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Aims: While it is well known that pilocytic astrocytomas are clinically distinct from diffuse astrocytomas, few comprehensive studies have focused on their genetic differences. The aim of this study was to examine pilocytic astrocytomas for genetic alterations that are commonly seen in diffuse astrocytomas., Methods and Results: By using molecular genetic and immunohistochemical techniques, we evaluated p16, p53, CDK4 and PTEN genes in 29 pilocytic astrocytomas. Mutation screening of p53 and PTEN was performed by single strand conformation polymorphism analysis followed by direct sequencing. Loss of heterozygosity (LOH) of p53, p16 and 10q23-25 loci was performed with microsatellite markers and genomic microsatellite instability (MSI) was also screened. Protein expression of p16, p53, CDK4 and PTEN was examined by immunohistochemistry. Five tumours were found to have single genetic alterations, which included a p53 mutation, a PTEN mutation, MSI at a single microsatellite marker of the p16 locus, and one single LOH at each p16 and 10q23 loci. Protein expressions of p16, CDK4 and PTEN were detected in 73%, 61% and 38% of tumours, respectively. Significantly and in sharp contrast to diffuse astrocytomas, no pilocytic astrocytoma in our series stained for p53 protein., Conclusion: Pilocytic astrocytomas have neither MSI phenotype nor recurrent alterations of the p53 and p116 genes. However, altered expression of PTEN may be important in the genesis of pilocytic astrocytomas. We conclude that pilocytic astrocytomas are genetically distinct from diffuse astrocytomas. Lack of p53 mutation/immunostaining may serve as a diagnostic adjunct for differentiating pilocytic astrocytomas from diffuse astrocytomas in small neurosurgical biopsies.

Aims: Central neurocytoma is a rare central nervous system tumour typically found in the lateral ventricles and at the septum pellucidum. Histologically, it resembles oligodendrogliomas and yet ultrastructurally, it shows neuronal differentiation. Its molecular oncogenesis is not known. The aim of this study was to examine whether major genetic events found in oligodendrogliomas and neuronal tumours, namely allelic deletions of chromosomes 1p and 19q and N-myc amplification, can be found in central neurocytomas. As there was one report describing gain of chromosome 7 in central neurocytomas, we also examined epidermal growth factor receptor (EGFR) amplification, as the EGFR gene is located at chromosome 7p., Methods and Results: Nine central neurocytomas and matched blood samples were examined for loss of heterozygosity (LOH) of 1p and 19q13.2-13.4 with 23 finely mapped microsatellite markers. N-myc amplification was studied by fluorescence in-situ hybridization using paraffin-embedded sections. EGFR amplification was tested for by differential PCR. Six of nine (67%) tumours showed LOH at one or more loci at 1p and 5/9 (56%) of cases showed LOH at 19q. However, common regions of deletion cannot be identified. The majority of informative markers are retained at 1p (84%) and 19q (86%). Only one tumour showed amplification of N-myc and none of the cases showed amplification of EGFR., Conclusion: Central neurocytomas are genetically distinct from oligodendrogliomas, and chromosomes 1p and 19q probably do not play an important role in their pathogenesis. N-myc and EGFR amplification are rare.

Aims: Oligodendroglial tumours follow genetic pathways different from but overlapping with those of astrocytic tumours. The aim of this study was to examine whether major genetic events such as loss of chromosome 10 and p53 mutation found in astrocytic gliomas are also involved in the development and anaplastic transformation of non-astrocytic gliomas and to correlate the findings with histopathological subtypes of these tumours., Methods and Results: Sixty-one formalin-fixed, paraffin-embedded oligodendroglial and ependymal tumours (16 oligodendrogliomas, 12 anaplastic oligodendrogliomas, seven oligoastrocytomas, 24 ependymomas and two anaplastic ependymomas) were examined for allelic deletions on chromosome 10q23 and 10q25-26 regions, mutations of PTEN/MMAC1 and p53, MDM2 gene amplification and apoptosis. The frequencies of allelic deletions at marker D10S2491 (which mapped within PTEN/MMAC1) and between markers D10S209 and D10S587 (where DMBT1 was located) were found to be < 30% in both types of non-astrocytic gliomas. High frequency of allelic deletions was detected at marker D10S215 (80%) at the proximal 10q23 region in both oligodendroglial and ependymal tumours and between markers D10S216 (42%) and D10S169 (67%) at distal 10q25-26 region in oligodendroglial tumours. No mutations of PTEN/MMAC1 were found. p53 mutations were detected in three oligoastrocytomas and one ependymoma; three out of five mutations were found in exon 4. MDM2 gene amplification was found in one ependymoma harbouring wild-type p53. The apoptotic index was lower in p53-mutated tumours than in tumours with wild-type p53., Conclusion: The telomeric end of chromosome 10q could be involved in the development and anaplastic transformation of oligodendroglial tumours. Mutations of PTEN/MMAC1 and p53, amplification of the MDM2 gene and allelic loss on chromosome 10q do not play a major part in the pathogenesis or anaplastic transformation of oligodendrogliomas and ependymal tumours.

Aims: Although necrosis is an important phenomenon with implications for grading and prognostication in meningiomas, the alternate form of cell death, apoptosis, has not been extensively studied. In this series, we aimed to determine whether apoptosis in meningiomas correlated with histological types and grading. We also looked for a relationship between expression of apoptosis-related genes bcl-2, p53, c-myc and apoptosis meningiomas., Methods and Results: Fifty-one meningiomas of diverse histological subtypes and grades were investigated with in situ end-labelling of DNA fragments as well as immunohistochemical analysis of three apoptosis-related genes: p53, bcl-2 and c-myc. Our results showed that the apoptosis index was significantly higher in high-grade meningiomas (0.12%, n = 12) in than the benign meningiomas (0.023%, n = 39) P = 0.001) but there was no difference among the different histological subtypes of the benign meningiomas (P = 0.125). There is no obvious relationship between p53, bcl-2 and c-myc staining and apoptosis index in this group of meningiomas., Conclusion: We conclude that apoptosis is an important phenomenon in meningiomas and that it is associated with atypical or malignant changes in meningiomas. Apoptosis in meningiomas has no clearcut relationship with expression of p53, bcl-2 and c-myc.

In an attempt to characterize the dual mesenchymal and epithelial differentiating potential of meningiomas, cryostat sections from 50 meningiomas of diverse histological subtypes were examined immunohistochemically with a panel of markers for epithelial and mesenchymal differentiation. The overall positivities were: keratins 50%, epithelial membrane antigen 94%, human milk fat globules 38%, carcinoembryonic antigen 4% (secretory meningiomas only), desmoplakins 64%, collagen I 82%, procollagen I 96%, collagen III 74%, collagen IV 60%, laminin 54%, fibronectin 98% and vimentin 98%. Such production of keratins was not found in many previous immunohistochemical analyses of meningiomas with paraffin sections. The extracellular matrix proteins were present in a pericellular distribution suggestive of their being produced by the tumour cells. The potential of dual epithelial and mesenchymal differentiation in meningiomas was further examined in seven cases established on short-term cultures. Morphologically, subcultured tumour cells resembled fibroblasts and in five cases revealed similar epithelial and mesenchymal immunohistochemical profiles as for direct tumour immunostaining. In two cases, cells from the primary cultures revealed a fine skeleton of intercellular matrix proteins stainable by immunohistochemical methods, providing further proof that meningioma cells possess the capability to elaborate extracellular matrix proteins, a major mesenchymal function akin to that of fibroblasts.

A case of undifferentiated carcinoma of the salivary gland occurring in the parotid gland of a southern Chinese was reported. Tumour cells showed immunofluorescence for Epstein-Barr virus (EBV)-associated nuclear antigen, and DNA hybridization demonstrated the presence of EBV-DNA in tumour tissue. The findings in this case, together with previous reports, suggest a causal relationship between EBV and salivary gland carcinoma. The relationships between EBV and undifferentiated epithelial tumours of the salivary glands, nasopharynx and thymus are also discussed.

This report describes two cases of alveolar rhabdomyosarcoma of the nasal cavity with unusual histological appearances mimicking clear cell carcinoma. The closely packed tumour cells were polygonal and arranged in sheets and packets. They had an appreciable amount of clear cytoplasm due to accumulation of glycogen. The diagnosis of rhabdomyosarcoma was confirmed by positive staining for desmin and myoglobin. Rhabdomyosarcoma should be included in the differential diagnosis of nasal clear cell tumours, particularly in young adults. A correct diagnosis is important, because chemotherapy is indicated even for apparently localized disease.

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.

Antisera to alpha 1-antichymotrypsin, alpha 1-antitrypsin and lysozyme were reacted with 20 cases of glioblastoma multiforme, seven anaplastic astrocytomas, eight astrocytomas, six oligodendrogliomas, four ependymomas and the cerebral cortex from six normal autopsy brains. In addition, two pleomorphic xantho-astrocytomas and two heavily lipidized malignant gliomas were similarly examined. All astrocytic lesions were confirmed with anti-GFAP antisera. Thirty astrocytic tumours (77%), four oligodendrogliomas (67%) and three ependymomas (75%) reacted positively with anti-alpha 1-antichymotrypsin; 25 astrocytic tumours (64%), three oligodendrogliomas (50%) and three ependymomas (75%) showed positive staining for alpha 1-antitrypsin. The pattern of staining with either of these two markers did not correlate with tumour grading. None of the gliomas examined stained positively with anti-lysozyme. Non-neoplastic glial elements did not react with any of the three antisera. The results of this study suggest that staining for alpha 1-antichymotrypsin and alpha 1-antitrypsin is of little value in the differential diagnosis of neuroepithelial or mesenchymal lesions in the brain.

Two cases of olfactory neuroblastoma which presented clinically as intracranial lesions are described. Prominent features of epithelial differentiation were present, which led to initial diagnoses of poorly differentiated carcinoma. The true nature of the lesions was only established subsequently by careful histological examination, immunohistochemistry and electron microscopy. The potential towards epithelial differentiation in such tumours was emphasized and certain new histological features were described, including a biphasic epithelial and stromal pattern, papillae formation and positive staining for cytokeratin. These two cases underline the importance of exhaustive examination of poorly differentiated epithelial-like lesions of the frontal lobes by conventional histology, immunohistochemistry and electron microscopy.

Nine cases of microcystic meningiomas, a distinct morphological variant of meningiomas, are reported. They are characterized by a vacuolated and myxomatous histological appearance with multiple cystic spaces lined by stellate-shaped tumour cells. Immunohistochemically, they shared a similar pattern of positive staining for epithelial membrane antigen and vimentin with other meningiomas. Their unusual histological features might lead to problems in differential diagnosis from other intracranial tumours, including schwannomas, chordomas, astrocytomas and angioblastic meningiomas.