Primary spinal cord tumors

Neuro-Oncology

Updated 01.11.2024
Released 01.11.2024
Expires For CME 01.11.2027

Primary spinal cord tumors

Authors: Kathryn Eszes MD, Nimish Mohile MD MS FAAN

See Contributor Disclosures

Editor: Rimas V Lukas MD

Primary spinal cord tumors

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Introduction

Overview

Primary tumors of the spinal cord and its surrounding structures present a unique challenge to the clinical neurologist. Often presenting with nonspecific symptoms, such as back pain, weakness, and sensory disturbance, these tumors have unique cell line derivations, imaging appearances, behaviors, and prognoses. Spinal cord tumors are categorized by their locations, with primary spinal tumors occupying the intradural extramedullary and intramedullary compartments. Due to their sensitive locations, even tissue diagnosis presents a barrier to care. To date, the general approach to treatment of these tumors is surgical, often with application of intraoperative neuromonitoring. In some cases, new chemotherapeutic agents hold the promise of nonsurgical management. This article provides a broad overview of several of the most common intradural spinal cord tumors.

Key points

	• Spinal cord tumors are classified by location within the spinal canal: extradural, intradural extramedullary, and intramedullary.
	• Hereditary cancer predisposition syndromes, including neurofibromatosis type 1, neurofibromatosis type 2-related schwannomatosis, and Von Hippel-Lindau disease each predispose to certain primary spinal cord tumors.
	• For most spinal cord tumors, the gold standard imaging is contrast-enhanced MRI.
	• For many spinal cord tumors, the preferred treatment when possible is gross total resection.
	• The use of intraoperative neuromonitoring, including somatosensory evoked potentials and motor evoked potentials is crucial during resection of these masses.

Clinical manifestations

Intradural extramedullary spinal cord tumors

Spinal meningioma.

	• Spinal meningiomas present with nonspecific symptoms, most commonly vertebral or radicular pain, although motor, sensory, and sphincter dysfunction may also be seen.
	• Most spinal meningiomas are slow-growing and benign WHO grade 1 tumors.
	• Spinal meningiomas affect women about four times more commonly than men.
	• Neurofibromatosis type 2-related schwannomatosis is a risk factor for the development of spinal meningiomas.

Spinal meningiomas are the most common type of intradural extramedullary spinal cord tumor. They are thought to comprise 25% to 46% of all spinal cord tumors and 3% to 10% of all meningiomas (28; 05). Like their intracranial counterparts, they are more common in women than in men at a ratio of about 4:1 (41; 40; 05). They most commonly present in the fifth decade of life or later. Earlier age of presentation or presence of multiple meningiomas should raise concern for an underlying diagnosis of NF2-related schwannomatosis or more aggressive tumor types (41).

When presenting with symptoms, the most common symptom is back pain or radicular pain (34). The next most common symptoms are sensory and motor symptoms followed by sphincter dysfunction. They tend to occur in the thoracic and cervical spinal regions more than the lumbosacral region (05; 34).

Schwannoma.

	• Schwannomas are the most common type of nerve sheath tumor.
	• Schwannomas rarely occur in children.
	• NF2-related schwannomatosis (NF2-SWN) is a significant risk factor for the development of spinal schwannomas.

Schwannomas are the most common type of nerve sheath tumor. They arise from Schwann cell progenitors. They affect males and females in equal proportions and can be both intradural and extradural. They most commonly occur in early and middle adulthood and are rarely seen in children (41; 01).

Schwannomas are seen with increased frequency in persons with NF2-related schwannomatosis as well as with other rarer syndromes involving mutations of LZTR1 and SMARCB1. They typically present with pain, weakness, or sensory symptoms (20; 02). When weakness is present, it is often due to compressive myelopathy from the mass effect of these lesions (20).

Neurofibroma.

	• Neurofibromas are less common than schwannomas of the spine.
	• The incidence of spinal neurofibromas is increased in persons with neurofibromatosis type 1 (NF1).

Neurofibromas are benign infiltrative tumors arising from the connective tissue of the peripheral nerve sheath, typically the endoneurium. They are seen sporadically and at increased incidence in people with neurofibromatosis type 1. They may be seen at all spinal nerve levels in a subtype of neurofibromatosis type 1 called spinal neurofibromatosis. They are less common than spinal schwannomas, occurring in up to 0.3 per 100,000 persons, and in up to 35% of persons with neurofibromatosis type 1 (05).

The most common symptom at onset is pain, followed by myelopathic symptoms and sphincter dysfunction (20). They are commonly asymptomatic.

Malignant peripheral nerve sheath tumor.

	• Malignant peripheral nerve sheath tumors are rare soft tissue sarcomas of the nerve sheath.
	• The risk for malignant peripheral nerve sheath tumors is increased in persons with neurofibromatosis type 1.

Malignant peripheral nerve sheath tumors are exceedingly rare, aggressive soft tissue sarcomas of the nerve sheath, arising from neural crest or Schwann cells and occurring with an estimated incidence of 1 in 100,000 persons overall and with a lifetime risk of 8% to 12% in persons with neurofibromatosis type 1 (11). The primary risk factor for their development is neurofibromatosis type 1. Typically they arise within the context of plexiform neurofibromas. They may infiltrate through the neural foramina and compress the spine.

Patients may present with a variety of symptoms, with pain and weakness being most commonly reported (08).

Paraganglioma.

	• Paragangliomas are rare WHO grade 1 tumors that can occur throughout the body, rarely in the spine.
	• Paragangliomas may or may not secrete catecholamines, similar to the related pheochromocytoma.
	• Paragangliomas are often associated with familial cancer predisposition syndromes, including Von Hippel-Lindau disease, multiple endocrine neoplasia type 2, neurofibromatosis type 1, and Carney syndrome.

Paragangliomas represent a small minority of intradural extramedullary spinal cord tumors. These are very rare tumors of the spine and can occur throughout the lifespan. These typically benign WHO grade 1 tumors are frequently associated with familial cancer predisposition syndromes, including Von Hippel-Lindau disease, multiple endocrine neoplasia type 2, neurofibromatosis type 1, and Carney syndrome (52).

These are tumors of neural crest cells and arise from sympathetic or parasympathetic chains. They more commonly occur in the abdominal or thoracic compartments and may or may not produce sympathetic symptoms similar to those produced in pheochromocytoma.

Solitary fibrous tumor.

• Solitary fibrous tumors, also called hemangiopericytomas, are highly vascular endothelial tumors that can be WHO grade 1, 2, or 3.

Solitary fibrous tumors, also called hemangiopericytomas, are rare CNS tumors, comprising approximately 1% to 2% of CNS tumors (43). An even smaller proportion of these are spinal tumors. They are tumors arising from endothelial cells and can occur anywhere in the body where capillaries are present. They are classified as WHO grade 1, 2, or 3 lesions based on histology (26). They may be located intradural extramedullary or intramedullary.

Solitary fibrous tumors typically occur in adulthood and produce nonspecific symptoms, including back pain, weakness, hypoesthesia, and sphincter dysfunction, depending on location (43).

Epidermoid or dermoid tumors.

	• Epidermoid and dermoid tumors or cysts are rare benign tumors that can occur anywhere in the body, including the spine.
	• The congenital form of this tumor is often associated with defects in neural tube closure or syrinx.
	• Aseptic meningitis can occur due to cyst rupture, and infectious meningitis can occur when there is an associated dermal sinus tract.

Dermoid or epidermoid tumors, also termed cysts, are rare benign tumors that comprise roughly 0.8% to 1.1% of all primary spinal tumors and can occur anywhere in the body, including in the spine (03; 28). They arise from ectodermal cells that are inappropriately located intraspinally. The distinction is primarily made based on histopathology; however, clinically, their courses and their appearance on imaging are also similar (42). They may occur congenitally due to abnormal cell disjunction during development or through abnormalities in cell-signaling factors. In these cases, there may be overlying skin changes, including hypertrichosis, dimple, or dermal sinus. There may also be associated spinal cord dysraphism, including spina bifida, diastematomyelia, or syringomyelia (03). They may also rarely occur iatrogenically from the introduction of dermal or epidermal cells into the CSF space during surgery or lumbar puncture (42).

The typical presenting symptoms include pain, flaccid weakness, or sensory symptoms. In cases where the tumor is connected to the skin by a sinus tract, the presenting symptom may be meningitis (42).

Intramedullary spinal cord tumors

Ependymal tumors.

	• Ependymal tumors of the spine include spinal subependymoma, myxopapillary ependymoma, and the MYCN-amplified and non-amplified spinal ependymomas.
	• Together they comprise the most common spinal cord tumor in adults and the second most common tumor in pediatrics.
	• The WHO 2021 classification update included changes to these tumor definitions and grades.

Ependymal tumors are the most common intramedullary spinal cord tumor among adults and the second most common tumor among children (41; 40; 23). They are more common among males than females and have a tendency to occur in middle age. These are tumors of ependymal cells. They are generally benign tumors and most commonly are classified as WHO grade 1 or 2 and occasionally grade 3 (26). Most ependymomas occur sporadically, but there is an increased risk of intramedullary spinal ependymomas in patients with neurofibromatosis type 2 (23; 33).

There are several subtypes of ependymal tumors that are differentiated based on histology, molecular markers, and location. The WHO 2021 classification of tumors updated the naming and grading of these tumors (26). The ependymal tumors more commonly located in the spinal cord include the WHO grade 1 subependymomas, the WHO grade 2 myxopapillary ependymomas (formerly WHO grade 1), and the spinal ependymomas, which can be grade 2 or grade 3 depending on histopathologic characteristics (26). In general, ependymomas are associated with 5-year survival rates of 55% to 80%, which varies by type of ependymoma (33). Additional factors that are associated with improved survival include older age, location of tumor in the spine, and gross total resection (33).

Subependymomas are very indolent and may be discovered incidentally. They occur more commonly in adults than in children. They more commonly occur in the fourth or lateral ventricle than in the spine. When in the spine they have a predilection for the cervical or cervicothoracic junction (23).

Myxopapillary ependymomas constitute approximately 25% of adult spinal cord ependymomas. Greater than 90% of these are located near the conus medullaris or cauda equina. Unlike the other ependymal tumors, they are often intradural extramedullary. They are slow-growing tumors with a favorable prognosis in general (23). They tend to present with back pain (35; 07).

Spinal ependymomas are located intramedullary and can occur at any location in the spinal cord, although they are most often found in the cervical and thoracic levels. They are often cystic and associated with a syrinx (36). Spinal ependymomas may be grade 2 or grade 3. In the 2021 WHO classification update, this was subdivided into MYCN-amplified and non-amplified spinal ependymoma (26). MYCN is a gene located on chromosome 2, which is a proto-oncogene (23). The amplified type behaves more aggressively and is at higher risk for dissemination and relapse (23).

Spinal cord astrocytoma.

	• Spinal cord astrocytomas are the most common intramedullary spinal cord tumor in pediatrics and the second most common in adults.
	• Spinal cord astrocytomas occur more frequently in persons with neurofibromatosis type 1.
	• Children tend to have lower-grade lesions with better prognosis than those found in adults.

Spinal cord astrocytomas are the most common intramedullary spinal cord tumor in children and the second most common among adults (40). They account for only 3% of astrocytomas overall. They are commonly associated with syrinx and occur at a higher rate in patients affected by neurofibromatosis type 1. When these tumors occur in children, they are more commonly lower-grade lesions, whereas they tend to be higher-grade tumors in adults (36).

Spinal astrocytomas can be classified as WHO grade 1, 2, 3, or 4 tumors (26). The vast majority in adults are WHO grade 1 or 2 (41). The incidence of primary spinal astrocytomas is estimated at 0.22 per 100,000 persons annually (27). They affect men and women with similar frequency. High-grade gliomas represent about 25% of adult intramedullary gliomas (41; 29). Some tumors that would have previously been classified as spinal cord astrocytomas or glioblastomas are now classified as diffuse midline gliomas H3K27-altered. Although H3K27-alterations are more common in pediatric tumors, spinal involvement of these tumors is observed more frequently in adults.

Primary intraspinal lymphoma.

	• Lymphoma is an exceptionally rare primary spinal cord tumor, estimated to comprise less than 1% of all primary lymphoma of the central nervous system.
	• Patients are often misdiagnosed initially due to the rarity and broad differential diagnosis.

Diffuse large B cell lymphoma of the central nervous system or primary CNS lymphoma is a rare category of primary CNS malignancy. Within this group, primary lymphoma of the spinal cord is even rarer, comprising an estimated less than 1% of cases (17). Patients affected by these tumors tend to be aged 50 years or older, although younger age is reported. They may occur following a subacute or insidious course (17). They most commonly affect the thoracic and cervical spinal cord.

Due to the rarity of this disease, there is commonly a delay in diagnosis. They typically present as a myelopathy syndrome. Nearly all cases are first diagnosed as another, more common entity (17). Differential diagnosis includes transverse myelitis or longitudinally extensive transverse myelitis, demyelinating disease (multiple sclerosis, neuromyelitis optica, acute disseminated encephalomyelitis, CIDP), other neoplasm (ependymoma, astrocytoma), infection, sarcoidosis. Patients may be immunocompetent or immunocompromised (16). Diagnosis is frequently preceded by nonspecific "B symptoms," including fever, chills, malaise, unintentional weight loss, myalgias.

Ganglioglioma.

	• Ganglioglioma are rare spinal tumors of both astrocyte and neural origin.
	• Ganglioglioma are more common in the pediatric patient population.

Gangliogliomas are rare CNS neoplasms, and comprise approximately 1% of spinal cord tumors (25). They consist of astrocyte and neural components. They are more common in children but can occur in early adulthood as well (01; 40). They typically present with back pain and weakness. In children they can present with scoliosis.

These tumors often originate in the cervical spinal cord and frequently span many segments, often extending throughout the spinal cord. Despite this, they tend to be WHO grade 1 or 2 tumors; however, there is small risk of malignant transformation of the astrocytic component (40).

Hemangioblastoma.

	• Hemangioblastomas are uncommon low-grade (WHO grade 1) tumors and are the third most common intramedullary spinal cord tumor.
	• Persons with Von Hippel-Lindau disease are at significantly increased risk for spinal cord hemangioblastoma.

Hemangioblastomas are mesenchymal-derived highly vascular tumors that comprise the third largest group of intramedullary spinal cord tumors (36; 40). Hemangioblastomas occur sporadically in roughly 50% of cases and in 50% of cases are associated with the inherited cancer predisposition syndrome of Von Hippel-Lindau disease. They occur most commonly in the third to fifth decade of life. In the central nervous system, the majority of hemangioblastomas are located in the cerebellum. When located in the spinal cord they tend to be located in the cervical or thoracic spinal cord. They are often located dorsally in the spinal cord (19). They may also involve the roots of the cauda equina.

Although these are WHO grade 1 tumors, they can cause significant neurologic disability and death. When presenting with symptoms, the most common symptom is pain, although degrees of sensory impairment and motor impairment are frequently also present (19). Syrinx is present in about 50% of cases (36; 19).

Biological basis

Genetics and cell biology

	• Spinal meningiomas demonstrate chromosome 22q deletions and expression of certain hormone receptors.
	• Schwannomas also harbor abnormalities in chromosome 22q.
	• Neurofibromas demonstrate loss of NF1 gene on chromosome 17, in addition to other chromosomal abnormalities.
	• Subependymomas often harbor chromosome 6q deletions.
	• Gangliogliomas may harbor BRAF mutations.

Intracranial and spinal meningiomas are genetically similar and demonstrate deletion in chromosome 22q, both in patients with neurofibromatosis type 2 and in patients without (34; 39). The 22q region contains the NF2 gene, which codes for the protein Merlin and has many functions both in myelin formation and in tumor suppressor or oncogene pathways. Most meningiomas express progesterone and somatostatin receptors, and some authors have shown that spinal meningiomas tend to express androgen and estrogen receptors more than intracranial ones. These receptors are thought to be the basis for the observation that meningiomas in general are more common in women and are known to grow during pregnancy (39). DOTATATE-PET imaging can serve as a means of evaluating the presence of somatostatin receptors and potentially differentiating meningioma from other tumors.

Many sporadic and NF2-related schwannomas demonstrate abnormalities in chromosome 22 and inactivation of the NF2 gene (01). This underlies the association between neurofibromatosis type 2 and schwannomas. Rarer mutations such as LZTR1 and SMARCB1 can also be found in a subset of schwannomas. Germline testing may play a role in the evaluation and management of these patients.

Both sporadic and NF1-related neurofibromas frequently show loss of the NF1 gene on chromosome 17. They may also have abnormalities in chromosomes 19, 22q, and 9p (01). This underlies the association between neurofibromatosis type 1 and neurofibromas.

Subependymomas have been found to harbor 6q deletions (23; 33). As previously discussed, the recent WHO classification update in 2021 delineated MYCN-amplified and non-amplified spinal ependymoma (26). These are separate entities, and the MYCN-amplified group tends toward higher recurrence and more aggressive behavior (23).

Gangliogliomas, particularly those in pediatric patients, are often found to harbor BRAF V600E mutations. Other chromosomal abnormalities that have been reported include gains on chromosomes 5, 6, 7, 8, and 12 and losses on chromosomes 9, 10, and 22q (01).

Differential diagnosis

Confusing conditions

• Initial differential diagnosis is often radiologic due to risk associated with biopsy.

Meningioma. The radiologic differential diagnosis includes the other more common intradural extramedullary spinal cord tumors: spinal schwannoma and spinal neurofibroma (12; 34).

Schwannoma, neurofibroma, and malignant peripheral nerve sheath tumors. Neurofibroma, schwannoma, and malignant peripheral nerve sheath tumors are frequently indistinguishable on MRI (28; 02).

Paraganglioma. The radiologic differential diagnosis includes myxopapillary ependymoma, schwannoma, neurofibroma, or meningioma (13).

Solitary fibrous tumor. The radiologic differential diagnosis includes astrocytoma, ependymoma, ganglioglioma, hemangioblastoma, paraganglioma, or metastatic disease (51).

Epidermoid or dermoid tumor. The radiologic differential diagnosis includes arachnoid cyst and neurenteric cyst (46).

Spinal ependymoma. For subependymoma, the radiologic differential diagnosis includes spinal ependymoma and astrocytoma (14). For myxopapillary ependymoma, the differential includes paraganglioma and schwannoma (49). In spinal ependymoma, the differential includes spinal astrocytoma, cavernous malformation, and diffuse midline glioma (45).

Spinal astrocytoma. The radiologic differential diagnosis includes ependymoma, particularly when cord expansion is present; however, astrocytomas are much less likely to have a hemorrhagic component (28; 29). Without cord expansion, the differential is broader and can include infectious, autoimmune, and demyelinating etiologies (44).

Primary intraspinal lymphoma. The differential diagnosis includes transverse myelitis or longitudinally extensive transverse myelitis, demyelinating disease (multiple sclerosis, neuromyelitis optica, acute disseminated encephalomyelitis, CIDP), other neoplasm (ependymoma, astrocytoma), infection, or sarcoidosis (17).

Ganglioglioma. The radiologic differential diagnosis includes astrocytomas and ependymomas as well as transverse myelitis (50).

Hemangioblastoma. The differential diagnosis for spinal hemangioblastoma is broad as they can be intradural extramedullary or intramedullary. This includes spinal meningioma, myxopapillary ependymoma, parenchymal metastatic disease, leptomeningeal metastatic disease, nerve sheath tumors, paraganglioma, spinal cord metastases, spinal astrocytoma or spinal ependymoma. Beyond this, the differential includes other vascular malformations including arteriovenous malformations, arteriovenous fistulas, and cavernous malformations (47).

Associated or underlying disorders

	• Neurofibromatosis type 1 and neurofibromas, malignant peripheral nerve sheath tumors, paraganglioma, spinal astrocytomas.
	• Neurofibromatosis type 2-related schwannomatosis and spinal meningiomas, schwannomas, spinal ependymomas.
	• Von Hippel-Lindau disease and hemangioblastomas, paraganglioma.

Diagnostic workup

	• Contrasted MRI is the imaging of choice for all spinal tumors.
	• Imaging appearance is helpful but often nondiagnostic for spinal cord tumors, necessitating biopsy for diagnostic confirmation.

Spinal meningioma. Diagnosis of spinal meningioma can often be made based on imaging. On MRI, spinal meningiomas are well-circumscribed lesions that are isointense on T1 and T2 sequences, although they may be slightly hypointense on T1 and slightly hyperintense on T2 and are typically homogenously enhancing (28; 12). There is often a dural tail, and calcifications may be seen. Compared to intracranial lesions, dural tails are less commonly seen, and calcifications are rarer and correlated with poorer functional outcomes postoperatively (39). If MRI is not available or possible due to patient factors, CT myelography may be performed. Spinal meningiomas are usually solitary, well-circumscribed lesions that do not invade adjacent tissue (28; 12). Compared to intracranial counterparts, they more rarely invade the pia, resulting in rarer parenchymal edema in the cord (39). Multiple meningiomas may be seen with neurofibromatosis type 2. As noted earlier, DOTATATE-PET can be used to evaluate for meningiomas and potentially differentiate them from other tumors.

Nerve sheath tumors.

Schwannoma. MRI aids in the diagnosis of schwannomas, but they are often indistinguishable from neurofibromas on MRI (28; 02). Schwannomas often arise from the dorsal root (05) and are more commonly associated with hemorrhage, vascular changes, cyst formation, and fatty degeneration than neurofibromas (28; 22). They may have a characteristic dumbbell shape if they extend through the neural foramen (40). On MRI, schwannomas are well-circumscribed solid masses that are T1 iso- or hypointense and hyperintense on T2 with homogenous contrast enhancement (01).

Neurofibroma. On the other hand, neurofibromas have less tendency towards hemorrhage, fatty degeneration, or cyst formation than schwannomas (28). On MRI, they are commonly also isointense on T1 and hyperintense on T2. They are strongly enhancing (01).

Malignant peripheral nerve sheath tumor. Frustratingly, malignant peripheral nerve sheath tumors may appear indistinguishable from schwannomas or neurofibromas on MRI. They also closely resemble other soft tissue sarcomas. Like those tumors, they are often T1 isointense and T2 isointense to slightly hypointense. Generally, the larger the lesion, the more likely it is to be malignant, particularly if there has been rapid growth on interval imaging or if vascularity and heterogeneity are prominent (21). Pathologic diagnosis is often required (01).

Paraganglioma. Diagnosis of paraganglioma can be aided in cases of functional tumors by checking levels of serum catecholamines and their metabolites (52). When found in the spine, the most common location is the filum terminale or cauda equina, and they tend to be highly vascular (30). On histology, there are characteristic Zellballen and Chief cells.

MRI is the preferred imaging modality, and paragangliomas are typically intradural, encapsulated, isointense on T1 and hyperintense on T2, and have heterogeneous contrast enhancement. Due to the potential for catecholamine production and expression of somatostatin receptors, a number of nuclear medicine scans can also be used (13). These tumors may also be positive on DOTATATE-PET.

Solitary fibrous tumor. Solitary fibrous tumors are highly vascular. On MRI, they can appear as well-defined tumors, which are sometimes dumbbell-shaped with signal flow voids indicating vascularity and avid contrast enhancement. They may also show erosion or destruction of adjacent bone. They are often T1 isointense to hypointense and markedly T2 hyperintense and may show peritumoral edema (43; 51).

Epidermoid and dermoid tumors. The diagnosis of epidermoid or dermoid cysts can often be made on MRI. They have a range of T1 and T2 intensities, although generally isointense to CSF, with no enhancement or just a thin rim of enhancement, and they are typically avidly diffusion-restricting (42; 46). They also commonly have cystic components that can rupture, causing aseptic meningitis. On gross pathology, they are pearly white (32).

Ependymal tumors.

Subependymoma. On MRI, subependymomas demonstrate eccentric growth with expansion of the involved cord and sometimes syrinx. They are isointense on T1 and hyperintense on T2 and may or may not exhibit contrast enhancement (14). There may be pseudo-rosettes on histology, although this is not universal (24).

Myxopapillary ependymoma. Myxopapillary ependymomas are well-defined, often large, and frequently sausage-shaped tumors. They are heterogenous, expansile, T1 isointense to hyperintense (which may be due to mucinous component), T2 hyper- to isointense, and have universal avid contrast enhancement. There is often a component of hemorrhage (22; 49). Tumors often span multiple spinal segments. Due to the risk of dissemination, full neuroaxis imaging is recommended at the time of diagnosis.

MRI is the imaging modality of choice, and these tumors typically show spinal cord expansion, are often unencapsulated but well-circumscribed, and are sometimes associated with tumoral cysts and often with nontumoral cysts (07). Up to 50% of cases can be associated with syrinx, and they are not usually calcified.

Spinal ependymoma. Spinal ependymomas tend to be T1 isointense or hypointense or T2 hyperintense with contrast enhancement and cord expansion (22; 45). Higher-grade lesions may be more isointense on T1 and T2 and have variable enhancement. Full neuroaxis neuroimaging is indicated as part of the diagnostic workup due to the risk of dissemination. On histology, they classically have perivascular pseudo-rosettes, true ependymal rosettes, and ependymal canals (24).

Spinal astrocytoma. On MRI, spinal astrocytomas appear as eccentric lesions that may even be exophytic (22; 29). They are mild to moderately enhancing, infiltrating spinal cord masses that typically do not span more than four segments (40). They may be associated with cysts or syrinx. They are usually T1 hypo- or isointense and T2 hyperintense (44). Histopathologic and genetic diagnoses are often necessary.

Molecular testing should be performed to differentiate various astrocytic-appearing tumors, including astrocytoma IDH mutant, glioblastoma IDHwt, and diffuse midline glioma H3K27-altered.

Primary intraspinal lymphoma. Unfortunately, for primary intraspinal lymphoma, MRI is notoriously nonspecific. Lesions are universally enhancing and often expansile. Cyst formation, syrinx, and hemorrhage are rare. On T1, they are usually isointense to the spinal cord; on T2, they may be hyperintense. PET scan is needed to rule out systemic lymphoma. Lesions will be hypermetabolic on PET. Spread to other CNS sites is common (48).

Lumbar puncture is often performed as part of the workup but is also nonspecific, often requiring biopsy for a definitive diagnosis (16). CSF studies almost always show elevated protein and lymphocytic pleocytosis (16). Other findings that may be seen include hypoglycorrhachia and neoplastic cells on flow cytometry or cytology. Importantly, even with multiple lumbar punctures, there will often be no abnormal cells discovered on cytology or flow cytometry (16; 17). Therefore, when lymphoma remains on the differential, biopsy can be critical in avoiding delays in treatment.

Ganglioglioma. On MRI, gangliogliomas have variable features, frequently with poor or patchy enhancement, syrinx, and absence of edema (25). They are often eccentric and contain cysts and areas of calcification. On T1, they have mixed signals due to multiple cellular elements, which is a unique feature. On T2, they are hyperintense (50).

Hemangioblastoma. Hemangioblastomas on MRI appear eccentric and may have an exophytic component. They are usually well-circumscribed, have discrete nodules, and often have associated cord expansion. They can bleed, resulting in subarachnoid hemorrhage or spinal cord hemorrhage. On T1, they have variable signal intensity. On T2, they are iso- or hyperintense with flow voids and surrounding edema. A hemosiderin cap may be noted. They avidly contrast enhance due to their vascular nature (47).

Management

	• Gross total resection is the treatment of choice when feasible for most primary intraspinal tumors.
	• Hemangioblastomas associated with Von Hippel-Lindau disease and plexiform neurofibromas associated with neurfibromatosis type 1 have oral chemotherapeutic options with FDA approval.
	• Radiotherapy is recommended as part of treatment in several tumor types, particularly in cases of subtotal resection, aggressive tumor grade, or recurrence.

Spinal meningioma. Gross total resection is the standard of care for managing symptomatic spinal meningiomas. In cases of asymptomatic lesions, periodic MRI surveillance can be pursued to monitor for growth. Surgical outcomes are generally favorable, with functional improvements often noted postoperatively. Gross total resection has been reported as attainable in more than 90% of patients (41). Due to the proximity of the meningioma to the spinal cord, it is common practice to utilize intraoperative neuromonitoring, including motor and somatosensory evoked potentials (41; 34).

Radiation is commonly used postoperatively in cases of anaplastic (WHO grade 3) meningioma at the time of recurrence or in cases of subtotal resection in atypical (WHO grade 2) meningioma (05; 34). Radiation may also be considered primary treatment in cases where surgery is considered too risky or would not be in alignment with patient goals of care (34).

Schwannoma. The treatment of choice for symptomatic schwannomas is surgery, with gross total resection often being curative. Tumors that traverse the neural foramina, those that carry the characteristic dumbbell shape, may be less amenable to gross total resection. Around 80% of patients experience symptom improvement or resolution following surgery (05). When gross total resection is achieved, recurrence rates are low, estimated at 4%, whereas with subtotal resection recurrence rates are approximately 50% (05). Intraoperative monitoring via somatosensory or motor-evoked potentials can help guide resection (40).

Radiosurgery is an option for patients in whom surgery is not feasible or desirable or at the time of recurrence (02).

Neurofibroma. Surgery is indicated for intractable pain or myelopathy due to neurofibromas; however, due to the close relationship between the neurofibroma and the involved nerve, gross total resection is only possible in a minority of cases. Despite this, nearly 70% have been reported to have symptom improvement in the short term, 16% with deterioration postoperatively. Recurrence occurs in approximately 13% (38; 05). Selumetinib, an oral MEK inhibitor, can be used in cases of inoperable plexiform neurofibroma. It is currently only approved in children (06). Adverse effects are consistent with other MEK inhibitors and broadly include cardiac, ocular, musculoskeletal, gastrointestinal, skin, and fetal toxicities (06).

Malignant peripheral nerve sheath tumor. The treatment of choice for malignant peripheral nerve sheath tumors is surgery, with gross total resection thought to be associated with improved prognosis. However, due to the infiltrative nature of the mass, subtotal resection is often the case (01). Adjuvant radiotherapy is often utilized. Chemotherapeutic regimens similar to those directed at other soft tissue sarcomas are often employed (08). Overall, recurrence rates are high, with one case series reporting up to 75% recurrence, with a 5-year survival of only 25% (08).

Paraganglioma. The treatment of choice for paraganglioma is complete surgical resection, which can be curative. One systematic review of primary spinal paraganglioma found that complete surgical resection was achieved in approximately 75% of cases (18). Radiation therapy can be used for residual tumor tissue or salvage therapy (30). Recurrence with total resection is reported rarely, with one study reporting a rate of 2.2% (18). Recurrence is slightly higher with subtotal resection, estimated between 5.4% and 10.5% (18).

Solitary fibrous tumor. The preferred treatment of solitary fibrous tumors is gross total resection, which often must be preceded by tumor embolization due to the highly vascular nature of these masses (30). Additionally, total resection may not be possible due to the risk of nerve injury and disability. In cases of subtotal resection, radiation therapy is indicated and greatly reduces the recurrence risk from 44.4% without radiation to 25.5% with radiation (43). Due to the high recurrence risk even with radiation and the risk for distant metastases, it is appropriate to do periodic tumor surveillance following intervention. The 5-year survival rate is 76% (43).

Epidermoid and dermoid tumors. For both epidermoid and dermoid tumors, the treatment of choice is complete surgical resection. With surgery, most patients experience improved stabilization of their neurologic function. In cases of subtotal resection, there is a risk for recurrence (42; 32).

Subependymoma. The treatment of choice for symptomatic subependymomas is resection, with favorable results observed in both gross total and subtotal resection. Care must be taken to avoid damaging surrounding structures intraoperatively (23; 33).

Myxopapillary ependymoma. The treatment of choice for myxopapillary ependymoma is gross total resection. This is often achievable due to good dissection planes. When achieved, most patients will experience symptom stabilization or improvement (23). This is also associated with reduced recurrence risk (23). In cases of subtotal resection, radiotherapy is often utilized (35). They have similar rates of recurrence to spinal ependymomas. Five-year progression-free survival in cases of gross total resection is greater than 90% (04; 10). Ten-year survival in another study was 72%, and progression-free survival was 57% in gross total resection (31). In subtotal resection, the risk for progression was increased six-fold, and in cases of infiltrative rather than encapsulated mass, progression risk was increased more than five-fold (04; 10). Intraoperative neurologic monitoring is often utilized.

Spinal ependymoma. As with other ependymomas, the treatment of choice is gross total resection (07; 37; 23). In grade 2 lesions, the prognosis is similar to myxopapillary ependymoma, with the primary risk for recurrence being subtotal resection and infiltrative nature (04, 07; 10). Postoperative neurologic deficits are common and the most reliable predictor of this is preoperative neurologic function (07). Intraoperative monitoring is recommended to avoid unintentional neurologic injury during surgery.

As with myxopapillary ependymoma, adjuvant radiotherapy is recommended in cases where gross total resection is not possible, although some studies suggest it may be helpful to prevent progression regardless of resection extent (09; 35). In cases of grade 3 or metastatic or disseminated disease, craniospinal radiation is often employed.

Spinal astrocytoma. The treatment of choice, when feasible, is gross total resection. This is not always possible even in grade 2 lesions and is even less likely to be achieved in higher grade tumors (36; 40; 29). Intraoperative monitoring is the standard of care to avoid further neurologic morbidity (29). The primary predictors of outcome are age, WHO grade or histology, and preoperative functional status (29).

Optimal radiation and systemic therapy-based management are uncertain as no randomized trials have evaluated therapeutic interventions in this patient population. Often, management is extrapolated from similar cranial tumors.

Primary intraspinal lymphoma. Unlike most other spinal cord tumors, resection is not recommended for these tumors. Instead, treatment consists of high-dose intravenous methotrexate. Other chemotherapeutic agents that are used include R-CHOP, CHOP, and combinations of rituximab and methotrexate (16). Due to delays in diagnosis, patients also often will have received steroids as part of empiric treatment for a different disease. Following treatment, most patients will have symptomatic improvement; however, relapse occurs on average at 1 to 6 months (16). Potential salvage therapy includes autologous stem cell transplant, radiation therapy, immunotherapy, or the chemotherapeutic agents listed above (16). Median survival in one case series was 16.5 months. Two-year survival from symptom onset was 36% (16).

Ganglioglioma. The treatment of choice for ganglioglioma is gross total resection. Intraoperative monitoring is indicated for removal to avoid further neurologic disability. The role of radiation is not well established and carries a theoretical risk of transformation of the astrocytic component (25).

Hemangioblastoma. Hemangioblastomas are treated with gross total resection. Vascular imaging before surgery can allow for tumor embolization in some cases, which reduces the risk of significant intraoperative blood loss (36; 37; 40). In a systematic review, gross total resection was reported in about 81% of cases (19).

Following resection, 90% of patients reported improved pain, and more than 70% reported improved sensory symptoms (19). Recurrence is 7.9% for sporadic cases and 22% in patients with Von Hippel-Lindau disease. Recurrence is also more likely with subtotal resection and when multiple CNS tumors are present (19). In 2021, a new drug named belzutifan, which is an oral daily medication that inhibits HIF-2a, was approved for several tumors associated with Von Hippel-Lindau disease, including hemangioblastomas (15; 53). The most commonly reported treatment-related side effects were decreased hemoglobin or anemia, fatigue, elevated creatinine, headache, dizziness, hyperglycemia, and nausea (15).

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All contributors' financial relationships have been reviewed and mitigated to ensure that this and every other article is free from commercial bias.

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Kathryn Eszes MD

Dr. Eszes of the University of Rochester has no relevant financial relationships to disclose.
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Nimish Mohile MD MS FAAN

Dr. Mohile of the University of Rochester has no relevant financial relationships to disclose.
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Editor

Rimas V Lukas MD

Dr. Lukas of Northwestern University Feinberg School of Medicine received honorariums from Novartis and Novocure for speaking engagements, honorariums from Cardinal Health, Novocure, and Merck for advisory board membership, and research support from BMS as principal investigator.
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Primary spinal cord tumors

Also Relevant

Dermoid and epidermoid tumors
Ganglioglioma
Intramedullary spinal cord metastatic tumors
Intraoperative neurophysiological monitoring
Neurofibromatosis 1
- Neurofibromatosis 2
- Scoliosis and kyphoscoliosis
- Spinal ependymoma
- Sporadic schwannomas and neurofibromas
- Syringomyelia
- Von Hippel-Lindau disease

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Neuro-Oncology

Primary spinal cord tumors

Primary spinal cord tumors

Introduction

Overview

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Clinical manifestations

Intradural extramedullary spinal cord tumors

Intramedullary spinal cord tumors

Biological basis

Genetics and cell biology

Differential diagnosis

Confusing conditions

Associated or underlying disorders

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Overview of neuropathology updates for infiltrating gliomas

Anti-LGI1 encephalitis

CNS germinoma

Vestibular schwannoma

Circumscribed astrocytic gliomas [Brief]

Pediatric-type diffuse high-grade gliomas [Brief]

Glioneuronal and neuronal tumors [Brief]

Mesenchymal non-meningothelial tumors [Brief]

Primary spinal cord tumors

Introduction

Overview

Key points

Clinical manifestations

Intradural extramedullary spinal cord tumors

Intramedullary spinal cord tumors

Biological basis

Genetics and cell biology

Differential diagnosis

Confusing conditions

Associated or underlying disorders

Diagnostic workup

Management

References

Contributors

Authors

Editor

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Also in This Category

Overview of neuropathology updates for infiltrating gliomas

Anti-LGI1 encephalitis

CNS germinoma

Vestibular schwannoma

Circumscribed astrocytic gliomas [Brief]

Pediatric-type diffuse high-grade gliomas [Brief]

Glioneuronal and neuronal tumors [Brief]

Mesenchymal non-meningothelial tumors [Brief]

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