CNS & pituitary tumors
Gliomas, glioneuronal tumors and neuronal tumors
Neuronal and mixed neuronal-glial tumors
Central neurocytoma
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Deputy Editor-in-Chief: Chunyu Cai, M.D., Ph.D.
Last author update: 2 June 2023
Last staff update: 11 October 2023
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PubMed Search: Central neurocytoma
Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Sites | Pathophysiology | Etiology | Diagrams / tables | Clinical features | Diagnosis | Radiology description | Radiology images | Prognostic factors | Case reports | Treatment | Clinical images | Gross description | Gross images | Frozen section description | Intraoperative frozen / smear cytology images | Microscopic (histologic) description | Microscopic (histologic) images | Virtual slides | Cytology description | Positive stains | Negative stains | Electron microscopy description | Electron microscopy images | Molecular / cytogenetics description | Molecular / cytogenetics images | Sample pathology report | Differential diagnosis | Additional references | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Child DD, Yoda R. Central neurocytoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/cnstumorcentralneurocytoma.html. Accessed December 21st, 2024.
Definition / general
- Rare, well differentiated, intraventricular neoplasm with neuroepithelial differentiation, typically arising near the foramen of Monro
Essential features
- Rare tumor, comprising 0.1 - 0.5% of all primary CNS neoplasms (J Neurooncol 2016;126:193)
- Intraventricular localization, usually involving the lateral or third ventricle(s) (Brain Pathol 1993;3:297)
- Clinical symptoms generally result from increased intracranial pressure due to obstructive hydrocephalus (Int J Radiat Oncol Biol Phys 2007;67:1145, J Clin Neurosci 2013;20:679)
- Microscopically appears as sheets of uniform, small - medium, round cells with fine chromatin stippling (salt and pepper) and occasional perinuclear clearing, interspersed with patches of fibrillary matrix (Brain Pathol 1993;3:297)
- CNS WHO grade 2 (Brain Tumor Res Treat 2016;4:49)
Terminology
- Central neurocytoma
ICD coding
- ICD-O:
- ICD-10:
- ICD-11:
Epidemiology
- ~0.1 - 0.5% of all primary brain tumors (J Neurooncol 2016;126:193)
- Overall incidence per 100,000 person years: 0.022, with individual rates varying by reported race (J Neurooncol 2019;143:123)
- Asian / Pacific Islander: 0.038
- Non-Hispanic White: 0.035
- Black: 0.026
- Hispanic White: 0.020
- Mean age at presentation: 20 - 34 years (J Neurooncol 2019;143:123)
- F:M = 1.02:1 (Brain Pathol 1993;3:297)
Sites
- Intraventricular mass, classically arising in the supratentorial ventricular system (Brain Pathol 1993;3:297)
- Anterior lateral ventricle (~50%)
- Lateral and third ventricle (~15%)
- Both lateral ventricles (~13%)
- Documented sites of origin include
- Foramen of Monro
- Septum pellucidum
- Corpus callosum
- Hypothalamus
- Large tumors may involve multiple sites
- Rarely reported in fourth ventricle and spinal cord (J Neurosurg 1994;81:288, Acta Neuropathol 2005;109:346, Mol Clin Oncol 2018;8:539)
- Neurocytomas occurring outside the ventricular system are termed extraventricular neurocytomas and are considered distinct entities (Acta Neurochir (Wien) 2014;156:349)
Pathophysiology
- Cell of origin
- Currently unknown, though favored to be a neuroglial progenitor cell due to dual differentiation potential (capable of forming both neurons and glial cells) (J Neurosci Res 1998;51:526, Lab Invest 1991;64:585)
- Frequent occurrence within lateral ventricle suggests origination from residual germinal matrix cells of subependymal plate (Lab Invest 1991;64:585, No Shinkei Geka 1995;23:1083)
- Infratentorial variants may arise from circumventricular organs (Acta Neuropathol 2005;109:346)
Etiology
- Unknown at this time
Diagrams / tables
Images hosted on other servers:
Coronal section diagram
Clinical features
- Most common presenting symptoms are related to increased intracranial pressure that is due to obstructive hydrocephalus (Int J Radiat Oncol Biol Phys 2007;67:1145, J Clin Neurosci 2013;20:679)
- Headache
- Vomiting
- Visual field changes
- Papilledema
- Presenting symptoms generally present for a short time prior to diagnosis (median: 1.7 - 3 months) (Int J Radiat Oncol Biol Phys 2007;67:1145)
Diagnosis
- Based primarily on histologic and immunophenotypic features (Brain Pathol 1993;3:297)
- Requires intraventricular localization, oligodendroglioma-like cytology and synaptophysin expression
- Correlation with radiologic studies (e.g., MRI, CT) is essential; supportive findings include
- Intraventricular localization (required)
- Enhancing, multicystic mass
- MRI: T1 isointense, T2 heterogeneous, FLAIR hyperintense
- CT: may show calcifications
- Methylation profiling may aid diagnosis in unresolved cases (J Neurooncol 2022;159:725)
Radiology description
- Noncontrast computed tomography (J Clin Neurosci 2013;20:679, Neurosurg Clin N Am 2015;26:11)
- Highly variable appearance, often with mixed solid and cystic components that appear isodense and hypodense, respectively, to surrounding brain parenchyma
- Calcifications may be seen, typically partial or punctate
- Evidence of hydrocephalus or hemorrhage may be visible
- Magnetic resonance imaging (J Clin Neurosci 2012;19:681, J Clin Neurosci 2013;20:679, Neurosurg Clin N Am 2015;26:11)
- Classically an intraventricular mass with a multicystic, soap bubble appearance characterized by T1 and T2 isointense solid components and T2 hyperintense, fluid filled cysts
- Peripheral cyst walls may form spicules and cause undulation of the adjacent lateral ventricle wall (scalloping)
- Calcifications and flow voids may be seen on T1 sequences
- Heterogenous contrast enhancement
- No surrounding peritumoral edema on T2 / FLAIR
- Proton magnetic resonance spectroscopy (Eur Radiol 2009;19:2049, J Clin Neurosci 2012;19:681, Neurosurg Clin N Am 2015;26:11)
- Characteristic glycine peak at 3.55 ppm
- Prominent choline peak
- Inverted alanine peak
Radiology images
Images hosted on other servers:
Intraventricular mass on MRI
Calcifications on CT
T1+C MRI
Prognostic factors
- Generally favorable prognosis (J Neurooncol 2016;126:193)
- 5 year overall survival rate: 96%
- 10 year overall survival rate: 82%
- Extent of resection is the only independent prognostic factor (Am J Surg Pathol 2012;36:220)
- Elevated proliferative index is associated with more aggressive behavior, with various thresholds proposed, but no single optimal cutoff established
- Proposed Ki67 thresholds: ~2 - 4% (J Neurooncol 2018;140:669, Neurology 2004;62:987, J Neuropathol Exp Neurol 1997;56:551, J Neurooncol 2016;126:193)
- e.g., Ki67 ≤ 4%: 90% 2 year progression free survival; Ki67 > 4%: 48% 2 year progression free survival (J Neurooncol 2016;126:193)
- Mitotic threshold of 3/10 HPF has been proposed (Am J Surg Pathol 2012;36:220, Int J Radiat Oncol Biol Phys 2007;67:1145)
- Proposed Ki67 thresholds: ~2 - 4% (J Neurooncol 2018;140:669, Neurology 2004;62:987, J Neuropathol Exp Neurol 1997;56:551, J Neurooncol 2016;126:193)
Case reports
- 8 year old girl with atypical central neurocytoma arising in the posterior fossa (BMJ Case Rep 2019;12:e231626)
- 13 year old boy with periventricular atypical central neurocytoma harboring unique WSR1::ATF1 fusion and MUTYH mutation (BMJ Case Rep 2019;12:bcr-2018-226455)
- 17 year old boy with right lateral ventricular central neurocytoma and intraventricular hemorrhage (Case Rep Surg 2022;2022:9731987)
- 48 year old man with atypical central neurocytoma and craniospinal drop metastases as well as concomitant pituitary macroadenoma (Asian J Neurosurg 2020;15:140)
- 79 year old woman with third ventricular central neurocytoma treated with gamma knife radiation (Medicine (Baltimore) 2018;97:e13657)
Treatment
- Surgical resection is standard of care (J Clin Neurosci 2013;20:1193)
- When complete resection is not possible, adjuvant radiotherapy improves survival (World Neurosurg 2020;137:e176)
- Adjuvant radiotherapy not recommended with complete resection of atypical central neurocytomas (Front Neurol 2020;11:834)
Clinical images
Images hosted on other servers:
Endoscopic view of intraventricular tumor
Gross description
- Gray, friable tissue (Brain Pathol 1993;3:297)
- May have macrocalcifications and hemorrhage (Brain Pathol 1993;3:297)
Gross images
Images hosted on other servers:
Intraventricular mass
Frozen section description
- Sheets of isomorphous, round cells in a fibrillary background
- Minimal pleomorphism
- Necrosis or mitotic figures are typically absent
- Reference: Acta Cytol 2004;48:194
Intraoperative frozen / smear cytology images
Contributed by Rebecca Yoda, M.D.
Cells with monotonous round nuclei
Intraoperative squash preparation
Microscopic (histologic) description
- Neuroepithelial neoplasm composed of uniform, small - medium cells growing in sheets with indistinct cytoplasm (Brain Pathol 1993;3:297)
- Nuclei are round with regular contours, finely stippled (salt and pepper) chromatin and micronucleoli
- Perinuclear clearing may be prominent (similar to oligodendrogliomas)
- Arborizing capillaries
- Large hyalinized blood vessels
- Other morphologic features may include
- Honeycomb-like architecture
- Patches of fibrillar, neuropil-like matrix mimicking pineocytomatous rosettes
- Perivascular pseudorosettes
- Homer-Wright rosettes
- Ganglioid cells
- Calcification is usually distributed throughout the tumor and may be prominent
- Lipomatous differentiation occurs rarely (World Neurosurg 2018;120:214)
- Hemorrhage is sometimes present; hemosiderin laden macrophages may be seen (Neurosurg Rev 2001;24:48)
- Designated as atypical central neurocytoma when anaplastic features are seen (J Neurosurg 1992;76:32, Brain Pathol 1993;3:297)
- Brisk mitotic activity
- Microvascular proliferation
- Necrosis
Microscopic (histologic) images
Contributed by Rebecca Yoda, M.D.
Circumscribed border
Fibrillary matrix
Perinuclear clearing
Perivascular pseudorosette
Neurocytic rosettes
Linear arrangement
Calcifications
Branching capillaries
Hyalinized vessels
Lipomatous change
Necrosis
Mitotic activity
Synaptophysin IHC
NeuN IHC
GFAP IHC
Contributed by Nazar M. T. Jawhar, M.D. (Case #119)
Circumscribed border
Perivascular pseudorosettes
Perinuclear clearing
Rosettes and perivascular pseudorosettes
Calcification
Linear cellular arrangement
Uniform, round cells
Virtual slides
Images hosted on other servers:
Left lateral ventricle tumor
Cytology description
- Cerebral spinal fluid cytology may be positive in the presence of disseminated tumor (J Neurosurg 1992;76:32)
- Crowded, cellular spheres composed of uniform small - medium cells
- Scant, cyanophilic cytoplasm on Papanicolau stain
- Neurocytic rosettes may be seen
- Squash preparations / direct smears (Acta Cytol 2004;48:194, Acta Cytol 2010;54:209)
- Monotonous, round cells with ill defined cytoplasm and without aggregation or clustering
- Nuclei tend to have finely granular chromatin and micronucleoli
- Hemosiderin laden macrophages or reactive astrocytes may be present
Positive stains
- Synaptophysin (Brain Pathol 1993;3:297)
- NeuN (Pathol Res Pract 2003;199:463)
- MAP2 (Brain Pathol 1993;3:297)
- Neuron specific enolase (Brain Pathol 1993;3:297)
- Ki67: cutoff for atypical central neurocytoma has not been established but suggested values range from ~2 - 4% (Neurology 2004;62:987, J Mol Biol 1989;210:709, J Neurooncol 2018;140:669, J Neuropathol Exp Neurol 1997;56:551)
- TTF1
- Clone 8G7G3/1 (7 - 21%) (World Neurosurg 2022;159:e62, Mod Pathol 2017;30:318)
- Clone SPT24 (47%) (Mod Pathol 2017;30:318)
Negative stains
- Chromogranin A (Brain Pathol 1993;3:297)
- Neurofilament (Am J Surg Pathol 2012;36:220)
- Olig2 (J Neurooncol 2017;135:57)
- GFAP: generally stains only entrapped astrocytes, though may be positive in rare cases (J Neuropathol Exp Neurol 1997;56:551, Acta Neuropathol 1996;91:573)
Electron microscopy description
- Not utilized in routine diagnostics
- Cells typically appear more uniform than on H&E preparations (Brain Pathol 1993;3:297)
- Nuclei (Brain Pathol 1993;3:297, Pathol Res Pract 1995;191:100, Acta Neuropathol 1997;94:425)
- Regular and round
- Finely dispersed chromatin
- Small, well defined nucleoli
- Cytoplasm (Brain Pathol 1993;3:297, Pathol Res Pract 1995;191:100, Acta Neuropathol 1997;94:425)
- Prominent golgi apparatus
- Abundant mitochondria
- Dumbbell shaped lysosomal inclusions
- Parallel microtubule arrays
- Membrane bound, dense core neurosecretory granules
- Matrix (Brain Pathol 1993;3:297, Pathol Res Pract 1995;191:100, Acta Neuropathol 1997;94:425)
- Numerous cytoplasmic projections separating adjacent cell bodies
- Occasional synapses
Electron microscopy images
Images hosted on other servers:
TEM showing neuronal features
Ultrastructure recapitulating neuropil and synapses
Molecular / cytogenetics description
- No known recurrent mutations or chromosomal imbalances (Acta Neuropathol 2018;136:181)
- Microarray analysis (Acta Neuropathol 2007;113:303)
- One study reports frequent copy number aberrations including frequent MYCN gain
- No strong sensitivity or specificity for any region
- Transcriptomic analysis showed overexpression of genes related to (Neuropathology 2013;33:149)
- Wnt / beta catenin signaling pathway
- Sonic hedgehog signaling pathway
- Calcium function
- Maintenance of neural progenitors
- Methylation profile is unique to central neurocytoma but cannot distinguish between classic and atypical variants (Acta Neuropathol 2018;136:181, J Neurooncol 2022;159:725)
- Negative for 1p / 19q codeletion (J Neurosurg 2002;97:1350)
Molecular / cytogenetics images
Images hosted on other servers:
DNA methylation based classification
Sample pathology report
- Brain, intraventricular mass, resection:
- Central neurocytoma, CNS WHO grade 2
Differential diagnosis
- Oligodendroglioma:
- Infiltrative growth
- IHC (J Neurooncol 2017;135:57)
- Strong and diffuse Olig2 positivity
- May be positive for IDH1 R132H
- Lacks diffuse neuronal differentiation (e.g., NeuN, synaptophysin)
- Molecular
- IDH1 / 2 mutation
- Chromosome 1p / 19q codeletion
- Infiltrative growth
- Ependymoma:
- Ganglioglioma:
- Mixed neuronal (ganglion cells) and glial neoplastic components
- IHC
- Positive for GFAP and CD56, frequently BRAF V600E positive (J Neurosci Rural Pract 2021;12:807, Pediatr Neurosurg 2019;54:36)
- Pineocytoma:
- Pineal region location
- IHC: positive for NFP (strong and diffuse)
- Distinct DNA methylation profile
- Choroid plexus papilloma
- Well developed papillary architecture
- IHC: positive for Kir7.1
- Subependymoma:
- Meningioma:
Additional references
Board review style question #1
A 29 year old woman with an intraventricular brain mass is diagnosed with a central neurocytoma with histologic findings shown above. Which of the following immunohistochemical stains is most likely to be diffusely positive in this neoplasm?
- Chromogranin
- GFAP
- Olig2
- Synaptophysin
Board review style answer #1
D. Synaptophysin. Synaptophysin expression is the most reliable diagnostic marker for central neurocytoma, which generally shows low to absent immunoreactivity for chromogranin, GFAP and Olig2.
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Reference: Central neurocytoma
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Reference: Central neurocytoma
Board review style question #2
Which of the following histological features is necessary for the designation of atypical central neurocytoma?
- Hypercellularity
- Lipomatous differentiation
- Macronucleoli
- Microvascular proliferation
Board review style answer #2
D. Microvascular proliferation: Brisk mitotic activity, necrosis and microvascular proliferation are the 3 histological features necessary for the classification of an atypical central neurocytoma. Answers A and C are incorrect because hypercellularity and macronucleoli are 2 of several criteria used for the diagnosis of an atypical meningioma but are not used to evaluate for atypical central neurocytoma. Answer B is incorrect because lipomatous differentiation may be seen in rare cases of central neurocytoma but does not confer an atypical designation.
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Reference: Central neurocytoma
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Reference: Central neurocytoma
