Cranial Nerve Tumors

Main Text

Preamble

Nerve sheath tumors occur throughout the CNS either sporadically (discussed here) or as part of tumor predisposition syndromes, such as neurofibromatosis types 1 and 2 (see Chapter 44).

The 2021 WHO classification of CNS tumors made several changes in the way tumors of the cranial and paraspinal nerves are classified. The four basic categories of schwannoma, neurofibroma, perineurioma, and malignant peripheral nerve sheath tumor were retained. Newly recognized tumors include hybrid nerve sheath tumor and malignant melanotic nerve sheath tumor. Cauda equina “CNS paraganglioma” is now termed cauda equina neuroendocrine tumor and is considered biologically distinct from paragangliomas elsewhere in the body. Cauda equine neuroendocrine tumor is briefly discussed in this chapter even though it is an intradural-extramedullary spinal neoplasm.

With the exception of vestibular schwannoma (VS), all intracranial nerve sheath tumors are rare, and the vast majority are benign. The two major tumor types that are found intracranially and at or near the skull base are schwannomas and neurofibromas. Both are discussed here as are melanotic and malignant peripheral nerve sheath tumors. Intracranial hybrid nerve sheath tumors and perineuriomas are very rare and are not included in this chapter.

Schwannomas

Schwannoma Overview

Terminology

Schwannomas are benign, slow-growing, encapsulated tumors of cranial and spinal nerves that are composed entirely of well-differentiated Schwann cells.

Etiology

General Concepts

Schwannomas originate from Schwann cells, which are derived from the embryonic neural crest. Schwannomas may arise along the course of any peripheral nerve or cranial nerves (CNs) III-XII (26-1). The olfactory and optic nerves do not contain Schwann cells so schwannomas do not arise from CNs I and II. “Olfactory groove schwannomas” are probably tumors that arise from olfactory ensheathing cells.

Schwann cells are also not a component of normal brain parenchyma. The exceptionally rare intraparenchymal schwannoma is thought to arise from neural crest remnants that later express aberrant Schwann cell differentiation.

Genetics

Inactivating mutations of the NF2 gene are detected in 50-75% of sporadic schwannomas. The majority of VSs—the most common nerve sheath tumor—present sporadically without identification of germline pathogenic variants, although recent studies have identified a 9p21.3 hotspot associated with an increased risk of VS tumorigenesis.

Germline mutations of either the SMARCB1 or LZTR1 tumor suppressor gene are found in many patients with familial schwannomatosis (see Chapter 43).

Pathology

Location

Schwannomas arise at the glial-Schwann cell junction of CNs III-XII (26-1). The distance from the brain to the interface where the glial covering terminates and Schwann cell ensheathing begins varies with each CN. In some—such as the oculomotor nerve (CNIII)—the junction is in close proximity to the brain. Here, schwannomas arise close to the exit of the parent nerve from the brain. In others—such as the vestibulocochlear nerve (CNVIII)—the junction lies at some distance from the nerve exit or entrance into the brainstem.

Sensory nerves are much more commonly affected by schwannomas compared with pure motor CNs. The vestibulocochlear nerve is by far the most common intracranial site (90%). The second most common site is the trigeminal nerve (CNV) (2-4%). Schwannomas of CNs other than CNVIII and CNV (e.g., jugular foramen or hypoglossal tumors) are very rare, accounting for just 1-2% of cases.

Size and Number

Most intracranial schwannomas are small, globose tumors with nerve fascicles draped over the tumor capsule (26-2). Some, especially trigeminal schwannomas, can attain huge size and involve both intra- and extracranial compartments.

Most schwannomas are “sporadic” or “solitary.” The presence of multiple schwannomas in the same individual suggests an underlying tumor predisposition syndrome (see Chapter 43).

Gross Pathology

Schwannomas arise eccentrically from their parent nerves and are smooth or nodular well-encapsulated lesions (26-3). Cystic change is common. Microhemorrhages occur, but gross macroscopic bleeds are rare (26-4).

Microscopic Features

So-called conventional schwannomas are well-encapsulated spindle cell tumors composed of well-differentiated Schwann cells. The large majority exhibit a biphasic histopathology. The Antoni A pattern consists of compact fascicles of elongated spindle cells. A less cellular, loosely textured, more haphazard arrangement with lipid-laden cells is called the Antoni B pattern (26-5). Schwannomas correspond to CNS WHO grade 1.

Diagnostic Molecular Pathology

Loss of chromosome 22q &/or mutation of NF2 are frequent but nonspecific findings in sporadic schwannomas. Schwannomas exhibit a distinct DNA methylation pattern.

Syndrome-associated schwannomas [neurofibromatosis type 2 (NF2) or schwannomatosis] are often associated with SMARCB1 or LZTR1 germline mutations followed by a somatic NF2 mutation on chromosome 22.

Clinical Issues

Intracranial schwannomas are relatively uncommon, constituting ~ 7% of all primary neoplasms. All ages are affected, but the peak incidence is in the 4th-6th decades. Schwannomas do occur in children but are uncommon unless associated with NF2. Symptoms are location specific; tinnitus and hearing loss are the most common symptoms in VSs.

Schwannomas are benign tumors that tend to grow very slowly. VS growth can be episodic and nonlinear. Some small intracanalicular VSs are monitored with a “wait-and-scan” management. Between 10-13% may exhibit volumetric tumor regression. The exception is VSs in young patients with NF2. These tumors have higher MIB-1 indices and may grow more rapidly.

Imaging

General Features

Neuroimaging findings reflect their slow growth and benign biologic behavior. A well-circumscribed extraaxial mass that originates within or near a CN and displaces but does not invade adjacent structures is typical (26-6).

CT Findings

Most schwannomas exhibit low to intermediate attenuation on NECT scans and show smooth expansion/remodeling of osseous foramina on bone CT. Cystic change is common. Gross intratumoral hemorrhage is uncommon, and calcification is rare. Strong, moderately heterogeneous enhancement after contrast administration is typical.

MR Findings

Schwannomas are generally isointense with cortex on T1WI (26-8B)and heterogeneously hyperintense on T2WI and FLAIR (26-8A). Although macroscopic intratumoral hemorrhage is rare, T2* (GRE, SWI) scans often reveal “blooming” foci of microbleeds.

Secondary changes of muscle edema or denervation with atrophy and fatty infiltration can occur with motor nerve schwannomas. Vagal nerve schwannomas may cause vocal cord paralysis.

Virtually all schwannomas enhance intensely (26-7) (26-8B). Approximately 15% have nonenhancing intratumoral cysts. Nonneoplastic peritumoral cysts occur in 5-10% of cases, especially with larger lesions (26-11).

Dynamic susceptibility contrast perfusion sequences may be helpful in distinguishing sporadic schwannomas from other infratentorial tumors, such as paragangliomas.

Differential Diagnosis

Cerebellopontine angle (CPA) masses that can mimic VS include meningioma and paraganglioma. Meningiomas often cap the internal auditory canal (IAC) like a mushroom and exhibit a dural tail sign. Paragangliomas of the jugular foramen have a salt and pepper enhancing pattern.

The differential diagnosis of a solitary enlarged enhancing CN includes schwannoma, multiple sclerosis, viral and postviral neuritis, Lyme disease, sarcoid, ischemia, and malignant neoplasms (metastases, lymphoma, and leukemia).

The most common cause of multiple enhancing CNs is metastasis. NF2, neuritis (especially Lyme disease), lymphoma, and leukemia are significantly less common than metastasis. Rare but important causes include multiple sclerosis and chronic inflammatory demyelinating polyneuropathy, a disorder that usually affects spinal nerves but may occasionally involve CNs.

Vestibular Schwannoma

Terminology

Vestibular schwannoma (VS) is the preferred term for a CNVIII schwannoma. VSs are also known as acoustic schwannomas and acoustic neuromas.

Etiology

VSs arise from the vestibular portion of CNVIII at the glial-Schwann cell junction inside the IAC near the porus acusticus. Schwannomas rarely arise from the cochlear portion of CNVIII. The majority of sporadic VSs have inactivating mutations of NF2.

Pathology

VSs may occur at any location along the course of the nerve. Small VSs are often completely intracanalicular. Larger lesions frequently protrude medially through the porus acusticus into the CPA cistern.

Small VSs are round or ovoid lesions that generally measure 2-10 mm in length. VSs that extend into the CPA cistern can become very large, up to 5 cm in diameter. Bilateral VSs are pathognomonic of NF2.

Clinical Issues

VS is by far the most common intracranial schwannoma. VS is also the most common CPA cistern mass, accounting for 85-90% of lesions in this location.

Peak presentation is 40-60 years of age. The most common presentation is an adult with slowly progressive unilateral sensorineural hearing loss (SNHL). Small VSs may present initially with tinnitus. Large lesions often present with trigeminal &/or facial neuropathy.

The growth rate of VSs varies. On average, they tend to enlarge between 1 mm or 2 mm per year. Approximately 60% grow very slowly (< 1 mm per year), whereas 10% of patients experience rapid enlargement of their lesions (> 3 mm per year).

Imaging

General Features

The classic imaging appearance of VS is an avidly enhancing mass that looks like ice cream on a cone (26-7). Many VSs extend medially from their origin within the IAC. The intracanalicular part of the tumor represents the “cone.” If a VS passes through the porus acusticus, it typically expands when it enters the CPA, forming the “ice cream” on the cone.

Precisely defining the size and extent of a VS is one of the most important goals of imaging. Some VSs remain as small, slow-growing lesions that are entirely intracanalicular (26-9) (26-10). Many intracanalicular VSs have a distinctive fundal “cap” of CSF interposed between the lesion and the modiolus (26-10). Others grow laterally, extending deep into the IAC fundus, and may eventually pass through the cochlear aperture into the modiolus.

CT Findings

CT is generally negative unless lesions are large enough to expand the IAC or protrude into the CPA cistern.

MR Findings

VSs are generally iso-/hypointense with brain on T1WI (26-8B). An intracanalicular VS appears as a hypointense filling defect within the bright CSF on CISS. Larger VSs are iso- to heterogeneously hyperintense on T2WI and may have associated cysts (26-11). Microhemorrhage on T2* is common, although macroscopic hemorrhage is rare (0.4% of all newly diagnosed VSs but 5-6% of anticoagulated patients).

Virtually all VSs enhance strongly following contrast administration (26-7). A schwannoma-associated dural tail sign occurs but is rare compared with CPA meningiomas.

Differential Diagnosis

The major differential diagnosis of VS is CPA meningioma. Most meningiomas “cap” the IAC and do not extend deep to the porus. However, a reactive dural “tail” in the IAC may make distinction between VS and meningioma difficult unless other dural “tails” along the petrous ridge are also present.

A facial nerve schwannoma confined to the IAC may be difficult to distinguish from a VS. Facial nerve schwannomas are much less common and usually have a labyrinthine segment “tail.” Metastases can coat the facial and vestibulocochlear nerves within the IAC. Metastases are usually bilateral with other lesions present.

Other CPA masses, such as epidermoid cysts, arachnoid cysts, and aneurysms, can usually be distinguished easily from VS. VSs occasionally have prominent intramural cysts, but a completely cystic schwannoma without an enhancing tumor rim is very rare.

Trigeminal Schwannoma

Although trigeminal schwannomas are the second most common intracranial schwannoma, they are rare tumors. They may involve any part of the CNV complex, including extracranial peripheral divisions of the nerve. Nearly 2/3 of all Meckel cave tumors are schwannomas.

Imaging

Trigeminal schwannomas arise from the junction of the gasserian ganglion and the trigeminal nerve root (26-12). Small lesions may be confined to Meckel cave. They have a very characteristic appearance on coronal T2WI, the winking Meckel cave sign. Because at least 90% of each Meckel cave is normally filled with CSF, any lesion that fills the cave with soft tissue contrasts sharply with the bright signal on the opposite normal side (26-13).

Bicompartmental tumors are common. Schwannomas that originate in Meckel cave can extend into the posterior fossa (through the porus trigeminus). These tumors have a characteristic dumbbell configuration (26-14). Tumors that involve all three locations are uncommon and termed three-compartment trigeminal schwannomas (26-15).

Schwannomas that involve the mandibular division (CNV3) may cause denervation atrophy of the muscles of mastication.

Differential Diagnosis

The appearance of a bi- or tricompartmental CNV schwannoma is distinctive. The major differential diagnoses of a Meckel cave schwannoma are meningioma and metastasis.

Jugular Foramen Schwannoma

Although schwannomas account for ~ 40% of all jugular foramen (JF) neoplasms, JF schwannomas constitute only 2-4% of all intracranial schwannomas.

Glossopharyngeal schwannomas are the most common JF schwannoma, but they are still rare. The vast majority present with vestibulocochlear symptoms secondary to compression and displacement, not CNIX symptoms. Glossopharyngeal schwannomas can occur anywhere along the course of CNIX, but the majority of symptomatic cases are intracranial/intraosseous.

Most vagal schwannomas are “dumbbell” lesions that extend from the basal cistern through the JF into the high, deep carotid space (26-16) (26-17).

The major differential diagnoses of JF schwannoma include meningioma, glomus jugulare tumor (paraganglioma), and metastasis. Only a JF schwannoma smoothly enlarges and remodels the jugular fossa. Paragangliomas exhibit a distinct salt and pepper appearance on contrast-enhanced sequences.

Facial Nerve Schwannoma

Facial nerve schwannomas (FNSs) are rare lesions that can arise anywhere along the course of the facial nerve, from its origin in the CPA to its extracranial ramifications in the parotid space (26-18)(26-19).

CPA-IAC FNSs are radiologically indistinguishable from vestibular schwannomas if they do not demonstrate extension into the labyrinthine segment of the facial nerve canal. Lesions that traverse the labyrinthine segment often have a dumbbell appearance.

Almost 90% of FNSs involve more than one facial nerve segment (26-20). The geniculate fossa is the most common site, involved in > 80% of all FNSs (26-21). The labyrinthine and tympanic segments are each involved in slightly over 1/2 of FNSs. Tympanic segment FNSs often pedunculate into the middle ear cavity, losing their tubular configuration.

Schwannomas of Other Intracranial Nerves

Less than 1% of intracranial schwannomas arise from CNs other than VIII, V, VII, and IX/X. Most resemble their more common counterparts on imaging studies.

Olfactory nerve “schwannomas” actually arise from modified glial cells, not Schwann cells. Once termed “olfactory groove schwannoma” or “subfrontal schwannoma,” these neoplasms are more accurately called olfactory ensheathing cell (OEC) tumors. Many reach a large size (26-22), causing frontal lobe signs, such as emotional lability and complex partial seizures.

Neoplasms of the optic nerve (a brain tract) are astrocytomas, not schwannomas. Intraorbital schwannomas arise from peripheral branches of CNs IV, V1, or VI or from sympathetic or parasympathetic fibers (not the optic nerve).

Oculomotor schwannomas are the most common of all the pure motor nerve schwannomas (26-23). The most frequent location of a CNIII schwannoma is in the interpeduncular cistern near the nerve exit from the midbrain (26-24). Trochlear schwannomas are uncommon (26-25). They cause diplopia (isolated unilateral superior oblique palsy) and compensatory head tilt that may be misdiagnosed clinically as “wry neck.” Most CNIV schwannomas are small and either simply watched or treated with prism spectacles.

Hypoglossal tumors are the rarest of the “other” schwannomas, accounting for only 5% of all nonvestibular intracranial schwannomas (26-26). Over 90% present with denervation hemiatrophy of the tongue. Most originate intracranially (26-27)but can also extend extracranially as a “dumbbell” tumor that expands and remodels the hypoglossal canal (26-28).

Parenchymal Schwannomas

Because the brain parenchyma does not normally contain Schwann cells, so-called ectopic schwannomas not associated with CNs are very rare (< 1% of cases). Most intraparenchymal schwannomas are solitary and nonsyndromic.

On imaging studies, most intracranial parenchymal schwannomas appear well demarcated. The most common imaging pattern is that of a cyst with a mural nodule and peripheral enhancement (26-29). One-third are solid tumors with strong homogeneous or heterogeneous enhancement. Peritumoral edema varies from none to moderate.

Schwannomatosis

Nonsyndromic schwannomas are almost always solitary lesions. Multiple schwannomas occur in the setting of two familial tumor syndromes, neurofibromatosis type 2 (NF2) and schwannomatosis. Bilateral vestibular schwannomas are pathognomonic of NF2. Multiple, mostly nonvestibular schwannomas in the absence of other NF2 features are characteristic of schwannomatosis. Both of these syndromes are discussed in Chapter 43.

Neurofibromas

Preamble

Neurofibromas (NFs) are much less common than schwannomas. In contrast to schwannomas, NFs consist of mature neoplastic Schwann cells intermixed with nonneoplastic cell types in a variable loose myxoid to collagenous stroma. NFs can affect the scalp, skull, some CNs (especially CNV1), or—rarely—the brain. They are found at all ages. Both sexes are affected equally.

NFs can be solitary or multiple. Multiple NFs and plexiform NFs occur only in connection with neurofibromatosis type 1 (NF1).

The gross appearance of NFs is different from that of schwannomas. Schwannomas are well-delineated encapsulated lesions that arise eccentrically from their parent nerve. Schwannomas typically displace elements of the normal parent nerve to one side (26-2).

NFs generally present as more diffuse nerve expansions and tend to infiltrate adjacent soft tissues. They display single (localized) or multiple (plexiform) fascicles that enter and leave the affected nerve. Axons of the parent nerve pass through NFs and are intermixed with tumor cells (26-30), distinguishing them from schwannoma.

NFs are all considered CNS WHO grade 1 neoplasms. Atypical histologic features, such as hypercellularity and mitoses, are rare. When present, these uncommon tumors are designated atypical neurofibromatous neoplasm of uncertain biological significance (ANNUBP) in the 2021 WHO.

Solitary Neurofibroma

Solitary NFs are the most common subtype of NFs. Unlike the diffuse and plexiform NF subtypes, they are generally not associated with NF1.

A solitary NF in the head and neck rarely—if ever—involves CNs. Solitary NFs affect patients of all ages and are usually sporadic (nonsyndromic). Most occur in the absence of NF1 and present as a painless scalp or skin mass.

Scalp solitary NFs are usually well-defined lesions measuring < 5 cm in diameter. They abut but do not invade the calvarium. Solitary NFs are iso- to mildly hyperintense to muscle on T1WI and hyperintense on STIR and T2WI (26-31). Strong but heterogeneous enhancement is typical. Solitary NFs do not undergo malignant degeneration.

Plexiform Neurofibroma

Plexiform NF1 (PNF) is defined by its involvement of multiple nerve fascicles. PNFs demonstrate a predominant intrafascicular growth pattern with redundant loops of expanded nerve fascicles intermixed with collagen fibers and mucoid material. PNFs are infiltrative intra- and extraneural neoplasms with a ropy or bag of worms gross appearance (26-32). PNFs are highly associated with NF1 and have an increased risk of transformation to malignant peripheral nerve sheath tumor (MPNST).

The most typical locations are the scalp, orbit, pterygopalatine fossa, and parotid gland.

PNFs are generally isodense with muscle on NECT. Calcification and hemorrhage are rare. CECT shows heterogeneous enhancement. Bone CT may show expansion of the superior orbital fissure and pterygopalatine fossa.

On MR, PNFs often appear as a bag of worms and are isointense on T1WI and hyperintense on T2WI. Strong, sometimes heterogeneous enhancement is common (26-33). A target sign of hypointensity within an enhancing tumor fascicle is seen in some benign PNFs.

NEUROFIBROMAS

Solitary Neurofibroma

• Most are sporadic (nonsyndromic)

• All ages (children to adults)

• Scalp, skin

• Rarely (if ever) involves CNs

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