Account-creators
1,040
edits
Difference between revisions of "Course:Introduction to Neuropathology"
Jump to navigation
Jump to search
Course:Introduction to Neuropathology (view source)
Revision as of 08:30, 6 October 2015
, 08:30, 6 October 2015day 2 molecular neurooncology
Jensflorian (talk | contribs) (→Typical staining patterns: last case) |
Jensflorian (talk | contribs) (day 2 molecular neurooncology) |
||
| 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 | [[ | 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 [[ | [[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 | [[ | 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 [[ | [[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 | | [[ | 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. [[ | [[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 | [[ | 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 [[ | [[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== | ||