Special Issue Article
Surgical management of primary tumors of the cervical spine: surgical considerations and avoidance of complications Paul E. Kaloostian, Ziya L. Gokaslan The Johns Hopkins Hospital, Baltimore, MD, USA Objective: Primary cervical spinal tumors are rare tumors of the spine and are associated with significant morbidity and mortality. Such tumors include multiple myeloma, chordomas, giant cell tumors, hemangiomas, osteosarcomas, chondrosarcomas, synovial sarcomas, aneurysmal bone cysts (ABC), hemangiomas, eosinophilic granulomas, osteoid osteomas, and osteoblastomas. We review the surgical decision-making process and identify critical key steps for surgical complication avoidance. We also present case illustrations demonstrating such pathological diagnoses and surgical treatments performed. Methods: We retrospectively review the literature regarding the most common primary cervical spinal tumors that have undergone surgical resection with or without adjuvant treatment. Results: En bloc resection of primary cervical tumors resulted in significantly increased progression-free survival and overall survival. From the limited data, adjuvant treatment with proton-beam therapy for chordomas has potential benefit. Neo-adjuvant chemotherapy for Ewing’s sarcoma and osteogenic sarcoma has shown some promise, with en bloc resection demonstrating stronger benefit for osteogenic sarcoma. Discussion: En bloc resection for primary spinal tumors has proven to be the standard of care in spinal oncology. Adjuvant and neo-adjuvant treatments such as chemotherapy and radiotherapy variants (conventional, proton beam, cyberknife) need to be studied further in most primary tumor types to become standard of care. Chordoma management is more widely studied with en bloc resection and adjuvant proton-beam therapy demonstrating improved progression-free survival and overall survival. Surgical management and adjuvant treatment strategies are case dependent, depending on tumor histology, patient neurological examination, prior surgeries at that level, and prior adjuvant treatment. Keywords: Cervical spine, En bloc, Primary tumors, Spinal chordomas, Spinal complication
Introduction The axial skeleton is a common site for both primary tumors and metastatic disease, with metastatic disease being most common. Distinguishing between the two is critical in terms of further therapeutic modalities, such as type of treatment, extent of resection, and post-operative adjunctive therapy. Primary bony tumors are seen to grow and flourish within the spinal axis, and although they are rare, the morbidity and mortality associated with them is not insignificant.1 We discuss a variety of primary bony tumors of the cervical spine, each of which display unique pathophysiological and histological properties that help determine current diagnostic and treatment modalities. Finally, we discuss surgical technique and common pitfalls that surgeons may encounter during
Correspondence to: Paul E. Kaloostian, The Johns Hopkins Hospital, 600 North Wolfe Street, Baltimore, MD 21205, USA. Email: paulkaloostian@ hotmail.com
ß W. S. Maney & Son Ltd 2014 DOI 10.1179/1743132814Y.0000000367
surgical resection, and methods of complication avoidance.
Differential Diagnosis The differential diagnosis of primary bony tumors of the spine is quite diverse. It includes pathology such as: multiple myeloma, chordomas, giant cell tumors, hemangiomas, osteosarcomas, chondrosarcomas, synovial sarcomas, aneurysmal bone cysts (ABC), hemangiomas, eosinophilic granulomas, osteoid osteomas, and osteoblastomas. Other lesions that may mimic primary spinal tumors include infection, metastatic disease, and possibly hematoma (either spontaneous or traumatic).
Diagnostic Process Patients with primary tumors of the spine will most commonly present to their primary care physician or emergency department with chronic and progressively worsening focal back pain. Depending on the
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morphologic characteristics of the spinal tumor, tumor size, and tumor infiltration to surrounding neural and vascular structures, patients will present with a variety of other symptoms. These symptoms may include paraspinal pain, intractable radicular pain due to foraminal involvement of tumor burden, and finally various degrees of myelopathy or cauda equina syndrome depending on location within the spinal canal. Paraspinal pain is due to infiltration of tumor into surrounding muscle and subcutaneous tissues. Radiculopathy is due to tumor extension into neural foramen compressing exiting nerve roots. Tumor burden extending within the spinal canal in the epidural space may cause spinal cord compression. For example, patients with cervical epidural tumor invasion may initially present with gait instability and weakness of hands. Patients will describe dropping objects from their hands that then may progress to severe weakness of arms and legs, requiring the use of a wheelchair. With further tumor extension, vascular supply to the spinal cord is compromised and the neural structures are compressed. Patients may also describe bowel and bladder deficits in cases of severe stenosis. Patients with predominantly primary sacral tumors with severe canal and foraminal involvement may present with severe low back pain and cauda equina syndrome with perineal numbness, bowel and bladder dysfunction, and/or lower extremity weakness.1–8 Physical examination is critical when evaluating patients with spinal lesions. Patients with cervical lesions with spinal cord compression will have signs of myelopathy on examination. These include positive Hoffman sign, hyperreflexia in upper and lower extremities, upgoing Babinski signs bilaterally, spastic weakness of upper and lower extremities, and gait instability. Patients with severe spinal cord compression may present with quadriplegia with a sensory or motor level. Patients with lumbosacral tumors with canal compromise may have weakness and/or numbness in one or both extremities, and evidence of perineal numbness and saddle anesthesia. Diagnostic modalities for primary tumors of the spine include computerized tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET) scans, and CT of the chest/ abdomen/pelvis. Computerized tomography scans of the entire spine are obtained to analyze the bony quality and bony anatomy at the site of tumor burden as well as to rule out other lesions within the spinal column. Computerized tomography scans can help determine extent of tumor erosion of vertebral anatomy and extent of destruction from anterior to posterior columns of the spine. Magnetic resonance imaging scans with and without contrast are critical to obtain for tumors of the spinal column. Magnetic
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resonance imaging may delineate more clearly the anatomy of the tumor and extent of tumor enhancement. Magnetic resonance imaging will identify regions of tumor that may be cystic or necrotic without enhancement, as well as extension of tumor burden into surrounding tissues. Also, MRI is important to identify tumor burden within the epidural space and extent of neural element compression or injury, either centrally or foraminally. Positron emission tomography scans are helpful in determining other areas of abnormal radioactive uptake of glucose throughout the body, signifying possible metastatic disease or tumor elsewhere. Computerized tomography of the chest/abdomen/ pelvis with and without contrast is often obtained to rule out other areas of tumor burden in order to rule out metastatic disease. Standard labs, including white blood cell count, red blood cell count, coagulation numbers, and electrolyte levels should be obtained to rule out infectious process and prepare the patient for possible surgical intervention. If no other lesions are noted elsewhere based on CT and PET scans, then an isolated spinal column lesion without acute deterioration should receive a core biopsy in order to obtain a definitive diagnosis. This can be done percutaneously by the interventional radiology team using fluoroscopic guidance. Once this is done and a diagnosis is obtained, the multidisciplinary treatment plan can be arranged. Determining whether the spinal column mass is a primary spinal tumor versus metastatic disease or infection is crucial before instituting surgical treatment. Metastatic disease is classically treated with intralesional resection due to tumor burden elsewhere, while over the last decade en bloc resection for primary spinal tumors has improved patient outcome and survival. Intralesional resection of primary spinal tumors will disseminate tumor elsewhere, whereby en bloc extracapsular resection may avoid tumor spread and provide negative surgical margins grossly and histopathologically. Unless acute neurological deterioration is observed, patients should follow this standard paradigm when being diagnosed with a spinal column mass.2–5
Primary Tumor Breakdown with General Treatment Paradigms Chordoma
N N N
Surgical management includes en bloc resection without violation of the tumor capsule, offering an increased progression-free survival of over 60% at 5 years while minimizing local recurrence.6,7 Subtotal resection provides a local recurrence rate of 8 months as opposed to over 2 years with en bloc resection. Adjunctive treatment includes post-operative protonbeam radiotherapy.8
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Hemangiomas
N N N N
Hemangiomas are benign and classically asymptomatic lesions that are typically located in the vertebral bodies of the thoracic spine. Radiographically, CT scans will demonstrate the ‘spikes of bone’ appearance within the vertebral body, while MRI will show an enhancing tumor with hemorrhage.9 Asymptomatic patients only require observation of the lesion, while symptomatic patients may receive radiation or surgical resection. Pre-operative embolization reduces the risk of intraoperative hemorrhage and should be performed when angiography identifies the arterial blood supply.10
Multiple myeloma
N N N N N
Diagnostic modalities include bone marrow aspiration, CT-guided biopsy of lesions, serum and urine electrophoresis and a CBC, and bone marrow biopsy demonstrating abnormal plasma cells. Immunohistochemical analysis is crucial in identifying lambda and kappa heavy chain and light chain distributions.11 Patients with stable spinal disease without deformity or neurological deficit may be managed non-operatively with pain management, conventional radiation therapy for focal disease, and/or chemotherapy for systemic disease. Patients with severe spinal instability, spinal deformity, and spinal cord compromise will require surgical intervention. The 5-year survival remains less than 30% despite aggressive surgical and adjuvant management.11
Giant cell tumor
N N N N
A CT-guided biopsy is often recommended to look for the classic mononuclear stromal cells with giant cells throughout. Conventional radiotherapy is recommended for focal disease and en bloc spondylectomy is recommended for large symptomatic lesions.12 The role of post-operative radiotherapy is currently unclear, as malignant transformation of the giant cell tumor has been reported. Local recurrence rates are noted to be at 40–67% within the mobile spine.12,13
Eosinophilic granuloma
N N N N
Eosinophilic granulomas of the spine are benign lesions that are typically found incidentally with vertebral flattening which precedes eventual vertebral collapse.14 If patient has not been diagnosed prior with histiocytosis X, then biopsy is indicated to confirm the diagnosis. Low-dose conventional radiotherapy is recommended for symptomatic lesions without neurological compromise and/or patients who are not operative candidates. Symptomatic lesions or growing lesions causing deformity, instability, or neurological decline will surgical resection. Data regarding en bloc versus intralesional resection are very limited.14
Osteoblastoma
N
Osteoblastomas are rare benign tumors of the spine in young adults that are similar to osteoid osteomas, but are larger than 2 cm in size.
N N
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Small tumors may be treated with observation and pain control. Larger tumors causing mass effect and neurological deficit require surgical treatment. Some studies advocate intralesional excision followed by conventional radiotherapy while others recommend en bloc resection in stages.15
Aneurysmal bone cyst
N N N N
Aneurysmal bone cysts are benign expansile lesions of bone composed of blood-filled cavities separated by septa of osteoclastic cells. Treatments include curettage, subtotal excision, en bloc resection, embolization, intralesional injection, and radiation. For lesions that are asymptomatic, conservative treatment with or without bracing is indicated. For larger lesions with neurological compromise, surgical treatment is recommended. Pre-operative embolization may play a role in management.16
Fibrous dysplasia
N N N
Biopsy may show curvilinear trabecular woven bone with a background of fibroblasts. Surgery is indicated in cases of neural compromise and/or instability. Surgical approach would depend on the location along the spinal axis but may require multi-stage corpectomy with instrumentation and fusion.17
Osteosarcomas
N N N N N
Sarcomas of the spine are quite complex but in cases of neurological compromise from compression and/or instability, surgical treatment is warranted. Recent evidence for chondrosarcomas, Ewing’s sarcomas, and osteogenic sarcomas has emerged showing an increased progression-free survival after en bloc resection without violation of tumor capsule. Neo-adjuvant treatment with chemotherapy for Ewing’s sarcoma and osteogenic sarcoma has shown improved patient survival. Additionally, conventional radiotherapy post-operatively has a role in patients with Ewing’s sarcoma. Osteogenic sarcomas are radioresistant.18
Osteoid osteomas
N N N N
Osteomas are typically self-limiting. When pain is intractable or patient’s tumor is causing instability or neural compromise, surgery is indicated. Surgical treatment generally involves instrumentation and fusion. The role of en bloc resection is unclear.
En bloc resection of primary spinal tumors Many studies have now been published validating the role of en bloc resection as standard of care for primary spinal column tumors. The goal of en bloc resection of tumor, as compared to the prior mainstay surgical treatment of all spinal tumors of piecemeal resection, is mainly to prevent seeding of tumor cells into surrounding tissues. The hypothesis was that this strategy would avoid dissemination of tumor and ultimately lead to a prolonged disease-free and overall survival. Talac et al. studied patients with primary sarcomas of the spine. Their studied cohorts
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included en bloc resection with negative margins, piecemeal resection with negative margins, and all resections with positive margins. They found recurrence rates of 11, 33, and 50–70% in these groups, respectively.5 Carpentier et al. noted in their study of 16 patients with occipitocervical chordomas, a 40% recurrence rate and 33% mortality rate over a 5-year follow up in these patients who underwent solely piecemeal resection.19 Additionally, Barrenechea et al. studied seven patients with intralesional piecemeal resections of cervical chordomas and noted an approximately 30% recurrence rate over a median of a 2-year follow up.20 Junming et al. analyzed 21 patients who underwent piecemeal resection of cervical giant cell tumors and noted a recurrence rate of 33% over a mean follow up of 68 months.21 Cloyd et al. studied two patients with cervical chordoma who underwent en bloc resection and performed a meta-analysis of the existing literature on cervical primary spinal tumors with en bloc resection. The analysis involved 10 articles comprising 18 cases, including the authors’ two cases. The authors identify a combined recurrence rate of 22% in all published studies for primary cervical spine tumors with a mean follow up of 47.4 months.22 They also note mean operative time, estimated blood loss, and length of hospital stay were 18.6 hours, 2.9 L, and 34.6 days, respectively. They noted three case of local recurrence at 12, 44, and 113 months along with one case of distant metastasis at 12 months post-operatively. The authors then calculated a disease-free survival rate of approximately 88 and 76% at 1 and 5 years, respectively. No factors were identified as predictive of recurrence in this meta-analysis.22 En bloc resection of cervical lesions is quite complex and is not without significant risk of morbidity and mortality. For this reason, preoperative understanding of patient pathology, involvement of neural and vascular structures, and even intracranial vascular anatomy are quite important in determining patient outcome. One such risk factor is injury to the vertebral artery(s). Depending on primary spinal tumor morphology and extension, the vertebral arteries may be encased with tumor on presentation, adding to the danger of surgical resection. While some studies have recommended a clear avoidance of en bloc vertebrectomy in the cervical spine due precisely to the risk posed to the vertebral arteries and cervical nerve roots, others have published data demonstrating safety and feasibility. Hoshino et al. published a study of 15 patients who underwent unilateral vertebral artery ligation during en bloc resection of cervical spinal tumors and noted no adverse events affecting the brain stem, spinal cord, or cerebellum.23 However, Cohen et al. presented a case report of a patient with C6 osteosarcoma managed with intralesional resection and post-operative chemotherapy as an
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adjuvant to en bloc resection.24 Despite the high risk, many studies have now described vertebral artery ligation during primary spinal tumor resection and have documented adequate results. The importance, however, of pre-operative cranial and spinal angiography, as well as temporary occlusion of the vertebral artery with somatosensory evoked potentials and motor evoked potential monitoring, is crucial prior to ligation of the vertebral artery. Cranial anastomotic anatomy to the posterior circulation is critical in case of bilateral or dominant vertebral artery injury or vasospasm intraoperatively and post-operatively. The presence of a neurovascular surgeon is helpful in cases requiring intracranial bypass procedures. During vertebral artery manipulation, any neurological decline in neuromonitoring while temporary clipping necessitates preserving the artery. In the meta-analysis by Cloyd et al. the authors note that 8 of the 18 patients who underwent en bloc resection of primary cervical spinal tumors had unilateral vertebral artery ligation without complication.22 Other possible risk factors involved in en bloc resection of primary cervical spinal tumors include infection, significant bleeding, dysphagia, aspiration, spinal instability, seeding of tumor cells into surrounding tissues and into the cerebrospinal fluid if a dural tear is encountered, spinal cord and/or nerve root injury, and large vessel injury including the internal carotid arteries, vertebral arteries, and internal jugular veins.22 Techniques of complication avoidance are critical for spinal surgeons who specialize in treating cervical spine tumors. A variety of important strategies exist to minimize complications intra-operatively in order to provide the most efficient patient outcome. For example, Tomita et al. describe the use of pre-operative embolization of vessels supplying spinal tumors. The authors note a significant decrease in intra-operative bleeding with pre-operative embolization, meticulous blunt dissection, and resection of tumor, and through the use of fibrin glue in the epidural venous plexus.4 Additionally, Tomita et al. describe the use of a Tsaw for pediculotomy or anterior column osteotomy.25 They note a decrease in tumor spread after the use of the T-saw. Others have described the use of rinsing instruments with cisplatin or distilled water to prevent tumor seeding.4 Meticulous blunt dissection and separation of tumor from surrounding prevertebral structures is crucial in avoiding inadvertent injury to the esophagus, trachea, and retropharyngeal mucosa. Placement of a silastic sheath anterior to the spinal cord and other nearby structures, as is done after an initial posterior cervical stage at the author’s institution, separating the now separated vital structures from tumor helps in removing the tumor en bloc during the second anterior stage of the procedure.
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This method allows clear demarcation of tumor and plays a vital role in diminishing intra-operative complications such as vascular or spinal cord injury. Surgical treatment of Ewing’s sarcoma and osteogenic sarcoma of the cervical spine has noted recent advances in the last decade. The Spinal Oncology Study Group has published data with strong recommendations and moderate quality evidence of neo-adjuvant (before surgery) chemotherapy with a weak recommendation with very low evidence for en bloc surgical resection for Ewing’s sarcoma of the spine. They note en bloc surgical resection to provide improved local control, but not improved overall survival. The authors mention that the use of radiation therapy alone or as adjuvant treatment may be used for local control, but this evidence is very low. For patients with osteogenic sarcoma, the authors have a strong recommendation with moderate quality evidence favoring neo-adjuvant chemotherapy. Additionally, the authors have a strong recommendation with very low evidence for en bloc resection providing improved local control and potentially improved overall survival.26 The role of adjuvant treatment with chemotherapy and radiation is still unclear in the treatment of primary cervical spinal tumors. Additionally, the role of different radiation modalities, such as radiosurgery, conventional radiation treatment, and proton-beam radiotherapy, remain debatable. The role of adjuvant treatment has been studied in spinal chordomas. Chordomas are classically relatively resistant to conventional radiation treatments at doses that are favorable to surrounding tissues at ,60 Gy.27 Small skull base chordomas have responded quite well to low doses of radiotherapy in a single case series.28 Proton-beam therapy, though, has proved in a few published studies to be of benefit to patients with spinal chordomas.27,28 Proton-beam therapy has the advantage of intensity modulated and extreme precision allowing for an effectively high dose of focused radiation at the chordoma with minimal surrounding tissue damage. For these reasons, it is recommended to use protonbeam therapy either pre-operatively or post-operatively for spinal chordomas.2,3,20 Neo-adjuvant chemotherapy for Ewing’s sarcomas and osteogenic sarcomas has shown clear benefit, along with radiotherapy for Ewing’s sarcoma. Non-operative treatment for cases of multiple myeloma without acute neurological decline would consist of radiotherapy for focal disease and chemotherapy for systemic disease. Some cases of multiple myeloma with epidural extension do not necessarily require surgical treatment, and have shown clear remission after conventional radiotherapy. Chemotherapy with imatinib mesylate has been shown in one study to benefit patients with spinal chordomas, though further studies are required.29
Surgical management of tumors of cervical spine
Complications associated with radiotherapy are not insignificant. These include wound breakdown and infection, particularly if performed at least 2 weeks before surgical treatment, neurological decline from radiation necrosis, and a small risk of developing radiation-induced malignancy. Case illustrations Case 1 A 35-year-old male presented to the emergency room with swallowing and upper airway obstruction (Fig. 1). On CT and MRI, the patient was found to have a large lesion extending from the C2 vertebral body with significant pre-cervical extension into the retropharyngeal space. The patient had a CT-guided biopsy of this lesion via a trans-oral route, which proved to be a chordoma. The patient then underwent a two-stage surgical procedure. With each surgery, neuromonitoring was utilized, along with awake fiberoptic intubation and placement of the patient into a prone position while awake to obtain adequate neurological examination on positioning and minimize neurological complication. Stage 1 involved a posterior approach for C1 through C3 bilateral complete laminectomies, bilateral mobilization of the tumor from the cervical and retropharyngeal structures, and ligation of the leftsided vertebral artery after no somatosensory evoked potential or motor evoked potential changes occurred on temporary occlusion. Ligation of the left vertebral artery was performed both proximal and distal to the tumor. Additionally, left C1–C2 and C2–C3 facetectomies and right-sided osteotomies with C2 medial facetectomy were performed, along with an occipitocervical fixation down to C5. The C1 and C2 nerve roots were sectioned bilaterally. A silastic barrier was placed between the tumor mass and the ventral aspect of the thecal sac in preparation for en bloc resection of the tumor. Cancelous solid graft bone chips and demineralized bone matrix were used for fusion. Stage 2 involved an anterior cervical approach for en bloc resection of the C1, C2, and C3 region chordoma with anterior reconstruction of the craniocervical junction from the left occipital condyle down to the C3 vertebral body. Post-operatively, the patient developed significant dysphagia and a transient left-sided hypoglossal nerve palsy which eventually resolved. Subsequently, the patient had a follow-up MRI 4 months after the initial surgical procedure that demonstrated dislodgement of the cage with anterior migration of the caudal end of the cage with significant compression of the supralaryngeal region with imminent airway obstruction. At that point, the patient was taken back to surgery for retrieval of the migratory cage and reconstruction of the craniocervical junction once again. The patient
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Figure 1 (A) Contrast-enhanced magnetic resonance imaging (MRI) of cervical spine demonstrating large homogenously enhancing biopsy-confirmed chordoma along the anterior cervical spine extending from occiput down to C4. (B) After multistage en bloc chordoma resection, extensive posterior and anterior reconstruction with instrumentation extending from occiput to T4. (C) Lateral X-ray immediately post-operatively demonstrating extensive anterior and posterior reconstruction instrumentation. (D) Sagittal CT reconstruction demonstrating extensive anterior and posterior reconstruction instrumentation.
had done well for a period of time and then developed a lesion ventral to the C4 vertebral body. This lesion was biopsied and was consistent with recurrent chordoma. He had been treated with chemotherapy in the form of Gleevec and despite the chemotherapeutic intervention, the tumor continued to grow. The patient had extensive tumor involvement involving vertebral bodies of C4 and C5, partial involvement of the vertebral body of C3 with extension laterally on the right side involving the nerve roots of C4, C5, and C6 and also involving the vertebral artery on the right side. He also had growth of tumor extending behind the oropharynx and esophagus and putting pressure upon and displacing the esophagus and also he has impingement upon the trachea. He had tumor growing along the sternocleidomastoid on the left hand side as well. At this point, the patient underwent corpectomy of C4 and C5, resection of the transverse processes of C3–C6, mobilization and skeletonization of the right vertebral artery, intralesional resection of recurrent chordoma behind the vertebral bodies of C4 and C5, and intralesional resection of recurrent chordoma from the retropharyngeal and retroesophageal spaces with navigation guidance. Subsequently, he received further radiation therapy and chemotherapy. Despite all this therapy, he continued to have progressive disease, and
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he had disease extending from C2 down through C7, both ventral and posterior to the spinal cord compressing the spinal cord. He was weaker in his upper and lower extremities. He underwent removal of posterior instrumentation with laminectomy from C3–T1, resection of epidural tumor, and re-instrumentation from occiput-T3. Despite the multiple recurrences and re-operations, the patient is neurologically improved, but continues to have significant weakness in the lower extremities. Case 2
A 18-year-old male who initially presented with significant complaints of neck pain and arm pain and weakness of the intrinsic muscles of the hands was noted on CT and MRI to have an extensive aneurysmal bone cyst emanating from the C7 vertebral body and posterior elements, and extending out laterally on the right hand side (Fig. 2). The lesion had been biopsied prior to presentation at an outside hospital and was noted to be an aneurysmal bone cyst. This had both an epidural extension as well as intraspinal and extraspinal extension extending all the way into the brachial plexus and upper chest on the right hand side. Over time, the tumor has demonstrated increased activity and growth, forcing surgical treatment of this extensive lesion.
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Figure 2 (A) Sagittal contrast-enhanced magnetic resonance imaging (MRI) of the cervical spine demonstrating an aneurysmal bone cyst within the vertebral body of C7 with extension into the pedicles. (B) Pre-operative embolization demonstrating occlusion of blood supply to this large tumor. (C) Sagittal computerized tomography (CT) scan demonstrating anterior cervical corpectomy with placement of cage after en bloc resection. (D) Coronal CT scan showing en bloc defect at C7 with posterior segmental instrumentation along the lateral masses and thoracic pedicles.
Stage 1 involved a posterior cervical thoracic exposure, C4–T2 lateral and pedicle screw instrumentation, C6 and T1 laminectomies with foraminotomies, osteotomy of right C7 pedicle, en bloc resection of tumor, first rib resection, and brachial plexus exploration for tumor resection. Stage 2 involved an anterior cervical exposure for C6– C7 discectomy, C7–T1 discectomy, left side sagittal osteotomy through C7 vertebral body, resection of vertebral body and tumor at C7 including the pedicle of C7, anterior reconstruction from C6–T1 with titanium cage. Over 18 months later, he continues to be neurologically intact with a solid arthrodesis. Case 3 (Figure 3)
A 20-year-old male, who originally presented to an outside hospital with approximately 16-month history of progressive worsening neck and arm pain, later developed leftsided arm weakness as well (Fig. 3). The patient’s MRI scan demonstrated a tumor involving the upper cervical spine at C3–C4 with involvement of the proximal nerve
roots and left vertebral artery. The patient then underwent a left-sided anterior cervical approach C3–C4 corpectomy, partial intralesional resection of the tumor, anterior cervical reconstruction, fixation, and fusion at the outside hospital. Pathology confirmed an epithelioid sarcoma. The patient was then evaluated by medical oncology and radiation oncology and they both felt that given the residual tumor and the proximity of the tumor to the spinal cord and the spinal cord deformation, the patient would not be a very good candidate for post-operative adjuvant therapy under the circumstances. The patient was transferred to our institution for further surgical intervention. A subsequent MRI demonstrated further progression of the tumor with severe spinal cord compression, T2 signal changes in the spinal cord, bilateral vertebral artery involvement, and involvement of the proximal nerve roots on the left side at the C3, C4, C5, and C6 levels. Stage 1 involved a posterior cervical exposure, C2–C6 bilateral laminectomy, left C2–C3, 3–4, 4–5, 5–6 total facetectomy, mobilization of left-sided C3–C4, C5–C6 nerve roots and brachial plexus, resection of dorsal
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Figure 3 (A, B) Sagittal contrast-enhanced magnetic resonance imaging (MRI) of cervical spine demonstrating prior anterior cervical corpectomy graft with heterogeneously enhancing epithelioid sarcoma along the graft site with extension into epidural space causing spinal cord compression. (C) Sagittal computerized tomography (CT) scan showing post-operative changes after revision en bloc resection of sarcoma with occipital to T4 instrumentation.
component of the tumor on the left side, skeletonization of the left-sided vertebral artery, intra-operative test occlusion of left vertebral artery with intra-operative somatosensory and motor evoked potential and brainstem evoked potential monitoring, ligation of the left vertebral artery proximal and distal to the tumor, rightsided C3, C4–C5 pediculotomies in preparation for en bloc spondylectomy for completion spondylectomy from anteriorly during the second stage, occiput to T4 fixation using an occipital plate, thoracic pedicle screws T1, T2, T3, and T4 bilaterally, and occipitocervical and thoracic fixation using bone putty demineralized bone matrix. Stage 2 involved an anterior cervical approach completion spondylectomy with resection of the ventral component of the tumor along with C3, C4, and C5 vertebral bodies and previously placed hardware, C2 through C6 anterior cervical reconstruction
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using a cage graft, and anterior cervical fusion using bone putty and demineralized bone matrix. The patient did well post-operatively but no followup data is available.
Key Points for Complication Avoidance during En bloc Spondylectomy for Primary Cervical Spinal Tumors 1.
2.
3.
4.
Meticulous pre-operative preparation including biopsy for definitive diagnosis and decision on surgical approach and strategy. Intra-operative use of neuromonitoring to identify signs of neural deterioration early and critical during vertebral artery temporary occlusion. Awake fiberoptic intubation and placing patient prone while awake to obtain neurological examination prior to anesthesia and avoid spinal cord injury on positioning. Careful blunt mobilization of adherent tumor from surrounding structures including retroesophageal
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5.
6. 7. 8.
9.
space (anteriorly), vertebral arteries (laterally), and retropharyngeal space (anteriorly). Use of a silastic sheet during a multi-stage procedure to isolate critical structures from tumor, allowing easier en bloc tumor removal during the next stage while minimizing inadvertent injury to structures not clearly visible deep in the wound. Appropriate levels of instrumentation above and below spondylectomy site with anterior and posterior constructs. Appropriate arthrodesis and fusion with allograft to reduce pseudoarthrosis. Depending on tumor histology, timely neo-adjuvant (before surgery) and adjuvant chemotherapy¡radiotherapy/proton-beam therapy to reduce recurrence risk. Multidisciplinary treatment in collaboration with the radiation oncologists, medical oncologists, physical therapists, nurses, and social workers ensuring best possible outcome for patient.
Conclusion Management of patients with primary cervical spinal tumors is quite complex. Precise and timely diagnosis with history, physical examination, imaging, and biopsy are critical first steps. Meticulous pre-operative planning for en bloc surgical resection of cervical spinal tumors is necessary for improved patient outcome and to minimize intra-operative and post-operative complications. The strategies mentioned above should be followed as an algorithm for purposes of complication avoidance. Adjuvant proton-beam therapy and/or chemotherapy may be used depending on tumor histology for improved local control and overall survival. Finally, treatment of patients with spinal tumors is a multidisciplinary process requiring the collaboration of multiple specialties including neurosurgery, orthopedic surgery, radiation oncology, medical oncology, physical therapy, occupation therapy, nurses and social workers.
Disclaimer Statements Contributors PK and ZLG contributed to the planning of this review paper, literature search and review, and to the preparation and final review of the manuscript prior to submission. Funding The authors did not receive outside funding for this study. Conflicts of interest The authors have no disclosures regarding the submitted manuscript. ZLG has stock (selfmanaged) in US Spine and Spinal Kinetics, Grants and research support from AOSpine, NREF, and Depuy. Ethics approval No IRB approval required for this retrospective review of the literature. Three case reports are included, with all identifying information scrupulously removed from images. There was no assessment of surgical techniques or devices for this review article.
References 1 Weinstein JN, McLain RF. Primary tumors of the spine. Spine. 1987;12:843–51. 2 Boriani S, Bandiera S, Biagini R, Bacchini P, Boriani L, Cappuccio M, et al. Chordoma of the mobile spine: fifty years of experience. Spine. 2006;31:493–503.
Surgical management of tumors of cervical spine
3 Boriani S, De Iure F, Bandiera S, Campanacci L, Biagini R, Di FioreM et al. Chondrosarcoma of the mobile spine: report on 22 cases. Spine. 2000;25:804–12. 4 Tomita K, Kawahara N, Murakami H, Demura S. Total en bloc spondylectomy for spinal tumors: improvement of the technique and its associated basic background. J Orthop Sci. 2006;11:3–12. 5 Talac R, Yaszemski MJ, Currier BL, Fuchs B, Dekutoski MB, Kim CW, et al. Relationship between surgical margins and local recurrence in sarcomas of the spine. Clin Orthop Relat Res. 2002;397:127–32. 6 Healey JH, Lane JM. Chordoma: a critical review of diagnosis and treatment. Orthop Clin North Am. 1989;20(3):417–26. 7 Bjornsson J, Wold LE, Ebersold MJ, Laws ER. Chordoma of the mobile spine. A clinicopathologic analysis of 40 patients. Cancer. 1993;71:735–40. 8 Park L, Delaney TF, Liebsch NJ, Hornicek FJ, Goldberg S, Mankin H, et al. Sacral chordomas: impact of high-dose proton/photon-beam radiation therapy combined with or without surgery for primary versus recurrent tumor. Int J Radiat Oncol Biol Phys. 2006;65:1514–21. 9 Ng VW, Clifton A, Moore AJ. Preoperative endovascular embolization of a vertebral haemangioma. J Bone Joint Surg Br. 1997;79(5):808–11. 10 Jankowski R, Nowak S, Zukiel R, Szymas´ J, Soko´ł B, et al. Surgical treatment of symptomatic vertebral haemangiomas. Neurol Neurochir Pol. 2011;45(6):577–82. 11 Palumbo A, Anderson K. Multiple myeloma. New Engl J Med. 2011;364(11):1046–60. 12 Filder MW. Surgical treatment of giant cell tumors of the thoracic and lumbar spine: report of nine patients. Eur Spine J. 2001;10(1):69–77. 13 Liljenqvist U, Lerner T, Halm H, Buerger H, Gosheger G, Winkelmann W. En bloc spondylectomy in malignant tumors of the spine. European Spine Journal. 2008;17(4):600–9. 14 Seimon LP. Eosinophil granuloma of the spine. J Pediatr Orthop. 1981;1(4):371–6. 15 Marsh BW, Bonfiglio M, Brady LP, Enneking WF. Benign osteoblastoma: range of manifestations. J Bone Joint Surg Am. 1975;57(1):1–9. 16 Ameli NO, Abbassioun K, Saleh H, Eslamdoost A. Aneurysmal bone cysts of the spine. Report of 17 cases. J Neurosurg. 1985;63:685–90. 17 Medow JE, Agrawal BM, Resnick DK. Polyostotic fibrous dysplasia of the cervical spine: case report and review of the literature. Spine J. 2007;7(6):712–5. 18 Hsieh PC, Xu R, Sciubba DM, McGirt MJ, Nelson C, Witham TF, et al. Long term clinical outcomes following en bloc resections for sacral chordomas and chondrosarcomas: a series of twenty consecutive patients. Spine. 2009;34(20):2233–9. 19 Carpentier A, Blanquet A, George B. Suboccipital and cervical chordomas: radical resection with vertebral artery control. Neurosurg Focus. 2001;10:E4. 20 Barrenechea IJ, Perin NI, Triana A, Lesser J, Costantino P, Sen C. Surgical management of chordomas of the cervical spine. J Neurosurg Spine. 2007;6:398–406. 21 Junming M, Cheng Y, Dong C, Jianru X, Xinghai Y, Quan H, et al. Giant cell tumor of the cervical spine: a series of 22 cases and outcome. Spine. 2008;33:280–8. 22 Cloyd JM, Chou D, Deviren V, Ames CP. En bloc resection of primary tumors of the cervical spine: report of two cases and systematic review of the literature. Spine J. 2009;9:928–35. 23 Hoshino Y, Kurokawa T, Nakamura K, Seichi A, Mamada T, Saita K, et al. A report on the safety of unilateral vertebral artery ligation during cervical spine surgery. Spine. 1996;21:1454–7. 24 Cohen ZR, Fourney DR, Marco RA, Rhines LD, Gokaslan ZL. Total cervical spondylectomy for primary osteogenic sarcoma. Case report and description of operative technique. J Neurosurg. 2002;97:386–92. 25 Tomita K, Kawahara N. The threadwire saw: a new device for cutting bone. J Bone Joint Surg Am. 1996;78:1915–7. 26 Sciubba DM, Okuno SH, Dekutoski MB, Gokaslan ZL. Ewing and osteogenic sarcoma: evidence for multidisciplinary management. Spine. 2004;34(22S):58–68. 27 Catton C, O’Sullivan B, Bell R, Laperriere N, Cummings B, Fornasier V, et al. Chordoma: long-term follow-up after radical photon irradiation. Radiother Oncol. 1996;41:67–72. 28 Igaki H, Tokuuye K, Okumura T, Sugahara S, Kagei K, Hata M, et al. Clinical results of proton beam therapy for skull base chordoma. Int J Radiat Oncol Biol Phys. 2004;60:1120–6. 29 Casali PG, Messina A, Stacchiotti S, Tamborini E, Crippa F, Gronchi A, et al. Imatinib mesylate in chordoma. Cancer. 2004;101:2086–97.
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Surgical management of primary tumors of the cervical spine: surgical considerations and avoidance of complications Paul E. Kaloostian, Ziya L. Gokaslan The Johns Hopkins Hospital, Baltimore, MD, USA Objective: Primary cervical spinal tumors are rare tumors of the spine and are associated with significant morbidity and mortality. Such tumors include multiple myeloma, chordomas, giant cell tumors, hemangiomas, osteosarcomas, chondrosarcomas, synovial sarcomas, aneurysmal bone cysts (ABC), hemangiomas, eosinophilic granulomas, osteoid osteomas, and osteoblastomas. We review the surgical decision-making process and identify critical key steps for surgical complication avoidance. We also present case illustrations demonstrating such pathological diagnoses and surgical treatments performed. Methods: We retrospectively review the literature regarding the most common primary cervical spinal tumors that have undergone surgical resection with or without adjuvant treatment. Results: En bloc resection of primary cervical tumors resulted in significantly increased progression-free survival and overall survival. From the limited data, adjuvant treatment with proton-beam therapy for chordomas has potential benefit. Neo-adjuvant chemotherapy for Ewing’s sarcoma and osteogenic sarcoma has shown some promise, with en bloc resection demonstrating stronger benefit for osteogenic sarcoma. Discussion: En bloc resection for primary spinal tumors has proven to be the standard of care in spinal oncology. Adjuvant and neo-adjuvant treatments such as chemotherapy and radiotherapy variants (conventional, proton beam, cyberknife) need to be studied further in most primary tumor types to become standard of care. Chordoma management is more widely studied with en bloc resection and adjuvant proton-beam therapy demonstrating improved progression-free survival and overall survival. Surgical management and adjuvant treatment strategies are case dependent, depending on tumor histology, patient neurological examination, prior surgeries at that level, and prior adjuvant treatment. Keywords: Cervical spine, En bloc, Primary tumors, Spinal chordomas, Spinal complication
Introduction The axial skeleton is a common site for both primary tumors and metastatic disease, with metastatic disease being most common. Distinguishing between the two is critical in terms of further therapeutic modalities, such as type of treatment, extent of resection, and post-operative adjunctive therapy. Primary bony tumors are seen to grow and flourish within the spinal axis, and although they are rare, the morbidity and mortality associated with them is not insignificant.1 We discuss a variety of primary bony tumors of the cervical spine, each of which display unique pathophysiological and histological properties that help determine current diagnostic and treatment modalities. Finally, we discuss surgical technique and common pitfalls that surgeons may encounter during
Correspondence to: Paul E. Kaloostian, The Johns Hopkins Hospital, 600 North Wolfe Street, Baltimore, MD 21205, USA. Email: paulkaloostian@ hotmail.com
ß W. S. Maney & Son Ltd 2014 DOI 10.1179/1743132814Y.0000000367
surgical resection, and methods of complication avoidance.
Differential Diagnosis The differential diagnosis of primary bony tumors of the spine is quite diverse. It includes pathology such as: multiple myeloma, chordomas, giant cell tumors, hemangiomas, osteosarcomas, chondrosarcomas, synovial sarcomas, aneurysmal bone cysts (ABC), hemangiomas, eosinophilic granulomas, osteoid osteomas, and osteoblastomas. Other lesions that may mimic primary spinal tumors include infection, metastatic disease, and possibly hematoma (either spontaneous or traumatic).
Diagnostic Process Patients with primary tumors of the spine will most commonly present to their primary care physician or emergency department with chronic and progressively worsening focal back pain. Depending on the
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morphologic characteristics of the spinal tumor, tumor size, and tumor infiltration to surrounding neural and vascular structures, patients will present with a variety of other symptoms. These symptoms may include paraspinal pain, intractable radicular pain due to foraminal involvement of tumor burden, and finally various degrees of myelopathy or cauda equina syndrome depending on location within the spinal canal. Paraspinal pain is due to infiltration of tumor into surrounding muscle and subcutaneous tissues. Radiculopathy is due to tumor extension into neural foramen compressing exiting nerve roots. Tumor burden extending within the spinal canal in the epidural space may cause spinal cord compression. For example, patients with cervical epidural tumor invasion may initially present with gait instability and weakness of hands. Patients will describe dropping objects from their hands that then may progress to severe weakness of arms and legs, requiring the use of a wheelchair. With further tumor extension, vascular supply to the spinal cord is compromised and the neural structures are compressed. Patients may also describe bowel and bladder deficits in cases of severe stenosis. Patients with predominantly primary sacral tumors with severe canal and foraminal involvement may present with severe low back pain and cauda equina syndrome with perineal numbness, bowel and bladder dysfunction, and/or lower extremity weakness.1–8 Physical examination is critical when evaluating patients with spinal lesions. Patients with cervical lesions with spinal cord compression will have signs of myelopathy on examination. These include positive Hoffman sign, hyperreflexia in upper and lower extremities, upgoing Babinski signs bilaterally, spastic weakness of upper and lower extremities, and gait instability. Patients with severe spinal cord compression may present with quadriplegia with a sensory or motor level. Patients with lumbosacral tumors with canal compromise may have weakness and/or numbness in one or both extremities, and evidence of perineal numbness and saddle anesthesia. Diagnostic modalities for primary tumors of the spine include computerized tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET) scans, and CT of the chest/ abdomen/pelvis. Computerized tomography scans of the entire spine are obtained to analyze the bony quality and bony anatomy at the site of tumor burden as well as to rule out other lesions within the spinal column. Computerized tomography scans can help determine extent of tumor erosion of vertebral anatomy and extent of destruction from anterior to posterior columns of the spine. Magnetic resonance imaging scans with and without contrast are critical to obtain for tumors of the spinal column. Magnetic
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resonance imaging may delineate more clearly the anatomy of the tumor and extent of tumor enhancement. Magnetic resonance imaging will identify regions of tumor that may be cystic or necrotic without enhancement, as well as extension of tumor burden into surrounding tissues. Also, MRI is important to identify tumor burden within the epidural space and extent of neural element compression or injury, either centrally or foraminally. Positron emission tomography scans are helpful in determining other areas of abnormal radioactive uptake of glucose throughout the body, signifying possible metastatic disease or tumor elsewhere. Computerized tomography of the chest/abdomen/ pelvis with and without contrast is often obtained to rule out other areas of tumor burden in order to rule out metastatic disease. Standard labs, including white blood cell count, red blood cell count, coagulation numbers, and electrolyte levels should be obtained to rule out infectious process and prepare the patient for possible surgical intervention. If no other lesions are noted elsewhere based on CT and PET scans, then an isolated spinal column lesion without acute deterioration should receive a core biopsy in order to obtain a definitive diagnosis. This can be done percutaneously by the interventional radiology team using fluoroscopic guidance. Once this is done and a diagnosis is obtained, the multidisciplinary treatment plan can be arranged. Determining whether the spinal column mass is a primary spinal tumor versus metastatic disease or infection is crucial before instituting surgical treatment. Metastatic disease is classically treated with intralesional resection due to tumor burden elsewhere, while over the last decade en bloc resection for primary spinal tumors has improved patient outcome and survival. Intralesional resection of primary spinal tumors will disseminate tumor elsewhere, whereby en bloc extracapsular resection may avoid tumor spread and provide negative surgical margins grossly and histopathologically. Unless acute neurological deterioration is observed, patients should follow this standard paradigm when being diagnosed with a spinal column mass.2–5
Primary Tumor Breakdown with General Treatment Paradigms Chordoma
N N N
Surgical management includes en bloc resection without violation of the tumor capsule, offering an increased progression-free survival of over 60% at 5 years while minimizing local recurrence.6,7 Subtotal resection provides a local recurrence rate of 8 months as opposed to over 2 years with en bloc resection. Adjunctive treatment includes post-operative protonbeam radiotherapy.8
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Hemangiomas
N N N N
Hemangiomas are benign and classically asymptomatic lesions that are typically located in the vertebral bodies of the thoracic spine. Radiographically, CT scans will demonstrate the ‘spikes of bone’ appearance within the vertebral body, while MRI will show an enhancing tumor with hemorrhage.9 Asymptomatic patients only require observation of the lesion, while symptomatic patients may receive radiation or surgical resection. Pre-operative embolization reduces the risk of intraoperative hemorrhage and should be performed when angiography identifies the arterial blood supply.10
Multiple myeloma
N N N N N
Diagnostic modalities include bone marrow aspiration, CT-guided biopsy of lesions, serum and urine electrophoresis and a CBC, and bone marrow biopsy demonstrating abnormal plasma cells. Immunohistochemical analysis is crucial in identifying lambda and kappa heavy chain and light chain distributions.11 Patients with stable spinal disease without deformity or neurological deficit may be managed non-operatively with pain management, conventional radiation therapy for focal disease, and/or chemotherapy for systemic disease. Patients with severe spinal instability, spinal deformity, and spinal cord compromise will require surgical intervention. The 5-year survival remains less than 30% despite aggressive surgical and adjuvant management.11
Giant cell tumor
N N N N
A CT-guided biopsy is often recommended to look for the classic mononuclear stromal cells with giant cells throughout. Conventional radiotherapy is recommended for focal disease and en bloc spondylectomy is recommended for large symptomatic lesions.12 The role of post-operative radiotherapy is currently unclear, as malignant transformation of the giant cell tumor has been reported. Local recurrence rates are noted to be at 40–67% within the mobile spine.12,13
Eosinophilic granuloma
N N N N
Eosinophilic granulomas of the spine are benign lesions that are typically found incidentally with vertebral flattening which precedes eventual vertebral collapse.14 If patient has not been diagnosed prior with histiocytosis X, then biopsy is indicated to confirm the diagnosis. Low-dose conventional radiotherapy is recommended for symptomatic lesions without neurological compromise and/or patients who are not operative candidates. Symptomatic lesions or growing lesions causing deformity, instability, or neurological decline will surgical resection. Data regarding en bloc versus intralesional resection are very limited.14
Osteoblastoma
N
Osteoblastomas are rare benign tumors of the spine in young adults that are similar to osteoid osteomas, but are larger than 2 cm in size.
N N
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Small tumors may be treated with observation and pain control. Larger tumors causing mass effect and neurological deficit require surgical treatment. Some studies advocate intralesional excision followed by conventional radiotherapy while others recommend en bloc resection in stages.15
Aneurysmal bone cyst
N N N N
Aneurysmal bone cysts are benign expansile lesions of bone composed of blood-filled cavities separated by septa of osteoclastic cells. Treatments include curettage, subtotal excision, en bloc resection, embolization, intralesional injection, and radiation. For lesions that are asymptomatic, conservative treatment with or without bracing is indicated. For larger lesions with neurological compromise, surgical treatment is recommended. Pre-operative embolization may play a role in management.16
Fibrous dysplasia
N N N
Biopsy may show curvilinear trabecular woven bone with a background of fibroblasts. Surgery is indicated in cases of neural compromise and/or instability. Surgical approach would depend on the location along the spinal axis but may require multi-stage corpectomy with instrumentation and fusion.17
Osteosarcomas
N N N N N
Sarcomas of the spine are quite complex but in cases of neurological compromise from compression and/or instability, surgical treatment is warranted. Recent evidence for chondrosarcomas, Ewing’s sarcomas, and osteogenic sarcomas has emerged showing an increased progression-free survival after en bloc resection without violation of tumor capsule. Neo-adjuvant treatment with chemotherapy for Ewing’s sarcoma and osteogenic sarcoma has shown improved patient survival. Additionally, conventional radiotherapy post-operatively has a role in patients with Ewing’s sarcoma. Osteogenic sarcomas are radioresistant.18
Osteoid osteomas
N N N N
Osteomas are typically self-limiting. When pain is intractable or patient’s tumor is causing instability or neural compromise, surgery is indicated. Surgical treatment generally involves instrumentation and fusion. The role of en bloc resection is unclear.
En bloc resection of primary spinal tumors Many studies have now been published validating the role of en bloc resection as standard of care for primary spinal column tumors. The goal of en bloc resection of tumor, as compared to the prior mainstay surgical treatment of all spinal tumors of piecemeal resection, is mainly to prevent seeding of tumor cells into surrounding tissues. The hypothesis was that this strategy would avoid dissemination of tumor and ultimately lead to a prolonged disease-free and overall survival. Talac et al. studied patients with primary sarcomas of the spine. Their studied cohorts
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included en bloc resection with negative margins, piecemeal resection with negative margins, and all resections with positive margins. They found recurrence rates of 11, 33, and 50–70% in these groups, respectively.5 Carpentier et al. noted in their study of 16 patients with occipitocervical chordomas, a 40% recurrence rate and 33% mortality rate over a 5-year follow up in these patients who underwent solely piecemeal resection.19 Additionally, Barrenechea et al. studied seven patients with intralesional piecemeal resections of cervical chordomas and noted an approximately 30% recurrence rate over a median of a 2-year follow up.20 Junming et al. analyzed 21 patients who underwent piecemeal resection of cervical giant cell tumors and noted a recurrence rate of 33% over a mean follow up of 68 months.21 Cloyd et al. studied two patients with cervical chordoma who underwent en bloc resection and performed a meta-analysis of the existing literature on cervical primary spinal tumors with en bloc resection. The analysis involved 10 articles comprising 18 cases, including the authors’ two cases. The authors identify a combined recurrence rate of 22% in all published studies for primary cervical spine tumors with a mean follow up of 47.4 months.22 They also note mean operative time, estimated blood loss, and length of hospital stay were 18.6 hours, 2.9 L, and 34.6 days, respectively. They noted three case of local recurrence at 12, 44, and 113 months along with one case of distant metastasis at 12 months post-operatively. The authors then calculated a disease-free survival rate of approximately 88 and 76% at 1 and 5 years, respectively. No factors were identified as predictive of recurrence in this meta-analysis.22 En bloc resection of cervical lesions is quite complex and is not without significant risk of morbidity and mortality. For this reason, preoperative understanding of patient pathology, involvement of neural and vascular structures, and even intracranial vascular anatomy are quite important in determining patient outcome. One such risk factor is injury to the vertebral artery(s). Depending on primary spinal tumor morphology and extension, the vertebral arteries may be encased with tumor on presentation, adding to the danger of surgical resection. While some studies have recommended a clear avoidance of en bloc vertebrectomy in the cervical spine due precisely to the risk posed to the vertebral arteries and cervical nerve roots, others have published data demonstrating safety and feasibility. Hoshino et al. published a study of 15 patients who underwent unilateral vertebral artery ligation during en bloc resection of cervical spinal tumors and noted no adverse events affecting the brain stem, spinal cord, or cerebellum.23 However, Cohen et al. presented a case report of a patient with C6 osteosarcoma managed with intralesional resection and post-operative chemotherapy as an
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adjuvant to en bloc resection.24 Despite the high risk, many studies have now described vertebral artery ligation during primary spinal tumor resection and have documented adequate results. The importance, however, of pre-operative cranial and spinal angiography, as well as temporary occlusion of the vertebral artery with somatosensory evoked potentials and motor evoked potential monitoring, is crucial prior to ligation of the vertebral artery. Cranial anastomotic anatomy to the posterior circulation is critical in case of bilateral or dominant vertebral artery injury or vasospasm intraoperatively and post-operatively. The presence of a neurovascular surgeon is helpful in cases requiring intracranial bypass procedures. During vertebral artery manipulation, any neurological decline in neuromonitoring while temporary clipping necessitates preserving the artery. In the meta-analysis by Cloyd et al. the authors note that 8 of the 18 patients who underwent en bloc resection of primary cervical spinal tumors had unilateral vertebral artery ligation without complication.22 Other possible risk factors involved in en bloc resection of primary cervical spinal tumors include infection, significant bleeding, dysphagia, aspiration, spinal instability, seeding of tumor cells into surrounding tissues and into the cerebrospinal fluid if a dural tear is encountered, spinal cord and/or nerve root injury, and large vessel injury including the internal carotid arteries, vertebral arteries, and internal jugular veins.22 Techniques of complication avoidance are critical for spinal surgeons who specialize in treating cervical spine tumors. A variety of important strategies exist to minimize complications intra-operatively in order to provide the most efficient patient outcome. For example, Tomita et al. describe the use of pre-operative embolization of vessels supplying spinal tumors. The authors note a significant decrease in intra-operative bleeding with pre-operative embolization, meticulous blunt dissection, and resection of tumor, and through the use of fibrin glue in the epidural venous plexus.4 Additionally, Tomita et al. describe the use of a Tsaw for pediculotomy or anterior column osteotomy.25 They note a decrease in tumor spread after the use of the T-saw. Others have described the use of rinsing instruments with cisplatin or distilled water to prevent tumor seeding.4 Meticulous blunt dissection and separation of tumor from surrounding prevertebral structures is crucial in avoiding inadvertent injury to the esophagus, trachea, and retropharyngeal mucosa. Placement of a silastic sheath anterior to the spinal cord and other nearby structures, as is done after an initial posterior cervical stage at the author’s institution, separating the now separated vital structures from tumor helps in removing the tumor en bloc during the second anterior stage of the procedure.
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This method allows clear demarcation of tumor and plays a vital role in diminishing intra-operative complications such as vascular or spinal cord injury. Surgical treatment of Ewing’s sarcoma and osteogenic sarcoma of the cervical spine has noted recent advances in the last decade. The Spinal Oncology Study Group has published data with strong recommendations and moderate quality evidence of neo-adjuvant (before surgery) chemotherapy with a weak recommendation with very low evidence for en bloc surgical resection for Ewing’s sarcoma of the spine. They note en bloc surgical resection to provide improved local control, but not improved overall survival. The authors mention that the use of radiation therapy alone or as adjuvant treatment may be used for local control, but this evidence is very low. For patients with osteogenic sarcoma, the authors have a strong recommendation with moderate quality evidence favoring neo-adjuvant chemotherapy. Additionally, the authors have a strong recommendation with very low evidence for en bloc resection providing improved local control and potentially improved overall survival.26 The role of adjuvant treatment with chemotherapy and radiation is still unclear in the treatment of primary cervical spinal tumors. Additionally, the role of different radiation modalities, such as radiosurgery, conventional radiation treatment, and proton-beam radiotherapy, remain debatable. The role of adjuvant treatment has been studied in spinal chordomas. Chordomas are classically relatively resistant to conventional radiation treatments at doses that are favorable to surrounding tissues at ,60 Gy.27 Small skull base chordomas have responded quite well to low doses of radiotherapy in a single case series.28 Proton-beam therapy, though, has proved in a few published studies to be of benefit to patients with spinal chordomas.27,28 Proton-beam therapy has the advantage of intensity modulated and extreme precision allowing for an effectively high dose of focused radiation at the chordoma with minimal surrounding tissue damage. For these reasons, it is recommended to use protonbeam therapy either pre-operatively or post-operatively for spinal chordomas.2,3,20 Neo-adjuvant chemotherapy for Ewing’s sarcomas and osteogenic sarcomas has shown clear benefit, along with radiotherapy for Ewing’s sarcoma. Non-operative treatment for cases of multiple myeloma without acute neurological decline would consist of radiotherapy for focal disease and chemotherapy for systemic disease. Some cases of multiple myeloma with epidural extension do not necessarily require surgical treatment, and have shown clear remission after conventional radiotherapy. Chemotherapy with imatinib mesylate has been shown in one study to benefit patients with spinal chordomas, though further studies are required.29
Surgical management of tumors of cervical spine
Complications associated with radiotherapy are not insignificant. These include wound breakdown and infection, particularly if performed at least 2 weeks before surgical treatment, neurological decline from radiation necrosis, and a small risk of developing radiation-induced malignancy. Case illustrations Case 1 A 35-year-old male presented to the emergency room with swallowing and upper airway obstruction (Fig. 1). On CT and MRI, the patient was found to have a large lesion extending from the C2 vertebral body with significant pre-cervical extension into the retropharyngeal space. The patient had a CT-guided biopsy of this lesion via a trans-oral route, which proved to be a chordoma. The patient then underwent a two-stage surgical procedure. With each surgery, neuromonitoring was utilized, along with awake fiberoptic intubation and placement of the patient into a prone position while awake to obtain adequate neurological examination on positioning and minimize neurological complication. Stage 1 involved a posterior approach for C1 through C3 bilateral complete laminectomies, bilateral mobilization of the tumor from the cervical and retropharyngeal structures, and ligation of the leftsided vertebral artery after no somatosensory evoked potential or motor evoked potential changes occurred on temporary occlusion. Ligation of the left vertebral artery was performed both proximal and distal to the tumor. Additionally, left C1–C2 and C2–C3 facetectomies and right-sided osteotomies with C2 medial facetectomy were performed, along with an occipitocervical fixation down to C5. The C1 and C2 nerve roots were sectioned bilaterally. A silastic barrier was placed between the tumor mass and the ventral aspect of the thecal sac in preparation for en bloc resection of the tumor. Cancelous solid graft bone chips and demineralized bone matrix were used for fusion. Stage 2 involved an anterior cervical approach for en bloc resection of the C1, C2, and C3 region chordoma with anterior reconstruction of the craniocervical junction from the left occipital condyle down to the C3 vertebral body. Post-operatively, the patient developed significant dysphagia and a transient left-sided hypoglossal nerve palsy which eventually resolved. Subsequently, the patient had a follow-up MRI 4 months after the initial surgical procedure that demonstrated dislodgement of the cage with anterior migration of the caudal end of the cage with significant compression of the supralaryngeal region with imminent airway obstruction. At that point, the patient was taken back to surgery for retrieval of the migratory cage and reconstruction of the craniocervical junction once again. The patient
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Figure 1 (A) Contrast-enhanced magnetic resonance imaging (MRI) of cervical spine demonstrating large homogenously enhancing biopsy-confirmed chordoma along the anterior cervical spine extending from occiput down to C4. (B) After multistage en bloc chordoma resection, extensive posterior and anterior reconstruction with instrumentation extending from occiput to T4. (C) Lateral X-ray immediately post-operatively demonstrating extensive anterior and posterior reconstruction instrumentation. (D) Sagittal CT reconstruction demonstrating extensive anterior and posterior reconstruction instrumentation.
had done well for a period of time and then developed a lesion ventral to the C4 vertebral body. This lesion was biopsied and was consistent with recurrent chordoma. He had been treated with chemotherapy in the form of Gleevec and despite the chemotherapeutic intervention, the tumor continued to grow. The patient had extensive tumor involvement involving vertebral bodies of C4 and C5, partial involvement of the vertebral body of C3 with extension laterally on the right side involving the nerve roots of C4, C5, and C6 and also involving the vertebral artery on the right side. He also had growth of tumor extending behind the oropharynx and esophagus and putting pressure upon and displacing the esophagus and also he has impingement upon the trachea. He had tumor growing along the sternocleidomastoid on the left hand side as well. At this point, the patient underwent corpectomy of C4 and C5, resection of the transverse processes of C3–C6, mobilization and skeletonization of the right vertebral artery, intralesional resection of recurrent chordoma behind the vertebral bodies of C4 and C5, and intralesional resection of recurrent chordoma from the retropharyngeal and retroesophageal spaces with navigation guidance. Subsequently, he received further radiation therapy and chemotherapy. Despite all this therapy, he continued to have progressive disease, and
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he had disease extending from C2 down through C7, both ventral and posterior to the spinal cord compressing the spinal cord. He was weaker in his upper and lower extremities. He underwent removal of posterior instrumentation with laminectomy from C3–T1, resection of epidural tumor, and re-instrumentation from occiput-T3. Despite the multiple recurrences and re-operations, the patient is neurologically improved, but continues to have significant weakness in the lower extremities. Case 2
A 18-year-old male who initially presented with significant complaints of neck pain and arm pain and weakness of the intrinsic muscles of the hands was noted on CT and MRI to have an extensive aneurysmal bone cyst emanating from the C7 vertebral body and posterior elements, and extending out laterally on the right hand side (Fig. 2). The lesion had been biopsied prior to presentation at an outside hospital and was noted to be an aneurysmal bone cyst. This had both an epidural extension as well as intraspinal and extraspinal extension extending all the way into the brachial plexus and upper chest on the right hand side. Over time, the tumor has demonstrated increased activity and growth, forcing surgical treatment of this extensive lesion.
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Figure 2 (A) Sagittal contrast-enhanced magnetic resonance imaging (MRI) of the cervical spine demonstrating an aneurysmal bone cyst within the vertebral body of C7 with extension into the pedicles. (B) Pre-operative embolization demonstrating occlusion of blood supply to this large tumor. (C) Sagittal computerized tomography (CT) scan demonstrating anterior cervical corpectomy with placement of cage after en bloc resection. (D) Coronal CT scan showing en bloc defect at C7 with posterior segmental instrumentation along the lateral masses and thoracic pedicles.
Stage 1 involved a posterior cervical thoracic exposure, C4–T2 lateral and pedicle screw instrumentation, C6 and T1 laminectomies with foraminotomies, osteotomy of right C7 pedicle, en bloc resection of tumor, first rib resection, and brachial plexus exploration for tumor resection. Stage 2 involved an anterior cervical exposure for C6– C7 discectomy, C7–T1 discectomy, left side sagittal osteotomy through C7 vertebral body, resection of vertebral body and tumor at C7 including the pedicle of C7, anterior reconstruction from C6–T1 with titanium cage. Over 18 months later, he continues to be neurologically intact with a solid arthrodesis. Case 3 (Figure 3)
A 20-year-old male, who originally presented to an outside hospital with approximately 16-month history of progressive worsening neck and arm pain, later developed leftsided arm weakness as well (Fig. 3). The patient’s MRI scan demonstrated a tumor involving the upper cervical spine at C3–C4 with involvement of the proximal nerve
roots and left vertebral artery. The patient then underwent a left-sided anterior cervical approach C3–C4 corpectomy, partial intralesional resection of the tumor, anterior cervical reconstruction, fixation, and fusion at the outside hospital. Pathology confirmed an epithelioid sarcoma. The patient was then evaluated by medical oncology and radiation oncology and they both felt that given the residual tumor and the proximity of the tumor to the spinal cord and the spinal cord deformation, the patient would not be a very good candidate for post-operative adjuvant therapy under the circumstances. The patient was transferred to our institution for further surgical intervention. A subsequent MRI demonstrated further progression of the tumor with severe spinal cord compression, T2 signal changes in the spinal cord, bilateral vertebral artery involvement, and involvement of the proximal nerve roots on the left side at the C3, C4, C5, and C6 levels. Stage 1 involved a posterior cervical exposure, C2–C6 bilateral laminectomy, left C2–C3, 3–4, 4–5, 5–6 total facetectomy, mobilization of left-sided C3–C4, C5–C6 nerve roots and brachial plexus, resection of dorsal
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Figure 3 (A, B) Sagittal contrast-enhanced magnetic resonance imaging (MRI) of cervical spine demonstrating prior anterior cervical corpectomy graft with heterogeneously enhancing epithelioid sarcoma along the graft site with extension into epidural space causing spinal cord compression. (C) Sagittal computerized tomography (CT) scan showing post-operative changes after revision en bloc resection of sarcoma with occipital to T4 instrumentation.
component of the tumor on the left side, skeletonization of the left-sided vertebral artery, intra-operative test occlusion of left vertebral artery with intra-operative somatosensory and motor evoked potential and brainstem evoked potential monitoring, ligation of the left vertebral artery proximal and distal to the tumor, rightsided C3, C4–C5 pediculotomies in preparation for en bloc spondylectomy for completion spondylectomy from anteriorly during the second stage, occiput to T4 fixation using an occipital plate, thoracic pedicle screws T1, T2, T3, and T4 bilaterally, and occipitocervical and thoracic fixation using bone putty demineralized bone matrix. Stage 2 involved an anterior cervical approach completion spondylectomy with resection of the ventral component of the tumor along with C3, C4, and C5 vertebral bodies and previously placed hardware, C2 through C6 anterior cervical reconstruction
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using a cage graft, and anterior cervical fusion using bone putty and demineralized bone matrix. The patient did well post-operatively but no followup data is available.
Key Points for Complication Avoidance during En bloc Spondylectomy for Primary Cervical Spinal Tumors 1.
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Meticulous pre-operative preparation including biopsy for definitive diagnosis and decision on surgical approach and strategy. Intra-operative use of neuromonitoring to identify signs of neural deterioration early and critical during vertebral artery temporary occlusion. Awake fiberoptic intubation and placing patient prone while awake to obtain neurological examination prior to anesthesia and avoid spinal cord injury on positioning. Careful blunt mobilization of adherent tumor from surrounding structures including retroesophageal
Kaloostian and Gokaslan
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space (anteriorly), vertebral arteries (laterally), and retropharyngeal space (anteriorly). Use of a silastic sheet during a multi-stage procedure to isolate critical structures from tumor, allowing easier en bloc tumor removal during the next stage while minimizing inadvertent injury to structures not clearly visible deep in the wound. Appropriate levels of instrumentation above and below spondylectomy site with anterior and posterior constructs. Appropriate arthrodesis and fusion with allograft to reduce pseudoarthrosis. Depending on tumor histology, timely neo-adjuvant (before surgery) and adjuvant chemotherapy¡radiotherapy/proton-beam therapy to reduce recurrence risk. Multidisciplinary treatment in collaboration with the radiation oncologists, medical oncologists, physical therapists, nurses, and social workers ensuring best possible outcome for patient.
Conclusion Management of patients with primary cervical spinal tumors is quite complex. Precise and timely diagnosis with history, physical examination, imaging, and biopsy are critical first steps. Meticulous pre-operative planning for en bloc surgical resection of cervical spinal tumors is necessary for improved patient outcome and to minimize intra-operative and post-operative complications. The strategies mentioned above should be followed as an algorithm for purposes of complication avoidance. Adjuvant proton-beam therapy and/or chemotherapy may be used depending on tumor histology for improved local control and overall survival. Finally, treatment of patients with spinal tumors is a multidisciplinary process requiring the collaboration of multiple specialties including neurosurgery, orthopedic surgery, radiation oncology, medical oncology, physical therapy, occupation therapy, nurses and social workers.
Disclaimer Statements Contributors PK and ZLG contributed to the planning of this review paper, literature search and review, and to the preparation and final review of the manuscript prior to submission. Funding The authors did not receive outside funding for this study. Conflicts of interest The authors have no disclosures regarding the submitted manuscript. ZLG has stock (selfmanaged) in US Spine and Spinal Kinetics, Grants and research support from AOSpine, NREF, and Depuy. Ethics approval No IRB approval required for this retrospective review of the literature. Three case reports are included, with all identifying information scrupulously removed from images. There was no assessment of surgical techniques or devices for this review article.
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Surgical management of tumors of cervical spine
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