Neuropathology tumours

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A brain stem astrocytoma. (WC)

The article covers tumours in neuropathology. Tumours are a large part of neuropathology. Cytopathology of CNS tumours is dealt with in the article CNS cytopathology.

There are separate articles for peripheral nerve sheath tumours and pituitary/peri-pituitary lesions.

Brain tumours - overview


For overview see here

By age group


Four most common types of brain tumours:[1]

  1. Metastatic brain tumours (barely edges out primary tumours)
  2. Glioblastoma, IDH-wildtype.
  3. Astrocytoma, IDH-mutant.
  4. Meningioma.


  1. Pilocytic astrocytoma.
  2. Medulloblastoma.
  3. Ependymoma.
  4. Pontine glioma, often Diffuse midline glioma, H3 K27-altered.

By location

Certain tumours like to hang-out at certain places:[2]



Sella turcica

less common:

Spinal cord

Filum terminale


less common:

  • Melanoma / Melanocytoma.
  • Lymphoproliferative diseases.
  • Sarcoidosis
  • Arachnoid cyst.
  • Disseminated oligodendroglial-like leptomeningeal tumour.
  • Desmoplastic infantile astrocytoma / ganglioglioma.
  • Meningioangiomatosis.
  • Calcifying pseudoneoplasm.


Skull base / Cerebellopontine angle

less common:

Primary versus secondary

  • AKA (primary) brain tumour versus metastatic cancer.


Glial tumours:

  • Cytoplasmic processes - key feature.
    • Best seen at highest magnification - usu. ~1 micrometer.
    • Processes may branch.
  • Ill-defined border/blend with the surrounding brain.


  • Lesion often dura-based.
  • Mesenchymal tumor (often contains collagen).


  • Primary CNS Lymphoma (PCNSL) is usu. a diffuse large B-cell lymphoma.
  • Large (lymphoid) cells, ergo usu. not a difficult diagnosis.
    • ~2x size of resting lymphocyte, nucleoli.
  • Lesion predominantly perivascular.


  • Carcinomas:
    • Well-demarcated border between brain and lesion - key feature.
    • No cytoplasmic processes.
    • Usu. have nuclear atypia of malignancy.
    • Nuclei often ~3-4x the size of a RBC.
    • +/-Glandular arrangement.
    • +/-Nucleoli.
  • Melanoma.
  • Secondary Lymphoma.
  • Sarcomas (rare).

By growth pattern

Infiltrative astrocytomas


    • Glial: "blends into brain"/gradual transition to non-tumour brain.

Non-infiltrative astrocytomas

Cystic tumours



    • Non-glial: no radiating glial processes.
  • Rosenthal fibres within the tumour... often seen in pilocytic astrocytoma.
    • Rosenthal fibres may be seen around a (very) slow growing tumour and represent a reactive process.
  • Inflammatory cells and macrophages should prompt consideration of an alternate diagnosis (e.g. cerebral infarct, multiple sclerosis) - esp. if this is a primary lesion.[5]


Nuclear pleomorphism present:

  • At least grade II (diffuse astrocytoma).

Mitotic figures present:

  • At least grade III (anaplastic astrocytoma).

Microvascular proliferation or necrosis with pseudopalisading tumour cells:

  • Grade IV (glioblastoma AKA glioblastoma multiforme).


  • Pseudopalisading tumour cells = high tumour cell density adjacent to regions of necrosis; palisade = a fence of poles forming a defensive barrier or fortification.
  • WHO Grading is currently based on expected biologiocal behaviour without treatment.
    • Grading does not reflect molecular divergent groups within a tumor class or response to therapy (Currently controversies in grading for IDH-mutant astrocytoma vs. IDH-wildtype astrocytoma).[6]


Common neuropathology tumours in a table

Type Key feature(s) Imaging History Notes IHC Images
Normal tissue cells regularly spaced, no nuc. atypia small lesion? / deep lesion? variable missed lesion? nil
Normal. (WC)
Reactive astrocytes astrocytes with well-demarcated eosinophilic cytoplasm, regular spacing, no nuc. atypia small lesion? / deep lesion? variable missed lesion / close to a lesion; non-specific pathologic process - need more tissue GFAP
Reactive astrocytes. (WC)
Schwannoma cellular areas (Antoni A), paucicelluar areas (Antoni B), palisading of nuclei (Verocay bodies) extra-axial + intradural old or young need frozen section to Dx, DDx: meningioma S100, SOX10
Schwannoma. (WC)
Meningioma whorls, psammomatous calcs, nuclear inclusions extra-axial + intradural old or young may be diagnosed on smear, DDx: schwannoma, choroid plexus EMA, PR, Ki-67
Meningioma. (WC)
Astrocytoma, IDH-mutant (CNS WHO grade 2 or grade 3) glial processes (esp. on smear), nuclear atypia (typical size var. ~3x, irreg. nuc. membrane, hyperchromasia), no Rosenthal fibres in the core of the lesion †, no microvascular proliferation, no necrosis often enhancing (suggests high grade), usu. supratentorial, usu. white matter usu. old, occ. young common IDH-1(R132H)+/-, GFAP+
High-grade astrocytoma. (WC)
Glioblastoma, IDH-wildtype (CNS WHO grade 4) glial processes (esp. on smear), nuclear atypia (typical size var. ~3x, irreg. nuc. membrane, hyperchromasia), no Rosenthal fibres in the core of the lesion †, microvascular proliferation or necrosis often enhancing (suggests high grade), usu. supratentorial, usu. white matter usu. old, occ. young very common, esp. glioblastoma IDH-1+/-, GFAP+
Glioblastoma. (WC)
Metastasis sharp interface with brain, often glandular, +/-nucleoli, no glial processes often cerebellular, well-circumscribed usu. old often suspected to have metastatic disease TTF-1, CK7, CK20, BRST-2
Metastasis. (WC)

† Rosenthal fibres at the periphery of a lesion are a non-specific finding seen in chronic processes.

Brain metastasis


See also: Molecular Neuropathology


Gliomas, glioneuronal tumours and neuronal tumours are often categorized together.

Astrocytic tumours


  • Glial processes - key feature.
    • Thin stringy cytoplasmic processes - best seen at high power in less cellular areas.
  • No Rosenthal fibres within the tumour itself.



Oligodendroglial tumours


Pediatric-type diffuse high-grade glioma

Pediatric-type diffuse low-grade glioma

Circumscribed astrocytic gliomas


  • No WHO grade yet.[11]
  • Very rare superficial tumor of young age.[12]
  • Large, cystic. Pushing margin towards CNS.
  • Vasocentric growth, plump cells with absence of fibrillary pattern.
  • GFAP+ve, Synaptohysin-ve, Olig-2-ve, focally EMA/panCK+ve. MIB-1: 1-18 %.
  • Molecular profile overlaps with classical CNS-PNET.
    • Gene fusions invoving meningioma gene (MN1)[13]

Chordoid glioma of the third ventricle

  • WHO grade II.
  • Slowly growing, non-invasive, in adults.
  • Clusters of epithelioid cells in mucinous stroma.
  • Lymphocytic infiltrates, adjacent Rosenthal fibers.
  • Fibrosis may be present.
  • Few mitoses.
  • GFAP+ve, MIB-1 1-3%.
  • TTF-1+ve.
  • CD34+ve.
  • IDH-1-ve, p53-ve.
  • PRKCA D463H mutations.[14]

Ependymal tumours

Choroid plexus tumours

Other neuroepithelial tumours

Cribiform neuroepithelial tumour


  • Not listed in the current WHO classification.
  • First description in 2009.[15]
  • Around ventricles.[16]
  • Young children.[17]
  • Small undifferentiated cells arranged in cribriform strands and trabeculae of varying thickness.
  • MAP2+ve, Synaptophysin+ve, CK+/-ve. MIB-1: 30%.
  • INI-1 loss, but no rhabdoid features and good prognosis.
  • Stable genomic profile.[18]

Neuronal and mixed neuronal/glial tumours

Desmoplastic infantile astrocytoma / Desmoplastic infantile ganglioglioma

  • Abbreviated DIA or DIG.
  • ICD-O code: 9412/1
  • Large, superficial, cystic tumor of the infancy.
  • Biologic course corresponds to WHO grade I.
  • Very rare, included in the WHO since 1993.
  • Prominent desmoplastic stroma.
  • Astrocytic cells within stroma.
    • GFAP+.
    • MIB-1 usu. 1%.
  • Frequent BRAF V600E or V600D mutations.[19]
  • Single case with BRAF indel or BRAF fusion.

Cerebellar liponeurocytoma

  • Previously called lipomatous medulloblastoma (name changed in WHO 2000).
  • Mean age: 50 years.
  • As the name states: A tumour of the cerebellum.
    • But cases outside cerebellum reported that would qualify.[20]
  • WHO grade II [21] (upgraded from WHO grade I in 2007)[22]
  • ICD-O code: 9506/1


  • Advanced neuronal and lipomatous differentiation.
  • Neurocytes: round to oval nuclei with clear cytoplasm.
  • Quite cellular.
  • Mitoses almost absent.


  • GFAP +/-ve (focal).
  • MAP2 +ve.
  • Synaptophysin +ve.
  • NeuN +ve.
  • MIB-1: usu 1-3%.


  • Distinct methylation profile.
  • Recurent losses on 2p and Chr. 14.[23]



  • Grade I WHO neuronal tumour.
    • ICD-O code: 9492/0
  • Groups of irregular large neurons.
  • Non-neoplastic, reticulin-rich glial stroma.


Not to be confused with ganglioneuroma.


  • Gangliolioma: Grade I WHO mixed neuronal-glial tumour (ICD-O code: 9505/1).
  • Anaplastic ganglioglioma: Grade III (ICD-O: 9505/3)
  • Rare (approx. 0.5% of all CNS tumors).
  • Usu. temporal lobe.
  • Predominantly children (mean age: 9 years).
  • Recognized as a cause of epilepsy.[24]
  • Favourable prognosis (survival rates up to 97%)
    • Insufficient data für anaplastic ganglioglioma.


  • Circumscribed lesion.
  • Usu. contrast enhancing.
  • Solid, but intracortical cysts may be present.
  • Little mass effect.



  • Dysplastic neurons.
    • Out of regular architecture / abnormal location.
    • Cytomegaly
    • Clustering
    • Binucleated (very occassionally).
  • Atypical glia.
  • Eosinophilic granular bodies.
  • Calcification.
  • Prominent capillary network.
  • Lymphocytic cuffing.
  • May contain some reticulin.
  • Glial component may resemble:
    • Fibrillary astrocytoma.
    • Oligodendroglioma.
    • Pilocytic astrocytoma.

Anaplastic ganglioglioma:

  • Brisk mitotic activity
  • Necrosis


  • Neurons:
    • MAP2 +ve
    • Synaptophysin +ve
    • Neurofilament +ve
  • Glia:
    • CD34+/-ve
  • BRAF V600E +ve (approx. 25%, mainly ganglion cells).


  • BRAF V600E-mutated(approx. 25%).
  • IDH1/2 wt.
  • No 1p/19q codeletion.
  • Usu. Chr. 7 gain.
  • CDKN2A deletions in anaplastic ganglioglioma.


  • DNT.
  • Oligodendroglioma.
  • Trapped cortical neurons in diffuse astrocytoma.
  • Papillary glioneuronal tumor.
  • Dysembryoplastic neuroepithelial tumor.


Lhermitte-Duclos disease

  • Abbreviated LDD.
  • AKA dysplastic cerebellar gangliocytoma.[25]
  • AKA dysplastic gangliocytoma of the cerebellum.

Papillary glioneuronal tumour

  • Abbreviated PGNT.
  • A benign, supratentorial tumor of childhood.
    • Biologic course corresponds to WHO grade I.
    • Before WHO 2000, considered a Ganglioglioma variant.
  • Prominent pseudopapillary architecture.
  • Neurocytes to medium-sized ganglion cells.
  • GFAP+ core, GFAP- layer
  • Rosenthal fibers, Eosinophilic Granular bodies and lymphocytic cuffing may be present.

Rosette-forming glioneuronal tumour of the fourth ventricle

  • Abbreviated RGNT.
  • Provisional ICD-O code: 9509/1
  • A rare benign infratentorial tumour of the midline of children and adults.
  • Biologic course corresponds to WHO grade I.
  • Glial component corresponds to pilocytic astrocytoma.
  • Neurocytic rosettes.
  • Eosinopil fibrillary cores / pseudorosettes.
  • GFAP+ in fibrillary areas, Syn+ in rosettes.
  • Neurocytic cells: MAP2+
  • MIB-1 usu. below 3%.

Polymorphous low-grade tumor of the young (PLNTY)

Pineal tumours

Embryonal tumours


Peripheral nerve sheath tumours

A classification:[26] Benign:



Not to be confused with ganglioglioma.




CNS lymphoma


  • Primary CNS lymphoma.
  • Non-primary CNS lymphoma - see lymphoma article.

General - primary CNS

  • Classically periventicular distribution.
  • Usually large B cell; can be considered a type of diffuse large B cell lymphoma (DLBCL).
    • Prognosis of CNS (DLBCL) lymphomas worse than nodal (non-CNS) DLBCL.[28]



  • Large cell lymphoma.
    • Size = 2x diameter normal lymphocyte.
    • Nucleolus - common.
  • Perivascular clustering.




Can be subclassified in GCB (germinal centre B-cell-like) and non-GCB by CD10, Bcl-6, MUM1/IRF-4, and Bcl-2.[28]

Common pattern:

  • CD20 +ve - key stain.
  • CD3 -ve.
  • Ki-67 ~40%.
  • Bcl-6 +ve.
  • Bcl-1 -ve.



  • Uncommon.
  • Part of the neuroblastic tumours group which includes:[29]



  • Ganglion-like cells with a prominent nucleolus.
  • Small undifferentiated cells with scant cytoplasm.



  • NSE +ve -- small cells.

Lesions of the sella turcica

Lesions of the sella turcica, the pituitary gland environs, is a topic for it self. The differential diagnosis for lesions in this area includes:

See also


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  11. The International Agency for Research on Cancer (Editors: Louis, D.N.; Ohgaki, H.; Wiestler, O.D.; Cavenee, W.K.) (2007). Pathology and Genetics of Tumours of Tumors of the Central Nervous System (IARC WHO Classification of Tumours) (4th ed.). Lyon: World Health Organization. pp. 88. doi:10.1007/s00401-007-0243-4. ISBN 978-9283224303.
  12. Narayan, S.; Kapoor, A.; Singhal, MK.; Jakhar, SL.; Bagri, PK.; Rajput, PS.; Kumar, HS.. "Astroblastoma of cerebrum: A rare case report and review of literature.". J Cancer Res Ther 11 (3): 667. doi:10.4103/0973-1482.140800. PMID 26458709.
  13. Sturm, D.; Orr, BA.; Toprak, UH.; Hovestadt, V.; Jones, DT.; Capper, D.; Sill, M.; Buchhalter, I. et al. (Feb 2016). "New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs.". Cell 164 (5): 1060-72. doi:10.1016/j.cell.2016.01.015. PMID 26919435.
  14. Goode, B.; Mondal, G.; Hyun, M.; Ruiz, DG.; Lin, YH.; Van Ziffle, J.; Joseph, NM.; Onodera, C. et al. (02 2018). "A recurrent kinase domain mutation in PRKCA defines chordoid glioma of the third ventricle.". Nat Commun 9 (1): 810. doi:10.1038/s41467-018-02826-8. PMID 29476136.
  15. Hasselblatt, M.; Oyen, F.; Gesk, S.; Kordes, U.; Wrede, B.; Bergmann, M.; Schmid, H.; Frühwald, MC. et al. (Dec 2009). "Cribriform neuroepithelial tumor (CRINET): a nonrhabdoid ventricular tumor with INI1 loss and relatively favorable prognosis.". J Neuropathol Exp Neurol 68 (12): 1249-55. doi:10.1097/NEN.0b013e3181c06a51. PMID 19915490.
  16. Arnold, MA.; Stallings-Archer, K.; Marlin, E.; Grondin, R.; Olshefski, R.; Biegel, JA.; Pierson, CR.. "Cribriform neuroepithelial tumor arising in the lateral ventricle.". Pediatr Dev Pathol 16 (4): 301-7. doi:10.2350/12-12-1287-CR.1. PMID 23495723.
  17. Park, JY.; Kim, E.; Kim, DW.; Chang, HW.; Kim, SP. (Oct 2012). "Cribriform neuroepithelial tumor in the third ventricle: a case report and literature review.". Neuropathology 32 (5): 570-6. doi:10.1111/j.1440-1789.2011.01293.x. PMID 22239490.
  18. Gessi, M.; Japp, AS.; Dreschmann, V.; Zur Mühlen, A.; Goschzik, T.; Dörner, E.; Pietsch, T. (Oct 2015). "High-Resolution Genomic Analysis of Cribriform Neuroepithelial Tumors of the Central Nervous System.". J Neuropathol Exp Neurol 74 (10): 970-4. doi:10.1097/NEN.0000000000000239. PMID 26352987.
  19. Wang, AC.; Jones, DTW.; Abecassis, IJ.; Cole, BL.; Leary, SES.; Lockwood, CM.; Chavez, L.; Capper, D. et al. (Jul 2018). "Desmoplastic Infantile Ganglioglioma/Astrocytoma (DIG/DIA) are Distinct Entities with Frequent BRAFV600 Mutations.". Mol Cancer Res. doi:10.1158/1541-7786.MCR-17-0507. PMID 30006355.
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External links