate, whereas those receiving 40 to 60 Gy had a 20% success rate. There has been a consistent movement toward achieving a higher dosage with conventional external-beam radiotherapy. Radiation therapy itself has severe risks, including tumor recurrence, brain radiation necrosis, and radiation vasculitis.

In 1993, Forsyth and coworkers reported the results of 39 patients treated with surgery and conventional radiation therapy.⁵² The overall survival rates were 51% at 5 years and 35% at 10 years. Fractionated proton-beam therapy exploits favorable dose-localization characteristics and can deliver between 70 and 80 Gy to the tumor, whereas nearby nervous structures receive much lower doses. Researchers at both Harvard and Berkley Laboratory have published results with this modality.^62–64 Their patients had an impressive actuarial control rate of 82% at 5 years and 58% at 10 years. Of the relapses, 95% were local recurrences, and 20% had distant metastasis. A poor prognosis was associated with tumors with a volume greater than 75 mL, more than 10% tumor necrosis, and involvement of the cervical spine. There was no histologic correlation with poor prognosis. Under this same protocol, 18 children, ranging in age from 4 to 18 years, were treated with proton-beam therapy. The median tumor dose was 69 Gy, with a 72-month median follow-up. Over a 5-year period, the actuarial survival was 68%, and the 5-year disease-free survival rate was 63%.

In summary, the data strongly support the view that radiation therapy, particularly proton-beam therapy combined with surgery, represents a substantial improvement over the natural history of chordoma (see Fig. 308-3C and D). Gamma-radiation therapy may deliver the benefits of proton therapy with fewer complications, but this remains to be demonstrated.⁶⁵

Surgical Intervention

It is difficult to cure a patient with chordoma by surgical resection alone. No single operative approach can be used for all craniocervical chordomas.^{15,47,51,54,55} I believe that most cases are best approached with the initial intent to resect rather than just biopsy the tumor. Location of the tumor is the single most important factor in determining the approach. In some cases, several different approaches are necessary for adequate resection (Fig. 308-4). The consensus is that gross surgical resection or near-total resection should be the goal. The overall rate of morbidity associated with management must be weighed against the rate of recurrence and the extent of tumor resection. A close follow-up with postoperative imaging is essential and may be needed every 3 months for the first year, especially for aggressive lesions. I reoperate on patients with gross tumor recurrence before subjecting them to radiation therapy. In subtotal resections, atypical lesions, and children, proton-beam therapy has been offered after immediate reduction of the tumor’s volume.

FIGURE 308-4 A, Endonasal resection of clivus chordoma in a 72-year-old man with headaches, facial pain, and diplopia. Composite of parasagittal (left) and coronal (right) reformation contrast-enhanced computed tomography demonstrates calcific and erosive mass distorting the basilar artery. B, Composite of axial (left) and midsagittal (right) T1-weighted magnetic resonance imaging (MRI) with gadolinium enhancement. A midclival midline mass is seen invaginating into the pons. C, Postoperative midsagittal gadolinium-enhanced MRI of brain. The retroclival tumor was removed via endonasal approach.

Plasmacytoma

Solitary plasmacytomas are clinical entities distinct from multiple myeloma, even though both are manifestations of a continuum of B-cell lymphoproliferative diseases.^5,41,66–68 The clinical distinction between the two is in the long-term prognosis. In a review of 84 patients with solitary plasmacytomas of the spine, McLain and Weinstein found that 44% of patients had developed disseminated disease at the end of 5 years, and the 5-year survival rate was 60%.⁶⁹ In contrast, the 5-year mortality rate of disseminated myeloma (multiple myeloma) of the spinal column is 82%. Despite this improved outlook for solitary plasmacytomas, once a solitary plasmacytoma disseminates, the disease behaves much like multiple myeloma.⁶⁷ The primary abnormality in multiple myeloma is slow, uncontrolled proliferation of immature and mature plasma cells in the bone marrow.^66,70 This monoclonal population of cells produces a homogeneous immunoglobulin composed of a single class of heavy chain and one type of light chain referred to as the M protein. Multiple myeloma is associated with plasmacytosis of the bone marrow and the presence of immunoglobulin A-X monoclonal immunoglobulin in the cytoplasm of the tumor cell as well as in the serum. These serum and bone marrow findings are diagnostic. In contrast, plasmacytoma does not appear in the bone marrow and is localized to the tissue involved. I have seen plasmacytomas in the craniovertebral junction involving the occipital bone, the axis, and the atlas vertebrae.^1,41,71

On gross examination, plasmacytomas are soft, grayish, moderately vascular lesions. They often reside within the diploic bone and only initially respect the cortices. When they expand, the cortex is destroyed. The tumor invades the vertebral bodies of the skull base and engulfs the vertebral vessels. When such tumors are present in the spinal canal, 20% involve the pedicles. The treatment of plasmacytoma involves diagnostic biopsy and stabilization. Because surgical attempts at resection can be fairly bloody, I advocate preoperative tumor embolization⁴¹ (Fig. 308-5). In my experience, surgery requires internal and external fixation with instrumentation, followed by radiation therapy. Occasionally, decompression of the cervicomedullary junction is essential and may be performed from a transoral-transpalatopharyngeal route or from a lateral extrapharyngeal-transcervical approach. Careful follow-up, including evaluation of serum, urine, and bone marrow, is essential.

FIGURE 308-5 A, Composite of midsagittal and parasagittal T1-weighted magnetic resonance imaging (MRI) of the cervical spine in a 48-year-old man with plasmacytoma of the axis. He presented with severe occipital headaches and neck pain. Note the replacement of the entire axis body and dorsal expansion into the cervical canal by the mass. B, Composite of midsagittal and parasagittal T2-weighted MRI of the craniocervical junction demonstrates the high signal intensity of the plasmacytoma in the axis body, which has expanded and caused ventral cervical spinal cord compression. C, Selective lateral vertebral angiogram demonstrating tumor blush in the axis body. This was successfully embolized. The patient underwent a transoral resection of the plasmacytoma and dorsal occipitocervical fusion.

Eosinophilic Granulomas

Eosinophilic granuloma affecting the spine is a childhood disease. The age of symptomatic involvement is 11 to 12 years. The most common area of occurrence is the thoracic and lumbar spine, although the upper cervical spine and clivus can be involved. The incidence of solitary eosinophilic granuloma of the spine is 8%. In children, multiple lesions occur in 38% of cases.^72–74

The presenting complaint is local segmental spinal pain and paravertebral muscle spasm. Neurological symptoms may develop as a result of vertebral collapse, which produces focal spasm and torticollis at the craniovertebral junction. The pathologic findings on plain radiographs are an osteolytic defect with an occasional sclerotic rim and various grades of vertebral collapse with flattening of the vertebral body. The latter feature has led to the term vertebra plana. Mild to moderate kyphosis may be present as a result of collapse or segmental paravertebral muscle spasm.

When treating patients with eosinophilic granuloma of the craniovertebral junction, I prefer to obtain a bone scan to identify lesions that may be present elsewhere. In some cases, an easily excised frontal bone or parietal bone lesion can lead to the diagnosis. The aim of treatment is to obtain an accurate diagnosis of a solitary lytic lesion. The differential diagnosis otherwise includes tuberculosis, pyogenic osteomyelitis, and osteochondritis. Percutaneous needle biopsy is an option, but I believe that the risk for hemorrhage and the frequently nondiagnostic nature of percutaneous specimens make open biopsy preferable. Posterior resection of bony elements should be avoided because the granuloma involves the vertebral body rather than the laminae and pedicles. Should the lesion require resection of the craniovertebral junction, it is extremely important to have bony reconstitution anteriorly and posteriorly when stabilization is performed.

Treatment of eosinophilic granuloma with low-dose radiation has been advocated and reported to be effective.^15,74,75 Simple biopsy and immobilization usually lead to reconstitution of the vertebral height²⁴ because eosinophilic granulomas spare the enchondral ossifications within the vertebral bodies. Multiple lesions with systemic conditions such as Letterer-Siwe disease and Hand-Schüller-Christian disease are the progressive form of this entity and require chemotherapy. Chemotherapy is not indicated for solid vertebral body lesions.

Calcium Pyrophosphate Masses or Pseudogout

Calcium pyrophosphate dihydrate deposition (CPPD) is a rare cause of retro-odontoid mass lesions in elderly individuals.¹⁵ This condition is severely underdiagnosed. There is an increasing geriatric population that presents with neurological deficits secondary to a large mass at the ventral foramen magnum and C1. In our series, 48 patients presented with an average age of 75 years.⁷⁶ The male-to-female ratio is equal. The duration of symptoms was 21 months, and pain was a major symptom in 90%. Paresthesias occurred in 44%, and cranial nerve deficits were seen in 44%. Neck pain occurred in 85% of individuals and paresthesias in 61%. Calcification of the mass or the transverse cruciate ligament was seen on CT in all patients. The mass may extend laterally into the joints between the occipital condyle and the lateral masses of C1 and C2.

A gross total resection was accomplished in every patient using the transoral-transpharyngeal route (Fig. 308-6). There were no recurrences, and improvement or resolution of preoperative neurological deficits occurred in 78% of individuals. A dorsal occipitoatlantoaxial fusion was necessary in 82%. We felt that fusion was not mandatory because concomitant ligamentous calcification was present and atlantoaxial joint ankylosis was seen in 18% of patients.⁷⁷

FIGURE 308-6 A, Composite of midsagittal T1-weighted magnetic resonance imaging (MRI) (left) and gadolinium-enhanced MRI of craniovertebral junction in a 73-year-old woman. The calcium pyrophosphate mass has caused severe cervicomedullary compression behind the C2 vertebral body. B, Axial MRI with gadolinium enhancement. Note the mass invaginating into the cervicomedullary junction.

The diagnosis of pseudogout should be suspected before surgery and confirmed at frozen section. The recognition of abnormal crystals on birefringence is well documented.⁷⁸ Unfortunately, these are older individuals who have significant comorbidities that must be taken into consideration before planning operative intervention.

Osteoid Osteomas and Osteoblastomas

These lesions are osteoblastic, with a propensity to involve the posterior elements of the cervical spine.⁴¹ Osteoblastomas and osteoid osteomas are differentiated from each other primarily on the basis of their size.¹ Osteoid osteomas are more common in males and are usually smaller than 1 to 1.5 cm. They are limited to the cortical framework and have no paraspinal extension. Patients with osteoid osteomas usually present in the second or third decade of life.^68,79,80 They commonly complain of neck pain that worsens at night and is relieved by salicylates.⁷⁶ Radiographically, these lesions have a central circular nidus that appears within a radiolucent area surrounded by a sclerotic border.⁶⁸ The lesion is well outlined by CT, and the bone scan is invariably positive.^79,80

In contrast, osteoblastomas have been called giant osteoids or osteofibromas. These highly vascular lesions are predominantly lytic; they expand into the spinal canal and creep into the paravertebral space. Osteoblastomas tend to involve the pedicles and laminae as well as the spinous processes.⁷³ The neoplasms expand the medullary bone and appear on radiographs as lytic lesions with expansion of the cortical margin. Less peripheral sclerosis is seen than with osteoid osteomas. Like osteoid osteomas, osteoblastomas are well localized on isotope bone scan.

The treatment of both osteoblastoma and osteoid osteoma is resection. Curettage and bone grafting of vertebral osteoblastomas have provided good long-term results.⁷⁶ Complete excision is desirable but may not be possible at the craniovertebral junction (Fig. 308-7). George and coworkers, in their manuscript reporting on bone tumors of the craniovertebral junction, had encountered eight osteoid osteomas and three osteoblastomas.⁶⁸ These had been located at the C1-2 level. The preoperative symptoms were pain and neck stiffness, and they improved or disappeared after surgical resection. They believed that CT-guided biopsies proved to be poor because an erroneous diagnosis was made on such biopsy, whereas the pathology at surgery changed to solitary plasmacytoma or fibromyosarcoma. In several other individuals being treated for abnormalities of the bone at the atlantoaxial level, CT-guided biopsies proved to be similarly erroneous until the final pathology was made at total excision.⁶⁸ Radiation therapy may be considered in individuals who have undergone subtotal resection and bone grafting. Radiation alone may provide reconstitution of bone and preserve spinal stability if immobilization is adequate. A very small number of such lesions may undergo malignant transformation. Long-term follow-up of treated patients is mandatory.

FIGURE 308-7 A, A 42-year-old man with neck pain and cervical myelopathy underwent C4-6 anterior osteophyte decompression and fusion. Note the absent atlas arch and retropharyngeal mass on lateral cervical radiograph. B, Composite of axial computed tomography (CT) at C1 and three-dimensional CT of cervical spine. An expansile erosive mass has replaced both lateral atlantal masses. C, Composite of parasagittal (left) and midsagittal (right) craniovertebral magnetic resonance imaging (MRI). Note the heterogeneous mass at C1. The odontoid process is posteriorly located. D, Composite of right carotid angiogram (left) and vertebral angiogram (right). Note the tumor blush. E, Axial CT through plane of occipital condyles (left) and atlas (right). An extensive embolization has been done. F, Postoperative lateral cervical radiograph. A high lateral extrapharyngeal approach was done to resect the mass followed by dorsal occipitocervical fusion.

Aneurysmal Bone Cyst at the Craniovertebral Junction

These bone cysts are benign, highly vascular lesions that are expansile and most often occur in long bones, flat bones, and less often the spinal column. They can present as primary bone lesions in association with other bony lesions such as giant cell tumor, osteoblastoma, chondroid myxofibroma, fibrous dysplasia, and osteosarcoma.⁵ Lesions that involve the atlas vertebra make up about 1% of all spinal aneurysmal bone cysts. The treatment of choice for accessible lesions is en bloc excision or curettage.^81,82 On CT, an expansile cystic mass with a thin rim of calcification is usually seen. Bony trabeculae within the cyst may be present. Unfortunately, this appearance can occur with osteoblastoma as well as giant cell tumor and bone. Fluid-filled levels identified on MRI, however, are characteristic of aneurysmal bone cyst. Although benign, aneurysmal bone cysts can grow rapidly and cause destruction of bone.

Histologically, aneurysmal bone cysts are composed of cavernous blood-filled spaces separated by bony trabeculae or osteoid tissue. The expansile nature of the lesion causes swelling, bone destruction, pain, and fractures.^83–85

Superselective embolization of arterial feeders has been used as a primary modality of treatment in long bone and thoracic spine areas.⁸⁶ The disadvantage of this is that treatment of aneurysmal bone cysts of the atlas includes the risk for embolizing the spinal cord and embolic complications. In addition, multiple embolization procedures are necessary to achieve clinical and radiographic healing of the cyst. Percutaneous intralesional injection of calcitonin and methylprednisolone as sclerosing agents into the aneurysmal bone cyst at the atlas has been reported.⁵³

Aneurysmal bone cysts have been recorded as occurring after radiation therapy such as for pontine and brainstem gliomas. In my series, a 15-year-old girl was seen 18 months after radiation for a primary brainstem glioma.⁵ The brainstem tumor responded to the radiation as well as chemotherapy. However, significant neck pain with moderate degree of rotary luxation of C1 on C2 and secondary odontoid invagination prompted further evaluation and care (Fig. 308-8). She was treated with superselective embolization made in three sittings. She was followed with brace immobilization, and at 5 months, the CT scan showed reconstitution of the entire lateral mass of C1 as well as calcification of the soft tissues that had come out of the bony shell.

FIGURE 308-8 A, Composite of axial T1-weighted magnetic resonance imaging with gadolinium through plane of medulla oblongata (left) and atlas (right) vertebra. This 15-year-old underwent radiation for primary brainstem glioma (left). Severe neck pain 18 months later prompted images revealing tumor expansion of left atlantal mass consistent with aneurysmal bone cyst. B, Composite of two-dimensional computed tomography (CT) reformatted image in left parasagittal plane (left) and coronal plane (right). Note the collapse and destruction of left C1 lateral mass. C, Composite of coronal (left) and left parasagittal (right) two-dimensional CT reformatted image made 8 months after C1 tumor embolization and bracing. There is remodeling of C1 tumor and new bone formation.

Foramen Magnum Meningiomas

Meningiomas are common at the foramen magnum and account for 2% to 3% of all meningiomas.^2,5,9,35,43 Females represent between 66% and 73% of cases. Typically, patients become symptomatic between 35 and 60 years old, although meningiomas occasionally occur at the foramen magnum in children. Foramen magnum meningiomas may occur in the setting of neurofibromatosis.^6,87,88

Typically, the lesions are attached to the anterior rim of the foramen magnum and frequently invade the region of the entrance around the vertebral artery and the exit of the cervical nerve roots.^5,51,89 These globoid and often fibrous lesions usually extend above and below the foramen magnum equally (Fig. 308-9). Occasionally, they show a marked predilection for either intracranial or intraspinal development. Many subtypes of meningioma have been identified at the foramen magnum, including meningothelial, transitional, fibrous, xanthomatous, clear cell, and lymphoplasmacytic-rich meningiomas.^90,91

FIGURE 308-9 A, Composite of axial T2-weighted magnetic resonance imaging (MRI) through posterior fossa in a 12-year-old boy with neurofibromatosis type 2. There is a ventrally located meningioma engulfing the right vertebral artery. B, Composite of T2-weighted MRI in parasagittal plane. Note the location of the vertebral artery. C, Composite of views through the microscope at posterolateral exposure approach to ventral medulla. D, Composite of operative photographs. Note the entire resection.

Plain radiographs may show evidence of increased pressure, such as erosion or calcification around the foramen magnum and widening of the interpedicular spaces of the upper cervical vertebrae. The concomitant finding of cervical spondylosis frequently results in an erroneous primary diagnosis of spondylosis as the cause of myelopathy.

MRI provides excellent high-resolution information about the tumor, vascular encasement, its relationship to the brainstem, and CSF spaces. Typically, meningiomas are isointense on T1-weighted images and isointense to hypointense on T2-weighted images and enhance intensely after gadolinium administration.⁷⁶ Magnetic resonance angiography provides critical arterial detail, including vertebral artery patency. It is used routinely as an alternative to conventional angiography.⁵¹ Magnetic resonance venography can be used to evaluate the vein of Labbé, sigmoid sinus, and dominance of the transverse sinus; thus, it can help plan the surgical approach in some patients.

Treatment

The mainstay of treatment for foramen magnum meningioma is surgical resection. Samii and colleagues⁸⁹ reported complete removal in 63% of cases and subtotal removal in 30%, and their patients’ mean Karnofsky performance scores increased from 63 to 73. George and associates⁴ reported complete removal in 86% and subtotal removal in 11% of their patients. Clinical grade improved in 90% of patients, stabilized in 2.5%, and worsened in 7.5%—the latter corresponding to the three deaths in their series.⁴

In a recent review of the manuscript of Bassiouni and associates,⁴³ George reports on his experience of more than 90 foramen magnum meningiomas operated on up to 2006. He believed that a retrocondylar route was sufficient in 95% of cases but did feel that vertebral artery mobilization was necessary. Bassiouni and associates, in 2006, reported on a series of 25 foramen magnum meningiomas approached through a posterolateral suboccipital retrocondylar route.⁴³ The dural attachment of the meningioma was anterior in 36% and anterolateral in 64% of cases. The occipital condyle was not resected in these individuals. Tumors were said to be completely removed in 23 of 25, with about 40% incidence of postoperative morbidity. CSF leak occurred in 5 of 25 patients. Simpson grade 2 resection was achieved in 89.3%. The transient complication rate was 40%, with a permanent rate of 7.1%.

In 2005, we reported on our series of 41 patients with foramen magnum meningiomas, four cases of which occurred in the pediatric population.¹⁵ The average age at diagnosis was 50.1 years, and 78% were in females. The symptom duration was an average of 12.4 months. Pain was the major presenter in 68%, with motor deficit seen in 26%. Gross involvement of the vertebral artery occurred in 32% of patients. The surgical treatment consisted of posterolateral approach to foramen magnum and the clivus. In five individuals, a combined presigmoid and retrosigmoid craniotomy allowed for gross total removal. Gross total resection was accomplished in 87% of foramen magnum meningiomas. Partial resection was made in 10% of patients, and a repeat surgical procedure was required in 3% of patients. Surgery was combined with radiation therapy in 13% of individuals with a diagnosis of clear cell or angioblastic meningioma.⁵ However, surgical complications with a new deficit were seen in 32% of individuals, and a resolution of symptoms occurred in half of these individuals. A fusion procedure was required in two individuals after a posterolateral transcondylar approach. Tracheostomy was required in two individuals with new hypoglossal or vagal nerve dysfunction that was not present preoperatively.

Meningiomas located at the ventral foramen magnum are more difficult to resect than those at the posterior foramen magnum. Two major reasons account for this difference. First, the posterolateral approaches required to expose the ventral foramen magnum are larger and more complex than the posterior approaches. Second, several critical structures, including the vertebral artery, occipital condyle, brainstem, and lower cranial nerves, impede exposure of the ventral foramen magnum. During a posterolateral approach, any of these structures can be subjected to injury, causing significant morbidity and mortality.

Despite these difficulties, Arnautovic and colleagues⁹² reported 67% gross total resections, 11% near-total resections, and 22% subtotal resections in patients harboring ventral foramen magnum meningiomas. These results are similar to the surgical results for all foramen magnum meningiomas. Further, Karnofsky performance scores increased postoperatively in 15 patients. Statistical analysis demonstrated that gross total or near-total resection and a higher preoperative Karnofsky score indicated a significantly improved outcome. These series demonstrate that complete resection of foramen meningiomas can be obtained in most cases, particularly during the first resection, and that resection can improve patients’ postoperative performance scores.

Postoperative lower cranial palsies are the most frequent complication. These palsies are significant because they are associated with longer periods of hospitalization.^89,92 Lower cranial nerve palsies resulting in aspiration pneumonia and death accounted for the mortality rates in several series. Multiple regression analysis indicated that recurrent tumor, arachnoid scarring, craniovertebral meningioma, and no preoperative cranial nerve deficits were predictors of postoperative aspiration. Aggressive, comprehensive treatment is recommended after these deficits are discovered, including speech therapy, possible vocal cord medialization or injection, tracheostomy, or gastric tube placement.

Severe preoperative deficits and poor Karnofsky performance scores are also predictors of postoperative morbidity and mortality. Weakness and poor mobility predispose patients to pneumonia, deep venous thrombosis, and pulmonary embolism, which may account for up to 50% of postoperative mortality.^4,89,92

Other postoperative complications include CSF leak, meningitis, and hydrocephalus that may require insertion of a ventriculoperitoneal shunt. Other cranial nerve palsies can occur, but most resolve. Occipitocervical instability can occur, but this complication can be eliminated with judicious resection of no more than one third to one half of the occipital condyle. In recent series, the overall morbidity rate has been about 30%, and perioperative mortality rates have ranged from 0% to 7.5%. Incomplete tumor removal and aggressive recurrence of invasive meningioma have responded to conventional radiation.^93–95

Muthukumar and colleagues reported their experience treating five foramen magnum meningiomas using stereotactic radiosurgery.⁹⁶ Patients with tumors less than 35 mm in diameter and with a reasonable performance status were selected for treatment. At a median follow-up of 36 months, no tumor growth had occurred, and cranial nerve deficits had not worsened, but the series was small, and follow-up data were limited. Furthermore, their population represented ideal surgical candidates, whose results were likely to be more favorable than those of nonideal patients for whom nonsurgical treatment would be preferable. Much more experience in patient selection is required before stereotactic radiosurgery can be considered a primary treatment for foramen magnum meningiomas. Others have performed surgical resection with low thresholds for leaving adherent tumor and used postoperative Gamma Knife radiosurgery to treat the residual tumor.⁹⁷ Therefore, stereotactic radiosurgery may represent a valuable adjunctive therapy.

Intradural Extramedullary Tumors at C1 and C2

The most common extramedullary intradural spinal tumors are meningiomas, neurofibromas, and schwannomas.^98,99 Together, these tumors represent about 55% of spinal tumors.^2,4,77,88,92 Other intradural tumors, such as hemangioblastoma, dermoids, epidermoids, neurenteric cysts, and mixed tumors, are uncommon.^{1,11,100–102} Many of these lesions are benign and resectable, and the outlook after surgical therapy is excellent.

Overall, the clinical presentation and examination of patients with intradural extra-axial tumors in the region of the atlas and axis are similar to those of patients with foramen magnum meningiomas. This is true for two reasons: tumors attached to the foramen magnum often expand caudally into the upper cervical canal, and tumors arising in the upper cervical canal expand rostrally through the foramen magnum. The radiographic evaluation is also similar in both groups of patients.

Neurofibromas produce symptoms in patients between 20 and 60 years old.^1,2,11 Patients with neurofibromatosis type 1 tend to develop symptoms at a younger age^5,10 and have multiple or bilateral tumors. Neurinomas occur more frequently at C2 than at C1. The median time from onset of symptoms to diagnosis is 24 months. Although neurinomas are associated with nerve roots, symptoms tend to manifest distally with weakness and poor coordination or, less commonly, in a radicular pattern.^98,103,104 Clinical signs also mirror those of foramen magnum meningiomas; however, hypesthesia in the second cervical division is an important localizing sign.

Although findings on plain radiography may be normal or demonstrate cervical spondylosis, the presence of an enlarged intervertebral foramen is highly suggestive of a nerve root tumor. Neurinomas are usually isointense to hypointense on T1-weighted MRI and hyperintense on T2-weighted MRI (Fig. 308-10).⁹⁹ Intratumoral hemorrhage and cyst formation can affect the postcontrast appearance of neurinomas (homogeneous, heterogeneous, and even ring enhancement). If necessary, magnetic resonance angiography can evaluate the vertebrobasilar arterial tree. CT provides detailed bony definition. If MRI is contraindicated, CT myelography may improve intradural visualization of the tumor.

FIGURE 308-10 Midsagittal T2-weighted magnetic resonance imaging (MRI) of the cervicomedullary junction in a 55-year-old man. A, The patient presented with severe right-sided occipital pain with quadriparesis weaker in the right arm and leg than on the contralateral side. The area of high signal intensity represents a discrete ventral neurofibroma in the subarachnoid space at C1. There is compression of the cervicomedullary junction dorsally. B, Parasagittal T2-weighted MRI through the neural foramen on the right side of the cervical canal demonstrates the high signal intensity tumor in the C1-2 neural foramen.

Neurenteric cysts are a developmental abnormality resulting in a cystic endodermal structure that can impinge on the spinal cord. Although most common in the cervical and thoracic regions, neurenteric cysts rarely appear in the region of the foramen magnum, typically in an anterior location. Their clinical presentation is similar to that of other foramen magnum lesions, with the exception that the cysts can lead to repeated episodes of meningitis.¹⁰² Plain radiographs can demonstrate vertebral segmentation failure. CT is useful for fully delineating bony abnormalities. MRI demonstrates a cystic structure with T1- and T2-weighted imaging characteristics similar to those of proteinaceous CSF (Fig. 308-11).¹⁰¹

FIGURE 308-11 A, T1-weighted midsagittal magnetic resonance imaging (MRI) through the craniocervical junction in a 24-year-old man with neurenteric cyst ventral to the cervicomedullary junction. Note the high signal caused by the proteinaceous material within the cystic mass. B, Axial T1-weighted MRI through just below the plane of foramen magnum. Note the cystic ventral extra-axial mass dorsally displacing the cervicomedullary junction. C, Operative photograph through the microscope after a posterolateral transcondylar exposure of the ventral cerebellopontine angle and cervicomedullary junction. There is an intra-arachnoid mass ventral to the cerebellum, medulla, and cervicomedullary junction. The dorsal branches of the posterior inferior cerebellar artery are seen at the top of the field and the upper cervical nerves visualized together with the spinal accessory nerve in the lateralmost portion of the ventral subarachnoid space. D, Operative photograph through the microscope after resection of the neurenteric cyst ventral to the medulla and cervicomedullary junction. The lower cranial nerves, upper cervical nerve roots, and posterior inferior cerebellar branches are preserved.

Treatment

The aim of the surgical approach is to maximize exposure of the tumor affecting the spinal cord or brainstem while minimizing bone removal to maintain the stability of the craniovertebral junction. Early diagnosis, when neurological deficits are minor and the tumor is small, tends to lead to better surgical outcomes and prognoses. Thus, neurologically devastated individuals are less likely to attain gainful resolution of their neurological deficits.

Preoperative cardiopulmonary assessment is essential, as is discussion with the patient and family about the possibility of prolonged postoperative tracheal intubation or tracheostomy. Patients with large lesions within the spinal canal require preoperative evaluation of cervical motion to assess stability and determine whether neurological deficits develop during flexion due to compression of the brainstem by the tumor.^1,105 This evaluation allows positioning under general anesthesia.

In most benign lesions, surgical exposure is obtained through a posterior midline or posterolateral approach. Surgical principles employed to remove benign tumors include the compulsory use of an operating microscope, tumor debulking early during the exposure, and gentle traction maintained away from the neural structures. In many cases, the use of an ultrasonic aspirator is beneficial. I have used electrophysiologic monitoring using motor and sensory evoked responses or bipolar recording rostral to the lesion, but this is not mandatory for such surgical procedures.

Although posterior approaches are most commonly used to resect neurinomas, use of the anterolateral⁴ and transoral exposures has been reported.²⁶ In rare instances, schwannomas of the craniovertebral junction may be ventral to the dentate ligament; in such cases, section of the ligament or even of the spinal accessory nerve may be required. Dumbbell neurofibromas can cause craniovertebral instability, and this possibility must be kept in mind at the time of reconstruction. The surgical outcome of neurinoma resection is excellent. Patients with myelopathy and quadriparesis typically improve significantly, or their symptoms resolve completely. Resection rarely causes new radicular symptoms and usually improves existing radicular symptoms.

Neurenteric cysts have been resected through several approaches: posterior midline, posterolateral, far lateral, and transoral. Complete resection is mandatory because cyst aspiration results in reaccumulation of the cyst contents and symptomatic recurrence. Resection is typically associated with significant improvement or resolution of symptoms.