Course:Introduction to Neuropathology - Revision history

Jensflorian: /* Molecular neuropathology */ Myopathology (Source: en. wikipedia.org + wikimedia commons)

2015-10-08T09:00:16Z

Molecular neuropathology: Myopathology (Source: en. wikipedia.org + wikimedia commons)

← Older revision		Revision as of 09:00, 8 October 2015
Line 271:		Line 271:
	Because [[IDH-1]] and IDH-2 mutations are found in up to 80% of [[astrocytoma]]s and [[oligodendroglioma]], IDH-1 R132H (which detects only the R132H substitution <ref name=pmid19798509>{{Cite journal \| last1 = Capper \| first1 = D. \| last2 = Zentgraf \| first2 = H. \| last3 = Balss \| first3 = J. \| last4 = Hartmann \| first4 = C. \| last5 = von Deimling \| first5 = A. \| title = Monoclonal antibody specific for IDH1 R132H mutation. \| journal = Acta Neuropathol \| volume = 118 \| issue = 5 \| pages = 599-601 \| month = Nov \| year = 2009 \| doi = 10.1007/s00401-009-0595-z \| PMID = 19798509 }}</ref>) stained negative cases are sequenced for other rare mutations that include IDH1 R132C or IDH2 R172K among others. These mutations are not only useful in differential diagnosis of brain tumours but also prognostic, because tumours carrying a IDH-1 or IDH-2 mutation usually show a more favourable course than their wild-type counterparts <ref name=pmid21088844>{{Cite journal \| last1 = Hartmann \| first1 = C. \| last2 = Hentschel \| first2 = B. \| last3 = Wick \| first3 = W. \| last4 = Capper \| first4 = D. \| last5 = Felsberg \| first5 = J. \| last6 = Simon \| first6 = M. \| last7 = Westphal \| first7 = M. \| last8 = Schackert \| first8 = G. \| last9 = Meyermann \| first9 = R. \| title = Patients with IDH1 wild type anaplastic astrocytomas exhibit worse prognosis than IDH1-mutated glioblastomas, and IDH1 mutation status accounts for the unfavorable prognostic effect of higher age: implications for classification of gliomas. \| journal = Acta Neuropathol \| volume = 120 \| issue = 6 \| pages = 707-18 \| month = Dec \| year = 2010 \| doi = 10.1007/s00401-010-0781-z \| PMID = 21088844 }}</ref>.		Because [[IDH-1]] and IDH-2 mutations are found in up to 80% of [[astrocytoma]]s and [[oligodendroglioma]], IDH-1 R132H (which detects only the R132H substitution <ref name=pmid19798509>{{Cite journal \| last1 = Capper \| first1 = D. \| last2 = Zentgraf \| first2 = H. \| last3 = Balss \| first3 = J. \| last4 = Hartmann \| first4 = C. \| last5 = von Deimling \| first5 = A. \| title = Monoclonal antibody specific for IDH1 R132H mutation. \| journal = Acta Neuropathol \| volume = 118 \| issue = 5 \| pages = 599-601 \| month = Nov \| year = 2009 \| doi = 10.1007/s00401-009-0595-z \| PMID = 19798509 }}</ref>) stained negative cases are sequenced for other rare mutations that include IDH1 R132C or IDH2 R172K among others. These mutations are not only useful in differential diagnosis of brain tumours but also prognostic, because tumours carrying a IDH-1 or IDH-2 mutation usually show a more favourable course than their wild-type counterparts <ref name=pmid21088844>{{Cite journal \| last1 = Hartmann \| first1 = C. \| last2 = Hentschel \| first2 = B. \| last3 = Wick \| first3 = W. \| last4 = Capper \| first4 = D. \| last5 = Felsberg \| first5 = J. \| last6 = Simon \| first6 = M. \| last7 = Westphal \| first7 = M. \| last8 = Schackert \| first8 = G. \| last9 = Meyermann \| first9 = R. \| title = Patients with IDH1 wild type anaplastic astrocytomas exhibit worse prognosis than IDH1-mutated glioblastomas, and IDH1 mutation status accounts for the unfavorable prognostic effect of higher age: implications for classification of gliomas. \| journal = Acta Neuropathol \| volume = 120 \| issue = 6 \| pages = 707-18 \| month = Dec \| year = 2010 \| doi = 10.1007/s00401-010-0781-z \| PMID = 21088844 }}</ref>.

	[[Oligodendroglioma]]s show a more favourable course and therfore are treated differently than [[astrocytoma]]s. A clear separation of these two entities is important, because [[H&E]] morphology is not always convincing. Succesful treatment depends on allelic losses on chromosomal arms 1p and 19q in oligodendroglioma that can be obtained by copy-number analysis or microsatellite PCR. By combining LOH (loss of heterozygosity) 1p/19q and [[ATRX]] status it is also possible to place the mixed [[oligoastrocytoma]]s into the astrocytoma or oligodendroglioma group.		[[Oligodendroglioma]]s show a more favourable course and therfore are treated differently than [[astrocytoma]]s. A clear separation of these two entities is important, because [[H&E]] morphology is not always convincing. Succesful treatment depends on allelic losses on chromosomal arms 1p and 19q in oligodendroglioma that can be obtained by copy-number analysis or microsatellite PCR. By combining LOH (loss of heterozygosity) 1p/19q and [[ATRX]] status it is also possible to place the mixed [[oligoastrocytoma]]s into the astrocytoma or oligodendroglioma group.

			===Day 1===

			====Immunofluorescence====

			Immunofluorescence is a technique used for light microscopy with a fluorescence microscope (usually a confocal microscope). This technique uses the specificity of antibodies to their antigen to target fluorescent dyes to specific biomolecule targets within a cell, and therefore allows visualisation of the distribution of the target molecule through the sample. The typical approach uses a unlabeled first (primary) antibody that specifically binds the target molecule, and the secondary antibody, which carries the fluorophore, recognises the primary antibody and binds to it. Advantages of immunofluorescence are the usually better resolution of the signals compared with standard light-microscope stains and the possibility to combine antibodies of different species to target two or more epitopes with different fluorophores. These different signals can be merged into a single image.

			<gallery>
			File:VIMENTIN.jpg \| Immunofluorescence staining for vimentin in human epithelial cells (green).
			File:Neuron in tissue culture.jpg \| Combined immunofluoerescence to visualize Neurofilament (green) and alpha-internexin (red).
			</gallery>

			====Myopathology====
			The skeletal muscle is anchored by tendons (or by aponeuroses at a few places) to bone and is used to effect skeletal movement such as locomotion and to maintain posture. Striated or skeletal muscle only contracts voluntarily, upon influence of the central nervous system.Skeletal muscle is further divided into several subtypes:
			* Type I, slow oxidative, slow twitch, or "red" muscle is dense with capillaries and is rich in mitochondria and myoglobin, giving the muscle tissue its characteristic red color. It can carry more oxygen and sustain aerobic activity.
			* Type II, fast twitch muscle, has three major kinds that are, in order of increasing contractile speed.
			Muscle biopsies are performed to obtain a specific diagnosis in persisting weakness or muscle pain.

			<gallery>
			File:1007 Muscle Fibes (large).jpg \| Structure of myofibers.
			File:Denervation atrophy - high mag.jpg \| Cross section of skeletal muscle (HE stain). The variation in size is due to loss of innervation (neurogenic atrophy).
			File:DM2 Histopathology.jpg \| Slow myosin staining in muscle cross section highlighting type 1 fibers (brown).
			File:Polymyositis HE.jpg \| Inflammatory cells in muscle fibers allow the diagnosis of myositis.
			File:Pompe vacuoles.jpg \| Defects in muscle enzymes result in abnormal storage - here vacuoles in acid maltase deficiency.
			File:LGMD2D alpha sarcoglycan.jpg \| Inherited diseases often affect elementar structural proteins, as seen here with alpha-sarcoglycan deficiency in limb-girdle musculary dystrophy (B).
			</gallery>

	==References==		==References==

Jensflorian: day 2 molecular neurooncology

2015-10-06T08:30:13Z

day 2 molecular neurooncology

← Older revision		Revision as of 08:30, 6 October 2015
Line 214:		Line 214:
	File:Neuropathology_case_IX_06.jpg \| MIB-1		File:Neuropathology_case_IX_06.jpg \| MIB-1
	File:Neuroparthology case IX 0125.jpg \| [[ATRX]]		File:Neuroparthology case IX 0125.jpg \| [[ATRX]]
	File:Neuropathology case IX.jpg \| [[~~IDH1~~]]		File:Neuropathology case IX.jpg \| [[IDH-1]]
	File:Neuropathology case IX.jpg \| panCK		File:Neuropathology case IX.jpg \| panCK
	</gallery>		</gallery>

	[[Glioblastoma]] is a pleomorphic astroglial tumor with endothelial proliferations and necrosis. As expected by a malignant tumor, the number of proliferating cells (MIB-1) is high. The tumour cells often stain for [[GFAP]]. There is no [[ATRX]] loss and the [[~~IDH1~~]] R132H mutation is absent (negative staining).		[[Glioblastoma]] is a pleomorphic astroglial tumor with endothelial proliferations and necrosis. As expected by a malignant tumor, the number of proliferating cells (MIB-1) is high. The tumour cells often stain for [[GFAP]]. There is no [[ATRX]] loss and the [[IDH-1]] R132H mutation is absent (negative staining).

	{{hidden\|Other language: German\| Glioblastome sind pleomorphe astrogliale Tumore mit Gefäßproliferaten und Nekrosen. Entsprechend einem malignen Tumor ist die Anzahl der proliferierenden Zellen (MIB-1) hoch. Die Tumorzellen markieren sich für GFAP. Es besteht kein Verlust von ATRX und die IDH1 R132H Mutationsfärbung ist negativ.		{{hidden\|Other language: German\| Glioblastome sind pleomorphe astrogliale Tumore mit Gefäßproliferaten und Nekrosen. Entsprechend einem malignen Tumor ist die Anzahl der proliferierenden Zellen (MIB-1) hoch. Die Tumorzellen markieren sich für GFAP. Es besteht kein Verlust von ATRX und die IDH1 R132H Mutationsfärbung ist negativ.
Line 229:		Line 229:
	File:Neuropathology case II 04.jpg \| MIB-1		File:Neuropathology case II 04.jpg \| MIB-1
	File:Neuroparthology case IX 0125.jpg \| [[ATRX]]		File:Neuroparthology case IX 0125.jpg \| [[ATRX]]
	File:IDH1 R132H in anaplastic ologodendroglioma.jpg \| [[~~IDH1~~]]		File:IDH1 R132H in anaplastic ologodendroglioma.jpg \| [[IDH-1]]
	File:Neuropathology case IX.jpg \| panCK		File:Neuropathology case IX.jpg \| panCK
	</gallery>		</gallery>

	[[Oligodendroglioma]] is a diffuse geowing glial tumour with clear cell morphology. In WHO grade II the MIB-1 proliferation index is rather low. GFAP stains the neuropil background and minigemistocytes (if present). There is no [[ATRX]] loss. The vast majority of oligodendrogliomas stain positively for [[~~IDH1~~]] R132H mutation.There is no expression of epithelial markers (panCK).		[[Oligodendroglioma]] is a diffuse geowing glial tumour with clear cell morphology. In WHO grade II the MIB-1 proliferation index is rather low. GFAP stains the neuropil background and minigemistocytes (if present). There is no [[ATRX]] loss. The vast majority of oligodendrogliomas stain positively for [[IDH-1]] R132H mutation.There is no expression of epithelial markers (panCK).

	{{hidden\|Other language: German\|Oligodendrogliome sind diffus wachsende gliale Tumore mit klarzelligem Aspekt in der Morphologie. In WHO Grad II Tumoren ist der MIB-1 Proliferationsindex gering. GFAP färbt vor allem das Neuropil im Hintergrund sowie Minigemistozyten, wenn diese im Tumor vorkommen. Es findet sich kein ATRX Verlust. Der Großteil der Oligodendrogliome ist positiv für die IDH1 R132H Mutation. Epitheliale Marker wie panCK werden nicht exprimiert.}}		{{hidden\|Other language: German\|Oligodendrogliome sind diffus wachsende gliale Tumore mit klarzelligem Aspekt in der Morphologie. In WHO Grad II Tumoren ist der MIB-1 Proliferationsindex gering. GFAP färbt vor allem das Neuropil im Hintergrund sowie Minigemistozyten, wenn diese im Tumor vorkommen. Es findet sich kein ATRX Verlust. Der Großteil der Oligodendrogliome ist positiv für die IDH1 R132H Mutation. Epitheliale Marker wie panCK werden nicht exprimiert.}}
Line 239:		Line 239:
	*Astrocytoma		*Astrocytoma
	<gallery>		<gallery>
	File:Astrocytoma whoII HE.jpg		File:Astrocytoma whoII HE.jpg \| [[H&E]]
	File:GFAP astrocytoma.jpg \| [[GFAP]]		File:GFAP astrocytoma.jpg \| [[GFAP]]
	File:Neuropathology case II 04.jpg \| MIB-1		File:Neuropathology case II 04.jpg \| MIB-1
	File:Neuropathology case II ATRX immunohistochemistry.jpg \| [[ATRX]]		File:Neuropathology case II ATRX immunohistochemistry.jpg \| [[ATRX]]
	File:IDH1R132H oligoastrocytoma.jpg \| \| [[~~IDH1~~]]		File:IDH1R132H oligoastrocytoma.jpg \| \| [[IDH-1]]
	File:Neuropathology case IX.jpg \| panCK		File:Neuropathology case IX.jpg \| panCK
	</gallery>		</gallery>

	[[Astrocytoma]] is a diffusely growing tumor with low cell density, neoplastic astrocytes resting in a fibrillary backrgound and low MIB1 index. [[GFAP]] is strong and also stains the cell processes. [[~~IDH1~~]] R132H postive astrocytomas usually exhibit nuclear [[ATRX]] loss. There is no expression of epithelial markers (panCK).		[[Astrocytoma]] is a diffusely growing tumor with low cell density, neoplastic astrocytes resting in a fibrillary backrgound and low MIB1 index. [[GFAP]] is strong and also stains the cell processes. [[IDH-1]] R132H postive astrocytomas usually exhibit nuclear [[ATRX]] loss. There is no expression of epithelial markers (panCK).

	{{hidden\|Other language: German\|Astrozytome sind diffus wachsende gliale Tumore mit sternförmigen Astrozyten auf einem fibrillärem Untergrund. In WHO Grad II Tumoren ist der MIB-1 Proliferationsindex gering. GFAP färbt die Tumorzellen und den Hintergrund stark an Es findet sich in IDH1 R132H mutierten Tumoren häufig ein ATRX Verlust. Epitheliale Marker wie panCK werden nicht exprimiert.}}		{{hidden\|Other language: German\|Astrozytome sind diffus wachsende gliale Tumore mit sternförmigen Astrozyten auf einem fibrillärem Untergrund. In WHO Grad II Tumoren ist der MIB-1 Proliferationsindex gering. GFAP färbt die Tumorzellen und den Hintergrund stark an Es findet sich in IDH1 R132H mutierten Tumoren häufig ein ATRX Verlust. Epitheliale Marker wie panCK werden nicht exprimiert.}}
Line 257:		Line 257:
	File:Neuropathology_case_XII_05.jpg \| MIB-1		File:Neuropathology_case_XII_05.jpg \| MIB-1
	File:Neuropathology_case_XIII_04.jpg \| [[ATRX]]		File:Neuropathology_case_XIII_04.jpg \| [[ATRX]]
	File:Neuropathology_case_XIII_06.jpg \| [[~~IDH1~~]]		File:Neuropathology_case_XIII_06.jpg \| [[IDH-1]]
	File:Neuropathology_case_XIII_02.jpg \| panCK		File:Neuropathology_case_XIII_02.jpg \| panCK
	</gallery>		</gallery>

	[[Brain_metastasis\|Brain metastases]] are usually circumscribed lesions that infiltrate the brain parenchyma. Most metastases are carcinomas as in this case of a renal clear cell carcinoma. At the first glance, it's morphology is similiar to [[oligodendroglioma]], but absence of [[GFAP]] and postive cytokeratin staining confirms epithelial origin. As expected from a malignant tumor, MIB-1 proliferation is elevated. There is no [[ATRX]] loss and no [[~~IDH1~~]] mutation present.		[[Brain_metastasis\|Brain metastases]] are usually circumscribed lesions that infiltrate the brain parenchyma. Most metastases are carcinomas as in this case of a renal clear cell carcinoma. At the first glance, it's morphology is similiar to [[oligodendroglioma]], but absence of [[GFAP]] and postive cytokeratin staining confirms epithelial origin. As expected from a malignant tumor, MIB-1 proliferation is elevated. There is no [[ATRX]] loss and no [[IDH-1]] mutation present.

	{{hidden\|Other language: German\|Hirnmetastasen sind in der Regel umschriebene Läsionen, die das Hirnparenchym infiltrieren. Die meisten Metastasen sind Karzinome, wie in diesem Fall eines klarzelligen Nierenzellkarzinom. Auf den ersten Blick ist die Morphologie zum Oligodendrogliom sehr ähnlich, aber das Fehlen von GFAP und die Immunreaktivität für pan-Zytokeratin bestätigen die epitheliale Herkunft. Wie bei malignen Tumoren zu erwarten, ist die MIB-1 Proliferationsrate erhöht. Es existiert kein ATRX-Verlust und keine IDH1-Mutation.}}		{{hidden\|Other language: German\|Hirnmetastasen sind in der Regel umschriebene Läsionen, die das Hirnparenchym infiltrieren. Die meisten Metastasen sind Karzinome, wie in diesem Fall eines klarzelligen Nierenzellkarzinom. Auf den ersten Blick ist die Morphologie zum Oligodendrogliom sehr ähnlich, aber das Fehlen von GFAP und die Immunreaktivität für pan-Zytokeratin bestätigen die epitheliale Herkunft. Wie bei malignen Tumoren zu erwarten, ist die MIB-1 Proliferationsrate erhöht. Es existiert kein ATRX-Verlust und keine IDH1-Mutation.}}

	A descriptive overview of various brain tumours is found [[Neuropathology tumours\|here]].		A descriptive overview of various brain tumours is found [[Neuropathology tumours\|here]].

			====Molecular neurooncology====

			Because [[IDH-1]] and IDH-2 mutations are found in up to 80% of [[astrocytoma]]s and [[oligodendroglioma]], IDH-1 R132H (which detects only the R132H substitution <ref name=pmid19798509>{{Cite journal \| last1 = Capper \| first1 = D. \| last2 = Zentgraf \| first2 = H. \| last3 = Balss \| first3 = J. \| last4 = Hartmann \| first4 = C. \| last5 = von Deimling \| first5 = A. \| title = Monoclonal antibody specific for IDH1 R132H mutation. \| journal = Acta Neuropathol \| volume = 118 \| issue = 5 \| pages = 599-601 \| month = Nov \| year = 2009 \| doi = 10.1007/s00401-009-0595-z \| PMID = 19798509 }}</ref>) stained negative cases are sequenced for other rare mutations that include IDH1 R132C or IDH2 R172K among others. These mutations are not only useful in differential diagnosis of brain tumours but also prognostic, because tumours carrying a IDH-1 or IDH-2 mutation usually show a more favourable course than their wild-type counterparts <ref name=pmid21088844>{{Cite journal \| last1 = Hartmann \| first1 = C. \| last2 = Hentschel \| first2 = B. \| last3 = Wick \| first3 = W. \| last4 = Capper \| first4 = D. \| last5 = Felsberg \| first5 = J. \| last6 = Simon \| first6 = M. \| last7 = Westphal \| first7 = M. \| last8 = Schackert \| first8 = G. \| last9 = Meyermann \| first9 = R. \| title = Patients with IDH1 wild type anaplastic astrocytomas exhibit worse prognosis than IDH1-mutated glioblastomas, and IDH1 mutation status accounts for the unfavorable prognostic effect of higher age: implications for classification of gliomas. \| journal = Acta Neuropathol \| volume = 120 \| issue = 6 \| pages = 707-18 \| month = Dec \| year = 2010 \| doi = 10.1007/s00401-010-0781-z \| PMID = 21088844 }}</ref>.

			[[Oligodendroglioma]]s show a more favourable course and therfore are treated differently than [[astrocytoma]]s. A clear separation of these two entities is important, because [[H&E]] morphology is not always convincing. Succesful treatment depends on allelic losses on chromosomal arms 1p and 19q in oligodendroglioma that can be obtained by copy-number analysis or microsatellite PCR. By combining LOH (loss of heterozygosity) 1p/19q and [[ATRX]] status it is also possible to place the mixed [[oligoastrocytoma]]s into the astrocytoma or oligodendroglioma group.






	==References==		==References==

Jensflorian: /* Typical staining patterns */ last case

2015-10-06T07:56:33Z

Typical staining patterns: last case

← Older revision		Revision as of 07:56, 6 October 2015
Line 218:		Line 218:
	</gallery>		</gallery>

	[[Glioblastoma]] is a pleomorphic astroglial tumor with endothelial proliferations and necrosis. As expected by a malignant tumor, the number of proliferating cells (MIB-1) is high. The tumour cells often stain for GFAP. There is no ATRX loss and the IDH1 R132H mutation is absent (negative staining).		[[Glioblastoma]] is a pleomorphic astroglial tumor with endothelial proliferations and necrosis. As expected by a malignant tumor, the number of proliferating cells (MIB-1) is high. The tumour cells often stain for [[GFAP]]. There is no [[ATRX]] loss and the [[IDH1]] R132H mutation is absent (negative staining).

	{{hidden\|Other language: German\| Glioblastome sind pleomorphe astrogliale Tumore mit Gefäßproliferaten und Nekrosen. Entsprechend einem malignen Tumor ist die Anzahl der proliferierenden Zellen (MIB-1) hoch. Die Tumorzellen markieren sich für GFAP. Es besteht kein Verlust von ATRX und die IDH1 R132H Mutationsfärbung ist negativ.		{{hidden\|Other language: German\| Glioblastome sind pleomorphe astrogliale Tumore mit Gefäßproliferaten und Nekrosen. Entsprechend einem malignen Tumor ist die Anzahl der proliferierenden Zellen (MIB-1) hoch. Die Tumorzellen markieren sich für GFAP. Es besteht kein Verlust von ATRX und die IDH1 R132H Mutationsfärbung ist negativ.
Line 233:		Line 233:
	</gallery>		</gallery>

	[[Oligodendroglioma]] is a diffuse geowing glial tumour with clear cell morphology. In WHO grade II the MIB-1 proliferation index is rather low. GFAP stains the neuropil background and minigemistocytes (if present). There is no ATRX loss. The vast majority of oligodendrogliomas stain positively for IDH1 R132H mutation.There is no expression of epithelial markers (panCK).		[[Oligodendroglioma]] is a diffuse geowing glial tumour with clear cell morphology. In WHO grade II the MIB-1 proliferation index is rather low. GFAP stains the neuropil background and minigemistocytes (if present). There is no [[ATRX]] loss. The vast majority of oligodendrogliomas stain positively for [[IDH1]] R132H mutation.There is no expression of epithelial markers (panCK).

	{{hidden\|Other language: German\|Oligodendrogliome sind diffus wachsende gliale Tumore mit klarzelligem Aspekt in der Morphologie. In WHO Grad II Tumoren ist der MIB-1 Proliferationsindex gering. GFAP färbt vor allem das Neuropil im Hintergrund sowie Minigemistozyten, wenn diese im Tumor vorkommen. Es findet sich kein ATRX Verlust. Der Großteil der Oligodendrogliome ist positiv für die IDH1 R132H Mutation. Epitheliale Marker wie panCK werden nicht exprimiert}}		{{hidden\|Other language: German\|Oligodendrogliome sind diffus wachsende gliale Tumore mit klarzelligem Aspekt in der Morphologie. In WHO Grad II Tumoren ist der MIB-1 Proliferationsindex gering. GFAP färbt vor allem das Neuropil im Hintergrund sowie Minigemistozyten, wenn diese im Tumor vorkommen. Es findet sich kein ATRX Verlust. Der Großteil der Oligodendrogliome ist positiv für die IDH1 R132H Mutation. Epitheliale Marker wie panCK werden nicht exprimiert.}}

	*Astrocytoma		*Astrocytoma
Line 247:		Line 247:
	</gallery>		</gallery>

	[Astrocytoma]] is a diffusely growing tumor with low cell density, neoplastic astrocytes resting in a fibrillary backrgound and low MIB1 index. GFAP is strong and also stains the cell processes. ~~IND1~~ R132H postive astrocytomas usually exhibit nuclear ATRX loss. There is no expression of epithelial markers (panCK).		[[Astrocytoma]] is a diffusely growing tumor with low cell density, neoplastic astrocytes resting in a fibrillary backrgound and low MIB1 index. [[GFAP]] is strong and also stains the cell processes. [[IDH1]] R132H postive astrocytomas usually exhibit nuclear [[ATRX]] loss. There is no expression of epithelial markers (panCK).

	{{hidden\|Other language: German\|Astrozytome sind diffus wachsende gliale Tumore mit sternförmigen Astrozyten auf einem fibrillärem Untergrund. In WHO Grad II Tumoren ist der MIB-1 Proliferationsindex gering. GFAP färbt die Tumorzellen und den Hintergrund stark an Es findet sich in IDH1 R132H mutierten Tumoren häufig ein ATRX Verlust. Epitheliale Marker wie panCK werden nicht exprimiert}}		{{hidden\|Other language: German\|Astrozytome sind diffus wachsende gliale Tumore mit sternförmigen Astrozyten auf einem fibrillärem Untergrund. In WHO Grad II Tumoren ist der MIB-1 Proliferationsindex gering. GFAP färbt die Tumorzellen und den Hintergrund stark an Es findet sich in IDH1 R132H mutierten Tumoren häufig ein ATRX Verlust. Epitheliale Marker wie panCK werden nicht exprimiert.}}

			*Carcinoma metastasis
			<gallery>
			File:Neuropathology_case_XIII_01.jpg \| HE
			File:Neuropathology_case_XIII_03.jpg \| [[GFAP]]
			File:Neuropathology_case_XII_05.jpg \| MIB-1
			File:Neuropathology_case_XIII_04.jpg \| [[ATRX]]
			File:Neuropathology_case_XIII_06.jpg \| [[IDH1]]
			File:Neuropathology_case_XIII_02.jpg \| panCK
			</gallery>

			[[Brain_metastasis\|Brain metastases]] are usually circumscribed lesions that infiltrate the brain parenchyma. Most metastases are carcinomas as in this case of a renal clear cell carcinoma. At the first glance, it's morphology is similiar to [[oligodendroglioma]], but absence of [[GFAP]] and postive cytokeratin staining confirms epithelial origin. As expected from a malignant tumor, MIB-1 proliferation is elevated. There is no [[ATRX]] loss and no [[IDH1]] mutation present.

			{{hidden\|Other language: German\|Hirnmetastasen sind in der Regel umschriebene Läsionen, die das Hirnparenchym infiltrieren. Die meisten Metastasen sind Karzinome, wie in diesem Fall eines klarzelligen Nierenzellkarzinom. Auf den ersten Blick ist die Morphologie zum Oligodendrogliom sehr ähnlich, aber das Fehlen von GFAP und die Immunreaktivität für pan-Zytokeratin bestätigen die epitheliale Herkunft. Wie bei malignen Tumoren zu erwarten, ist die MIB-1 Proliferationsrate erhöht. Es existiert kein ATRX-Verlust und keine IDH1-Mutation.}}

	A descriptive overview of various brain tumours is found [[Neuropathology tumours\|here]].		A descriptive overview of various brain tumours is found [[Neuropathology tumours\|here]].

Jensflorian: Jensflorian moved page Course Neuropathology to Course:Introduction to Neuropathology

2015-10-06T06:31:40Z

Jensflorian moved page Course Neuropathology to Course:Introduction to Neuropathology

← Older revision	Revision as of 06:31, 6 October 2015
(No difference)

Jensflorian: /* Typical staining patterns */ case 3

2015-10-02T14:23:58Z

Typical staining patterns: case 3

← Older revision		Revision as of 14:23, 2 October 2015
Line 208:		Line 208:
	====Typical staining patterns====		====Typical staining patterns====

			*Glioblastoma
	<gallery>		<gallery>
	File:Neuropathology_case_IX_02.jpg \| [[H&E]]		File:Neuropathology_case_IX_02.jpg \| [[H&E]]
	File:Neuropathology_case_IX_04.jpg \| [[GFAP]]		File:Neuropathology_case_IX_04.jpg \| [[GFAP]]
	File:Neuropathology_case_IX_06.jpg \| MIB-1		File:Neuropathology_case_IX_06.jpg \| MIB-1
	File:~~Neuropathology~~ case IX.jpg \| [[ATRX]]		File:Neuroparthology case IX 0125.jpg \| [[ATRX]]
	File:~~Neuroparthology~~ case IX ~~0125~~.jpg \| [[IDH1]]		File:Neuropathology case IX.jpg \| [[IDH1]]
	File:~~Neuroparthology~~ case IX ~~0125~~.jpg \| panCK		File:Neuropathology case IX.jpg \| panCK
	</gallery>		</gallery>

Line 222:		Line 223:
	}}		}}

			*Oligodendroglioma
	<gallery>		<gallery>
	File:Oligodendroglioma1 low mag.jpg \| [[H&E]]		File:Oligodendroglioma1 low mag.jpg \| [[H&E]]
	File: x \| GFAP		File:Oligodendorglioma GFAP.jpg\| [[GFAP]]
	File:Neuropathology case II 04.jpg \| MIB-1		File:Neuropathology case II 04.jpg \| MIB-1
	File:Neuroparthology case IX 0125.jpg \| ATRX		File:Neuroparthology case IX 0125.jpg \| [[ATRX]]
	File:IDH1 R132H in anaplastic ologodendroglioma.jpg \| [[IDH1]]		File:IDH1 R132H in anaplastic ologodendroglioma.jpg \| [[IDH1]]
	File:Neuropathology case IX.jpg \| panCK		File:Neuropathology case IX.jpg \| panCK
	</gallery>		</gallery>

	[[Oligodendroglioma]] is a diffuse geowing glial tumour with clear cell morphology. In WHO grade II the MIB-1 proliferation index is rather low. GFAP stains the neuropil background and minigemistocytes (if present). There is no ATRX loss. The vast majority of oligodendrogliomas stain positively for IDH1 R132H mutation.		[[Oligodendroglioma]] is a diffuse geowing glial tumour with clear cell morphology. In WHO grade II the MIB-1 proliferation index is rather low. GFAP stains the neuropil background and minigemistocytes (if present). There is no ATRX loss. The vast majority of oligodendrogliomas stain positively for IDH1 R132H mutation.There is no expression of epithelial markers (panCK).

			{{hidden\|Other language: German\|Oligodendrogliome sind diffus wachsende gliale Tumore mit klarzelligem Aspekt in der Morphologie. In WHO Grad II Tumoren ist der MIB-1 Proliferationsindex gering. GFAP färbt vor allem das Neuropil im Hintergrund sowie Minigemistozyten, wenn diese im Tumor vorkommen. Es findet sich kein ATRX Verlust. Der Großteil der Oligodendrogliome ist positiv für die IDH1 R132H Mutation. Epitheliale Marker wie panCK werden nicht exprimiert}}

			*Astrocytoma
			<gallery>
			File:Astrocytoma whoII HE.jpg
			File:GFAP astrocytoma.jpg \| [[GFAP]]
			File:Neuropathology case II 04.jpg \| MIB-1
			File:Neuropathology case II ATRX immunohistochemistry.jpg \| [[ATRX]]
			File:IDH1R132H oligoastrocytoma.jpg \| \| [[IDH1]]
			File:Neuropathology case IX.jpg \| panCK
			</gallery>

			[Astrocytoma]] is a diffusely growing tumor with low cell density, neoplastic astrocytes resting in a fibrillary backrgound and low MIB1 index. GFAP is strong and also stains the cell processes. IND1 R132H postive astrocytomas usually exhibit nuclear ATRX loss. There is no expression of epithelial markers (panCK).

			{{hidden\|Other language: German\|Astrozytome sind diffus wachsende gliale Tumore mit sternförmigen Astrozyten auf einem fibrillärem Untergrund. In WHO Grad II Tumoren ist der MIB-1 Proliferationsindex gering. GFAP färbt die Tumorzellen und den Hintergrund stark an Es findet sich in IDH1 R132H mutierten Tumoren häufig ein ATRX Verlust. Epitheliale Marker wie panCK werden nicht exprimiert}}

	A descriptive overview of various brain tumours is found [[Neuropathology tumours\|here]].		A descriptive overview of various brain tumours is found [[Neuropathology tumours\|here]].

Jensflorian: + case 2

2015-10-02T13:44:36Z

+ case 2

← Older revision		Revision as of 13:44, 2 October 2015
Line 214:		Line 214:
	File:Neuropathology case IX.jpg \| [[ATRX]]		File:Neuropathology case IX.jpg \| [[ATRX]]
	File:Neuroparthology case IX 0125.jpg \| [[IDH1]]		File:Neuroparthology case IX 0125.jpg \| [[IDH1]]
			File:Neuroparthology case IX 0125.jpg \| panCK
	</gallery>		</gallery>

	[[Glioblastoma]] is a pleomorphic astroglial tumor with endothelial proliferations and necrosis. As expected by a malignant tumor, the number of proliferating cells (MIB-1) is high. The tumour cells often stain for GFAP. There is no ATRX loss and the IDH1 R132H mutation is absent (negative staining).		[[Glioblastoma]] is a pleomorphic astroglial tumor with endothelial proliferations and necrosis. As expected by a malignant tumor, the number of proliferating cells (MIB-1) is high. The tumour cells often stain for GFAP. There is no ATRX loss and the IDH1 R132H mutation is absent (negative staining).

			{{hidden\|Other language: German\| Glioblastome sind pleomorphe astrogliale Tumore mit Gefäßproliferaten und Nekrosen. Entsprechend einem malignen Tumor ist die Anzahl der proliferierenden Zellen (MIB-1) hoch. Die Tumorzellen markieren sich für GFAP. Es besteht kein Verlust von ATRX und die IDH1 R132H Mutationsfärbung ist negativ.
			}}

			<gallery>
			File:Oligodendroglioma1 low mag.jpg \| [[H&E]]
			File: x \| GFAP
			File:Neuropathology case II 04.jpg \| MIB-1
			File:Neuroparthology case IX 0125.jpg \| ATRX
			File:IDH1 R132H in anaplastic ologodendroglioma.jpg \| [[IDH1]]
			File:Neuropathology case IX.jpg \| panCK
			</gallery>

			[[Oligodendroglioma]] is a diffuse geowing glial tumour with clear cell morphology. In WHO grade II the MIB-1 proliferation index is rather low. GFAP stains the neuropil background and minigemistocytes (if present). There is no ATRX loss. The vast majority of oligodendrogliomas stain positively for IDH1 R132H mutation.

Jensflorian: /* Day 2 */ sample 1

2015-10-02T12:09:54Z

Day 2: sample 1

← Older revision		Revision as of 12:09, 2 October 2015
Line 205:		Line 205:

	*'''ATRX''' - Alpha thalassemia/mental retardation syndrome X-linked is a member of the WSI/SNF chromatin remodelling family of proteins that have an important roel in sgegation of chromosomes during mitosis. It is expressed in the nuclei of all normal tissues and is lost in [[astrocytoma]]s that use alternative lengthening of telomeres (ALT) as their telomere maintenance mechanism. Since nuclear staining is lost only in IDH1 mutated astrocytomas, the antibody is a very usefula diagnostic biomarker to separate astrocytoma from [[oligodendroglioma]]. Itis however not useful to separate primary glioblastoma from other ATRX-positive tumors such as oligodendroglioma or brain metastases.		*'''ATRX''' - Alpha thalassemia/mental retardation syndrome X-linked is a member of the WSI/SNF chromatin remodelling family of proteins that have an important roel in sgegation of chromosomes during mitosis. It is expressed in the nuclei of all normal tissues and is lost in [[astrocytoma]]s that use alternative lengthening of telomeres (ALT) as their telomere maintenance mechanism. Since nuclear staining is lost only in IDH1 mutated astrocytomas, the antibody is a very usefula diagnostic biomarker to separate astrocytoma from [[oligodendroglioma]]. Itis however not useful to separate primary glioblastoma from other ATRX-positive tumors such as oligodendroglioma or brain metastases.

			====Typical staining patterns====

			<gallery>
			File:Neuropathology_case_IX_02.jpg \| [[H&E]]
			File:Neuropathology_case_IX_04.jpg \| [[GFAP]]
			File:Neuropathology_case_IX_06.jpg \| MIB-1
			File:Neuropathology case IX.jpg \| [[ATRX]]
			File:Neuroparthology case IX 0125.jpg \| [[IDH1]]
			</gallery>

			[[Glioblastoma]] is a pleomorphic astroglial tumor with endothelial proliferations and necrosis. As expected by a malignant tumor, the number of proliferating cells (MIB-1) is high. The tumour cells often stain for GFAP. There is no ATRX loss and the IDH1 R132H mutation is absent (negative staining).



	A descriptive overview of various brain tumours is found [[Neuropathology tumours\|here]].		A descriptive overview of various brain tumours is found [[Neuropathology tumours\|here]].

Jensflorian: /* Day 2 */ tbc

2015-10-02T10:36:30Z

Day 2: tbc

← Older revision		Revision as of 10:36, 2 October 2015
Line 203:		Line 203:

	*'''IDH1''' (IDH1 R132H) The isocitrate dehydrogenase is an important enzyme catalyzing the oxidative decarboxylation of isocitrate to 2-oxoglutarate. Mutations in motochondrial IDH1 and its cytoplasmic homologue IDH2 are among the most frequent mutations in diffuse gliomas, including [[astrocytoma]], [[oligodendroglioma]] and the secondary [[glioblastoma]]s that are derived therof. In contrast primary (de novo) glioblastomas usually do not carry this mutation. IDH1 mutations are heterozygous, typically involving an amino acid substitution in the active site of the enzyme in codon 132. The employed antibody is specific for the very common R132H amino acid exchange. It doesn't detect rare R132C or other IDH2 mutations. In such cases direct sequencing is necessary. Because the R132H mutation is tumor specfic, positive staining (oligodendrogliomas are ideal controls) is proves presence of a neoplasm.		*'''IDH1''' (IDH1 R132H) The isocitrate dehydrogenase is an important enzyme catalyzing the oxidative decarboxylation of isocitrate to 2-oxoglutarate. Mutations in motochondrial IDH1 and its cytoplasmic homologue IDH2 are among the most frequent mutations in diffuse gliomas, including [[astrocytoma]], [[oligodendroglioma]] and the secondary [[glioblastoma]]s that are derived therof. In contrast primary (de novo) glioblastomas usually do not carry this mutation. IDH1 mutations are heterozygous, typically involving an amino acid substitution in the active site of the enzyme in codon 132. The employed antibody is specific for the very common R132H amino acid exchange. It doesn't detect rare R132C or other IDH2 mutations. In such cases direct sequencing is necessary. Because the R132H mutation is tumor specfic, positive staining (oligodendrogliomas are ideal controls) is proves presence of a neoplasm.

			*'''ATRX''' - Alpha thalassemia/mental retardation syndrome X-linked is a member of the WSI/SNF chromatin remodelling family of proteins that have an important roel in sgegation of chromosomes during mitosis. It is expressed in the nuclei of all normal tissues and is lost in [[astrocytoma]]s that use alternative lengthening of telomeres (ALT) as their telomere maintenance mechanism. Since nuclear staining is lost only in IDH1 mutated astrocytomas, the antibody is a very usefula diagnostic biomarker to separate astrocytoma from [[oligodendroglioma]]. Itis however not useful to separate primary glioblastoma from other ATRX-positive tumors such as oligodendroglioma or brain metastases.

	A descriptive overview of various brain tumours is found [[Neuropathology tumours\|here]].		A descriptive overview of various brain tumours is found [[Neuropathology tumours\|here]].

Jensflorian: /* Antibodies in neurooncology */ IDh

2015-10-01T20:08:07Z

Antibodies in neurooncology: IDh

← Older revision		Revision as of 20:08, 1 October 2015
Line 201:		Line 201:

	*'''GFAP''' (Ab-1) The 49kDa glial fibrillary acidic protein is an intermediate filament protein that is expressed by numerous cell types of the CNS including astrocytes and ependymal cells. It is related to otherintermediate filaments such as desmin and vimentin. Loss of GFAP through mutations results in Alexanders Disease where the white matter degenerates. Brain tumors that are derived of astrocytes ([[astroccatoma]] and [[glioblastoma]] stain for GFAP, that is absent in metastatic carcinomas and oligodendrogliomas [except for [[minigemistocyte]]s. Local and reactive astrocytes between brain tumor cells may mark for GFAP and should not confused with tumour positivity. White matter serves as ideal positive control. Cross-reactivity is seen with peripheral Schwann cells.		*'''GFAP''' (Ab-1) The 49kDa glial fibrillary acidic protein is an intermediate filament protein that is expressed by numerous cell types of the CNS including astrocytes and ependymal cells. It is related to otherintermediate filaments such as desmin and vimentin. Loss of GFAP through mutations results in Alexanders Disease where the white matter degenerates. Brain tumors that are derived of astrocytes ([[astroccatoma]] and [[glioblastoma]] stain for GFAP, that is absent in metastatic carcinomas and oligodendrogliomas [except for [[minigemistocyte]]s. Local and reactive astrocytes between brain tumor cells may mark for GFAP and should not confused with tumour positivity. White matter serves as ideal positive control. Cross-reactivity is seen with peripheral Schwann cells.

			*'''IDH1''' (IDH1 R132H) The isocitrate dehydrogenase is an important enzyme catalyzing the oxidative decarboxylation of isocitrate to 2-oxoglutarate. Mutations in motochondrial IDH1 and its cytoplasmic homologue IDH2 are among the most frequent mutations in diffuse gliomas, including [[astrocytoma]], [[oligodendroglioma]] and the secondary [[glioblastoma]]s that are derived therof. In contrast primary (de novo) glioblastomas usually do not carry this mutation. IDH1 mutations are heterozygous, typically involving an amino acid substitution in the active site of the enzyme in codon 132. The employed antibody is specific for the very common R132H amino acid exchange. It doesn't detect rare R132C or other IDH2 mutations. In such cases direct sequencing is necessary. Because the R132H mutation is tumor specfic, positive staining (oligodendrogliomas are ideal controls) is proves presence of a neoplasm.

	A descriptive overview of various brain tumours is found [[Neuropathology tumours\|here]].		A descriptive overview of various brain tumours is found [[Neuropathology tumours\|here]].

Jensflorian: /* Antibodies in neurooncology */ +gfap

2015-10-01T19:25:55Z

Antibodies in neurooncology: +gfap

← Older revision		Revision as of 19:25, 1 October 2015
Line 198:		Line 198:
	* '''Ki-67''' (Kiel-67, clone MiB-1 which stands for Made in Borstel) is a nuclear protein that is associated with cellular proliferation. During interphase, the Ki-67 antigen can be exclusively detected within the cell nucleus, whereas in mitosis most of the protein is relocated to the surface of the chromosomes. Ki-67 protein is present during all active phases of the cell cycle (G1, S, G2, and mitosis), but is absent from resting cells (G0).<ref name="pmid10653597">{{Cite journal \| last1 = Scholzen \| first1 = T. \| last2 = Gerdes \| first2 = J. \| title = The Ki-67 protein: from the known and the unknown. \| journal = J Cell Physiol \| volume = 182 \| issue = 3 \| pages = 311-22 \| month = Mar \| year = 2000 \| doi = 10.1002/(SICI)1097-4652(200003)182:3<311::AID-JCP1>3.0.CO;2-9 \| PMID = 10653597 }}</ref> Ki-67 is an excellent marker to determine the growth fraction of a given cell population. The fraction of Ki-67-positive tumor cells (the Ki-67 labeling index) is often correlated with the clinical course of cancer. <ref>https://en.wikipedia.org/wiki/Ki-67_%28protein%29</ref> An [[astrocytoma]] with 2% positive tumor cells is growing considerably slower than a [[glioblastoma]] with a labelling index of 20%. Cells with a quick turnover therefore serve as good positive controls for this antibody.		* '''Ki-67''' (Kiel-67, clone MiB-1 which stands for Made in Borstel) is a nuclear protein that is associated with cellular proliferation. During interphase, the Ki-67 antigen can be exclusively detected within the cell nucleus, whereas in mitosis most of the protein is relocated to the surface of the chromosomes. Ki-67 protein is present during all active phases of the cell cycle (G1, S, G2, and mitosis), but is absent from resting cells (G0).<ref name="pmid10653597">{{Cite journal \| last1 = Scholzen \| first1 = T. \| last2 = Gerdes \| first2 = J. \| title = The Ki-67 protein: from the known and the unknown. \| journal = J Cell Physiol \| volume = 182 \| issue = 3 \| pages = 311-22 \| month = Mar \| year = 2000 \| doi = 10.1002/(SICI)1097-4652(200003)182:3<311::AID-JCP1>3.0.CO;2-9 \| PMID = 10653597 }}</ref> Ki-67 is an excellent marker to determine the growth fraction of a given cell population. The fraction of Ki-67-positive tumor cells (the Ki-67 labeling index) is often correlated with the clinical course of cancer. <ref>https://en.wikipedia.org/wiki/Ki-67_%28protein%29</ref> An [[astrocytoma]] with 2% positive tumor cells is growing considerably slower than a [[glioblastoma]] with a labelling index of 20%. Cells with a quick turnover therefore serve as good positive controls for this antibody.

	* '''panCK''' (MNF-116) Cytokeratins are proteins of keratin-containing intermediate filaments found in the intracytoplasmic cytoskeleton of eukaryontic epithelial tissue and their derived tumours. The 20 different cytokeratins can be divided into low versus high molecular weight solely based on their molecular weight. The current cocktail detects almost all types of epithelial, from simple glandular to stratfied squamous epithelia and therefore is ideal to detect malignant epithelial tumours ([[carcinoma]]s). Rarely a cross-reaction with dendritic cells in the tonsil or smooth muscle cells of vessels is observed. Most brain metastases are carcinomas of breast, lung or prostrate and therefore stain intensely for pan-cytokeratin. In contrast, glial and neuronal brain tumours as well as melanomas do not stain for this marker. Expression of these cytokeratin types is frequently organ or tissue specific. Pathologists employ different cytokeratins to detect the cell of origin of various tumors. As an example, [[Cytokeratin_7\|CK7]] is typically expressed in the ductal epithelium of the genitourinary tract and [[Cytokeratin_20\|CK20]] most commonly in the gastrointestinal tract. Best results are obtained with Trypsin or Pronase pretreatment for antigen demasking. Normal epithelial tissue (gut, skin) may serve as positive control.		* '''panCK''' (MNF-116) Cytokeratins are proteins of keratin-containing intermediate filaments found in the intracytoplasmic cytoskeleton of eukaryontic epithelial tissue and their derived tumours. The 20 different cytokeratins can be divided into low versus high molecular weight solely based on their molecular weight. The current cocktail detects almost all types of epithelial, from simple glandular to stratfied squamous epithelia and therefore is ideal to detect malignant epithelial tumours ([[carcinoma]]s). Rarely a cross-reaction with dendritic cells in the tonsil or smooth muscle cells of vessels is observed. Most brain metastases are carcinomas of breast, lung or prostrate and therefore stain intensely for pan-cytokeratin. In contrast, glial and neuronal brain tumours as well as melanomas do not stain for this marker. Expression of these cytokeratin types is frequently organ or tissue specific. Pathologists employ different cytokeratins to detect the cell of origin of various tumors. As an example, [[Cytokeratin_7\|CK7]] is typically expressed in the ductal epithelium of the genitourinary tract and [[Cytokeratin_20\|CK20]] most commonly in the gastrointestinal tract. Best results are obtained with Trypsin or Pronase pretreatment for antigen demasking. Normal epithelial tissue (gut, skin) may serve as positive control.

			*'''GFAP''' (Ab-1) The 49kDa glial fibrillary acidic protein is an intermediate filament protein that is expressed by numerous cell types of the CNS including astrocytes and ependymal cells. It is related to otherintermediate filaments such as desmin and vimentin. Loss of GFAP through mutations results in Alexanders Disease where the white matter degenerates. Brain tumors that are derived of astrocytes ([[astroccatoma]] and [[glioblastoma]] stain for GFAP, that is absent in metastatic carcinomas and oligodendrogliomas [except for [[minigemistocyte]]s. Local and reactive astrocytes between brain tumor cells may mark for GFAP and should not confused with tumour positivity. White matter serves as ideal positive control. Cross-reactivity is seen with peripheral Schwann cells.

	A descriptive overview of various brain tumours is found [[Neuropathology tumours\|here]].		A descriptive overview of various brain tumours is found [[Neuropathology tumours\|here]].

← Older revision		Revision as of 08:30, 6 October 2015
Line 214:		Line 214:
	File:Neuropathology_case_IX_06.jpg \| MIB-1		File:Neuropathology_case_IX_06.jpg \| MIB-1
	File:Neuroparthology case IX 0125.jpg \| [[ATRX]]		File:Neuroparthology case IX 0125.jpg \| [[ATRX]]
	File:Neuropathology case IX.jpg \| [[~~IDH1~~]]		File:Neuropathology case IX.jpg \| [[IDH-1]]
	File:Neuropathology case IX.jpg \| panCK		File:Neuropathology case IX.jpg \| panCK
	</gallery>		</gallery>

	[[Glioblastoma]] is a pleomorphic astroglial tumor with endothelial proliferations and necrosis. As expected by a malignant tumor, the number of proliferating cells (MIB-1) is high. The tumour cells often stain for [[GFAP]]. There is no [[ATRX]] loss and the [[~~IDH1~~]] R132H mutation is absent (negative staining).		[[Glioblastoma]] is a pleomorphic astroglial tumor with endothelial proliferations and necrosis. As expected by a malignant tumor, the number of proliferating cells (MIB-1) is high. The tumour cells often stain for [[GFAP]]. There is no [[ATRX]] loss and the [[IDH-1]] R132H mutation is absent (negative staining).

	{{hidden\|Other language: German\| Glioblastome sind pleomorphe astrogliale Tumore mit Gefäßproliferaten und Nekrosen. Entsprechend einem malignen Tumor ist die Anzahl der proliferierenden Zellen (MIB-1) hoch. Die Tumorzellen markieren sich für GFAP. Es besteht kein Verlust von ATRX und die IDH1 R132H Mutationsfärbung ist negativ.		{{hidden\|Other language: German\| Glioblastome sind pleomorphe astrogliale Tumore mit Gefäßproliferaten und Nekrosen. Entsprechend einem malignen Tumor ist die Anzahl der proliferierenden Zellen (MIB-1) hoch. Die Tumorzellen markieren sich für GFAP. Es besteht kein Verlust von ATRX und die IDH1 R132H Mutationsfärbung ist negativ.
Line 229:		Line 229:
	File:Neuropathology case II 04.jpg \| MIB-1		File:Neuropathology case II 04.jpg \| MIB-1
	File:Neuroparthology case IX 0125.jpg \| [[ATRX]]		File:Neuroparthology case IX 0125.jpg \| [[ATRX]]
	File:IDH1 R132H in anaplastic ologodendroglioma.jpg \| [[~~IDH1~~]]		File:IDH1 R132H in anaplastic ologodendroglioma.jpg \| [[IDH-1]]
	File:Neuropathology case IX.jpg \| panCK		File:Neuropathology case IX.jpg \| panCK
	</gallery>		</gallery>

	[[Oligodendroglioma]] is a diffuse geowing glial tumour with clear cell morphology. In WHO grade II the MIB-1 proliferation index is rather low. GFAP stains the neuropil background and minigemistocytes (if present). There is no [[ATRX]] loss. The vast majority of oligodendrogliomas stain positively for [[~~IDH1~~]] R132H mutation.There is no expression of epithelial markers (panCK).		[[Oligodendroglioma]] is a diffuse geowing glial tumour with clear cell morphology. In WHO grade II the MIB-1 proliferation index is rather low. GFAP stains the neuropil background and minigemistocytes (if present). There is no [[ATRX]] loss. The vast majority of oligodendrogliomas stain positively for [[IDH-1]] R132H mutation.There is no expression of epithelial markers (panCK).

	{{hidden\|Other language: German\|Oligodendrogliome sind diffus wachsende gliale Tumore mit klarzelligem Aspekt in der Morphologie. In WHO Grad II Tumoren ist der MIB-1 Proliferationsindex gering. GFAP färbt vor allem das Neuropil im Hintergrund sowie Minigemistozyten, wenn diese im Tumor vorkommen. Es findet sich kein ATRX Verlust. Der Großteil der Oligodendrogliome ist positiv für die IDH1 R132H Mutation. Epitheliale Marker wie panCK werden nicht exprimiert.}}		{{hidden\|Other language: German\|Oligodendrogliome sind diffus wachsende gliale Tumore mit klarzelligem Aspekt in der Morphologie. In WHO Grad II Tumoren ist der MIB-1 Proliferationsindex gering. GFAP färbt vor allem das Neuropil im Hintergrund sowie Minigemistozyten, wenn diese im Tumor vorkommen. Es findet sich kein ATRX Verlust. Der Großteil der Oligodendrogliome ist positiv für die IDH1 R132H Mutation. Epitheliale Marker wie panCK werden nicht exprimiert.}}
Line 239:		Line 239:
	*Astrocytoma		*Astrocytoma
	<gallery>		<gallery>
	File:Astrocytoma whoII HE.jpg		File:Astrocytoma whoII HE.jpg \| [[H&E]]
	File:GFAP astrocytoma.jpg \| [[GFAP]]		File:GFAP astrocytoma.jpg \| [[GFAP]]
	File:Neuropathology case II 04.jpg \| MIB-1		File:Neuropathology case II 04.jpg \| MIB-1
	File:Neuropathology case II ATRX immunohistochemistry.jpg \| [[ATRX]]		File:Neuropathology case II ATRX immunohistochemistry.jpg \| [[ATRX]]
	File:IDH1R132H oligoastrocytoma.jpg \| \| [[~~IDH1~~]]		File:IDH1R132H oligoastrocytoma.jpg \| \| [[IDH-1]]
	File:Neuropathology case IX.jpg \| panCK		File:Neuropathology case IX.jpg \| panCK
	</gallery>		</gallery>

	[[Astrocytoma]] is a diffusely growing tumor with low cell density, neoplastic astrocytes resting in a fibrillary backrgound and low MIB1 index. [[GFAP]] is strong and also stains the cell processes. [[~~IDH1~~]] R132H postive astrocytomas usually exhibit nuclear [[ATRX]] loss. There is no expression of epithelial markers (panCK).		[[Astrocytoma]] is a diffusely growing tumor with low cell density, neoplastic astrocytes resting in a fibrillary backrgound and low MIB1 index. [[GFAP]] is strong and also stains the cell processes. [[IDH-1]] R132H postive astrocytomas usually exhibit nuclear [[ATRX]] loss. There is no expression of epithelial markers (panCK).

	{{hidden\|Other language: German\|Astrozytome sind diffus wachsende gliale Tumore mit sternförmigen Astrozyten auf einem fibrillärem Untergrund. In WHO Grad II Tumoren ist der MIB-1 Proliferationsindex gering. GFAP färbt die Tumorzellen und den Hintergrund stark an Es findet sich in IDH1 R132H mutierten Tumoren häufig ein ATRX Verlust. Epitheliale Marker wie panCK werden nicht exprimiert.}}		{{hidden\|Other language: German\|Astrozytome sind diffus wachsende gliale Tumore mit sternförmigen Astrozyten auf einem fibrillärem Untergrund. In WHO Grad II Tumoren ist der MIB-1 Proliferationsindex gering. GFAP färbt die Tumorzellen und den Hintergrund stark an Es findet sich in IDH1 R132H mutierten Tumoren häufig ein ATRX Verlust. Epitheliale Marker wie panCK werden nicht exprimiert.}}
Line 257:		Line 257:
	File:Neuropathology_case_XII_05.jpg \| MIB-1		File:Neuropathology_case_XII_05.jpg \| MIB-1
	File:Neuropathology_case_XIII_04.jpg \| [[ATRX]]		File:Neuropathology_case_XIII_04.jpg \| [[ATRX]]
	File:Neuropathology_case_XIII_06.jpg \| [[~~IDH1~~]]		File:Neuropathology_case_XIII_06.jpg \| [[IDH-1]]
	File:Neuropathology_case_XIII_02.jpg \| panCK		File:Neuropathology_case_XIII_02.jpg \| panCK
	</gallery>		</gallery>

	[[Brain_metastasis\|Brain metastases]] are usually circumscribed lesions that infiltrate the brain parenchyma. Most metastases are carcinomas as in this case of a renal clear cell carcinoma. At the first glance, it's morphology is similiar to [[oligodendroglioma]], but absence of [[GFAP]] and postive cytokeratin staining confirms epithelial origin. As expected from a malignant tumor, MIB-1 proliferation is elevated. There is no [[ATRX]] loss and no [[~~IDH1~~]] mutation present.		[[Brain_metastasis\|Brain metastases]] are usually circumscribed lesions that infiltrate the brain parenchyma. Most metastases are carcinomas as in this case of a renal clear cell carcinoma. At the first glance, it's morphology is similiar to [[oligodendroglioma]], but absence of [[GFAP]] and postive cytokeratin staining confirms epithelial origin. As expected from a malignant tumor, MIB-1 proliferation is elevated. There is no [[ATRX]] loss and no [[IDH-1]] mutation present.

	{{hidden\|Other language: German\|Hirnmetastasen sind in der Regel umschriebene Läsionen, die das Hirnparenchym infiltrieren. Die meisten Metastasen sind Karzinome, wie in diesem Fall eines klarzelligen Nierenzellkarzinom. Auf den ersten Blick ist die Morphologie zum Oligodendrogliom sehr ähnlich, aber das Fehlen von GFAP und die Immunreaktivität für pan-Zytokeratin bestätigen die epitheliale Herkunft. Wie bei malignen Tumoren zu erwarten, ist die MIB-1 Proliferationsrate erhöht. Es existiert kein ATRX-Verlust und keine IDH1-Mutation.}}		{{hidden\|Other language: German\|Hirnmetastasen sind in der Regel umschriebene Läsionen, die das Hirnparenchym infiltrieren. Die meisten Metastasen sind Karzinome, wie in diesem Fall eines klarzelligen Nierenzellkarzinom. Auf den ersten Blick ist die Morphologie zum Oligodendrogliom sehr ähnlich, aber das Fehlen von GFAP und die Immunreaktivität für pan-Zytokeratin bestätigen die epitheliale Herkunft. Wie bei malignen Tumoren zu erwarten, ist die MIB-1 Proliferationsrate erhöht. Es existiert kein ATRX-Verlust und keine IDH1-Mutation.}}

	A descriptive overview of various brain tumours is found [[Neuropathology tumours\|here]].		A descriptive overview of various brain tumours is found [[Neuropathology tumours\|here]].

			====Molecular neurooncology====

			Because [[IDH-1]] and IDH-2 mutations are found in up to 80% of [[astrocytoma]]s and [[oligodendroglioma]], IDH-1 R132H (which detects only the R132H substitution <ref name=pmid19798509>{{Cite journal \| last1 = Capper \| first1 = D. \| last2 = Zentgraf \| first2 = H. \| last3 = Balss \| first3 = J. \| last4 = Hartmann \| first4 = C. \| last5 = von Deimling \| first5 = A. \| title = Monoclonal antibody specific for IDH1 R132H mutation. \| journal = Acta Neuropathol \| volume = 118 \| issue = 5 \| pages = 599-601 \| month = Nov \| year = 2009 \| doi = 10.1007/s00401-009-0595-z \| PMID = 19798509 }}</ref>) stained negative cases are sequenced for other rare mutations that include IDH1 R132C or IDH2 R172K among others. These mutations are not only useful in differential diagnosis of brain tumours but also prognostic, because tumours carrying a IDH-1 or IDH-2 mutation usually show a more favourable course than their wild-type counterparts <ref name=pmid21088844>{{Cite journal \| last1 = Hartmann \| first1 = C. \| last2 = Hentschel \| first2 = B. \| last3 = Wick \| first3 = W. \| last4 = Capper \| first4 = D. \| last5 = Felsberg \| first5 = J. \| last6 = Simon \| first6 = M. \| last7 = Westphal \| first7 = M. \| last8 = Schackert \| first8 = G. \| last9 = Meyermann \| first9 = R. \| title = Patients with IDH1 wild type anaplastic astrocytomas exhibit worse prognosis than IDH1-mutated glioblastomas, and IDH1 mutation status accounts for the unfavorable prognostic effect of higher age: implications for classification of gliomas. \| journal = Acta Neuropathol \| volume = 120 \| issue = 6 \| pages = 707-18 \| month = Dec \| year = 2010 \| doi = 10.1007/s00401-010-0781-z \| PMID = 21088844 }}</ref>.

			[[Oligodendroglioma]]s show a more favourable course and therfore are treated differently than [[astrocytoma]]s. A clear separation of these two entities is important, because [[H&E]] morphology is not always convincing. Succesful treatment depends on allelic losses on chromosomal arms 1p and 19q in oligodendroglioma that can be obtained by copy-number analysis or microsatellite PCR. By combining LOH (loss of heterozygosity) 1p/19q and [[ATRX]] status it is also possible to place the mixed [[oligoastrocytoma]]s into the astrocytoma or oligodendroglioma group.






	==References==		==References==

← Older revision		Revision as of 14:23, 2 October 2015
Line 208:		Line 208:
	====Typical staining patterns====		====Typical staining patterns====

			*Glioblastoma
	<gallery>		<gallery>
	File:Neuropathology_case_IX_02.jpg \| [[H&E]]		File:Neuropathology_case_IX_02.jpg \| [[H&E]]
	File:Neuropathology_case_IX_04.jpg \| [[GFAP]]		File:Neuropathology_case_IX_04.jpg \| [[GFAP]]
	File:Neuropathology_case_IX_06.jpg \| MIB-1		File:Neuropathology_case_IX_06.jpg \| MIB-1
	File:~~Neuropathology~~ case IX.jpg \| [[ATRX]]		File:Neuroparthology case IX 0125.jpg \| [[ATRX]]
	File:~~Neuroparthology~~ case IX ~~0125~~.jpg \| [[IDH1]]		File:Neuropathology case IX.jpg \| [[IDH1]]
	File:~~Neuroparthology~~ case IX ~~0125~~.jpg \| panCK		File:Neuropathology case IX.jpg \| panCK
	</gallery>		</gallery>

Line 222:		Line 223:
	}}		}}

			*Oligodendroglioma
	<gallery>		<gallery>
	File:Oligodendroglioma1 low mag.jpg \| [[H&E]]		File:Oligodendroglioma1 low mag.jpg \| [[H&E]]
	File: x \| GFAP		File:Oligodendorglioma GFAP.jpg\| [[GFAP]]
	File:Neuropathology case II 04.jpg \| MIB-1		File:Neuropathology case II 04.jpg \| MIB-1
	File:Neuroparthology case IX 0125.jpg \| ATRX		File:Neuroparthology case IX 0125.jpg \| [[ATRX]]
	File:IDH1 R132H in anaplastic ologodendroglioma.jpg \| [[IDH1]]		File:IDH1 R132H in anaplastic ologodendroglioma.jpg \| [[IDH1]]
	File:Neuropathology case IX.jpg \| panCK		File:Neuropathology case IX.jpg \| panCK
	</gallery>		</gallery>

	[[Oligodendroglioma]] is a diffuse geowing glial tumour with clear cell morphology. In WHO grade II the MIB-1 proliferation index is rather low. GFAP stains the neuropil background and minigemistocytes (if present). There is no ATRX loss. The vast majority of oligodendrogliomas stain positively for IDH1 R132H mutation.		[[Oligodendroglioma]] is a diffuse geowing glial tumour with clear cell morphology. In WHO grade II the MIB-1 proliferation index is rather low. GFAP stains the neuropil background and minigemistocytes (if present). There is no ATRX loss. The vast majority of oligodendrogliomas stain positively for IDH1 R132H mutation.There is no expression of epithelial markers (panCK).

			{{hidden\|Other language: German\|Oligodendrogliome sind diffus wachsende gliale Tumore mit klarzelligem Aspekt in der Morphologie. In WHO Grad II Tumoren ist der MIB-1 Proliferationsindex gering. GFAP färbt vor allem das Neuropil im Hintergrund sowie Minigemistozyten, wenn diese im Tumor vorkommen. Es findet sich kein ATRX Verlust. Der Großteil der Oligodendrogliome ist positiv für die IDH1 R132H Mutation. Epitheliale Marker wie panCK werden nicht exprimiert}}

			*Astrocytoma
			<gallery>
			File:Astrocytoma whoII HE.jpg
			File:GFAP astrocytoma.jpg \| [[GFAP]]
			File:Neuropathology case II 04.jpg \| MIB-1
			File:Neuropathology case II ATRX immunohistochemistry.jpg \| [[ATRX]]
			File:IDH1R132H oligoastrocytoma.jpg \| \| [[IDH1]]
			File:Neuropathology case IX.jpg \| panCK
			</gallery>

			[Astrocytoma]] is a diffusely growing tumor with low cell density, neoplastic astrocytes resting in a fibrillary backrgound and low MIB1 index. GFAP is strong and also stains the cell processes. IND1 R132H postive astrocytomas usually exhibit nuclear ATRX loss. There is no expression of epithelial markers (panCK).

			{{hidden\|Other language: German\|Astrozytome sind diffus wachsende gliale Tumore mit sternförmigen Astrozyten auf einem fibrillärem Untergrund. In WHO Grad II Tumoren ist der MIB-1 Proliferationsindex gering. GFAP färbt die Tumorzellen und den Hintergrund stark an Es findet sich in IDH1 R132H mutierten Tumoren häufig ein ATRX Verlust. Epitheliale Marker wie panCK werden nicht exprimiert}}

	A descriptive overview of various brain tumours is found [[Neuropathology tumours\|here]].		A descriptive overview of various brain tumours is found [[Neuropathology tumours\|here]].

← Older revision		Revision as of 19:25, 1 October 2015
Line 198:		Line 198:
	* '''Ki-67''' (Kiel-67, clone MiB-1 which stands for Made in Borstel) is a nuclear protein that is associated with cellular proliferation. During interphase, the Ki-67 antigen can be exclusively detected within the cell nucleus, whereas in mitosis most of the protein is relocated to the surface of the chromosomes. Ki-67 protein is present during all active phases of the cell cycle (G1, S, G2, and mitosis), but is absent from resting cells (G0).<ref name="pmid10653597">{{Cite journal \| last1 = Scholzen \| first1 = T. \| last2 = Gerdes \| first2 = J. \| title = The Ki-67 protein: from the known and the unknown. \| journal = J Cell Physiol \| volume = 182 \| issue = 3 \| pages = 311-22 \| month = Mar \| year = 2000 \| doi = 10.1002/(SICI)1097-4652(200003)182:3<311::AID-JCP1>3.0.CO;2-9 \| PMID = 10653597 }}</ref> Ki-67 is an excellent marker to determine the growth fraction of a given cell population. The fraction of Ki-67-positive tumor cells (the Ki-67 labeling index) is often correlated with the clinical course of cancer. <ref>https://en.wikipedia.org/wiki/Ki-67_%28protein%29</ref> An [[astrocytoma]] with 2% positive tumor cells is growing considerably slower than a [[glioblastoma]] with a labelling index of 20%. Cells with a quick turnover therefore serve as good positive controls for this antibody.		* '''Ki-67''' (Kiel-67, clone MiB-1 which stands for Made in Borstel) is a nuclear protein that is associated with cellular proliferation. During interphase, the Ki-67 antigen can be exclusively detected within the cell nucleus, whereas in mitosis most of the protein is relocated to the surface of the chromosomes. Ki-67 protein is present during all active phases of the cell cycle (G1, S, G2, and mitosis), but is absent from resting cells (G0).<ref name="pmid10653597">{{Cite journal \| last1 = Scholzen \| first1 = T. \| last2 = Gerdes \| first2 = J. \| title = The Ki-67 protein: from the known and the unknown. \| journal = J Cell Physiol \| volume = 182 \| issue = 3 \| pages = 311-22 \| month = Mar \| year = 2000 \| doi = 10.1002/(SICI)1097-4652(200003)182:3<311::AID-JCP1>3.0.CO;2-9 \| PMID = 10653597 }}</ref> Ki-67 is an excellent marker to determine the growth fraction of a given cell population. The fraction of Ki-67-positive tumor cells (the Ki-67 labeling index) is often correlated with the clinical course of cancer. <ref>https://en.wikipedia.org/wiki/Ki-67_%28protein%29</ref> An [[astrocytoma]] with 2% positive tumor cells is growing considerably slower than a [[glioblastoma]] with a labelling index of 20%. Cells with a quick turnover therefore serve as good positive controls for this antibody.

	* '''panCK''' (MNF-116) Cytokeratins are proteins of keratin-containing intermediate filaments found in the intracytoplasmic cytoskeleton of eukaryontic epithelial tissue and their derived tumours. The 20 different cytokeratins can be divided into low versus high molecular weight solely based on their molecular weight. The current cocktail detects almost all types of epithelial, from simple glandular to stratfied squamous epithelia and therefore is ideal to detect malignant epithelial tumours ([[carcinoma]]s). Rarely a cross-reaction with dendritic cells in the tonsil or smooth muscle cells of vessels is observed. Most brain metastases are carcinomas of breast, lung or prostrate and therefore stain intensely for pan-cytokeratin. In contrast, glial and neuronal brain tumours as well as melanomas do not stain for this marker. Expression of these cytokeratin types is frequently organ or tissue specific. Pathologists employ different cytokeratins to detect the cell of origin of various tumors. As an example, [[Cytokeratin_7\|CK7]] is typically expressed in the ductal epithelium of the genitourinary tract and [[Cytokeratin_20\|CK20]] most commonly in the gastrointestinal tract. Best results are obtained with Trypsin or Pronase pretreatment for antigen demasking. Normal epithelial tissue (gut, skin) may serve as positive control.		* '''panCK''' (MNF-116) Cytokeratins are proteins of keratin-containing intermediate filaments found in the intracytoplasmic cytoskeleton of eukaryontic epithelial tissue and their derived tumours. The 20 different cytokeratins can be divided into low versus high molecular weight solely based on their molecular weight. The current cocktail detects almost all types of epithelial, from simple glandular to stratfied squamous epithelia and therefore is ideal to detect malignant epithelial tumours ([[carcinoma]]s). Rarely a cross-reaction with dendritic cells in the tonsil or smooth muscle cells of vessels is observed. Most brain metastases are carcinomas of breast, lung or prostrate and therefore stain intensely for pan-cytokeratin. In contrast, glial and neuronal brain tumours as well as melanomas do not stain for this marker. Expression of these cytokeratin types is frequently organ or tissue specific. Pathologists employ different cytokeratins to detect the cell of origin of various tumors. As an example, [[Cytokeratin_7\|CK7]] is typically expressed in the ductal epithelium of the genitourinary tract and [[Cytokeratin_20\|CK20]] most commonly in the gastrointestinal tract. Best results are obtained with Trypsin or Pronase pretreatment for antigen demasking. Normal epithelial tissue (gut, skin) may serve as positive control.

			*'''GFAP''' (Ab-1) The 49kDa glial fibrillary acidic protein is an intermediate filament protein that is expressed by numerous cell types of the CNS including astrocytes and ependymal cells. It is related to otherintermediate filaments such as desmin and vimentin. Loss of GFAP through mutations results in Alexanders Disease where the white matter degenerates. Brain tumors that are derived of astrocytes ([[astroccatoma]] and [[glioblastoma]] stain for GFAP, that is absent in metastatic carcinomas and oligodendrogliomas [except for [[minigemistocyte]]s. Local and reactive astrocytes between brain tumor cells may mark for GFAP and should not confused with tumour positivity. White matter serves as ideal positive control. Cross-reactivity is seen with peripheral Schwann cells.

	A descriptive overview of various brain tumours is found [[Neuropathology tumours\|here]].		A descriptive overview of various brain tumours is found [[Neuropathology tumours\|here]].