• Clinicopathological studies ³ have indicated that the presence of brain invasion confers a more aggressive clinical course, and this finding alone justifies a diagnosis of grade II meningioma (Fig. 4-2, D).

Fig. 4-2 Atypical features in meningiomas. A, Patternless or sheet-like growth pattern. B, Focus of spontaneous necrosis. C, A hypercellular area containing cells with prominent nucleoli and mitotic figures. D, Glial fibrillary acidic protein immunohistochemical stain of tumor in Fig. 4-1, A highlighting brain parenchyma between the infiltrating tumor nests (×100). (A-C, hematoxylin–eosin stain; A and B, ×100; C, ×400.)

Grade III

PAPILLARY

• This subtype, commonly found in the pediatric population, is composed of cells in a pseudopapillary arrangement with a fibrovascular core.

• The histologic differential diagnosis includes ependymoma and other papillary neoplasms, which can be characterized based on immunophenotypic profiles.

RHABDOID

• The rhabdoid subtype is composed of cells with abundant eosinophilic cytoplasm and eccentrically positioned nuclei (Fig. 4-3). This meningioma subtype typically has an association with high mitotic rate and other cytoarchitectural anaplastic features, as well as evidence of brain invasion.^4,⁵

Fig. 4-3 Rhabdoid meningioma. Eccentrically located nuclei and abundant pinkish cytoplasm are seen (hematoxylin–eosin stain, ×400).

RADIOLOGY

• The location of meningioma is typically intradural, extramedullary. However, it is rarely located in intraosseous, extradural, or even paraspinous areas. On T1-weighted images (T1WI), the signal of the mass is isointense to the spinal cord (Figs. 4-4 and 4-5).

• On T2-weighted images (T2WI), most parts of the mass show iso-signal to the spinal cord (see Figs. 4-4 and 4-5).

• If a calcified area is included, the signal may change to low. When the meningioma is very vascular, prominent flow void can be displayed.

• With contrast material, a homogeneous enhancement pattern is common.

• A dural tail sign may be seen, which is less common than in intracranial meningiomas.

• Grossly the tumor mass is gray to white and of a slightly hard consistency (Fig. 4-6).

Fig. 4-4 Sagittal MRI of intradural meningioma. On T2WI, a small, round mass is seen in the intradural space at the T7 level (left). The mass signal is isointense to the spinal cord. It is located in the subarachnoid space posterior to spinal cord. On T1WI, the mass signal also is isointense to the spinal cord (middle). With contrast, a homogeneous enhancement pattern is shown (right).

Fig. 4-5 MRI axial images of intradural meningioma. On T1WI, a large iso-signal round mass is located at the posterolateral side of the intradural space (left image) with a homogeneous enhancement pattern (middle image). The spinal cord is compressed and displaced to the right anterior side. On T2 axial image adjacent caudal level to the tumor mass, a widened subarachnoid space is seen as bright high signal area (right image).

Fig. 4-6 Intraoperative view of spinal cord meningioma. After dural opening, the arachnoid membrane is seen to cover the tumor mass. Arachnoid dissection is done. A gray to white mass of slightly hard consistency is adhered to the pial membrane of the spinal cord (left image). After resection is completed from dural attachment, en bloc removal of the tumor mass is achieved (right image).

NERVE SHEATH TUMOR—SCHWANNOMA

EPIDEMIOLOGY

• Schwannomas account for approximately 30% of all spinal tumors.

• The peak incidence for schwannomas is in the fourth to seventh decades of life.

• As with meningiomas, there is a high incidence of schwannomas in patients with NF-2.

• One variety, psammomatous melanotic schwannoma, is a characteristic manifestation of the Carney complex.⁶

DISTRIBUTION

• Schwannomas may be found throughout all levels of the spinal cord and involve the sensory nerve roots.

• Schwannomas may have both intradural and extradural components; an intramedullary location is rare.

• Cellular schwannomas usually are located in paravertebral locations.

HISTOLOGY/GRADING

• Schwannomas are proliferations of neoplastic Schwann cells, which may have variable appearances (e.g., spindled, epithelioid, melanotic).

• Classic schwannoma (grade I)

• Histologic sections show Antoni A (densely cellular) and Antoni B (less cellular, sometimes cystic) areas (Fig. 4-7, A).

• Within Antoni A regions, Verocay bodies (small groups of fibrils surrounded by parallel rows of neoplastic cells) are commonly found.

• Cellular atypia alone (usually in Antoni B areas) in otherwise unremarkable schwannomas reflect degenerative (so-called “ancient”) changes and confers no prognostic significance. Other reactive and degenerative features, including cyst formation, macrophage and lymphocyte infiltration, and hemosiderin-laden cells, are commonly found in Antoni B areas (Fig. 4-7, B).

• The nerve from which the schwannoma arises may be identified in the specimen and, if so, is compressed to the edge of the tumor (Fig. 4-7, C).

• The vessels within schwannomas are often thick-walled and sclerotic (Fig. 4-7, D).

• Schwannomas demonstrate uniform, diffuse S100 protein immunoreactivity (Fig. 4-7, E).

• A histologic differential diagnosis for schwannomas usually only arises when less-than-classic microscopic features are present. Meningiomas, particularly of the fibrous subtype, may enter the differential and can be distinguished from schwannomas by the presence of diffuse EMA and patchy S100 protein immunoreactivity in the former lesion. Tumors with concurrent schwannoma and meningioma features have been reported.^7,⁸

• Because of their rarity, intramedullary schwannomas more often need to be distinguished from gliomas, particularly anaplastic astrocytomas, which can be accomplished through immunohistochemical staining.

• Cellular schwannomas (grade I [Fig. 4-8, A])

• Cellular schwannomas have an overall greater degree of cellularity than classic schwannomas and are composed almost exclusively of Antoni A regions with an absence of Verocay bodies.

• Modest mitotic activity and increased Ki-67 labeling indices (Fig. 4-8, B), cellular atypia, and a fascicular growth pattern are typical histologic findings in cellular schwannomas.

• Because of their greater cellularity, lack of the pathognomonic histologic features of classic schwannomas, and potential morphologic similarity to other spindle cell lesions, immunohistochemical staining is often performed.

Fig. 4-7 Histologic features of classic schwannomas. A, Antoni A region with numerous Verocay bodies. B, Degenerative changes in schwannoma with cyst formation. C, Compression of nerve (arrow) to periphery of schwannoma. D, Vessels with hyalinized walls within schwannoma. E, Diffuse, strong S100 protein immunoreactivity characteristic of schwannoma (×200). (A-D, hematoxylin–eosin stain; A, C, and D, ×100; B, ×40.)

Fig. 4-8 Histologic features of cellular schwannoma. A, Densely cellular proliferation lacking characteristic histologic features of classic schwannoma (hematoxylin–eosin stain, ×200). B, Modestly increased Ki-67 labeling index in cellular schwannoma (×200).

RADIOLOGY

• Typical morphology of the schwannoma is a well-circumscribed, round, or lobulated mass in the spinal canal or extraspinal location.

• Seventy percent of the schwannomas are located in the intradural space (Fig. 4-9), and 15% of them occupy the extradural space. The rest of them take on a dumbbell shape (combined intradural and extradural; Figs. 4-10 and 4-11).

• On simple radiography, benign bony change may be seen. Interpedicular distance can be widened, and posterior vertebral margin may be eroded. The width of the pedicle can be thinned, and the intervertebral foramen may be enlarged.

• On computed tomography (CT) scan, the density is isodense to the spinal cord. Cystic change may commonly be seen.

• On magnetic resonance imaging (MRI), the signal of the mass is isointense or hypointense to spinal cord on T1WI. The signal is hyperintense in most cases on T2WI. The enhancement pattern is uniform or heterogeneous (Figs. 4-10 to 4-13).

Fig. 4-9 Sagittal images of the extradural schwannoma. On T2WI, extradural mass posterior to the spinal cord is seen as a high signal mass at the T7–8 level (left). On T1WI, the mass signal is low (middle). With gadolinium, the mass has a homogeneous enhancement pattern (right).

Fig. 4-10 Axial images of the extradural schwannoma. The mass has several components: intraspinal cystic portion, extraforaminal solid portion, and ventral part that eroded the vertebral body. On T2WI, the signal is mixed (left). On TIWI, the signal is low (middle). With contrast enhancement, a diffuse enhancement pattern is seen (right).

Fig. 4-11 Intraoperative view of extraforaminal schwannoma. Right side thoracotomy is done and intrathoracic mass is seen. The mass is covered with parietal pleura (left). The mass that is en-bloc removed reaches to 5-cm long (middle). After the mass removal, the extraforaminal area is seen (right).

Fig. 4-12 Sagittal MRI of intradural schwannoma at L3 level. On T2WI, the high signal mass with low signal rim is located in the intradural space (left). On T1WI, the signal is low (middle). With contrast, a dense enhancement pattern is seen (right).

Fig. 4-13 Intraoperative view of intradural schwannoma. At first, the dura is opened and arachnoid dissection is done. A round tumor mass with smooth surface is seen ventral to the spinal cord (left). After placement of cottonoid, careful dissection of the tumor mass from the spinal cord surface is performed at cephalad side (middle). The tumor mass is easily dissected and removed. The origin nerve rootlet can be sacrificed (right).

NEUROFIBROMA

EPIDEMIOLOGY

• Neurofibromas of the spine can occur spontaneously but are found at a high frequency in patients with neurofibromatosis type 1 (NF-1).

• Spinal nerve sheath tumors constitute one-fourth of all spinal tumors and more than one-third of intradural extramedullary tumors of the spinal cord.⁹

• They commonly occur at an age between 25 and 50 years of age, with no clear discrepancy between men and women.⁹

• The incidence of spinal neurofibromas has been reported to be equivalent to or slightly greater than that of spinal meningiomas.

DISTRIBUTION

• In NF-1 patients, neurofibromas preferentially involve the cervical spine.¹⁰

• Neurofibromas are typically extradural lesions that may extend proximally to an intradural location.

• Neurofibromas can be located entirely inside the dural sac (intradural), entirely outside the dural sac (extradural), or partly inside and partly outside the dural sac, according to the location of the tumor origin along the spinal nerve root.

• In the literature, 70–80% of spinal neurofibromas are intradural, and those extending through the dural aperture as a dumbbell mass with both intradural and extradural components account for another 15%.⁹

• Tumors with an extraforaminal component decrease from the cervical region to the lumbar region of the spinal axis.

• A spinal nerve sheath tumor originates from the spinal nerve root and grows along the spinal nerve root.

• The ratio of the intradural segment to the extradural segment of the spinal nerve root within the spinal canal gradually increases from the high cervical region to the sacral region. Similarly, the length of the nerve root within the spinal canal gradually increases from the rostral region to the caudal region.¹¹

HISTOLOGY/GRADING

• Neurofibromas are grade I lesions, which represent a proliferation of all components of a nerve, including Schwann cells, collagen, and perineurial cells, resulting in a fusiform expansion (Fig. 4-14).

• Unlike schwannomas, fragments of the axons in the native nerve are “peppered” throughout the neoplasm rather than eccentrically compressed.

• Neurofibromas often have a myxoid matrix in which mast cells are common. The appearance of small, haphazardly arrayed aggregates of collagen has been likened to “shredded carrots” (Fig. 4-15).

• Plexiform neurofibromas are visually complex appearing lesions with interdigitating fascicles. This form of neurofibroma typically involves larger nerve trunks and is nearly pathognomonic for NF-1.

• In contrast to schwannomas, neurofibromas demonstrate less dense S100 protein immunoreactivity (Fig. 4-16).

Fig. 4-14 Combined proliferation of all the elements of the peripheral nerve, including axons, Schwann cells, and fibroblasts. The cells usually have markedly elongated nuclei, with a wavy, serpentine configuration and pointed ends (hematoxylin–eosin stain, ×200).

Fig. 4-15 Abundant collagen fibers are seen in neurofibroma (hematoxylin–eosin stain, ×100).

Fig. 4-16 Pattern of S100 protein immunoreactivity is less dense in neurofibroma compared that shown in Fig. 4-7, E (×200).

RADIOLOGY

• The best diagnostic clue is bulky, multilevel spinal nerve root tumors in patients with stigmata of NF-1.

• The location of the tumor is variable: intradural extramedullary, extradural intraspinal, or extraspinal (paraspinal). In the extraspinal area, the tumor can develop from the spinal nerve root, neural plexus, peripheral nerve, or end organs.

• On CT, the mass shows isodense image to the spinal cord. Neural foramen enlargement can accompany the mass.

• On T2WI MRI, neurofibroma can be of isointense or hyperintense signal intensity. Sometimes, central high signal and peripheral low signal may be seen (Target sign) (Fig. 4-17).

• On T1WI MRI, the mass signal is similar to the spinal cord (Fig. 4-18).

• With contrast, the mass demonstrates moderate or bright enhancement (Figs. 4-19 and 4-20).

• In cases of extraspinal neurofibroma, the signal of the mass is similar to intraspinal neurofibroma (Figs. 4-21 to 4-24).

Fig. 4-17 T2 sagittal MR of patient with NF. Multiple isointense or hyperintense small, round masses are scattered along the spinal cord and cauda equina. The largest mass is seen along the posterior side of the spinal cord at the T10 level.

Fig. 4-18 T1 sagittal MR of patient with NF. Multiple small masses are seen in the spinal canal. The signal is similar to the spinal cord.

Fig. 4-19 Gadolinium enhanced sagittal MR of patient with NF. Well-enhancing, small, round masses are observed along the conus and cauda equina.

Fig. 4-20 Gadolinium-enhanced axial MR of patient with NF. Well-enhancing masses are seen at T6 (left), T10 (middle), and L4 (right) vertebral body level. The location of tumor mass is posterior or posterolateral to the spinal cord or cauda equina.

Fig. 4-21 T2-weighted MR of extraspinal neurofibroma. The mass signal is low at the central portion and high at the peripheral portion. The mass is located at the left foraminal and extraforaminal areas at the C7 level. The mass grows downward to the T2 level.

Fig. 4-22 T1-weighted MR of extraspinal neurofibroma. The signal of the mass is low.

Fig. 4-23 Gadolinium-enhanced MR of extraspinal neurofibroma. A homogeneous enhancement pattern is shown. The vertebral artery is displaced to the anterior side of the tumor mass (left image). On axial image, the mass has a dumbbell shape (right image).

Fig. 4-24 Coronal view of extraspinal neurofibroma. The mass is located between the right side of the cervical vertebral body and the anterior scalenus muscles.

PARAGANGLIOMA

EPIDEMIOLOGY

• Pheochromocytomas are catecholamine-secreting tumors of the adrenal medulla chromaffin cells. Extra-adrenal pheochromocytomas are called paragangliomas and only rarely produce catecholamine excess.¹² All but a small fraction of extra-adrenal paragangliomas arise from the carotid body and glomus jugulare.

• Paragangliomas of the spine are uncommon lesions that usually present as intradural tumors within the cauda equina.¹³ More than 70 cases have been reported since 1972.

• Spinal paragangliomas arise slightly more frequently in males than in females, with a peak incidence in the fourth to sixth decades of life.¹

• Spinal paragangliomas are believed to be predominantly of the sympathetic type, but the majority of paragangliomas in the carotid and jugular bodies are parasympathetic in type.¹⁴

DISTRIBUTION

• Most primary central nervous system extra-adrenal paragangliomas arise in the region of the cauda equina.

• Spinal paragangliomas are intradural lesions.

• Extra-adrenal pheochromocytomas of the neural crest-derived sympathetic ganglia are known as paragangliomas and account for approximately 15% of all pheochromocytomas.¹³

HISTOLOGY/GRADING

• Grossly, all of the tumors located in the intradural extramedullary space are well encapsulated, red-black, very soft or friable, and bleed easily. Tumor mass is adherent to a vascular pedicle or a rich vascular network.

• Most of paragangliomas in cauda equina are known to originate from the filum terminale.

• Extra-adrenal paragangliomas are composed of neurosecretory cells, which may assume a number of architectural patterns. A nested pattern is common in which the cells are clustered into packets (“zellballen”) that are separated by numerous thin-walled vessels. Supporting, slender sustentacular cells (modified Schwann cells) surround the cell nests (Fig. 4-25, A).

• More magnified images show that the nuclei are uniformly round to oval with a regular chromatin pattern. Nucleoli are observed, and the cytoplasm is finely granular. No mitosis is observed.¹⁵

• Neuronal differentiation can be identified in a proportion of spinal paragangliomas.

• The neurosecretory cells have a characteristic “salt and pepper” chromatin pattern and are immunoreactive for synaptophysin, chromogranin, and neuron-specific enolase (Fig. 4-25, B). The sustentacular cells demonstrate S100 protein immunoreactivity (Fig. 4-25, C).

• The histologic differential diagnosis includes ependymoma, the diagnosis initially applied to the first reported case of paraganglioma of the filum terminale. These two entities can be discerned through immunohistochemical staining with immunoreactivity for chromogranin and S100 protein (as previously discussed) in paragangliomas and glial fibrillary acidic protein immunoreactivity in ependymomas.

• Paragangliomas are grade I neoplasms, although rare circumstances of aggressive growth and malignant progression have been documented.

Fig. 4-25 Spinal paraganglioma. A, One of the common architectural patterns consisting of packets of cells (zellballen) surfaced by sustentacular cells with a rich vascular network (hematoxylin–eosin stain, ×200). B, Strong chromogranin immunoreactivity in neuroendocrine cells (×200). C, S100 protein immunoreactivity in sustentacular cells (×200).

RADIOLOGY

• The diagnosis of pheochromocytoma or functioning paraganglioma is made by the measurements of the levels of catecholamines and their metabolites in plasma or urine.

• The sensitivity of plasma metanephrine levels for the detection of pheochromocytoma has been reported to be as high as 100%, compared with 82% for urinary and plasma catecholamine levels.¹⁶

• The location of the tumor can usually be identified with abdominal CT or MRI scans.

• The m-[¹²³I]iodobenzylguanidine scanning approach relies on nuclide uptake by the tumor and is particularly useful for locating extra-adrenal tumors.¹⁶

• The typical MR finding is a well-demarcated mass with low/intermediate signal intensity on T1WI and intermediate/high signal intensity on T2WI, in comparison with spinal cord tissue.

• On T2WI, heterogeneous signal intensity is observed. A hypointense tumor margin is commonly observed on T2WI, which indicative of paramagnetic effects from hemosiderin.¹⁴

• The hypervascular nature of paragangliomas results in punctuate areas of flow void interspersed in a matrix of increased signal intensity caused by slow flow and tumor cells. This produces a salt-and-pepper appearance on T2WI, which is considered to be a characteristic of paragangliomas (Fig. 4-26).

• Gadolinium administration produces intense heterogeneous enhancement, and high-velocity flow through the hypervascular tumors produces multiple serpiginous areas of signal void with all sequences.¹⁷

• The differential diagnosis should be considered with myxopapillary ependymoma, schwannoma, meningioma, and metastasis.

Fig. 4-26 Sagittal MR of lumbar paraganglioma. The mass is isointense on T1WI (left) and hyperintense on T2WI (middle) and demonstrates homogeneous enhancement with gadolinium (right). On T2WI, a focal hypointensity spot is seen in the tumor mass.

GANGLIONEUROMA

EPIDEMIOLOGY

• Ganglioneuromas belong to a group of neuronal tumor in which the neoplastic cells express a mature neuronal phenotype.¹⁸ They show a benign and slow-growing nature.

• The peripheral nervous system is much more commonly involved than the central nervous system. Peripheral ganglioneuroma arises from pluripotential neural crest cells and is closely related to the embryological development of the sympathetic nervous system.

• Common sites for peripheral ganglioneuromas include the adrenal medulla and the sympathetic nervous system in the neck, mediastinum, and retroperitoneum.¹⁹

• Central ganglioneuroma, or gangliocytoma, is less common.¹⁹ Analogous to their peripheral counterpart, both tumors represent the product of differentiation and maturation of the progeny of an initially primitive neuroblastic population.

• In contrast to the established link between peripheral ganglioneuroma and the sympathetic nervous system, the histogenesis of central ganglioneuroma remains poorly defined. Spinal ganglioneuroma encompasses the features of both the central and the peripheral types of ganglioneuroma.

• Ganglioneuromas occur most commonly in children and young adults younger than 30 years old.¹⁹ The ratio of male to females is approximately 3:2.