Kasim Abul-Kasim and Pia C. Sundgren
Modifi ed and limited scheme for WHO grading system for spinal cord tumors
Neuroepithelial tumors WHO-grade Astrocytic tumors (glial tumors)
Pilocytic astrocytoma I Pleomorphic xanthoastrocytoma II Fibrillary astrocytomas II Anaplastic astrocytomas III Glioblastoma multiforme IV Oligodendroglial tumors
Oligodendroglioma II
Anaplastic oligodendroglioma III Ependymal cell tumors
Ependymoma II
Myxopapillary ependymoma I
Subependymoma I
Mixed gliomas
Mixed oligoastrocytoma II Anaplastic oligoastrocytoma III Neuronal and mixed neuronal –glial tumors
Gangliocytoma I
Ganglioglioma I–II
Anaplastic ganglioglioma III Desmoplastic infantile ganglioglioma I DNT (Dysembryoplastic
Neuroepithelial tumor)
I
Paraganglioma I
Peripheral nerve tumors
Schwannoma I
Neurofi broma I
Malignant peripheral nerve sheath tumor (MPNST)
II–IV Tumors of the meninges
Meningiothelial tumors
Meningioma I
Atypical meningioma II
Anaplastic meningioma III
Clinical Features of Spinal Cord Tumors
The clinical features of intradural tumors vary widely. The factors that infl uence the clinical pre- sentation of intradural spinal tumors are:
1. Tumor size: Small intradural extramedullary tumors are often asymptomatic whereas large intradural extramedullary tumors give rise to symptoms related to compression of spinal
cord, medullary conus or nerve roots. Intradural intramedullary tumors usually present with evidence of myelopathy.
2. Histopathological grade: Intradural metasta- ses are rapidly progressive, have a relentless course and usually presents with sudden onset of neurological defi cit. In low grade astrocy- toma and ependymoma the average duration of symptoms before establishing the diagnosis is 2–2.5 years.
3. Tumor location is one of the most important factors in determining the types of symptoms.
(a) Intradural extramedullary. The following are the possible presenting clinical features:
(i) Pain: Radicular pain, often related to exertion, which unusually does not make it diffi cult to distinguish these tumors from e.g., disc extrusion.
(ii) Neurological defi cit secondary to spinal cord compression: Paresis, paresthesia and bladder dysfunction.
(iii) Brown-Séquard syndrome second- ary to unilateral cord compression.
The patients present with ipsilateral paresis, hyperrefl exia and sensory loss of position and vibration sense.
There is also contralateral sensory loss of pain and temperature sense.
(b) Intradural intramedullary. The following are the possible presenting clinical features:
(i) Slow, progressive neurological defi - cit with paresis and paresthesia.
(ii) Bladder dysfunction, impotence and gait disturbance.
(iii) Pain is seldom the presenting feature and is often localized and not radiating.
(iv) Symptoms related to syrinx:
Dystonia, balance disturbance, mus- cle atrophy and scoliosis.
(v) Symptoms related to involvement of long tracts: Hyperrefl exia, clonus, positive Babinski sign and Hoffman’s sign.
4. Occurrence of spinal cord edema and syrinx may accelerate the time course of the disease.
5. Pre-existing spinal pathology e.g., disc protrusion in the vicinity of a tumor may con- tribute to deterioration of the physical status of the patient.
Intradural Extramedullary Tumors Schwannomas, also called neurinoma or neurilemmoma . Schwannomas which are con- sidered benign nerve sheath tumors (WHO grade I), are the most common intradural extramedullary spinal tumor (30% of primary spinal tumors are schwannomas) (Osborn et al . 2004 ) . Schwannomas are more commonly seen in adults 30–60 year old and affect males and females equally. In children, schwannomas are often multiple and are associ- ated with neurofi bromatosis type II (NF-II) with high risk for malignant transformation. The tumor commonly arises from Schwann cells in the cer- vical or the lumbar dorsal spinal sensory roots with less frequent involvement of the thoracic region. Seventy percent of schwannomas are intradural. Fifteen percent are completely extra- dural while 15% are “Dumbbell tumors” which are located both intradurally and extradurally.
Intramedullary schwannomas are very rare.
The most common sign and symptom of schwannomas are referred pain which is not unusually correlated to movement and exertion and thus is diffi cult to distinguish from sciatic pain caused by e.g., disc protrusion. Progressive paresthesia of distinct dermatome or paraparesis of distinct muscle groups is the next most com- mon symptom. Bladder dysfunction and gait dis- turbance occur only in cases of giant schwannoma.
Schwannomas are usually small solid tumors typically seen in the lumbar region. Giant schwan- noma are often multilobular and are more com- mon in the lumbosacral region. On CT, large schwannomas may give rise to the widening of neural foramen and scalloping of posterior cortex of adjacent vertebral body.
On MRI, schwannomas are commonly isoin- tense to spinal cord on T1WI and markedly hyperintense on T2WI. Hemorrhage and calcifi - cations are uncommon and signal inhomogeneity on both T1W- and T2W images. Forty percent of
schwannomas are cystic. Almost all schwannomas show contrast enhancement which may vary in intensity. Contrast enhancement can be intense and homogenous or only show faint peripheral enhancement (De Verdelhan et al . 2005 ) . Based on imaging fi ndings, it is diffi cult to distinguish schwannomas from neurofi bromas in patients with NF-II. When the contrast enhancement is faint or absent, it is diffi cult to distinguish schwannoma from perineural cysts, which are often a com- mon accidental radiological fi nding. Intradural schwannomas displace the spinal cord, medul- lary conus, or fi lum terminale to the contralateral side as they grow. Schwannomas a few millime- ters in size are only detected on MRI following contrast administration and are often an accidental fi nding. Large extradural schwannomas can be seen as a large soft tissue mass on plain radiogra- phy and might cause thinning of pedicular cortex.
Schwannomas are usually slow-growing tumors with good prognosis. However schwannomas associated with NF-II, multiple schwannomas (schwannomatosis) and melanocytic schwannoma have less favorable prognosis as there is a risk for recurrence and continuous development of new lesions.
Meningiomas are benign tumors classifi ed as WHO grade I in more than 95% of cases. They are the second most common intraspinal tumors and account for about 25% of primary spinal tumors.
They occur most frequently in elderly patients with peak age in the fi fth and sixth decades. Male to female incidence is 1:4. Only 10% of menin- giomas are extradural or dumbbell-shaped tumors.
Eighty percent of meningiomas arise in the thoracic region, with less common involvement of the cervical (15%) or lumbar (5%) regions (Osborn 1994 ) . Several different subtypes exist and the surgical outcome as well as prognosis may differ depending on the subtype of the tumor (Schaller 2005 ) . Meningiomas are often located posterolaterally in the thoracic region and anteri- orly in the cervical region (Osborn 1994 ) . Pure extradural or intraosseous meningiomas are rare in the spinal canal. They are often solitary tumors of variable size, but multiple meningiomas, which are encountered in 2% of cases, are most often associated with neurofi bromatosis type II.
Approximately, 50% of patients present with non-radiating back pain with no association to exertion. Sensory loss and spastic paresis often indicate onset of myelopathy secondary to cord compression. Bladder dysfunction, gait distur- bance, Brown-Sequard syndrome, and kyphosco- liosis occur in cases of large meningioma.
Meningiomas are often single, solid and well- circumscribed tumors with broad attachment to the dura. The dura tail and calcifi cation may be seen, but they are less common than in intracra- nial meningiomas (Fig . 3.1 ). On CT, meningiomas are often hyperdense or isodense to the spinal cord with intense contrast enhancement. Widening of ipsilateral subarachnoid space may be seen in large tumors. Hyperostosis of adjacent skeletal structures may occur but is not as common as with intracranial meningiomas. Meningiomas are isointense or hypointense to the spinal cord on T1WI and isointense or slightly hyperintense on T2W1. Large meningiomas are very vascular tumors and may occasionally show fl ow void.
Cystic degeneration is uncommon in meningiomas.
In general, meningiomas demonstrate strong homogenous enhancement after gadolinium administration, except for calcifi ed areas (De
Verdelhan et al . 2005 ) . Large meningiomas cause compression and displacement of the spinal cord and adjacent nerve roots. Patients with myelopa- thy might exhibit signal changes in the spinal cord secondary to compression. Occurrence of calcifi - cations, dural tail and thoracic location makes it easier to differentiate meningiomas from other types of intradural tumors. Meningiomas are slow growing solitary tumors. Total surgical excision is possible in 95% of cases. Prognosis is less favorable in infi ltrative meningiomas, atypical meningiomas, angioblastic meningiomas and in meningiomas with incomplete surgical excision.
Neurofi bromas are benign tumors (WHO grade I) of the peripheral nerve sheath.
Neurofi bromas account for 5% of all benign soft tissue tumors. Neurofi bromas are rare intraspinal extramedullary tumors except in patients with neurofi bromatosis type I (NF-I). Up to 65% of patients with NF I develop neurofi bromas, often multiple. Intraspinal neurofi bromas are usually localized tumors whereas peripheral nerve neuro- fi bromas can be localized, diffuse, or plexiform.
Plexiform neurofi bromas often affect brachial plexus and lumbosacral plexus in patients with NF-I (Khong et al . 2003 ; Mautner et al . 1995 ) . Neurofi bromas are more common in the cervical region. Neurofi bromas affect males and females equally with peak age at presentation of about 20–30 years. The most common presenting symp- tom is a palpable mass. Radicular pain and focal neurological defi cit occur in spinal neu- rofi bromas. Patients with NF-I often have other stigmata of NF-I.
In contrast to schwannomas, neurofi bromas encase rather than displace the nerve roots.
Calcifi cation and hemorrhage are uncommon.
They are often small tumors but large intraspinal neurofi broma may occur in the lumbar region.
They are typically rounded or fusiform tumors and can be seen on CT only when they are large and cause widening of neural foramen, scallop- ing of adjacent vertebral bodies and thinning of pedicular cortex. On MRI, neurofi bromas are isointense to spinal cord and nerve roots on T1WI and markedly hyperintense on T2WI. A target sign with peripheral high signal intensity (tumor) and central isointensity (encased nerve root) on
Fig. 3.1 Meningioma. Coronal contrast-enhanced T1-weighted image demonstrate a well-circumscribed, homogeneously enhancing intradural extramedullary lesion in the posterolateral aspect of the spinal canal with broad dural attachment on the left side at the level of T4–T5
T2WI is suggestive but not pathognomonic for neurofi broma (Osborn et al . 2004 ) . After contrast administration, moderate and often homogenous enhancement is seen. Some neurofi bromas show only peripheral enhancement. Plexiform neurofi - bromas are often diffuse growing tumors that exhibit low signal intensity on T1WI and high signal intensity on T2WI compared with that of the adjacent muscles. An important differential diagnosis in multiple neurofi bromas is intradural extramedullary metastasis, especially in patients who do not have NF-I. In single neurofi broma the main differential diagnosis is schwannoma which usually displaces rather than encases the affected nerve roots. Neurofi bromas are slow-growing tumors with the exception of 3–5% of patients with neurofi bromas associated with NF-I who developed malignant peripheral nerve sheath tumors (MPNST). These patients together with patients with non-resectable plexiform neurofi - bromas usually have less favorable prognosis with regard to survival and cure respectively.
Paragangliomas are also called glomus tumors or chemodectomas. They are rare intra- dural spinal tumors that are considered benign (WHO grade I) but can present with a more aggressive growth pattern and even metastasis (Sundgren et al . 1999 ) . Only 10–20% of extraad- renal glomus tumors are spinal tumors. They are usually found in cauda equina, medullary conus, and fi lum terminale (Sundgren et al . 1999 ) but are rare in the cervical or thoracic region. Like other extra adrenal glomus tumors, the spinal paragangliomas are endocrinologically inactive.
Females are more frequently affected than males with peak age at presentation of 40–50 years. The most common presenting symptoms are pain and radiculopathy. Slowly progressive cauda equina syndrome is another type of clinical presentation.
Subarachnoid hemorrhage with headache and neck rigidity is rarely the presenting symptom.
Spinal paragangliomas are well circumscribed vascular tumors commonly found in the cauda equina. Hemorrhage is not unusual and calcifi cation may be present, whereas cystic changes are uncommon. On CT, paraganglioma is an intra- dural extramedullary tumor that is isodense to the spinal cord, shows strong enhancement and causes
bony remodeling of the adjacent skeletal struc- tures. In aggressive tumors they may cause bony erosion. On MRI, they are isointense to spinal cord on T1WI, hyperintense on T2WI, show fl ow void and demonstrate marked contrast enhance- ment. Hemorrhage and intratumoral vessels with fl ow void are common features of this tumor (Sundgren et al . 1999 ) and may contribute to sig- nal inhomogeneity on T2WI. Paragangliomas are often diffi cult to distinguish from myxopapillary ependymoma based on imaging studies as both tumors have predilection to cauda equina and medullary conus. Paragangliomas are slow grow- ing benign tumors that often need preoperative embolization. Following total resection the rate of recurrence amounts to 5%.
Leptomeningeal metastases may arise from hematogenous dissemination from extracranial neoplasms, such as a breast cancer, lung cancer, malignant melanoma or as drop metastases from the spread of central nervous system (CNS) tumors. Common primary CNS tumors that may spread to the leptomeninges are anaplastic astro- cytomas, ependymomas or medulloblastomas (Gorgulu et al . 2005 ) . Choroid plexus cancer and germinomas also can give rise to drop metasta- ses. Leptomeningeal metastases which account for 5% of all spinal metastases may affect any part of the spinal canal and vary in size and pat- tern. They can be solitary, nodular or diffuse.
Leptomeningeal metastases should be suspected in patients with a known primary tumor presented with severe radicular pain. Focal neurological defi cit and evidence of myelopathy usually occur in large advanced tumors.
Usually, CT is normal except in cases of large solitary metastases which demonstrate intense contrast enhancement. On MRI, leptomeningeal metastases may manifest with different imaging patterns: (1) diffuse, enhancing coating of the surface of the spinal cord and nerve roots; (2) multiple small enhancing nodules on the surface of the spinal cord, cauda equina and/or nerve roots; and (3) as a single mass in the lowest part of the thecal sac (Van Goethem et al . 2004 ; DeAngelis 1998 ) . These tumors are often isoin- tense to the spinal cord on T1WI and T2WI and show strong contrast enhancement. In advanced
dissemination, the thecal sac may be fi lled with tumor that elevates the CSF-signal intensity on T1WI and makes CSF indistinguishable from spinal cord. Leptomeningeal carcinomatosis is a progressive disease with poor prognosis.
Malignant peripheral nerve sheath tumors (MPNST) account for 5–10% of all soft tissue tumors. Up to 3–5% of patients with NF-I develop MPNST (Osborn et al . 2004 ) . They are malignant tumors of spinal roots, peripheral nerves, plexus and end organs (WHO grade II–IV). Histopathologically, these tumors are classifi ed into malignant schwannoma and neu- rofi brosarcoma. They are large infi ltrative tumors, often located in the paraspinal region with secondary extension into the spinal canal, often along the neurovascular bundles. They usually affect patients in the fi fth decade with a slight male predominance in cases associated with NF-I. The patients usually present with soft tissue mass. Radicular pain, paraparesis and paresthesia are also common presenting symptoms. Other stigmata of NF-I are usually present at the time of presentation of these soft tissue tumors.
The tumors present as soft tissue masses along the brachial plexus, the lumbosacral plexus, the sciatic nerve and the peripheral nerves in the upper or lower extremities. On CT they are isodense or hypodense to the adjacent muscles with strong contrast enhancement. Calcifi cation, widening of neural foramen, bone remodeling and erosion of the adjacent bony structure are common. On MRI, MPNST is often a solitary infi ltrative mass that demonstrates isointense signal to muscles on T1WI and hyperintense signal on T2WI with intense contrast enhance- ment. Calcifi cation and hemorrhage give rise to inhomogeneity of signal intensity and contrast enhancement. Infi ltration into the surrounding soft tissue and spread through neural foramen into spinal canal occur relatively early in the course of the disease. MPNST are malignant tumors with a high recurrence rate because of the infi ltrative nature of the tumors and diffi culties of total resection. Metastases to lungs, bones and lever occur in up to 20–65% of cases (Osborn et al . 2004 ) .
Intradural Intramedullary Tumors Ependymomas are the most common spinal cord tumors in adults and the second most common tumors in children, with a peak incidence in the fourth and fi fth decades (Yoshii et al . 1999 ) . Thirty percent of ependymomas are spinal where they account for 60% of all spinal intramedullary tumors (Bourgouin et al . 1998 ; Baleriaux 1999 ; Van Goethem et al . 2004 ) . The majority of ependymomas arise in the cervical spinal cord (44% in the cervical cord alone and 23% involving the upper thoracic spinal cord as well). Together with schwannomas and meningiomas, ependymo- mas constitute the tumors most commonly encountered in patients with neurofi bromatosis.
Cellular ependymomas (cellular or mixed), also called de novo ependymoma, commonly pre sent in the cervical or upper thoracic region.
They are classifi ed as WHO grade II (grade III in cases of anaplastic ependymomas). They arise from the ependymal lining of central canal and are therefore often concentric in location.
Ependy momas are often locally growing tumors but CSF and local tumor spread may occur.
Metastases to lungs, kidneys and lymph nodes are rare.
Neck or lumbar pain, often radicular, simulat- ing disc protrusion and paraparesis and/or par- esthesia are the most common presenting features.
Evidence of subarachnoidalt non-aneurysmal hemorrhage with headache and neck rigidity and subsequent development of hydrocephalus may be encountered in some cases. Neurological defi - cit, gait disturbance, bladder dysfunction and impotence that developed slowly often contribute to a delay of 2 years before the diagnosis is established.
The intramedullary ependymomas are rela- tively well-circumscribed masses with symmetri- cal cord expansion typically involving more than 3–4 vertebral segments. On CT ependymoma causes enlargement of the spinal cord, widening of neural foramen, thinning of pedicles and scalloping of posterior part of adjacent vertebral body. On MRI, ependymoma commonly are isointense or slightly hypointense to the spinal
cord on T1WI and hyperintense on T2WI (Osborn 1994 ; Kahan et al . 1996 ; Sun et al . 2003 ) . “Cap sign” with substantial drop of signal intensity at the periphery of the tumor is seen in 20–50% of cases and indicates the presence of hemosiderin.
Ependymomas demonstrate marked but often inho- mogeneous enhancement after contrast adminis- tration. Cyst formation and hemorrhage is common (occur in up to 50% of tumors), whereas calcifi - cation is rare. Syrinx is also a common fi nding as it is seen in more than 50% of cases. Medullary edema on either side of the tumor is variable, but often demonstrated in the large multisegmental tumors. Cellular ependymomas are slowly pro- gressive tumors with a 5 year survival rate of 82%. Bad prognostic markers are large tumors, sacral tumors, subtotal resection, disseminating tumor and occurrence of medullary atrophy.
Myxopapillary ependymomas are the most common tumors (90%) of the medullary conus, cauda equina and fi lum terminale. They are twice as common in males with peak age at presentation in the fourth decade. Thirty percent of ependymo- mas are myxopapillary. They are classifi ed as WHO grade I–IV. They arise from the ependymal cells of fi lum terminale and are often locally growing tumors. CSF- and local tumor spread may occur whereas metastases to lungs and lymph nodes are rare. Primarily paraspinal ependymomas may occur and are often located in the sacral and sacrococcygeal region.
Local or radicular pain is the most common presenting feature of this type of ependymoma.
Progressive cauda equina syndrome may be encountered in 25% of cases of myxopapillary ependymoma. Evidence of subarachnoidalt non- aneurysmal hemorrhage may be the presenting feature of the tumor. Myxopapillary ependymo- mas may vary in size and are well-defi ned oval or multilobular masses. If very large, myxopapil- lary ependymomas are associated with scallop- ing of the vertebral body, pedicular erosion, scoliosis, and enlargement of the neural foramen.
They usually present as isointense or hyperintense mass (accumulation of mucin) on T1WI and hyperintense mass on T2WI. They demonstrate strong somewhat inhomogeneous contrast enhance- ment. Hemorrhage is a common feature and con-
tributes to signal inhomogeneity. Myxopapillary ependymomas usually have good a prognosis following complete tumor resection which is possible in 80–90% of cases.
Astrocytomas of the spinal cord are the most commonly seen intramedullary tumors in children and the second most common spinal cord tumors in adults, with an average age of 10–30 years at the time of presentation and a slight male predilection.
They account for 30% of all spinal intramedul- lary tumors and 5–10% of all CNS-tumors.
Similar to cellular ependymoma, astrocytomas are more common in the cervical region, followed by the upper thoracic spinal cord (Fig. 3.2 ). They are classifi ed into pilocytic and fi brillary astrocy- tomas (WHO grade I–II, 90%) and anaplastic astrocytoma and glioblastoma multiforme (WHO grade III–IV, 10%). They are infi ltrative tumors that arise from astrocytes of spinal cord.
Slowly progressive neurological defi cit with paresis and sensory loss, bladder dysfunction,
Fig. 3.2 Fibrillary astrocytoma. A Sagittal contrast- enhanced T1-weighted image shows a large heteroge- neously enhancing tumor with marked cord expansion at the level of C1–C3