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Part I: Spinal-cord neoplasms—intradural neoplasms
Review
Part I: Spinal-cord neoplasms—intradural neoplasms David E Traul, Mark E Shaffrey, David Schiff
Intradural spinal-cord tumours are an uncommon but important consideration in the differential diagnosis of patients with back pain, radicular pain, sensorimotor deficits, or sphincter dysfunction. Intradural spinal tumours can be divided into intramedullary and extramedullary spinal-cord tumours on the basis of their anatomical relation to the spinal parenchyma. The heterogeneous cell composition of the intradural compartment allows the formation of neoplasms, arising from glial cells, neurons, and cells of spinal vasculature. Additionally, developmental tumours, metastases, and intradural extension of extradural tumours are represented. In this Review, we discuss the published work on intradural spinal-cord tumours in terms of epidemiological, radiographic, and histological characteristics. Surgical and adjuvant treatment strategies are also reviewed.
Lancet Oncol 2007; 8: 35–45
Introduction
Correspondence to: Dr David Schiff, University of Virginia Health System, NeuroOncology Center, P.O. Box 800432, Charlottesville, VA 22908,USA [email protected] Part II: Spinal-cord neoplasms— primary tumours of the bony spine and adjacent soft tissues will be published in February 2007.
Nerve-sheath tumours Schwannomas and neurofibromas account for up to a third of intradural spinal-cord tumours in the adult population but are less common in children. Peak
Michael English/Custom Medical Stock Photo/Science Photo Library
Spinal-cord neoplasms (SCNs; figure 1) are an uncommon cause of back pain, radicular pain, and sensorimotor deficits in both adult and paediatric patients. SCNs can be divided into extradural and intradural tumours on the basis of their relation to the thecal sac that surrounds the spinal cord and cauda equina. Extradural tumours, located outside the thecal sac, account for almost 60% of SCNs. About 30% of tumours are contained within the thecal sac and are, therefore, intradural neoplasms. Concomitant intradural and extradural components are associated with roughly 10% of SCNs. Within the intradural compartment, tumours can originate adjacent to (extramedullary) or within (intramedullary) the spinalcord parenchyma. In view of the heterogeneous cell composition within the intradural compartment, the histogenesis of neoplasms located at this site is varied (panel). Differentiation and diagnosis of intramedullary spinal-cord tumours (IMSCTs) and extramedullary spinal-cord tumours (EMSCTs) are widely achievable through clinical examination and radiographic techniques. MRI is the preferred method of radiographic assessment of intradural spinal tumours and can suggest histological subtype. Other radiographic examinations, such as CT and myelogram, are useful if MRI is contraindicated. Magnetic resonance angiogram (MRA) or spinal arteriogram can be beneficial if the tumour has a vascular component. Histological examination of the tumour after biopsy or surgical resection is able to establish the histogenesis of intradural tumours in almost all cases.
Patients with symptomatic EMSCTs most often present with symptoms of spinal-cord compression indistinguishable from non-neoplastic causes. Most patients will be symptomatic at the time of diagnosis, and onset of symptoms can precede diagnosis by months to years. Local or radicular pain is the most common presenting symptom in patients with EMSCTs, and has highest incidence with tumours located in the lumbar spine.1 Paresthaesias and numbness are common symptoms, and hypesthesia or anesthesia at and below a level of the spinal cord is often evident on clinical examination. Patterns of sensory deficits, such as posterior-cord syndrome, can suggest tumour localisation. Motor weakness in the form of spastic paraparesis is common too, but findings of monoparesis, hemiparesis, or even paraplegia might be present at diagnosis. Sphincter dysfunction can develop early in the course of the disease, especially with tumours of the cauda equina. Ataxia, torticollis, and skeletal deformities are less common presenting symptoms.1
Department of Neurology (D E Traul MD, D Schiff MD), Department of Neurosurgery (M E Schaffrey MD, D Schiff), and Neuro-Oncology Center (M E Shaffrey, D Schiff), University of Virginia Health System, Charlottesville, VA, USA
Extramedullary tumours EMSCTs account for more than 70% of intradural spinalcord tumours in adults and are only slightly less common in children. The most common primary EMSCTs are derived from sheath cells covering the spinal-nerve roots (schwannomas and neurofibromas) or meningial cells located along the spinal-cord surface (meningiomas). Myxopapillary ependymomas are extramedullary tumours arising from the conus medullaris and filum terminalis. Other tumour types, such as hemangiopericytomas, lipomas, paragangliomas, epidermoid cysts, and dermoid cysts are less common. http://oncology.thelancet.com Vol 8 January 2007
Figure 1: Spinal-cord neoplasms are extradural or intradural tumours according to their relation to the thecal sac
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Panel: Intradural spinal-cord neoplasms Intramedullary tumours Neuroepithelial tumours Astrocystic astrocytomas Ependymal ependymomas Oligodendroglial oligodendrogliomas Mixed neuronal–glial gangliogliomas Embryonal neuroblastomas Other CNS tumours Benign mesenchymal lipomas Germ cell teratomas Uncertain hemangioblastomas Vascular malformations Capillary hemangiomas Cavernous hemangiomas Intramedullary metastases Small-cell lung cancer Non-small-cell lung cancer Lymphoma Renal-cell carcinoma Others Extramedullary tumours Neuroepithelial tumours Ependymal myxopapillary ependymomas Other CNS tumours Meningial meningiomomas Benign mesenchymal lipomas Malignant mesenchymal hemangiopericytomas Tumours of spinal nerves Nerve sheath schwannomas Nerve sheath neurofibromas Local extension of regional tumours Paragangliomas Tumour-like cysts Dermoid Epidermoid Extramedullary metastases Mass lesions from neoplastic meningitis
incidence of nerve-sheath tumours is in the fourth to fifth decade of life, and there is equal incidence in both men and women. Schwannomas are more common than neurofibromas and usually present as solitary tumours. Occasionally, multiple spinal schwannomas are seen with schwannomatosis or neurofibromatosis type II. Neurofibromas often show multiplicity, especially when associated with neurofibromatosis type 1. About 60–80% of nerve-sheath tumours arise from nerve roots before leaving the dural sac. A further 10% arise as the nerve root leaves the dural sac and becomes surrounded by the dural-root sleeve. These tumours, therefore, display both intradural and extradural components (dumbbell tumour). Nervesheath tumours that are entirely extradural or 36
Figure 2: Schwannoma Lumbar MRI shows half-dumbbell mass in left T-12 neural foramen. Mass showed heterogeneous enhancement with gadolinium on T1-weighted images and was identified as schwannoma after resection.
intramedullary are less common. Intradural nervesheath tumours most commonly affect the lumbosacral region, but cervical and thoracic tumours have been reported too.2 Intradural nerve-sheath tumours might be more common in the lumbosacral region because of the longer intradural segment of the caudal spinalnerve roots in the neuraxis.3 Nerve-sheath tumours are generally regarded as benign neoplasms, but can be malignant in a few cases, where they are designated the term malignant peripheral nerve-sheath tumours (MPNSTs). Although more than 50% of MPNSTs are associated with neurofibromatosis type 1, only a small percentage of patients with this disease have malignant neoplasms. Anatomically, schwannomas tend to arise from the dorsal-nerve root whereas neurofibromas are more common on the ventral root. Other than this difference, schwannomas and neurofibromas are indistinguishable on MRI. Nerve-sheath tumours have an isointense signal on T1-weighted images and a hyperintense signal on T2-weighted images. Gadolinium adds variable enhancement ranging from a homogeneous to a peripheral ring-like enhancement (figure 2).4 Although an irregular enhancement pattern is associated with malignant tumours, differentiation from benign entities is unreliable with radiographic methods. Histologically, schwannomas display neoplastic Schwann cells without nerve fibres. Neurofibromas more frequently invade the nerve root, and display Schwann cells, nerve fibres, and fibroblasts. The primary treatment of nerve-sheath tumours is directed at total surgical resection, which is obtainable in most cases. Subtotal resection of these tumours might be an option when the tumour is attached to the http://oncology.thelancet.com Vol 8 January 2007
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Figure 3: Meningioma Thoracic MRI with gadolinium contrast showed a mass with strong homogeneous enhancement on T1-weighted axial (A) and sagittal (B) images. Mass was hyperintense on T2-weighted images (C).
spinal cord, or when the tumour exhibits an extradural component closely associated with vital structures, such as the vertebral artery in the cervical region.3 To obtain total resection, the ventral or dorsal roots are commonly sacrificed; however, resection of the nerve root is usually not associated with pronounced postoperative motor or sensory deficit.3 Because schwannomas arise from dorsal-nerve roots and are less invasive than neurofibromas, surgical resection less often results in pronounced motor deficits than does resection of neurofibromas. Postoperative morbidity can be affected by spinal location of nerve-sheath tumours, with cervical and thoracic lesions predicting worse neurological outcome than more caudal sites.2 Radiotherapy or chemotherapy is usually reserved for tumours that have malignant histological characteristics. Tumour recurrence is less than 5% and might have a high association with subtotal tumour removal.2
images and a hyperintense signal on T2-weighted images. The addition of gadolinium contrast gives strong homogeneous enhancement (figure 3). Calcifications are frequent and could preclude gadolinium enhancement.4 Most intradural meningiomas are non-invasive, benign neoplasms, helping with gross total resection of the tumour. Even when considering the technical challenges of anterior locations, total surgical resection of meningiomas is attainable in more than 90% of patients.8 The tumour recurrence rate with total or subtotal resection is between 3% and 7%.5,6,8 Atypical and anaplastic spinal meningiomas have a higher tumour recurrence rate and rarely metastasise. Radiotherapy could be considered after subtotal resection or recurrence of spinal meningiomas by analogy with management of intracranial meningiomas.
Hemangiopericytoma Meningioma Spinal meningiomas account for up to 46% of spinal neoplasms,5 and are more common intradurally than extradurally. A small percentage of spinal meningiomas are located extradurally, and extension of these tumours into the intradural compartment is common. The thoracic level is the most frequent site for spinal meningiomas, and these tumours have a predilection for women in the fifth to seventh decade of life. Intradural meningiomas are mostly located lateral or posterior to the spinal cord, with the anterior location being less frequent.5,6 Although intradural meningiomas are usually solitary lesions, multiplicity might be encountered when these tumours are associated with neurofibromatosis type 2. Intradurally, meningothelial and psammomatous meningiomas are the most common histological subtypes of spinal meningioma. Intradural clear-cell meningioma is less frequent and associated with a worse prognosis.7 Atypical or anaplastic spinal meningiomas are rare. On MRI, spinal meningiomas have a hypointense to isointense signal on T1-weighted http://oncology.thelancet.com Vol 8 January 2007
Hemangiopericytomas are uncommon neoplasms of the CNS with uncertain histogenesis. Spinal hemangiopericytoma is rarely encountered, with fewer than ten reported cases involving an intradural extramedullary hemangiopericytoma.9–11 Hemangiopericytomas are hypercellular with frequent mitoses and necrosis seen on microscopic examination. These malignant characteristics predict the aggressive clinical course of these tumours and recurrence is common.9 Accordingly, surgical resection is usually needed. Because of the notable vascularity of these tumours, preoperative embolisation of hemangiopericytomas through interventional angiographic techniques is often attempted. Radiotherapy has proven effective in reducing recurrence of intracranial hemangiopericytomas, but there is insufficient evidence relating to spinal locations.
Lipoma Lipomas are congenital, benign tumours uncommon in the intradural compartment. When present, intradural extramedullary lipomas are associated with spinal dysraphism in about a third of cases. Children are more 37
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commonly affected than adults. Intradural extramedullary lipomas are usually located in the lower thoracic and lumbosacral levels. A tethered-cord syndrome present at birth or developing during infancy can be encountered with lipomas of the cauda equina. This syndrome consists of sensorimotor deficits, pain, skeletal deformities, and sphincter dysfunction, and is less common in adults with lumbrosacral lipomas.12 On MRI, intradural lipomas have a hyperintense signal on T1-weighted images and a hypointense signal on T2weighted images. Microscopically, lipomas consist of mature adipose cells and connective tissue. Decompressive surgical resection is recommended for symptomatic intradural lipomas. When there is widespread involvement of the cord, conus, or nerve roots, subtotal resection is usually undertaken to prevent postoperative morbidity. Intraoperative electrophysiological stimulation with evoked EMG monitoring is often used to allow differentiation between the functional spinal cord and the mass. When unassociated with a tethered cord, prophylactic resection of asymptomatic lipomas of the filum terminalis can prevent subsequent neurological decline.13
Myxopapillary ependymoma Myxopapillary ependymomas account for roughly 40–50% of spinal ependymomas and are more common in the adult population than in children.14 Ependymomas of the myxopapillary variant arise in the filum terminalis and account for up to 80% of ependymomas found in the cauda equina. This variant is distinguished from other ependymomas by the mucinous changes undergone by the tumour cells. Patients normally present with a long history of radicular pain, lower extremity sensorimotor deficit, and sphincter dysfunction. Myxopapillary ependymomas are typically benign, well-circumscribed tumours. MRI reveals a circumscribed mass with hypointense signal on T1-weighted images and hyperintense signal on T2-weighted images. Contrast enhancement with gadolinium is usually homogeneous. Histologically, myxopapillary ependymomas display ependymal rosettes or perivascular pseudorosettes, with the characteristic deposition of myxoid material around blood vessels. Total surgical resection of myxopapillary ependymomas is feasible if the nerve roots in the cauda equina are not entrapped within the tumour. In an attempt to keep to a minimum postoperative neurological morbidity, subtotal resection is not uncommon. Focal fractionalised radiotherapy seems to be effective at improving neurological outcome and reducing tumour recurrence rate after subtotal tumour resection or piecemeal total excision.15 Recurrence of wholly resected tumours is generally rare, but is associated with a poor outcome.16 These tumours can seed the spinal subarachnoid space, in which case broader field 38
radiation is used, but this is uncommon. Although chemotherapy is sometimes started for recurrent or disseminated myxopapillary ependymomas, results are unconvincing.
Paraganglioma Paragangliomas are derived from autonomic-nervoussystem paraganglion cells and are uncommon in the CNS. Spinal paragangliomas are generally nonsecreting, sympathetic neoplasms,17 which tend to occur in the fourth to fifth decade of life and show a male predominance. The most frequent intradural location for paragangliomas is the cauda equina and lumbar spine regions, apart from intradural thoracic or cervical paragangliomas.18,19 On MRI, paragangliomas present as a well circumscribed mass with a hypointense to isointense signal on T1-weighted images and a hyperintense signal on T2-weighted images. Paragangliomas are characteristically hypervascular, and gadolinium contrast administration produces a heterogeneous salt and pepper pattern of enhancement.20 Scanning using radiolabelled metaiodobenzylguanidine (mIBG), a noradrenaline analogue with uptake independent of catecholamine secretion, can allow visualisation of paragangliomas.21 Histological appearance of paragangliomas displays a highly vascularised tumour bed containing round and polygonal cells grouped in clusters called zellballen. Immunohistological methods to detect chromogranin and synaptophysin can be useful for diagnosis. Intradural paragangliomas are mainly benign neoplasms, and gross total surgical resection is the preferred treatment. Although catecholamine-secreting spinal paragangliomas are uncommon, preoperative screening for a hyperadrenergic state is necessary to prevent hypertensive crisis during tumour removal. Recurrence rate after total or subtotal resection of intradural paragangliomas is less than 5% and is not reduced by concomitant radiotherapy or chemotherapy. Although iodine-131 labelled mIBG (131I-mIBG) can slow progression and improve remission rate for metastatic paragangliomas,21 efficacy in primary intradural paragangliomas is unproven.
Dermoid and epidermoid cysts Dermoid and epidermoid cysts are usually congenital neoplasms arising from heterotopic ectodermal-cell implantation into the neural tube early in embryonic development. Dermoid and epidermoid cysts represent only 1% of CNS tumours, and are rarely located in the spinal column. These tumours most commonly affect the lumbosacral region, with rare reports of thoracic involvement.22 Dermoid and epidermoid cysts are usually diagnosed in the first two decades of life, with dermoid cysts presenting earlier than epidermoid cysts.23 http://oncology.thelancet.com Vol 8 January 2007
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On gross appearance, dermoid cysts can be differentiated from epidermoid cysts by the appearance of skin appendages such as hair follicles; however, the distinction between these tumours is often difficult by imaging. Both intradural dermoid and epidermoid cysts have variable MRI appearance, with hypointense to hyperintense signal on T1-weighted images and isointense to hyperintense signal on T2-weighted images. There is usually minimum enhancement with gadolinium. Histologically, dermoid and epidermoid cysts are composed of a lining of epithelial tissue supported by a collagenous network. Dermoid cysts contain sebaceous or apocrine glands in the thicker portions of the epithelial lining. Gross total resection of dermoid and epidermoid cysts is desirable when possible, but adhesion to neural tissue can prevent aggressive techniques. When subtotal resection is done, emptying of the cystic contents and removal of a portion of the capsule is encouraged. Dissemination of the cystic contents spontaneously or during tumour removal might produce a granulomatous meningitis treatable with corticosteroids.24 Recurrence of resected intradural dermoid and epidermoid cysts is uncommon, and malignant tumours are rare. Adjuvant radiotherapy or chemotherapy for non-operable or malignant cases has not been thoroughly studied.
Extramedullary metastasis Intradural extramedullary spinal-cord metastasis is seen at autopsy in fewer than 5% of patients who have died from cancer. These tumours are commonly the result of drop lesions from intracranial metastasis from adenocarcinoma of the lung, prostate cancer, breast cancer, melanoma, or lymphoma.25,26 Alternatively, intradural extramedullary metastases represent drop lesions from intracranial neoplasms such as gliomas and medulloblastomas. Metastatic spread from intracranial lesions can involve dissemination of neoplastic cells through the CSF, and multiple lesions are common. Intradural extramedullary metastases are most common in the thoracolumbar or thoracic spine, and tend to present as localised pain and spinal tenderness. With involvement of the nerve roots of the cauda equina, a radicular pattern of pain might be evident. Motor and sensory deficits, especially the Brown-Sequard syndrome, are common. Sphincter dysfunction is present in about a third of patients. Because intradural extramedullary metastasis usually indicates advanced widespread progression of the systemic malignancy, aggressive surgical resection of lesions is usually not done. Treatment is, therefore, directed towards palliative and functional goals. Radiotherapy allows improvement in neurological function in a large population of patients. Adjuvant treatment with intravenous or oral corticosteroids can improve neurological function as well and provide symptomatic relief. http://oncology.thelancet.com Vol 8 January 2007
Intramedullary tumours IMSCTs account for 20–30% of intradural tumours in adults, and up to 50% of intradural tumours in children.27,28 Glial tumours, such as astrocytomas and ependymomas, represent up to 80% of IMSCTs, with a paediatric predominance of astrocytomas and an adult predominance of ependymomas. Oligodendrogliomas, mixed gliomas, neuron-derived tumours, gangliogliomas, hemangioblastomas, lipomas, and developmental tumours are uncommon. Finally, metastatic intramedullary spinal-cord tumours account for only 1–3% of IMSCTs. Non-neoplastic processes, such as multiple sclerosis and granulomatous disease, can account for up to 4% of intramedullary lesions, usually foreseen by an acute or subacute course and systemic involvement.29,30 Patients with IMSCTs most often present with myelopathic symptoms with insidious onset, with preoperative symptom duration measured in months to years. Localised pain and upper-extremity paresthaesias are the initial symptoms in 50–90% of the adult population with cervical IMSCTs.28,31 Thoracic IMSCTs can present with lower-extremity sensory loss that extends proximally with upper-motor-neuron signs in the lower extremities. Radicular pain becomes more prominent with IMSCTs of the lumbosacral spine affecting the nerve roots in the cauda equina. Disruption of sphincter function is seen in up to 44% of IMSCTs in adults.32 In the paediatric population, pain is less often an initial symptom but is present in more than 40% of children with IMSCTs. Motor weakness is a complaint in 36–90% of paediatric patients, and gait disturbances are reported in 27–66%.27,33 Urinary dysfunction is seen in almost 20% of children with IMSCTs. Torticollis or kyphoscoliosis could be the initial complaint too.27,33
Astrocytoma Astrocytomas account for 80–90% of IMSCTs in childhood and roughly 60% of IMSCTs in adolescence.27,33–37 Intramedullary astrocytomas have peak incidence in the third decade of life, but are not as common as intramedullary ependymomas in this age group. In adults, astrocytomas make up almost 25% of all IMSCTs.37 There seems to be equal incidence in men and women. Intramedullary astrocytomas are predominantly located in the cervicothoracic or thoracic region in the paediatric population,27,35 but cervical involvement becomes more common in the adult population. Lower thoracic and lumbosacral levels are rarely affected. At the time of diagnosis, astrocytomas have usually extended to multiple bone levels and 30–60% of tumours are associated with rostral, caudal, or intratumoral cysts.4,27 Elongated cysts extending several levels from the tumour location represent syringomelia. Low-grade pilocytic astrocytomas and fibrillary astrocytomas account for almost two-thirds of intramedullary astrocytomas in adults, and almost 90% of 39
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Figure 4: Pilocytic astrocytoma Cervical MRI shows isointense mass at C5–6 on T1-weighted images (A) that enhanced with gadolinium contrast (B). Mass was hyperintense (arrow) on T2-weighted images (C).
intramedullary astrocytomas in children. MRI of lowgrade astrocytomas reveals an enlarged homogeneous mass with a hypointense to isointense signal on T1-weighted images and a hyperintense signal on T2weighted images.4 There is little to no surrounding oedema or haemorrhage with low-grade astrocytomas. Most intramedullary astrocytomas enhance with gadolinium contrast, and calcifications are rare.38 Pilocytic astrocytomas (figure 4) can be well-delineated, but fibrillary astrocytomas are poorly defined with irregular tumour margins. Microscopically, low-grade spinal astrocytomas show a low degree of cellularity, a low mitotic activity, and an absence of both necrosis and endothelial microvascular proliferation. Pilocytic astrocytomas typically contain Rosenthal fibres. Highgrade anaplastic astrocytoma and glioblastoma multiforme account for about 10% of intramedullary astrocytomas. On MRI, these high-grade tumours often display heterogeneous enhancement caused by the presence of intratumoral cysts, necrosis, and surrounding oedema.38 Microscopically, anaplastic astrocytoma and glioblastoma multiforme show moderate to high cellularity, and increased mitotic activity. Glioblastoma multiforme usually exhibits necrosis and endothelial microvascular proliferation. Treatment of intramedullary astrocytomas is directed at total surgical resection; however, less extensive surgical intervention could be considered with higher grade, more infiltrative tumours to avoid pronounced postsurgical morbidity. Most surgeons prefer electrophysiological monitoring of the spinal cord during surgical treatment of IMSCTs. Motor-evoked potential and somatosensory-evoked potential monitoring are the most common modalities. Gross total resection of pilocytic astrocytomas is achievable in many instances, as these tumours are often well circumscribed. However, because of the infiltrative nature of even low-grade fibrillary astrocytomas, gross total resection of these tumours is difficult without risking perioperative and postoperative morbidity and mortality. Gross total resection rates range between 30% and 70%.27,32,33 40
Subtotal resection of fibrillary astrocytomas is appropriate in many cases, and there does not seem to be any significant difference in survival rates between total and subtotal resection techniques when long-term data are compared within tumour grades.35,39,40 Intramedullary fibrillary astrocytomas have a high recurrence rate, ranging from 25% in low-grade tumours to almost 100% in high-grade tumours.27,28 Adjuvant radiotherapy at diagnosis of high-grade astrocytomas or with tumour recurrence is advocated. The role of concomitant chemotherapy is uncertain, but the postoperative course of both low-grade and high-grade spinal astrocytomas can be changed with this adjuvant treatment.41 In low-grade intramedullary astrocytomas, 5-year survival rates range from 80% to 100%.33 Patients with intramedullary anaplastic astrocytomas or glioblastoma multiformes have an average life expectancy of 15 months.9,27,33
Ependymoma Intramedullary ependymomas represent almost 40–60% of adults with IMSCTs with a peak incidence in the fourth to fifth decade of life.28,32,37 Intramedullary ependymomas account for only 16–35% of IMSCTs in the paediatric population.35,37 Most intramedullary ependymomas arise in the cervical or cervicothoracic region; however, thoracic and thoracolumbar ependymomas are not uncommon.35,42,43 True intramedullary ependymomas are most often of the cellular variant; however, papillary, clear-cell, anaplastic, and mixed subtypes occur in the spinal cord too.37,42 MRI shows a lesion hypointense on T1-weighted imaging and hyperintense on T2-weighted imaging.4 Intramedullary ependymomas homogeneously enhance with contrast (figure 5).4 Although not encapsulated, intramedullary ependymomas often show a distinct plane between the tumour and the adjacent spinal cord, despite frequent association with cysts, syrinxes, and haemorrhage. Microscopically, spinal ependymomas might display ependymal rosettes but perivascular pseudorosettes are more prominent. http://oncology.thelancet.com Vol 8 January 2007
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Figure 5: Ependymoma Thoracic MRI shows mass at T3–T8 levels. Mass was hypointense to isointense on T1-weighted images (A), and enhanced with gadolinium contrast (B). Mass was hyperintense on T2-weighted axial (C) and sagittal (D) images. Arrows indicate extent of thoracic spinal-cord involvement.
Intramedullary ependymomas are mostly wellcircumscribed tumours, which helps with total surgical resection in 70–100% of cases.35,44,45 Tumour recurrence after gross total resection is less than 10%, but can be delayed by the slow growth rate of ependymomas. With subtotal resection, tumour recurrence is seen in 50–70% of cases.45,46 Therefore, prognosis for patients with intramedullary ependymomas is dependent on the extent of surgical resection. Postoperative radiation treatment remains controversial but could increase tumour-free survival rates of adult patients with high-grade or subtotally resected tumours.46–48 In children, the use of radiotherapy has been debated because of radiationinduced damage to the CNS.49 Additonally, in both adult and paediatric populations, prior adjuvant radiotherapy might make subsequent surgical interventions more difficult and heighten postoperative neurological morbidity. The 5-year survival rates for low-grade intramedullary ependymomas range between 83% and 100%,42,45,50 but decline rapidly with higher grade ependymomas.47
Subependymoma Subependymomas of the spinal cord are rare representations of IMSCTs with less than 50 cases reported. These tumours have a higher incidence in men and typically present in the fourth or fifth decade of life.51 Intramedullary subependymomas are most commonly located in the cervical cord, although involvement of the thoracic cord has been reported.52 On MRI, intramedullary subependymomas have characteristics similar to ependymomas, showing spinal-cord enlargement with a hypointense signal on T1-weighted images and a hyperintense signal on T2-weighted images with heterogeneous enhancement.51,53 Microscopically, intramedullary subependymomas display a dense fibrillary background separating sparse clusters of tumour cells with well-defined, ovoidnuclei-containing stippled chromatin. Although http://oncology.thelancet.com Vol 8 January 2007
ependymal rosettes might be seen, mitotic activity is usually absent. Treatment for intramedullary subependymomas is directed at total gross resection whenever possible. Frequently, intramedullary subependymomas are eccentrically located in the spinal cord, which can help differentiate these tumours from the more centrally located ependymomas on a surgical basis.51,53 Intramedullary subependymomas are sharply circumscribed which helps with gross tumour removal. Adjuvant radiotherapy or chemotherapy is usually not used after total or partial tumour removal.
Oligodendroglioma Intramedullary oligodendrogliomas represent a small percentage of spinal-cord tumours and fewer than 2% of CNS oligodendrogliomas.54,55 These tumours have highest incidence in the second or third decade of life, and spinal deformities often accompany neurological symptoms. Intramedullary oligodendrogliomas are most often located at the thoracic levels, with cervical and lumbar levels less common. Radiographically, intramedullary oligodendrogliomas present as an irregular mass with associated spinal-cord enlargement and possible syrinx. MRI shows a lesion with an isointense signal on T1-weighted images and a hyperintense signal on T2-weighted images with heterogeneous enhancement.54 Microscopically, oligodendrogliomas display densely arranged cells resembling mature oligodendrocytes surrounded by a halo, resulting in a characteristic, so-called, fried-egg appearance. Anaplastic oligodendrogliomas can show mitotic activity, vascularisation, and necrosis. Total surgical resection of intramedullary oligodendrogliomas is difficult as a result of their frequent infiltration of surrounding neural tissue. Additionally, these tumours frequently manifest leptomeningeal metastasis, which complicates management and worsens overall prognosis.56 Adjuvant radiotherapy of an 41
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rare representations of IMSCTs and are most commonly located at the cervical level, but can present as diffuse lesions across multiple spinal levels.63 Treatment is surgical resection and there are insufficient data to evaluate adjuvant radiotherapy.
Lipoma
Figure 6: Hemangioblastoma Thoracic MRI shows an intensely enhancing mass at T5 level (arrow) on T1-weighted images (A). T2-weighted imaging (B) showed extensive syrinx formation above and below the tumour (arrows).
intramedullary anaplastic oligodendroglioma has shown to be effective in one case.54
Ganglioglioma Gangliogliomas are composed of a mixture of neoplastic neurons and glial cells with a predilection for the pediatric population. Intramedullary gangliogliomas are uncommon tumours, accounting for roughly 1% of spinal-cord neoplasms.57,58 Peak incidence is in childhood and these tumours are rarely reported after the fourth decade of life.59 Intramedullary gangliogliomas are located predominately at cervicothoracic or thoracic levels, and can span multiple vertebral segments.60 There could be a mild sex bias for men. Intramedullary gangliogliomas are usually isointense to hyperintense on T1-weighted imaging and hyperintense on T2-weighted imaging with heterogeneous contrast enhancement and frequent syrinxes.61 Microscopically, gangliogliomas are composed of a mixture of neoplastic ganglion and glial cells, mostly astrocytic elements. Immunohistochemistry techniques might be required to distinguish neoplastic ganglion and glial elements from non-neoplastic tissue. Treatment of intramedullary gangliogliomas is directed at gross total tumour resection, which can be achieved in 80–90% of cases.60,61 Tumour recurrence after resection ranges from 30% to 47% and 5-year actuarial survival rate ranges between 88% and 89%.60,62 Adjuvant radiation can be beneficial with subtotal resection of spinal gangliogliomas59; however, there are insufficient data to support chemotherapy. Malignant transformation of residual tumour cells is rare.
Neuroblastoma Neuroblastic tumours of the spinal cord include primitive neuroblastomas and tumours containing differentiated neuroblasts, ganglion cells, and schwannian stroma such as ganglioneuromas. They are 42
The incidence of intramedullary spinal lipomas ranges from 1% to 11% of spinal tumours.32 Most intramedullary lipomas involve the cervical or thoracic spinal cord, with rare reports of holocordal involvement.64 Spinal lipomas are congenital and usually become symptomatic in early adulthood. When not associated with spinal dysraphism, displacement of the spinal cord by lipomas can produce earlier symptom onset. Intramedullary lipomas have hyperintense signals on T1-weighted images and hypointense signals on T2-weighted images indicating the high proportion of tumour adipose tissue. Lobulated fatty tissue with interspersed connective and neural tissue on histological preparations confirms diagnosis. Surgical resection of symptomatic intramedullary lipomas is directed at debulking the tumour rather than gross total resection. Congenital lipomas can impede normal development of the surrounding neural tissue, and, therefore, postsurgical improvement is often absent.65
Teratoma Intradural location of teratomas is rare and intramedullary teratomas are especially unusual. Case reports of intramedullary teratomas tend to describe tumour location in the conus medullaris.66,67 Histologically, intramedullary teratomas are usually mature and regarded as benign. Surgical resection provides good postoperative outcome and tumour recurrence is uncommon.
Hemangioblastoma Hemangioblastomas of the spinal cord are predominantly intramedullary, although these tumours can be extramedullary and extradural. Intramedullary hemangioblastomas represent about 4% of spinal tumours and occur sporadically or in association with von Hippel-Lindau syndrome. Almost 25% of patients diagnosed with intramedullary hemangioblastomas have von Hippel-Lindau syndrome.68 Sporadic intramedullary hemangioblastomas have a peak incidence in the third or fourth decade of life and men are more affected than women. Hemangioblastomas associated with this syndrome have an earlier age of onset than sporadic cases of hemangioblastoma.69 Most are solitary tumours, although multiple lesions are not uncommon.69 Intramedullary hemangioblastomas are predominately located in the cervical or thoracic levels.70 On MRI, intramedullary hemangioblastomas often appear as cysts with enhancing mural nodules. http://oncology.thelancet.com Vol 8 January 2007
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Associated syringobulbia and syringomyelia are common (figure 6). Gadolinium provides homogeneous enhancement of small tumours and heterogeneous enhancement in larger tumours.4 Feeding arteries and draining veins can also be visible with contrasted MRI. Because of the highly vascularised nature of hemangioblastoma, spinal angiography can be useful for diagnosis and surgical planning. Microscopically, hemangioblastomas display a reticular pattern of small capillaries and foamy stromal cells. Gross total resection of symptomatic intramedullary hemangioblastomas is the preferred treatment and is generally associated with low morbidity.69–71 In patients with multiple hemangioblastomas of the spinal cord, tumour resection should be directed at the symptomatic neoplasm. When intramedullary hemangioblastomas are part of a systemic presentation of von Hippel-Lindau syndrome, tumour resection should be considered on a case-by-case basis. To our knowledge, there have been no reports of adjuvant chemotherapy or radiotherapy in the treatment of intramedullary hemangioblastomas of sporadic origin or in association with von HippelLindau syndrome. However, there are a few published works on treating intracranial hemangioblastomas with antiangiogenic drugs like thalidomide, interferon-alfa, and SU5416.
Angiomatous lesions Angiomatous lesions of the spinal cord are considered vascular malformations rather than true neoplasms. They are uncommon, affecting only a small percentage of paediatric and adult patients. Clinical presentation of intramedullary angiomatous tumours is similar to that of other IMSCTs; however, subacute or stepwise symptom onset can be seen with repeated haemorrhaging from dilated vessels.72 They are divided into capillary and cavernous subtypes on the basis of the size of the dominant vessel, and capillary hemangiomas have a higher incidence than the capillary subtype. Because of their larger size, however, cavernous hemangiomas are more likely to be symptomatic at presentation. Most cavernous angiomas are located in the cervical or thoracic spine, and multiplicity is not uncommon.73 There does not appear to be a sex preference. Radiographic assessments of intramedullary angiomatous lesions display a focal lesion without enlargement of the spinal cord. If the malformation produces venous congestion, then the tumour could be associated with local oedema and spinal-cord swelling.74 Intramedullary angiomatous lesions have a heterogeneous hyperintense signal on T1-weighted and T2-weighted images, with an area of hypointense signal surrounding the lesion on T2-weighted images.72 These tumours are usually non-enhancing with gadolinium contrast. Total surgical resection of symptomatic intramedullary angiomatous lesions is generally possible and patient http://oncology.thelancet.com Vol 8 January 2007
Search strategy and selection criteria Data for this review were identified by searches of MEDLINE, PubMed, and references from relevant articles using the following search terms: “spinal”, “intradural”, “intramedullary”, “extramedullary”, “schwannoma”, “neurofibroma”, “myxopapillary ependymoma” “epidermoid”, “dermoid”, “hemangiopericytoma”, “lipoma”, “meningioma”, “paraganglioma”, “metastasis”, “astrocytoma”, “ependymoma”, “ganglioglioma”, “hemangioblastoma”, “lipoma”, “neuroblastoma”, “neurofibroma”, “oligodendroglioma”, “subependymoma”, and “teratoma”. The final reference list was generated from original papers published in English between the years 1985 and 2006.
outcome is excellent. Intraoperative haemorrhagic complications are uncommon as angiomatous lesions are usually low-pressure vascular malformations. Haemorrhage in unresected intramedullary angiomatous lesions has an incidence of 1·4% per year.73
Intramedullary metastasis Intramedullary spinal-cord metastasis (ISCM) is an uncommon complication of systemic cancer, affecting fewer than 1% of all patients dying from systemic malignancies.75 However, with the advent of sensitive MRI techniques to identify intramedullary lesions, the incidence of ISCM appears to be higher than previously shown. Usually, patients with ISCM already have metastatic disease to other organs, including the brain. ISCM is predominately associated with lung cancer, with metastasis from small-cell lung cancer disproportionately represented. Renal-cell carcinoma, breast cancer, and melanoma are less commonly associated with ISCM.76 ISCM mainly affects the conus and cervical levels of the spinal cord, with the thoracic cord less commonly involved. Most cases involve a single lesion. As patients with ISCM usually have metastatic spread to other organs, treatment of ISCM is directed towards palliative and functional goals. Radiotherapy, often with concomitant corticosteroids, can help alleviate pain and preserve residual neurological function. Although open biopsy of some lesions is needed, aggressive surgical resection is usually deferred. Outlook after diagnosis of ISCM is poor, with median survival of 3 months and only 15% survival at 1 year.
Conclusion Although uncommon, intradural spinal-cord tumours should be an important consideration in the differential diagnosis of the adult or paediatric patient presenting with back or radicular pain associated with neurological deficits. The heterogeneous cell composition within the intradural compartment allows the presence of a 43
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histologically variable group of neoplasms. Radiographic assessment combined with histological examination helps with the identification of the histogenesis of these tumours, which is vital when exploring surgical and adjuvant treatment options and patient management. Conflicts of interest We declare no conflicts of interest. References 1 el-Mahdy W, Kane PJ, Powell MP, Crockard HA. Spinal intradural tumours: Part I--Extramedullary. Br J Neurosurg 1999; 13: 550–57. 2 Conti P, Pansini G, Mouchaty H, et al. Spinal neurinomas: retrospective analysis and long-term outcome of 179 consecutively operated cases and review of the literature. Surg Neurol 2004; 61: 34–43. 3 Jinnai T, Koyama T. Clinical characteristics of spinal nerve sheath tumors: analysis of 149 cases. Neurosurgery 2005; 56: 510–15. 4 Van Goethem JW, van den Hauwe L, Ozsarlak O, et al. Spinal tumors. Eur J Radiol 2004; 50: 159–76. 5 Roux FX, Nataf F, Pinaudeau M, et al. Intraspinal meningiomas: review of 54 cases with discussion of poor prognosis factors and modern therapeutic management. Surg Neurol 1996; 46: 458–63. 6 Gezen F, Kahraman S, Canakci Z, Beduk A. Review of 36 cases of spinal cord meningioma. Spine 2000; 25: 727–31. 7 Oviedo A, Pang D, Zovickian J, Smith M. Clear cell meningioma: case report and review of the literature. Pediatr Dev Pathol 2005; 8: 386–90. 8 Solero CL, Fornari M, Giombini S, et al. Spinal meningiomas: review of 174 operated cases. Neurosurgery 1989; 25: 153–60. 9 Ciappetta P, Celli P, Palma L, Mariottini A. Intraspinal hemangiopericytomas. Report of two cases and review of the literature. Spine 1985; 10: 27–31. 10 Dufour H, Metellus P, Fuentes S, et al. Meningeal hemangiopericytoma: a retrospective study of 21 patients with special review of postoperative external radiotherapy. Neurosurgery 2001; 48: 756–62. 11 Betchen S, Schwartz A, Black C, Post K. Intradural hemangiopericytoma of the lumbar spine: case report. Neurosurgery 2002; 50: 654–57. 12 Gupta SK, Khosla VK, Sharma BS, et al. Tethered cord syndrome in adults. Surg Neurol 1999; 52: 362–69. 13 Pierre-Kahn A, Zerah M, Renier D, et al. Congenital lumbosacral lipomas. Childs Nerv Syst 1997; 13: 298–334. 14 Celli P, Cervoni L, Cantore G. Ependymoma of the filum terminale: treatment and prognostic factors in a series of 28 cases. Acta Neurochir (Wien) 1993; 124: 99–103. 15 Schweitzer JS, Batzdorf U. Ependymoma of the cauda equina region: diagnosis, treatment, and outcome in 15 patients. Neurosurgery 1992; 30: 202–07. 16 Gagliardi FM, Cervoni L, Domenicucci M, et al. Ependymomas of the filum terminale in childhood: report of four cases and review of the literature. Childs Nerv Syst 1993; 9: 3–6. 17 Walsh JC, O’Brien DF, Kumar R, Rawluk D. Paraganglioma of the cauda equina: a case report and literature review. Surgeon 2005; 3: 113–16. 18 Sundgren P, Annertz M, Englund E, et al. Paragangliomas of the spinal canal. Neuroradiology 1999; 41: 788–94. 19 Silverstein AM, Quint DJ, McKeever PE. Intradural paraganglioma of the thoracic spine. AJNR Am J Neuroradiol 1990; 11: 614–16. 20 Shin JY, Lee SM, Hwang MY, et al. MR findings of the spinal paraganglioma: report of three cases. J Korean Med Sci 2001; 16: 522–26. 21 Noorda RJ, Wuisman PI, Kummer AJ, et al. Nonfunctioning malignant paraganglioma of the posterior mediastinum with spinal cord compression. A case report. Spine 1996; 21: 1703–09. 22 Scarrow AM, Levy EI, Gerszten PC, et al. Epidermoid cyst of the thoracic spine: case history. Clin Neurol Neurosurg 103: 220–22. 23 Shikata J, Yamamuro T, Mikawa Y, Kotoura Y. Intraspinal epidermoid and dermoid cysts. Surgical results of seven cases. Arch Orthop Trauma Surg 1988; 107: 105–09. 24 Lunardi P, Missori P, Gagliardi FM, Fortuna A. Long-term results of the surgical treatment of spinal dermoid and epidermoid tumors. Neurosurgery 1989; 25: 860–64.
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Matsumoto K, Nakagaki H. Intramedullary subependymoma occupying the right half of the thoracic spinal cord–case report. Neurol Med Chir 2002; 42: 349–53. Jallo GI, Zagzag D, Epstein F. Intramedullary subependymoma of the spinal cord. Neurosurgery 1996; 38: 251–57. Nam DH, Cho BK, Kim YM, et al. Intramedullary anaplastic oligodendroglioma in a child. Childs Nerv Syst 1998; 14: 127–30. Fountas KN, Karampelas I, Nikolakakos LG, et al. Primary spinal cord oligodendroglioma: case report and review of the literature. Childs Nerv Syst 2005; 21: 171–75. Ushida T, Sonobe H, Mizobuchi H, et al. Oligodendroglioma of the “widespread” type in the spinal cord. Childs Nerv Syst 1998; 14: 751–55. Park SH, Chi JG, Cho BK, Wang KC. Spinal cord ganglioglioma in childhood. Pathol Res Pract 1993; 189: 189–96. Miller DJ, McCutcheon IE. Hemangioblastomas and other uncommon intramedullary tumors. J Neurooncol 2000; 47: 253–70. Hamburger C, Buttner A, Weis S. Ganglioglioma of the spinal cord: report of two rare cases and review of the literature. Neurosurgery 1997; 41: 1410–15. Jallo GI, Freed D, Epstein FJ. Spinal cord gangliogliomas: a review of 56 patients. J Neurooncol 2004; 68: 71–77. Park CK, Chung CK, Choe GY, et al. Intramedullary spinal cord ganglioglioma: a report of five cases. Acta Neurochir (Wien) 2000; 142: 547–52. Lang FF, Epstein FJ, Ransohoff J, et al. Central nervous system gangliogliomas. Part 2: clinical outcome. J Neurosurg 1993; 79: 867–73. Tripathy LN, Forster DM, Timperley WR. Ganglioneuroblastoma of the cauda equina. Br J Neurosurg 2000; 14: 264–66. Razack N, Jimenez OF, Aldana P, Ragheb J. Intramedullary holocord lipoma in an athlete: case report. Neurosurgery 1998; 42: 394–96.
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Part I: Spinal-cord neoplasms—intradural neoplasms David E Traul, Mark E Shaffrey, David Schiff
Intradural spinal-cord tumours are an uncommon but important consideration in the differential diagnosis of patients with back pain, radicular pain, sensorimotor deficits, or sphincter dysfunction. Intradural spinal tumours can be divided into intramedullary and extramedullary spinal-cord tumours on the basis of their anatomical relation to the spinal parenchyma. The heterogeneous cell composition of the intradural compartment allows the formation of neoplasms, arising from glial cells, neurons, and cells of spinal vasculature. Additionally, developmental tumours, metastases, and intradural extension of extradural tumours are represented. In this Review, we discuss the published work on intradural spinal-cord tumours in terms of epidemiological, radiographic, and histological characteristics. Surgical and adjuvant treatment strategies are also reviewed.
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Introduction
Correspondence to: Dr David Schiff, University of Virginia Health System, NeuroOncology Center, P.O. Box 800432, Charlottesville, VA 22908,USA [email protected] Part II: Spinal-cord neoplasms— primary tumours of the bony spine and adjacent soft tissues will be published in February 2007.
Nerve-sheath tumours Schwannomas and neurofibromas account for up to a third of intradural spinal-cord tumours in the adult population but are less common in children. Peak
Michael English/Custom Medical Stock Photo/Science Photo Library
Spinal-cord neoplasms (SCNs; figure 1) are an uncommon cause of back pain, radicular pain, and sensorimotor deficits in both adult and paediatric patients. SCNs can be divided into extradural and intradural tumours on the basis of their relation to the thecal sac that surrounds the spinal cord and cauda equina. Extradural tumours, located outside the thecal sac, account for almost 60% of SCNs. About 30% of tumours are contained within the thecal sac and are, therefore, intradural neoplasms. Concomitant intradural and extradural components are associated with roughly 10% of SCNs. Within the intradural compartment, tumours can originate adjacent to (extramedullary) or within (intramedullary) the spinalcord parenchyma. In view of the heterogeneous cell composition within the intradural compartment, the histogenesis of neoplasms located at this site is varied (panel). Differentiation and diagnosis of intramedullary spinal-cord tumours (IMSCTs) and extramedullary spinal-cord tumours (EMSCTs) are widely achievable through clinical examination and radiographic techniques. MRI is the preferred method of radiographic assessment of intradural spinal tumours and can suggest histological subtype. Other radiographic examinations, such as CT and myelogram, are useful if MRI is contraindicated. Magnetic resonance angiogram (MRA) or spinal arteriogram can be beneficial if the tumour has a vascular component. Histological examination of the tumour after biopsy or surgical resection is able to establish the histogenesis of intradural tumours in almost all cases.
Patients with symptomatic EMSCTs most often present with symptoms of spinal-cord compression indistinguishable from non-neoplastic causes. Most patients will be symptomatic at the time of diagnosis, and onset of symptoms can precede diagnosis by months to years. Local or radicular pain is the most common presenting symptom in patients with EMSCTs, and has highest incidence with tumours located in the lumbar spine.1 Paresthaesias and numbness are common symptoms, and hypesthesia or anesthesia at and below a level of the spinal cord is often evident on clinical examination. Patterns of sensory deficits, such as posterior-cord syndrome, can suggest tumour localisation. Motor weakness in the form of spastic paraparesis is common too, but findings of monoparesis, hemiparesis, or even paraplegia might be present at diagnosis. Sphincter dysfunction can develop early in the course of the disease, especially with tumours of the cauda equina. Ataxia, torticollis, and skeletal deformities are less common presenting symptoms.1
Department of Neurology (D E Traul MD, D Schiff MD), Department of Neurosurgery (M E Schaffrey MD, D Schiff), and Neuro-Oncology Center (M E Shaffrey, D Schiff), University of Virginia Health System, Charlottesville, VA, USA
Extramedullary tumours EMSCTs account for more than 70% of intradural spinalcord tumours in adults and are only slightly less common in children. The most common primary EMSCTs are derived from sheath cells covering the spinal-nerve roots (schwannomas and neurofibromas) or meningial cells located along the spinal-cord surface (meningiomas). Myxopapillary ependymomas are extramedullary tumours arising from the conus medullaris and filum terminalis. Other tumour types, such as hemangiopericytomas, lipomas, paragangliomas, epidermoid cysts, and dermoid cysts are less common. http://oncology.thelancet.com Vol 8 January 2007
Figure 1: Spinal-cord neoplasms are extradural or intradural tumours according to their relation to the thecal sac
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Panel: Intradural spinal-cord neoplasms Intramedullary tumours Neuroepithelial tumours Astrocystic astrocytomas Ependymal ependymomas Oligodendroglial oligodendrogliomas Mixed neuronal–glial gangliogliomas Embryonal neuroblastomas Other CNS tumours Benign mesenchymal lipomas Germ cell teratomas Uncertain hemangioblastomas Vascular malformations Capillary hemangiomas Cavernous hemangiomas Intramedullary metastases Small-cell lung cancer Non-small-cell lung cancer Lymphoma Renal-cell carcinoma Others Extramedullary tumours Neuroepithelial tumours Ependymal myxopapillary ependymomas Other CNS tumours Meningial meningiomomas Benign mesenchymal lipomas Malignant mesenchymal hemangiopericytomas Tumours of spinal nerves Nerve sheath schwannomas Nerve sheath neurofibromas Local extension of regional tumours Paragangliomas Tumour-like cysts Dermoid Epidermoid Extramedullary metastases Mass lesions from neoplastic meningitis
incidence of nerve-sheath tumours is in the fourth to fifth decade of life, and there is equal incidence in both men and women. Schwannomas are more common than neurofibromas and usually present as solitary tumours. Occasionally, multiple spinal schwannomas are seen with schwannomatosis or neurofibromatosis type II. Neurofibromas often show multiplicity, especially when associated with neurofibromatosis type 1. About 60–80% of nerve-sheath tumours arise from nerve roots before leaving the dural sac. A further 10% arise as the nerve root leaves the dural sac and becomes surrounded by the dural-root sleeve. These tumours, therefore, display both intradural and extradural components (dumbbell tumour). Nervesheath tumours that are entirely extradural or 36
Figure 2: Schwannoma Lumbar MRI shows half-dumbbell mass in left T-12 neural foramen. Mass showed heterogeneous enhancement with gadolinium on T1-weighted images and was identified as schwannoma after resection.
intramedullary are less common. Intradural nervesheath tumours most commonly affect the lumbosacral region, but cervical and thoracic tumours have been reported too.2 Intradural nerve-sheath tumours might be more common in the lumbosacral region because of the longer intradural segment of the caudal spinalnerve roots in the neuraxis.3 Nerve-sheath tumours are generally regarded as benign neoplasms, but can be malignant in a few cases, where they are designated the term malignant peripheral nerve-sheath tumours (MPNSTs). Although more than 50% of MPNSTs are associated with neurofibromatosis type 1, only a small percentage of patients with this disease have malignant neoplasms. Anatomically, schwannomas tend to arise from the dorsal-nerve root whereas neurofibromas are more common on the ventral root. Other than this difference, schwannomas and neurofibromas are indistinguishable on MRI. Nerve-sheath tumours have an isointense signal on T1-weighted images and a hyperintense signal on T2-weighted images. Gadolinium adds variable enhancement ranging from a homogeneous to a peripheral ring-like enhancement (figure 2).4 Although an irregular enhancement pattern is associated with malignant tumours, differentiation from benign entities is unreliable with radiographic methods. Histologically, schwannomas display neoplastic Schwann cells without nerve fibres. Neurofibromas more frequently invade the nerve root, and display Schwann cells, nerve fibres, and fibroblasts. The primary treatment of nerve-sheath tumours is directed at total surgical resection, which is obtainable in most cases. Subtotal resection of these tumours might be an option when the tumour is attached to the http://oncology.thelancet.com Vol 8 January 2007
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A
B
C
Figure 3: Meningioma Thoracic MRI with gadolinium contrast showed a mass with strong homogeneous enhancement on T1-weighted axial (A) and sagittal (B) images. Mass was hyperintense on T2-weighted images (C).
spinal cord, or when the tumour exhibits an extradural component closely associated with vital structures, such as the vertebral artery in the cervical region.3 To obtain total resection, the ventral or dorsal roots are commonly sacrificed; however, resection of the nerve root is usually not associated with pronounced postoperative motor or sensory deficit.3 Because schwannomas arise from dorsal-nerve roots and are less invasive than neurofibromas, surgical resection less often results in pronounced motor deficits than does resection of neurofibromas. Postoperative morbidity can be affected by spinal location of nerve-sheath tumours, with cervical and thoracic lesions predicting worse neurological outcome than more caudal sites.2 Radiotherapy or chemotherapy is usually reserved for tumours that have malignant histological characteristics. Tumour recurrence is less than 5% and might have a high association with subtotal tumour removal.2
images and a hyperintense signal on T2-weighted images. The addition of gadolinium contrast gives strong homogeneous enhancement (figure 3). Calcifications are frequent and could preclude gadolinium enhancement.4 Most intradural meningiomas are non-invasive, benign neoplasms, helping with gross total resection of the tumour. Even when considering the technical challenges of anterior locations, total surgical resection of meningiomas is attainable in more than 90% of patients.8 The tumour recurrence rate with total or subtotal resection is between 3% and 7%.5,6,8 Atypical and anaplastic spinal meningiomas have a higher tumour recurrence rate and rarely metastasise. Radiotherapy could be considered after subtotal resection or recurrence of spinal meningiomas by analogy with management of intracranial meningiomas.
Hemangiopericytoma Meningioma Spinal meningiomas account for up to 46% of spinal neoplasms,5 and are more common intradurally than extradurally. A small percentage of spinal meningiomas are located extradurally, and extension of these tumours into the intradural compartment is common. The thoracic level is the most frequent site for spinal meningiomas, and these tumours have a predilection for women in the fifth to seventh decade of life. Intradural meningiomas are mostly located lateral or posterior to the spinal cord, with the anterior location being less frequent.5,6 Although intradural meningiomas are usually solitary lesions, multiplicity might be encountered when these tumours are associated with neurofibromatosis type 2. Intradurally, meningothelial and psammomatous meningiomas are the most common histological subtypes of spinal meningioma. Intradural clear-cell meningioma is less frequent and associated with a worse prognosis.7 Atypical or anaplastic spinal meningiomas are rare. On MRI, spinal meningiomas have a hypointense to isointense signal on T1-weighted http://oncology.thelancet.com Vol 8 January 2007
Hemangiopericytomas are uncommon neoplasms of the CNS with uncertain histogenesis. Spinal hemangiopericytoma is rarely encountered, with fewer than ten reported cases involving an intradural extramedullary hemangiopericytoma.9–11 Hemangiopericytomas are hypercellular with frequent mitoses and necrosis seen on microscopic examination. These malignant characteristics predict the aggressive clinical course of these tumours and recurrence is common.9 Accordingly, surgical resection is usually needed. Because of the notable vascularity of these tumours, preoperative embolisation of hemangiopericytomas through interventional angiographic techniques is often attempted. Radiotherapy has proven effective in reducing recurrence of intracranial hemangiopericytomas, but there is insufficient evidence relating to spinal locations.
Lipoma Lipomas are congenital, benign tumours uncommon in the intradural compartment. When present, intradural extramedullary lipomas are associated with spinal dysraphism in about a third of cases. Children are more 37
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commonly affected than adults. Intradural extramedullary lipomas are usually located in the lower thoracic and lumbosacral levels. A tethered-cord syndrome present at birth or developing during infancy can be encountered with lipomas of the cauda equina. This syndrome consists of sensorimotor deficits, pain, skeletal deformities, and sphincter dysfunction, and is less common in adults with lumbrosacral lipomas.12 On MRI, intradural lipomas have a hyperintense signal on T1-weighted images and a hypointense signal on T2weighted images. Microscopically, lipomas consist of mature adipose cells and connective tissue. Decompressive surgical resection is recommended for symptomatic intradural lipomas. When there is widespread involvement of the cord, conus, or nerve roots, subtotal resection is usually undertaken to prevent postoperative morbidity. Intraoperative electrophysiological stimulation with evoked EMG monitoring is often used to allow differentiation between the functional spinal cord and the mass. When unassociated with a tethered cord, prophylactic resection of asymptomatic lipomas of the filum terminalis can prevent subsequent neurological decline.13
Myxopapillary ependymoma Myxopapillary ependymomas account for roughly 40–50% of spinal ependymomas and are more common in the adult population than in children.14 Ependymomas of the myxopapillary variant arise in the filum terminalis and account for up to 80% of ependymomas found in the cauda equina. This variant is distinguished from other ependymomas by the mucinous changes undergone by the tumour cells. Patients normally present with a long history of radicular pain, lower extremity sensorimotor deficit, and sphincter dysfunction. Myxopapillary ependymomas are typically benign, well-circumscribed tumours. MRI reveals a circumscribed mass with hypointense signal on T1-weighted images and hyperintense signal on T2-weighted images. Contrast enhancement with gadolinium is usually homogeneous. Histologically, myxopapillary ependymomas display ependymal rosettes or perivascular pseudorosettes, with the characteristic deposition of myxoid material around blood vessels. Total surgical resection of myxopapillary ependymomas is feasible if the nerve roots in the cauda equina are not entrapped within the tumour. In an attempt to keep to a minimum postoperative neurological morbidity, subtotal resection is not uncommon. Focal fractionalised radiotherapy seems to be effective at improving neurological outcome and reducing tumour recurrence rate after subtotal tumour resection or piecemeal total excision.15 Recurrence of wholly resected tumours is generally rare, but is associated with a poor outcome.16 These tumours can seed the spinal subarachnoid space, in which case broader field 38
radiation is used, but this is uncommon. Although chemotherapy is sometimes started for recurrent or disseminated myxopapillary ependymomas, results are unconvincing.
Paraganglioma Paragangliomas are derived from autonomic-nervoussystem paraganglion cells and are uncommon in the CNS. Spinal paragangliomas are generally nonsecreting, sympathetic neoplasms,17 which tend to occur in the fourth to fifth decade of life and show a male predominance. The most frequent intradural location for paragangliomas is the cauda equina and lumbar spine regions, apart from intradural thoracic or cervical paragangliomas.18,19 On MRI, paragangliomas present as a well circumscribed mass with a hypointense to isointense signal on T1-weighted images and a hyperintense signal on T2-weighted images. Paragangliomas are characteristically hypervascular, and gadolinium contrast administration produces a heterogeneous salt and pepper pattern of enhancement.20 Scanning using radiolabelled metaiodobenzylguanidine (mIBG), a noradrenaline analogue with uptake independent of catecholamine secretion, can allow visualisation of paragangliomas.21 Histological appearance of paragangliomas displays a highly vascularised tumour bed containing round and polygonal cells grouped in clusters called zellballen. Immunohistological methods to detect chromogranin and synaptophysin can be useful for diagnosis. Intradural paragangliomas are mainly benign neoplasms, and gross total surgical resection is the preferred treatment. Although catecholamine-secreting spinal paragangliomas are uncommon, preoperative screening for a hyperadrenergic state is necessary to prevent hypertensive crisis during tumour removal. Recurrence rate after total or subtotal resection of intradural paragangliomas is less than 5% and is not reduced by concomitant radiotherapy or chemotherapy. Although iodine-131 labelled mIBG (131I-mIBG) can slow progression and improve remission rate for metastatic paragangliomas,21 efficacy in primary intradural paragangliomas is unproven.
Dermoid and epidermoid cysts Dermoid and epidermoid cysts are usually congenital neoplasms arising from heterotopic ectodermal-cell implantation into the neural tube early in embryonic development. Dermoid and epidermoid cysts represent only 1% of CNS tumours, and are rarely located in the spinal column. These tumours most commonly affect the lumbosacral region, with rare reports of thoracic involvement.22 Dermoid and epidermoid cysts are usually diagnosed in the first two decades of life, with dermoid cysts presenting earlier than epidermoid cysts.23 http://oncology.thelancet.com Vol 8 January 2007
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On gross appearance, dermoid cysts can be differentiated from epidermoid cysts by the appearance of skin appendages such as hair follicles; however, the distinction between these tumours is often difficult by imaging. Both intradural dermoid and epidermoid cysts have variable MRI appearance, with hypointense to hyperintense signal on T1-weighted images and isointense to hyperintense signal on T2-weighted images. There is usually minimum enhancement with gadolinium. Histologically, dermoid and epidermoid cysts are composed of a lining of epithelial tissue supported by a collagenous network. Dermoid cysts contain sebaceous or apocrine glands in the thicker portions of the epithelial lining. Gross total resection of dermoid and epidermoid cysts is desirable when possible, but adhesion to neural tissue can prevent aggressive techniques. When subtotal resection is done, emptying of the cystic contents and removal of a portion of the capsule is encouraged. Dissemination of the cystic contents spontaneously or during tumour removal might produce a granulomatous meningitis treatable with corticosteroids.24 Recurrence of resected intradural dermoid and epidermoid cysts is uncommon, and malignant tumours are rare. Adjuvant radiotherapy or chemotherapy for non-operable or malignant cases has not been thoroughly studied.
Extramedullary metastasis Intradural extramedullary spinal-cord metastasis is seen at autopsy in fewer than 5% of patients who have died from cancer. These tumours are commonly the result of drop lesions from intracranial metastasis from adenocarcinoma of the lung, prostate cancer, breast cancer, melanoma, or lymphoma.25,26 Alternatively, intradural extramedullary metastases represent drop lesions from intracranial neoplasms such as gliomas and medulloblastomas. Metastatic spread from intracranial lesions can involve dissemination of neoplastic cells through the CSF, and multiple lesions are common. Intradural extramedullary metastases are most common in the thoracolumbar or thoracic spine, and tend to present as localised pain and spinal tenderness. With involvement of the nerve roots of the cauda equina, a radicular pattern of pain might be evident. Motor and sensory deficits, especially the Brown-Sequard syndrome, are common. Sphincter dysfunction is present in about a third of patients. Because intradural extramedullary metastasis usually indicates advanced widespread progression of the systemic malignancy, aggressive surgical resection of lesions is usually not done. Treatment is, therefore, directed towards palliative and functional goals. Radiotherapy allows improvement in neurological function in a large population of patients. Adjuvant treatment with intravenous or oral corticosteroids can improve neurological function as well and provide symptomatic relief. http://oncology.thelancet.com Vol 8 January 2007
Intramedullary tumours IMSCTs account for 20–30% of intradural tumours in adults, and up to 50% of intradural tumours in children.27,28 Glial tumours, such as astrocytomas and ependymomas, represent up to 80% of IMSCTs, with a paediatric predominance of astrocytomas and an adult predominance of ependymomas. Oligodendrogliomas, mixed gliomas, neuron-derived tumours, gangliogliomas, hemangioblastomas, lipomas, and developmental tumours are uncommon. Finally, metastatic intramedullary spinal-cord tumours account for only 1–3% of IMSCTs. Non-neoplastic processes, such as multiple sclerosis and granulomatous disease, can account for up to 4% of intramedullary lesions, usually foreseen by an acute or subacute course and systemic involvement.29,30 Patients with IMSCTs most often present with myelopathic symptoms with insidious onset, with preoperative symptom duration measured in months to years. Localised pain and upper-extremity paresthaesias are the initial symptoms in 50–90% of the adult population with cervical IMSCTs.28,31 Thoracic IMSCTs can present with lower-extremity sensory loss that extends proximally with upper-motor-neuron signs in the lower extremities. Radicular pain becomes more prominent with IMSCTs of the lumbosacral spine affecting the nerve roots in the cauda equina. Disruption of sphincter function is seen in up to 44% of IMSCTs in adults.32 In the paediatric population, pain is less often an initial symptom but is present in more than 40% of children with IMSCTs. Motor weakness is a complaint in 36–90% of paediatric patients, and gait disturbances are reported in 27–66%.27,33 Urinary dysfunction is seen in almost 20% of children with IMSCTs. Torticollis or kyphoscoliosis could be the initial complaint too.27,33
Astrocytoma Astrocytomas account for 80–90% of IMSCTs in childhood and roughly 60% of IMSCTs in adolescence.27,33–37 Intramedullary astrocytomas have peak incidence in the third decade of life, but are not as common as intramedullary ependymomas in this age group. In adults, astrocytomas make up almost 25% of all IMSCTs.37 There seems to be equal incidence in men and women. Intramedullary astrocytomas are predominantly located in the cervicothoracic or thoracic region in the paediatric population,27,35 but cervical involvement becomes more common in the adult population. Lower thoracic and lumbosacral levels are rarely affected. At the time of diagnosis, astrocytomas have usually extended to multiple bone levels and 30–60% of tumours are associated with rostral, caudal, or intratumoral cysts.4,27 Elongated cysts extending several levels from the tumour location represent syringomelia. Low-grade pilocytic astrocytomas and fibrillary astrocytomas account for almost two-thirds of intramedullary astrocytomas in adults, and almost 90% of 39
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Figure 4: Pilocytic astrocytoma Cervical MRI shows isointense mass at C5–6 on T1-weighted images (A) that enhanced with gadolinium contrast (B). Mass was hyperintense (arrow) on T2-weighted images (C).
intramedullary astrocytomas in children. MRI of lowgrade astrocytomas reveals an enlarged homogeneous mass with a hypointense to isointense signal on T1-weighted images and a hyperintense signal on T2weighted images.4 There is little to no surrounding oedema or haemorrhage with low-grade astrocytomas. Most intramedullary astrocytomas enhance with gadolinium contrast, and calcifications are rare.38 Pilocytic astrocytomas (figure 4) can be well-delineated, but fibrillary astrocytomas are poorly defined with irregular tumour margins. Microscopically, low-grade spinal astrocytomas show a low degree of cellularity, a low mitotic activity, and an absence of both necrosis and endothelial microvascular proliferation. Pilocytic astrocytomas typically contain Rosenthal fibres. Highgrade anaplastic astrocytoma and glioblastoma multiforme account for about 10% of intramedullary astrocytomas. On MRI, these high-grade tumours often display heterogeneous enhancement caused by the presence of intratumoral cysts, necrosis, and surrounding oedema.38 Microscopically, anaplastic astrocytoma and glioblastoma multiforme show moderate to high cellularity, and increased mitotic activity. Glioblastoma multiforme usually exhibits necrosis and endothelial microvascular proliferation. Treatment of intramedullary astrocytomas is directed at total surgical resection; however, less extensive surgical intervention could be considered with higher grade, more infiltrative tumours to avoid pronounced postsurgical morbidity. Most surgeons prefer electrophysiological monitoring of the spinal cord during surgical treatment of IMSCTs. Motor-evoked potential and somatosensory-evoked potential monitoring are the most common modalities. Gross total resection of pilocytic astrocytomas is achievable in many instances, as these tumours are often well circumscribed. However, because of the infiltrative nature of even low-grade fibrillary astrocytomas, gross total resection of these tumours is difficult without risking perioperative and postoperative morbidity and mortality. Gross total resection rates range between 30% and 70%.27,32,33 40
Subtotal resection of fibrillary astrocytomas is appropriate in many cases, and there does not seem to be any significant difference in survival rates between total and subtotal resection techniques when long-term data are compared within tumour grades.35,39,40 Intramedullary fibrillary astrocytomas have a high recurrence rate, ranging from 25% in low-grade tumours to almost 100% in high-grade tumours.27,28 Adjuvant radiotherapy at diagnosis of high-grade astrocytomas or with tumour recurrence is advocated. The role of concomitant chemotherapy is uncertain, but the postoperative course of both low-grade and high-grade spinal astrocytomas can be changed with this adjuvant treatment.41 In low-grade intramedullary astrocytomas, 5-year survival rates range from 80% to 100%.33 Patients with intramedullary anaplastic astrocytomas or glioblastoma multiformes have an average life expectancy of 15 months.9,27,33
Ependymoma Intramedullary ependymomas represent almost 40–60% of adults with IMSCTs with a peak incidence in the fourth to fifth decade of life.28,32,37 Intramedullary ependymomas account for only 16–35% of IMSCTs in the paediatric population.35,37 Most intramedullary ependymomas arise in the cervical or cervicothoracic region; however, thoracic and thoracolumbar ependymomas are not uncommon.35,42,43 True intramedullary ependymomas are most often of the cellular variant; however, papillary, clear-cell, anaplastic, and mixed subtypes occur in the spinal cord too.37,42 MRI shows a lesion hypointense on T1-weighted imaging and hyperintense on T2-weighted imaging.4 Intramedullary ependymomas homogeneously enhance with contrast (figure 5).4 Although not encapsulated, intramedullary ependymomas often show a distinct plane between the tumour and the adjacent spinal cord, despite frequent association with cysts, syrinxes, and haemorrhage. Microscopically, spinal ependymomas might display ependymal rosettes but perivascular pseudorosettes are more prominent. http://oncology.thelancet.com Vol 8 January 2007
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Figure 5: Ependymoma Thoracic MRI shows mass at T3–T8 levels. Mass was hypointense to isointense on T1-weighted images (A), and enhanced with gadolinium contrast (B). Mass was hyperintense on T2-weighted axial (C) and sagittal (D) images. Arrows indicate extent of thoracic spinal-cord involvement.
Intramedullary ependymomas are mostly wellcircumscribed tumours, which helps with total surgical resection in 70–100% of cases.35,44,45 Tumour recurrence after gross total resection is less than 10%, but can be delayed by the slow growth rate of ependymomas. With subtotal resection, tumour recurrence is seen in 50–70% of cases.45,46 Therefore, prognosis for patients with intramedullary ependymomas is dependent on the extent of surgical resection. Postoperative radiation treatment remains controversial but could increase tumour-free survival rates of adult patients with high-grade or subtotally resected tumours.46–48 In children, the use of radiotherapy has been debated because of radiationinduced damage to the CNS.49 Additonally, in both adult and paediatric populations, prior adjuvant radiotherapy might make subsequent surgical interventions more difficult and heighten postoperative neurological morbidity. The 5-year survival rates for low-grade intramedullary ependymomas range between 83% and 100%,42,45,50 but decline rapidly with higher grade ependymomas.47
Subependymoma Subependymomas of the spinal cord are rare representations of IMSCTs with less than 50 cases reported. These tumours have a higher incidence in men and typically present in the fourth or fifth decade of life.51 Intramedullary subependymomas are most commonly located in the cervical cord, although involvement of the thoracic cord has been reported.52 On MRI, intramedullary subependymomas have characteristics similar to ependymomas, showing spinal-cord enlargement with a hypointense signal on T1-weighted images and a hyperintense signal on T2-weighted images with heterogeneous enhancement.51,53 Microscopically, intramedullary subependymomas display a dense fibrillary background separating sparse clusters of tumour cells with well-defined, ovoidnuclei-containing stippled chromatin. Although http://oncology.thelancet.com Vol 8 January 2007
ependymal rosettes might be seen, mitotic activity is usually absent. Treatment for intramedullary subependymomas is directed at total gross resection whenever possible. Frequently, intramedullary subependymomas are eccentrically located in the spinal cord, which can help differentiate these tumours from the more centrally located ependymomas on a surgical basis.51,53 Intramedullary subependymomas are sharply circumscribed which helps with gross tumour removal. Adjuvant radiotherapy or chemotherapy is usually not used after total or partial tumour removal.
Oligodendroglioma Intramedullary oligodendrogliomas represent a small percentage of spinal-cord tumours and fewer than 2% of CNS oligodendrogliomas.54,55 These tumours have highest incidence in the second or third decade of life, and spinal deformities often accompany neurological symptoms. Intramedullary oligodendrogliomas are most often located at the thoracic levels, with cervical and lumbar levels less common. Radiographically, intramedullary oligodendrogliomas present as an irregular mass with associated spinal-cord enlargement and possible syrinx. MRI shows a lesion with an isointense signal on T1-weighted images and a hyperintense signal on T2-weighted images with heterogeneous enhancement.54 Microscopically, oligodendrogliomas display densely arranged cells resembling mature oligodendrocytes surrounded by a halo, resulting in a characteristic, so-called, fried-egg appearance. Anaplastic oligodendrogliomas can show mitotic activity, vascularisation, and necrosis. Total surgical resection of intramedullary oligodendrogliomas is difficult as a result of their frequent infiltration of surrounding neural tissue. Additionally, these tumours frequently manifest leptomeningeal metastasis, which complicates management and worsens overall prognosis.56 Adjuvant radiotherapy of an 41
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rare representations of IMSCTs and are most commonly located at the cervical level, but can present as diffuse lesions across multiple spinal levels.63 Treatment is surgical resection and there are insufficient data to evaluate adjuvant radiotherapy.
Lipoma
Figure 6: Hemangioblastoma Thoracic MRI shows an intensely enhancing mass at T5 level (arrow) on T1-weighted images (A). T2-weighted imaging (B) showed extensive syrinx formation above and below the tumour (arrows).
intramedullary anaplastic oligodendroglioma has shown to be effective in one case.54
Ganglioglioma Gangliogliomas are composed of a mixture of neoplastic neurons and glial cells with a predilection for the pediatric population. Intramedullary gangliogliomas are uncommon tumours, accounting for roughly 1% of spinal-cord neoplasms.57,58 Peak incidence is in childhood and these tumours are rarely reported after the fourth decade of life.59 Intramedullary gangliogliomas are located predominately at cervicothoracic or thoracic levels, and can span multiple vertebral segments.60 There could be a mild sex bias for men. Intramedullary gangliogliomas are usually isointense to hyperintense on T1-weighted imaging and hyperintense on T2-weighted imaging with heterogeneous contrast enhancement and frequent syrinxes.61 Microscopically, gangliogliomas are composed of a mixture of neoplastic ganglion and glial cells, mostly astrocytic elements. Immunohistochemistry techniques might be required to distinguish neoplastic ganglion and glial elements from non-neoplastic tissue. Treatment of intramedullary gangliogliomas is directed at gross total tumour resection, which can be achieved in 80–90% of cases.60,61 Tumour recurrence after resection ranges from 30% to 47% and 5-year actuarial survival rate ranges between 88% and 89%.60,62 Adjuvant radiation can be beneficial with subtotal resection of spinal gangliogliomas59; however, there are insufficient data to support chemotherapy. Malignant transformation of residual tumour cells is rare.
Neuroblastoma Neuroblastic tumours of the spinal cord include primitive neuroblastomas and tumours containing differentiated neuroblasts, ganglion cells, and schwannian stroma such as ganglioneuromas. They are 42
The incidence of intramedullary spinal lipomas ranges from 1% to 11% of spinal tumours.32 Most intramedullary lipomas involve the cervical or thoracic spinal cord, with rare reports of holocordal involvement.64 Spinal lipomas are congenital and usually become symptomatic in early adulthood. When not associated with spinal dysraphism, displacement of the spinal cord by lipomas can produce earlier symptom onset. Intramedullary lipomas have hyperintense signals on T1-weighted images and hypointense signals on T2-weighted images indicating the high proportion of tumour adipose tissue. Lobulated fatty tissue with interspersed connective and neural tissue on histological preparations confirms diagnosis. Surgical resection of symptomatic intramedullary lipomas is directed at debulking the tumour rather than gross total resection. Congenital lipomas can impede normal development of the surrounding neural tissue, and, therefore, postsurgical improvement is often absent.65
Teratoma Intradural location of teratomas is rare and intramedullary teratomas are especially unusual. Case reports of intramedullary teratomas tend to describe tumour location in the conus medullaris.66,67 Histologically, intramedullary teratomas are usually mature and regarded as benign. Surgical resection provides good postoperative outcome and tumour recurrence is uncommon.
Hemangioblastoma Hemangioblastomas of the spinal cord are predominantly intramedullary, although these tumours can be extramedullary and extradural. Intramedullary hemangioblastomas represent about 4% of spinal tumours and occur sporadically or in association with von Hippel-Lindau syndrome. Almost 25% of patients diagnosed with intramedullary hemangioblastomas have von Hippel-Lindau syndrome.68 Sporadic intramedullary hemangioblastomas have a peak incidence in the third or fourth decade of life and men are more affected than women. Hemangioblastomas associated with this syndrome have an earlier age of onset than sporadic cases of hemangioblastoma.69 Most are solitary tumours, although multiple lesions are not uncommon.69 Intramedullary hemangioblastomas are predominately located in the cervical or thoracic levels.70 On MRI, intramedullary hemangioblastomas often appear as cysts with enhancing mural nodules. http://oncology.thelancet.com Vol 8 January 2007
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Associated syringobulbia and syringomyelia are common (figure 6). Gadolinium provides homogeneous enhancement of small tumours and heterogeneous enhancement in larger tumours.4 Feeding arteries and draining veins can also be visible with contrasted MRI. Because of the highly vascularised nature of hemangioblastoma, spinal angiography can be useful for diagnosis and surgical planning. Microscopically, hemangioblastomas display a reticular pattern of small capillaries and foamy stromal cells. Gross total resection of symptomatic intramedullary hemangioblastomas is the preferred treatment and is generally associated with low morbidity.69–71 In patients with multiple hemangioblastomas of the spinal cord, tumour resection should be directed at the symptomatic neoplasm. When intramedullary hemangioblastomas are part of a systemic presentation of von Hippel-Lindau syndrome, tumour resection should be considered on a case-by-case basis. To our knowledge, there have been no reports of adjuvant chemotherapy or radiotherapy in the treatment of intramedullary hemangioblastomas of sporadic origin or in association with von HippelLindau syndrome. However, there are a few published works on treating intracranial hemangioblastomas with antiangiogenic drugs like thalidomide, interferon-alfa, and SU5416.
Angiomatous lesions Angiomatous lesions of the spinal cord are considered vascular malformations rather than true neoplasms. They are uncommon, affecting only a small percentage of paediatric and adult patients. Clinical presentation of intramedullary angiomatous tumours is similar to that of other IMSCTs; however, subacute or stepwise symptom onset can be seen with repeated haemorrhaging from dilated vessels.72 They are divided into capillary and cavernous subtypes on the basis of the size of the dominant vessel, and capillary hemangiomas have a higher incidence than the capillary subtype. Because of their larger size, however, cavernous hemangiomas are more likely to be symptomatic at presentation. Most cavernous angiomas are located in the cervical or thoracic spine, and multiplicity is not uncommon.73 There does not appear to be a sex preference. Radiographic assessments of intramedullary angiomatous lesions display a focal lesion without enlargement of the spinal cord. If the malformation produces venous congestion, then the tumour could be associated with local oedema and spinal-cord swelling.74 Intramedullary angiomatous lesions have a heterogeneous hyperintense signal on T1-weighted and T2-weighted images, with an area of hypointense signal surrounding the lesion on T2-weighted images.72 These tumours are usually non-enhancing with gadolinium contrast. Total surgical resection of symptomatic intramedullary angiomatous lesions is generally possible and patient http://oncology.thelancet.com Vol 8 January 2007
Search strategy and selection criteria Data for this review were identified by searches of MEDLINE, PubMed, and references from relevant articles using the following search terms: “spinal”, “intradural”, “intramedullary”, “extramedullary”, “schwannoma”, “neurofibroma”, “myxopapillary ependymoma” “epidermoid”, “dermoid”, “hemangiopericytoma”, “lipoma”, “meningioma”, “paraganglioma”, “metastasis”, “astrocytoma”, “ependymoma”, “ganglioglioma”, “hemangioblastoma”, “lipoma”, “neuroblastoma”, “neurofibroma”, “oligodendroglioma”, “subependymoma”, and “teratoma”. The final reference list was generated from original papers published in English between the years 1985 and 2006.
outcome is excellent. Intraoperative haemorrhagic complications are uncommon as angiomatous lesions are usually low-pressure vascular malformations. Haemorrhage in unresected intramedullary angiomatous lesions has an incidence of 1·4% per year.73
Intramedullary metastasis Intramedullary spinal-cord metastasis (ISCM) is an uncommon complication of systemic cancer, affecting fewer than 1% of all patients dying from systemic malignancies.75 However, with the advent of sensitive MRI techniques to identify intramedullary lesions, the incidence of ISCM appears to be higher than previously shown. Usually, patients with ISCM already have metastatic disease to other organs, including the brain. ISCM is predominately associated with lung cancer, with metastasis from small-cell lung cancer disproportionately represented. Renal-cell carcinoma, breast cancer, and melanoma are less commonly associated with ISCM.76 ISCM mainly affects the conus and cervical levels of the spinal cord, with the thoracic cord less commonly involved. Most cases involve a single lesion. As patients with ISCM usually have metastatic spread to other organs, treatment of ISCM is directed towards palliative and functional goals. Radiotherapy, often with concomitant corticosteroids, can help alleviate pain and preserve residual neurological function. Although open biopsy of some lesions is needed, aggressive surgical resection is usually deferred. Outlook after diagnosis of ISCM is poor, with median survival of 3 months and only 15% survival at 1 year.
Conclusion Although uncommon, intradural spinal-cord tumours should be an important consideration in the differential diagnosis of the adult or paediatric patient presenting with back or radicular pain associated with neurological deficits. The heterogeneous cell composition within the intradural compartment allows the presence of a 43
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histologically variable group of neoplasms. Radiographic assessment combined with histological examination helps with the identification of the histogenesis of these tumours, which is vital when exploring surgical and adjuvant treatment options and patient management. Conflicts of interest We declare no conflicts of interest. References 1 el-Mahdy W, Kane PJ, Powell MP, Crockard HA. Spinal intradural tumours: Part I--Extramedullary. Br J Neurosurg 1999; 13: 550–57. 2 Conti P, Pansini G, Mouchaty H, et al. Spinal neurinomas: retrospective analysis and long-term outcome of 179 consecutively operated cases and review of the literature. Surg Neurol 2004; 61: 34–43. 3 Jinnai T, Koyama T. Clinical characteristics of spinal nerve sheath tumors: analysis of 149 cases. Neurosurgery 2005; 56: 510–15. 4 Van Goethem JW, van den Hauwe L, Ozsarlak O, et al. Spinal tumors. Eur J Radiol 2004; 50: 159–76. 5 Roux FX, Nataf F, Pinaudeau M, et al. Intraspinal meningiomas: review of 54 cases with discussion of poor prognosis factors and modern therapeutic management. Surg Neurol 1996; 46: 458–63. 6 Gezen F, Kahraman S, Canakci Z, Beduk A. Review of 36 cases of spinal cord meningioma. Spine 2000; 25: 727–31. 7 Oviedo A, Pang D, Zovickian J, Smith M. Clear cell meningioma: case report and review of the literature. Pediatr Dev Pathol 2005; 8: 386–90. 8 Solero CL, Fornari M, Giombini S, et al. Spinal meningiomas: review of 174 operated cases. Neurosurgery 1989; 25: 153–60. 9 Ciappetta P, Celli P, Palma L, Mariottini A. Intraspinal hemangiopericytomas. Report of two cases and review of the literature. Spine 1985; 10: 27–31. 10 Dufour H, Metellus P, Fuentes S, et al. Meningeal hemangiopericytoma: a retrospective study of 21 patients with special review of postoperative external radiotherapy. Neurosurgery 2001; 48: 756–62. 11 Betchen S, Schwartz A, Black C, Post K. Intradural hemangiopericytoma of the lumbar spine: case report. Neurosurgery 2002; 50: 654–57. 12 Gupta SK, Khosla VK, Sharma BS, et al. Tethered cord syndrome in adults. Surg Neurol 1999; 52: 362–69. 13 Pierre-Kahn A, Zerah M, Renier D, et al. Congenital lumbosacral lipomas. Childs Nerv Syst 1997; 13: 298–334. 14 Celli P, Cervoni L, Cantore G. Ependymoma of the filum terminale: treatment and prognostic factors in a series of 28 cases. Acta Neurochir (Wien) 1993; 124: 99–103. 15 Schweitzer JS, Batzdorf U. Ependymoma of the cauda equina region: diagnosis, treatment, and outcome in 15 patients. Neurosurgery 1992; 30: 202–07. 16 Gagliardi FM, Cervoni L, Domenicucci M, et al. Ependymomas of the filum terminale in childhood: report of four cases and review of the literature. Childs Nerv Syst 1993; 9: 3–6. 17 Walsh JC, O’Brien DF, Kumar R, Rawluk D. Paraganglioma of the cauda equina: a case report and literature review. Surgeon 2005; 3: 113–16. 18 Sundgren P, Annertz M, Englund E, et al. Paragangliomas of the spinal canal. Neuroradiology 1999; 41: 788–94. 19 Silverstein AM, Quint DJ, McKeever PE. Intradural paraganglioma of the thoracic spine. AJNR Am J Neuroradiol 1990; 11: 614–16. 20 Shin JY, Lee SM, Hwang MY, et al. MR findings of the spinal paraganglioma: report of three cases. J Korean Med Sci 2001; 16: 522–26. 21 Noorda RJ, Wuisman PI, Kummer AJ, et al. Nonfunctioning malignant paraganglioma of the posterior mediastinum with spinal cord compression. A case report. Spine 1996; 21: 1703–09. 22 Scarrow AM, Levy EI, Gerszten PC, et al. Epidermoid cyst of the thoracic spine: case history. Clin Neurol Neurosurg 103: 220–22. 23 Shikata J, Yamamuro T, Mikawa Y, Kotoura Y. Intraspinal epidermoid and dermoid cysts. Surgical results of seven cases. Arch Orthop Trauma Surg 1988; 107: 105–09. 24 Lunardi P, Missori P, Gagliardi FM, Fortuna A. Long-term results of the surgical treatment of spinal dermoid and epidermoid tumors. Neurosurgery 1989; 25: 860–64.
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