a case for discussion (part 2)

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    A case for !!?Prof. Gamal Dawood

    (Part 2)

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    IMMUNOHISTOCHEMISTRY

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    SNF.

    Note positivity in three locations:

    In neurpil (tissue located between the cell bodies of neoplastic cells);

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    SNF.

    Note positivity in three locations:

    Occasionally in structures suggestive of pseudorosettes of Homer Wright;

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    SNF.

    Note positivity in three locations:

    In the cytoplasm of some cells.

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    SNF.

    Homer Wright pseudorosettes

    These structures are characteristic of tumors of neuronal lineage

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    NeuN nuclear antigen

    Advanced stages of neuronal maturation, immunolabeling is shared by many

    central neurocytomas and attests to their well-differentiated nature.

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    NSE.

    Strong cytoplasmic positivity in part of cells, compatible with neuronal differentiation.

    However, NSE (neuron-specific enolase) is, in reality, little specific, being positive also in

    gliomas, as oligodendrogliomas and ependymomas.

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    NSE.

    Strong cytoplasmic positivity in part of cells, compatible with neuronal differentiation.

    However, NSE (neuron-specific enolase) is, in reality, little specific, being positive also in

    gliomas, as oligodendrogliomas and ependymomas.

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    CGR.

    It is observed focally in the cytoplasm.

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    CGR.

    It is observed focally in the cytoplasm.

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    Cromogranin

    Dot positivity in standard. In this case, the positivity is denoted in only a small rounded

    area of cytoplasm.

    It is assumed that the marking occurs in the Golgi apparatus, where the protein is being

    modified after synthesis in the endoplasmic reticulum.

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    Cromogranin

    Dot positivity in standard. In this case, the positivity is denoted in only a small rounded

    area of cytoplasm.

    It is assumed that the marking occurs in the Golgi apparatus, where the protein is being

    modified after synthesis in the endoplasmic reticulum.

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    NF.

    Negative throughout the sample. The negativity indicates that neoplastic cells,

    although showing neuronal differentiation, as evidenced by the reactivity to NFC and

    CGR, are in an intermediate stage. Only cells with advanced degree of differentiation

    into neurons tend to be positive for neurofilament.

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    Small group of astrocytes interpreted as reactive to the presence of

    the tumor (non neoplastic). Have more abundant cytoplasm, with

    aspect of gemistocytic astrocytes, denser and afforestation.

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    GFAP.

    The great majority of cells positive for GFAP are small, with short

    extensions or simplified, making it unlikely that are pre-existing cells.

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    GFAP

    Positive cells, apparently belonging to tumor, at least in the majority.

    In addition, there are fine cellular extensions attending between negative

    cells.

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    GFAP.

    Positivity in pseudorosettes.Homer Wright pseudorosettes in this case are densely

    populated by prolongations GFAP-positive, so astrocytes, make

    this tumor

    Astrocytic differentiation in tumor cells had been observed inseveral cases but positive GFAP filaments in pseudorosettes

    never had found. Usually, these structures are positive for

    neuronal markers, especially synaptophysin, but not to a glial

    marker. This suggests that in intimate coexistence of rosettesthere may be an extension of two cell lines, as in normal

    nervous tissue.

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    GFAP. Positivity in perivascular astrocytic extensions. Small vessels in the tumor are often

    surrounded by positive GFAP cellular extensions.

    As in normal nervous tissue there is intimate relationship between the prolongations of

    astrocytes with vessels, apparently these small primitive cells, but with incipient astrocytic

    differentiation, reproduce a morpho-physiological patternof adult astrocytes.

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    GFAP. Positivity in perivascular astrocytic extensions. Small vessels in the tumor are often

    surrounded by positive GFAP cellular extensions.

    As in normal nervous tissue there is intimate relationship between the prolongations of

    astrocytes with vessels, apparently these small primitive cells, but with incipient astrocytic

    differentiation, reproduce a morpho-physiological patternof adult astrocytes.

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    VIM.

    neoplastic cells with suspected astrocytic differentiation, as

    already seen with GFAP

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    VIM.

    neoplastic cells with suspected astrocytic differentiation, as

    already seen with GFAP

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    VIM.

    neoplastic cells with suspected astrocytic differentiation, as

    already seen with GFAP

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    .

    The results with vimentin virtually reproduce with GFAP. There are marking a

    portion of the small tumor cells, and of pseudorosettes of Homer Wright. The

    vessels are always positive for vimentin, since this intermediate filament is

    present on endothelial cells.

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    .

    The results with vimentin virtually reproduce with GFAP. There are marking a

    portion of the small tumor cells, and of pseudorosettes of Homer Wright. The

    vessels are always positive for vimentin, since this intermediate filament is

    present on endothelial cells.

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    VIM.

    As neurons do not express this marker, the positivity for vimentin is further evidence of

    astrocytic differentiation i.e. divergent differentiation in a primitive cell tumor.

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    S-100.

    Fuzzy Positivity, but highlighting cells that, by their extensions, suggest

    astrocytic differentiation as already discussed above for GFAP and VIM

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    S-100.

    Fuzzy Positivity, but highlighting cells that, by their extensions, suggest

    astrocytic differentiation as already discussed above for GFAP and VIM

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    CD34.

    This quality is excellent for demonstrating the rich vascularization. The vast network of

    capillaries regularly spaced and very thin walls stands out against the tumor tissue.

    There is no endothelial proliferation.

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    CD34.

    Positive in endothelial cells. Distributed capillary network

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    CD34.

    Positive in endothelial cells. Distributed capillary network

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    Ki-67.

    The number of cores marked was valued at around 3%, a visual estimate of multiple

    fields, without counting. The photos were made in the richer areas. Mitoses are

    difficult to find, even with this method.

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    Ki-67.

    The number of cores marked was valued at around 3%, a visual estimate of multiple

    fields, without counting. The photos were made in the richer areas. Mitoses are

    difficult to find, even with this method.

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    Differential Diagnosis

    The main differential diagnoses are : Central Neurocytoma

    Oligodendroglioma: Neurocytic neoplasms are further (and mostefficiently) distinguished by a neuronal immunophenotype that includesdiffuse matrix labeling for synaptophysin and, in many instances,widespread immunoreactivity for the neuronal nuclear antigen (NeuN).This is not to dismiss evidence that oligodendrogliomas occasionallyexercise a potential for neuronal differentiation.

    Chromosome 1p/19q co-deletions, a common feature of histologicallytypical oligodendrogliomas are not harbored by central neurocytomas orclear cell ependymomas

    Oligodendroglioma GFAP Vimentin

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    NSE Synaptophysin

    Unfortunately, there does not exist at present an immunocytochemical reagent that

    consistently and specifically identifies neoplastic cells as oligodendroglial. Immunolabeling

    for S-100 protein, membranous Leu7 (CD57) reactivity, and cytoplasmic expression of

    carbonic anhydrase Cand MAP-2 are characteristic but shared by other tumor types.

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    Ependymoma

    Pineocytoma

    Dnet (dysembryoplasic neuroepitelial tumor):

    It is a benign, mixed glial-neuronal cortical

    neoplasm of children and young adults

    GFAPEpendymoma

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    EMAVimentin

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    SynaptophysinGFAPVimentin

    Central Neurocytoma

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    Central Neurocytoma