A case for

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Prof. Gamal Dawood (Part 2)

IMMUNOHISTOCHEMISTRY

SNF. Note positivity in three locations: In neurpil (tissue located between the cell bodies of neoplastic cells);

SNF. Note positivity in three locations: Occasionally in structures suggestive of pseudorosettes of Homer Wright;

SNF. Note positivity in three locations: In the cytoplasm of some cells.

SNF. Homer Wright pseudorosettes These structures are characteristic of tumors of neuronal lineage

NeuN nuclear antigen Advanced stages of neuronal maturation, immunolabeling is shared by many central neurocytomas and attests to their well-differentiated nature.

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.

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.

CGR. It is observed focally in the cytoplasm.

CGR. It is observed focally in the cytoplasm.

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.

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.

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.

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.

GFAP. The great majority of cells positive for GFAP are small, with short extensions or simplified, making it unlikely that are pre-existing cells.

GFAP Positive cells, apparently belonging to tumor, at least in the majority. In addition, there are fine cellular extensions attending between negative cells.

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 in several 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 rosettes there may be an extension of two cell lines, as in normal nervous tissue.

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.

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.

VIM. neoplastic cells with suspected astrocytic differentiation, as already seen with GFAP

VIM. neoplastic cells with suspected astrocytic differentiation, as already seen with GFAP

VIM. neoplastic cells with suspected astrocytic differentiation, as already seen with GFAP

. 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.

. 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.

. 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.

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.

S-100. Fuzzy Positivity, but highlighting cells that, by their extensions, suggest astrocytic differentiation as already discussed above for GFAP and VIM

S-100. Fuzzy Positivity, but highlighting cells that, by their extensions, suggest astrocytic differentiation as already discussed above for GFAP and VIM

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.

CD34. Positive in endothelial cells. Distributed capillary network

CD34. Positive in endothelial cells. Distributed capillary network

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.

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.

Differential Diagnosis
The main differential diagnoses are : Central Neurocytoma Oligodendroglioma: Neurocytic neoplasms are further (and most efficiently) distinguished by a neuronal immunophenotype that includes diffuse matrix labeling for synaptophysin and, in many instances, widespread immunoreactivity for the neuronal nuclear antigen (NeuN). This is not to dismiss evidence that oligodendrogliomas occasionally exercise a potential for neuronal differentiation.

Chromosome 1p/19q co-deletions, a common feature of histologically typical oligodendrogliomas are not harbored by central neurocytomas or clear cell ependymomas

Oligodendroglioma

GFAP

Vimentin

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 C and MAP-2 are characteristic but shared by other tumor types.

 Ependymoma Pineocytoma Dnet (dysembryoplasic neuroepitelial tumor): It is a benign, mixed glial-neuronal cortical neoplasm of children and young adults

Ependymoma

GFAP

Vimentin

EMA

Vimentin

GFAP

Synaptophysin

Central Neurocytoma

Central Neurocytoma