Typical meningioma specimen malignancy grade I showing an example of the common transitional meningioma with multiple whorles (a few marked with arrows). Meningiomas generally expand and displace but do not invade adjacent brain or spinal chord. Invasion of the dura and skull does occur and has no significance for malignancy grading. Invasion of the skull may elicit an osteoblastic reaction. Brain invasion can occur in meningiomas of all malignancy grades and indicates a greater likelihood of recurrence, but is not considered sufficient criteria alone to increase the malignancy grade.
The higher incidence of meningiomas in women, the apparent manifestation of tumours during pregnancy, and the association of meningiomas with breast and genital cancer have suggested oestrogen and progesterone dependency of the tumours. Meningiomas generally express progesterone receptors and some cases also express oestrogen receptors.
Meningiomas were one of the first solid tumours in humans to be shown to have consistent chromosomal abnormalities, the loss of one copy of chromosome 22. The fact that the second most common tumour in neurofibromatosis type 2 patients was meningioma pointed to the NF2 gene as a target on chromosome 22.
Loss of wild copy NF2 is found in roughly half of sporadic and the majority of NF2 associated meningiomas. In the sporadic cases this is usually by the loss of one copy (monosomy 22) and mutation of the retained copy. The NF2 gene encodes a protein known variously as merlinor schwannomen. This protein has been shown to be involved in control of cell growth and motility in culture.
Genetically engineered mice with only one wild-type allele have been shown to develop many tumour forms while tissue specific inactivation in Schwann cells or leptomeningeal cells results in schwannoma or meningioma formation, respectively.
As stated above meningiomas may progress from grade I tumours to tumours of higher malignancy grade. This is associated with losses on chromosomal arms 1p, 6q, 9p, 10p and q, 14q, 18q, as well as gains and some amplifications on many other chromosomes. The genes targeted by these abnormalities are mostly unknown, but the losses on 9p are associated with loss of both wild-type copies of CDKN2A, p14ARF, and CDKN2B as is commonly seen in the de novo glioblastomas and anaplastic oligodendrogliomas.
CONCLUSIONS
The goal for all histopathology is to provide—on the basis of an analysis of the tissue received—as much useful information as possible to the clinician, informing him/her of all the details of any pathological process present, and forming the basis for the choice of the most appropriate treatment, and a judgement of prognosis. Up until relatively recently this process was mainly based on a morphological analysis.
However, as different forms of treatment become more and more based on targeting molecular mechanisms, the analysis of the specimens received must be extended to provide relevant data. This has already occurred examples include determination of oestrogen receptor, or HER2 expression in breast cancer, which will determine whether the patient will benefit from tamoxifen or herceptin treatment.
New technologies currently being introduced will permit a detailed analysis of the genome and transcriptosome of clinical material impossible in the past and the integration of genetic and expression data with the histological information. Eventually we can hope that the molecular information will provide the basis for specific treatments that will only annihilate brain tumour cells, leaving the brain and the rest of the patient unharmed.
