Central neurocytoma (CN) is an important consideration in the differential diagnosis of any intraventricular lesion. Initial evaluation should include noncontrast CT, MRI with and without gadolinium contrast, and magnetic resonance (MR) spectroscopy, if available. CN classically appear as a partially calcified mass on CT, arising from the septum pellucidum or foramen of Monro, with a soap-bubble multicystic appearance on MR T2-imaging and heterogeneous enhancement on MR T1 postcontrast imaging. MR perfusion/permeability and dynamic contrast imaging are experimental and promising tools in the diagnosis of CN.
Key points
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Central neurocytomas (CN) are classically found in the lateral or third ventricles, particularly in proximity to the septum pellucidum and the foramen of Monro; however, they can arise anywhere throughout the neuroaxis.
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On CT, CN appear as mixed density, partially calcified masses, and cysts and hemorrhage can occasionally be seen.
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On MRI, CN are isointense to brain on T1, have a “soap-bubble” multicystic appearance on T2, often exhibit fluid-attenuated inversion recovery hyperintensity, may have heterogeneous enhancement with gadolinium, and may have vascular flow voids; hemorrhage may be seen, but edema is usually minimal.
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A spectrum with an inverted alanine peak at 1.5 ppm, a notable glycine peak at 3.55 ppm, and the presence of N-acetyl aspartate (NAA) are most consistent with CN.
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Rarely, extraventricular or even spinal neurocytomas may be found. Similar characteristics of calcification, cystic components, associated hemorrhage, and vascular flow voids may be seen, although the characteristic cystic soap-bubble appearance is often absent.
Introduction: nature of the problem
Background/History
First documented in 1982 by Hassoun and colleagues, central neurocytomas (CN) are formally classified as a benign World Health Organization (WHO) grade 2 neoplasms of neural origin, arising from the glial cells lining the septum pellucidum and subependymal glial cells, particularly near the foramen of Monro. CN were initially considered to be an intraventricular variant of oligodendroglioma until pathologic analysis revealed cellular differences and a population of immature neurons, usually without anaplasia and with a low MIB-1 labeling index. Immunohistochemical analysis revealed that CN stained positive for synaptophysin, neuron specific enolase (NSE), and neuronal nuclear antigen, unlike oligodendrogliomas, and later genetic analysis revealed genotypic differences (absence of 1p,19q codeletion, and isocitrate dehydrogenase 1 [IDH1] mutations ). Further subtypes of neurocytomas have since been characterized, including extraventricular neurocytoma (EVN), which is officially recognized as distinct from CN by the WHO, and reports of spinal neurocytoma.
CN represent less than 0.5% of all cerebral neoplasms. As of 2006, 438 cases had been reported, and it is currently estimated that between 500 and 600 cases exist in the literature. The peak prevalence of CN is in the third through fifth decades of life, although cases in infants and the elderly have been described. Patients commonly present with symptoms of an intraventricular mass causing noncommunicating hydrocephalus, such as headaches (88%–90%) and visual disturbances (25%–38%). Motor symptoms (19.8%) and altered mental status (10.9%) have also been commonly reported. Rarely, seizures have been reported as the presenting symptom of EVN disease in the temporal lobe. CN and EVN may present with either intratumoral, intraparenchymal, or intraventricular hemorrhage, with all of the attendant sequelae of those processes. CN most commonly arise in the lateral and third ventricles, but reports of fourth ventricular, pineal, and aqueductal CN exist.
CN are a rare, but important consideration in the differential diagnosis of intraventricular lesions. Because CN are benign lesions that often have an excellent prognosis with gross total surgical resection compared with difficult, infiltrative, or higher-grade lesions (and particularly oligodendrogliomas ), establishing the diagnosis early may guide surgical planning and patient management. CN may not require postoperative radiation therapy depending on the extent of resection, unlike most gliomas. Fortunately, CN have several classical characteristics on CT, MRI, and magnetic resonance (MR) spectroscopy (MRS), which can assist clinicians in making the correct diagnosis.
Introduction: nature of the problem
Background/History
First documented in 1982 by Hassoun and colleagues, central neurocytomas (CN) are formally classified as a benign World Health Organization (WHO) grade 2 neoplasms of neural origin, arising from the glial cells lining the septum pellucidum and subependymal glial cells, particularly near the foramen of Monro. CN were initially considered to be an intraventricular variant of oligodendroglioma until pathologic analysis revealed cellular differences and a population of immature neurons, usually without anaplasia and with a low MIB-1 labeling index. Immunohistochemical analysis revealed that CN stained positive for synaptophysin, neuron specific enolase (NSE), and neuronal nuclear antigen, unlike oligodendrogliomas, and later genetic analysis revealed genotypic differences (absence of 1p,19q codeletion, and isocitrate dehydrogenase 1 [IDH1] mutations ). Further subtypes of neurocytomas have since been characterized, including extraventricular neurocytoma (EVN), which is officially recognized as distinct from CN by the WHO, and reports of spinal neurocytoma.
CN represent less than 0.5% of all cerebral neoplasms. As of 2006, 438 cases had been reported, and it is currently estimated that between 500 and 600 cases exist in the literature. The peak prevalence of CN is in the third through fifth decades of life, although cases in infants and the elderly have been described. Patients commonly present with symptoms of an intraventricular mass causing noncommunicating hydrocephalus, such as headaches (88%–90%) and visual disturbances (25%–38%). Motor symptoms (19.8%) and altered mental status (10.9%) have also been commonly reported. Rarely, seizures have been reported as the presenting symptom of EVN disease in the temporal lobe. CN and EVN may present with either intratumoral, intraparenchymal, or intraventricular hemorrhage, with all of the attendant sequelae of those processes. CN most commonly arise in the lateral and third ventricles, but reports of fourth ventricular, pineal, and aqueductal CN exist.
CN are a rare, but important consideration in the differential diagnosis of intraventricular lesions. Because CN are benign lesions that often have an excellent prognosis with gross total surgical resection compared with difficult, infiltrative, or higher-grade lesions (and particularly oligodendrogliomas ), establishing the diagnosis early may guide surgical planning and patient management. CN may not require postoperative radiation therapy depending on the extent of resection, unlike most gliomas. Fortunately, CN have several classical characteristics on CT, MRI, and magnetic resonance (MR) spectroscopy (MRS), which can assist clinicians in making the correct diagnosis.
Preimaging planning
Relevant Anatomy
CN typically arise in the lateral ventricles near the foramen of Monro ( Fig. 1 ), but may arise from any cerebral spinal fluid (CSF) space including the third ventricle and the fourth ventricles. EVN may be found in any location within the parenchyma, cranial nerves, sella, or even the skull base. In several series, the median size of CN at diagnosis is reported as 4.6 to 5.2 cm. CN range from subcentimeter asymptomatic lesions to up to 9 cm. EVN have variable appearance on imaging but are largely similar to CN. Although rare, spinal neurocytomas may be found with an associated syrinx or other sequelae of obstruction to CSF flow and may arise at any location within the spinal cord or nerve roots. Accordingly, the treating physician should select imaging modalities that will permit visualization of the entire cranial vault (or entire neuroaxis if spinal disease is suspected).
Choice of Imaging Modality
Noncontrast computed tomography scan
Traditionally the initial imaging modality for the evaluation of any potential intracranial process, CT is often obtained during the initial assessment of altered mental status and is often ordered by a general practitioner or in the emergency department. CT is usually the most rapid and facile neuroimaging modality, at the cost of exposure to ionizing radiation. In the diagnosis of CN, CT is particularly valuable in rapidly evaluating the status of the ventricular system and in looking for calcification. CT can sometimes be useful in diagnosing the location of CN, although the solid component of CN is often isodense to brain and small CN can be missed on CT.
Magnetic Resonance Imaging with and Without Gadolinium Contrast
MRI is typically the second step in the diagnostic algorithm for most intracranial lesions, unless a contraindication to CT scanning exists. Because the precise diagnosis will not be known at the time of ordering the MRI, it is wise to use a standard brain tumor protocol with specific sequences capable of evaluating midline and ventricular lesions. Most institutions have a standard brain tumor protocol that includes T1 precontrast and postcontrast, T2, and fluid-attenuated inversion recovery (FLAIR) sequences. Additional sequences such as gradient echo or proton density sequences can be helpful in diagnosing hemorrhage. Multiplanar imaging, particularly imaging in the sagittal plane, is necessary for midline lesions. In the setting of spinal lesions, an additional MRI of the relevant spinal levels should be obtained. Most spinal tumor protocols contain a fat-suppressed sequence such as short tau inversion recovery, which may be helpful for evaluating spinal neurocytoma.
Magnetic resonance spectroscopy
Because of the difficulty in making a definitive radiographic diagnosis using CT and conventional MRI, neuroradiology researchers have turned to MRS. MRS, traditionally performed using protons, allows a target region of interest to be examined for the presence and concentration of various target molecules. There is increasing interest in using MRS in combination with other advanced MR techniques to improve diagnostic yield and avoid operating on nonsurgical targets.
Digital subtraction angiography, computed tomography angiography, magnetic resonance angiography
Although not traditionally used for the evaluation of CN or other intraventricular tumors at the authors’ institution in the present era, there are reports of angiography performed to evaluate these lesions. Given the prominent flow voids and hemorrhagic features, it is reasonable to consider angiography or noninvasive vascular imaging (CT angiography [CTA]/MR angiography [MRA]) to rule out other associated vascular lesions and to visualize associated venous drainage for operative planning.
Diagnostic imaging technique
Noncontrast Computed Tomography Scan of the Head
For this disease entity, standard noncontrast CT scan protocols available at most institutions can be followed. Typically, a series of 3- or 5-mm width axial slices of the cranial vault is acquired. Specific protocols for CT scan integration with intraoperative neuronavigation may be used, although the authors’ preference is to navigate based on MRI scans. Contrast-enhanced CT scanning is generally not indicated because MRI with contrast will often be performed.
Magnetic Resonance Imaging Before and After Gadolinium Contrast
At the authors’ institution, they use commercially available MRI systems of either 1.5-T or 3-T field strength with standard MRI acquisition protocols. After localized scans in multiple planes are obtained, they proceed with a standard brain tumor protocol.
According to current brain tumor protocol, the authors routinely obtain axial T1 precontrast and postcontrast, T2 and T2 FLAIR, gradient echo T2, diffusion-weighted imaging, and associated apparent diffusion coefficient map as well as a thin-slice axial T1 postcontrast sequence of the entire head for neuronavigation. Additional sagittal and coronal plane imaging is obtained, typically at least a sagittal T1 postcontrast for midline pathologic abnormality and a postcontrast FLAIR sequence to evaluate for leptomeningeal disease. Further sequences are obtained at the discretion of the treating physician. The authors administer a commercially available, Food and Drug Administration–approved, gadolinium-based contrast agent for contrast.
Magnetic Resonance Spectroscopy
Proton MRI spectroscopy is obtained at the request of the treating physician. When available, a 3-T magnet may be used to improve signal-to-noise ratio and better separate metabolic peaks, although acceptable results have been reported throughout the literature using standard 1.5-T units. For a good overview of various MRS techniques, see a basic-science oriented summary by Drost and colleagues and the recent MRS consensus group paper.
Typically the authors perform MRS at a representative location completely within the target lesion, avoiding fat. Single or multiple locations may be sampled. A standard fluid-suppression technique (ie, Chemical Shift Selective or Inversion Recovery) and specific pulse sequence for spectroscopy such as stimulated echo acquisition mode or point resolved spectroscopy (PRESS) should be used based on institutional experience and preference. The authors recommend using PRESS with a echo time (TE) of at least 135 ms to allow differentiation between glycine and myoinositol (MI), in addition to a standard short TE technique. The obtained spectra can be specifically examined for lactate (1.30 ppm), alanine (1.48 ppm), NAA (2.02 ppm), Cr (3.0 ppm), Cho (3.22 ppm), and MI/Gly (3.55 ppm).
Interpretation/assessment of clinical images
Computed Tomography Scan
The appearance of CN on CT scan is highly variable. The tumor mass itself is typically isodense to brain parenchyma. Areas of hypodensity associated with cystic degeneration are not uncommon. Hyperdense calcification is typical, although far from universal: Osborn cites a 50% to 70% rate of calcification. When present, calcifications are usually partial or punctate. The size of CN may vary, from smaller subcentimeter lesions, usually found incidentally, to large biventricular lesions causing symptoms as previously described.
Ventricular abnormalities may also be seen. Hydrocephalus associated with larger, bilateral, or third ventricular lesions can occur and may require intervention, particularly if transependymal flow is seen. Acute hemorrhage, as mentioned previously, may be the presenting symptom of CN and may be intraventricular in the case of CN, or intraparenchymal with CN or more commonly EVN. Old blood products may be seen.
The use of contrast-enhanced CT is not particularly helpful in the diagnosis of CN. CN may appear avidly enhancing, heterogeneously enhancing, or completely nonenhancing.
Magnetic Resonance Imaging
MRI remains the preferred evaluation modality for establishing a preoperative diagnosis of CN. On MRI, CN are notably heterogeneous on all sequences owing to variable cystic, solid, vascular, calcified, and hemorrhagic components. At the time of diagnosis, the mean diameter of CN is approximately 4–5 cm in largest dimenson. MR T1-weighted sequences demonstrate solid, isointense components and hypodense areas consistent with calcification as well as allowing visualization of flow voids. T2 sequences show the bubbly, cystic appearance with bright hyperintense fluid and generally isointense solid components. In one study, this “classic” appearance was seen in 7 of 12 CN compared with 9 of 19 non-CN tumors of the foramen of Monro, making strict adherence to these characteristics somewhat nonspecific and nonsensitive. The presence of scalloping of the ventricular wall and spicules at the cyst border is reported to be more sensitive and specific for CN, although this is a subtle finding requiring significant subjective judgment. Enhancement with gadolinium contrast may be seen, although usually only heterogenous enhancement is observed. In the largest single hospital series, 36 of 78 (45%) CN enhanced after gadolinium. In one early series of 13 neurocytomas, 85% had cystic appearance on MRI, 69% had calcification, and 62% had vascular flow voids. Bowing of the septum pellucidum on coronal imaging may be seen. Importantly, peritumoral edema on FLAIR or T2 sequences is typically not seen.
Several studies have shown that CN may demonstrate restriction on diffusion-weighted imaging. This diffusion-weighted imaging restriction is greater than expected relative to both high-grade and low-grade astrocytomas and to other gliomas. The classic appearance of CN is demonstrated in Fig. 2 , a teaching case from the authors’ institution.
