Course:Introduction to Neuropathology: Difference between revisions

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 ====Typical staining patterns====
+*Glioblastoma
 <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 | [[ATRX]]
-File:Neuroparthology case IX 0125.jpg | [[IDH1]]
+File:Neuropathology case IX.jpg | [[IDH-1]]
-File:Neuroparthology case IX 0125.jpg | panCK
+File:Neuropathology case IX.jpg | panCK
 </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.
 }}
+*Oligodendroglioma
 <gallery>
 File:Oligodendroglioma1 low mag.jpg | [[H&E]]
-File: x | GFAP
+File:Oligodendorglioma GFAP.jpg| [[GFAP]]
 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
 </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 [[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.}}
+*Astrocytoma
+<gallery>
+File:Astrocytoma whoII HE.jpg | [[H&E]]
+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 | | [[IDH-1]]
+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. [[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.}}
+*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 | [[IDH-1]]
+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 [[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.}}
 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.
+===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==

Course:Introduction to Neuropathology: Difference between revisions

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