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.

Contents

Brain tumours - overview

Alphabetical

For overview see here

By age group

Adult

Four most common types of brain tumours:[1]

  1. Metastatic brain tumours (barely edges out primary tumours)
  2. Glioblastoma (previously known as glioblastoma multiforme).
  3. Anaplastic astrocytoma.
  4. Meningioma.

Children

  1. Pilocytic astrocytoma.
  2. Medulloblastoma.
  3. Ependymoma.

By location

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

Cerebrum

Cerebellum

Sella turcica

less common:

Spinal cord

Filum terminale

Meninges

less common:

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

Skull

Skull base / Cerebellopontine angle

less common:

Cystic tumours

DDx:[3]

Primary versus secondary

  • AKA (primary) brain tumour versus metastatic cancer.

Primary

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.

Meningioma:

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

Lymphoma:

  • Large (lymphoid) cells, ergo usu. not a difficult diagnosis.
    • ~2x size of resting lymphocyte, nucleoli.
  • Lesion predominantly perivascular.

Secondary

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.

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 nil
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
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)
Infiltrative astrocytoma (WHO grade II or grade III) 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+/-, GFAP+
High-grade astrocytoma. (WC)
Glioblastoma (WHO grade IV) 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

Infiltrative astrocytomas

Overview

Notes:

Microscopic

Features:[5][6]

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

Images:

Notes:

  • Glial vs. non-glial tumours:
    • Glial: "blends into brain"/gradual transition to non-tumour brain.
    • Non-glial: no glial processes.
  • Rosenthal fibres within the tumour... make it into a 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.[7]

Grading

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).

Notes:

  • 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).[8]

Images

Glioblastoma:

Anaplastic astrocytoma:

IHC

  • GFAP - should stain cytoplasm of tumour cells and the perikaryon (nuclear membrane).
  • Ki-67 - usu. high >20% of cells.
  • p53 - often +ve.
  • IDH-1 (isocitrate dehydrogenase 1).
    • +ve in tumours that arose from low-grade gliomas.[9]
  • H3F3A K27M -ve
  • ATRX -ve in tumors with low-grade precursor(most of them also IDH1/2 mutant).

Notes:

  • IDH1 and IDH2 mutations - better survival.[10]

Molecular

See also: Molecular Neuropathology

Astrocytic tumours

Oligodendroglial tumours

Ependymal tumours

Choroid plexus tumours

Other neuroepithelial tumours

Astroblastoma

  • 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]

Cribiform neuroepithelial tumour

AKA: CRINET.

  • 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%.
  • Frquent BRAF V600E or V600D mutations.[19]

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

Histo

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

IHC

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

Molecular

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

DDx

Gangliocytoma

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

Ganglioglioma

Not to be confused with ganglioneuroma.

General

  • 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.

Macroscopic

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


Microscopic

Features:

  • 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

IHC

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

Molecular

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

DDx:

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

Images

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%.

Pineal tumours

Embryonal tumours

Peripheral nerve sheath tumours

A classification:[26] Benign:

Malignant:

Ganglioneuroma

Not to be confused with ganglioglioma.


Meningioma

Chordoma

Hemangioblastoma

CNS lymphoma

Classification:

  • 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]

Microscopic

Features:

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

Images

www:

IHC

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.


Ganglioneuroblastoma

General

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

Microscopic

Features:

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

Images:

IHC

  • 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

References

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  10. Houillier C, Wang X, Kaloshi G, et al. (October 2010). "IDH1 or IDH2 mutations predict longer survival and response to temozolomide in low-grade gliomas". Neurology 75 (17): 1560–6. doi:10.1212/WNL.0b013e3181f96282. PMID 20975057.
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  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.
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External links