bromochloroacetic-acid and Oligodendroglioma

Mass lesions of the central nervous system (CNS) that may assume a clear cell appearance are diverse in nature. Primary conditions in this category include oligodendroglioma, hemangioblastoma, germinoma (seminoma), clear cell and chordoid meningioma, pleomorphic xanthoastrocytoma, and lipid-rich glioblastoma. These proliferations usually can be identified by attention to clinical presentation, topographic location, radiographic details, and histological nuances. Occasionally, however, electron microscopy or immunohistological analysis may be necessary. A recommended panel of reagents for the evaluation of clear cell primary CNS lesions include antibodies to glial fibrillary acidic proteins, S-100 protein, epithelial membrane antigen, vimentin, keratins, placental-like alkaline phosphatase, and synaptophysin. This article reviews the salient clinicopathologic attributes of such proliferations, elaborates a practical approach to their diagnosis, and discusses important differential diagnostic considerations. The latter include malformative lesions, infarcts, inflammatory conditions, and secondary lymphomas, carcinomas, and melanomas.

Topics: Alkaline Phosphatase; Carcinoma, Renal Cell; Central Nervous System Neoplasms; Diagnosis, Differential; Germinoma; Glial Fibrillary Acidic Protein; Hemangioblastoma; Humans; Immunohistochemistry; Keratins; Meningioma; Mucin-1; Oligodendroglioma; S100 Proteins; Synaptophysin; Vimentin; Xanthomatosis

Metastatic carcinoma, which is a common malignant tumor seen in the central nervous system is often difficult to distinguish from glioblastoma multiforme. In general, neoplastic cells maintain fidelity in the expression of parent cell intermediate filament and immunohistochemistry remains the mainstay in diagnosis. A panel consisting of GFAP (usually positive for astrocytic tumors) and cytokeratin (usually positive for metastatic carcinomas) is most commonly used for this purpose. However, co-expression of two or more classes of intermediate filament proteins by neoplasms is a widespread phenomenon and there are reports of glial neoplasms expressing keratin markers. Our aims and objectives were to analyse the expression of both cytokeratin and GFAP in different glial tumors and metastatic carcinomas. Cases were collected for a period of two years. All the cases were diagnosed as primary or metastatic intracranial tumors. Formalin-fixed paraffin-embedded thin sections were taken on egg-albumin coated slides and immunostaining with GFAP and polyclonal cytokeratin was done. Forty-five tumors were analysed, including 35 glial neoplasms and 10 metastatic carcinomas of which 7 of the 32 astrocytic neoplasms (22%) showed focal immunoreactivity with pancytokeratin. All of the glial tumors but none of the metastatic carcinomas were positive with GFAP. So our conclusion was that co-expression of GFAP and CK is a fairly common phenomenon, especially in case of undifferentiated and high grade gliomas and this must be kept in mind while differentiating these cases from metastatic carcinoma, as CK positivity does not rule out the diagnosis of a glial neoplasm. Further studies with an expanded panel of CK is most useful for this.

Topics: Astrocytoma; Biomarkers, Tumor; Brain Neoplasms; Carcinoma; Diagnosis, Differential; Glial Fibrillary Acidic Protein; Glioblastoma; Glioma; Humans; Immunohistochemistry; Keratins; Oligodendroglioma

We examined the expression of glial- and neuronal-specific mRNAs within human gliomas using in situ hybridization. We found that low-grade astrocytomas contained a high number of proteolipid protein (PLP) mRNA-positive cells and that the number of PLP-stained cells decreased markedly with increasing tumor grade. Interestingly, the ratio of PLP mRNA-stained cells:myelin basic protein (MBP) mRNA-stained cells in normal white matter and low-grade astrocytoma was about 2:1 but approached 1:1 with increasing tumor grade. This parameter appeared to be a good indicator of tumor infiltration in astrocytomas, so we tested this in the analysis of other gliomas. Unlike astrocytomas, oligodendrogliomas were found consistently to contain few PLP mRNA- or MBP mRNA-expressing cells. In contrast, gemistocytic astrocytomas, typically highly invasive tumors, contained high numbers of PLP-positive cells and a ratio of PLP mRNA:MBP mRNA-stained cells of about 1.5:1, similar to low-grade astrocytomas. Nonradioactive in situ hybridization also enabled the morphological identification of specific cells. For example, gemistocytic astrocytes, which were found to be strongly vimentin mRNA positive, contained little glial fibrillary acidic protein mRNA and did not stain for PLP or MBP mRNAs. Neuronal mRNAs, such as neurofilament 68, were observed in small numbers of entrapped neurons within gliomas but were uninformative with respect to predicting tumor grade. Our results suggest that oligodendrocytes survive low-grade tumor infiltration and that glial tumor cells, unlike cell lines derived from them, do not express oligodendrocyte or neuronal mRNAs. In addition, the expression of mRNAs for the two major myelin protein genes, PLP and MBP, could be used to predict the grade and extent of tumor infiltration in astrocytomas.

Topics: Astrocytoma; Brain Neoplasms; Gene Expression Regulation, Neoplastic; Glial Fibrillary Acidic Protein; Glioma; Humans; In Situ Hybridization; Keratins; Myelin Basic Protein; Myelin Proteolipid Protein; Neurofilament Proteins; Neuroglia; Neurons; Oligodendroglia; Oligodendroglioma; RNA, Messenger; RNA, Neoplasm; Vimentin

From a human oligodendroglioma cell line cDNA library, ten intermediate filament (IF) cDNA clones were isolated. Five clones corresponded to vimentin mRNA, two corresponded to cytokeratin K7 mRNA, and two corresponded to cytokeratin K8 mRNA. One clone encoded a novel IF mRNA. The expression of these and other IF protein genes was examined in five cell lines derived from human oligodendroglioma, astrocytoma and neuroblastoma tumors. Vimentin mRNA and K18 mRNA were expressed in all the cell lines. The K7 and K8 genes were expressed only in the oligodendroglioma cell lines. Surprisingly, nestin mRNA was expressed in the astrocytoma lines and the neuroblastoma line, but was not expressed in the oligodendroglioma lines. These results indicate that oligodendroglioma cell lines express Types I and II cytokeratin genes. This pattern of IF gene expression was different from that of the astrocytoma and neuroblastoma cell lines, which expressed IF genes usually associated with the mature cell types or with differentiating fetal neural precursor cells, i.e. GFAP and neurofilament-L. The results also suggest that the oligodendroglioma cell lines are more epithelial in character and do not reflect the gene expression of mature oligodendrocytes.

Topics: Blotting, Northern; Brain Neoplasms; Cloning, Molecular; DNA, Complementary; Gene Expression; Glial Fibrillary Acidic Protein; Humans; Intermediate Filament Proteins; Keratins; Nerve Tissue Proteins; Nestin; Oligodendroglioma; RNA, Messenger; Tumor Cells, Cultured

Monoclonal antibodies (AE1/3, CAM 5.2 and PKK-1) and polyclonal antisera against the cytokeratin proteins were reacted with a range of astrocytic tumours, oligodendrogliomas and ependymomas. Seven of 12 cases (58%) of glioblastoma multiforme, five of eight (63%) anaplastic astrocytomas and two of five (40%) well-differentiated astrocytomas were immunoreactive with AE1/3 but not with the other anti-cytokeratin antibodies. In oligodendrogliomas, AE1/3 stained isolated astrocyte-like cells as well as scattered neoplastic oligodendrocytes in four of eight cases (50%) cases. Four ependymomas were negative for all cytokeratin markers examined. The immunostaining of astrocytomas and oligodendrogliomas with AE1/3 might represent co-expression of cytokeratin with glial fibrillary acidic protein by gliomas and calls for caution in the use of these antibodies in the differential diagnosis between gliomas and carcinomas.

Topics: Adult; Antibodies, Monoclonal; Astrocytoma; Child; Glioblastoma; Humans; Immunohistochemistry; Keratins; Oligodendroglioma