Oligodendroglioma malignancy grade II (H&E) with the typical tumour cell morphology—round nuclei and swollen cytoplasm. Note the microcalcifications (arrows) mainly in the lower right of the field. This is a common feature in oligodendrogliomas but is not unique to this form of glioma.
Increases in nuclear pleomorphism and hyperchromatism, as well as pronounced hypercellularity, brisk mitotic activity, prominent microvascular proliferation, and/or spontaneous necrosis, results in a picture that is histologically classified as anaplastic oligodendroglioma (malignancy grade III). Anaplastic forms of oligoastrocytomas also occur and similar criteria are used to distinguish them from oligoastrocytomas.
Since 1990, when combination chemotherapy (procarbazine, lomustin, and vincristine (PCV)) was demonstrated to result in sometimes a dramatic tumour response, the identification of all forms of glioma with oligodendroglial components has become crucial. Oligodendrogliomas show relatively specific genetic abnormalities that differ from the other gliomas. Loss of genetic information from 1p and 19p was demonstrated in a genomic wide analysis in 1994 and this was later linked to a good response to PCV treatment, an association that is currently under intense scrutiny as it provides the first molecular indicator of treatment response in brain tumours.
The losses on 1p and 19q are most common among the grade II oligodendrogliomas (reports of up to 90%) and are present in over 50% of anaplastic oligodendrogliomas (malignancy grade III). Despite the fact that almost 10 years has elapsed since the identification of these relatively specific losses the genes targeted on these two chromosomes are still unknown.
Oligodendrogliomas grade II also show methylation of p14ARF, over-expression of EGFR and both ligands and receptors of the platelet derived growth factor (PDGF) system. Malignant progression is associated with additional genetic abnormalities similar to those described above for the astrocytic tumours—that is, disruption of the Rb1 pathway due to homozygous deletions or in some cases hypermethylation of the CDKN2A/p14ARF locus, or the RB1 locus or CDK4 amplification and overexpression as is also seen in the progression of the diffuse astrocytic tumours.
Some anaplastic oligodendrogliomas have no wild-type PTEN although this is usually in tumours without 1p and 19q loss. Anaplastic oligodendrogliomas also have abnormalities of many other chromosomal regions including chromosomes 4, 6, 7, 11, 13, 15, 18, and 22. Oligoastrocytomas and anaplastic oligoastrocytomas tend to have either aberrant genetic patterns similar to the oligodendroglial tumours or the diffuse astrocytic tumours. As yet there are no specific abnormalities associated with these mixed glial tumours.
Meningiomas
Meningiomas are usually solitary lobulated tumours arising in the meninges and attached to the dura. They are believed to develop from meningothelial (arachnoidal) cells, despite the fact that the meningothelial form is far from the most common. Symptomatic meningiomas represent 13–26% of primary intracranial tumours, are most common in middle aged and elderly patients, and show a pronounced female predominance.
Small asymptomatic meningiomas are found incidentally in 1.4% of necropsies. Patients with NF2 and members of some other non-NF2 familial syndromes may develop multiple meningiomas, often early in life. Ionising radiation is a well recognised predisposing factor. The cellular morphology, growth pattern, and the presence of extracellular material allow differentiation into the various histological subtypes (fig 7). Meningiomas are graded as malignancy grade I, atypical meningiomas as malignancy grade II, and anaplastic meningiomas as grade III.
Meningeal sarcomas are WHO malignancy graded as IV. The vast majority (about 80%) of meningiomas are of malignancy grade I. Atypical meningiomas constitute less than 20% of meningiomas while anaplastic variants are unusual (< 2%). Both atypical and anaplastic meningiomas are more common in men. Meningiomas may progress and therefore should be thoroughly sampled to identify areas with a histology associated with a more aggressive behaviour.
The histological criteria indicating a more aggressive behaviour and thus an increase in the malignancy grade include frequent mitoses, regions of hypercellularity, sheet-like growth, high nuclear–cytoplasmic ratio, prominent nucleoli, and spontaneous necrosis. The criteria for the different malignancy grades are strictly defined by WHO.
Some subtypes, characterised by particular tumour cell phenotypes, are associated with more frequent recurrence and they are now classified as malignancy grade II or III. For example, tumours with a papillary growth pattern or areas of rhabdoid cells (rounded tumour cells with an eccentric nucleus with nucleolus and a prominent eosinophilic cytoplasm) are classified as papillary and rhabdoid meningiomas, respectively (malignancy grade III) as they have been documented to behave in a very aggressive fashion.
