Neuropathology tumours

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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 is a separate article for peripheral nerve sheath tumours.

Brain tumours - overview

Adult

Four most common types of brain tumours:[1]

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

Children

  1. Astrocytoma.
  2. Medulloblastoma.
  3. Ependymoma.

Location (most common)

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

  • 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:[3]

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

Cerebellopontine angle

DDx:[4]

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

Primary vs. secondary

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/.

Common brain tumours in a table

Type Key feature(s) Imaging History Notes IHC Images
Normal tissue regular spacing, no atypia small lesion? variable missed lesion? nil [1], [2]
Reactive astrocytes astrocytes with well-demarcated eosinophilic cytoplasm, regular spacing, no atypia nil small lesion? missed lesion / close to a lesion nil [3]
Astrocytoma glial processes (on smear), nuclear atypia (size var. ~3x, irreg. nuc. membrane, hyperchromasia) enhancing, usu. supratentorial, usu. white matter usu. old, occ. young very common, esp. glioblastoma IDH-1+/- [4], [5]
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 [6], [7]
Meningioma whorls, psammomatous calcs, nuclear inclusions extra-axial + intradural old or young may be diagnosed on smear, DDx: choroid plexus, schwannoma EMA, PR, Ki-67 [8]
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 S100 [9]

Metastatic tumours

General

  • Most common brain tumour in adults.

Microscopic

Features:

  • Vary by subtype.

Images:

Astrocytomas

Overview

  • Pilocytic astrocytomas (WHO Grade I).
  • Dysembryoplastic neuroepithelial tumour (DNT), (WHO Grade I).
  • Low-grade (diffuse) astrocytomas (Grade II).
  • Anaplastic astrocytomas (Grade III).
  • Glioblastoma (Grade IV).

Microscopic

Features:[5][6]

  • Glial processes - key feature.
    • Thin stringy cytoplasmic processes - best seen at high power in less cellular areas.

Images:

Notes:

  • Glial vs. non-glial tumours:
    • Glial: "blends into brain"/gradual transition to non-tumour brain.
    • Non-glial: no glial processes.

Grading

At least grade II:

  • Nuclear pleomorphism.

At least grade III:

  • Mitotic figures.

At least grade IV:

  • Microvascular proliferation or necrosis with pseudopalisading tumour cells.
    • Pseudopalisading tumour cells = high tumour cell density adjacent to regions of necrosis; palisade = a fence of pales forming a defense barrier or fortification.

Glioblastoma 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).

Notes:

  • IDH1 and IDH2 mutations - better survival.[8]

Gliosarcoma

General

  • Considered to be a variant of glioblastoma by WHO.[9]
  • Rare ~ 200 cases reported in the literature.[9]
  • Definition: gliosarcoma = glioblastoma + sarcomatous component.[10]
  • Usual location (like glioblastoma): temporal lobe.

Microscopic

Features:

  • Glioblastoma.
  • Sarcomatous component (one of the following):[9][10]
    • Fibroblastic.
    • Cartilaginous.
    • Osseous.
    • Smooth muscle.
    • Striated muscle.
    • Adipocyte.

Image: Gliosarcoma - elastic von Gieson (WC).

Pilocytic astrocytoma

General

  • Low-grade astrocytoma.
  • Classically in the cerebellum in children; most common glioma in children.[11]
  • The optic glioma associated with neurofibromatosis 1.

Gross

Features:[11]

  • Usually well-circumscribed.
  • Cystic or solid.
  • Do not smear. (Ref. ?)

Microscopic

Features:[12]

  • Classically biphasic (though either may be absent):
    1. Fibrillar.
    2. Microcystic/loose.
  • Hair-like fibres ~ 1 micrometer; pilo- = hair.[13]
    • Best seen on smear or with GFAP IHC.
  • Rosenthal fibres - key feature.
    • May be rare. Not pathognomonic (see below).
  • Eosinophilic granular bodies.
  • Low cellularity - when compared to medulloblastoma and ependymoma.

Notes:

  • +/-Microvascular proliferation.
  • +/-Focal necrosis.
    • Necrosis with pseudopalisading more likely glioblastoma.
  • +/-Mitoses - not significant in the context of the Dx.

Images:

DDx (of Rosenthal fibers):[14]

  • Chronic reactive gliosis.
  • Subependymoma.
  • Ganglioma.
  • Alexander's disease (rare leukodystrophy).

DDx of pilocystic astrocytoma (brief):

  • Piloid gliosis.
  • Oligodendroglioma.
  • Glioblastoma (uncommon - but important).

IHC/special stains

Features:[15]

  • GFAP +ve (fibres).
  • PAS-D: eosinophilic granular bodies +ve.
  • CD68: may have a significant macrophage component.
  • KI-67: may be "high" (~20% ???).

Grading

  • WHO Grade I by definition.

Pilomyxoid astrocytoma

General

Features:[16]

  • A variant of pilocytic astrocytoma.
    • Some have suggested it is a unique entity.[17]
  • Childhood or adolescence.

Gross

Features:[16]

  • Classically - hypothalamic location.
  • Solid.
  • Well-circumscribed.

Microscopic

Features:[16]

  • Consists of small round/ovoid bland cells in a myxoid stroma.
  • Hair-like fibres ~ 1 micrometer.
    • Often difficult to appreciate on standard (H&E) histologic sections.
  • Usually angiocentric (surround blood vessel) - key feature.

Notes:[16]

  • Rosenthal fibres are absent - key negative.
  • Monophasic (unlike classical pilocytic astrocytomas) - key negative.
  • May rarely have eosinophilic granular bodies.

Grading

  • WHO Grade II by definition.[16]

Atypical teratoid/rhabdoid tumour

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

General

  • Usually supratentorial, occasionally in posterior fossa, case reports of spinal cord.

Microscopic

Features:

  • Cellular.
  • Small round cells usu. with a prominent nucleolus.
  • Rhaboid cells.
    • Cells with eosinophilic granular cytoplasm + eccentric nucleus. (???)
  • Mitoses.

Images:

DDx:

  • Primitive neuroectodermal tumour (PNET).
  • Diffuse astrocytoma.
  • Choroid plexus carcinoma.
  • Embryonal carcinoma.

IHC

  • BAF-47 -ve (AKA INI1) - virtually diagnostic.
    • Endothelial cells +ve control.
  • S-100 +ve.
    • Few other brain tumours express it.
  • Vimentin +ve (perinuclear condensation).

Others:

  • GFAP +ve (focal - in tumour cells).
  • EMA +ve (patchy cytoplasmic).
  • Smooth muscle actin +ve.

Oligodendroglioma

General

  • Do not arise from oligodendrocytes.
    • Arise from glial precursor cells.

Usual location:

  • Fourth ventricle.
  • Intramedullary spinal cord.

Prognosis by flavours (average survival):[18]

  • WHO grade II: 10-15 years.
  • WHO grade III: 3-5 years.

Microscopic

Features:

  • Highly cellular lesion composed of:
    • Cells resembling fried eggs (oligodendrocytes) with:
      • Round nucleus - key feature.
      • Distinct cell borders.
      • Moderate-to-marked nuclear atypia.
      • Clear cytoplasm - useful feature (if present).
        • Some oligodendrogliomas have eosinophilic cytoplasm with focal perinuclear clearing.
    • Acutely branched capillary sized vessels - "chicken-wire" like appearance.
      • Abundant, delicate appearing; may vaguely resemble a paraganglioma at low power.
  • Calcifications - important feature.[19]

Images:

Notes:

  • Few neural tumours have round nuclei - DDx:
    • Oligodendroglioma.
    • Lymphoma.
    • Clear cell variant of ependymoma.
    • Germ cell tumour (dysgerminoma/seminoma).

Histologic grading

Come in two flavours:

  1. WHO grade II.
    • This is most oligodendrogliomas.
  2. WHO grade III.
    • Features for calling high grade:[18]
      • Endothelial hypertrophy.
        • Plump/large endothelial cells.
      • Necrosis.
      • High mitotic rate (6 mitoses/10 HPF for whatever "HPF" means, see HPFitis).

IHC

Features:

  • MAP-2 +ve.[20]
  • GFAP -ve.
    • Some subtypes +ve - should not be used to distinguish.[21]
  • EMA +ve.
  • IDH-1 -ve. (???).
  • p53 -ve.
    • Useful for differentiating astrocytoma vs. oligodendroglioma.
  • Ki-67.

Molecular pathology

Losses of 1p and 19q both helps with diagnosis and is prognostic:[22]

  • Greater chemosensitivity
  • Better prognosis.

Oligoastrocytoma

General

  • Mixed tumour.

Microscopic

Features:

  • Astrocytoma-like and oligodendroglioma-like:
    1. Oligodendroglioma-like cells = round nucleus, peri-nuclear clearing.
    2. Astrocytoma-like cells = non-ovoid/elongated nucleus.

DDx:

  • Anaplastic astrocytoma.
  • Oligodendroglioma. (???)

IHC

  • Oligodendroglioma-like cells: MAP-2 +ve (cytoplasm).
  • Astrocytoma-like cells: GFAP +ve (cytoplasm, nuclear membrane).

Others:

  • Ki-67 ~10%. (???)
  • p53 - focally +ve. (???)
  • IDH-1 -ve. (???)

Meningioma

Main article: Meningioma

General

  • Very common.
  • May be part of a syndrome.

Microscopic

Features (memory device WTC):

  • Whorled appearance - key feature.
  • Calcification, psammomatous.

Grading: see meningioma.

Peripheral nerve sheath tumours

Main article: Peripheral nerve sheath tumours

A classification:[23]

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

Schwannoma

Main article: Peripheral nerve sheath tumours#Schwannoma

General

  • Tumour of tissue surrounding a nerve.
    • Axons adjacent to the tumour are normal... but may be compressed.

Microscopic

Features:[23]

  • Antoni tissue (type A and type B).
  • Verocay bodies - paucinuclear area surrounded by nuclei.

Notes:

  • Tumour does not smear well.[24]

Antoni A

  • Cellular.
  • 'Fibrillary, polar, elongated'.

Comment: May look somewhat like scattered matchsticks.

Antoni B

  • Loose microcystic tissue.
  • Adjacent to Antoni A.

Micrographs:

Neurofibroma

Main article: Peripheral nerve sheath tumours#Neurofibroma

General

Microscopic

Features:[23]

  • Plexiform growth pattern - "bag of worms".

Image:

Ganglioneuroma

General

  • AKA ganglioma.[25]
  • May be retroperitoneal.

Microscopic

Features:

  • Ganglion cells - key feature.
    • Large cells with large nucleus.
      • Prominent nucleolus.
  • Disordered fibrinous-like material.
  • Eosinophilic granular bodies.[26]

Images:

See: Adrenal gland.

Ependymoma

General

  • Called the forgotten glial tumour.

Comes in two flavours:

  1. Ependymoma (not otherwise specified).
  2. Myxopapillary ependymoma.
    • Classically at filum terminale.

Microscopy

Classic ependymoma

Features:

  • Cells have a "tadpole-like" morphology.
    • May also be described as ice cream cone-shaped.[27]
  • Rosettes - cells arranged in a pseudoglandular fashion.
  • "Nucleus free zones" - cells arranged around a blood vessel (perivascular pseudorosettes); nuclei of cells distant from the blood vessel, i.e. a rim of cytoplasm (from tumour cells) surrounds the blood vessel.

Perivascular pseudorosettes = (tumour) cells arranged around a blood vessel; nuclei of cells distant from the blood vessel, i.e. rim of cytoplasm (from tumour cells) surround blood vessel (nucleus-free zone)

    • The nucleus free zone is composed of tumour cell cytoplasm that is adjacent to an unseen blood vessel.
  • Nuclear feature monotonous, i.e. "boring".[28]
    • There is little variation in size, shape and staining.

Images:

DDx (classic ependymoma):

  • Subependymoma.
  • Glioblastoma (GBM).
    • Invasive border = GBM; circumscribed border of lesion = ependymoma.

Myxopapillary ependymoma

Features:

  • Perivascular pseudorosettes:
    • Myxoid material surround blood vessels.
      • Myxoid material surrounded by tumour cells.

Images:

Grading

Easy:

  • Subependymoma = WHO grade I.
  • Myxopapillary ependymoma = WHO grade I.

Not-so-easy:

  • Classic ependymoma = WHO grade II.
  • Anaplastic ependymoma = WHO grade III.

Grade II vs. Grade III:

  • Cellular density.
  • Mitoses.
  • Necrosis.
  • Microvascular proliferation.

Notes:

  • Many tumours fall between grade II and grade III. These are called "indeterminate" by many.

IHC

  • Reticulin.
  • GFAP.
  • MIB-1.

Choroid plexus papilloma

Microscopy

Features:

  • Simple epithelium.
  • Papillae.
  • Psammoma bodies.

Image:

Chordoma

General

  • Location: usually sacrum or clivus.

Microscopic

Features:[29]

  • Architecture: islands of cells surrounded by fibrous tissue.
    • Also described as "lobulated" architecture; may not be apparent.
  • Myxoid background - grey extracellular material, variable amount present.
  • Mixed cell population:
    1. Abundant eosinophilic cytoplasm.
    2. Physaliphorous cells or bubble cells - key feature.
      • Have a very large clear bubble with a sharp border; bubble does not compress nucleus - nucleus may be in bubble.

Images:


IHC

Features:

  • S100 +ve.
  • CK +ve.
  • Brachyury +ve -- key stain.
    • Protein important for axial development, affects notochord development.[30]
    • Brachyury literally means short tail.[31]

Hemangioblastoma

General

Microscopic

Features:[33]

  • Vascular.
  • Polygonal stromal cells with:
    • Hyperchromatic nuclei.
    • Vacuolar cytoplasm.

Images:

DDx:

  • Metastatic clear cell renal cell carcinoma.

IHC

Features:[34]

  • Alpha-inhibin +ve (cytoplasm).
  • EMA -ve.
    • RCC typically +ve.
  • NSE +ve (nucleus + cytoplasm).
    • RCC typically -ve.

Medulloblastoma

General

Gross

  • Location: cerebellum - key feature.
    • Morphologically identical supratentorial tumours are called primitive neuroepithelial tumour (PNET).

Microscopic

Features:[35]

  • Homer-Wright rosettes= rosette with a meshwork of fibers (neuropil) at the centre.[36]

Image:

Subtypes

  • Classic medulloblastoma (~85% of all medulloblastomas).
  • Variants of medulloblastoma (~15% of all medulloblastomas together):
    1. Anaplastic variant.
    2. Large cell variant.
    3. Desmoplastic/nodular medulloblastoma (DNMB).
    4. Medulloblastoma with extensive nodularity (MBEN).

Notes:

  • Prognosis:[37][38] DNMB & MBEN > classic > anaplastic variant, large cell variant.
Anaplastic variant

Features:

  • Larger cells.
  • Severe anaplasia.
  • Polygonal cells.

Primitive neuroepithelial tumour

General

  • Abbreviated PNET.

Microscopic

Features:

  • See medulloblastoma.

DDx: Embryonal tumor with abundant neuropil and true rosettes (ETANTR).[39]

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.[40]

Microscopic

Features:

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

IHC

Can be subclassified in GCB (germinal centre B-cell-like) and non-GCB by CD10, Bcl-6, MUM1/IRF-4, and Bcl-2.[40]

Common pattern:

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

See also

References

  1. ↑ http://neurosurgery.mgh.harvard.edu/abta/primer.htm
  2. ↑ URL: http://www.msdlatinamerica.com/ebooks/DiagnosticNeuropathologySmears/files/4ce563fb7e8e48fc9ed8b42e296a7747.gif and http://www.msdlatinamerica.com/ebooks/DiagnosticNeuropathologySmears/sid117213.html. Accessed on: 2 November 2010.
  3. ↑ JLK. 31 May 2010.
  4. ↑ R. Kiehl. 8 November 2010.
  5. ↑ Rong Y, Durden DL, Van Meir EG, Brat DJ (June 2006). "'Pseudopalisading' necrosis in glioblastoma: a familiar morphologic feature that links vascular pathology, hypoxia, and angiogenesis". J. Neuropathol. Exp. Neurol. 65 (6): 529–39. PMID 16783163.
  6. ↑ http://dictionary.reference.com/browse/palisading
  7. ↑ Yan H, Parsons DW, Jin G, et al. (February 2009). "IDH1 and IDH2 mutations in gliomas". N. Engl. J. Med. 360 (8): 765–73. doi:10.1056/NEJMoa0808710. PMC 2820383. PMID 19228619. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2820383/.
  8. ↑ 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.
  9. ↑ 9.0 9.1 9.2 Han SJ, Yang I, Tihan T, Prados MD, Parsa AT (February 2010). "Primary gliosarcoma: key clinical and pathologic distinctions from glioblastoma with implications as a unique oncologic entity". J. Neurooncol. 96 (3): 313–20. doi:10.1007/s11060-009-9973-6. PMC 2808523. PMID 19618114. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2808523/.
  10. ↑ 10.0 10.1 Ayadi L, Charfi S, Khabir A, et al. (March 2010). "[Cerebral gliosarcoma: clinico-pathologic study of 8 cases]" (in French). Tunis Med 88 (3): 142–6. PMID 20415184.
  11. ↑ 11.0 11.1 Perry, Arie; Brat, Daniel J. (2010). Practical Surgical Neuropathology: A Diagnostic Approach: A Volume in the Pattern Recognition series (1st ed.). Churchill Livingstone. pp. 82. ISBN 978-0443069826.
  12. ↑ Perry, Arie; Brat, Daniel J. (2010). Practical Surgical Neuropathology: A Diagnostic Approach: A Volume in the Pattern Recognition series (1st ed.). Churchill Livingstone. pp. 82-4. ISBN 978-0443069826.
  13. ↑ URL: http://dictionary.reference.com/browse/pilo-. Accessed on: 24 November 2010.
  14. ↑ MUN. 9 Mar 2009.
  15. ↑ Perry, Arie; Brat, Daniel J. (2010). Practical Surgical Neuropathology: A Diagnostic Approach: A Volume in the Pattern Recognition series (1st ed.). Churchill Livingstone. pp. 84. ISBN 978-0443069826.
  16. ↑ 16.0 16.1 16.2 16.3 16.4 Perry, Arie; Brat, Daniel J. (2010). Practical Surgical Neuropathology: A Diagnostic Approach: A Volume in the Pattern Recognition series (1st ed.). Churchill Livingstone. pp. 86. ISBN 978-0443069826.
  17. ↑ Komotar RJ, Mocco J, Jones JE, et al. (June 2005). "Pilomyxoid astrocytoma: diagnosis, prognosis, and management". Neurosurg Focus 18 (6A): E7. PMID 16048293.
  18. ↑ 18.0 18.1 Perry, Arie; Brat, Daniel J. (2010). Practical Surgical Neuropathology: A Diagnostic Approach: A Volume in the Pattern Recognition series (1st ed.). Churchill Livingstone. pp. 98. ISBN 978-0443069826.
  19. ↑ URL: http://www.emedicine.com/radio/topic481.htm.
  20. ↑ Suzuki SO, Kitai R, Llena J, Lee SC, Goldman JE, Shafit-Zagardo B (May 2002). "MAP-2e, a novel MAP-2 isoform, is expressed in gliomas and delineates tumor architecture and patterns of infiltration". J. Neuropathol. Exp. Neurol. 61 (5): 403–12. PMID 12025943.
  21. ↑ Perry, Arie; Brat, Daniel J. (2010). Practical Surgical Neuropathology: A Diagnostic Approach: A Volume in the Pattern Recognition series (1st ed.). Churchill Livingstone. pp. 98. ISBN 978-0443069826.
  22. ↑ Fontaine D, Vandenbos F, Lebrun C, Paquis V, Frenay M (2008). "[Diagnostic and prognostic values of 1p and 19q deletions in adult gliomas: critical review of the literature and implications in daily clinical practice]" (in French). Rev. Neurol. (Paris) 164 (6-7): 595–604. doi:10.1016/j.neurol.2008.04.002. PMID 18565359.
  23. ↑ 23.0 23.1 23.2 23.3 Wippold FJ, Lubner M, Perrin RJ, Lämmle M, Perry A (October 2007). "Neuropathology for the neuroradiologist: Antoni A and Antoni B tissue patterns". AJNR Am J Neuroradiol 28 (9): 1633–8. doi:10.3174/ajnr.A0682. PMID 17893219. http://www.ajnr.org/cgi/reprint/28/9/1633.
  24. ↑ MUN. 24 November 2010.
  25. ↑ URL: http://medical-dictionary.thefreedictionary.com/ganglioma. Accessed on: 8 November 2010.
  26. ↑ R. Kiehl. 8 November 2010.
  27. ↑ http://www.pathology.vcu.edu/WirSelfInst/tumor-2.html
  28. ↑ MUN. 6 Oct 2009.
  29. ↑ Tadrous, Paul.J. Diagnostic Criteria Handbook in Histopathology: A Surgical Pathology Vade Mecum (1st ed.). Wiley. pp. 184. ISBN 978-0470519035.
  30. ↑ URL:http://www.ncbi.nlm.nih.gov/omim/601397. Accessed on: 18 May 2010.
  31. ↑ URL: http://www.jstor.org/pss/86845. Accessed on: 18 May 2010.
  32. ↑ URL: http://www.expertconsultbook.com/expertconsult/ob/book.do?method=display&type=bookPage&decorator=none&eid=4-u1.0-B978-1-4160-4580-9..00019-8--sc0155&isbn=978-1-4160-4580-9. Accessed on: 9 December 2010.
  33. ↑ URL: http://emedicine.medscape.com/article/340994-media. Accessed on: 23 June 2010.
  34. ↑ URL: http://www.nature.com/modpathol/journal/v18/n6/full/3800351a.html. Accessed on: 9 December 2010.
  35. ↑ URL: http://moon.ouhsc.edu/kfung/jty1/neurotest/Q93-Ans.htm. Accessed on: 26 October 2010.
  36. ↑ Wippold FJ, Perry A (March 2006). "Neuropathology for the neuroradiologist: rosettes and pseudorosettes". AJNR Am J Neuroradiol 27 (3): 488–92. PMID 16551982.
  37. ↑ Gulino A, Arcella A, Giangaspero F (November 2008). "Pathological and molecular heterogeneity of medulloblastoma". Curr Opin Oncol 20 (6): 668–75. doi:10.1097/CCO.0b013e32831369f4. PMID 18841049.
  38. ↑ Rutkowski S, von Hoff K, Emser A, et al. (November 2010). "Survival and Prognostic Factors of Early Childhood Medulloblastoma: An International Meta-Analysis". J Clin Oncol 28 (33): 4961–4968. doi:10.1200/JCO.2010.30.2299. PMID 20940197.
  39. ↑ Buccoliero AM, Castiglione F, Degl'Innocenti DR, et al. (February 2010). "Embryonal tumor with abundant neuropil and true rosettes: morphological, immunohistochemical, ultrastructural and molecular study of a case showing features of medulloepithelioma and areas of mesenchymal and epithelial differentiation". Neuropathology 30 (1): 84–91. doi:10.1111/j.1440-1789.2009.01040.x. PMID 19563506.
  40. ↑ 40.0 40.1 Raoux D, Duband S, Forest F, et al. (June 2010). "Primary central nervous system lymphoma: Immunohistochemical profile and prognostic significance". Neuropathology 30 (3): 232–40. doi:10.1111/j.1440-1789.2009.01074.x. PMID 19925562.

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