CNS neoplasia II: Special situations

Pathology

Nearly all tumours are benign pituitary adenomas. The incidence increases with age: 20% of 80-year-olds have small adenomas at postmortem examination. Prolactinomas represent 60–70%, growth hormone-secreting tumours 10%, non-secreting tumours 30% and tumours secreting thyroid-stimulating hormone or adrenocorticotrophic hormone are rare. Less common pituitary lesions are craniopharyngiomas, meningiomas, metastases and granulomatous diseases.

Clinical features

These include endocrine malfunction, visual disturbance and headache.

Endocrine disturbance may be due to abnormal excessive hormone secretion or impaired hormone secretion following damage to hormone-secreting cells. The most common features in adults are infertility, amenorrhoea, loss of libido and hypothyroidism. Acromegaly, gigantism, Cushing’s syndrome, diabetes insipidus and hypoadrenalism occur less commonly.

Visual disturbance occurs because of compression of the optic chiasm and is typically chronic or subacute deterioration of vision in both eyes. The chiasmal lesion leads to a bitemporal hemianopia, especially to red pin, and may lead to reduced acuity. The fundi are usually normal but there may be papilloedema or optic atrophy. Eye movement abnormalities occur if the tumour has expanded into the cavernous sinus and compresses the 3rd, 4th or 6th nerves.

Headache is a late feature and may reflect bony erosion or hydrocephalus.

A rare but important presentation is with pituitary apoplexy, characterized by acute visual disturbance associated with headache, malaise and systemic collapse. This is due to infarction of a pituitary tumour causing swelling and acute adrenal failure. It may occur after postpartum haemorrhage in women with pituitary tumours.

Investigations

A highly elevated serum prolactin level (>4000 mU/l (normal <400)) implies a prolactinoma. More moderate elevations may be seen with other pituitary tumours that block the inhibition of prolactin release by dopamine. The tumours and their relation to other structures, especially the optic chiasm, are best seen on MRI (Fig. 1) but may also be seen on a CT scan with dedicated pituitary views. Endocrine assessment may be required, for example thyroid function, adrenal function, follicle-stimulating hormone and luteinizing hormone.

Fig. 1 MRI scan of a pituitary tumour.

Treatment

Pituitary tumours can be divided into two main categories: prolactin-secreting prolactinomas that can usually be treated with medication alone; and other tumours that require surgery. Prolactinomas respond to dopaminergic agonists such as bromocriptine or cabergoline. These not only prevent secretion of the hormone but also cause tumour shrinkage. Surgery is not usually required unless vision is immediately threatened. Growth hormone-secreting tumours may also respond to dopaminergic agonists or octreotide (an analogue of somatostatin) but other tumour types need surgery if there is any suggestion of neurological compromise. Radiotherapy may be of value in some inoperable cases. Endocrine failure requires appropriate treatment. The prognosis with modern treatment is good.

Pathology

Most commonly acoustic nerve Schwannomas (often referred to as acoustic neuromas); see also neurofibromatosis type II. Also meningiomas of trigeminal, facial and acoustic nerves and cholesteatoma.

Clinical features

Seventy-five per cent of patients present with progressive deafness in one ear. Any patient with unilateral sensorineural hearing loss requires investigation to exclude this diagnosis. Less commonly, there may be ipsilateral facial weakness, facial sensory loss, ataxia and headache. Neurological deficits in the limbs occur later with brain stem compression.

Investigation

An MRI scan (Fig. 2) (a CT scan may miss early tumours) and audiometry to document hearing loss.

Fig. 2 MRI scan of a cerebellopontine angle tumour.

Treatment

Surgical resection can be undertaken via various routes. Suboccipital transmeatal microdissection minimizes risk to the facial nerve, which is immediately adjacent to the 8th nerve in the auditory canal. Function can be monitored perioperatively by facial nerve electromyography and auditory evoked potentials. The prognosis is good, especially for early tumours.

Malignant meningitis

Malignant infiltration of the meninges may present with chronic meningitis, often with communicating hydrocephalus. Common features are headache, radicular pain, multiple cranial nerve palsies and polyradiculopathy in the limbs, usually evolving over a few weeks. Common causes are adenocarcinoma, lymphoma, leukaemia and melanoma. Diagnosis is made from the clinical picture and on CSF examination. In 25% of cases it may not be possible to identify malignant cells even with two lumbar punctures. MRI may help in identifying bulky meningeal masses and meningeal enhancement. Occasionally meningeal biopsy is indicated. The prognosis is very poor. Palliative intrathecal chemotherapy (methotrexate, cytarabine or thiotepa) may improve prognosis and prevent neurological deterioration.

Inherited tumour syndromes

A variety of inherited diseases present with nervous system tumours, some with typical skin abnormalities (Table 1). They are rare. Most are inherited as autosomal dominant traits. The genetic locus of some of these conditions has been characterized but the pathophysiology is not yet understood.

Paraneoplastic syndromes

The nervous system is especially susceptible to non-metastatic manifestations of malignancy (Table 2). In some cases, humoral factors have been demonstrated, for example antibodies to Purkinje cells of the cerebellum in paraneoplastic cerebellar disorders, but it is not always clear if they are pathogenic. Certain tumours are particularly prone to causing these syndromes, especially small cell bronchial carcinoma, breast and female genital tract carcinoma and lymphoma. Paraneoplastic syndromes affecting other parts of the nervous system include: subacute myelopathy, retinopathy, stiff person syndrome and Lambert–Eaton myasthenic syndrome.

Table 2 Paraneoplastic central nervous system disorders