Key points

Introduction

Central neurocytoma (CN), first described by Hassoun and colleagues in 1982, is classified by the World Health Organization as grade II. CNs are characterized as rare, neuronal differentiated tumors that account for less than 1% of all primary brain tumors and often affect young adults. CNs are typically located in the third ventricle or the anterior portion of the lateral ventricle, but there are rare cases of extraventricular neurocytoma in other locations, including spinal dissemination. Most neurocytomas have a benign clinical course with an excellent prognosis following surgical resection. As such, it is imperative to make an accurate diagnosis of CN to implement the optimal treatment modality to improve morbidity and mortality. Common differential diagnoses include oligodendrogliomas, ependymomas, non-Hodgkin lymphomas, and astrocytomas. This article discusses clinical features related to epidemiology, symptoms, radiology, and immunohistochemistry of CN and its rare variants.

Introduction

Central neurocytoma (CN), first described by Hassoun and colleagues in 1982, is classified by the World Health Organization as grade II. CNs are characterized as rare, neuronal differentiated tumors that account for less than 1% of all primary brain tumors and often affect young adults. CNs are typically located in the third ventricle or the anterior portion of the lateral ventricle, but there are rare cases of extraventricular neurocytoma in other locations, including spinal dissemination. Most neurocytomas have a benign clinical course with an excellent prognosis following surgical resection. As such, it is imperative to make an accurate diagnosis of CN to implement the optimal treatment modality to improve morbidity and mortality. Common differential diagnoses include oligodendrogliomas, ependymomas, non-Hodgkin lymphomas, and astrocytomas. This article discusses clinical features related to epidemiology, symptoms, radiology, and immunohistochemistry of CN and its rare variants.

Clinical presentation

Most CNs occur within young adults. Approximately 70% of all cases are reported in adults aged 20 to 40 years old, with the highest incidence of 25% in the third decade of life. The ages reported in the literature range from 8 days to 67 years, although pediatric manifestations tend to be rare.

CN is equally prevalent in males and females, although some authors suggest a male predominance. While, Sharma and colleagues suggest the possibility of a genetic predisposition that causes an increased incidence in Asian populations (particularly in India, Korea, and Japan), though most authors suggest that prevalence is equal for all races.

Symptoms

Initial clinical presentations develop gradually, as increasing obstructive hydrocephalus induces increased intracranial pressure. The most prevalent presenting symptoms are headache, dizziness, nausea, vomiting, papilledema, and ataxia caused by the lesion’s location within the ventricular system. Symptom duration generally lasts for a few months, with a reported range of several hours to 2 years.

Symptoms are caused, in part, by the tumor mass effect on the ventricles and occlusion of cerebral spinal fluid passage, resulting in intracranial hypertension. A total of 27 patients and their initial complaints were assessed by Schild and colleagues, in which 25 reported headaches, 10 reported visual complications, and eight reported nausea and vomiting, with symptom duration from 3 days to 2 years. The clinical presentation in this series is consistent with others found in the literature.

Other symptoms, such as persistent alteration in mental status, memory loss, ataxia, limb numbness, weakness, epilepsy, unsteady gait, and blurred vision, have been reported, although not as commonly. Intraventricular and intratumoral hemorrhage have also been observed in several cases, but is considered a rare occurrence for CN.

Imaging

CNs are intraventricular tumors located within the supratentorial ventricular system, near the foramen of Monro, and arise from the septum pellucidum, lateral ventricle walls, or third ventricle. According to Wong and colleagues, 77% of all typical CNs occur within the anterior lateral ventricles, whereas 21% occur within the lateral ventricles and extend into the third ventricle. They have also been reported in the fornix, corpus callosum, thalamus, and head of the caudate nucleus, although not as commonly. Hassoun and colleagues reviewed 127 cases where 98 were located within the lateral ventricle and 33 within the third ventricle.

Computed tomography scans usually show a well-circumscribed, isointense or marginally hyperdense mass that displays mild to moderate contrast enhancement. The mass appears midline, with an attachment to the lateral or superior ventricular walls. The appearance of hypodense areas signifies cystic degeneration, whereas calcification appears clumped, amorphous, and dotted.

T1-weighted MRI are generally heterogeneously isointense or hypointense, whereas T2-weighted MRI are hyperintense, and gadolinium-enhanced T1-weighted MRI are heterogeneously enhanced. On T1- and T2-weighted MRI, patches without signal or low intensity could be illustrative of a cyst or calcification. CNs are frequently described as having a spongy or a “soap bubble”-like appearance on MRI.

Magnetic resonance spectroscopy

Magnetic resonance spectroscopy (MRS) is used to provide characteristic biochemical information of CN. MRS demonstrating elevated glycine and choline, small or missing N -acetyl-aspartate (NAA) and creatine peaks, and absence of alanine or lactate can be indicative of CN. Elevated glycine originates from the glycinergic synapses of immature neurons from which CN are derived and the high levels of choline results from the highly dense and uniform cells without the presence of necrosis. Some authors suggest that the small or missing NAA is a result of the arrest of neurocyte differentiation in more mature neurons.

Immunohistochemistry

All CNs positively stain for synaptophysin on immunohistochemical evaluation due to their origins from glial and neuronal differentiation. In addition, the tumor may exhibit expression of neuron-specific enolase, neuronal nuclear antigen, and glial fibrillary acidic protein (GFAP). Synaptophysin and neuron-specific enolase are used to verify the neuronal origin of the lesion. Furthermore, neuronal nuclear antigen is used to confirm terminal neuronal differentiation in the tumor. GFAP expression, however, is important because cell passages in CN typically exhibit a shift from synaptophysin to GFAP expression. The bipotential characteristic of CN is indicative of the presence of GFAP immunopositive cells. In the study by Li and colleagues of 15 patients, all tumors expressed synaptophysin, whereas 12 expressed neuron-specific enolase and 3 expressed GFAP. Although not all tumors may express neuron-specific enolase or GFAP, synaptophysin positivity is typical in CN.

Histology

Characteristic cytologic features of CN are uniform isomorphic round cells, small lobulated nuclei with speckled chromatin, and areas of acellular fibrillar stroma or neuropils. The cells have scant eosinophilic cytoplasm and are typically arranged in sheets or rosettes, whereas the perivascular acellular areas and neuropils are spread into neuropil islands. Each individual case may have variations including the presence of calcification, small inconspicuous nucleoli (“fried egg” appearance), and long capillary-sized vessels, as first reported by Barbosa and colleagues in 1990. In 1999, Ng was the first to describe neurocytic rosette-like structures and perinuclear haloes. Although Sugita and colleagues also found similar features, they reported one case with large cells engulfing hemosiderin granules located between tumor cells. Their study suggested that this was a characteristic of CN, but similar findings have not been confirmed elsewhere.

Differential diagnosis

Oligodendrogliomas, non-Hodgkin lymphomas, ependymomas, and other tumors have overlapping features with CN. Thus, clinicians must distinguish between the tumor types to discern the most optimal treatment modality.

Oligodendrogliomas are the most common differential diagnosis for CN because of their similar cytologic characteristics. They are composed of a monomorphic cell group with scant cytoplasm, ill-defined nonfribrillary matrix, and a variegated pattern. Oligodendrogliomas and CN can have perinuclear haloes and calcospherites, but only CN has speckled chromatin, acellular neuropil islands, eosinophilic granular bodies, and rosette appearance. In addition, oligodendroglioma tends to have a less defined margin and its solid areas appear hypointense on T1-weighted MRI with a lower density on computed tomography scans.

Ependymomas are also considered within the differential diagnosis because they are one of the most common periventricular tumors. They appear as a monotonous round cell group with scant cytoplasm and oval nuclei. A crucial difference is that ependymomas have nuclear grooves, poorly formed acini, and fibrillary processes. Clear cell ependymomas, a distinct class of highly aggressive ependymomas, can also be distinguished from CN with their oval-shaped cells, long cytoplasmic processes, and nuclear grooves without perinuclear haloes.

Other less common differential diagnoses include lymphomas and astrocytomas. Non-Hodgkin lymphomas show a monotonous round group of cells with a blue cytoplasm arranged in a similar pattern as CN, but have lymphoglandular bodies that differ from CN neuropils. Subependymal giant cell astrocytomas have large cells containing grouped nuclei and eosinophilic cytoplasm. They also have a less defined margin than CN and have solid parts that appear hypointense on T1-weighted MRI.

Extraventricular neurocytomas

Extraventricular neurocytomas, first reported in 1989 by Ferreol and colleagues, are extremely rare and have similar histologic presentations as CN. They can be found within the cerebral cortex, thalamus, amygdala, retina, or even spinal cord through spinal dissemination. The most common site for extraventricular neurocytomas is in the frontal lobe, with the temporal, parietal, and occipital lobes following.

Extraventricular neurocytomas also affect young adults with a range of 5 to 76 years and a median of 34 years. Like CN, extraventricular neurocytomas have equal incidence in men and women. Zhu and colleagues reported a study of 17 patients, with an approximately equal gender distribution (10 males and 7 females) ranging from 4 to 41 years (mean, 27.4 years); 76% of these patients were between 20 and 40 years, consistent with the demographics of CN.

Patients typically present with symptoms caused by increased intracranial pressure and obstructive hydrocephalus. Huang and colleagues report in their study an average age of 25 years with a range of 11 to 37 years, who typically present with headache, dizziness, epileptic seizures, emesis, and cranial nerve paralysis; and in more rare cases hemiparesis, tinnitus, hemorrhage, and diplopia are noted. Lesions in the frontal and temporal lobe cause seizures, making it the most common symptom of extraventricular neurocytoma. Patients who present with headaches or hemiparesis often have tumors located within the frontal or parietal lobes, and those with diplopia, tinnitus, and other cranial nerve dysfunctions may have a tumor in the pons.

MRI for extraventricular neurocytomas displays similar characteristics as CN within their respective locations. Lesions located in the parietal and frontal lobes may demonstrate cystic degeneration, edema, hemorrhage, and heterogeneous enhancement. Govindan and colleagues report a cranial MRI showing a cystic mass in the right parieto-occiptal location with a cyst-mural nodule configuration and lower cellularity than typical CN. The cyst-mural nodule are typically only reported in extraventricular neurocytomas, not in CN. In addition, MRI appearance of extraventricular neurocytomas are described as less spongy than CN, although calcifications have the same appearance in both.

Few studies of MRS have been described in the literature for extraventricular neurocytomas, although they show similar results. In these reports, a missing NAA peak and large choline peak suggests extraventricular neurocytoma. Although NAA peak can appear in CN, it does not seem to be present for the extraventricular counterpart. Some authors reason that this is because the differentiated cells of extraventricular neurocytoma are still too immature to generate NAA.

Histologically, extraventricular neurocytomas display the same uniform round cells, speckled chromatin, and fine neuropils as their CN counterpart, but with a wider spectrum. They are also arranged in rosettes with neuropil islands and can develop calcification, capillary-sized vessels, and perinuclear haloes. Furthermore, they have similar immunohistochemical features as CN.