Most recent classifications of brain tumours build on the 1926 work of Bailey and Cushing.2 This classification named tumours after the cell type in the developing embryo/fetus or adult which the tumour cells most resembled histologically. The cell of origin of the majority of brain tumours is unknown as no pre-malignant states are recognised, as is the case in some epithelial tumour forms.
In some tumours, cells may be so atypical that it is difficult to compare them with any normal cell type—hence the use of terms such as glioblastoma. Many unsound or illogical terms have remained in the classifications, as once established in a complex medical setting they are difficult to change. In this paper the terminology and definitions of the World Health Organization classification of 2000 will be exclusively used.
There are more than 120 entities in this classification and here we will concentrate on those that most frequently occur in adults and children. These are the pilocytic astrocytomas, ependymomas, and medulloblastomas in children, and the diffuse astrocytic tumours (including astrocytoma, anaplastic astrocytomas, and glioblastomas), oligodendrogliomas, and meningiomas in adults.
Tumours of the central nervous system often have a wide morphological spectrum and classification is dependent on the recognition of areas with the characteristic histology for a particular tumour type. Immunocytochemical methods may be required to demonstrate the expression by the tumour cells of an antigen typically expressed by a particular cell type and thus to assist in classification. Unfortunately there are no antibodies that unequivocally identify the different tumour types. The presence or absence of an antigen only adds a further piece of information helping to indicate the tumour type.
Four malignancy grades are recognised by the WHO system, with grade I tumours the biologically least aggressive and grade IV the biologically most aggressive tumours. The histological criteria for malignancy grading are not uniform for all tumour types and thus all tumours must be classified before the malignancy grade can be determined. Only one or two malignancy grades can be attributed to some tumour types. Brain tumours are well known to progress, becoming more malignant with time. Such progression will initially be focal. A patient’s diagnosis is based on the most malignant part of the tumour. Thus it is of the utmost importance to sample the tumour adequately in order to determine its type and judge its malignant potential. It follows that malignancy grading on biopsies/stereotactic biopsies is always a minimum grading as more anaplastic regions may be present in non-biopsied areas.
Cytotoxic or radiation therapy before histological diagnosis may make classification and malignancy grading extremely difficult or impossible. The clinical implications of tumour classification and malignancy grading have been empirically determined. The application of objective methods of measuring cell proliferation and death in tumours to malignancy grading is conceptually attractive but have yet to be accepted and utilised in the malignancy grading of brain tumours.
The MIB 1 antibody recognising the same antigen as Ki67 as well as other antibodies identifying antigens associated with proliferation (for example, Cdc6 and Mcm5) can be used efficiently on formalin fixed, paraffin embedded tissues following microwave antigen retrieval.
However, wide variations in the proliferation indices are observed in different areas of individual brain tumours and this has resulted in difficulties in defining relevant proliferation levels. The same applies to the assessment of the numbers of cells undergoing apoptosis. The advances in neuroradiology and parallel improvements in stereotactic and surgical techniques permit the biopsy of just about any neoplastic or non-neoplastic lesion in the central nervous system (CNS). The list of potential diagnoses is thus vast.
The neuropathologist may be expected to make a diagnosis on the basis of often very small and fragmented biopsies. He thus needs to know the clinical background of the case. Information must be provided: age, neuroradiological findings including location of the tumour, relevant clinical and family history, and whether the patient has received any treatment, including steroids.
As can be deduced from the above, morphology combined with immunocytochemistry may only provide a differential diagnosis and the most likely diagnosis will then only be reached by considering all the information available at a multidisciplinary team meeting. The vast majority of brain tumours are sporadic. A number of familial syndromes are well documented with an increased incidence of brain tumours (see table 1 and the references therein). However, even in the most common syndromes (neurofibromatosis type 1 and neurofibromatosis type 2), the precise relative risk is difficult to deffine.
