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Intradural , Carra et al. Intradural Spinal Neoplasms: A Case Based Review

Bradley J. Carra, M.D.a, Paul M. Sherman, M.D.a,b

aDepartment of Radiology, Wilford Hall Ambulatory Surgical Center, Joint Base San Antonio-Lackland, TX bDepartment of Radiology, Uniformed Services University of the Health Sciences, Bethesda, MD

Introduction

Spine neoplasms are classified based on their abnormalities, and other spine pathology, while not location as either extradural, intradural extramedullary discussed further in this review, can have a similar (IDEM), or intramedullary. This review will focus on appearance to cord tumors and should always be intradural neoplasms including both extra- and considered. When tumor is suspected, however, intramedullary. While neoplasms are relatively certain diagnoses can be favored based on lesion uncommon compared with other types of spine location, patient demographics such as gender and pathology, recognition of their imaging appearance age, and select imaging findings. and understanding the principles of spine tumor imaging is necessary as MRI is the primary tool for establishing a differential diagnosis, guiding the Intramedullary Neoplasms diagnostic workup, and formulating a treatment plan. Intramedullary tumors represent 5-10% of all spine tumors and are more common in children.1 The most Spine Tumor Imaging common primary intramedullary neoplasms are ependymoma, , and . MRI is the imaging modality of choice for assessing , metastasis, and primary lymphoma are the spine because of its high soft tissue contrast; less common. Intramedullary neoplasms share many therefore, its use will be emphasized in this review. common imaging features. Abnormal cord signal The first step in forming a pertinent differential intensity and expansion, whether from tumor itself or diagnosis is assessing the location of the abnormality. from cord edema, commonly spans several spinal Intramedullary neoplasms are characterized by levels, and may involve the entire . abnormal cord signal and expansion. IDEM tumors are Contrast enhancement is the rule, and unlike most contained within the thecal sac but displace rather intracranial neoplasms, even low-grade spinal tumors than expand the spinal cord. A CSF cleft may be seen characteristically enhance. Syringohydromyelia and separating the tumor from the cord. Use of cyst formation is common. Two types of cysts exist: gadolinium based contrast agents should be standard tumoral cysts and rostral/caudal cysts. The former are in suspected spinal tumors. Enhancement is a lined with neoplastic cells and typically demonstrate hallmark of spine neoplasms and helps to differentiate rim-enhancement; the latter are reactive and do not tumor from cord edema and reactive cysts, an contain neoplastic cells or enhance. Distinction is important distinction for surgical planning to limit the important as the former need to be surgically resected size of laminectomy to that of the tumor. Additionally, while the latter can simply be aspirated. imaging of the entire neuraxis is necessary in The majority of intramedullary neoplasms are low suspected tumors as many metastasize through CSF grade and slow-growing. Therefore, patients typically dissemination, can be multiple as part of a syndromic have a prolonged clinical course extending over many disorder, or themselves may represent metastatic years prior to diagnosis. Common symptoms include disease from other parts of the CNS. back pain and sensory disturbances. In general, Many of the imaging features of IDEM neoplasms treatment consists of surgical resection, with or are nonspecific, which means most cases will have a without adjuvant radiation and chemotherapy. list of differential considerations. In terms of intramedullary pathology, infection, demyelinating disease, vascular malformations, metabolic

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Ependymoma. Ependymomas are the most common intramedullary in adults and the second most common in children.2 Mean age of presentation is in the 4th to 5th decades of life, and there is no gender predilection.3 They arise from ependymal cells lining the , and are therefore typically centrally located. The cervical cord is the most common location.4 While they share many of the histologic characteristics of intracranial ependymomas, they are considered genetically different and carry a better prognosis. Gross total resection results in extremely low recurrence rates.1 Five histologic subtypes of ependymoma exist, including cellular, clear cell, papillary, tanycytic, and myxopapillary (discussed in the IDEM section). The Figure 1. Ependymoma. 34 year-old patient with a centrally cellular subtype is most common and is typically WHO located mass enlarging the cervical cord. Sagittal T1W (A) and T2W (C) images demonstrate a heterogeneous, solid grade II. Sensory symptoms predominate in the intramedullary mass with rostral and caudal cyst formation and clinical presentation, possibly from involvement of the cord edema. Low T2 signal along the caudal margin is the central crossing spinothalamic tracts. Ependymomas “hemosiderin cap” (arrow). Diffuse heterogeneous enhancement can be seen as part of (NF) type 2 is seen on post-gadolinium (B) sagittal T1-weighted sequences. (“MISME” syndrome — multiple inherited , , and ependymomas), though the majority are sporadic. Ependymomas are characteristically well- circumscribed masses in the central portion of the cord. They generally demonstrate T1 iso- to hypo- intensity and T2 hyperintensity relative to the spinal cord. Cyst formation is common. Due to their highly vascular nature, profound low T2 signal at the cranial or caudal margins, known as the “hemosiderin cap”, is a distinguishing feature (Fig. 1). While the classic enhancement pattern is homogeneous and intense, this was seen in only 38% of cases according to one series, with heterogeneous, rim, and minimal enhancement patterns collectively making up the remaining majority.5

Astrocytoma. Intramedullary arise from astrocytic cells within the cord and represent the most common cord neoplasm in children and the second most Figure 2. Astrocytoma. Cervical spinal cord intramedullary common in adults. There is a slight male mass in this child causes fusiform enlargement of the cord 3,6 spanning several vertebral levels. Pre- (A) and post-gadolinium predominance. The majority are low-grade WHO I (B) sagittal and axial (C and D) T1W images demonstrate and II, pilocytic and fibrillary variants, respectively. heterogeneous, irregular ring-enhancement with eccentric WHO grade III and IV tumors, anaplastic and involvement of the cord and poorly defined rostral margins. gliobastoma multiforme (GBM) subtypes, together Pathology revealed a WHO grade III .

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Figure 3. Hemangioblastoma. Solid and cystic components within a mass at the cervicomedullary junction demonstrated on sagittal T2W (A) and T1W (B) images. Sagittal post gadolinium T1W image (C) demonstrates enhancement of the caudal solid component (cyst-mural nodule pattern of enhancement). Faint marginal enhancement surrounding the cystic component is also identified. form only 10-15%.7 GBM’s are rare, representing a the literature,11,12 in conjunction with cerebellar minority of the higher grade cord astrocytomas. , retinal angiomas, and Expectedly, high-grade tumors have a higher rate of endolymphatic sac tumors in the CNS and head and recurrence and metastasis and carry a worse prognosis neck. There is a slight male predominance, and the with average survival on the order of months.8 All mean age of diagnosis is in the 4th decade of life, subtypes demonstrate infiltrative growth along - non though they tend to present about a decade earlier neoplastic scaffolding of the cord. Cyst formation is when associated with VHL.13 frequently seen. Cervical and thoracic cord 1 MR imaging characteristics include a well- involvement predominates. delineated, uniformly T2 hyperintense mass in smaller Many imaging features suggest a diagnosis of lesions. Location is subpial, typically along the astrocytoma over ependymoma. As opposed to posterior aspect of the cord. Cyst and syrinx formation ependymomas, astrocytomas are more are common, and the cyst-mural-nodule appearance characteristically eccentrically located and are less well classically seen in cerebellar hemangioblastomas may -defined secondary to their infiltrative growth pattern be seen with larger lesions (Fig. 3). Due to the highly (Fig. 2). MRI signal characteristics are similar, with T1 vascular nature of this entity, enlarged feeding vessels iso- to hypointensity and T2 hyperintensity compared and flow voids in larger masses may be seen. Uniform to cord, though hemorrhage is less common. Partial and intense enhancement is characteristic of smaller mild-moderate intensity heterogeneous enhancement masses. is characteristic, though no enhancement was seen in 20-30% in one series.9 Despite the lack of enhancement, neoplasm should still be suggested Metastases. based on characteristic cord expansion and signal Spinal cord metastases are uncommon, seen in only 14 abnormality. 0.9-2.1% of autopsied cancer patients in one series. They represent approximately 3% of metastases to the spine.15 The most common primary tumors are lung15 Hemangioblastoma. and breast and arise either through hematogenous Hemangioblastomas are far less common than dissemination or CSF spread through the central canal. ependymomas and astrocytomas, accounting for 3.3% The cervical cord is the most common site of of spinal cord tumors.10 They represent a low-grade involvement.16 Intratumoral hemorrhage may be seen (WHO grade I) vascular neoplasm, though their cell of with certain types of primary neoplasm. While they origin is yet to be delineated. Association with von may be solitary, multiple lesions or multifocal Hippel-Lindau (VHL) syndrome ranges from 17-38% in involvement, including the osseous spine, may be key

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Intradural Neoplasms, Carra et al. to distinguishing the diagnosis. Unlike primary spinal The MRI appearance is nonspecific with respect to cord neoplasms, metastases tend to have a more rapid other intramedullary neoplasms, typically onset and disease progression, on the order of weeks demonstrating T1 isointensity and T2 hyperintensity to to months rather than years. Prognosis is uniformly the spinal cord. The T2 hyperintensity reported in poor with life expectancy on the order of months, as cases within the literature18 is in distinction to the this represents an advanced stage of disease. typical T2 hypointensity seen in primary lymphoma of 19 Imaging features vary based upon the primary the brain because of the high cellular content. tumor. Common features include a relatively small Contrast enhancement is heterogeneous. mass with extensive edema that is out of proportion for that expected based upon the size of the mass. Ganglioglioma. Cord enlargement, if present, is not pronounced, and 16 Ganglioglioma is uncommon, accounting for only cysts are uncommon. Enhancement is common 20 (Fig. 4). T1 hyperintensity can be seen with 1.1% of spinal neoplasms. It is a low grade slow melanoma metastases and with hemorrhage. growing tumor composed of a mixture of neoplastic neuronal and glial elements. Children are more commonly affected with a classic clinical presentation Lymphoma. of painful scoliosis. Cervicothoracic cord involvement Lymphoma has a variety of disease patterns predominates but holocord involvement is not involving the spine, including osseous, epidural, uncommon. leptomeningeal, and spinal cord involvement. Several MRI findings are suggestive of Intramedullary spinal involvement is the least gangliolioma.20 Length of involvement tends to be common, accounting for only 3.3% of CNS lymphoma larger with an average of 8 vertebral segments, and cases.17 As in other areas of the CNS, non-Hodgkin they are eccentrically located within the cord. lymphoma predominates over Hodgkin disease, Enhancement is patchy with more than half though some of the reported cases of spinal demonstrating extension to the pial surface. Tumoral lymphoma are of T-cell lineage,18 an atypical feature of cysts are common. Signal intensity on T1-weighted CNS lymphoma. Cord involvement favors the cervical images is heterogeneous, and the amount of cord spine. edema is relatively unimpressive based upon the size of the tumor.

Intradural Extramedullary Neoplasms

IDEM tumors are more common in adults. Schwannomas and meningiomas are the most common, together accounting for 45% of all primary spinal cord neoplasms.21 The differential diagnosis also includes , malignant , lymphoma, myxopapillary ependymoma, , and metastatic disease.

Schwannoma. Schwannomas arise from support cells of the nerve Figure 4. Intramedullary and Osseous Metastases. sheath and are the most common IDEM spinal Abnormal high T2 signal (arrows) on sagittal (A) and axial (C) neoplasm. Nerve sheath tumors account for 25% of all images with avid irregular contrast enhancement on T1W images (B, D, and E) represent intramedullary metastases intradural spinal tumors in adults, with the majority 22 from a known cerebral GBM. Multiple heterogeneously being schwannomas. While they may occur in any enhancing masses in the lumbar and sacral vertebrae (*) are spinal compartment, they are most commonly consistent with metastatic disease.

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Spinal schwannomas can be difficult to distinguish from meningiomas on imaging. They are typically well -circumscribed T2 hyperintense masses with signal intensity approaching that of fluid. Cyst formation is more common than with meningiomas. Their enhancement pattern is typically uniform (Fig. 6), though heterogeneous and ring-enhancement patterns do occur. Imaging features useful in distinguishing from include foraminal enlargement and osseous remodeling, involvement of the cauda equina, fluid intensity T2 Figure 5. Dumbbell (intradural extramedullary and signal, and ring-enhancement.23 extradural) Schwannoma. Axial T2W image (A) shows a

large dumbbell schwannoma exiting and widening the right neural foramen consistent with both an intradural and Meningioma. extradural component. CSF cleft (arrow) along the superior margin of the mass on the sagittal T2W image B( ) confirms Meningiomas are the second most common IDEM the extramedullary location. spinal neoplasm. They arise from arachnoid cap cells within the dura and are most commonly seen in females in the 5th-7th decades of life.22 The majority are solitary and sporadic; however, there are multiple syndromic associations, the most common of which is NF2 (see “MISME” in ependymoma section above). Thoracic cord involvement is typical and unlike schwannomas, cystic degeneration is uncommon. WHO grade I tumors are by far the most common, and total resection is generally curative. Meningiomas are typically seen as well circumscribed masses along the ventral or ventrolateral aspect of the cord (Fig. 7). MR signal

Figure 6. Multiple Schwannomas in NF2. Multiple uniformly enhancing (A thru C) small extramedullary intradural masses are demonstrated along the pial surface of the distal spinal cord and the cauda equina. Multiplicity of the masses suggests the diagnosis of NF2. intradural and extramedullary in location within the thoracic or lumbar spine.23 The classic “dumbbell” lesion extending through the neural foramen is considered both intra- and extradural, occurring in 10- 24 15% of cases (Fig. 5). Most are solitary and sporadic. Figure 7. Meningioma. Sagittal (A) and axial (B and C) post- Syndromic associations include NF2, Carney complex, gadolinium T1WI sequences reveal an IDEM mass abutting and schwannomatosis. Schwannomas are typically the ventrolateral aspect of the cervical cord which displaces the exiting right nerve root (B and C). There is a broad dural low grade (WHO grade I) tumors. Total resection of an base and the presence of a dural tail (arrows) which suggests intradural schwannoma is considered curative. the diagnosis of meningioma.

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Intradural Neoplasms, Carra et al. characteristics include T1 iso- and T2 iso- to hyperintensity relative to the spinal cord. A broad dural attachment, or “dural tail”, was seen in 58% of meningiomas in one series, best demonstrated on post -contrast imaging.23 In this same series, calcification, Figure 8. in NF1. which is easily identified on CT, was also identified in Several IDEM masses of the 58%. Post-contrast imaging typically reveals diffuse cauda equina with peripheral T2 hyperintensity (“target sign”), and prominent enhancement. A solitary IDEM suggestive of neurofibromas. thoracic spine mass in a middle-age female should Multiplicity suggests NF1. suggest the diagnosis.

Neurofibroma. Neurofibromas are much less common than schwannomas within the spine. They are most commonly seen in the 3rd-4th decades of life and have no gender predilection.1 The classic association of NF1 with plexiform neurofibroma is virtually pathognomonic. However, the majority of lesions are sporadic. They can be intradural and/or extradural and can be seen at any spinal level. Neurofibromas are WHO grade I neoplasms. While total resection is considered curative, tumors with extensive paraspinal involvement and subtotal resection have a propensity to recur and require follow up imaging. It is often difficult if not impossible to Figure 9. Malignant Peripheral Nerve Sheath Tumor. distinguish solitary spinal neurofibromas from A large heterogeneous T2 hyperintense dumbbell mass (A schwannomas based on imaging alone. Peripheral T2 and C) extends through and widens the neural foramen in hyperintensity, the “target sign,” is more suggestive of this patient with NF1. Contrast enhancement is avid (B and neurofibroma but not pathognomonic (Fig. 8). Cystic D). Findings are consistent with a peripheral nerve sheath degeneration and hemorrhage are also less common tumor. However, the large size and infiltration of the paraspinal musculature (*) (C and D) raises suspicion for than schwannoma. Involvement of a ventral nerve malignancy. The serpentine enhancing structure (arrow) 1 root is more suggestive of neurofibroma. Extradural posterior to the cord in (B) is an enlarged vein from tumor extension can be prominent as a plexiform or compression. (Case courtesy of Dr. William T. O’Brien, Sr.) infiltrative soft tissue mass. Myxopapillary Ependymoma.

The myxopapillary variant represents roughly 30% Malignant Peripheral Nerve Sheath Tumor. 25 of all intraspinal ependymomas. It can be Malignant peripheral nerve sheath tumor (MPNST) distinguished based on its characteristic location represents a soft tissue sarcoma with histologic within the conus medullaris, filum terminale, or cauda features of peripheral nerves either occurring de novo equina where it is the most common tumor. Peak or arising from malignant degeneration of a incidence is in the 3rd-5th decades of life, and there is a neurofibroma. They are WHO grade II-IV tumors. slight male predominance.1 Despite its WHO I grading, Roughly half are associated with NF1 while the it may cause subarachnoid seeding. Hemorrhage, 1 remainder are sporadic. They most commonly calcification, and cyst formation are common. The involve the paravertebral soft tissues with rare tumor can become intimately involved with the nerve intraspinal involvement. Masses are typically roots of the cauda equina making total resection markedly heterogeneous and infiltrating (Fig. 9). difficult. When accomplished, recurrence rates are Prognosis is poor. low.

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Figure 10. Myxopapillary Ependymoma. A heterogeneous, mixed Figure 12. Paraganglioma. Markedly T2 hyperintense (A), solid and cystic (axial T2W images B and C) sausage-shaped mass circumscribed mass along the dorsal aspect of the distal occupies much of the lower lumbar spinal canal and enhances spinal cord shows avid enhancement on post-gadolinium avidly (post-gadolinium T1W images A, D, and E). T1W images (B and C). Myxopapillary ependymomas are sausage-shaped masses that can occupy the entire lumbosacral canal (Fig. 10). Unlike other histologic variants of spinal ependymoma, the myxopapillary type may have intrinsic T1 hyperintensity secondary to its high mucin content, seen in 67% of cases in one series.5 Other imaging features, such as the hemosiderin cap and intralesional flow voids, are similar to other ependymoma variants.

Lymphoma. As discussed above, spine lymphoma has a variety of different disease patterns, which include leptomeningeal involvement. The majority occur as spread from intracranial lymphoma. Patient demographics are similar to that of other types of lymphoma, most commonly occurring in middle age adults. Imaging hallmarks include thickened nerve roots and smooth or nodular leptomeningeal enhancement; IDEM mass formation can occur in extreme cases (Fig. 11).

Figure 11. CSF Dissemination of Mantle Cell Lymphoma. Paraganglioma. 64 year-old woman with known lymphoma presented with cauda equina syndrome. Imaging shows abnormal low T2 are neural crest tumors of which (A) and intermediate T1 (B) signal that fills the lumbar the intra-adrenal form, pheochromocytoma, is the spinal canal and encases the conus medullaris and cauda most common. Extra-adrenal paragangliomas most equina. Post-gadolinium T1W images (C and D) best depict the mass which is avidly enhancing. commonly occur in the head and neck near the carotid bulb, jugular foramen, and within the temporal bone. When they occur in the spine, they are

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Figure 13. CSF metastases. Multiple small masses of the Figure 14. CSF metastases. Pre- (A) and post-gadolinium (B cauda equina are isointense to the cord on T2W images (A and C) T1W images show diffuse and slightly nodular and C) and avidly enhance on post-gadolinium T1W images enhancement along the surface of the conus medullaris and (B and D). Metastatic deposits in this patient were from a cauda equina, known as “sugar coating,” representative of primary thoracic cord GBM. widespread deposits of metastatic lung cancer throughout the CSF. characteristically located within the lumbar spine, sensitivity for detection of metastatic lesions. MRI is involving the cauda equina or filum terminale where an important adjunct to lumbar puncture with CSF they are almost always non-secreting. analysis in diagnosing CSF metastasis; cytology alone Paragangliomas typically appear as a well- has a significant false-negative rate and frequently circumscribed mass within the cauda equina. They are must be repeated. It is important to remember, T2 hyperintense and highly vascular (Fig. 12). however, that chemical meningitis can cause Hemosiderin cap and flow voids may be seen in larger enhancement and thickening of nerve roots, lesions. MR imaging features are nonspecific and may mimicking metastatic disease. Imaging should mimic myxopapillary ependymoma, schwannoma, and therefore precede lumbar puncture and craniotomy. meningioma, which are much more common. The diagnosis can be suggested with avid uptake on Summary nuclear medicine metaiodobenzylguanidine (MIBG) scan. While neoplasms are a relatively uncommon form of spine pathology, recognition of their imaging features plays an essential role in providing a meaningful Metastasis. differential diagnosis and guiding further evaluation CSF seeding with malignant cells may occur through and treatment. While many of the imaging a hematogenous route or may represent spread from characteristics are nonspecific with significant overlap, a CNS primary. The most common primary when tumors are suspected, certain diagnoses can be malignancies outside of the CNS include lung, breast, suggested based upon location, clinical and patient 26 and melanoma. CNS primary tumors with a demographics, and certain specific imaging features. tendency for CSF dissemination include high-grade astrocytomas, ependymomas, germ cell tumors, , and neoplasms. The views expressed in this material are those of the author, and do not reflect the official Imaging findings mirror patterns of disease policy or position of the U.S. Government, the involvement, which include solitary masses (Fig. 13), Department of Defense, or the Department of diffuse smooth or nodular coating of the cord and the Air Force. nerve roots (Fig. 14), and thickening of the cauda equina. Use of intravenous contrast increases the

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