Spinal Tumors

Epidemiology

Ependymomas are the most common intramedullary spinal tumors in adults, accounting for up to 60% of all intramedullary tumors. The mean age at presentation is around 40 years, and there is a slight male predominance. Spinal ependymomas constitute 30% of all CNS ependymomas.

These tumors are usually solitary, but multiple ependymomas of the spinal cord, often in association with other spinal masses (i.e., meningiomas and schwannomas), may be present in patients with neurofibromatosis type 2 (NF2). Multiple or isolated ependymomas in the intramedullary but most often in the extramedullaryintradural space may also appear as secondary metastases of a primary intracranial or spinal ependymoma (see Fig. 15-9C, D ).

Myxopapillary ependymoma of the filum terminale is a histologic variant accounting for about 13% of all ependymomas but more than 80% of all ependymomas that are located in the conus medullaris and filum terminale. These tumors are located extramedullary and occur predominantly in males. The mean age at presentation is slightly younger than 35 years.

Subependymoma, another variant of ependymoma, appears rarely in the spinal cord, and only about 40 cases have been reported in the literature. It is estimated that because of their benign course 50% are asymptomatic during life and therefore mostly found incidentally at autopsies. When symptomatic, patients are usually male (2:1) and older than 40 years of age.

Primary low-grade ependymomas of the spine (World Health Organization [WHO] grade I and II, i.e., myxopapillary ependymoma and classic ependymoma, respectively) are far more common than high-grade lesions (WHO grade III, i.e., anaplastic ependymomas).

Clinical Presentation

Patients present with a history of mild and slowly progressive neurologic impairment. The tumor's slow growth rate and tendency to compress instead of infiltrate the adjacent neural tissue often lead to a delay in primary diagnosis. The mean duration of symptoms before diagnosis is 36 months. At diagnosis, most patients complain of back pain and focal sensory and/or motor deficits, depending on the segmental location of the tumor. Sensory symptoms are the predominant complaints, probably due to compression or interruption of the crossing spinothalamic tracts around the central canal. An unusual presentation reported in spinal ependymomas is cranial nerve palsy. Spinal ependymomas have a tendency for causing microhemorrhages, and a delay in diagnosis may lead to superficial hemosiderosis with involvement of the caudal cranial nerves around the brain stem, producing cranial nerve symptoms. An otherwise unexplained superficial hemosiderosis in a cranial MRI study should prompt a spinal investigation with MRI for the exclusion of a spinal ependymoma.

Myxopapillary ependymomas, owing to their most frequent caudal location, usually present as lower back and leg pain and sphincter dysfunction.

Approximately 50% of subependymomas are asymptomatic. If symptomatic, patients usually complain of a long history of progressive back pain. Motor or sensory deficit may also appear, according to the segmental localization.

Pathophysiology

Ependymomas are ependymal cell tumors and are classified according to the WHO grading system for spinal cord tumors as ependymoma (WHO grade II), myxopapillary ependymoma (WHO grade I), subependymoma (WHO grade I), and anaplastic ependymoma (WHO grade III).

Classic ependymomas originate from the ependymal cells of the central canal. Myxopapillary ependymomas arise from the ependymal glia of the filum terminale. The origin of subependymomas is uncertain. They may derive from cells of the subependymal plate or residual periventricular matrix or from tanycytes (bridging cells between the pial and ependymal layers).

Ependymomas have been documented to appear in up to 89% of patients with confirmed NF2, an autosomal dominant disorder caused by mutations of the NF2 gene on chromosome 22q. On confirmation of NF2, clinical and radiologic evaluation, including MRI of the entire neuraxis, is crucial because presymptomatic diagnosis of spinal tumors improves the outcome of therapeutic management and the prognosis.

Pathology

Ependymomas are usually well-demarcated, grayish, soft tumors ( Fig. 15-2A ). Myxopapillary ependymomas are often encapsulated, lobulated, sausage-shaped masses and show a soft, grayish appearance (see Fig. 15-2B ). Subependymomas usually present as well-demarcated, firm nodules of variable size.

Classic ependymomas are well delineated and moderately cellular. The tumor cells are uniform and mainly possess a round-to-oval nucleus with speckled (“salt and pepper”) chromatin ( Fig. 15-3A ). A typical hallmark for ependymomas is the formation of perivascular pseudorosettes or ependymal rosettes (see Fig. 15-3B ). Blood vessels are often hyalinized. If ependymomas undergo malignant transformation (anaplastic ependymoma), cell density, mitotic activity, and proliferative indices are higher (see Fig. 15-3C ) and necroses and vascular proliferations are common features.

On immunohistochemistry ependymomas show positivity for glial fibrillary acidic protein (GFAP), S-100 protein, and vimentin in the majority of cases. They often show a typical dot-like staining pattern for epithelial membrane antigen (EMA).

In most myxopapillary ependymomas, areas with a papillary tumor pattern of columnar to cuboid tumor cells on a fibrovascular stroma ( Fig. 15-4A ) can be found. A myxoid matrix rich in microcysts is seen between tumor cells and blood vessels as well as in the tumor capsule (see Fig. 15-4B ).

On immunohistochemical staining, myxopapillary ependymomas are typically positive for GFAP and S-100 and typically lack immunoreaction for cytokeratins.

Spinal subependymomas are characterized by clusters of cells surrounded by a dense fibrillary matrix ( Fig. 15-5 ). The tumor cells exhibit ependymal and astrocytic differentiation markers. Microcystic changes are observed, although less commonly than in the other types of ependymomas. On immunohistochemistry they typically stain for GFAP and, to a lesser extent, for neuronal markers. Compared with the classic ependymoma, subependymomas have a very low rate of cellular proliferation, usually with an MIB-1 index below 1%.

Classic ependymomas are most commonly located in the cervical (67%) cord with or without extension into the upper thoracic region. Approximately 26% are located in the thoracic spine and 7% in the conus medullaris.

Myxopapillary ependymomas are tumors of the filum terminale and the conus medullaris and, thus, they are the most common neoplasms of this region (83%).

The localization pattern of subependymomas is most often cervical and then thoracic and thoracolumbar.

Imaging

MRI

Ependymomas (except for the rare ectopically located ependymomas) arise from the ependymal cells of the central canal and, therefore, when small, have a central intramedullary location generating a focal, symmetric enlargement of the spinal cord. On MRI these tumors appear as circumscribed masses that are commonly hypointense/isointense to cord on T1-weighted (T1W) images and are typically hyperintense on T2W images. A variable degree of contrast enhancement is seen in more than 80% of cases ( Fig. 15-6 ). About 80% of ependymomas are associated with cysts, which are most often reactive cysts (polar cysts) (see Box 15-1 ) as opposed to tumoral cysts, which occur more often with astrocytic tumors (see Fig. 15-11 ). Spinal cord edema surrounding the tumor to a variable extent is present in 60% of cases and more often evident in large lobular tumors (see Figs. 15-6C and 15-7C ). In 20% to 30% of cases, ependymomas may be outlined by a linear T2 signal hypointensity showing hemosiderin deposition as a result of chronic microbleedings (see Fig. 15-7C ), which helps in their differentiation from other contrast-enhancing glial tumors. Calcification is uncommon, as opposed to intracranial ependymomas. Owing to the central intramedullary location of the tumor, compression or disruption of medullary spinal tracts may be found on DTI (see Fig. 15-6D ).

BOX 15-1

Ependymoma

PATIENT HISTORY

A 62-year-old woman presented with a chief complaint of progressive pain in the shoulders and neck for 2 years. Initially the pain was restricted to the left shoulder and then progressed to involve the right shoulder and neck. The patient had a subtotal resection of the thyroid gland 10 years earlier owing to struma multinodosa. Otherwise, her past medical history was free of disease. MRI was performed 1 year after onset of the symptoms in another institution and showed only degenerative changes of the cervical spine. In the past months new onset of hypesthesia of the arms and hands led to a new consultation. Carpal tunnel syndrome was suspected and ruled out with neurophysiologic studies.

TECHNIQUE

Axial and sagittal T2W, sagittal T1W, and axial and sagittal T1W contrast-enhanced sequences (gadolinium, 0.1 mmol/kg) were obtained of the cervical spine.

FINDINGS

There is an intramedullary tumor on cord segment C3-4 ( Fig. 15-104 ).

COMMENT

The patient was admitted to the neurosurgical department for operative treatment. Preoperative neurologic examination was normal except for hypesthesia of the arms and hands without a clear dermatome pattern. The patient underwent a laminectomy of C3-C4 and the tumor was resected (see Fig. 15-104E ). Histopathologic examination confirmed the diagnosis of a cellular ependymoma (WHO grade II). Postoperative neurologic examination revealed ataxia and disturbance of fine motor skills, especially of the left hand. Postoperative MRI showed no residual tumor (see Fig. 15-104F-G ). The patient underwent rehabilitation and 3 months later showed evidence on follow-up examination of a full recovery.

In contrast to other ependymomas, myxopapillary ependymomas show a predilection for the conus medullaris and filum terminale and are extramedullary. They appear as isointense/hypointense masses on T1W images and as isointense/hyperintense masses on T2W images ( Fig. 15-8 ). They are often associated with cystic components and invariably enhance after administration of gadolinium. Occasionally, hyperintensity on both T1W and T2W images is seen in the cystic components of the mass, reflecting mucin or hemorrhage.

Spinal subependymomas present on MRI as fusiform masses with well-defined borders. Enhancement is present in 50% of cases. This histologic subtype is often difficult to differentiate from other intramedullary tumors. A distinctive feature reported in subependymomas is their eccentric location in contrast to the central location of ependymomas.

Anaplastic ependymomas (WHO grade III) have a malignant behavior. At the time of diagnosis they tend to appear as multifocal lesions involving multiple segments of the spinal cord ( Fig. 15-9 ). They are frequently associated with prominent edema and hemorrhage and show a rapid progression on follow-up examinations.

Association with scoliosis, vertebral body scalloping, pedicle erosion, and laminar thinning has also been described in ependymal tumors, but these features are more often seen with extramedullary spinal neoplasms.

Epidemiology

Astrocytomas are the second most common intramedullary tumors after ependymomas in adults. In children, astrocytic gliomas seem to be the most commonly found intramedullary tumors, especially owing to the high frequency of pilocytic astrocytoma. The incidence of primary spinal cord astrocytoma is reported as 2.5 per 100,000 per year, being 10-fold less than primary astrocytomas of the brain. Low-grade astrocytomas are more common than high-grade tumors. Primary glioblastoma multiforme of the spinal cord is very rare, accounting only for 0.2% to 1.5% of all spinal cord astrocytomas. Radiation-induced glioblastoma multiforme is extremely rare, with only a few reported cases in the literature. Secondary spinal astrocytomas from metastatic dissemination of a primary intracranial malignant astrocytoma are more frequent than primary spinal cord astrocytic gliomas.

In adults, the average age at onset is 29 years, a presentation that is earlier than that for ependymomas. Men are more commonly affected.

Clinical Presentation

The course of disease is related to the histologic grade of the tumor. Patients with low-grade tumors have mild neurologic impairment and a slowly progressive course, whereas high-grade tumors are associated with rapidly progressing neurologic symptoms. The neurologic deficits depend on the segmental localization of the mass and are nonspecific. Chronic back pain and focal sensory and/or motor deficits are the most common complaints. Because conus medullaris involvement is rare, bowel and bladder dysfunctions are also uncommon.

Because of the infiltrative nature of astrocytomas, resection is not feasible and the prognosis is far worse than that for classic ependymomas.

Pathophysiology

Spinal cord astrocytomas are glial cell tumors and are classified according to the WHO grading system for spinal cord tumors as low grade, including pilocytic astrocytoma (WHO grade I) and diffuse astrocytoma (WHO grade II), and high grade, including anaplastic astrocytoma (WHO grade III) and glioblastoma multiforme (WHO grade IV).

Several genetic mutations have been reported in low- and high-grade tumors, including mutation of the well-known tumor suppressor TP53 , growth factor receptors (platelet-derived growth factor/receptor [PDGF/R] overexpression and epidermal growth factor receptor [EGFR] amplification), RB mutation, cell cycle protein CDK4 amplification, PTEN loss, 19q loss, 11p loss, INK4a/ARF loss, gain of chromosome 7, and loss of chromosome 10 or 10q.

Pathology

Pilocytic astrocytomas are usually sharply delineated and often show cystic formations.

Diffuse astrocytomas show diffuse borders owing to their infiltrative growth pattern. The normal CNS tissue is usually infiltrated but not destroyed. Cyst formation is occasionally present.

Glioblastoma multiforme is usually poorly delineated. The internal composition of the lesion is very inhomogeneous, showing hemorrhages and necroses.

Pilocytic astrocytomas are of low to moderate cell density with varying proportions of bipolar cells with Rosenthal fibers. Microcysts and eosinophilic granular bodies/hyaline droplets are frequently found ( Fig. 15-10A ). On immunohistochemical stains the tumor cells are positive for GFAP and S-100. The MIB-1 proliferation index is usually low (up to 4%).

Low-grade diffuse astrocytomas show low cell density with tumor cells of uniform morphology within a dense fibrillary matrix (see Fig. 15-10B ). On immunohistochemical staining the tumor cells are positive for GFAP and S-100. The MIB-1 proliferation index is usually low (less than 4%).

Glioblastomas are highly cellular pleomorphic astrocytic tumors. The hallmarks are necroses, which are often accompanied by hypercellular pseudopalisading border zones and vascular proliferations (see Fig. 15-10C ). On immunohistochemistry a large fraction of tumor cells stain positive for GFAP and S-100. The MIB-1 proliferation index is usually high, often more than 15% (see Fig. 15-10D ).

The thoracic cord is the most common site of involvement, followed by the cervical cord.

Imaging

MRI

On MRI, pilocytic astrocytomas may enhance homogeneously or heterogeneously or may show no enhancement at all ( Figs. 15-11 and 15-12 ).

Diffuse astrocytomas also often present as hypointense to isointense masses on T1W images and appear hyperintense on T2W images. They have poorly defined margins, and differentiation of the tumor border from adjacent edema is difficult. Contrast enhancement is usually mild and may be focal or diffuse or may be completely absent ( Fig. 15-13 ). Enhancement alone cannot be used to differentiate between low and high-grade gliomas. The tumor may extend to several vertebral segments, and multifocal or even holocord variants have also been described (especially in association with pilocytic astrocytoma). Associated cysts are commonly observed (more frequently than in ependymomas), particularly with pilocytic type tumors, and they can be reactive or tumorous (see Fig. 15-11C ). Hemorrhage is uncommon, in contrast to ependymomas. As astrocytomas arise from the parenchyma of the cord, they are usually eccentrically located in the cord, as opposed to ependymomas, which are typically centrally located (see Analysis and Fig. 15-97 , later). The accurate cross-sectional localization of the tumor on axial T2W images is important for planning the operative approach and should always be reported. Exophytic components, similar to brain stem gliomas, have also been described with spinal cord astrocytomas (see Fig. 15-9A,B ).

Primary glioblastoma multiforme of the spinal cord is a rare entity, and only few reports are found in the literature. Like intracranial primary glioblastoma multiforme, the intraspinal counterpart also shows a strong peripheral enhancement, surrounding edema, as well as, in 60% of cases, a leptomeningeal spread, which helps to differentiate it from other intramedullary tumors ( Fig. 15-14 ).

Epidemiology

Primary spinal oligodendroglioma is a very rare pathologic entity representing 2% of spinal cord tumors and 1.5% of all oligodendrogliomas. Fewer than 50 cases have been reported in the literature. Among these cases, 60% of patients were older than age 16 years and 40% were younger. A slight male predominance was observed.

Clinical Presentation

Depending on the involved segment, the clinical presentation is one of long-standing back pain and sensorimotor symptoms.

Pathophysiology

Oligodendrogliomas arise from oligodendroglial cells of the neural tissue.

Pathology

Oligodendrogliomas usually appear as soft, well-defined grayish masses. The frequently observed calcification may impart a gritty texture to the tissue.

The tumors appear moderately cellular and are composed of monomorphic cells with round nuclei that are often surrounded by an empty halo (“honeycomb” appearance). A dense network of branching capillaries and microcalcifications are also typical features. If oligodendrogliomas undergo malignant transformation (anaplastic oligodendroglioma, WHO grade III), cell density, mitotic activity, and proliferation are higher and necroses and vascular proliferations are common. A specific immunohistochemical marker for oligodendrogliomas is not available, although a perinuclear staining pattern of microtubule associated protein-2 (MAP2) is typical for these tumors.

The most common site of involvement is the thoracic and cervical spine with much fewer cases in the lumbar area. Cases of holocord involvement are also reported, with all these patients being younger than 16 years of age.

Imaging

MRI

Oligodendrogliomas are isointense to spinal cord on T1W images and hyperintense on T2W images and show inhomogeneous, spotty contrast enhancement. Intratumoral hemorrhages, calcification, and associated syringohydromyelia are common findings.

Epidemiology

Overall, around 90 cases of spinal intramedullary gangliogliomas have been described in the literature. Ganglio-gliomas account for 1% of spinal cord tumors and 0.4% to 6.5% of all primary CNS tumors. The mean age at presentation is 19 years of age with a predominance in childhood. There is no gender predilection.

Clinical Presentation

Gangliogliomas are usually considered slow-growing, nonaggressive, benign tumors and, therefore, the clinical course is mostly slowly progressive. Duration of symptoms ranges from 1 month to 5 years. The most common symptom is paraparesis (50%), followed by segmental pain (46%), but gait disturbance, sensory deficit, and sphincter disturbance have also been reported. Scoliosis is often associated.

In general, the symptoms are very mild considering the extent of the tumor as seen on the MRI examination, which often involves several spinal cord segments at the time of diagnosis. In the very rare cases of malignant variant (anaplastic ganglioglioma, WHO grade III), the clinical symptoms are rapidly progressive.

Pathophysiology

The histologic classification of gangliogliomas is based on the relative differentiation of the neuronal component and the presence of glial elements. When composed of mature neuronal components without a glial component, that is, when tumors contain only mature ganglion cells, they are classified as gangliocytomas (WHO grade I). When additional neoplastic astrocytic elements are present, they are classified as gangliogliomas (WHO grade I/II). Lessdifferentiated types are extremely rare and include the anaplastic ganglioglioma (WHO grade III).

Pathology

Gangliogliomas usually appear as well-circumscribed solid lesions. Cysts and calcifications are seen less frequently than in their intracranial counterparts.

Gangliogliomas are composed of neuronal and glial components. The neuronal component often consists of large, multipolar or multinucleated neurons (“dysplastic” neurons), whereas the glial component may resemble other low-grade glial tumors such as pilocytic astrocytoma, diffuse astrocytoma, or oligodendroglioma ( Fig. 15-15 ).

In immunohistochemistry the neuronal component is usually stained by antibodies for neural proteins such as MAP2, NeuN, neurofilament, or synaptophysin. The glial component usually stains for GFAP.

Gangliogliomas of the spinal cord have a preference for the cervical and thoracic segments. They frequently extend to multiple segments and may involve the entire spinal axis (holocord presentation).

Imaging

MRI

Gangliogliomas do not have any specific imaging feature that would help differentiating them from low-grade glial tumors of the spinal cord. They result in fusiform enlargement of the spinal cord and they are eccentrically located (like astrocytomas), preferentially in the cervical cord and thoracic cord, with only few cases reported in the conus medullaris (like astrocytomas). The only helpful feature in the characterization might be the mixed signal intensity on T1W images, which is speculated to be the reflection of the dual cellular composition from glial and neuronal elements. On T2W images gangliogliomas are mostly hyperintense ( Fig. 15-16 ), and on contrast-enhanced T1W images there is a mostly absent or a mild patchy enhancement pattern. Calcifications occur much less frequently in spinal gangliogliomas than in intracranial gangliogliomas.

Epidemiology

Hemangioblastomas represent the third most frequent intramedullary spinal cord tumor after ependymoma and astrocytoma. They account for up to 1% to 7% of all spinal cord neoplasms and show no gender predilection. The age at presentation is younger than 40 years.

Clinical Presentation

Because of the tumor's preferential location in or near the dorsal columns, sensory deficits are the most common clinical presentation, especially with deficits in proprioception. Back pain and motor dysfunction are also common. The course of symptoms is usually slowly progressive owing to the slow growth of these lesions. The mean duration of symptoms is 38 months. Patients may also present with acute subarachnoidal or intramedullary hemorrhage due to the high vascularity of these tumors, which may lead to spontaneous or chronic microhemorrhages.

Pathophysiology

Hemangioblastoma can occur as a solitary tumor in up to 70% of cases or as multiple lesions as part of the von Hippel-Lindau (VHL) syndrome in up to 30%. VHL is an autosomal dominant disorder characterized by the development of tumors in different organs. Apart from cerebellar and spinal hemangioblastomas, other associated tumors include retinal hemangioblastomas, pheochromocytomas, renal cell carcinomas, renal cysts, pancreatic cystadenomas, and pancreatic neuroendocrine tumors. The incidence of VHL is estimated to be 1:40,000 live births, and nearly 70% of patients with VHL will develop hemangio-blastomas of the CNS as part of the syndrome during their life. The VHL syndrome is classified as type 1 when pheochromocytoma is not part of the clinical features and as type 2 when it is present. Type 2 is further classified into subtype A when renal cell carcinoma is present and subtype B when it is absent. VHL is a tumor suppressor gene located on chromosome 3p25-26 and is responsible for this disease spectrum on inactivation. Genetic testing for mutations in VHL should therefore be considered in patients with hemangioblastomas and other neoplasms of the VHL syndrome.

Pathology

Hemangioblastomas appear as well-circumscribed, highly vascular reddish nodules ( Fig. 15-17 ) and are often found along the wall of large cysts with prominent dilated vessels. These tumors consist of large and often vacuolated stromal cells that lie in a “matrix” of abundant vascular cells forming thin-walled vessels ( Fig. 15-18 ).

On immunohistochemistry, the stromal cells variably express S-100 and neuron-specific enolase while the endothelial cells stain for various endothelial markers (CD31, CD34).

Spinal cord hemangioblastomas present in the thoracic region in up to 50% of cases, followed by the cervical region in up to 40% of cases. This distribution probably reflects the longest length of the thoracic cord with its 12 segments. Up to 75% of these tumors appear intramedullary, and 25% can involve the intradural or extradural space.

Imaging

MRI

The classic MR appearance of hemangioblastoma is a strongly enhancing tumor nodule with tortuous flow voids, representing feeding arteries, in the periphery of a cyst (cyst with a mural nodule) (see Box 15-3 ). Extensive spinal cord enlargement is common owing to venous congestion and edema ( Fig. 15-19 ). Hemangioblastomas appear isointense/hypointense on T1W images and hyperintense on T2W images. The tumor nodule enhances homogeneously and intensively after intravenous administration of a contrast agent. MR angiography (MRA) is an important noninvasive method for the preoperative evaluation of the tumor, particularly when endovascular embolization is performed before surgery. Contrast-enhanced MRA provides detailed information about the tumor's vascular architecture by demonstrating the dilated and tortuous feeding arteries as well as the perimedullary draining veins (see Analysis and Fig. 15-99 , later). The solid nodule of the tumor is mostly small, measuring a few millimeters, but it has the potential to extend over several segments. Hemangioblastomas, particularly when associated with VHL disease, can be multiple (see Box 15-3 ); and, therefore, it is important that the entire spinal axis is included in the diagnostic MRI protocol. Associated cysts are a common feature of cerebellar hemangioblastomas, but in the spinal cord entirely solid lesions are more frequent.

BOX 15-3

Hemangioblastoma

PATIENT HISTORY

A 15-year-old girl presented with amaurosis fugax. Diagnostic imaging led to the finding of a retinal hemangioma and two additional tumors located in the foramen magnum and the cervical spinal cord ( Fig. 15-106A, B ). Because of initial MRI findings the diagnosis of multifocal hemangioma in association with von Hippel-Lindau syndrome was suspected and was genetically confirmed. The patient was treated first in the ophthalmology department owing to the retinal hemorrhage that led to the amaurosis fugax. Because of lack of additional neurologic symptoms no further treatment of the additional hemangioblastomas was initially indicated.

The patient presented for follow-up after 15 months. Clinically, only a minimal hypesthesia of the dermatome C8 on the left side was documented with no other neurologic deficit.

TECHNIQUE

Contrast-enhanced sagittal T1W and T2W MR images were obtained.

FINDINGS

In control MRI of the spinal cord a progression of the hemangiomas in the foramen magnum and cervical cord is observed (see Fig. 15-106C, D ).

COMMENT

Because of the growth of the hemangioblastomas and the new symptom the patient was admitted for neurosurgical therapy and underwent a suboccipital craniotomy, a laminectomy at C1, and a hemilaminectomy at C2-3. The foramen magnum lesions were removed, and the cyst at C2-C4 was drained (see Fig. 15-106E, F ). Postoperatively only a minimal rest hypesthesia of the dermatome C8 on the left was observed. Three months later the patient complained of a new recurring mild paresthesia of the right hand. Control MRI showed a new cyst formation at the level of C2-C4 (see Fig. 15-106G, H ). Further therapy is not yet planned.

MRI is an important modality for screening of patients with a positive family history of VHL syndrome.

Epidemiology

Intramedullary metastases are very rare, with a reported incidence of up to 2% in patients with different types of cancer. Metastatic disease of the spinal cord is more often extramedullary in location, arising via cerebrospinal fluid (CSF) seeding from a primary intracranial CNS neoplasm, or more uncommonly is intramedullary from hematogenous spread of other systemic carcinomas. The most common primary sources of intramedullary metastatic disease are lung cancer (61%), breast cancer (11%), melanoma (5%), renal cell carcinoma (4%), colorectal carcinoma (3%), lymphoma (3%), and tumors of unknown origin (5%).

Clinical Presentation

The most common complaints are pain, bowel and bladder dysfunction, and paresthesia. The clinical course is usually rapidly progressive, and in most cases the duration of symptoms is less than 1 month before diagnosis. Survival after diagnosis ranges from weeks to months in most series.

Pathophysiology

Metastatic disease may develop due to vascular (hematogenous) or lymphatic (lymphogenic) spreading or directly via CSF (drop metastasis) with finally seeding of the neoplastic cells into the spinal cord, generating intramedullary metastasis.

Pathology

Metastases are often circumscribed, rounded, gray-white or tan masses. They often show central necrosis or hemorrhages or contain mucous material in the case of adenocarcinoma.

Tumor metastases often resemble their tissue of origin; therefore, they would all be different histologically.

Intramedullary metastasis may occur anywhere along the spinal cord.

Imaging

MRI

In general, intramedullary metastasis results in mild expansion of the spinal cord with high signal intensity on T2W images, representing the tumor but also edema and syrinx ( Fig. 15-20 ). The associated edema is disproportionately extensive compared with the size of the tumor. Accompanying tumorous cysts are rare, as opposed to primary intramedullary tumors. Contrast enhancement is intensive with or without central necrotic areas ( Fig. 15-21 ). There are no typical features for characterizing the different metastatic neoplasms; the only clue is the histologically verified primary tumor.

Epidemiology

Nerve sheath tumors (schwannoma + neurofibroma) represent the most common primary neoplasia (30%) in the spine as well as in the intradural extramedullary space (30%). The incidence of spinal nerve sheath tumors is reported to be slightly higher or equal to that of spinal meningiomas.

The peak incidence of nerve sheath tumors is in the fourth to fifth decades, and they affect men and women equally. Schwannomas are much less common in children, representing less than 10% of intraspinal tumors. The presence of multiple schwannomas in a young child should prompt further investigations for NF2, particularly owing to the higher risk of malignant transformation and the predisposition of NF2 to other neoplasms in addition to nerve sheath tumors such as intramedullary ependymomas. Neurofibromas are much less common than schwannomas.

Clinical Presentation

Symptoms related to the presence of a nerve sheath tumor may precede the diagnosis by more than 2 years because there is usually little functional impairment. The most frequent symptoms, common to all nerve sheath tumors, are pain and radiculopathy.

Malignant transformation of a nerve sheath tumor should be suspected if there is rapid growth or exacerbation of pain.

Pathophysiology

Schwannomas (WHO grade I) are usually solitary lesions and are most commonly sporadic. They arise from a single focus, most commonly in the dorsal sensory roots, and usually develop asymmetrically forming a well-encapsulated, lobulated, firm mass that compresses the adjacent tissue without invading the involved nerve.

Multiple schwannomas occur with NF2, a phacomatosis caused by inactivation or deletion of NF2 on chromosome 22 that occurs sporadically in 50% of cases and as an autosomal dominant disorder in another 50% of cases. A subgroup of patients with multiple schwannomas in the absence of bilateral vestibular schwannomas (which is pathognomonic of NF2) has also been described. This condition is known as schwannomatosis in the literature, although it is still controversial as to whether it is a distinct clinicopathologic entity or a phenotypic manifestation of NF2.

Neurofibromas (WHO grade I) are commonly associated with neurofibromatosis type 1 (NF1), particularly when multiple, but can also occur sporadically. Neurofibromas associated with NF1 are related to a defect or loss of NF1 on chromosome 17.

Melanotic schwannoma is differentiated from a typical schwannoma by heavy pigmentation. Psammoma bodies can be visualized in more than 50% of melanotic schwannomas. Half of patients with such “psammomatous melanotic schwannomas” have Carney complex, a dominantly transmitted autosomal disorder consisting of myxomas (cardiac, cutaneous, and mammary), mucocutaneous spotty pigmentation, and pigmented adrenal tumors with endocrine overactivity.

Malignant types of nerve sheath tumors (WHO grade III/IV) are rare (2% to 6% of cases) and arise either de novo from the nerve sheath or as a malignant degeneration of preexisting nerve sheath tumors (more often neurofibromas than schwannomas). Plexiform neurofibromas associated with NF1 show malignant degeneration in 3% to 5% of cases, and 50% to 60% of malignant peripheral nerve sheath tumors (MPNSTs) are associated with NF1. Malignant nerve sheath tumors have a variety of names such as malignant neuroma, malignant schwannoma, nerve sheath fibrosarcoma, and neurofibrosarcoma, reflecting their histologic heterogeneity. Malignant nerve sheath tumors only rarely arise in the CNS but may arise more peripherally and then infiltrate back into the spinal column.

Pathology

Schwannomas arise from the Schwann cells of the nerve axon's myelin sheath. They are usually encapsulated globoid masses ( Fig. 15-22 ) with a cut surface of light tan tissue with yellow patches (see Box 15-4 ).

Neurofibromas are usually firm, fusiform, and wellcircumscribed lesions that are grayish tan on cut surface.

Schwannomas are composed of neoplastic Schwann cells that grow in two distinct growth patterns, either as compact areas with elongated cells and occasional nuclear palisading (Antoni A pattern) or as less cellular regions with indistinct processes (Antoni B pattern). They are usually composed of a variable mix of both patterns but can also be composed exclusively of one of these patterns ( Fig. 15-23A ). Most tumor cells show a basement membrane along their surface as demonstrated by a reticulin stain. Vessels in schwannomas are often highly hyalinized (see Fig. 15-23A ).

Schwannomas may also demonstrate extensive cystic change (see Fig. 15-23B ). A rare subtype of schwannoma is the melanocytic schwannoma (see Fig. 15-23C, D ). These tumors resemble schwannomas but additionally contain melanosomes, leading to a brownish coloration of a fraction of tumor cells. They are strongly reactive to various melanoma markers.

Neurofibromas are to a large part composed of small Schwann cells along fewer numbers of intermixed fibroblasts in a matrix of collagen fibers and myxoid material (see Fig. 15-23E ). On immunohistochemistry, neurofibromas are invariably stained by antibodies against S-100. Staining for neurofilament often demarcates remnants of infiltrated nerve disrupted by infiltrating tumor cells (see Fig. 15-23F ).

Rarely schwannomas and more often neurofibromas may show transformation to an epithelial malignant peripheral nerve sheath tumor (EMPNST) or to an angiosarcoma and then display a high grade of nuclear pleomorphism and cellular density. Mitotic figures are frequently seen (see Fig. 15-23G ) and the proliferation index is high (see Fig. 15-23H ). On immunohistochemistry, the tumor cells strongly express S-100, and staining for basal lamina (collagen IV) often demonstrates a surface staining of most cells. The staining for S-100 is often weak after transformation to EMPNSTs.

Seventy to 80 percent arise from the nerve roots (most commonly the dorsal sensory nerve roots) before leaving the dural sac and are entirely intradural ( Fig. 15-24A ). A further 10% to 20% arise as the nerve root leaves the dural sac and therefore display both intradural and extradural components (dumbbell tumors) (see Fig. 15-24B ). Entirely extradural schwannomas are less common (<10%) (see Fig. 15-24C, D ). Intramedullary schwannomas are very rare (<1%) and are believed to arise from the perivascular nerve sheaths that accompany penetrating spinal cord vessels.

Most commonly affected are the cervical regions, with less frequent involvement of the thoracic and lumbar spine.

Neurofibromas are histologically more complex lesions of proliferated Schwann cells and fibroblasts mixed with acid polysaccharides that enlarge within the nerve itself, spreading apart the axons to produce a fusiform lesion. Brachial or lumbar plexus neurofibromas may extend centrally into the intradural space along multiple nerve roots and may even result in subpial extension.

Imaging

CT

CT is not the primary modality for imaging of spinal tumors and is only indicated in cases when there are contraindications to MRI, in which case a CT myelography should be performed for better anatomic delineation of the lesion in the intradural extramedullary space and its relationship to nerve roots. CT provides additional information related to the consequences of the tumor on the adjacent bony structures. Foraminal enlargement with erosion of the pedicles and thinned laminae and posterior vertebral scalloping are adequately demonstrated on bone window CT images and may provide useful information for the preoperative planning. The tumor itself appears as an isodense or slightly hypodense soft tissue mass displacing the cord. After contrast agent administration a variable degree of contrast enhancement is observed, ranging from moderate to intense, depending on the consistency of the tumor (see Fig. 15-24 ). Calcifications and gross hemorrhages are rare. Melanotic schwannomas present as hyperdensity on native CT (see Fig. 15-27 ).

MRI

MRI provides an excellent delineation of nerve sheath tumors and their location relative to the dural sac, and the cord is depicted accurately in most cases (see Fig. 15-24 ). Schwannomas and neurofibromas are mostly indistinguishable on imaging, although there are some hints that help in the characterization (see Analysis and Fig. 15-101 , later). They appear as solid, circumscribed masses, isointense to slightly hypointense on T1W images and hyperintense on T2W images compared with cord. Schwannomas often demonstrate a heterogeneous signal on T2W images, corresponding to the mixed Antoni A and B pattern (i.e., compact areas and less cellular regions, respectively). A schwannoma may also present predominantly with one or the other pattern (see Analysis and Fig. 15-103 , later). On postcontrast T1W images, they show an intense contrast enhancement ( Fig. 15-25 ).

Intraforaminal and extraforaminal lesions can be better delineated on short tau inversion recovery (STIR) images owing to the suppression of the epidural intraforaminal and paraspinal intermuscular fat (see Fig. 15-24D ).

Most schwannomas are small (a few millimeters), but they can be large as well. By definition a lesion is called a “giant schwannoma” if it (1) stretches over two vertebral levels or (2) extends extraspinally more than 2.5 cm or (3) extends into the myofascial plains (see Box 15-4 ; see Fig. 15-24D ). These tumors require biopsy because the differential diagnosis includes malignant nerve sheath tumor. Spinal schwannomas may rarely result in hemorrhages in all compartments of the spine (intramedullary, subarachnoidal, subdural, intratumoral bleeding).

Schwannomas may show a cystic morphology; however, nodular thickening of the wall on contrast-enhanced images helps to differentiate them from other cystic lesions of the spine ( Fig. 15-26 ).

A subtype of schwannomas is the melanotic/melanocytic schwannoma, which is characterized by cytoplasmic deposition of melanin pigment. This is also reflected by the hypointensity on T2W images and hyperintensity on T1W images (and hyperdensity on native CT) due to the paramagnetic effect of the melanin ( Fig. 15-27 ). It is dif-ficult to differentiate this tumor from metastatic malignant melanoma by MRI.

Intraosseous schwannoma has been reported in the literature with an extensive bony destruction.

Malignant transformation may be suspected in the presence of a rapidly increasing tumor mass on follow-up examination, ill-defined tumor margins with unclear separation from the cord parenchyma, prominent tumor heterogeneity with central necrosis, and prominent edematous changes in the compressed cord tissue. Malignant transformation is most commonly associated with plexiform neurofibromas and NF1.

Epidemiology

Meningioma is a common tumor among primary spinal neoplasms, accounting for 25% to 46% of cases, and is the second most common tumor (25%) after schwannomas in the subarachnoid space (extramedullary intradural location) in the spine. Ten to 13 percent of all meningiomas arise in the spine.

Females are most often affected (82%), with tumors occurring most frequently in middle-aged and elderly women. Most of the patients are 40 to 80 years old; however, some cases in children have also been reported.

Ossified meningiomas are extremely rare and estimated to be 0.7% to 5.5% of all spinal meningiomas.

Clinical Presentation

The predominant symptom is localized or radicular pain (83%), followed by sensory loss (50%). Paresis is present in 83% of the patients at the time of diagnosis. Bladder or bowel disturbances occur in 36% of cases. Meningiomas are benign, slow-growing tumors; therefore, the duration of symptoms before diagnosis may range from 4 months to 2 years. The very rare anaplastic meningiomas follow an aggressive clinical course with 70% recurrence rate and 30% metastasis rate.

Pathophysiology

Spinal meningiomas arise either from cap cells of the arachnoid membrane (meningothelial cells), hence the name meningotheliomatous meningioma, or from fibroblasts or trabecular cells of the deep arachnoid layers, hence the name fibrous and transitional meningioma.

It has been suggested that the histologic progression and growth of spinal meningiomas depend on genetic changes as well as on sex steroid hormones. Genetic studies showed a loss of one homologue of the long arm of chromosome 22, which is supposed to be the site of a putative tumor suppressor gene.

Almost 99% of all spinal meningiomas are WHO grade I. WHO grade II spinal meningioma has not yet been reported and grade III meningioma occurs only in 1.3% of all spinal meningiomas. WHO grade II and III meningiomas occur far less frequently in the spine than in intracranial locations, which can be explained by different meningeal development in these regions. A dural tail sign is present in 57% to 67% of all meningiomas regardless of intraspinal or intracranial location. It can represent either tumor invasion or hypervascularity with vessel congestion or both. The dural tail sign (either intracranial or intraspinal) is not specific for meningiomas, and it has been identified with other intradural tumors (e.g., metastasis, lymphoma, sarcoidosis). However, spinal schwannoma with dural tail has not yet been reported; therefore, it seems to be a useful feature in distinguishing meningiomas from schwannomas in the spine.

Pathology

The adjacent bony structures are much less affected (sclerosis, infiltration) in the spine than intracranially, probably owing to the wider and fat-filled epidural space.

Meningiomas arise from various cells of the arachnoidal layer with potential infiltration of the adjacent dura.

The adjacent nerves are displaced through the tumor.

Meningiomas appear as firm or rubbery ( Fig. 15-28 ), well-demarcated globular masses often with a broad attachment to the dura. The cobblestoned external contour is reflected by the characteristic lobulated cut surface of these lesions.

Meningiomas show a wide range of histologic appearance. The most common benign subtypes are meningotheliomatous (syncytial) and fibrous and transitional meningiomas. Most meningioma subtypes share some histologic features, including indiscernible cellular borders (“pseudosyncytial appearance”), frequent cytoplasmic-nuclear inclusions, whorl formation, a collagen-rich matrix with foci of spindle cells, and the occurrence of calcification in the form of psammoma bodies. The subtypes of meningiomas show a characteristic combination of these features. For example, psammomatous meningioma is characterized by excessive numbers of psammomatous bodies ( Fig. 15-29A ) while meningotheliomatous meningioma shows large pseudosyncytial lobules, less well-formed whorls, and only a few psammomatous bodies (see Fig. 15-29B ). On immunohistochemistry the vast majority of meningiomas stain for EMA.

Because the thoracic spine is the longest segment of the spine, most meningiomas present there (55%-80%); however, the cervical (15%-18%) and the lumbar (2%) spine can be involved as well. The location of meningiomas is completely intradural-extramedullary in 83%-87%, intramedullary in 3%, and extradural in 14% of the cases. Meningiomas are most often located lateral (50%-68%), posterior (18%-31%), and anterior (15%-19%) to the spinal cord.

Imaging

CT

CT reveals the hyperdense calcifications of the lesion as well as the adjacent dura mater ( Fig. 15-30D ). Osseous sclerosis or infiltration in the spine is rare, as opposed to the intracranial meningiomas.

MRI

Meningiomas are well-circumscribed lesions with a lobular architecture. Characteristic signal intensity of spinal meningiomas is relative homogeneous isointensity or hyperintensity both on T1W and T2W images compared with the spinal cord. These tumors show relatively homogeneous and moderate contrast media enhancement (in contrast to the strong and irregular contrast enhancement of schwannomas (see Analysis and Fig. 15-103 , later). Meningiomas are somewhat lobular with a slightly irregular surface, and they have a broad dural attachment. Although thickening and strong contrast enhancement of the dura adjacent to the tumor (“dural tail sign”) is not specific for meningiomas, it occurs in most (57%-67%) of the cases ( Fig. 15-31 ).

Epidemiology

Nondysraphic intradural lipoma is a rare lesion, accounting for 4% of all spinal lipomas. It represents less than 1% of all spinal tumors.

Filum terminale lipoma accounts for 12% of spinal lipomas. It is a relatively common lesion, with an incidence of 4% to 6% in the population.

Spinal lipoma is commonly associated with spinal dysraphism; 84% of all spinal lipomas belong to the lipo/myelo/meningocele group.

Angiolipoma, myolipoma, and liposarcoma represent very rare histopathologic entities.

Clinical Presentation

Nondysraphic lipomas become symptomatic in early adulthood, usually in the second decade of life. Compression of the spinal cord produces a slow, progressive deterioration of neurologic function, including spinal pain, dysesthesias, paraparesis and tetraparesis, ataxia, and incontinence, usually followed by rapid progression of the symptoms. Although lipomas are not neoplasms, they have the potential to grow with increasing body fat or in association with metabolic changes, such as in pregnancy.

Pathophysiology

Nondysraphic lipomas are congenital, benign lesions of the adipose tissue. They are considered to be hamartomas by development from pluripotent embryonic mesenchymal cells (e.g., meninx primitiva) that may occur during neural tube closure. As a consequence, there is no clear cleavage plane between lipoma and spinal cord, which can make total removal impossible, especially when lipomas incorporate adjacent nerve roots.

Pathology

Lipomas are bright yellow lesions and often adhere to the spinal cord. They may show a delicate encapsulation and septation on cut surface.

Because lipids are lost during histologic preparation in alcohol and xylene, only the empty cells remain for histology. The lesion is practically indistinguishable from mature adipose tissue and presents as a typical chicken-wire appearance ( Fig. 15-32A ). In some cases the abundance of blood vessels (especially capillary blood vessels) has led to the designation of angiolipoma; in many cases, how-ever, as in this example, the differentiation of angiolipomas from fat-rich hemangiomas is not possible (see Fig. 15-32B ). In some lumbar lipomas with developmental origin, skeletal muscle or smooth muscle may be an additional feature (see Fig. 15-32C ). Because the histologic appearance of lipomas is so typical, generally no immunohistochemistry is required for diagnosis.

Among nondysraphic lipomas, the thoracic and cervicothoracic locations are the most common, followed by the cervical spine. Most of the lumbosacral lipomas are associated with a dysraphic state. They are almost always located in a dorsal, juxtamedullary position with anterolateral compression of the spinal cord and encasement of the nerve roots ( Fig. 15-33 ). Most often, they extend over several spinal levels and may reach a significant size before diagnosis.

Filum fibrolipomas are located in the filum terminale. Most angiolipomas arise in the thoracic epidural spine.

Imaging

MRI

MRI demonstrates specific patterns that help differentiate lipoma from other primary spinal tumors. Both on T1W and T2W images these tumors show a hyperintense signal with no particular contrast enhancement (see Fig. 15-33 ). They are well-circumscribed, lobulated masses. An imaging technique with suppression of the fat (hypointense to CSF) confirms the diagnosis.

Filum fibrolipomas demonstrate a hyperintense mass in the region of the filum terminale and can be associated with a low-lying conus and tethered cord ( Fig. 15-34 ).

Myolipoma can be indistinguishable from teratoma or dermoid cyst ( Fig. 15-35 ).

Epidemiology

There is no age or gender predominance. The average age at presentation is 45 to 50 years.

Clinical Presentation

Because paraganglioma is most frequently located in the region of the conus medullaris and cauda equina, common symptoms are back or leg pain, sensory or motor disturbances, and bowel/bladder incontinence. The duration of symptoms ranges from days to years. Most of the spinal paragangliomas are not functional, that is, they do not produce catecholamines.