Neuropathology tumours

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

Adult

Four most common types of brain tumours:

1. Metastatic brain tumours (barely edges out primary tumours)
   • Lung (most common).
   • Breast.
   • Melanoma.
   • Renal cell carcinoma (RCC).
2. Glioblastoma (previously known as glioblastoma multiforme).
3. Anaplastic astrocytoma.
4. Meningioma.

Children

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

Location (most common)

Certain tumours like to hang-out at certain places:

• Cerebrum:
  • Cortical based - oligodendroglioma.
  • Grey-white junction - metastases.
  • White matter - astrocytoma, glioblastoma.
  • Periventricular - CNS lymphoma.
  • Cystic - ganglioglioma, pilocytic astrocytoma, pleomorphic xanthoastrocytoma.
• Cerebellum:
  • Midline/central - medulloblastoma.
  • Cystic lesion - pilocytic astrocytoma (younger individual), hemangioblastoma (older individual).
  • Solid lesion (older individual) - metastasis.
• Spinal cord:
  • Ependymoma, glioblastoma.
  • Filum terminale - myxopapillary ependymoma, paraganglioma.

Filum terminale

• Filum terminale = bottom end of the spinal cord - has a limited differential.

DDx:

• Meningioma.
• Myxopapillary ependymoma.
• Neurofibroma.
• Schwannoma.
• Paraganglioma.

Cerebellopontine angle

• Abbreviated CP angle.

DDx:

• Schwannoma.
• Meningioma.
• Dermoid cyst/epidermoid cyst.
• Ependymoma.
• Choroid plexus papilloma.

Cystic tumours

DDx:

• Pilocytic astrocytoma.
• Pleomorphic xanthoastrocytoma.
• Ganglioglioma.
• Hemangioblastoma.
• Craniopharyngioma.

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.

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

Main article: Brain metastasis

Infiltrative astrocytomas

Main article: Astrocytoma

Overview

• Low-grade (diffuse) astrocytomas (WHO Grade II).
• Anaplastic astrocytomas (WHO Grade III).
• Glioblastoma(WHO Grade IV).
  • Gliosarcoma (WHO Grade IV).
• Gliomatosis cerebri (Grade III/IV).

Notes:

• Non-infiltrative astrocytomas:
  • Pilocytic astrocytoma (WHO Grade I).
    • Pilomyxoid astrocytoma (WHO Grade II).
  • Pleomorphic xanthoastrocytoma (WHO grade II).
  • Subependymal giant cell astrocytoma (WHO grade I).

Microscopic

Features:

• 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:

• Endothelial proliferation in a GBM (ouhsc.edu).
• Endothelial proliferation (ouhse.edu).
• Gemistocytic astrocytoma - several images (upmc.edu).

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.

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.

Images

Glioblastoma:

• 

  Glioblastoma - pseudopalisading of tumour cells (WC)

• 

  Glioblastoma with fragment of near-normal white matter - high mag. (WC)

Anaplastic astrocytoma:

• 

  Anaplastic astrocytoma - very high mag. (WC)

• 

  Anaplastic astrocytoma - GFAP - very high mag. (WC)

Table of common gliomas - grading

Histomorphologic comparison of common gliomas:

Entity	Rosenthal fibres / EGBs	Nuclear atypia	Mitoses	Necrosis or MVP	Infiltrative	Image
Pilocytic astrocytoma	yes	usu. no	usu. no	usu. no	no
Low-grade astrocytoma	no	yes	no	no	yes
Anaplastic astrocytoma	no	yes	yes	no	yes
Glioblastoma	no	yes	yes	yes	yes

Notes:

• MVP = microvascular proliferation.
• EGBs = eosinophilic granular bodies.

IHC

• GFAP - should stain cytoplasm of tumour cells and the perikaryon (nuclear membrane).
• Ki-67 - usu. high >20% of cells.
• p53 - often +ve.
• IDH1 (isocitrate dehydrogenase 1).
  • +ve in tumours that arose from low-grade gliomas.
    • Image: IDH1 +ve in glioblastoma (WP).

Notes:

• IDH1 and IDH2 mutations - better survival.

Pilocytic astrocytoma

Main article: Pilocytic astrocytoma

Pilomyxoid astrocytoma

Main article: Pilomyxoid astrocytoma

Pleomorphic xanthoastrocytoma

• Abbreviated PXA.

Main article: Pleomorphic xanthoastrocytoma

Subependymal giant cell astrocytoma

• Abbreviated SEGA.

Main article: Subependymal giant cell astrocytoma

Oligoastrocytoma

Main article: Oligoastrocytoma

Oligodendroglioma

Main article: Oligodendroglioma

Subependymoma

Main article: Subependymoma

Myxopapillary Ependymoma

Main article: Myxopapillary Ependymoma

Ependymoma

Main article: Ependymoma

Choroid plexus papilloma

• Grade I WHO or Grade II WHO (atypical CPP)

Main article: Choroid plexus papilloma

Choroid plexus carcinoma

Main article: Choroid plexus carcinoma

Angiocentric glioma

• Grade I WHO neuroepithelial tumour.

Main article: Angiocentric glioma

Chordoid glioma of the 3rd ventricle

• WHO grade II.
• Slowly growing, non-invasive.
• Clusters of epithelioid cells in mucinous stroma.
• Lymphocytic infiltrates, adjacent Rosenthal fibers.
• Few mitoses.
• GFAP+ve, MIB-1 1-3%.

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

• Grade I WHO mixed neuronal-glial tumour.
• ICD-O code: 9505/1 (Anaplastic ganglioglioma: 9505/3)
• Rare.
• Usu. temporal lobe.
• Recognized as a cause of epilepsy.

Microscopic

Features:

• Dysplastic neurons.
  • Out of regular architecture / abnormal location.
  • Cytomegaly
  • Clustering
  • Binucleated (very occassionally).
• Atypical glia.
• Calcification.
• Lymphocytic cuffing.

Anaplastic ganglioglioma:

• Brisk mitotic activity
• Necrosis

IHC

• Neurons:
  • MAP2 +ve
  • Synaptophysin +ve
  • Neurofilament +ve
• Glia:
  • CD34+/-ve

DDx:

• DNT.
• Oligodendroglioma.
• Trapped cortical neurons in diffuse astrocytoma.

Images

• 

  Lymphocytic cuffing in ganglioglioma (WC/jensflorian)

• 

  Calcification in ganglioglioma (WC/jensflorian)

• 

  CD34 immunostain in ganglioglioma (WC/jensflorian)

• Ganglioglioma - case 1 (upmc.edu).
• Ganglioglioma - case 2 (upmc.edu).

Dysembryoplastic neuroepithelial tumour

• Abbreviated DNT.

Main article: Dysembryoplastic neuroepithelial tumour

Atypical teratoid/rhabdoid tumour

See also: Extrarenal malignant rhabdoid tumour.

• Commonly abbreviated AT/RT.
• May be written atypical teratoid rhabdoid tumour, i.e. without the forward slash, or atypical teratoid-rhabdoid tumour (AT-RT).

Main article: Atypical teratoid/rhabdoid tumour

Medulloblastoma

Main article: Medulloblastoma

• Tumour of cerebellum - key feature.
• Morphologically identical supratentorial tumours are called primitive neuroectodermal tumour (PNET).

Primitive neuroectodermal tumour

Main article: Primitive neuroectodermal tumour

Embryonal tumour with abundant neuropil and true rosettes

• Abbreviated ETANTR.

Main article: Embryonal tumour with abundant neuropil and true rosettes

Astroblastoma

• No WHO grade yet.
• Very rare superficial tumor of young age.
• Large, cystic. Pushing margin towards CNS.
• Vasocentric growth, plump cells with absence of fibrillary pattern.
• GFAP+ve, Synaptohysin-ve, focally EMA/panCK+ve. MIB-1: 1-18 %.

• 

  HE. (WC/jensflorian)

• 

  HE. (WC/jensflorian)

• 

  Astroblastoma (AFIP)

Meningioma

Main article: Meningioma

Peripheral nerve sheath tumours

Main article: Peripheral nerve sheath tumours

A classification:

• Benign:
  • Schwannoma.
  • Neurofibroma.
  • Perineurioma.
  • Traumatic neuroma.
• Malignant:
  • Malignant peripheral nerve sheath tumour (MPNST).

Schwannoma

Main article: Schwannoma

Neurofibroma

Main article: Neurofibroma

Ganglioneuroma

Not to be confused with ganglioglioma.

• AKA ganglioma.

Main article: Ganglioneuroma

Chordoma

Main article: Chordoma

Hemangioblastoma

Main article: 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.

Microscopic

Features:

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

Images

www:

• CNS lymphoma (frontalcortex.com).
• Primary CNS lymphoma - several images (upmc.edu).

• 

  CNS lymphoma - low mag. (WC)

• 

  CNS lymphoma - intermed. mag. (WC)

• 

  CNS lymphoma - high mag. (WC)

• 

  CNS lymphoma - very high mag. (WC)

• 

  CNS lymphoma. (WC/KGH)

• 

  CNS lymphoma. (WC/KGH)

IHC

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

Common pattern:

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

Neurocytoma

Main article: Neurocytoma

Central neurocytoma

• Abbreviated CNC.

Main article: Central neurocytoma

Lhermitte-Duclos disease

• Abbreviated LDD.
• AKA dysplastic cerebellar gangliocytoma.
• AKA dysplastic gangliocytoma of the cerebellum.

Main article: Lhermitte-Duclos disease

Ganglioneuroblastoma

Main article: Neuroblastoma

General

• Uncommon.
• Part of the neuroblastic tumours group which includes:
  • Ganglioneuroma (benign).
  • Ganglioneuroblastoma (intermediate).
  • Neuroblastoma (aggressive).

Microscopic

Features:

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

• 

  Adrenal Ganglioneuroblastoma - Low power (SKB)

• 

  Adrenal Ganglioneuroblastoma - Medium power (SKB)

• 

  Adrenal Ganglioneuroblastoma - High power (SKB)

• 

  Adrenal Ganglioneuroblastoma - High power (SKB)

• 

  Adrenal Ganglioneuroblastoma - High power (SKB)

Images:

• Ganglioneuroblastoma - several images (upmc.edu).

IHC

• NSE +ve -- small cells.

Lesions of the sella turcica

Main article: Pituitary gland

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

• Pituitary adenoma.
• Craniopharyngioma.
• Rathke cleft cyst.
• Germ cell tumour.
• Meningioma.
• Pilomyxoid astrocytoma - in children.

See also

• Neuropathology.
• Muscle biopsy.

External links

• Neuropathology (neuropathologyweb.org).
• Neuropathology Mini-Course (pathology.vcu.edu).
• Neuropathology Mini-Course (pathology.vcu.edu).