Immunohistochemistry of central nervous system tumors

Its contributions to neurosurgical diagnosis

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✓ Immunofluorescence and immunoperoxidase (peroxidase-antiperoxidase, PAP) techniques for the demonstration of neural and non-neural cell markers are contributing greatly to increase the diagnostic accuracy of difficult tumors of the central nervous system. Well characterized nervous system markers include glial fibrillary acidic (GFA) protein, the three protein subunits of neurofilaments, neuron-specific enolase (NSE), myelin basic protein, and S-100 protein. The most important and reliable of these is GFA protein, which is widely in use for the immunohistochemical diagnosis of tumors of the glioma group. Its many practical applications are reviewed and illustrated. Other neural markers, in particular the specificity of NSE and S-100 protein, need to be critically evaluated. Problems related to the immunohistochemical diagnosis of central neuroepithelial tumors of putative neuroblastic origin remain complex and still need to be resolved. Non-neural markers, such as vimentin, desmin, cytokeratins, Factor VIII, alpha-fetoprotein, human chorionic gonadotropin, and immunoglobulins have well defined, although more restricted, applications in surgical neuropathology.

Article Information

Dr. Bonnin is supported by American Cancer Society Clinical Fellowship 5732, and by Neuropathology Research Training Grant T32 NS07236 of the National Institute of Neurological and Communicative Disorders and Stroke, U.S. Department of Health and Human Services.

Address reprint requests to: Jose M. Bonnin, M.D., Division of Neuropathology, Department of Pathology, University of Virginia School of Medicine, Charlottesville, Virginia 22908.

© AANS, except where prohibited by US copyright law.

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    Examples of immunohistochemistry. A: Glial fibrillary acidic (GFA) protein-positive tumor cells in an astrocytoma occupying the leptomeninges. Immunoperoxidase stain for GFA protein, × 800. B: GFA protein-positive tumor cells in a subependymal giant-cell astrocytoma. Immunoperoxidase stain for GFA protein, × 500. C: Mixed glioblastoma and fibrosarcoma (gliosarcoma). Negative sarcomatous portion (lower left) adjacent to strongly GFA protein-positive glioblastoma. Immunoperoxidase stain for GFA protein, × 500. D: Ganglioglioma composed of GFA protein-positive astrocytes admixed with GFA protein-negative ganglion cells. Immunoperoxidase stain for GFA protein, × 500. E: Astrocytic differentiation in metastatic medulloblastoma cells occupying the bone marrow. Immunoperoxidase stain for GFA protein, × 800. F: Uptake of GFA protein by stromal cells in a capillary hemangioblastoma. Vacuoles (presumably lipid) are present in the cytoplasm of the stromal cells. Immunoperoxidase stain for GFA protein, × 200. G: Foci of GFA protein-positive glial (presumably ependymal) differentiation in a choroid plexus papilloma. Immunoperoxidase stain for GFA protein. × 200. H: Peripheral ganglioneuroblastoma showing variable positivity of tumor cells for neuron-specific enolase (NSE). Immunoperoxidase stain for NSE, × 500. I: Endodermal sinus tumor of the pineal gland showing positivity for alpha-fetoprotein (AFP). Immunoperoxidase stain for AFP, × 200.

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