Extra-axial Tumors

Abstract

A variety of different neoplasms are united in the category of extra-axial brain tumors, ranging from benign to highly malignant entities, which often occur in distinct anatomical locations. Imaging features may include visibility of a CSF cleft or meningeal tumor base, and for some lesions, growth in the ventricular system is typical. Aggressive extra-axial tumors may invade the adjacent skull or brain. In many cases, the combination of patient demographics, lesion site and image signal generates a narrow list of differentials, or even a single diagnosis. Cancers and nonneoplastic conditions may mimic certain benign tumors, in some cases identifiable through subtle morphological differences. The following sections will discuss meningeal neoplasms, pineal region tumors, intraventricular tumors, and cranial nerve tumors with a focus on the value of clinical neuroradiology in their diagnosis. By the end of this chapter, readers will be familiar with characteristic and nonspecific imaging appearances of extra-axial tumors on different radiological techniques, able to devise a suitable imaging protocol based on lesion site, and to provide a comprehensive diagnostic report which can guide surgical planning and follow-up.

This publication is endorsed by: European Society of Neuroradiology (www.esnr.org).

Meningeal Neoplasms

The brain is covered by three meningeal layers: dura, arachnoid, and pia. The dura in turn consists of one outer sheet, which is attached to the inner table of the skull at the osseous sutures and one inner “arachnoid” sheet. Normal meninges are not readily delineated on clinical imaging, but it is often possible to distinguish tumors with a broad dural base from leptomeningeal lesions confined to the cortical surface.

Meningioma

Definition of Entity and Clinical Highlights

Meningiomas are extra-axial tumors arising from the inner layer of the dura. They share histological similarities with arachnoid cells and are believed to originate from a common meningothelial precursor, which could explain their propensity for location near the dural venous sinuses. Most meningiomas are indolent, whereby less than 10% ever become symptomatic. Large meningiomas may cause progressive signs of raised intracranial pressure, commencing with headaches and nausea. Depending on location, some meningiomas become quite large before causing specific signs, whereas smaller lesions can produce neurological deficits, occasionally seizures, when situated near eloquent cortex or cranial nerves.

Basic Epidemiology/Demographics/Pathophysiology

Meningiomas are the commonest adult intracranial tumor comprising approximately 25% of intracranial neoplasms. Typical locations include the cerebral convexity dura, falx, sphenoid bone, parasellar region, olfactory groove, and the cerebellopontine angle. With a peak in mid-age, they are more common in women (1:1.5–3) and may carry progesterone or estrogen receptors making them susceptible to hormonal influences. This theory is supported by enhanced meningioma growth in pregnancy, breast cancer, obesity, and during hormonal treatment for prostate cancer. Exposure to ionizing radiation represents an established risk factor with reported latency periods of up to 30 years (Wiemels et al. 2010). The molecular genetics and pathogenesis of meningioma are incompletely understood, especially in how far meningioma subtypes are distinct entities or arise from a pluripotent progenitor. Certain familial genetic predispositions, specifically NF2 and other tumor suppressor gene mutations, are associated with multiple meningiomas. The best-defined chromosomal aberration in meningioma is the tumor suppressor gene deletion on chromosome 22 in NF2 (present in >50% of meningiomas), but further mutations have emerged, which may influence tumor location and subtype. For example, cerebral convexity meningioma more often harbors chromosome 22 defects, and TRAF7/AKT1 tumors predominate anteriorly, exhibiting a meningothelial or transitional subtype (Clark et al. 2013). Matching their clinical course, 70–90% meningiomas are benign WHO grade I tumors. Atypical (WHO II) meningiomas constitute around 10% of tumors, and malignant meningiomas (WHO III) are rare (<1%). Multiplicity and malignant behavior occur more frequently in familial and syndromic meningiomatosis. Figure 1 shows histopathological examples of meningioma.

Fig. 1

Histopathology of meningioma (WHO grades I, II, III). Meningothelial meningioma (a, WHO grade I) shows uniform bland nuclei, no mitotic activity, and the histoarchitectural formation of tight whorls. Atypical meningioma (b, WHO grade II) (right) invades the brain (left). The tumor forms tongues and islands pushing against, and infiltrating the adjacent brain parenchyma. Anaplastic malignant meningioma (c, WHO grade III) shows histologically high grade features, including loss of the typical whorled histoarchitecture, formation of streams of tumor cells, high density of cells and a high mitotic rate (exceeding 20 mitoses per 10 high-power fields). Arrows highlight mitotic figures. Recently, a proportion of these tumors have been shown to have a mutation in the TERT promoter region (Goutagny et al. 2014)

Clinical Scenario and Indications for Imaging

As with most brain tumors, meningioma symptoms depend on the location rather than the tumor type. Sustained headaches, particularly when combined with a neurological deficit, should prompt urgent neuroimaging. Computed tomography (CT) permits rapid assessment for pathology requiring neurosurgical intervention. It can also provide clues to the diagnosis by depicting calcification and focal skull hyperostosis. MRI aids anatomical assessment of the tumor and surrounding structures at risk, in many cases leading to an unambiguous diagnosis of meningioma (Zakhari et al. 2017). Targeted thin-section MRI can provide additional information about relations to the visual pathways, cavernous sinus or cranial nerves in support of surgical planning. Advanced MR techniques are infrequently required but can add information in cases of atypical features or to selectively exclude differentials.

Imaging Features of Meningioma

Meningiomas are iso- to hyperattenuating on CT with up to 50% lesions showing punctate or diffuse calcifications. Hyperostosis is common, but bone destruction is rare and should prompt consideration of alternative etiologies. On MRI, most meningiomas show distinct borders, are T2-isointense or mildly hyperintense, and T1-isointense to hypointense to brain parenchyma. When visible, a CSF cleft surrounding the tumor confirms its extra-axial location. Almost all meningiomas display avid homogeneous enhancement (Fig. 2); they may have small capping cysts but large areas of necrosis are uncommon (Fig. 3) (Zakhari et al. 2017). An enhancing “dural tail” is typical but not pathognomonic. On diffusion imaging, meningiomas tend to exhibit mildly raised ADC compared to normal brain. Lower ADC signal has been reported in malignant and atypical meningiomas, yet diffusivity varies and seems to be an overall unreliable predictor of WHO grade (Santelli et al. 2010).

Fig. 2

Typical imaging features of meningioma. Case 1: CT showing calcified a cerebral convexity meningioma and associated hyperostosis (a–b). Case 2: T2w, ADC, Gadolinium T1w (c–e), and DSA (f) demonstrating a large petroclival meningioma encasing the basilar artery. Case 3: Small bilobed cerebral convexity meningioma (g) with tracer uptake on Ga-68-DOTA PET (h) and elevated DSC-derived rCBV (i). Case 4: Intraventricular meningioma (j). Case 5: Olfactory meningioma (k)

Fig. 3

Atypical meningioma (post-Gad T1w). Case 1: Centrally necrotic dural mass arising at the greater sphenoid wing (a–b); despite the unusual features, the histological diagnosis was WHO I meningioma. Case 2: Right frontal dural mass at presentation (c) and 5 months later (d) showing growth and peripheral irregularity. The tissue diagnosis here was atypical meningioma WHO II with evidence of brain invasion

Meningiomas are highly vascular tumors usually supplied by hypertrophied meningeal arterial branches with occasional recruitment of additional pial blood supply. The feeding vessels may be visible as central T2 flow voids. Occasionally, digital subtraction angiography (DSA) is indicated to inform surgical planning or with a view to embolization. Elevated perfusion parameters, such as rCBV and rCBF, are characteristic of meningiomas on dynamic susceptibility contrast-enhanced (DSC) and arterial spin labeling (ASL) studies; furthermore, permeability may be increased. Anaplastic and angiomatous subtypes show the highest perfusion parameters, but rCBV values can reach ≥7 even in benign meningiomas (Zhang et al. 2008). Associated vasogenic brain edema can occur independent of the size of the meningioma, whereby geographically extensive edema does not predict meningioma malignancy.

MR spectroscopy has a less well-defined role in supporting the diagnosis of meningioma, with a semi-specific Alanine peak identified at 1.48 ppm, which may be lacking in anaplastic grades. Up to 100% of meningiomas exhibit somatostatin receptors, which is exploited by nuclear medicine techniques such as gallium-68–labeled DOTA-D-Phe-Tyr3-octreotide-PET. As a caveat, false positive results can rarely occur in dural metastases, which share somatostatin receptor expression. Note also that certain cancer types (e.g. lung, breast) can occasionally metastasize into a meningioma.

Pitfalls and Meningioma Mimics

Rarely, benign meningiomas display features such as tumor cysts, brain invasion, or hemorrhage (Zakhari et al. 2017). Such atypical appearances do not equal high WHO grade, but they should raise concern regarding anaplasia or an alternative diagnosis. A recent study of dural masses, for which meningioma was reported as an imaging differential, identified >15 mimics including hemangiopericytoma, lymphoma, solitary fibrous tumors, schwannoma, metastases, plasmacytoma, and chordoma (Starr and Cha 2017). The following lesion attributes were highlighted as suggestive of mimics: homogeneous T2 hypointensity (as a sign of hypercellularity, e.g. in lymphoma) or marked T2 hyperintensity (reflecting high water content of cartilaginous/gelatinous tumors), bone destruction adjacent to the mass, leptomeningeal extension, and absence of a dural tail (Starr and Cha 2017). Specifically, heterogeneous enhancement may be a feature of metastases (Fig. 4). Nonneoplastic meningioma mimics include Ig4 disease, rheumatoid nodules, Rosai-Dorfman, and Castleman’s disease. A comparison of meningioma and its mimics is provided in Table 1.

Fig. 4

Malignant dural masses . Case 1: FLAIR and post-Gad T1w images (a–b) of a dural based frontal tumor featuring signal heterogeneity with reduced contrast uptake. Histological analysis revealed a breast cancer metastasis. Case 2: T2w hypointense, avidly enhancing mass (c–d) with irregular borders centered on the falx – biopsy proven as dural lymphoma. Diffusion restriction was lacking in this case (ADC map not shown)

Table 1 Meningioma versus mimics

Treatment Monitoring: Follow-Up Scheme and Findings/Pitfalls

Small asymptomatic meningiomas can often be safely followed up by serial imaging. For meningiomas requiring surgery, the target is resection of the entire tumor and dural tail. The recurrence rate of WHO I meningioma is low (around 10%) but higher for anaplastic lesions (up to 80% for WHO III meningioma). Meningiomas are radiosensitive, which is widely utilized as part of primary therapy and for recurrent tumors. Gamma knife radiosurgery is increasingly used as a minimally invasive treatment for meningiomas. In particular, this is advantageous for lesions with difficult surgical access, for example, near the skull base. Gamma knife therapy is only suitable for small (<2–3 cm) lesions, can produce unwanted brain parenchymal injury (radiation necrosis), and is subject to dose limitations. The type and frequency of follow-up imaging for meningioma should be oriented on lesion grade and location, for example, tumors near the visual pathway may require additional high-resolution sequences to depict anatomical relations in detail.

Hemangiopericytoma (Solitary Fibrous Tumor Spectrum)

Definition of Entity and Clinical Highlights

Hemangiopericytomas are low-grade malignant neoplasms of mesenchymal differentiation. Their exact origin remains controversial; they probably stem either from pericytes, which are undifferentiated smooth muscle cells surrounding capillaries and venules, or from fibroblasts. In the latest WHO classification, dural hemangiopericytomas are classified as the more aggressive subgroup within the spectrum of solitary fibrous tumors. They may arise anywhere that capillaries are found, including the soft tissues of the head and neck, extremities, and body. Because of more rapid growth, hemangiopericytomas may become symptomatic earlier than meningioma.

Basic Epidemiology/Demographics/Pathophysiology

Hemangiopericytomas are rare, representing less than 1% of all primary CNS tumors and 2–4% of meningeal neoplasms. Their occurrence is most common in middle age (4th–5th decade), younger than meningioma with a mild preponderance in men. Chromosomal aberrations have been suspected as a possible influencing mechanism, but there is currently no well-known risk factor. Since the 2007, WHO classification of CNS tumors, hemangiopericytoma, and solitary fibrous tumor have been combined into one disease spectrum. Within this classification, solitary fibrous tumors are WHO I lesions, whereas hemangiopericytomas are WHO grade II or III tumors. Hemangiopericytomas are most commonly supratentorial, in locations similar to meningioma but are more aggressive locally and can produce extracranial metastases (e.g., bone, lung, and liver). Figure 5 shows histopathology examples of solitary fibrous tumor/hemangiopericytoma.

Fig. 5

Histopathology examples of solitary fibrous tumor/hemangiopericytoma according to the three-tiered grading system (WHO grade I, II, and III) based on histological criteria regarding cellularity, mitotic activity, and presence of necrosis (Louis et al. 2014). Solitary fibrous tumor/hemangiopericytoma (a, example WHO grade III) is a highly cellular tumor composed of patternless and haphazardly orientated sheets of moderately pleomorphic cells with round to ovoid nuclei and scanty cytoplasm, and brisk mitotic activity (arrows). An essential diagnostic criterion is the immunohistochemical detection of nuclear expression of the STAT6 protein (b), a result of a fusion of the NAB2 and STAT6 genes (Chmielecki et al. 2013; Robinson et al. 2013)

Clinical Scenario and Indications for Imaging

Clinical circumstances may be indistinguishable from meningioma, except that patients tend to be more likely symptomatic at discovery. Imaging plays an important role in the identification of hemangiopericytoma, firstly for accurate estimation of the anatomical tumor extent, but also because this may be the first time point at which concern regarding a nonmeningioma diagnosis is raised. In confirmed hemangiopericytoma, body staging (CT, PET/CT) should form part of the initial workup.

Imaging Features of Hemangiopericytoma

On CT, the most common finding is that of a isodense or mildly hyperdense, noncalcified dural based mass. This is characteristically accompanied by adjacent skull destruction and transcranial extension (Fig. 6). As a differentiating feature from meningioma, hyperostosis does not occur and intratumoral calcification is exceedingly rare (Pang et al. 2015). On MRI, the typical finding is of a lobulated dural based mass arising from the falx, tentorium, or near dural venous sinuses. On first glance, hemangiopericytoma may resemble a meningioma but often returns a more heterogeneous signal, with solid areas isointense to brain on T1 and T2, and many hemangiopericytomas are large reaching 4–5 cm. This is often in contrast with a relative paucity of perilesional edema. Gadolinium contrast enhancement is pronounced and may be homogeneous or heterogeneous with foci of necrosis, or less commonly cyst formation. A dural tail may be present in up to 50%, whereby the appearance of the dural attachment varies from broad-based to narrow resembling more a “mushroom configuration” (Sibtain et al. 2007). Hemangiopericytomas are hypervascular, often to a greater extent than meningioma, and usually contain large flow voids. Angiography classically shows a dual dural-pial vessel supply and can guide preoperative embolization to reduce bleeding risk. No specific advanced imaging features exist, although myo-inositol (3.56 ppm) has been proposed as a possible differentiating feature from meningioma (Barba et al. 2001).

Fig. 6

CT and MR features of hemangiopericytoma. Parietal vertex noncalcified mass with CT evidence of bone destruction (a). T2w, ADC, and post-Gad T1w MR images (b–d) in the same patient demonstrate a large dural tumor with internal heterogeneity, multiple vascular flow voids, and avid enhancement

Treatment Monitoring: Follow-Up Scheme and Findings/Pitfalls

Although 5-year survival lies in the region of 80%, hemangiopericytomas have a propensity for local recurrence, therefore maximum safe resection is desirable. Long-term imaging follow-up is mandatory, as disease relapses have been observed many years later. Hemangiopericytomas are not chemotherapy sensitive and results on the benefit of radiotherapy are conflicting (Champeaux et al. 2017; Zhang et al. 2017), which limits adjuvant options. For small volume disease relapses, gamma knife radiosurgery might be useful to achieve local disease control.

MR Imaging Technique and Recommended Protocol for Meningeal Tumors

Standard Brain Tumor protocol

• Axial T2

• T2-FLAIR (isotropic 3D desirable)

• Precontrast T1 (isotropic 3D desirable)

• DWI (b0, b1000)

• Postcontrast T1 (isotropic 3D desirable)

NB – Axial angulation to follow hypophysis-fastigium line

Additional Imaging

For tumors near the skull base, orbit, or cavernous sinus consider:

• Thin-section (≤3 mm) T2, pre- and post-Gadolinium T1 in ≥2 planes

• if possible, apply fat saturation to post-Gad T1

For atypical masses in proximity to skull consider

• High convolution kernel CT to assess for osseous destruction

Occasionally, meningeal tumors may benefit from perfusion, spectroscopy, and/or nuclear medicine imaging, which should be considered on a case by case basis.

Interpretation Checklist and Structured Reporting for Meningeal Tumors

• Description of primary tumor

  • Location, size

  • Intra-axial/extra-axial

  • Tumor extent/relation to surrounding structures

  • Mass effect upon the ventricles/basal cisterns/herniation

  • T2 signal intensity and ADC (suggestive of high cellularity?)

  • Calcification

  • Enhancement intensity and pattern

  • Relation to eloquent structures (at risk?), dural venous sinuses

  • Other lesions

• Peritumoral signal abnormalities:

  • Vasogenic edema

  • Bone abnormality (hyperostosis versus destruction)

  • For treated tumors, also comment on surgical defects, post-chemoradiation leukoencephalopathy or other features suggestive of therapy-related changes

Pineal Region Tumors

Pineal region tumors are overall rare (1% of CNS masses), and most commonly occur in children and young adults. As the predominant group, these include pineal germ cell tumors, consisting of numerous subtypes. Distinct from this are pineal parenchymal neoplasms; furthermore, tumors of the surrounding brain may advance into the pineal region.

Germ Cell Tumors

Definition of Entity and Clinical Highlights

Pineal germ cell tumors (GCT) are thought to arise from pluripotent stem cells, which subsequently differentiate into their definitive cell type. It remains unknown, if this developmental process occurs at the definitive tumor site or is facilitated by embryological cell migration. The most common pineal GCT is germinoma (syn. dysgerminoma) with a cellular composition equivalent to its gonadal counterpart, testicular seminoma. “Nongerminomatous ” GCT consist of several subtypes: mature and immature teratoma, embryonal carcinoma, choriocarcinoma, yolk sac tumor, and mixed lesions.

Clinical signs are initially nonspecific with neurological symptoms developing progressively, ranging from headaches to nausea and vertical gaze palsy (“Parinaud syndrome”) heralding dorsal midbrain compression. Endocrine disturbances (e.g., precocious puberty) can occur, more so for germ cell tumors involving the pituitary region. It should be noted that in infants, signs of raised intracranial pressure can be nonspecific including apathy, irritability, or developmental delay.

Basic Epidemiology/Demographics/Pathophysiology

The reported incidence of intracranial GCT varies from approximately 1–2% of all CNS tumors up to 10–15% of pediatric brain tumors in Asia, where GCT appear more frequent. Germinoma is the most common pineal region tumor, contributing around two thirds of brain GCT with a mean onset at 17 years (range 10–30 years) and predominance in males. Teratoma is the second most common (15–20%) intracranial GCT and may present in the neonatal period as a large, sometimes holocranial mass (Jennings et al. 1985). It is believed to arise from embryonic stem cells early in the third and fourth week of gestation. Both immature and mature teratoma may contain a mixture of all three cell layers with the latter being defined by greater cell differentiation, which may correspond to a less aggressive clinical course. Pineal choriocarcinoma is a rare (5%), highly malignant neoplasm, with a mean onset at 12 years, often accompanied by metastases at presentation. GCT occurs sporadically but can be associated with in Klinefelter (XXY) syndrome, Down syndrome, and other chromosomal abnormalities including TP53 tumor suppressor gene mutations. All intracranial GCT types have a predilection for the midline, which may have embryological origins, with the pineal region being the predominant site for germinoma. GCT WHO grades range from I to III, whereby germinoma falls into WHO II. Figure 7 shows histopathological appearances of germinoma and embryonic carcinoma.

Fig. 7

Histopathology of germinoma and embryonal carcinoma. Germinoma is a malignant germ cell tumor. The tumor cells are large and have a pleomorphic appearance with prominent nucleoli and abundant clear cytoplasm (a, black arrow). The majority of germinomas contain a substantial population of associated reactive lymphoid cells (blue arrow). Germinomas express the transcription factor OCT3/4 in the nucleus of the large tumor cell component (b). This example of a mixed germ cell tumor with embryonal carcinoma component (c) shows large pleomorphic epithelioid cells with prominent nucleoli showing a solid architectural arrangement. Mitotic activity, including bizarre profiles, is frequent (arrows). Embryonal carcinoma with diffuse membranous staining for CD30 on immunohistochemistry (d) . (Courtesy of Prof. S. Brandner, London)

Clinical Scenario and Indications for Imaging

Patients typically present with hydrocephalus secondary to aqueduct obstruction, and/or with Parinaud syndrome, consisting of upward gaze paralysis and impaired convergence. Nongerminomatous GCT are often larger causing greater neurological compromise at the time of diagnosis. The identification of CSF oncoproteins (β–HCG, α-fetoprotein, placental alkaline phosphatase) plays an important role in the confirmation and differential diagnosis of GCT. In fact, the most important predictor of tumor type is the combination of patient age and specific tumor marker elevation (Packer et al. 2000). Signs of hydrocephalus such as sustained headaches and nausea, with or without gaze palsy, are indications for urgent imaging.

Imaging Features of Pineal Germ Cell Tumors

Depending on size, some pineal lesions are easily overlooked on CT, unless the midline is specifically reviewed. Germinomas may show increased attenuation due to high cellularity. On MRI, GCT may not initially appear pineal in origin, as they tend to surround or engulf the gland (Fig. 8). Germinomas appear T1 isointense and T2 iso- to mildly hyperintense and typically display moderately avid homogeneous enhancement. Bithalamic tumor extension and marked edema have been proposed as specific features of germinoma, which could allow a distinction from pineal parenchymal masses (Awa et al. 2014). Cystic-necrotic areas and hemorrhage are occasionally seen, if tumors become large. Diffusion restriction occurs and ADC values tend to be higher in germinoma than in pineoblastoma (Choudhri et al. 2015).

Fig. 8

Imaging of pineal germinoma. CT image (subsequent to shunt insertion for hydrocephalus) showing a hyperattenuating lesion engulfing the calcified pineal gland (a). T2w, ADC, and post-Gad T1w images (b–f) of the same patient demonstrating a pineal region, on first glance bithalamic appearing mass

Fig. 9

Pineal embryonal carcinoma (with permission from Fang AS, Meyers SP. Insights Imaging. 2013 Jun;4(3):369–82). The tumor involving the pineal gland (arrow) has lobulated margins with intermediate to high signal on axial T2-weighted image (a). The tumor shows heterogeneous contrast enhancement on sagittal T1-weighted image (b) related to its solid and cystic portions

Mature teratomas are often readily identified by imaging due to their mixed fluid, fat and tissue content, sometimes featuring calcification or even formed teeth. Fat-suppression and susceptibility weighting can be useful adjuncts to characterize tissue elements. For the rare primary intracranial choriocarcinoma, heterogeneity with markedly T2-hypointense areas, T1 shortening indicative of hemorrhage, and heterogeneous, ring-like, or intratumoral nodular enhancement have been recognized as potentially typical features, which may permit diagnosis in combination with HCG levels to avoid biopsy of this easily disseminating tumor (Lv et al. 2010). Few imaging descriptions exist of yolk sac tumor with no specific features identified to date.

Treatment Monitoring: Follow-Up Scheme and Findings/Pitfalls

Pure germinomas are sensitive to radiation and chemotherapy with approximately 80–90% of patients surviving beyond 5 years. Other GCT have an overall worse prognosis, with outcome strongly dependent on the histological subtype. Long-term follow-up should include not only brain imaging but also post-Gadolinium sequences of the whole spine, as spinal dissemination is common. The sacral thecal termination must always be included as part of spine imaging, so not to miss this potential location for drop metastases.

Pineal Parenchymal Tumors

Definition of Entity and Clinical Highlights

Pineal parenchymal tumors develop from pineocytes or their embryological precursors. They consist of pineocytoma (WHO I), pineal parenchymal tumor of intermediate differentiation (WHO II-III) and pineoblastoma (WHO IV). Their clinical presentations are similar as for GCT, dictated by anatomical location. Due to proximity of the aqueduct and tectal plate, even smaller pineal tumors can become symptomatic.

Basic Epidemiology/Demographics/Pathophysiology

Pineal parenchymal tumors account for a smaller proportion (around 15%) of pineal region masses. They are overall more common in children and young adults but may arise at all ages equally in both genders. Pineocytoma is the most frequent (45%) and slow growing subtype with a good 5-year survival of approximately 85%. Pineoblastomas are undifferentiated neoplasms with highly malignant behavior (WHO IV) and a dismal prognosis (approximate survival 1.5–2 years). They are relatively common (35–40% of pineal parenchymal tumors) and almost universally produce obstructive hydrocephalus, signifying their rapid proliferation. Pineoblastoma may rarely be encountered as a triad of “trilateral retinoblastoma,” caused by RB1 mutation(s) on chromosome 13q14, with neuroendocrine retinal and pineal common precursor cells becoming genetically susceptible to tumor growth (de Jong et al. 2015).

Pineal parenchymal tumors of intermediate differentiation neither fulfill the histological criteria for pineocytoma or pineoblastoma and are classed in between (WHO II). Papillary tumors of the pineal gland were first recognized as a morphologically distinct entity in the 2007 WHO classification; they are rare neuroepithelial neoplasms with an adult onset (mean 30 years), thought to originate from specialized ependymal cells of the subcommisural organ, a structure of incompletely known function bordering the third ventricular aqueduct. This tumor subgroup is yet to be fully defined, but its biological behavior known to date appears to correspond to WHO grade II–III. Figure 10 shows histopathology features of pineal parenchymal tumors.

Fig. 10

Histopathology of pineal parenchymal tumors. Pineoblastoma (a, WHO grade IV) The histoarchitecture of pineoblastomas typically shows highly cellular patternless sheets of small round blue cells. Cells have hyperchromatic nuclei and scanty eosinophilic cytoplasm. Pineoblastoma mitotic activity is usually brisk (with an associated high Ki67 proliferation index) (b). The Ki67 antigen is expressed during the cell cycle and a sensitive indicator for proliferation. Pineal parenchymal tumor of intermediate differentiation (c, WHO grade II/III) with solid diffuse sheets and lobules of mildly pleomorphic cells with rounded nuclei, stippled chromatin pattern, and frequent peri-nuclear clearing in a fibrillary background with occasional pseudorosettes (arrow). Pineocytoma (d, WHO grade I): sheets of tumor cells, resembling pinealocytes, with small round uniform nuclei, stippled chromatin set within a coarsely granular/fibrillary neuronal matrix. Occasional pineocytomatous rosettes are also observed (arrows) . (Courtesy of Dr. Z. Jaunmuktane, London)

Imaging Features of Pineal Parenchymal Tumors

There is significant overlap of radiological features for pineal region masses, which limits the accuracy of imaging to predict tumor subtypes. Certain features can be useful clues to the most likely diagnosis prior to tissue and tumor marker results: whereas GCT tend to engulf the pineal gland from the periphery, pineal parenchymal tumors grow more centrally, characteristically resulting in an “exploded” appearing calcification pattern. Pineocytomas tend to be smaller tumors, though this is not universally the case (Fig. 11a–e). They typically display low to intermediate T1 and (mildly) raised T2 signal with variably avid enhancement and sometimes contain cysts. When cysts are present in pineocytoma, these typically show thick, nodular rim enhancement (Lensing et al. 2015). Several studies performed to date found no evidence for pineocytoma meeting the criteria for a simple cyst (Fig. 11f–g), suggesting that long-term follow-up in such circumstances is unnecessary.

Fig. 11

CT and MR imaging of pineocytoma. Case 1: CT image (a) of an isodense pineal mass with punctate peripheral (“exploded”) calcifications displaced anteriorly. T2w, ADC, pre- and post-Gad T1w sequences (b–e) in the same individual showing a well-defined, solid-cystic enhancing tumor with heterogeneous, slightly increased ADC signal to normal brain. Case 2: Not a tumor: Typical appearances of a unilocular simple pineal cyst (f–g) without solid elements. Minimal, thin wall enhancement is present, reflecting normal gland elements

Pineoblastomas are often large, poorly marginated masses with peripheral calcification that exhibit diffusion restriction as a sign of high cellularity (Fig. 12). This can be matched by hyperattenuation on CT, intermediate to low signal on T2 with marked, commonly heterogenous contrast uptake, which may be accompanied by visible infiltration of surrounding brain. Despite the aggressive nature of pineoblastoma, vasogenic edema is not necessarily present. Prominent glutamate and taurine peaks have been encountered on MRS of pineoblastoma.

Fig. 12

CT and MR imaging of pineoblastoma. Eccentric pineal tumor displaying increased CT attenuation (a), T2w hypointensity and low diffusion (b–d) suggestive of high cellularity, accompanied by avid contrast uptake (e–f)

No unique imaging findings have emerged for pineal parenchymal tumors of intermediate differentiation, but they are usually larger and more heterogeneous than pineocytoma, sometimes invading surrounding brain (Komakula et al. 2011).

Papillary pineal tumors may appear similar to pineocytomas; in several cases, intrinsic T1 shortening has been observed together with Gadolinium enhancement and cystic foci (Fig. 13). Occasionally, T1 shortening in the form of hemorrhage may be present in pineal lesions complicated by apoplexy.

Fig. 13

MR image examples: Case 1: Pineal parenchyma tumor of intermediate differentiation (a–d), with T2w, postcontrast features and diffusivity intermediate between pineocytoma and pineoblastoma. Case 2: Papillary tumor of the pineal gland (e–g) exhibiting greater internal heterogeneity due to small cysts

Treatment Monitoring: Follow-Up Scheme and Findings/Pitfalls

For staging and follow-up, spinal imaging postcontrast should be included; up to 15% of pineoblastomas may show evidence of spinal dissemination at presentation. Despite maximum safe resection plus adjuvant radiation and chemotherapy, pineoblastoma may recur rapidly and requires frequent, vigilant monitoring.

Tectal Plate Glioma

Tectal plate gliomas are rare (<5% of childhood brainstem tumors) intrinsic neoplasms initially separate from the pineal gland, which can sometimes be discovered incidentally. In the vast majority, they are indolent WHO II astrocytomas with a favorable prognosis, and observation represents therefore the standard care. On imaging, they are usually small, of similar T1 signal to brain and mildly T2 hyperintense, with absent or subtle contrast enhancement (Fig. 14) (Igboechi et al. 2013). Very rarely, tectal plate gliomas may show significant progression and therefore short-term follow-up is recommended initially until stable behavior has been demonstrated. In some cases, CSF diversion may become necessary for obstructive hydrocephalus.

Fig. 14

MRI of tectal plate glioma. T2w, T1w pre- and post-Gadolinium images (a–c) demonstrating a small T2-hyperintense, nonenhancing tumor separate from the pineal gland

Imaging Technique and Recommended Protocol for Pineal Region Tumors

Standard Brain Tumor Protocol

• Axial T2

• T2-FLAIR (isotropic 3D desirable)

• Precontrast T1 (isotropic 3D desirable, if only 2D must include thin section (≤ 2 mm) images in at least 2 planes – sagittal desirable)

• DWI (b0, b1000)

• Postcontrast T1 (isotropic 3D desirable, if only 2D must include thin section (≤ 2 mm) images in at least 2 planes – sagittal desirable)

NB – Axial angulation to follow hypophysis-fastigium line

Additional Imaging

• Thin-section heavily T2-weighted steady state sequences (e.g. CISS, FIESTA) in at least 2 planes including sagittal midline views

• For all pineal tumors, perform post-Gad T1 whole spine (≤3 mm) staging to screen for drop metastases

• In cases of uncertainty regarding leptomeningeal dissemination, consider double dose contrast +/− postcontrast FLAIR brain imaging

Interpretation Checklist and Structured Reporting for Pineal Region Tumors

• Description of primary tumor

  • Location, size

  • Pineal calcification central or peripheral (“exploded”)

  • Tumor extent/relation to surrounding structures (bithalamic extension?)

  • Mass effect upon the aqueduct/ventricles/basal cisterns

  • T2 signal intensity and ADC (suggestive of high cellularity?)

  • Enhancement intensity and pattern

  • Cysts

  • Other lesions? Coexisting pituitary mass?

• Peritumoral signal abnormalities:

  • Vasogenic edema

  • For treated tumors, also comment on surgical defects, post-chemoradiation leukoencephalopathy or other features suggestive of therapy-related changes

  • Assess for intracranial and spinal leptomeningeal dissemination

• Consider clinical factors for interpretation

  • Patient age, sex

  • Tumor marker results, if available

Intraventricular Tumors

The upcoming chapter will focus on primary tumors of the ventricular lining and choroid plexus. It should be noted that a variety of other tumors, which preferentially occur elsewhere may occasionally arise inside ventricles (e.g. meningioma) or invade these (glioblastoma, lymphoma, craniopharyngioma). Ventricular involvement may also occur in systemic malignancy and inflammatory conditions.

Ependymoma

Definition of Entity and Clinical Highlights

Ependymomas probably derive from radial glia, which are periventricular stem cells supporting neuronal development and migration in the embryonic central nervous system. Ependymomas may develop anywhere along the ventricular margins, but some can appear solely intraparenchymal. Supratentorial tumors are often larger at presentation, presumably because hydrocephalus takes longer to develop compared to the posterior fossa.

Basic Epidemiology/Demographics/Pathophysiology

Ependymomas constitute around 2% of primary CNS tumors in adults (with a peak in the 30s) and are the third most common (5–6%) childhood brain tumor, with infratentorial ependymomas occurring at a younger age (mean 5 years). Overall, infratentorial location dominates (70%), and a slight male predilection has been inconsistently reported. Ependymoma is classified as a WHO II tumor, and anaplastic ependymoma as WHO III. However, the histological grading of ependymoma has been controversial, and there is lack of association between tumor grade and patient outcome (Pajtler et al. 2017).

By now, several molecular subgroups of ependymoma have been defined according to key (epi)genetic alterations, which predict prognosis and may inform future targeted therapies. Among posterior fossa ependymomas, group A occurs in infants exhibiting a CpG island methylator phenotype with poor survival, whereas group B tumors occur in older children and adults associated with a better outcome. In the supratentorial compartment, YAP1 mutant ependymomas affect younger children with excellent survival (approaching 100%), whereas RELA fusion tumors recur rapidly with dismal outcomes (Pajtler et al. 2017). Figure 15 demonstrates ependymoma histopathology appearances.

Fig. 15

Histopathology of ependymoma. Ependymoma (a, WHO grade II): a glial tumor, which typically shows on low power magnification a distinctive pattern resembling leopard skin, formed by characteristic anucleate zones around a central tumor vessel (ependymal pseudorosettes – arrows). Anaplastic Ependymoma (b, WHO grade III): Highly cellular, densely packed, and moderately pleomorphic tumor cells with brisk mitotic activity, florid microvascular proliferation (arrows) and associated surrounding ependymal pseudorosettes. Importantly, the histological grade does not correlate with clinical outcome. A number of molecular signatures have been described and are prognostically more relevant (Pajtler et al. 2017).

Imaging Features of Ependymoma

Ependymomas tend to be isodense to mildly hyperdense on CT, frequently (50%) containing coarse calcification and occasionally (10%) hemorrhage. A combination of cysts (which may be larger in supratentorial tumors), blood product and calcification is suggestive of the diagnosis (Fenchel et al. 2012). Ependymomas are typically iso- to hypointense T1w and iso- to hyperintense on T2w, displaying heterogeneous contrast enhancement. Tumors may appear molded into the fourth ventricle, bulging outwards through the foramina of Luschka and/or Magendie. The diffusion signal of posterior fossa ependymomas tends to be intermediate (Fig. 16) between WHO I (pilocytic astrocytoma) and medulloblastoma, but overlapping ADC values limit specificity. On perfusion MR studies, ependymomas often demonstrate intermediate blood volume, with greater rCBV representing a potential predictor of poor outcome (Tensaouti et al. 2016). Ependymomas do not have a specific metabolite pattern on MRS.

Fig. 16

MRI features of ependymoma. Case 1: T2w, T2*w, ADC, and T1w post-Gadolinium images (a–f) showing a heterogeneous, barely mineralized mass with patchy avid enhancement protruding through the fourth ventricular foramina. Case 2: Differential diagnosis – note slightly greater diffusivity of ependymoma (d) compared to lower ADC signal in the solid elements of medulloblastoma (g–h)

Treatment Monitoring: Follow-Up Scheme and Findings/Pitfalls

The overall outcome of ependymoma is good approaching a 10-year survival of 80%, but this varies by subtype. Increased knowledge of molecular factors will likely support prognostication and treatment planning in years to come. To date, unequivocal survival benefits have been shown for maximum resection and adjuvant radiotherapy. A proportion (<15%) of ependymomas show spinal dissemination at presentation so that whole neuroaxis staging is mandatory. Leptomeningeal dissemination, evident as smooth or nodular enhancement (Fig. 17), is common in relapse therefore spine imaging should also form part of long-term ependymoma follow-up. Always ensure inclusion of the sacral thecal sac margins on imaging, because this is a common site for drop metastases (Yuh et al. 2009).

Fig. 17

Image example of spinal drop metastasis. Post-Gadolinium T1w images showing a subtle thoracic leptomeningeal deposit (a), which is more readily appreciated on the axial corresponding image (b)

Subependymoma

Definition of Entity and Clinical Highlights

Subependymomas are rare, slow growing neoplasms of low malignant potential, the exact origin of which remain unknown. As implied by nomenclature, subependymomas arise immediately beneath the ventricular wall. They share features of ependymal and glial cell lineage, with astrocytoma elements coexisting in some subependymomas. 5% to 20% of subependymomas may harbor foci of classic or even anaplastic ependymoma. Despite being slowly proliferative, subependymomas may produce obstructive hydrocephalus, more so below the tentorium.

Basic Epidemiology/Demographics/Pathophysiology

Subependymomas make up <1% of CNS neoplasms. Their natural clinical course is mostly benign and often lesions remain asymptomatic over years. The peak incidence is in mid-life (4th–6th decade) with a predominance in men and occurrence in childhood is rare. Subependymomas most commonly (60%) arise at the margins of the fourth ventricle in the region of the foramen of Magendie, and if small can be easily overlooked on imaging. Less commonly and mostly in adults, subependymomas may develop in the lateral ventricles, where they may be larger at discovery. Figure 18 shows histopathology findings in subependymoma.

Fig. 18

Histopathology of subependymoma. Subependymomas (WHO grade I) are mild to moderately cellular tumors composed of clusters of small round nuclei within ample fibrillary matrix. Subependymomas are subtypes of ependymomas and are included in the molecular stratification of ependymal tumors (Pajtler et al. 2017)

Imaging Features of Subependymoma

Most subependymomas are well defined smooth or lobulated intraventricular masses. They are often, though not universally small (1–2 cm). Being hypo- or isoattenuating, subependymomas can be challenging to visualize on CT. On MRI, T1w hypointense to isointense and T2w hyperintense signal is typical (Fig. 19); enhancement can vary and may be absent (Bi et al. 2015). Lack of contrast uptake can be a helpful distinguishing property in contrast to ependymoma, subependymal giant cell astrocytoma and neurocytoma, all of which predominantly enhance. Microcysts are common, sometimes only appreciated on histological evaluation; hemorrhage and calcification are only occasionally present, usually in larger lesions. Vasogenic edema is not a feature of subependymoma and should prompt consideration of an alternative diagnosis. Limited benefit can be expected from advanced imaging of subependymoma, which shows low cerebral blood volume and no specific spectroscopic features.

Fig. 19

MRI features of subependymoma. T1w and T2w images demonstrating a small, innocuous mass in the fourth ventricular outflow tract. This lesion has remained stable over several years, demonstrating imaging features typical for subependymoma (no tissue diagnosis)

Treatment Monitoring: Follow-Up Scheme and Findings/Pitfalls

For asymptomatic lesions morphologically consistent with subependymoma, observational management is considered an appropriate strategy. In cases, where surgery is performed because of symptoms or to secure the diagnosis, curative resection is achievable for most patients. CSF seeding can occasionally complicate subependymoma, and therefore spinal screening should complement the primary work up.

Central Neurocytoma

Definition of Entity and Clinical Highlights

This tumor type arises from neural progenitor cells in the septum pellucidum and often grows in proximity to the foramen of Monroe. While neurocytoma is known to resemble oligodendroglioma on microscopic inspection, its neuronal origins can be distinguished readily on a molecular basis with IDH and 1p19q genes being preserved. Central neurocytoma produces symptoms (headaches, nausea, and visual disturbances) secondary to raised intracranial pressure; occasionally focal neurological deficits ensue.

Basic Epidemiology/Demographics/Pathophysiology

Central neurocytomas are rare (0.5% of CNS neoplasms) sporadic tumors, which arise at any age with a peak in the 3rd–5th decade of life. They are categorized as WHO II neoplasms and only rarely show anaplastic behavior. Despite being uncommon overall, central neurocytomas contribute up to 50% of intraventricular tumors for 20–40 year olds and should be considered as a differential particularly in this age range. No risk factor or syndromic association has been established. A histopathology example of central neurocytoma is provided in Fig. 20.

Fig. 20

Histopathology of central neurocytoma. Central neurocytoma (a, WHO grade II) has a distinctive histological appearance with rounded monomorphic cells and formation of thin perinuclear clear rims, so-called halos. Central neurocytomas are neuronal tumors and therefore strongly express the neuronal protein synaptophysin (b)

Imaging Features of Central Neurocytoma

Accurate midline delineation, especially demonstration of attachment to the septum pellucidum supports the diagnosis of central neurocytoma and informs operative planning. Central neurocytoma infrequently results in CSF dissemination, and therefore whole neuro-axis screening may be considered during initial workup.

Central neurocytomas are often large, measuring several centimeters at diagnosis. They are identifiable on CT imaging, appearing variably isodense or hyperdense with frequent (50–70%) calcification. On MRI, heterogeneous signal with a “soap-bubble” T2 appearance is characteristic (Fig. 21) (Donoho and Zada 2015). Enhancement is usually irregular, but approximately half of all neurocytomas lack contrast uptake. Some lesions may contain visible vascular flow voids or blood product, and occasionally intratumoral hemorrhage can be the first clinical presentation. Neurocytomas most commonly occupy one lateral ventricle but can involve both lateral ventricles or the third ventricle. They are exceedingly rare in the fourth ventricle. Overall similar features have been reported for extraventricular neurocytoma (Donoho and Zada 2015), which has been suspected to be a more aggressive disease variant. Perfusion MRI may demonstrate intermediate rCBV values, typically lower than in meningioma and glioblastoma. Neurocytomas may have high Cho/Cr ratios, belying their low malignant potential, and a peak at 3.55 ppm has been reported, which may link to presence of glycine (Liu et al. 2012).

Fig. 21

Imaging of central neurocytoma. Case 1: T2w, FLAIR, ADC, and T1w post-Gadolinium images (a–e) of a large, markedly heterogeneous neurocytoma within the right lateral ventricle draped along the septum pellucidum (displaced to the left). Case 2: As a possible differential, subependymal giant cell astrocytoma (SEGA, f–g) can occur in a similar location but is often identifiable by hallmarks of tuberous sclerosis such as calcified subependymal nodules (h)

Treatment Monitoring: Follow-Up Scheme and Findings/Pitfalls

The optimal management of neurocytomas remains controversial with research limited by the rarity of the disease. Surgery is the principal treatment for central neurocytoma and often (65–75%) curative with 5-year survival exceeding 90% (Rades et al. 2005). Radiotherapy has been shown to improve local disease control and progression free survival for incompletely resected neurocytomas. For small volume disease recurrence, gamma knife radiosurgery has been trialed with some success.

Choroid Plexus Tumors

Definition of Entity and Clinical Highlights

These rare neoplasms of neuroectodermal origin arise from choroid plexus secretory epithelium. As a unique clinical feature, choroid plexus tumors may not only obstruct the ventricular system but cause secretory hydrocephalus through overproduction of CSF. They generally present with features of elevated intracranial pressure and prior to cranial suture closure may cause an enlarging head circumference with a bulging fontanelle.

Basic Epidemiology/Demographics/Pathophysiology

Choroid plexus tumors are the most common brain neoplasm under the age of 1. They overall contribute 2–5% of childhood CNS neoplasms with >85% presenting by 5 years and are uncommon in adults. Any intracranial site containing choroid plexus may be affected; in children lateral ventricular papillomas predominate, and in adults the fourth ventricle is more commonly affected. Overall, supratentorial location (50%) slightly exceeds incidence in the fourth ventricle (40%). Choroid plexus papillomas (WHO I) are by far the most common (>80%). The remainder are atypical papillomas (WHO II) or choroid plexus carcinomas (WHO III). Carcinomas afflict young children, usually arising de novo rather than from papillomas. Associations have been reported with Aicardi and Li-Fraumeni syndromes and Simian Virus 40, which has also been isolated in ependymoma (Bergsagel et al. 1992). Heritable p53 tumor suppressor gene mutations are present in up to 40% of carcinomas but rarely in papillomas. For this reason, genetic testing is indicated in children with choroid plexus carcinoma to determine the risk of future malignancies (Gozali et al. 2012). Figure 22 shows histopathology examples of choroid plexus tumors.

Fig. 22

Histopathology of choroid plexus tumors. Choroid plexus papilloma (a, WHO grade I): Fibrovascular papillary fronds lined by a single layer of uniform cuboidal/columnar cells composed of basally located monomorphic oval nuclei. There is practically no mitotic activity. Choroid plexus carcinoma (b, WHO grade III) show loss of the papillary architecture and form a more solid architecture. The tumor cells are pleomorphic, with hyperchromatic nuclei and prominent nucleoli. Mitotic figures are frequent (arrows) and many tumors have areas of necrosis and hemorrhage and some can also infiltrate into adjacent brain parenchyma (not shown)

Clinical Scenario and Indications for Imaging

Indications for imaging are as for other intraventricular masses. One specific consideration for suspected choroid plexus tumors is that of high bleeding risk. In addition to high-resolution anatomical imaging for tumor characterization, angiography may be considered in concerning cases.

Imaging Features

Choroid plexus tumors vary in size, commonly measuring several centimeters at the time of discovery with attenuation equal to or slightly greater than normal brain. On MRI, papillomas are typically well defined, and when present, a fine-lobulated “cauliflower” morphology is distinctive (Fig. 23). T1 signal is isointense to hypointense, and T2 signal isointense to mildly hyperintense, displaying avid enhancement with variable internal heterogeneity. Small tortuous or stippled flow voids may be observed as a sign of hypervascularity (Yan et al. 2013). Approximately one-third of choroid plexus tumors may show calcification. Cystic-necrotic foci and perilesional edema occur more frequently in anaplastic papillomas and carcinoma and may be interpreted as a suspicious feature (awaiting Fig. 24 – choroid plexus carcinoma). Owing to their vascularity, choroid plexus tumors may demonstrate markedly raised rCBV on perfusion studies.

Fig. 23

MRI appearances of choroid plexus papilloma. T2w and post-Gadolinium T1w images (a–d) of an enhancing choroid plexus papilloma in the fourth ventricle. Best appreciated on the enhanced sequences, the tumor surface has characteristic fine lobulations (“cauliflower morphology”), and there is subtle internal signal heterogeneity (“stippling”)

Fig. 24

MRI example of choroid plexus carcinoma. T2w, ADC, T1 pre- and post-Gadolinium images showing a solid, avidly enhancing mass in the posterior fossa featuring cystic-necrotic components. (Courtesy of Dr. C. Dudau, Kings College Hospital, London)

Treatment Monitoring: Follow-Up Scheme and Findings/Pitfalls

Surgical resection is the standard of care and often curative for papilloma with almost 100% patients surviving to 5 years. For atypical papillomas and carcinomas, removal may be subtotal due to greater disease extent or intraoperative bleeding, with recurrence being more common. Chemotherapy and radiotherapy have shown outcome benefit for progressive lesions, but in young children, radiation should be avoided wherever possible to avoid damage to the developing brain. Papillomas can rarely disseminate to the spinal leptomeninges.

Epidermoid and Dermoid Cysts

Definition of Entity, Clinical Highlights, and Demographics

Epidermoids are squamous epithelial remnants, thought to be entrapped during neural tube closure in early gestation around 3–5 weeks. Dermoid cysts in addition contain dermal elements such as hair, sweat glands, mineralization, or teeth. Epidermoid cysts often adopt a paramedian position within the cerebellopontine angle or the parasellar region, possibly due to developmental lateralization (otic capsule formation) (Nagasawa et al. 2011). Rarely, epidermoids undergo malignant transformation to squamous cell carcinoma or become infected following surgical manipulation. Dermoids are more often located in the midline and enlarge more rapidly than epidermoids, thereby becoming symptomatic at a younger age (typically 2–3rd decade). Figure 25 demonstrates histopathology findings of inclusion cysts.

Fig. 25

Histopathology of inclusion cysts. Epidermoid cysts (a) form from ectopic (displaced) remnants of epithelium. Histologically, they resemble the surface of the skin (stratified squamous epithelium – black arrow); and like the skin, they shed keratin flakes, which form the cyst contents (blue arrow). Dermoid cysts (b) have the same pathogenesis as epidermoid cysts but contain additional skin adnexal structures such as hair follicles (arrow)

Imaging Features of Dermoid/Epidermoid Cysts

Epidermoids characteristically appear bright on diffusion-weighted images, and do not enhance, or take up minimal contrast peripherally (Fig. 26). Calcification may occasionally be present. In a proportion of lesions, T1 shortening may be present (“white epidermoid”). The combination of fat, fluid, solid tissue +/− calcium defines a dermoid cyst (synonym mature teratoma).

Fig. 26

Imaging example of an epidermoid cyst. Pathognomonic diffusion restriction (a–b) and paucity of Gadolinium uptake (c) within the mass

Treatment Monitoring: Follow-Up Scheme and Findings/Pitfalls

The surgical cure rate depends on lesion type and location but for epidermoids lies in the region of 80%. Residual lesions may grow slowly over years, or in some cases remain entirely stable. For epidermoids, DWI is the most important MR sequence during follow-up and is well suited to distinguish postoperative changes from residual tumor. Fat sensitive sequences such as T1 but also SWI may be helpful to identify and monitor small fat droplets of dermoids, e.g., following intervention or in the context of previous cyst rupture. Susceptibility effects of fat are attributable to chemical shift properties (Mehemed et al. 2013).

MR Imaging Technique and Recommended Protocol for Intraventricular Tumors

Standard Brain Tumor Protocol

• Axial T2

• T2-FLAIR (isotropic 3D desirable)

• Precontrast T1 (isotropic 3D desirable, if only 2D must include thin section (≤2 mm) images in at least 2 planes – sagittal desirable)

• DWI (b0, b1000)

• Postcontrast T1 (isotropic 3D desirable, if only 2D must include thin section (≤2 mm) images in at least 2 planes – sagittal desirable)

NB – Axial angulation to follow hypophysis-fastigium line

Additional Imaging

• To delineate anatomical relations, consider thin-section T2-weighted sequences (e.g., CISS, FIESTA)

• Perform post-Gad T1 whole spine (≤3 mm) staging to exclude for drop metastases

• In cases of uncertainty regarding leptomeningeal dissemination, consider double dose contrast +/− postcontrast FLAIR brain imaging

Interpretation Checklist and Structured Reporting for Intraventricular Tumors

• Description of primary tumor

  • Location, size

  • Intra-axial/extra-axial

  • Tumor extent/relation to surrounding structures (foraminal obstruction, hydrocephalus?)

  • Mass effect upon the basal cisterns/herniation

  • T2 signal intensity and ADC (suggestive of high cellularity?)

  • Enhancement intensity and pattern

  • Calcification, hemorrhage, fat or multiple tissue elements?

  • Other (ventricular) lesions

• Peritumoral signal abnormalities:

  • Vasogenic edema

  • Spinal leptomeningeal metastases?

  • For treated tumors, also comment on surgical defects, post-chemoradiation leukoencephalopathy or other features suggestive of therapy-related changes

Cranial Nerve Tumors

Primary cranial nerve tumors almost exclusively consist of schwannoma. Secondary tumors occur in the form of perineural malignant spread, e.g., from sinonasal cancers or melanoma. Meningioma may grow along intracranial nerve sheaths, and nonneoplastic diseases such as sarcoid may also involve the cranial nerves. The upcoming chapter is focused on primary neoplasms.

Schwannoma

Definition of Entity and Clinical Highlights

Schwannomas are named after their origin from peripheral nerve myelinating “Schwann” cells. They are mostly slow growing, encapsulated tumors. Symptoms arise due to proximity to eloquent structures, namely other cranial nerves and the brainstem. Clinical presentations vary by tumor location – for vestibular schwannoma, complaints include asymmetric hearing loss (75%), imbalance (20%), and tinnitus (<20%). Hydrocephalus may develop due to lesions sited in the posterior fossa, reflecting the limited space of the compartment.

Basic Epidemiology/Demographics/Pathophysiology

Schwannomas constitute around 5–10% of adult CNS tumors. They almost exclusively (≥90%) arise from the vestibular branch of the VIIIth cranial nerve, showing an average growth rate of 1 mm/year. The remaining schwannomas preferentially affect sensory nerves, with exception of the olfactory and optic nerves, in which Schwann cells are absent. Germline mutations (SMARCB1 or LZTR1 tumor suppressor genes) have been identified in 86% of familial and 40% of sporadic schwannomatosis patients (Kehrer-Sawatzki et al. 2017). Bilateral schwannomas occur in association with NF2 tumor suppressor gene on chromosome 22. The role of NF1 in the development of intracranial schwannomas is not clear and has not been well explored biologically (Scott et al. 2013). Growth in the first year of observation appears to be an important predictor of vestibular schwannoma biological behavior: tumors that show evidence of early progression and atypical features such as hemorrhage or macrocysts will often expand at up to 4 mm/year (Paldor et al. 2016). Two different types of histological composition are distinguished in schwannoma: Tightly comprised cells (Antoni A) and loosely packed, less cellular regions with cyst formation and microscopic hemorrhages (Antoni B). It has been suggested the predominance of Antoni B in large schwannomas could be responsible for their growth through creating a cycle of dystrophic tumor proliferation and hypoxia. Typical histopathology features of Schwannoma are shown in Fig. 27.

Fig. 27

Histopathological features of Schwannoma. Schwannomas usually have a distinctive histoarchitecture (a) with spindled hyperchromatic nuclei, aligning in alternating parallel rows and forming nuclear palisades (arrows). Schwannomas can have two distinct histoarchitectural features, the so-called Antoni A and Antoni B areas. Compact Antoni A areas (b, left) and looser textured, edematous Antoni B areas (b, right) with associated hyalinized vessels

Imaging Features of Schwannoma

Schwannomas are non-calcified masses, which may range from millimeters to centimeters in size, with an “ice cream on a cone” shape being typical. There are no specific CT features for schwannoma, which may be difficult to identify when small, in the absence of necrosis or hydrocephalus. The combination of location and natural benign behavior is most predictive of the diagnosis. Schwannomas are iso- to hypointense on T1 and iso- to hyperintense on T2 with avid contrast enhancement, variably containing cystic-necrotic foci (Fig. 28).

Fig. 28

Imaging of Schwannoma. Case 1: Typical T2w and post-Gadolinium T1w appearances of a large cerebellopontine angle schwannoma, containing cystic-necrotic foci presumed to represent “Antoni B” elements (a–c). Case 2: T2w steady-state, T1w pre- and post-Gadolinium images of a small, predominantly solid appearing vestibular schwannoma (d–f) with a typical “ice-cream on a cone” shape and avid enhancement

Treatment Monitoring: Follow-Up Scheme and Findings/Pitfalls

Because many vestibular schwannomas are slowly proliferative, a proportion can be conservatively managed. Surgery is often curative with a recurrence rate below 10%. The choice of the surgical approach depends on lesion accessibility and on the presence of nerve deficits. Generally, the aim is to especially preserve intact functions, e.g., a subtotal resection may be chosen for a lesion in proximity to the facial nerve when there is no deficit (Xu et al. 2017). For smaller lesions, stereotactic surgery can be a less invasive alternative.

Note that diagnosing every internal auditory meatus tumor as vestibular schwannoma can become a pitfall (Fig. 29): Occasionally, malignancy and nonneoplastic diseases (granulomatosis, sarcoid, viral infections including HIV) may produce nerve enhancement, with or without a mass.

Fig. 29

Pitfall case. Although vestibular schwannoma is by the far the most common diagnosis for cerebellopontine angle lesions, this is not universally the case. T2w steady-state, T1w pre- and post-Gadolinium images (a–d) showing biopsy proven Wegener’s disease. Mixed signal involvement of the middle cerebellar peduncle with a punctate focus of enhancement (arrow) and heterogeneity of the IAM lesion served as first clues for an alternative diagnosis here. Also note that metastatic disease may occasionally strike in this location

Neurofibroma

Neurofibromas are exceedingly rare in the cranial cavity and more commonly occur as sporadic spine tumors or as somatic hallmarks of NF1. They can occasionally develop in the region of the trigeminal ganglion (Fig. 30).

Fig. 30

Imaging example of intracranial neurofibroma. T1w post-Gadolinium images (a–b) showing a rare case of trigeminal neurofibroma. Trigeminal schwannoma could appear morphologically similar in this location . (Courtesy of Dr. W. Mbatha, London)

MR Imaging Technique and Recommended Protocol for Cranial Nerve Tumors

Standard Brain Tumor Protocol

• Axial T2

• T2-FLAIR (isotropic 3D desirable)

• Precontrast T1 (isotropic 3D desirable, if only 2D must include thin section (≤ 2 mm) images in at least 2 planes – sagittal desirable)

• DWI (b0, b1000)

• Postcontrast T1 (isotropic 3D desirable, if only 2D must include thin section (≤ 2 mm) images in at least 2 planes – sagittal desirable)

NB – Axial angulation to follow hypophysis-fastigium line

Additional Imaging

• To delineate anatomical relations, consider thin-section T2-weighted sequences (e.g., CISS, FIESTA) in ≥2 planes (ideally axial and coronal)

• Perform thin-section (≤1 mm) pre- and post-Gadolinium imaging in ≥2planes (ideally axial and coronal)

• For subtle pathology, aim to visualize the cranial nerve “end on”

Interpretation Checklist and Structured Reporting for Cranial Nerve Tumors

• Description of primary tumor

  • Location, size

  • Intra-axial/extra-axial

  • Tumor extent/relation to surrounding structures (especially brainstem)

  • Extent into IAM

  • Mass effect on the ventricles/basal cisterns? Hydrocephalus?

  • Any lesional or perilesional features inconsistent with Schwannoma

  • Other (enhancing) lesions

  • Check contralateral IAM

• Peritumoral signal abnormalities:

  • Vasogenic edema

  • For treated tumors, also comment on surgical defects, post-chemoradiation leukoencephalopathy or other features suggestive of therapy-related changes

Example Case and Report

Clinical indication: 75-year-old female with a short history frontal headaches followed by facial droop and left limb weakness? Acute pathology.

Imaging reports (case shown in Fig. 31):

Fig. 31

Case example showing CT (a, b) and MR (c–f) images of a right frontal mass under investigation

CT: Noncontrast study. A right frontal mildly hyperattenuating noncalcified mass with a dural base is shown measuring approximately 4.5 cm, surrounded by parenchymal low attenuation in keeping with edema. There is significant mass effect with midline shift to the left. The frontal bone overlying the tumor demonstrates lysis with indistinct margins. Typical features of hyperostosis are absent.

Conclusion: Brain tumor, likely extra-axial. The bone destruction is unexpected for a meningioma, therefore the differential includes malignancy.

MRI: T2w, T2w-FLAIR, DWI/ADC, T1w pre- and post-Gadolinium images were obtained.

Comparison is made with the recent CT dated xx/xx/xx.

A large T2w hyperintense extra-axial mass is shown arising from the right frontal dura measuring 4.7 × 4.3 cm in maximum axial diameter. The tumor exhibits avid, mildly heterogeneous enhancement. There is contrast uptake and diffuse thickening of the right cerebral convexity dura and falx. Surrounding edema contributes to mass effect with midline shift to the left including subfalcine herniation. There is right frontal bone contrast uptake in the region of the bone destruction (as shown on the recent CT), suggesting localized infiltration. No further intracranial lesions are evident.

Conclusion: Dural tumor, suspicion for malignancy.

Final result: The histological diagnosis in this case was plasmocytoma.