NEOPLASMS OF THE CENTRAL NERVOUS SYSTEM
Astrocytomas account for approximately one third of gliomas and the incidence appears to be increasing. They occur at all ages and affect all parts of the central nervous system. Most cases in adults are seen within the cerebral hemispheres but they are found more commonly in the cerebellum, hypothalamus and brainstem in children and young adults. Incidence decreases after the fifth decade.
The degree of localisation varies considerably from cases to case and they may show widespread infiltration (Figure 1), the most diffuse of which is called gliomatosis cerebri. They may contain cysts. Astrocytomas show several histological variants including fibrillary (Figure 2), protoplasmic and gemistocytic (Figure 3) forms and may contain foci of calcification.
The pilocytic variant is the commonest form found in children, usually in the cerebellum or floor of the 3rd ventricle (Figure 4). Rosenthal fibres are particularly characteristic, although not diagnostic, and the neoplastic cells tend to be bipolar.
Cytological characteristics vary from well differentiated fibre forming astrocytes to neoplasms showing greater pleomorphism and the presence of mitotic figures when the neoplasm is regarded as anaplastic. The most undifferentiated neoplasms may show evidence of vascular hyperplasia, necrosis, thrombosis and/or haemorrhage, when the neoplasm is referred to as glioblastoma multiforme.
An unusual variant, known as pleomorphic xanthoastrocytoma, tends to occur superficially in the younger age groups and be relatively well localised. It shows marked pleomorphism with multinucleate forms, but may have a favourable prognosis. Some cells contain large amounts of lipid (Figure 5).
Glioblastoma multiforme accounts for approximately 50% of all gliomas. It usually shows areas of astrocytic differentiation, defining its cell of origin, but similar neoplasms can occasionally be derived from oligodendrocytes. A well differentiated glioma may progress to glioblastoma multiforme but some neoplasms appear with a picture of glioblastoma multiforme with no evidence of progression from a better differentiated form.
Most glioblastomas occur in middle life and have a rapidly fatal course. Most frequently they involve the white matter of the cerebral hemispheres, the frontal lobes being the most common site of origin.
Macroscopically they may appear to be relatively well demarcated and show obvious areas of haemorrhage and necrosis (Figure 6). The neoplastic cells show marked pleomorphism, often with multi-nucleate cells; mitotic figures are prominent and there is evidence of vascular hyperplasia and foci of necrosis. Sometimes there is a sarcomatous component. (Figure 7).
Oligodendrogliomas account for approximately 6% of gliomas. They are almost invariably found within the cerebral hemispheres and calcification is common, which may be visible on x-rays. Anaplastic forms are uncommon. The cells have a characteristic histological appearance with central round or oval nuclei surrounded by abundant clear cytoplasm (Figure 8). Mitotic figures are difficult to find. There are often foci of calcification. Occasionally a neoplasm composed of a mixture of oligodendrocytes and astrocytes is seen. Progression from a well differentiated to an anaplastic form may occur.
These constitute about 6% of intracranial gliomas and are usually seen within the region of the fourth ventricle or spinal cord in children or young adults, and less commonly, within the region of the ventricles of the cerebral hemispheres in adults. Their situation within the wall of the ventricles may result in obstructive hydrocephalus (Figure 9). Ependymoma is one of the common tumours of the spinal cord.
The degree of differentiation varies considerably from case to case and even within the same neoplasm. Diagnosis requires the finding of ependymal canals (Figure 10) and/or perivascular pseudo rosettes. The former consist of tubules lined by ciliated ependymal cells; the latter consist of fibre forming ependymal cells producing a halo of fine processors between the cell nucleus and an adjacent blood vessel. Some tumours may show a papillary pattern and a particular form of ependymoma occurring in the region of the filum terminale shows marked myxomatous change and hyaline areas.
SUBEPENDYMOMA is a neoplasm of uncertain type, showing a highly fibrillary pattern, occurring beneath the ependyma and is thought to be a neoplasm derived from subependymal astrocytes, and is not a true ependymoma (Figure 11). They may cause symptoms by obstructing the CSF pathways.
NEOPLASMS OF THE CHOROID PLEXUS
Papillomas of the choroid plexus are rare and occur mainly in children and young adults. They most commonly arise within the fourth ventricle but may occur within the wall of the third or lateral ventricles. The neoplasm shows a marked papillary pattern covered by columnar or cuboidal epithelium which may be stratified It can be distinguished from papillary ependymoma by the presence of a basement membrane overlying vascularised connective tissue (Figure 12). Malignant forms occur and are known as choroid plexus carcinoma.
Choroid cysts are usually found within the anterior third ventricle in young adults. They may cause hydrocephalus by obstructing the foramen of Monro.
TUMOURS CONTAINING NEURONS
A variety of neoplasms containing neurons, often mixed with glial cells have been described and these show variable degrees of differentiation. The mixture is usually one of neurons and astrocytes and these neoplasms are named Gangliogliomas (Figure 13). They are usually found in adolescents or young adults within the temporal lobe or hypothalamus. Anaplastic variants occur. A variety of names had been used to describe neoplasms composed mainly of neurons, varying in the degree of differentiation. Gangliocytoma is composed of mature ganglion cells. (Figure 14) and Central Neurocytoma is a well differentiated neoplasm has been described in young adults, usually within the lateral ventricles, composed of uniform round cells with immunohistochemical and ultra structural features of neuronal differentiation. This lesion carries a favourable prognosis after resection. (Figure 15).
Dysembryoplastic neuroepithelial tumour is a benign neoplasm showing mixed glial/neuronal differentiation, occurring within the supratentorial region and often associated with cortical dysplasia. It usually corresponds to grade 1 and usually does not recur after surgical resection.
Desmoplastic infantile ganglioglioma is a neoplasm of infancy and contains a dense fibrous stromal component and usually shows a favourable course after surgery.
Dysplastic Gangliocytoma of the Cerebellum is composed of cells that resemble Purkinje cells; it may be associated with a variety of congenital malformations and may be familial.
Olfactory Neuroblastoma occurs at the roof of the nose and is composed of immature neuronal cells. It tends to infiltrate adjacent structures.
MEDULLOBLASTOMAis the commonest tumour of the central nervous system in children and usually occurs in the cerebellum. It is composed of cells with hyperchromatic nuclei surrounded by small amounts of cytoplasm; the nuclei are often slightly elongated. The histological pattern is variable and may show differentiation to a variety of cell types including neuronal, glial, ependymal, melanin-producing cells, or rhabdomyoblasts. Another rare variety form contains abundant collagen and is referred to as the desmoplastic form. (Figure 16).
Meningiomas are derived from the meninges and account for approximately 15% of primary intracranial neoplasms. They occur in adult life and are approximately twice as common in females as males. They are derived from arachnoidal endothelial cells and occur wherever arachnoidal villi are found. The commonest site is adjacent to the sagittal sinus (Figure 17). They may be multiple. They usually show evidence of slow progressive growth but malignant transformation can occur.
A variety of types have been described and they usually show some evidence of whorling. The patterns most commonly found are:
TUMOURS OF SCHWANN CELLS
Schwannomas- these may arise wherever Schwann cells are normally found but most commonly occur on the eighth cranial nerve (Figure 22) when they are referred as acoustic neuromas. They are composed of a mixture of spindle-shaped cells (Antoni type A) and foamy cells (Antoni type B). The spindle-shaped cells tend to form whorls and show palisading of nuclei (Figure 23). Malignant change is very rare.
Neurofibroma - these may occur as solitary subcutaneous or nerve-sheath tumours or they may be multiple and form part of the syndrome known as neurofibromatosis. They are usually multiple and histologically show myelinated and non-myelinated nerve fibres, Schwann cells, fibroblasts, and variable amounts of collagen (Figure 24). Antoni type A and B patterns are not seen but they may show focal whorling or palisading. Malignant varieties are occasionally seen. A form known as plexiform neurofibroma involves several branches of a nerve and form a racemose pattern. A significant proportion of this form of neoplasm undergoes malignant transformation.
This neoplasm is usually found in children and young adults. It is usually associated with a cyst and appears as a dark red nodule within the wall. They may be associated
with extensive haemorrhage which can destroy the histological characteristics of the neoplasm. The microscopic appearance is that of numerous interweaving capillaries, which may vary considerably in size, separated by variable numbers of stromal cells of uncertain type (Figure 25). The stromal cells may form large groups and can closely resemble metastatic carcinoma of the kidney. Immunohistochemical staining for epithelial membrane antigen helps in the differential diagnosis in that haemangioblastoma shows a negative reaction whereas metastatic renal carcinoma is positive. Both neoplasms may contain abundant glycogen. Capillary haemangioblastoma together with retinal angiomatosis, renal cysts, and sometimes renal carcinoma can occur together as part of von Hippel-Lindau disease. The neoplasm may be associated with the production of erythropoietin, causing polycythemia.
Malformations of blood vessels of various types occur, such as capillary telangiectases, cavernous angiomas and arteriovenous malformations. These may be associated with haemorrhage and in the case of the latter in particular with progressive neurological signs and symptoms which may mimic neoplasm. Sturge-Weber disease, it is an association of cutaneous capillary angioma (port wine stain) within the trigeminal region of the face, with intracranial arteriovenous malformation.
TUMOURS OF THE PITUITARY GLAND
Pituitary adenomas are classified according to the type of hormone(s) produced by the neoplastic cells. They vary considerably in size and may compress the optic pathways or involve the hypothalamus (Figure 26). They are composed of polygonal cells showing variable degrees of granularity of the cytoplasm (Figure 27). A panel of immunohistochemical stains are used to determine this and sometimes electron microscopy can be helpful. Some pituitary adenomas show no clinical evidence of hormonal activity and these neoplasms usually present as a result of pressure on adjacent structures such as the optic chiasm, where they produce bitemporal hemianopia progressing to blindness, or destruction of other anterior pituitary endocrine cells causing hypopituitarism. Symptoms of raised intracranial pressure are rare. Radiology may demonstrate disruption of the sella turcica.
Clinical syndromes of excessive hormone production clearly depend upon the nature of the hormone, the most commonly recognised of which are due to secretion of prolactin, growth hormone, and ACTH.
Neoplasms showing no evidence of hormone secretion are referred to as null cell adenomas.
TUMOURS OF THE PINEAL GLAND AND TERATOMAS
Pinealoma is rare and mainly affects children; they can occur in adults.
Arising in the roof of the mid brain (Figure 28). They frequently produce abnormalities of conjugate upward gaze and they may be associated with precocious puberty in young children. Compression of the aqueduct in the mid brain may cause a rise of intracranial pressure and obstructive hydrocephalus. They are sometimes associated with disturbances of hypothalamic function.
Some neoplasms are highly cellular and composed of small cells with a high nuclear/cytoplasmic ratio, resembling medulloblastoma; they are frequently referred to as primitive neuroectodermal tumours (PNET) or pineoblastoma (Figure 29). Other neoplasms are composed of larger cells resembling pineocytes sometimes arranged in perivascular rosettes and these are referred to as pineocytomas (Figure 30). Some of these tumours show neuronal differentiation, and occasionally retinal differentiation, which may be demonstrated by the presence of a positive histochemical reaction for retinal S-antigen. Tumours showing a mixed pattern of pineoblastoma and pineocytoma also occur.
Another type of tumour produces a histological picture identical to that of seminoma of the testes or dysgerminoma of the ovary and is referred to as germinoma. They are composed of a mixture of large cells with prominent nucleoli, and small cells resembling lymphocytes. (Figure 31).
The pineal gland has a predilection for intracranial teratoma, although these are extremely rare and are seen mainly in children. They may contain a variety of tissues from all three embryological layers (ectoderm, mesoderm and endoderm) and the tissue vary in their degree of differentiation from one case to another (Figure 32). Both benign and malignant forms are therefore encountered. Other tumours of germ cell type include embryonal carcinoma, yolk sac tumour, choriocarcinoma, and a variety of mixed germ cell tumours.
Occasionally a tumour identical to those found within the pineal gland is found in an extra-pineal site such as the third ventricle or hypothalamus and these are referred to as ectopic pinealoma.
Chordomas arise from remnants of notochord. They are rare but usually arise in the intrasellar region and clivus in the region of the foramen magnum or within the sacro-coccygeal region in the spinal canal (Figure 33). They are usually slow growing but progressively destructive and are radio-resistant. They therefore have a poor prognosis.
Histologically chordomas are composed of cells with vacuolated cytoplasm, known as physaliphorous cells, often arranged in cords or small packets within a loose myxoid matrix (Figure 34).
Chordoma can be difficult to differentiate from cartilaginous tumours, particularly chondrosarcoma. Chordomas stain positively for cytokeratins and epithelial membrane antigen whereas chondrosarcoma does not.
This is an epithelial cell tumour arising in the region of the pituitary fossa or hypothalamus. They are thought to be derived from remnants of the anterior pituitary gland which is derived embryologically from the stomatodeum. It is composed of trabeculae of epithelium containing squamous areas, keratin, cholesterol clefts, areas of calcification, and there may be cysts (Figure 35). Examination of the cyst fluid may reveal cholesterol or crystals. Some forms have a papillary pattern. Histologically they behave as grade 1 but tend to recur locally following surgery.
DERMOID AND EPIDERMOID CYSTS
These are rare neoplasms with a predilection for the posterior fossa, the intra and suprasellar regions, and the lumbosacral region of the spinal canal. The wall of an epidermoid cyst is composed of keratinizing squamous epithelium whereas that of a dermoid cyst contains a variety of structures found in the dermis such as hair follicles, sweat glands, and sebaceous glands. The lumen of the cyst may contain hairs.
TUMOUS OF THE SKULL AND SPINE
A variety of tumours derived from bone and cartilage, both benign and malignant, occur, such as chondroma, osteoma, angioma, chondrosarcoma and osteosarcoma.
Metastatic Tumoursare common and particularly frequent over the age of 60. Lung and breast are the two commonest types but in many cases the primary site is uncertain. They are often multiple. Although rare in children they can occur and sometimes involve the central nervous system in relapse in acute lymphoblastic leukaemia.
The vast majority of lymphomas occurring within the central nervous system are non-Hodgkin lymphomas of B cell type (Figure 36). Primary lymphomas of the central nervous system may occur sporadically or in patients showing evidence of immunodeficiency from a variety of causes. T cell lymphomas are rare. They can be classified according to the Kiel classification in a similar way to lymphomas occurring elsewhere.
Plasmacytoma occurs in the skull and occasionally in the intracranial dura. Some progress to, or are associated with, multiple myeloma. Multiple myeloma is more common in men than women and has a peak incidence between the fifth and seventh decades. The lesions are osteolytic and are associated with the production of monoclonal globulin. Penetration of the dura is rare. The solitary plasmacytoma is usually better differentiated than the plasma cells of multiple myeloma.
This is a benign tumour but is histologically identical to paraganglioma occurring outside the nervous system (Figure 37). It usually occurs in the region of the filum terminale. They give a positive reaction for chromogranin, somatostatin or synaptophysin and dense core granules and microtubules may be demonstrated by electron microscopy.
A wide variety of cystic lesions occur in the nervous system:
A benign lesion usually situated within the midline in the region of the corpus callosum, third ventricle or midbrain. They may occur within the spinal canal and occasionally within the region of the sylvian fissure or cerebello-pontine angle. Some cases may be associated with the presence of numerous blood vessels and in this case they have been classified as angiolipoma.
PRIMARY MELANOCYTIC LESIONS and tumours containing melanin
A variety of neoplasms of melanocytes occur and these vary from benign to malignant. Approximately one quarter of them are associated with a neurocutaneous melanosis syndrome. Diffuse melanosis consists of the widespread proliferation of melanocytes within the leptomeninges and the brain may have a dark appearance (Figure 38). Melanocytes may proliferate to form a nodular lesion known as a melanocytoma and occasionally a malignant neoplasm of melanocytes occurs within the meninges which may rarely be amelanotic.
A wide variety of neoplasms of the central nervous system may contain melanin pigment, including choroid plexus papilloma, Schwannoma, neurofibroma, ependymoma, meningioma, medulloblastoma and malignant neoplasms of peripheral nerve sheath.